Coenzymes as fossils of an earlier metabolic state. A metabolic system composed of nucleic acid enzymes is proposed to have existed prior to the evolution of ribosomal protein synthesis. Vestiges of these nucleic acid enzymes persist in contemporary coenzymes. This proposal rationalizes the fact that many coenzymes are nucleotides or heterocyclic bases which could be derived from nucleotides.


Structural characterization of thermal prebiotic polypeptides. Thermal polycondensation of amino-acids as a possible prebiotic path of chemical evolution of life has been critically examined. The polymeric materials studied by nmr methods have scarce resemblance to natural peptidic material because beta, gamma and eplision peptide bonds largely predominate over a-peptide bonds.


Conservation of repeated DNA base sequences in Crustacea: a molecular approach to decapod phylogeny. Analysis of data obtained from molecular hybridization of 3H-labeled repetitious DNA has been utilized to reconstruct the broad outlines of phylogenetic relationships among decapod Crustacea. This molecular reconstruction agrees reasonably well with the paleontological record, and with other schemes obtained by comparative morphological and serological approaches. Preliminary  evidence is in line with the hypothesis that continuous addition of new repeated sequence families to the genome over long periods of time may in part account for the correlation observed between percent repetitious DNA hybridized and divergence time. It is tentatively concluded that a core of DNA base sequence homology has been highly conserved throughout the evolution of the Crustacea. Demonstration of inter-species sequence homology has important implications to models which relegate a genetic regulatory function to repeated DNAs.


Studies on the biological disposition of diethylstilbestrol in rats and humans. Studies were conducted to elucidate the processes involved in the biological disposition of diethylstilbestrol (DES). The apparent biological half-life of [14C] DES decreased with increasing age in immature rats. The half-life of DES in adult rats (14 min) was reached between the 15th and 25th day after birth. Comparison of the intestinal absorption of [14C] DES and [14C]DES monoglucuronide showed the unconjugated drug to be absorbed much more rapidly. Hydrolysis of the conjugate took place in the lower intestine, and this permitted the drug to undergo enterohepatic cycling.


Isolation and identification of metabolites of 14C-labeled estradiol in cattle. A total of six steers and six heifers received three daily injections containing either 200 muCi (1 mg) of [4-14C] estradiol-17beta or 312 muCi (2.16 mg) of [4-14C] estradiol 17beta 3-benzoate. Major metabolites of the administered estradiol-17beta and estradiol-17beta 3-benzoate were identified in muscle, fat, liver, and kidney samples obtained 3 hr after the final injection. Estradiol benzoate was nondetectable in the tissues analyzed, suggesting rapid hydrolysis of the benzoate ester. Consequently, the relative proportions of the various metabolites were similar for both the injected estrogens. Estradiol-17beta and estrone, which together accounted for 80-90% of the total extracted radioactivity, appear to be the major metabolites in both muscle and fats. In contrast, the major metabolites present in liver and kidney appear in the conjugate fraction. Most of the conjugated metabolites were glucuronates, which represent 85-95% of the total recovered conjugate radioactivity.


Estrogen concentrations in bovine and porcine tissues. Using an estrogen antiserum that measures biologically active estrogen (estradiol-17beta + estrone), a series of studies have been completed to describe the normal plasma levels of estrogen in cows and sows during various stages of reproduction. The levels are lower in the nonpregnant cow (less than 25 pg/ml) than in most species. Only during late pregnancy are the levels easily assayed. The levels in the nonpregnant sow are 2-3 times greater than in the cow. In both species there is a preovulatory peak of estrogen that is responsible for estrus. Plasma estrogen concentrations were also determined after induction of multiple ovulations by exogenous gonadotropin (PMSG) in the cow and sow and after treatment of cows with either a progestin (MGA) or a prostaglandin (PGF2alpha). (These two drugs have been used to synchronize estrus in the cow.) Estrogen levels rise greatly after treatment with PMSG but show little effect from MGA or PGF2alpha. Data are also presented on the validation of an assay for E2beta and E1 in beef tissue. Less than 20 pg of E2beta and E1 was measured per gram bovine muscle tissue. Considerable effort must be expended to apply radioimmunoassay to the assay of estrogens in tissues.


Studies on metabolism and effects of estrogen on pituitary prolactin and LH secretion. The effect of a subcutaneous injection of estradiol on the secretion of pituitary prolactin in the rat and the relationship between serum estradiol level and luteinizing hormone (LH) secretion in mare were reviewed. In addition, the effect of estradiol injection on LH secretion and the metabolism of [14C] estradiol in intact and bile duct fistulated pony mares were studied. Low (0.1 mug/day/rat) to moderate dose (5 mug/day/rat) of estradiol benzoate injected subcutaneously to mature or immature rats significantly increased pituitary content of prolactin and serum prolactin level five- to tenfold. On the other hand, high dose of estradiol (10 mug/day/rat or more) was less effective in stimulating prolactin secretion, and it appeared that progesterone injected concurrently with estradiol had some inhibitory action on the stimulatory effect of estradiol. Studies in pony mares showed that the physiologic level of serum estradiol during proestrus was important for the induction of the ovulatory surge of LH. Intramuscular injection of a low dose (2 or 4 mg/mare) of estradiol was stimulatory, whereas a high dose (8 mg/mare) was inhibitory for LH secretion in pony mares. Results of the estradiol metabolism studies indicated a relatively long half-life for estradiol in the mare. The majority of the [14C] estradiol metabolites appeared in the urine within 24 hr following intravenous injection. Enterohepatic circulation appeared to be important for estradiol metabolism in mare.


Reproductive endocrinology of female chimpanzees: a suitable model of humans. Similarities between reproductive processes in humans and chimpanzees have led to speculation that the chimpanzee might be an excellent reproductive-endocrine model of humans. Data comparing patterns and concentrations of serum gonadotropins, prolactin, and sex steroids in female humans, chimpanzees, and rhesus monkeys sustain this concept. The striking evidence that levels of estrone, estradiol, estriol, progesterone, and chorionic gonadotropin are similar during human and chimpanzee pregnancy support the contention that chimpanzees, like humans but unlike rhesus monkeys, have a definitive fetoplacental unit. Likewise, during normal menstrual cycles serum patterns of LH, FSH, progesterone, and estradiol are similar in women and chimpanzees, but differ in rhesus monkeys. Thus by using the chimpanzee it may be possible to accurately assess the safety for human use of compounds that might affect reproductive-endocrine processes without direct exposure to humans.


The superior gluteal: an artery at risk in blunt pelvic trauma. Five patients with pelvic fractures were studied arteriographically and all were found to have injury to one or both superior gluteal arteries, in addition to other injuries. In three of the five patients no adjacent bony damage was seen on plain pelvic roentgenograms. A possible explanation for this finding is given in terms of anatomic relationships within the pelvis. The importance of early arteriography in the diagnosis management of blunt pelvic trauma is emphasized.


The effect of hypertonic glucose upon survival in hemorrhagic shock utilizing a re-stress model in sheep. Twenty-three adult sheep were subjected to hemorrhagic shock using a re-stress model. Eleven of the animals served as controls and were resuscitated with shed blood and crystaloid. The remaining twelve were resuscitated in the same manner with the addition of hypertonic glucose. There was a highly significant increase in survival of the animals given hypertonic glucose.


Role of protein binding of cytotoxic anions in post-traumatic pulmonary insufficiency. Anions of fatty acids infused intravenously into dogs clearly duplicate the clinical syndrome of post-traumatic pulmonary insufficiency (congestive atelectasis, shock lung, traumatic wet lung). Neutral fat embolized to the lungs is incapable of producing this syndrome within the time investigated. The incubation of fatty acid anions with human serum albumin before injection obviates the severe desaturation of blood and ultrastructure disruption caused by FAA alone.


The value of ethambutol in the treatment of tuberculous meningitis. This is a prospective treatment study of 86 patients with tuberculous meningitis admitted to the Abbassia Fever Hospital Cairo, Egypt. The causative organism was cultured from the cerebro spinal fluidin 47 patients, was identified by Zeihl Nelson stain in five and in the remaining 34 patients the diagnosis was based on the clinical course and changes in the CSF chemistry and cell count. The data indicate that ethambutol can be used as a companion drug to INH and streptomycin in the treatment of the disease and that the mortality is directly dependent on the state of consciousness upon initiation of therapy.


Leishmaniasis in Brazil: XI. Observations on the morphology of Leishmania of the brazilensis and mexicana complexes. The present work shows that the amastigotes of L. m. amazonensis are morphologically distinguishable from those of L. b braziliensis. The authors consider that such differences add further support to the use of the name braziliensis and mexicana at the specific level.


An evaluation of factors relevant to the diagnosis of bronchial carcinoma in Sri Lanka. The incidence of bronchial carcinoma in Sri Lanka is low. The extent to which its pattern varies from that prevailing in western countries is demonstrated by a study of 84 cases diagnosed over a 10-year period. Of the patients examined 45-2 per cent were non-smokers, all 17 women belonging to this category. A negative smoking history, especially in women, was not a useful guide in assessing a suspected lesion. Adenocarcinoma, which is usually peripheral, comprised a high proportion of the tumours (22-6%). The majority of cases (70-3%) had had peripheral tumours which were beyond bronchoscopic visibility. Therefore, bronchoscopy was not as useful a diagnostic procedure as in the West. Digital clubbing was seen in less than half the males, while only two females had this sign.


Toxoplasma infection of stray cats in Egypt. A seroepidemiological survey of cats for Toxoplasma antibody revealed a high infection rate. No significant difference was detected between males and females or between rural and urban areas, although acute infection seems to be more prevalent in males and in rural areas as revealed by the high titres of the dye test. Toxoplasmosis in cats, as revealed by serologic surveys, seems to prevail more during the warm rather than the hot season of the year being favoured by milder temperature and higher relative humidity and rainfall in the former season. Futhermore, it was concluded that infection rate with Toxoplasma increases with the age of the host. Toxoplasma antibody in the young age groups is to a great extent of maternal origin. Study of the relationship of Toxoplasma to Isospora showed no cross immunity. They follow a reversed pattern with increasing age of the host. Data also shows the high specificity of dye testing for detection of Toxoplasma antibody. Feeding experiments show that a relatively high percentage of cats shed oocysts in their faeces. Not only seropositive but also seronegative cats excrete oocysts, though at a lower rate in the latter case. The majority of cats shedding oocysts are those with either low positive titres or seronegative cats.


Massive renal hemorrhage associated with parturition. Spontaneous massive renal hemorrhage, during or after parturition, not associated with blood dyscrasias or other recognizable etiology is rare. Two new cases are added to the 7 cases previously reported. The related literature is reviewed.


Renovascular hypertension: does the renal vein renin ratio predict operative results? Renal vein renin ratios from 56 hypertensive patients who were operated upon for unilateral stenosis of a main renal artery were compared to blood pressure response to a corrective operation. In patients with renal vein renin ratios greater then 2.0, the upper limits of normal for essential hypertension (95 per cent confidence limits), the cure/improvement rate approximated 90 per cent. However, in patients operated upon despite lesser ratios the cure/improvement rate was also high--83 per cent in our series and 57 per cent in collected reports from the literature. Thus, the test may be falsely negative in a high percentage of patients. Renal vein renin ratios would appear to be most useful in confirming but not necessarily in denying the functional significance of a renal artery stenosis.


Hepatorenal artery bypass in the management of renovascular hypertension. Infrequently, when the aorta cannot be used for a standard renal bypass operation because of a previous aortic operation, severe degenerative atherosclerosis or complete aortic thrombosis, a unilateral (hepatic) or bilateral (hepatic and splenic) visceral bypass should be contemplated. Patients with abdominal aortic aneurysms extending above the renal arteries might benefit from concomitant bilateral visceral bypass procedures followed by aortic replacement during the same operative session. The hepatic circulation with its common anatomic variations, indications, surgical technique and effects of hepatorenal artery bypass on the renal and hepatic circulation are discussed.


Transplantation of human renal cell carcinoma to the nude mice: as an intermediate of in vivo and in vitro studies. Five human renal cell carcinomas were transplanted successfully to nude mice fed and grown under a specific pathogen-free condition. The histology of the transplanted tumor tissue was a close reproduction of the original human cancer tissue in situ. The transplanted tumor tissue possessed an abundant supply of blood vessels, which was considered to be of host animal origin. All transplanted tumor cells grew easily when transferred to an in vitro cell culture system from the nude mice. In this latter cell culture system tumor cells demonstrated a growth pattern characteristic of epithelial cells. The electron microscopy of these cells showed some characteristic morphological features that indicated their cytological origin.


Bacillus Calmette-Guerin in the treatment of adenocarcinoma of the kidney. Of 18 patients with renal adenocarcinoma 10 with metastatic disease received Bacillus Calmette-Guerin immunotherapy. Objective responses were recorded in 4 patients. When the intradermal route and relatively small amounts of vaccine were used the complications were minimal and self-limiting. Bacillus Calmette-Guerin immunotherapy appears to be more effective than other modalities in the treatment of renal adenocarcinoma. However, definitive conclusions cannot be drawn since there is no control group. A prospective clinical trial is now in progress at this institution.


Anergy and tryptophan metabolism in bladder cancer. The tryptophan loading test and cutaneous antigen test were done on 55 patients with various stages of bladder cancer. Patients with an abnormality of tryptophan metabolism showed a greater degree of unreactivity to cutaneous delayed hypersensitivity testing. Of the 23 patients with normal tryptophan metabolism 47 per cent were unreactive to 2 or 3 skin antigens. Of 13 patients with 1 abnormal tryptophan metabolite 62 per cent were unreactive to 2 or 3 skin antigens. Of 19 patients with 2 or more abnormal tryptophan metabolites 68 per cent were unreactive to 2 or 3 antigens.


Cysts of the ducts of Cowper's glands.

Cysts of the ducts of Cowper's glands. We describe 4 patients, 3 of whom were children, with cysts in the ducts of Cowper's glands. Presenting symptoms were testicular pain and urethritis. Voiding urethrography with dilute contrast medium is the best diagnostic aid short or urethroscopy. The cysts were effectively treated by avulsion with a bent wire.


Urinary continence after repair of membranous urethral stricture in prostatectomized patients. Prostatectomy by open or transurethral techniques usually destroys the function of the internal sphincter (bladder neck), which is the first line of defense against incontinence. Urinary continence then depends upon the intrinsic smooth muscle sphincter of the membranous urethra and the striated external sphincter. Unfortunately, a significant incidence of membranous urethral stricture occurs after a prostatic operation. Most such strictures can be managed with periodic dilatation but some are difficult and dangerous to dilate. Complications such as recurrent acute retention, bacteremia, false passages, stone formation, fistulas and so forth are indications for surgical cure of the stricture. However, can urethroplasty of the membranous urethra be carried out in these patients without inevitable incontinence? At our center 33 prostatectomized patients have had a 2-stage urethroplasty for refractory membranous urethral strictures. Nine patients had troublesome stress incontinence after the first-stage operation but only 4 of these had continuing incontinence after the second-stage operation. These patients had been noted to have transient postoperative stress incontinence after the prostatectomy. Although there is a risk of incontinence after urethroplasty of the membranous urethra in prostatectomized patients, the risk is sufficiently low that the operation should not be denied patients with refractory strictures in whom the only alternative eventually will be some form of urinary diversion.


Mucoid cysts of the penile skin.

Mucoid cysts of the penile skin. A study of 28 patients with mucoid cysts of the penile skin is reported. The lesions were seldom diagnosed correctly, either clinically or pathologically. The distinctive histologic features of the cysts include a lining of stratified columnar epithelium, often associated with intra-epithelial mucous cells and/or mucous glands. These cysts most likely arise from ectopic urethral mucosa sequestered in the penile skin during embryologic development.


Early carcinoma of the prostate: comparison of stages A and B. Stage A--occult, latent, preoperatively undiagnosed, incidentally found, stage I or T0--carcinoma of the prostate has been considered to be an earlier stage than stage B--II, T1 or T2, palpable nodule. In a comparative study of 118 patients with stage A lesions and 115 patients with stage B lesions we have found more focal lesions in A than in B. The A lesions were also less highly malignant than the B. However, the survival of patients with A lesions was a little less than those with B lesions. Age differences and more extensive growth before a detection may account for the differences. Patients with diffuse lesions and those with the more highly malignant lesions had a shorter survival than those with focal lesions and with a lower grade of malignancy in stages A and B. All available preoperative diagnostic data and a through histopathological examination of the surgical specimen are necessary to accurately stage prostatic carcinoma. Other well recognized diagnostic tests, such as the lymphangiogram, acid phosphatase value bone scan and so forth, are also necessary to accurately assess the extent of the disease.


Treatment of advanced carcinoma of the prostate with estramustine phosphate. Estramustine phosphate has been useful in the treatment of advanced carcinoma of the prostate. Objective remissions were obtained with this therapy in 6 of 17 patients (35 per cent). The results presented herein indicate that the clinical response is to a certain extent caused by an estrogen effect, which was clearly demonstrable in a previously untreated patient. A specific cytostatic effect of estramustine phosphate, which is not yet clearly explained, may be responsible for remissions in some patients who have become resistant to conventional hormonal treatment.


Extended therapy of stage D carcinoma of the prostate with oral estramustine phosphate. We treated 50 patients with stage D carcinoma of the prostate with 15 mg. per kg. per day oral estramustine phosphate for 3 to 24 months. We are able to evaluate 44 patients. Objective remissions were induced in 8 of the 44 patients (19 per cent) and subjective remission occurred in all objective responders and in 7 additional patients for a subjective response of 15 of 44 (36 per cent). No hematologic or renal toxicity was encountered. Transient nausea occurred early in half of the patients and was dose limiting in 3 patients. One case of hepatic toxicity was seen. Oral estramustine phosphate is well tolerated and long-term therapy is feasible.


Urinary supersaturation with calcium oxalate before and during orthophosphate therapy. The concentrations of sodium, potassium, calcium, magnesium, phosphorus, sulfate, citrate and oxalate in the urine of normal subjects were compared to the concentrations in urine of calcium oxalate stone-forming patients. Because of the large volume excreted by stone-forming patients the urine contained less concentrations of sodium, potassium, magnesium, phosphorus, sulfate and citrate than did the urine from normal subjects. The urinary concentrations of calcium and oxalate were similar in the 2 groups and, thus, the calculated supersaturation of calcium oxalate was greater in the urine of stone-forming patients than in the urine of normal subjects. Orthophosphate therapy increased the urinary concentration of alkali ions and phosphate but reduced urinary calcium concentration, thereby causing a reduction in urine supersaturation with calcium oxalate. There was no discernible correlation between the phosphate-induced changes in urine supersaturation and the presence or absence of continued calculus formation.


Amyloidosis of the lower genitourinary tract. Three patients with amyloidosis of the lower genitourinary tract are described. In the cases of primary localized amyloidosis of the urethra and primary systemic amyloidosis involving the prostate the clinical presentation mimicked cancer of the respective sites. In the case of secondary localized amyloidosis of the seminal vesicles chronic perineal pain suggested seminal vesiculitis.


Carbon dioxide urethral pressure profile. In an evaluation of patients with lower urinary tract symptoms, particularly incontinence, the role played by the urethra is crucial. One of the most important methods of evaluation of urethral dysfunction is the urethral pressure profile. From among the many simple and more sophisticated methods of urethral pressure profile measurements we have chosen to describe a simple office procedure and a reliable method of urethral pressure profile evaluation, using the carbon dioxide cystometer. Slow withdrawal of the special catheter connected to the carbon dioxide cystometer allows the determination of the resistance of the urehtral wall at sequential centimeter levels along the entire length of the urethra. Carbon dioxide urethral pressure profile is a safe office procedure that is easy to perform for immediate recording and interpretation of results. The cystometer is easy to calibrate. We have had no complications in 450 consecutive urethral pressure profile determinations. The shortcoming of the procedure is the compressibility of the gas (carbon dioxide), giving a lag in the register's response to pressure differential. The use of carbon dioxide urethral pressure profile is demonstrated in male incontinence, in female incontinence and in patients with neurogenic bladder dysfunction, and the results are discussed.


Voiding cystourethrography with patient in the standing position. The method for voiding cystourethrography with the patient in the standing position is described. Cystourethrography is much easier to perform when the patient is standing and the results are as good as those obtained with the patient supine.


Surgical correction of vesicoureteral reflux in children with neurogenic bladder. The reported success rate for correction of vesicoureteral reflux in the neurogenic bladder has been low. Reflux was corrected in 33 of 37 ureters in 23 selected children with neurogenic bladder-treated by reimplantation. Selection was based on good bladder capacity, little or no trabeculation and the expectation that the bladder would be useful in future management of the patient. Preoperative preparation and surgical technique are emphasized.


Our experience with the adrenogenital syndrome: a review of 16 cases. An analysis of 16 children with the adrenogenital syndrome illustrates the diversity of the clinical and laboratory features of the disorder. The need for critical periodic evaluation of individual assessment of each child and the dosage of corticosteroids being used is emphasized.


Case report: simple renal cyst in child. A case of a large renal cyst of the right kidney suggesting a nephroblastoma is reported. Preoperative differentiation was diffucult.


Intermittent bladder paresis in the pseudoclaudication syndrome. The pseudoclaudication syndrome, now a well known neurological entity, can simulate intermittent claudication of arterial origin in its clinical appearance. Walking and sometimes simply standing upright for a while can cause transitory pain, numbness or weakness in the legs. The symptoms are caused by entrapment of the cauda equina fibers. Intermittent bladder paresis with total inability of micturition despite urgency to void may sometimes be a prominent feature of the syndrome, a fact that seems to be less well known as seen from a review of the literature.


Neisseria catarrhal urethritis: a case report. A case of Neisseria catarrhal urethritis presenting with a gonorrhea-like discharge is reported. Prior treatment was not a factor in its isolation and the patient responded well to penicillin.


The characteristics of diastolic pressure-volume relationships in primary myocardial disease. Utilizing the pressure-volume relationship, the indices of left ventricular diastolic compliance, SV/EDP-DP, dV/dP, and dV/VdP, ventricular stiffness index, I/P(dV/dP), and myocardial stiffness index, I/S(dD/dS) were evaluated of seven patients with normal left ventricle, eleven patients with hypertrophic and seven with congestive type of primary myocardial disease. Myocardial stiffness index was obtained from the equation of S = aekD, where S is a wall stress, a; a constant, D; a length of short axis, K; a stiffness constant. The mean values and standard errors of the means of SV/EDP DP, dV/dP, dV/VdP, I/P(dV/dP), and I/S(dD/dS) for normal group are 16.7 +/- 8.7 (ml/mmHg), 16.03 +/- 6.98 (ml/mmHg), 0.1259 +/- 0.0447 (mmHg-1), 0.0059 +/- 0.0032 (ml-1) and 0.603 +/- 0.153 (cm-1), for hypertrophic type are 10.5 +/- 5.5 (ml/mmHg), 7.23 +/- 7.42 (ml/mmHg), 0.0599 +/- 0.0736 (mmHg-1), 0.0174 +/- 0.0097 (ml-1) and 1.3555 +/- 0.3395 (cm-1), and for congestive type are 17.5 +/- 3.4 (ml/mmHg), 3.91 +/- 2.13 (ml/mmHg), 0.0250 +/- 0.0239 (mmHg-1), 0.0308 +/- 0.0126 (ml-1), and 3.287 +/- 1.272 (cm-1). There were highly significant differences between normal and primary myocardial disease in each indices except SV/EDP-DP. I/P(dV/dP), and I/S(dD/dS) had highly significant differences between hypertrophic and congestive type, the latter is stiffer than the former. The compliance index was not sensitive enough to separate two types of primary myocardial disease.


Column chromatographic analysis of relationship between hypertension-inducing potency and renin content of kidney extract. The relationship between hypertension-inducing potency and renin content of kidney extract was analyzed in rats using Sephadex G-100, CM-Sephadex C-50, DEAE-Cellulose or Concanavalin A-Sepharose column chromatography. Hypertension-inducing potency of each fraction obtained was evaluated in the basis of the final blood pressure level attained by repeated injections into the test animals for 10 days. Hypertension-inducing potency was found mainly in the renin-contaning fractions. And it seems reasonable to conclude that renin is implicated in the pathogenesis of hypertension produced by kidney extract. However, there were significant discrepancies between hypertension-inducing potency and renin content of subdivided fractions of these renin-containing eluates. Possible explantations for the discrepancies disclosed--including the possibility of the involvement of an unknown substance(s)--have been discussed. In addition, it was suggested from the results of Concanavalin A-Sepharose chromatography that rat renal renin has a glycoprotein nature.


Histochemical studies of monoamine oxidase in experimental myocardial infarctions. Sequential histochemical studies were conducted to determine the level of monoamine oxidase (MAO) activity in the infarcted tissue of the experimental myocardial infarction in dog. MAO activity was not found in the normal heart muscle, but the activities were present in the wall of the coronary artery histochemically. Fibroblasts and collagen fibers began to take the place of the destroyed heart muscles in the infarcted area from 10 days after the coronary occlusion in dogs, and MAO activities were noted sporadically in the fibroblasts and the interstices of the collagen fibers in the infarcted area. MAO activities increased histochemically in the fibroblasts and the fiber interstices in the infarcted area 10 days or more after the coronary occlusion. These findings suggested the presence of the active collagen metabolism outside the myocardial cells in the infarcted area in the recovery stage of the experimental myocardial infarction. It was also suggested that the interstices of the collagen fibers in the myocardial wall constituted the lymphatic ducts outside the blood vessels and that the MAO activity in serum determined by the method in which tryptamine hydrochloride was used as substrate might indicate the grade of fibrosis of the myocardial tissue in the infarcted areas.


Non-invasive assessment of the performance of the right heart during dynamic exercise, a study of left-sided heart disease. A simplified, non-invasive method for assessment of the performance of the right heart during supine leg exercise was described, which necessitated no more than a bicycle "ergometer" for leg exercise, a radiocardiograph for recording cardiac index (CI) and a "water" manometer for measuring cubital venous pressure (VP). Because the use of a cardiac catheter was omitted, right atrial pressure (RA), right ventricular diastolic pressure (RVd) or pulmonary arterial pressure (PA) were not measured. In 11 healthy subjects and 25 patients with primarily left-sided valvular disease and hypertension, the observed shift of CI-VP plot with exercise was similar to the published records of exercise-induced shift of CI-RA plot or CI-RVd plot in normal subjects and the same types of heart disease. With levels of load used in this study, a dividing line separating normal from abnormal elevation of VP during supine leg exercise (deltaVP) could be drawn at deltaVP = 35 mm H2O, because (1) none of the healthy subjects had deltaVP in excess of 35 mm H2O and (2) in these types of heart disease, deltaVP in excess of 35 mm H2O was always associated with a "subnormal" increase in CI (deltaCI less than 0.8 lit. min-1. M-2) with exercise, except in a few cases who appeared, clinically, to be in what may be termed "latent heart failure". Factors probably responsible for an impaired pumping ability of the right heart during exercise in left-sided heart disease were discussed, in relation to deltaVP.


[Therapeutic effect of amoxicillin in the surgical field (author's transl)]. 1. Amoxicillin was used for treatment of 15 cases of infectious diseases in the surgical field and for prevention of 4 cases of postoperative infection, and good result was obtained in all 19 cases. Especially in the latter 4 cases, amoxicillin showed good preventive effect. 2. Any side effect probably due to amoxicillin was observed in no case. 3. Amoxicillin at a daily  dose of 1,000 mg (potency) exhibited sufficient effect in treatment of infectious diseases in the surgical field and in prevention of postoperative infection.


[Clinical study of amoxicillin used for treatment of infections of the lower urinary tracts (author's transl)]. The following results were obtained from treatment of 29 cases of lower urinary tract infections with amoxicillin. 1. Amoxicillin was remarkably effective in 13 cases of acute cystitis, in terms of effect according to dose and bacterial species. 2. The effective rate of amoxicillin in 10 cases of chronic cystitis amounted only to 30% due to complications and resistant bacteria. (The group given 1,500 mg/day was a little higher in the effective rate than the 750 mg/day group.) 3. Amoxicillin was low in effect against infections with Pseudomonas aeruginosa and hardly effective against bacteria resistant to amoxicillin. 4. So far as this study is concerned, amoxicillin produced good clinical results at a half dose of ampicillin, as in the fundamental experiment. 5. Any severe side effect was observed in no case.


[Clinical study of amoxicillin used in the otorhinolaryngological field (author's transl)]. The following results were obtained from oral administration of amoxicillin to 20 cases of acute otorhinolaryngological infections for 5 consecutive days; the daily dose was 1,500 mg for adult and 750mg for child. 1. Six cases with acute tonsillitis, 6 with acute pharyngolaryngitis, 5 with acute otitis media, 2 with furuncle of the nose and 1 with acute laryngitis were treated with amoxicillin. This drug was remarkably effective in 2 of 20 cases in total, effective in 15, slightly effective in 1 and non-effective in 2. 2. The sensitivity test to amoxicillin by the use of ampicillin sensitivity disk revealed that all of isolated bacteria were remarkably sensitive to amoxicillin, except one strain of Staphylococcus aureus which was moderately sensitive. 3. Side effect occurred at the rate of 25%; 4 cases of eruption and 1 of esophagitis. Other severe side effects were not observed. From the above results, amoxicillin is considered to be an effective drug for clinical application in the otorhinolaryngological field.


[Clinical results in treatment of purulent dermatoses with amoxicillin (author's transl)]. The following are the clinical results of amoxicillin used for 21 cases of purulent dermatoses. Amoxicillin was remarkably effective in 5 of total 21 cases, effective in 12, slightly effective in 2 and non-effective in 2; that is, amoxicillin produced good results. One case each of drug eruption and abdominal distention were observed as side effects. Judging from its level in the blood, amoxicillin is expected to exhibit good therapeutical effect at a daily dose of 750 approximately 1,000 mg. Amoxicillin can be considered to be an effective drug for purulent dermatoses without severe side effect.


[Experience with amoxicillin therapy in urological field (author's transl)]. Amoxicillin (AMPC), an oral preparation of broad spectrum synthetic penicillin, was used for treatment of 10 cases with urological infection, and the following results were obtained. 1. AMPC at a daily dose of 750 approximately 1,500 mg was administered for 7 approximately 49 days to 5 cases of acute cystitis, 2 cases of acute epididymitis and one case each of calculous hydronephrosis, chronic prostatitis and postoperative cystitis. As the result, AMPC was found remarkably effective in 2 cases, effective in 7 cases and ineffective in one case; that is, the effective rate was 9/10 (90.0%). 2. Total 8 strains of bacteria, comprising 5 strains of Escherichia coli and one strain each of Klebsiella, Staphylococcus epidermidis and Pseudomonas, were isolated from the urine. These bacteria were relatively responsive to AMPC as well as to ABPC. 3. The side effect possibly due to AMPC was slight gastro-intestinal disorder only in 2 of 10 cases. No other side effect was observed.


[Clinical experience with amoxicillin (Pacetocin 'Kyowa') in urology (author's transl)]. Amoxicillin (Pacetocin 'Kyowa') was orally administered in a daily dose of 1 g (potency) to 5 cases with urological infections and 15 cases with postoperative infections. As a result the drug was found remarkably effective in one case, effective in 15 cases and ineffective in 3 cases; in one case, the response to amoxicillin was uninterpretable. No severe side effect was observed during the treatment.


[Clinical experience with amoxicillin in otorhinolaryngology (author's transl)]. This paper reports the clinical trial of amoxicillin. (1) A daily dose of 750 approximately 1,000 mg of amoxicillin was orally administered for 3 approximately 12 days to 20 patients, 7 of which were with acute suppurative tympanitis, 3 with furuncle of the ear, 2 with furuncle of the nose and 8 with acute amygdalitis. As a result, amoxicillin proved remarkably effective or effective in 17 patients (85.0%). (2) Amoxicillin was effective against: Staphylococcus aureus in 10 of 11 patients (90.9%) Staphylococcus epidermidis in 2 of 2 patients (100%) Streptococcus hemolyticus in 3 of 4 patients (75%) Streptococcus viridans in 1 of 1 patient (100%) Diplococcus pneumoniae in 1 of 1 patient (100%) (3) Although one patient developed drug eruption, there were no side effects that necessitated cessation of administration. From the above results, it is concluded that amoxicillin can be used in the treatment of otorhinolaryngologic infections.


[Blood concentration and urinary excretion in human of OE-7, a gastric hard capsule containing enteric-coated granules. I  (author's transl)]. The investigation of physico-chemical properties and measurement of blood concentration and amount of excretion into urine in human of OE-7 (main constituent is erythromycin stearate) were performed as the fundamental studies. The results obtained were as follows; i) OE-7 is a gastric hard capsule containing enteric coated granules. ii) The contents of OE-7 capsule (granules) were resistant to acid and was favarable in the enteric solubility. iii) In comparison with the conventional erythromycin stearate capsule in healthy adults, OE-7 showed a relatively small individual difference in blood concentration after administration. iv) OE-7 was higher in the mean blood concentration and was superior in the persistence of effective blood concentration compared with the conventional erythromycin stearate capsules.


Effect of taurine on responses to noradrenaline, acetylcholine and ouabain in isolated auricles from digitalized guinea pigs. Responses of the isolated heart from the guinea pig treated chronically with digitoxin until the T wave had disappeared were studied. The development of the abnormal ECG pattern was abolished by a simultaneous injection of taurine and digitoxin. Taurine also inhibited the change by digitoxin of the responses to acetylcholine and ouabain but not to noradrenaline. The causal relationship between the inhibitory effect of taurine and prevention of the development of arrhythmias remains obscure.


Comparison of local anesthetic activities between cis and trans isomers of DL-1-benzoyloxy-2-dimethylamino-1,2,3,4-tetrahydronaphthalene. The local anesthetic activities of cis- and trans- dl-1-benzoyloxy-2-dimethylamino-1,2,3,4-tetrahydronaphthalene were compared using several methods with guinea-pigs. The cis compound (YAU-17) was 2.9 to 6 times as potent as its trans isomer and exceeded procaine, lidocaine and cocaine in potencies of corneal anesthesia, intracutaneous anesthesia and sciatic nerve block. In another experiment on isolated frog sartorius muscle, all of the local anesthetics suppressed the twitch contractions elicited by stimulation of the sciatic nerve. The neuromuscular blocking activity of the cis compound was more pronounced than that of the trans form. Supersensitivity to noradrenaline was produced by both of the stereoisomers in isolated vas deferens of guinea-pigs although there was no difference in the activity. The sensitizing action was also demonstrable with cocaine and lidocaine but not with procaine. When injected intravenously into mice, the cis compound was twice as toxic as its isomer. It is postulated that stereoselectivity is to some extent involved in the mechanisms of action of the local anesthetic agents.


Studies on monoamine oxidase (report XXXIV). Effects of ammonium sulfate on mitochondrial MAO in beef liver. The effects of ammonium sulfate on mitochondrial monoamine oxidase (MAO) in beef liver were studied. The initial stage of the reaction was measured with an oxygen electrode and the long term reaction was measured manometrically. With tyramine or benzylamine as substrate, addition of ammonium sulfate increased the initial reaction but decreased the long term reaction. Ammonium sulfate had similar effects on solubilized MAO. Inhibition of MAO activity in both the initial and long term reaction by excess substrate was diminished by addition of ammonium sulfate. The effects of ammonium sulfate on MAO were reversible. Salts having an -SO4 group, such as Na2SO4 and K2SO4, increased MAO activity in the initial reaction while salts having an -NH4 group, such as NH4Cl and NH4NO3, inhibited it. However, all these salts inhibited MAO activity in the long term reaction. The mechanism of activation of MAO activity by addition of ammonium sulfate is discussed.


Effects of Na+ and other monovalent cations on Ca-efflux from synaptosomes. Effects of monovalent cations on Ca-efflux were examined in rat brain cortex slices, synaptosomes and synaptic plasma membranes. Effluxes of 45Ca from brain slices and synaptosomes were stimulated by Na+ in medium and the effects of Na+ on the 45Ca-effluxes disappeared at low temperature. Furthermore, we observed that Rb+ had more effect than Na+ on 45Ca-efflux from the synaptosomes, while Li+ had less effect. On the other hand, release of 45Ca from the synaptic plasma membranes which had been preincubated with ATP, MG++ and 45Ca was stimulated by Na+ and Li+. But Cs+ and Rb+ were less effective on the release. These results indicate occurrence of Na-dependent Ca-efflux at nerve endings. However, the assumption that ATP-dependent Ca-binding with synaptic plasma membranes may be a partial reaction of Ca-efflux was not supported by these experiments.


Centrally mediated cardiovascular responses to intracisternal injections of sympathomimetic amines in anesthetized rats. The cardiovascular effects resulting from intracisternal (i.c.) injections of sympathomimetic amines were studied in alpha-chloralose-urethanized rats. Norepinephrine (0.5-5 mug i.c.) caused a typical rise in blood pressure with no significant change in heart rate and a fall in blood pressure with a bradycardia, which were completely blocked after treatment with phentolamine (10-50 mug i.c.) L-isoproterenol (0.05-0.5 mug i.c.) and trimetoquinol (0.5-3 mug i.c.), a beta-sympathomimetic agent, usually caused a fall in blood pressure with a tachycardia, which was reduced after treatment with propranolol (10-50 mug i.c.), but trimetoquinol was inclined to cause a rise in blood pressure with a tachycardia. Epinephrine (5 mug i.c.) showed both centrally mediated alpha- and beta-sympathomimetic effects. Tyramine (0.5-1 mg i.c.) caused mixed blood pressure responses presumably due to a release of norepinephrine and epinephrine, and these responses were partially blocked after treatment with phentolamine (100 mug i.c.) or propranolol (50 mug i.c.). These observations suggest that both alpha- and beta-sensitive adrenergic zones may exist on the vasomotor center of the pons and medulla in rats, and both norepinephrine and epinephrine might centrally play a physiological role as the neurotransmitters controlling blood pressure in rats.


Serotonin antagonism in isolated canine cerebral arteries. In helically-cut strips of canine cerebral arteries, the dose-response curve of serotonin was not influenced by 10(-7) M phentolamine but was slightly moved to the right and downward at 10(-6) M. The contractile response to serotonin was unaffected by cocaine (3 X 10(-6)M), atropine (10(-6) M) and propranolol (10(-6) M). The addition of lysergic acid diethylamide (LSD), ergotamine and methysergide caused a dose-dependent contraction. Treatment with LSD (10(-9) and 10(-8) M), ergotamine (10(-10) to 10(-8) M) and methysergide (10(-8) to 10(-6) M) shifted the dose-response curve of serotonin to the right and downward in a dose-dependent manner. The inhibitory effect of methysergide was reversed by washing, while that of ergotamine was not reversed. Apparent pA2 values of LSD, ergotamine and methysergide were 9.17, 9.63 and 7.92, respectively. Contractile responses to 20 mM K+ were not significantly influenced by these blocking agents even in the highest concentrations used. It may be concluded that an alpha-adrenergic mechanism is not involved in the genesis of serotonin-induced contractions and that serotonin acts directly on serotonergic receptors in canine cerebral arteries.


Effects of 5-hydroxytryptamine and morphine on the stomach motility in situ. The effects of 5-hydroxytryptamine and morphine on the stomach motility were determined in in situ experiments. 5-Hydroxytryptamine and morphine inhibited stomach motility of unanaesthetized cats but did produce a slight contraction of the stomach of anaesthetized cats. In unanaesthetized rabbits, 5-hydroxytryptamine caused a contraction, followed by an inhibition of motility, and morphine depressed motility. The 5-hydroxytryptamine-induced contraction is a direct action on smooth muscle and the inhibition of spontaneous movement due to 5-hydroxytryptamine may be, in part, mediated through catecholamine-release and in part, result from paralysis of the receptors for 5-hydroxytryptamine in the cholinergic nerves in the stomach. In anaesthetized rabbits, 5-hydroxytryptamine produced contraction and morphine had no effect. In unanaesthetized guinea pigs, 5-hydroxytryptamine caused a contraction and morphine abolished spontaneous movement of the stomach. In anaestetized guinea-pigs, 5-hydroxytryptamine caused contraction and morphine produced no effect. The 5-hydroxytryptamine-induced contraction of the guinea pig stomach is indirect. From these results it is concluded that the differences in the modes of actions of 5-hydroxytryptamine and morphine on gastric motility are related to differences in species and experimental conditions such as anaesthesia.


"Calcium-induced release of calcium" in rectal smooth muscle of mice. Contractile responses to K, ACh, Ba and exogenous Ca of rectal strips from mice were recorded isotonically. These responses consisted of phasic contraction and subsequent tonic contraction. In Ca-depleted preparations exposed to Ca-free bath medium, the contractions by K and ACh disappeared but the contraction by Ba remained constant. This residual contraction by Ba is presumably due to a direct stimulation of Ba to contractile elements of muscle. Metabolic inhibitors (anoxia and DNP) abolished tonic contraction without affecting phasic contraction by exogenous Ca. In Ca-free bath medium, tonic contraction by exogenous Ca immediately disappeared whereas phasic contraction gradually decreased and about 3 hr later remained constant in parallel with the occurrence of residual contraction by Ba. After pretreatment with the removal of Na from bath medium, which produced Ca-release action, phasic contractions by exogenous Ca in Ca-free bath medium were depressed like those by K, ACh and Ba. These results suggest that the phasic contraction by exogenous Ca is produced mainly by release of Ca and partly by influx of Ca. Thus, it is suggested that the same mechanism of Ca-induced release of Ca from the storage sited as described in skeletal muscle is also operating in rectal smooth muscle of mice.


[The effect of indomethacin on basal and stimulated plasma renin activity in normal subjects (author's transl)]. The influence of indomethacin, a potent inhibitor of prostaglandin synthesis, on basal and stimulated plasma renin activities in normal human subjects was determined. Stimulation of the renin activity was achieved by orthostasis or by furosemide. Indomethacin led to a considerable decrease of both basal and stimulated plasma renin activity in chronic and acute experiments. Our experiments provide no evidence that major changes in the sodium balance are responsible for the effects observed. It is concluded that some antagonistic function of the renin angiotensin system and prostaglandins seems probable. These antagonistic actions might play a role in the regulation of the kidney circulation or the arterial blood pressure.


[The effect of clonidine on renin-release (author's transl)]. In patients with primary hypertension, intravenous administration of 150 mug Clonidin caused a decrease in arterial pressure, renin activity, RPF, GFR and electrolyte excretion. Activation of intracerebral adrenergic alpha-receptors and diminished sympathetic outflow seem to be responsible for the decrease of renin release.


[The treatment of excessive arterial hypertension by a permanent cardiac pacemaker system: a case report concerning the possibility to influence the disturbed harmonization between the heart and the arterial system (author's transl)]. In a 63 year old female patient with a history of longstanding arterial hypertension the implantation of a permanent cardiac pacemaker system resulted in a drastic reduction of the elevated blood pressure values, allowing to reduce the formerly necessary high dosage of antihypertensive drugs. It can be assumed that in the case presented the insertion of the permanent pacemaker leads to several hemodynamic changes: firstly, the heart rate is elevated slightly, secondly, the course of the ejection of the stroke volume is changed and consequently the contour of the pulse wave. Especially the latter factor may have an influence on various regulating mechanisms of the circulatory system and thereby on the lowering of the arterial blood pressure and the consecutive reduction of the hypertrophy of the left ventricle. Most probably the baroreceptor reflex system may be of additional great importance. In addition the "desynchronization" of the spread of excitation by the cardiac pacer might be assumed to change the action of the heart in the beginning of the ejection phase into a "softer" way of pumping. The alteration of a rather "rigid" pump (during normal excitation) into a "soft" pump (during desynchronized excitation) thus may lead to a lowering of the arterial pressure a) by decreasing the speed of ejection of the stroke volume and b) by improving the matching between the heart and the arterial "Windkessel".


[Somatostatin -- a review (author's transl)]. Somatostatin, a peptide isolated from ovine hypothalami, prevents growth hormone secretion in vivo and in vitro. Moreover, somatostatin interferes with the secretion of various other hormones: TSH insulin, glucagon, gastrin, VIP and GIP. Under certain conditions a blunting effect on the secretion of prolactin and ACTH can be demonstrated.


Effects of free fatty acids on electrophysiological properties of ventricular myocardium. Several metabolic factors have been regarded as a cause of ventricular tachyarrhythmias in cardiac ischemia, i.e. hypoxia, acidosis, intracellular potassium loss, local catecholamine release as well as an increased catecholamine concentration and an evaluation of serum free fatty acids. The arrhythmogenic properties of anoxia and hypoxic acidosis, catecholamines as well as potassium depletion are well known. However, the relationship between elevated free fatty acids concentration and the occurrence of ventricular arrhythmias remain obscure. The micro-electrode technique was applied to examine the electrophysiological effects of free fatty acids in papillary heart muscle fibres. Both linoleate and palmitate cause a concentration-dependent decrease of action potential duration and a corresponding shortening of the functional refractory period in the presence of sufficient oxygen supply. The results suggest that a high concentration of free fatty acids may play an additional role in the genesis of ventricular tachyarrhythmias in cardiac ischemia.


[Pulmonary gas exchange after myocardial infarction in the late period of recovery. I. Investigation at rest]. In the late period of recovery after myocardial infarction (13-25 months p. infarctum) lung function of 23 patients was examined at rest. Spirometric values and parameters of pulmonary gas exchange showed alterations caused by pathological left ventricular function. Arterial Po2 was slightly decreased (chi=74.5 +/- 5.9 Torr), AaDo2 (chi=33.6 +/- 7.7 Torr) and aADco2 (chi=8.6 +/- 3.7 Torr) were increased. Pathological changes of arterial Pco2 (chi=40.6 +/- 2.5 Torr) were not observed. Mixed venous Po2 and cardiac output in 9 patients suggested cardiac failure. In a number of pulmonary parameters measured at rest correlations could prove a dependence on the patients physical work capacity.


[Pulmonary gas exchange after myocardial infarction in the late period of recovery. II. Investigations during exercise (author's transl)]. After myocardial infarction in the late period of recovery (13-25 months p. infarctum) pulmonary gas exchange in 23 patients was measured besides as hemodynamic parameters during exercise. The parameters take a course similar to that of subjects without lung and heart diseases. Arterial blood gas tensions (Pa02, Paco2) remain unchanged compared to resting values. Alveolar ventilation did show no difference in any of the patients. Minute ventilation VE, the various dead spaces, alveolar-arterial gas differences (AaDo2, aADco2) and ventilation-perfusion ratios of the whole lung VA/Q suggest however that these parameters show different courses according to the physical capacity of the patients. As the physical capacity of each patient is due to different cardiac functions taken by cardiac output and mixed venous blood gas tensions alterations of pulmonary gas exchange seemed to be dependent on the respective left ventricular function of the heart. Of the twenty-three patients, twelve with cardiac failure under exercise showed the most pronounced alterations in pulmonary gas exchange. Therefore, the different physical work capacity of the patients are determined only by cardiac function. No limitation of the productivity due to impeded lung function could be proved.


[Experimental studies to the teratogen effects of virus-induced fever (author's transl)]. Fever was induced in pregnant rabbits at the 9th day of gestation by injection of a heat inactivated virus which had not lost its pyrogenic activity. The mother rabbits were killed on the 29th day of pregnancy, the fetuses taken out and the uteri examined for resorptions. The fetuses were inspected for organ malformations macroscopically and for skeleten malformations microscopically. The results were compared with those of control animals. The rise of temperature up to a maximum 2,1 degrees C above normal temperature resulted in no higher resorption and malformation rate.


[State of vascular regulation and regional hemodynamics in the crew of "Soiuz-12" and "Soiuz-13" spaceships before and after flight]. Postflight rheographic examinations carried out at rest and during postural tests showed noticeable changes in the vascular regulation and significant blood redistribution. On the recovery day there were no signs of the intracranical venous congestion to weightlessness. The tone of cerebral vessels, however, increased to prevent the development of cerebral venous congestions during the antiorthostatic test. This may be a result of weightlessness adaptation. These cerebral hemodynamic reactions were more pronounced in the crewmembers who made an 8-day flight than in those who made a two-day flight, i. e. in the cosmonauts who returned to Earth after weightlessness adaptation.


[Model of the thermoregulation physiological system]. A mathematical model of the thermoregulation system that allows two steady-state states (the state of rest and autooscillation regimen) has been developed. Certain relationships required for a quantitative description of thermoregulation system are presented.


[Study of the flight work capacity of pilots during simulated motion sickness]. With the aid of a modified procedure of reading instrumental indications of an aircraft the professional performance of pilots was studied during simulated motion sickness. A ball system was developed to assess the results of reading the instrumental indications. After five exposures to double rotation statokinetically stable pilots developed a latent form and statokinetically unstable pilots developed an overt form of motion sickness. The latent form of motion sickness manifested itself in deteriorated professional performance. The overt form of motion sickness was preceded by a decline of professional performance.


[Effect of hyperoxia on indices of external respiration, cardiovascular system and blood gas composition]. In eight healthy male test subjects, aged 19-32, pulmonary ventilation, oxygen consumption, partial pressure of oxygen and carbon dioxide in the alveolar air, arterial and venous blood, ECG, arterial pressure and skin microcirculation were measured during 20 min inhalation of 70% oxygen. In hyperoxic subjects cardiac output remained unaltered, respiration rate decreased, respiration volume increased, alveolar-arterial and arterio-venous difference of PO2 increased, the difference between the actual and expected Q-T slightly decreased, capillary cirulation changed indicating a spactic reaction of peripheral vessels. At the same time oxygen consumption, ventilation equivalent, coefficient of oxygen utilization, partial pressure of carbon dioxide in the alveolar air, arterial and venous blood, heart rate, maximum arterial pressure remained essentially unchanged.


[Possible methods of evaluating the work capacity of ship operators]. By identifying correlation between physiological changes that develop in work and professional errors of ship operators the complex of informative parameters to be used in assaying ther performance has been determined. The complex includes: latent period of a complex sensorimotor response with a choice, critical frequence of fusion of light oscillations, heart rate, tolerance to static force, pulse arterial pressure and index of a two-minute step-test. With the aid of the complex of clinical, physiological and psychophysiological methods it has been shown that indirect indices of performance of operators in long voyages deteriorate two or three weeks earlier than its direct signs. It has been found that the operator's performance can in principle be quantified. It can be done by taking into consideration changes in the informative indices during a specific operation and contribution of each of them to the integrative evaluation of the operator's performance.


[Results of mammalian cell culture exposure on artificial earth satellites]. The paper presents the results of an exposure of cells of the Syrian hamster strain VNK-21 to space flight effects. In contrast to the cell culture kept in a thermostat at 29 degrees C, the cell culture that was maintained in thermally uncontrolled conditions developed noticeable structural and physiological changes induced by suboptimal temperatures. It was concluded that a 6-day exposure to weightlessness exerted no adverse effect on mammalian cells in vitro and produced no stable structural or physiological changes. Some changes that were detected in the cell culture--faster ageing, stable tendency to an increase of the number of cells with enlarged nuclei, an increase of the mitotic index at an early stage of cultivation--need further investigation.


[Study of the rate of acoustic reception of radiotelegraphic signals during the psychological selection of candidates for flight training]. Psychophysiological characteristics and results of training of cadets of pilot schools who had excellent and bad marks in the reception of radiotelegraph signals by ear were examined. The cadets who had excellent marks in that subject also had better marks in the velocity of the skill development, attention parameters and results of flying training. They also showed a higher value of the EEG alpha-rhythm. The procedure of measuring the capacity of candidates to develop a complex sensomotor skill in the reception of radiotelegraph signals by ear may be well used in the psychophysiological selection of pilot-cadets.


[Effect on mitotic activity of prolonged exposure to constant and alternating 1000 oersted magnetic fields]. During a prolonged (15 days) exposure to a constant magnetic field of 1000 oersted two-phasic changes in the mitotic index of the corneal epithelium and bone marrow were noted. The initial decrease of the index was replaced with its recovery and hyperregeneration. The cell count of the tissues varied insignificantly and rapidly returned to normal when the field was switched off. The every day change in the field direction with respect to the body position of the test animals induced no increase in the inhibition of the mitotic activity; however, the effectiveness of adaptive processes declined noticeably. These exposures did not induce chromosome aberrations in the cells of the tested tissues.


[Clinical and physiological studies of flight personnel with 1st stage hypertensive disease]. An examination of the functional state of the cardiovascular system of 30 pilots with hypertension of the I stage showed that the parameters expressing an increase of the blood ejected to the vascular bed were the most informative hemodynamic and polycardiographic values. It was found that the stroke volume, cardiac output, volume velocity of the ejection, power of the left ventricle, energy expenditure per I 1 of cardiac output and time of the isometric contraction phase increased. The interactions of the cardiac output and peripheral resistance made it possible to distinguish hemodynamic modifications of the hypertensive disease: cardiac-increased cardiac output (15 pilots), vascular--increased peripheral resitance (11 pilots) and mixed--simultaneous increase of both parameters (4 pilots). The identification of the modification is important for proper treatment and expertise.


Changes in rat milk quantity and quality due to variations in litter size and high ambient temperature. The effects of variations in suckling stimulus (changes in letter size) and exposure to high ambient temperatures on the quality and quantity of rat's milk and mammary tissue structure were determined. By increasing the number of suckling pups per dam, it was found that the amount of milk produced by the animals was proportionally increased, as each pup was able to drink the same amount of milk per day. With more than 6 pups per litter, the quality of the milk was not significanly changed. Smaller letters led to changes in the amount of milk suckled per milking and to considerable changes in the content of the milk. Exposure to high ambient temperatures, although for only 8 hr per day, drastically affected the amount of milk produced by the lactating rat as well as the quality of the milk produced. Microscopic examination of mammary tissue revealed changes in the alveolar area and height of the alveolar cells as the suckling stimulus varied. After heat exposure the gland changed to one of diminished synthesizing capability. It was concluded that 10-pup litters are the optimal litter size for research concerning rat milk, and the exposure to high ambient temperatures affects the milk yield by directly affecting the alveolae.


Increased fertility in rhesus monkeys by breeding after the preovulatory LH surge. Fertility in a rhesus monkey breeding colony was significantly increased by caging females with males immediately after detection of the preovulatory luteinizing hormone (LH) surge. LH was measured in daily serum samples by a rapid (24-hr) radioimmunoassay which used iodinated ovine LK as tracer and an antiserum to human LH.


[Reactions of granulation tissue fibroblasts in regenerating skin to chronic hypoxia]. An investigation of the effect of chronic hypoxia on fibroblasts of the granulation tissue of a regenerating wound showed that an appreciable portion of fibroblasts degenerated and died. Some of the cells retained their capability to synthesize collagen but its excretion outside the cell was disordered. It also demonstrated an inhibition of fibrillogenesis and thus delayed regeneration of an experimental lesion.


T-strain mycoplasma in the chimpanzee.

T-strain mycoplasma in the chimpanzee. Specimens from 4 chimpanzees were cultured for T-strain mycoplasma and Mycoplasma hominis. T-strain mycoplasmas were recovered from the genital tract and throat of a male and the genital tract of his female cagemate; neither had clinical evidence of infection. Two other male chimpanzees were culturally negative for T-strain mycoplasmas. M hominis was not isolated from any of the animals. The chimpanzee may serve as a suitable experimental model for studying the role of T-strain mycoplasmas in human urethritis and reproductive failure.


Disseminated staphylococcal disease in laboratory rabbits (Oryctolagus cuniculus). The pathologic findings in 13 cases of staphylococcal disease in New Zealand white rabbits were described. Subcutaneous abscesses and embolic pyemic abscesses in kidney, heart, brain, and lung were found. Conjunctivitis, rhinitis, otitis media, and fibrinous pneumonia also occurred. One rabbit had a valvular endocarditis. Staphylococcus aureus, coagulase-positive, and fermenting mannitol were isolated from the lesions described. Staphylococcal disease was diagnosed in 13 of the 171 (7.6%) rabbits necropsied during a 3-yr period. Disseminated staphylococcal lesions were observed only in rabbits during this time.


An autoclavable intensive care isolator for the adult gnotobiotic dog. A lightweight stainless steel isolator which allows 3 investigators simultaneous access to an adult gnotobiotic dog for the purpose of rendering intensive care was designed and constructed. This isolator is 54'' high X 60'' long X 42'' wide. It has an 18'' diam entry port at 1 end and a pair of gloves mounted beneath a window on each of the other 3 sides. The chamber rests on a 12'' high pallet and is moved about the laboratory by a portable hydraulic platform lift. It can be rapidly cleansed with soap and water and sterilized in a large autoclave. Over the past 2 yr. this intensive care isolator has enabled us to perform a variety of manipulations on the adult gnotobiotic dog in a safe, convenient, and efficient manner.


An improved method for repeated plasmapheresis in the rat. An improved method for plasmapheresis in the rat was designed. The rat was anesthetized with ketamine hydrochloride, and venipuncture of the iliac vein was performed with a 21-ga butterfly infusion set with 12'' of flexible tubing. Six ml of blood were drawn into a heparinized syringe and centrifugated. After the plasma was separated, the rbc were reinfused through the phlebotomy apparatus. This procedure was performed on each rat weekly for 10 wk without apparent harm to the animals. There were no changes in total serum protein and albumin, and body weights in most animals remained constant. This method should prove valuable in studies in which long-term plasmapheresis is indicated.


Cellular aspects of rabbit Masugi nephritis. III. Mesangial changes. Lytic disarrangement of mesangial matrix was noted in acute proliferative glomerulonephritis induced in the rabbit by injection of duck nephrotoxic antibody. The severity of the change was variable depending upon dose of the antibody injected. With severe mesangiolysis, mesangial areas were highly obscured by marked hypertrophy and proliferation of mesangial cells along with massive infiltration of monocytes into the loosened mesangium and subendothelial space. In addition, there was random mobilization of the mesangial cells as shown by peripheral interposition and intraluminal projection with capillary subdivision. Glomerular capillaries were thus narrowed and distorted. The ultrastructural hallmark of the proliferated mesangial cells was prominence of the Golgi complex and endoplasmic reticulum which suggested accelerated protein synthesis, most likely for repair of the damaged matrix. In the affected glomeruli, exclusive of those undergoing rapid obliteration due to basement membrane rupture, resolution of the acute inflammatory process occurred within 2 weeks. At this stage, two types of glomerular changes became manifest, consisting of: (1) prominent mesangial stalk thickening and cellularity with occasional peripheral interposition of mesangial cells, and (2) segmental capillary subdivisions due to mesangial bridges built between the original mesangium and peripheral loop. It is suggested that chronic glomerular disease may develop based upon these persistent alterations of the glomerular structure. When a smaller dose of the duck antibody was employed, the process was much less prominent and complete recovery from acute glomerulonephritis took place.


Protein synthesis in liver injury. Soluble factors of protein synthesis in the cytosol from ischemic rat liver. The high speed supernatant (cell sap) obtained from ischemic livers is less efficient than normal in supporting protein synthesis in cell-free systems. Cell saps from ischemic livers contain a reduced amount of transfer-RNA; the transfer of leucine to the specific tRNA is impaired; the incorporation of leucyl-tRNA into protein is reduced, although less than the incorporation of the corresponding amino acid. The binding of aminoacyl-tRNA to ribosomal subunits and exogenous messengers (polyuridylic acid and uridyl-3'-5'-uridyl-3'-5'-guanosine), is less efficient with ischemic than with normal cells sap, thus indicating a defective activity of elongation factor 1. The total amount-and possibly the intracellular distribution-of elongation factor 2 is also altered in ischemic livers. These changes, which are the expression of a multifunctional deficit of ischemic cell sap, are in general correlated with the duration of ischemia and do not seem to appear around the "point of no return" of the ischemic liver cells.


Experimental canine atherosclerosis and its prevention. The dietary induction of severe coronary, cerebral, aortic, and iliac atherosclerosis and its prevention by safflower oil. Severe atherosclerotic lesions were produced without thyroid suppression in seven out of eight dogs by feeding semisynthetic diets containing 5 per cent cholesterol and 16 per cent hydrogenated coconut oil for 12 to 14 months. Occlusive plaques were located in the coronary arteries and major cerebral arteries as well as in the aorta and iliac vessels. The lesions were characterized by an intense sclerotic reaction to areas of lipid deposition and foam cell accumulation in the intima. The diet induced a rapid elevation of plasma-free and esterfied cholesterol, triglyceride, and phospholipid, and the extent of aortic atherosclerosis was shown to be partially dependent on mean plasma cholesterol concentration. A second group of eight dogs were fed a diet identical with the first except for the replacement of 4 per cent hydrogenated coconut oil by 4 per cent safflower oil. Despite receiving the same amounts of dietary cholesterol and fat, this second group of dogs was completely protected from the atherogenic process. Plasma lipids became only slightly elevated and no induced atherosclerotic lesions were found at autopsy. Circulating thyroid hormone concentrations were similar between the two groups of dogs and the thyroid glands had a normal morphology in both groups.


A scanning electron microscopic study of the glycerol model of acute renal failure. Previous studies have implicated both intrarenal vasconstriction and reduced glomerular permeability in the pathogenesis of acute renal failure. Studies were performed to examine further the role of vasconstriction and glomerular structural abnormalities in this syndrome. Six rats (group I) given angiotensin II (180 ng. per 100 gm. per minute) did not develop acute renal failure (blood urea nitrogen 28.6 mg. per 100 ml. at 24 hours). Twenty-five rats (group II), allowed free access to water and given glycerol intramuscularly (8 ml. per kg.), developed mild acute renal failure (blood urea nitrogen 41.6 mg. per 100 ml. at 24 hours). Ten nondehydrated rats (group III), given both glycerol and angiotensin II, developed a more severe form of acute renal failure (blood urea nitrogen 120.4 mg. per 100 ml. at 24 hours p less than 0.001); this value was not significantly different from that of 14 rats (group IV) dehydrated 24 hours prior to glycerol administration (blood urea nitrogen 137 mg. per 100 ml. at 24 hours).


Glomerular permeability to proteins. Effects of hemodynamic factors on the distribution of endogenous immunoglobulin G and exogenous catalase in the rat glomerulus. The distribution of endogenous immunoglobulin G (IgG) and exogenous catalase was delineated in the rat glomerulus under normal and abnormal hemodynamic conditions. IgG was identified by an ultrastructural immunoperoxidase technique using antirat IgG Fab fragments conjugated to horseradish peroxidase; catalase was identified by a cytochemical reaction. When superficial glomeruli in anesthetized Munich-Wistar rats were rapidly fixed in situ by dripping glutaraldehyde onto the renal surface, IgG and catalase were largely confined to the glomerular capillary lumen, with only small amounts in the lamina rara interna immediately beneath the endothelial fenestrae, and none deeper in the basement membrane (GBM) or in the urinary space. If cortical tissue was subjected to routine immersion fixation, or if fixation was performed in situ after ligation of the renal artery, IgG and catalase were found throughout the GBM but not in the urinary space. If fixation was performed in situ after ligation of the renal artery and vein (or artery, vein, and ureter), IgG and catalase were found in the GBM and in the urinary space. If blood flow was restored for 10 minutes after 5 minutes of occlusion of the renal artery and vein, the distribution of IgG and catalase returned to that seen during good blood flow, i.e. neither showed significant penetration beyond the endothelial layer. Thus, as was found previously for albumin, glomerular barrier function for IgG and catalase depends upon the maintenance of normal blood flow conditions. We propose that such conditions impose functional restrictions may be mediated by molecular sieving phenomena during normal ultrafiltration across the GBM, perhaps in association with concentration-polarization or charge effects or both. The epithelial slit pores may significantly modulate solute flux across the GBM by controlling the over-all rate of hydrodynamic flow during ultrafiltration.


Transendothelial vesicular transport of protein following compression injury to the spinal cord. Routes of vascular leakage resulting in trauma-induced edema have not been clarified. To explore the problem we followed the fate of intravascular horseradish peroxidase (HRP) after compression injury to the thoracic cord (cats). At 90 seconds and 15 minutes, HRP was confined to the gray matter, occupying perivascular spaces, unexpanded extracellular channels, and cytoplasmic compartments of injured cells. Adjoining segments contained similar but lesser deposits. At 4 hours, tracer occupied the expanded extracellular spaces of the lesion's white matter; gray matter deposits were present up to 4 cm. distal. Vessels revealed no evidence of rupture. Open interendothelial junctions were not found. Counts of HRP-labeled vesicles in the endothelium of gray matter capillaries revealed a significant intensification of vesicular activity in the lesion and in adjacent areas up to 9 cm. caudal. Morphologically, labeled vesicles exhibited a wide diversity in shape and size. Typical pinocytotic (700A) and tubular forms measured 400 to 700 A in width; vacuolar forms measuring up to 0.7 mum. across were frequently observed. Continuity between the three types was often evident. Where basement membrane and perivascular clefts were not yet inundated with HRP, sites of vesicular emptying of HRP at the tissue front were identified. Serial sections revealed that vesicles may be contiguous from luminal to abluminal surfaces, thus providing facilitated transport pathways. The data suggest that vesicular transport plays a role in the genesis of trauma-induced edema.


Ultrastructure of mouse mononuclear phagocytes in bone marrow colonies grown in vitro. Recently a new method was developed to culture bone marrow cells in a liquid medium on a glass surface. Two kinds of colonies develop in these cultures, namely mononuclear phagocyte and granulocyte colonies. The study of the ultrastructure of the cells in the mononuclear phagocyte colonies was the primary aim of the present study. The architecture of the mononuclear phagocyte colonies appeared to be quite different from that of the granulocyte colonies, since in the latter, the cells lie close together in dense clusters, whereas in mononuclear phagocyte colonies the cells are more loosely dispersed with the highest cell density at the center and stellate orientation of the cells at the periphery. However, both kind of colonies grow entirely separate from each other and mixed colonies are not observed. Electron microscopy showed that there are three types of cell in the mononuclear phagocyte colonies, i.e., monoblasts, promonocytes, and macrophages. The ultrastructure of the promonocytes and macrophages of the colonies is similar to that of the same types of cell isolated directly from the mouse. The monoblast, the most immature cell of mononuclear phagocyte colonies has not been characterized before. The ultrastructure of this cell is clearly distinct from that of the promonocyte in having a round contour without pseudopods, a nuclear to cytoplasmic ratio greater than one, a cytoplasm that contains many polyribosomes, a few small granules, and a small Golgi complex surrounded by a few short strips of rough endoplasmic reticulum.


Heterogeneity in the conformation of different protein fractions from the human erythrocyte membrane. We have isolated 5 families of proteins from human red blood cell membranes and characterized their secondary structure by ultraviolet circular dichroism measurements. The protein families were prepared by selective solubilization from ghosts under nondenaturing conditions. We find that the intact ghost has a mean alpha-helix fraction of 0.37, whereas a low-ionic-strength extract (bands 1, 2, 5, "spectrin") has a substantially higher helix fraction, 0.55. Further extraction of the ghosts with para-chloromercuribenzoate yields bands 2.1, 4.1, 4.2, and 6; their helix content is only 0.17. Finally, the major intrinsic protein, band 3, was solubilized by a non-ionic detergent. Its helix fraction is 0.38.


The exchange of erythrocyte membrane phospholipids with rat liver extracts in vitro. Intact rat or human erythrocytes and their isolated (ghost) membranes were incubated with the high speed supernatant fraction of homogenates derived from 32P-labeled rat livers. Phospholipid molecules were transferred between the red cell membranes and the liver extracts, as reflected by the convergence of their specific radioactivities with time. Whereas ghosts usually approached isotopic equilibrium with the liver supernatant fraction during a few hours of incubation at 37 degrees C, the exchange of phospholipids by intact cells was no more than one-half, even after 18 hr. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and sphingomyelin were all exchanged in both intact cells and ghosts, albeit to different extents. (A control experiment, incubating 32P-labeled rat erythrocytes or ghosts with unlabeled rat liver extracts, also demonstrated the exchange of all four major phospholipids.) These data may signify that the phospholipids on the cytoplasmic side of the membrane of intact erythrocytes do not exchange with the phospholipids in exogenous liver extracts. If so, all four major phospholipid classes would appear to be present to some extent at both membrane surfaces. The first inference is in agreement with several other studies on this membrane, while the second inference is not.


The cytochemical localization of adenylate cyclase activity in mucous and serous cells of the salivary gland. The present study was undertaken to localize adenylate cyclase activity in salivary glands by cytochemical means. For the study, serous parotid glands and mixed sublingual glands of the rat were used. Pieces of the fixed glands were incubated with adenosine triphosphate (ATP) or adenylyl-imidodiphosphate (AMP-PNP) as substrate: inorganic pyrophosphate or PNP liberated upon the action of adenylate cyclase on the substrates is precipitated by lead ions at their sites of production. In both glands, the reaction product was detected along the myoepithelial cell membranes in contact with secretory cells, indicating that a high level of adenylate cyclase activity occurs in association with these cell membranes. The association with a high level of the enzyme activity might be related to the contractile nature of myoepithelial cells which are supposed to aid secretory cells in discharging secretion products. A high level of adenylate cyclase activity was also detected associated with serous secretory cells (acinar cells of the parotid gland and demilune cells of the sublingual gland), but not with mucous secretory cells. In serous cells, deposits of reaction product were localized along the extracellular space of the apical cell membrane bordering the lumen. This is the portion of the cell membrane which fuses with the granule membranes during secretion. Since the granule membranes are not associated with a detectable level of adenylate cyclase activity, it appears that the enzyme activity becomes activated or associated with the granule membranes as they become part of the cell membrane by fusion. The association with a high level of adenylate cyclase activity appears to be related to the ability of the membrane to fuse with other membranes. It is likely, since the luminal membrane of mucous cells which does not fuse with mucous granule membranes during secretion is not associated with a detectable enzyme activity.


Some kinetic and chromatographic properties of detergent-dispersed adenylate cyclase. Studies on the reaction kinetics and chromatographic properties of detergent-dispersed adenylate cyclase are described. Detergent-dispersed enzyme was prepared from whole rat cerebellum and from partially purified plasma membranes from rat liver. Data were simulated to fit kinetic models for which an inhibitor is added in constant proportion to the variable substrate. Models were chosen to distinguish whether the adenylate cyclase reaction may be controlled by an inhibitory action of free ATP--4 (or HATP--3) or by a stimulatory action of free divalent cations. The various kinetic models were then tested with the dispersed brain adenylate cyclase with both Mg++ and Mn++ and in two different buffer systems. The experimental data indicate that this enzyme has a distinct cation binding site, but exhibits no significant inhibition by HATP--3 or ATP--4. The detergent-dispersed adenylate cyclase both from liver plasma membranes and from brain have been chromatographed on anion exchange material and have been subjected to gel filtration. The presence of detergent was required for elution of cyclase activity from DEAE-Sephadex but was not required when DEAE-agarose was used. Dispersed brain cyclase was also chromatographed on agarose-NH(CH2)3NH(CH2)3-NH2 which exhibits both ionic and hydrophobic properties. Fifty percent of the applied activity was recovered with a fivefold increase in specific activity. The data suggest that the relative effectiveness of a given chromatographic procedure for detergent-dispersed adenylate cyclase may reflect the influence of both hydrophobic and ionic factors.


The HLB dependency for detergent solubilization of hormonally sensitive adenylate cyclase. The HLB dependency for the solubilization of membrane proteins and adenylate cyclase activity from a plasma membrane-enriched fraction from rat liver has been determined. The HLB (hydrophilic/lipophilic/balance) number of a detergent is an empirical measure of its relative hydrophobicity. Detergent HLB numbers vary systematically with the length of the ethylene oxide chain for a homologous series of detergents such as the Triton X series. These detergents have a constant hydrophobic moiety, octylphenyl, and a variable polar portion, polyethoxyethanol. Basal-NaF-epinephrine-, and glucagon-stimulated adenylate cyclase activities were solubilized in the HLB range of 16.8-17.4. Solubilization was most effective in 0.01 M Tris buffers at pH 7.5 containing 1-5 mM mercaptoethanol, 1 mM MgCl2, and 0.1% Triton X-305. The detergent to membrane protein ratio used in these studies was 3:1. Criteria for solubilization included lack of sedimentation at 100,000 X g, the absence of particulate material in the supernatant when examined by electron microscopy, and inclusion of hormonally sensitive adenylate cyclase activity in Sephadex G-200 gels. The apparent molecular weight of the solubilized enzyme was approximately 200,000 in the presence of Triton X-305. The solubilized enzyme was stimulated 5-fold by NaF, 7-fold by glucagon, and 20-fold by epinephrine compared to the particulate enzyme used in this study which was stimulated 10-fold, 3.4-fold, and 4-fold by NaF, epinephrine, and glucagon, respectively. The solubilized enzyme is stable for several weeks when stored at -60 degrees C.


Perturbation of the chemotactic tumbling of bacteria. The bacterial sensing system has been studied on three levels. First, a quantitative method has been devised for measuring the "action spectrum" of the bacterium in response to a sudden addition of attractant. Second, a technique has been developed for the rapid isolation of mutants defective in the transmission part of the sensing system. Third, a study of the effects of light on the transmission system reveals two components, one which generates, tumbling and another which inhibits it.


Binding of agonists and antagonists to muscarinic receptors. The binding of one irreversible and two reversible radioactive antagonists to muscarinic receptors in synaptosome preparations of rat cerebral cortex has been studied. The ligands all bind to the same receptor pool and directly and competitively yield self-consistent binding constants closely similar to those obtained by pharmacological methods on intact smooth muscle. The binding process for antagonists seems to be a simple mass action-determined process with a Hill slope of 1.0. The quantitative correlations strongly support the view that the receptor studied by ligand binding corresponds to the receptor studied by pharmacological methods. Inhibition of antagonist binding by most agonists shows a reduced Hill slope which also applies to direct binding studies of [3H] acetylcholine. Mechansims that might account for the behavior of agonists are discussed but do not conclusively point to any single mechanism.


Effect ofcholinergic ligands on the lipids of acetylcholine receptor-rich membrane preparations from Torpedo californica. Ion permeation, triggered by ligand-receptor interaction, is associated with the primary events of membrane depolarization at the neuromuscular junction and synaptic connections. To explore the possible sites of ion permeation, the long-lived fluorescent probe pyrene (fluorescence lifetime approximately 400 nsec) has been inserted into the lipid phase of acetylcholine receptor-rich membrane (AcChR-M) preparations from Torpedo californica. The pyrene probe is susceptible to both fluidity and permeability changes in the lipid bilayer. These changes are detected by variations in the rate of decay of the excited singlet state of pyrene after pulsation with a 10-nsec ruby laser flash. Variations of these lifetimes in the membrane preparations alone or in the presence of quenchers show that binding of cholinergic agonists and antagonists, neurotoxins, and local anesthetics to AcChR-M produces varying effects on the properties of the pyrene probe in the lipid phase. It is concluded that binding of cholinergic ligands to the receptor does not significantly alter the fluidity of permeability of the lipids in the bilayer contact with pyrene. On the other hand, local anesthetics do affect these properties.


The regulatory control of beta-receptor dependent adenylate cyclase. The characteristics of the beta-receptor in turkey erythrocyte adenylate cyclase were studied using both kinetics of enzyme activation and direct binding measurement of the beta-agonists and antagonists to the beta-receptor. The regulatory ligands Gpp(NH)p and Ca2+ do not have any direct effect on the beta-receptor, but modulate the enzyme activity through the interaction with specific regulatory sites.


Reconstitution of a purified acetylcholine receptor. Dialysis of the purified acetylcholine receptor from Torpedo californica electroplax with lipids from the same organ results in a vesicular membrane system in which the receptor is embedded in the bilayer and oriented so that most of the neurotoxin-binding sites appear to be on the outer surface. The reconstituted vesicles are chemically excitable by acetylcholine and carbamylcholine, as measured by 22Na+ efflux. The excitability is specifically blocked by the antagonist alpha-bungarotoxin. These results demonstrate that the purified reconstituted receptor system not only can specifically bind neurotransmitter but can also trigger ion translocation. It therefore has the properties necessary to effect postsynaptic depolarization in vivo.


Case report of metastatic carcinoid tumor to the neck. Since their origianl description in 1838 carcinoid tumors have interested physicians. This case represents another unusual presents another unusual presentation of a carcinoid tumor in which the cervical area has rarely been reported. In addition, it demonstrates the elusiveness of the tumor despite exhaustive diagnostic studies.


Thoracic duct cannulation in a patient with lung cancer. Previously the authors demonstrated limited effectiveness of tumor specific active immunotherapy adjunct to radical surgery in patients with lung cancer. In order to improve the therapeutic effectiveness, a patient with inoperable lung carcinoma was treated with a radical surgery, tumor vaccination, and "unblocking procedures" which consisted of splenectomy and throacic duct canulation. In vitro studies demonstrated the evidence of sensitization of the patient against his own tumor, removal of blocking factor by the thoracic duct fistual from the circulation.


Analysis of variance and covariance for colorectal adenocarcinomas in man as a logical prelude to "staging". This study reports initial experience at the Ellis Fischel State Cancer Hospital (EFSCH), Columbia, Missouri, with the analysis of variance and covariance as applied to the ability to predict the lethality associated with colorectal neoplasms as influenced by tumor,host, and treatment variables considered individually and as multivariate clusters. The application of the methods to the clinical setting is based on the fact that each patient has one survival time. However, in the mathematical sense, each patient is composed of many different variables interacting simultaneously in highly complex ways to determine this uniqueness. The feasibility of determining the prognostic score or weight of many variables is illustrated. The combinatory effect of these scores can provide prognostic scores for clusters of variables providing a tool of much greater specificity than is provided by traditional staging systems such as the TNM.


Tritiated thymidine labeling index of benign and malignant human breast epithelium. 38 specimens of benign breast tissue from young women and 92 primary breast carcinomas were evaluated for tritiated thymidine ([3H]TdR) labeling index (TLI) by in vitro pulse labeling. The TLI on nonneoplastic, terminal breast ducts was significantly higher during the latter half than during the first half of the menstrual cycle (P less than 0.001), and a geometric mean TLI of 1.5 during the latter half of the cycle is consistent with approximately 47% turnover of these cells during the menstrual cycle. Ducts of fibroadenomas showed similar menstrual variation TLI. The range of TLI observed in the carcinomas was 0.04-18.6, arithmetic mean 3.7, geometric mean 2.1. The TLI of carcinomas was not significantly correlated with size of the tumor, but tended to be higher in women less than 50 yr old than in women older than 50 yr (P less than 0.05), and in the presence of two or more metastatic axillary lymph nodes than when fewer than two nodes were involved (P less than 0.02).


Metastatic hypernephroma to the head and neck. Hypernephroma is one of the most common visceral adenocarcinomas which metastasize to the head and neck. The metastasis may precede discovery of the primary or follow it. The most common sites of metastatic hypernephroma to the head and neck are the sinonasal tract, skin, cervical lymphatics, and mandible. Three cases of metastatic hypernephroma are presented and one of these is the first documented report of a metastasis to the parotid gland. The other two were found in the sinonasal tract.


Surgical management of congenital cardiovascular anomalies with the use of profound hypothermia and circulatory arrest. Analysis of 180 consecutive cases. An initial series of 180 patients subjected to definitive repair of cardiac malformations during infancy is presented. The operations were performed with profound hypothermia and circulatory stasis. Statistics relating to the entire series of patients are presented and discussed, after which the results among eleven individual groups of patients categorized by type of cardiovascular lesion are analyzed. There was 113 survivors, representing an over-all mortality rate of 37 per cent. The mortality rate was highest among patients severely ill preoperatively and among those with complex malformations. Deaths were also more frequent among infants under 6 months of age and less than 5 kilograms in weight. Analysis shows a steady increase in percentage of patient survival over the years reported from December, 1967, to April, 1975.


Special pacemaker catheter techniques. The transmediastinal placement of sensing electrodes. The clinical utilization of atrial programmed pacemakers is limited by the lead systems available for sensing of atrial activity. The endocardial method of lead placement is burdened by a dislodgement rate of up to 30 per cent. Alternatively, the patient must submit to the risks of a thoracotomy. Thirty-one patients have been treated with a transmediastinally, retrocardially positioned atrial detector electrode. In 20 patients (65 per cent) the detector performed as desired with no postimplant revision. In 11 patients (35 per cent) corrective measures were required primarily to correct lead placement; seven of these were corrected under local anesthesia merely by pulling the catheter. Spontaneous lead dislocation occurred in four patients. Four patients (13 per cent) underwent remediastinoscopy due to cranial displacement of the detector electrode with a resulting decrease in atrial potential to less than 0.5 mV. For technical reasons, the lead placements were performed without the benefit of x-ray illumination, with only an ECG check of the posterior atrial wall, and this may account for the relatively high incidence of revision. Transmediastinal placement of sensing electrodes presents a practicable alternative to methods presently used.


Hemodynamic effects of pacing-induced heart rate augmentation. A study in patients early after mitral and aortic valve operations. Heart rate augmentation induced by atrial and ventricular pacing was carried out in 23 patients early after intracardiac valve operations. The series comprised two groups of patients: 11 with aortic and 12 with mitral valve surgery. A different pattern of hemodynamic responses emerged during heart rate augmentation in each group. Atrial pacing produced, in the aortic group, a significant increase in cardiac output and mean aortic pressure and a reduction in left atrial pressure. The changes in the mitral group were not significant. During ventricular pacing the left atrial pressure rose in both groups. Although there was a decrease in the mean cardiac output in the aortic group and an increase in the mitral group, these changes did not reach statistical significance. A similar distinction between the aortic and mitral groups was observed when comparing the results of atrial and ventricular pacing at the same heart rate. The hemodynamic benefit appeared to be confined to the aortic group. The different pattern of response in each group of patients was probably due to clinical, hemodynamic, and therapeutic factors related to the condition and management of patients with each type of valve surgery.


Late results of valvoplasty for mitral regurgitation due to rupture of chordae of the posterior (mural) cusp. Nine patients with rupture of chordae tendinea of the posterior cusp of the mitral valve are presented. All have been treated by plication of the posterior cusp and atrial wall. The presenting postoperative features have been described: 89 per cent are markedly improved; two patients have normal heart sounds with no murmurs; 6 patients have only a Grade 1 pansystolic apical murmur. The advantages of this procedure compared with mitral valve replacement for the same condition have been presented.


Supravalvular stenotic mitral ring. A new case with surgical correction. In this report, we present a case of supravalvular stenotic mitral ring in a child. The lesion created a picture of severe mitral stenosis and was successfully managed by resection of the ring. No other malformations of the mitral apparatus or left ventricular outlfow tract were found. On analyzing the diagnostic criteria, we concluded that there appears to be only one useful criterion--the angiographic morphology. However, when ther- is an associated ventricular septal defect or findings of Shone's complex, we should suspect supravalvular ring rather than any other form of mitral stenosis.