[The infarction of the right ventricle and the connections with coronary sclerosis and chronic cor pulmonale (author's transl)]. The infarction of the right ventricle as a spatial and temporal mosaic-infarct and the lesions following it were investigated. Its frequency and its connections with the infarction of the left ventricle, coronary sclerosis and hypertrophy of the right ventricle as cor mitrale and cor pulmonale were reported, treated on 11 073 post-mortem examinations of adults separated in males and females. Three groups were divided: 1. isolated lesions of the right ventricle 2. separated lesions--spatially and/or temporally of the right and left ventricle 3. lesions overlapping from the left on the right ventricle. The infarct of the right ventricle respectively cicatrices were observed in 1.2%. The coronary sclerosis was detected in all cases, and specially the hypertrophy of the right ventricle as cor pulmonale or cor mitrale were important for the pathogenesis of right-cardiac infarcts. The pulmonary embolism was more frequent in isolated infarcts of the right ventricle.


[A comparative study of the role of domestic cats and dogs in the epidemiology of toxoplasmosis]. A total of 2643 persons in 5 different regions were examined for toxoplasmosis by the immunofluorescence test and toxoplasmin skin test. The presence in the house of cats and dogs was taken into account. In two of the five regions under study there was revealed an increased incidence of toxoplasmosis in persons keeping cats; this confirmed the role of these animals as a source of toxoplasmosis infection. The absence of such increase in the incidence of the disease in other regions in explained by the character of buildings admitting migration of cats or the presence in the given region of other active sources of infection. Toxoplasmosis incidence in persons who kept or didn't keep dogs displayed no significant difference.


[Rhabdomere adenosine triphosphatase systems of the squid Todarodes sloanei pacificus]. Highly purified fraction of squid photoreceptor membranes exhibits relatively low activity of Na+,K+-ATPase. No correlation was observed between the distribution of rhodopsin and Na+,K+-ATPase activity among photoreceptor membrane subfractions obtained from rhabdomeres. On the basis of these data, it is suggested that Na+,K+-ATPase and rhodopsin are localized in different membrane structures. In most purified fractions of rhabdomeres, the ratio of rhodopsin to total protein amounted up to 45--50%. In Triton X-100 extracts from membrane fractions, significant enrichment in rhodopsin content was observed.


[Ultrastructural localization of Mg++- and Ca++-activated adenosine triphosphatase spinal ganglia of the sheep and goat]. Light and electron microscopic investigations on the Mg++- and Ca++-activated ATPase of sheep and goat dorsal root ganglion have been carried out. Reaction products occur in plasma membranes and interfaces between neurons and sheath cells, between adjacent sheath cells and on the surface of unmyelinated fibers. Cytoplasmic protrusions of ganglion cells and numerous surface increasing invaginations of sheath membranes form close connections between neurons and sheath cells.


Mixed lymphocyte reaction in multiple sclerosis. The mixed lymphocyte reaction (MLR) as measured by the macrophage electrophoretic mobility (MEM) test is markedly reduced between unrelated multiple sclerosis (MS) patients. This is not the case with other neurological diseases (OND). Within an MS family, the MLR between the propositus and members of the family falls into the low (MS type) range or into the normal or OND range. Those members who give the low results are those who have a MEM-LAD test result of about 77 per cent, i.e. halfway between that of normal and MS. There is thus a parallelism between the anomalous response to linoleic acid and an unexpectedly low MLR with known MS lymphocytes. Lymphocytes from apparently normal children who have a high (MS-type) linoleic acid depression result take part in an MLR with MS cells, as if they were themselves true MS cells. Some possible implications these findings may have for the pathogenesis of MS are discussed.


On tubal function in presence of central perforation of drum in chronic otitis media. Clinical methods and preoperative analyses - 132 cases. Opinions differ on the value of preoperative testing of tubal function. The results vary widely, but so far no comparative investigation between different tubal function tests seems to have been published. On 132 ears with central tympanic perforation, 9 of which were traumatic and the remaining following chronic otitis media, tubal function was studied with a closed manometric method and open flow volume method which measures the tubal volume passage. The results of the closed and open techniques agreed in 96%. The open method is more sensitive, but the closed method is easier. 70% of the total material had aspiration capacity, i.e. could neutralise middle ear pressures, which is better than earlier results. Toynbee's test is a good screening test and when positive, it means good tubal function. A close correlation was found between tubal function and the volume of the air cell system as an effect of the systemic mucosal damage.


[Chronic mucosynechial pemphigoid: so-called ocular pemphigus]. The so-called ocular pemphigus is an oculocutaneomucosal disease, the clinical manifestations of which have been recognized for over a century while its recognition as a nosological and histopathological unit is quite recent. The clinical picture in the eye consists essentially of progressive scar contraction which, preceded by a transient bullous phase, leads to symblepharon, entropion and trichiasis. Corneal complications, such as bullous eruption, erosions, proliferation of vasculoconnective tissue, supervene later. The final appearance is that of complete xerosis with total symblepharon producing a typical 'statute eye'. This local process may be accompanied by bullous lesions of the skin and mucous membranes but the general condition of the patient invariably remains good. In the advanced stages of the disease the appearance is described as 'pemphigoid facies'. The nosological place of ocular pemphigus has been a matter of debate. At various times it has been identified with pemphigus vulgaris, dermatitis herpetiformis of Duhring-Brocq, erythema multiforme of Hebra, Stevens-Johnson syndrome, syphilitic dermatitis bullosa and other bullous dermatoses. At present the condition is universally recognized as a clinical entity, referred to as chronic mucosynechial pemphigoid (CMSP). The anatomopathological picture is quite peculiar. The elementary lesion is a sub-epidermic bulla, hence easily distinguished from that of pemphigus vulgaris, which is situated in the Malpighian layer. This difference applies to the lesions of the skin as well as to those of the mucous membranes including the conjuctiva. In the conjunctiva, epithelial changes suggestive of its epidermization were demonstrated. The Malpighian layer shows a high glycogen and DNA content with overall reduction in enzyme activity. The dermis shows infiltration by lymphocytes, histiocytes and plasma cells, and a considerable increase in hyaluronic acid content. There are many areas of dermoepidermal separation with formation of bullae and the basal membrane is often missing. In some cases, in the centre of the bullae, we were able to demonstrate one or more lumps, consisting almost exclusively of hyaluronic acid, probably filtered in from the dermis across the altered basal membrane. Similar changes are met with also in other mucous membranes, that of buccal cavity in particular, even in ostensibly healthy areas. The histological and histochemical findings are sufficiently typical to justify early diagnostic biopsy in all suspected cases. The aetiology of the CMSP still remains debated. Two theories are under consideration at the moment, viral and autoimmune. The main argument in favour of the viral theory is that a cytopathogenic agent can be isolated from the blood of patients with different dermatoses of the pemphigus group, including the CMSP, whose cytotoxic activity can be passed through and potentiated by passage in cell cultures...


A multicentre controlled trial of the effects of different dosage of gold therapy, followed by a maintenance dosage. In a combined clinical trial with gold in patients with rheumatoid arthritis (RA) 95 patients were treated with a high initial dosage of 2,500 mg aurothioglucose in 21 weeks. Afterwards 48 of these patients received a maintenance dosage of gold and 47 patients placebo injections. Another group of 101 patients received 1,000 mg gold in 21 weeks. Finally a maintenance dose of gold was administered to 49 of these patients, to the other 52 patients placebo injections were administered. For the treatment of RA a high dosage of a gold compound offers no advantage over a low dosage. After a high dosage one can expect a significantly higher number of side effects. The development of toxicity does not influence the ultimate results. A second course of gold has hardly any benificial effect. Prolonged administration of gold is usually well-tolerated; whether it has substantial and sustained therapeutic value remains dubious. Progression of radiological abnormalities can be observed at the same moment that signs and other symptoms of the disease show improvement.


Biological roles of rodent anaphylactic IgG1 antibodies. Described and mainly studied in guinea-pigs and mice (Benacerraf, Ovary, Bloch and Franklin, 1963; Fahey, Wunderlich and Mishell, 1964) (but also demonstrated in rats and hamsters, and others), IgG1 immunoglobulins are a fascinating class of antibodies. Long known for their anaphylactic properties, they have now been also studied in our laboratory for their cooperative, protective and immunoregulatory properties. Like other immunoglobulin classes of antibody, their biological activity is exerted through their Fc portion and expressed only after the immunoglobulin has been activated by fixation on corresponding antigen through their Fab portions. My purpose is to present a summary of the work done in our laboratory on the biological role of IgG1 antibodies. This presentation will be divided into 3 parts respectively concerned with their inflammatory properties in specific hypersensitivity reactions such as anaphylaxis and Arthus, their protective action (as a final result) of the antigen-bearing target in the facilitation reaction, and finally the relations (and common denominator) between the two types of properties.


Long-term evaluation of early repolarization syndrome (normal variant RS-T segment elevation). The electrocardiograms of 65 patients with the "early repolarization syndrome" (normal variant of RS-T elevation) were analyzed to delineate the features and evaluate the natural history of this electrocardiographic entity. Maximal follow-up was 26 years. The syndrome was characterized by (1) an upward concave elevation of the RS-T segment with distinct or "embryonic" J waves, slurred downstroke of R waves or distinct J points or both; (2) RS-T segment elevation commonly encountered in the precordial leads and more distinct in these leads; (3) rapid QRS transition in the precordial leads with counterclockwise rotation; and (4) persistence of these characteristics for many years although some intraindividual changes were common. Less commonly found were (5) tall R and T waves in the precordial leads; (6) "labile" or "juvenile" T wave patterns; (7) "pseudo-R" waves; and (8) "isolated T negativity syndrome." These changes commonly simulate pericarditis, myocardial ischemia, left ventricular hypertrophy and right bundle branch block.


Comparative response of right and left ventricles to volume overload. The cardiac volume data of 49 normal children were compared with those of 23 with secundum atrial septal defect and 24 with patent ductus arteriosus. Significantly smaller ventricular end-diastolic volumes were observed in the normal infants than in older children (right ventricle 53.9 versus 75.5 cm3/m2; left ventricle 46.7 versus 63.6 cm3/m2). "Distensibility" of the right ventricle (DRV), left ventricle (DLV) and left atrium increased normally with age. DRV and DLV were similar shortly after birth; thereafter, DRV increased more rapidly than DLV (mean DRV 12.7; mean DLV 7.8 cm3/m2 per mm Hg, P less than 0.001). In both atrial septal defect and patent ductus arteriosus, the ipsilateral (involved) ventricles had increased volume, increased output, normal ejection fraction and increased distensibility. The contralateral (left) ventricle in atrial septal defect was smaller than normal (39.6 versus 49.7 cm3, P less than 0.001), and had a smaller ejection fraction (0.63 versus 0.71, P less than 0.01) and output (3.70 versus 4.57 liters/min per m2, P less than 0.005). In contrast, the contralateral (right) ventricle in patent ductus arteriosus remained normal. Left atrial maximal volume was larger than normal in atrial septal defect (46.6 versus 35.9 cm3/m2, P less than 0.001). The left atrial and left ventricular volumes in patent ductus arteriosus were, respectively, 152 and 142 percent of normal, indicating comparable response to the volume load. The left head changes in atrial septal defect may be related both to a functionally restrictive defect and to the difference in distensibility of the ventricles.


Long-term follow-up of valvulotomy for congenital aortic stenosis. The data were reviewed of 42 patients who had valvulotomy for severe aortic valve stenosis before 1968. All were over age 2 years (mean age 11.3 years). The mean time of follow-up after surgery was 10.6 years (range 6 to 16.3 years). No patient died at operation. Two late deaths were from endocarditis with aortic regurgitation, and one patient with severe arotic regurgitation died suddenly; three patients had valve replacement for aortic regurgitation and one required repeat valvulotomy. Five patients could not be traced. Major symptoms were alleviated in all patients. Left ventricular pressures were obtained in 15 patients before and after operation; the mean gradient averaged 100 mm Hg before and 43 mm Hg after operation. No patient had significant aortic regurgitation before operation. Twelve had moderate to severe regurgitation after operation. The incidence of late valve calcification at a mean time of 10.6 years after operation was small, and restenosis was uncommon. Because moderate or severe incompetence can be produced and stenosis is often incompletely relieved, the operation is palliative, but the low morbidity and mortality rates suggest that it is an effective procedure if stenosis is severe and life-threatening.


Atrial myxoma in a family.

Atrial myxoma in a family. A family is described in which the mother and three of seven children had atrial myxoma. The mother had biatrial myxoma; surgical treatment resulted in massive intraoperative embolization and death. Surgery was sucessful in two sons with left atrial myxoma and systemic arterial embolization. A third son had calcified right atrial myxoma with destruction of the tricuspid valve and episodes of syncope and pulmonary embolism; surgery including valve replacement, was successful. The mother's father and a brother had died suddenly without a definite diagnosis. The family data are consistent with dominant transmission. The possibility of finding affected relatives should be borne in mind when studying patients with atrial myxoma.


Examination of stomach wall Mg2+-Na+-K+-dependent ATPase, ATP, and ADP in pylorus-ligated rats. Stomach wall Mg2+-Na+-K+-dependent ATPase, ATP, and ADP were studied in rats, at 4, 7, 17, and 24 hr after pylorus ligation, in order to relate H+ secretion and ulcer development. It was observed, in both parts of forestomach and corpus + antrum, that the stomach wall Mg2+-Na+-K+-dependent ATPase significantly increased at 4 and 7 hr, while it significantly decreased at 24 hr, after pylorus ligation. Contrary to this, stomach-wall ATP decreased at 4 hr, relatively increased at 7 hr, thereafter significantly decreased in forestomach and corpus + antrum. Ouabain inhibited the H+ secretion, ulcer development, and stomach wall Mg2+-Na+-K+-dependent ATPase activity. The possible causal interrelationships between the examined parameters are studied.


Cytogenetic darkroom magic: now you see them, now you don't. Customary procedures used to determine chromosomal inheritance do not disclose many of the chromosomal polymorphisms known to be present, resulting in uninformative families. The sequential printing of individual chromosomes presented here is a technique that has increased the number of informative families in our studies. This technique has revealed previously unseen heritable chromosome differences and allowed the designation of parental origin.


Plasma vitamin A levels--a diagnostic indicator of hepatitis in an institutionalized mentally retarded population. Based on hepatitis-associated antigen carrier status as a model liver disease, level of vitamin A can be a useful diagnostic indicator in mentally retarded individuals. It was found that vitamin A levels and age were linearly related by the equation A = (B + CD), where A is the plasma vitamin A in mugms per 100 mls of plasma, B is the sex dependent constant of 25.9 for males and 28.4 for females, C is a sex dependent constant of 0.64 for males and 0.77 for females, and D is age in years. Above age 20, D becomes a constant with a value of 20. With this equation, if the observed vitamin A value is less than 79 percent of the predicted value, then liver damage should be suspected. This information presented graphically allows one to predict liver damage by observing the plasma vitamin A levels and then locating the point on the appropriate graph.


The pattern and rates of metabolism of maternal plasma dehydroisoandrosterone sulfate in human pregnancy. The present study was done to map the metabolic pathways and rates of maternal plasma clearance of dehydroisoandrosterone sulfate (MCRDS) in pregnancy. In the present study, maternal plasma dehydroisoandrosterone sulfate (DS) metabolism was largely accounted for by two major pathways not present or not prominent in the nonpregnant woman. The first major pathway was clearance of maternal plasma DS by placental aromatization of DS to form estradiol (E2). This pathway accounted for approximately 35 per cent of the total clearance. The second major pathway of metabolism of maternal plasma DS was by 16 alpha-hydroxylation within the maternal compartment. This pathway accounted for approximately 32 per cent of maternal plasma DS clearance. Two other minor pathways of DS metabolism, that is, loss to the fetus and excretion as unaltered DS into urine, accounted for less than 1 per cent of total metabolism in each instance. The final pathway of DS metabolism was excretion as neutral steroids such as urinary 17-ketosteroids and other undefined losses. By combining the rate of DS clearance  (MCRDS) from maternal plasma via all pathways with that fraction of DS removed uniquely by placental conversion of DS to estradiol (DS leads to E2), the placental clearance of DS leads to E2 (PCDSE2) may be measured. The measurement of PCDSE2 may be expected to reflect uteroplacental perfusion and as such may provide an investigative tool capable of assessing the dynamics of uteroplacental function in a variety of clinical conditions.


Diagnostic laparoscopy: a prognostic aid in the surgical management of infertility. Laparoscopy was utilized as the final step in the infertility investigation of 155 indigent patients. Unnecessary laparotomy was avoided in 72 (46 per cent) of these patients. Depending upon the endoscopic findings, the presence of additional infertility factor(s) either positively or negatively affected prognosis. With the same anesthetic, 83 (54 per cent) of the 155 patients underwent conservative infertility operations. Unless even greater selectivity can be achieved by prior diagnostic laparoscopy, the postoperative term pregnancy rate (11 per cent) does not justify infertility operations in a population prone to pelvic inflammatory disease, particularly in those individuals with other infertility factors.


Endometriosis in the black woman.

Endometriosis in the black woman. Endometriosis has heretofore been considered rare in black women. Laparoscopy in 190 black women, in many of whom pelvic inflammatory disease was previously diagnosed clinically and treated, revealed endometriosis to be present in 21 per cent. The importance of this finding for clinical practice is discussed.


Spring clip sterilization: one-year follow-up of 1,079 cases. This is a report of 1,079 patients who underwent laparoscopic clip sterlization as of March, 1974. A one-year follow-up was obtained on 977 patients, or 90.5 per cent. Complications due to the clip technique appear limited to postoperative cramps for 24 to 48 hours in 26 per cent of patients. No ectopic pregnancies were detected. Pregnancies, when corrected for unsuspected existing pregnancies and surgical and manufacturing errors, occurred in 2 to 6 cases, for a method failure rate of 2 to 6/1,000. This report documents that experienced laparoscopists can perform this practice with local anesthesia, in combination with first-trimester abortion, and in hospital facilities other than an operating room.


Progestational agents and blood coagulation. VII. Thromboembolic and other complications of oral contraceptive therapy in relationship to pretreatment levels of blood coagulation factors: summary report of a ten-year study. During a ten-year period, 348 women were studied for a total of 5,877 patient months in four separate studies relating oral contraceptives to changes in hematologic parameters. Significant increases in certain factors of the blood coagulation and fibrinolysin systems (factors I,II,VII,VIII,IX, and X and plasminogen) were observed in the treated groups. Severe complications developed in four patients. All four had an abnormal blood coagulation profile, suggesting "hypercoagulability" before initiation of therapy. Some of these findings represented the most extreme abnormalities seen in the entire group of patients; some increased further during therapy. One of these patients developed a myocardial infarction before receiving any medication, shortly after the base-line values were obtained. One patient developed retinopathy 19 months after she began therapy, and another developed thrombophlebitis after 27 months of therapy. The fourth patient developed thrombophlebitis 14 days after initiation of contraceptive therapy. All four patients were of the A or AB blood group. Previous studies suggested the possiblility of increased propensity for thromboembolic episodes in patients possessing the A antigen. It appears from these data that hematologic work-ups may be useful in women who are about to start long-term oral contraceptive therapy.


Membranoproliferative glomerulonephritis. Localization of early components of complement in glomerular deposits. A body of evidence suggests that in membranoproliferative glomerulonephritis (MPGN), complement is activated by the alternate pathway. Therefore, deposition of early components of complement should not be expected in glomeruli. The renal tissues of 16 patients--13 with classic MPGN and 3 with dense deposit disease, a variant of MPGN--were studied by light and electron microscopy and by means of elution and immunofluorescence for the localization of complement (C1q, C4, and C3), immunoglobulins (1gG, IgM, and 1gA), and other serum proteins. Variable amounts of C3, C4 and/or C1q, and IgM were detected in the glomeruli of all patients, whereas IgG and IgA were present, respectively, in 15 of 16 and 6 of 16 patients. Deposits were localized in mesangium and in peripheral capillary loops in a typical lobular distribution. The specificity of each antiserum was verified by immunodiffusion, immunoelectrophoresis, and blocking experiments utilizing unlabeled antibody. Glomerular-bound IgG was eluted with acid citrate buffer, suggesting that IgG might be complexed with antigen(s) in glomerular deposits. By light microscopy, lesions ranged from focal proliferation and lobulation to more severe involvement with typical splitting of glomerular basement membranes, sclerosis, and less frequently, crescent formation. Ultrastructurally, all patients with classic MPGN exhibited mesangial and subendothelial deposits, and in 5 of these patients, subepithelial deposits were demonstrated. With the exception of ultrastructural lesions, patients with the dense deposit variant lacked distinguishable features when compared with those with classic MPGN. The significance of these findings is discussed in relation to a) activation of complement and the possible role of an immune complex mechanism and b) the variability of the morphologic expression.


The Sparks' mandril graft. A seven year follow-up of mandril grafts placed by Charles H. Sparks and his associates. A clinical follow-up study of the Sparks' mandril graft used for lower extremity revascularization between 1968 and 1973 is presented. Of seventy-three mandril grafts placed, sixty were used to revascularize lower extremities in fifty-four patients. Results show 100 per cent patency in the ilioiliac and ilio-femoral sites, 26 per cent patency in the femoropopliteal sites, and 0 per cent patency in the femorotibial and axillofemoral grafts. Complications include poor maturation of the graft, early thrombosis, postoperative hemorrhage, and aneurysm.


Extrathoracic repair of branch occlusions of the aortic arch. Thirty extrathoracic operations in twenty-six patients with occlusive disease involving the primary branches of the aortic arch were reviewed. Spanning a fourteen year experience, these operations included carotid-subclavian artery bypass, retrograde common carotid artery thrombectomy, carotid-carotid artery bypass, and femoral-axillary artery bypass. Dacron bypass grafts were used primarily for reconstruction, but saphenous vein bypass and endarterectomy were also employed. Indications for operation, the presence of concomitant cardiovascular disease, surgical technics, patient survival, and late patency of the reconstructions were reviewed. One patient died postoperatively (3.85 per cent). All Dacron grafts were patent on late follow-up examinations. Low mortality and excellent late functional results make extrathoracic repair the approach of choice in the management of occlusive disease of the branches of the aortic arch.


Immunological responses in identical twins with renal transplants from a common donor. Two identical twins suffering from end stage renal failure due to chronic pyelonephritis received cadaver renal allografts from one donor. Immune status was measured in both by in vitro responses to vegetable mitogens and by reactivity in mixed lymphocyte culture with a random volunteer. Both patients underwent rejection episodes at different times; these were of differing severity. Reactivity to PHA and in MLC was minimal during rejection and increased following recovery in spite of continued high levels of immunosuppression. In contrast, reactivity to pokeweed mitogen and concanavalin A increased at the time of rejection and fell with recovery. The changes seen in the twins, while qualitatively similar, differed in magnitude and timing. It is concluded that environmental factors as well as histocompatibility play a part in influencing immune responsiveness, and that studies of immune responsiveness should be interpreted with caution in the management of renal allograft recipients.


Use of dacron vascular graft in arterial stenosis following renal allotransplantation. Stenosis of the artery supplying the kidney allograft can produce a decrease in kidney function. A case is presented in which surgical reconstruction necessitated the use of a synthetic graft.


Uterovaginal agenesis.

Uterovaginal agenesis. Experience in the diagnosis and treatment of certain developmental anomalies of the reproductive tract is described, with particular reference to uterovaginal agenesis and the operation of vulvavaginaplasty.


[Transduction transmission of the extrachromosomal markers of antibiotic resistance in staphylococcal populations]. Transduction of extrachromosomal markers of resistance to penicillin and erythromycin in staphylococcal strains isolated from patients was studied. Two transduction methods were compared, i. e. transduction with a phage filtrate of the donor culture resistant to erythromycin and transduction on mixed cultivation of the donor and recipient. A higher transduction rate was observed with the latter method. Mixed cultivation of the donor cultures resistant to penicillin or erythromycin and the recipient strains of the wild type sensitive to these antibiotic resulted in transduction of the respective markers. Transductants which acquired prophage 6 simultaneously with marker Egg became donors of erythromycin resistance.


Assay of topical corticosteroids. Efficacy of suppression of experimental Rhus dermatitis in humans. Rhus dermatitis, experimentally induced in humans, was used as a model for determining the efficacy of various proprietary topical steroids. One-centimeter squares of vesicular dermatitis were induced by patch application of Rhus oleoresin. The steroids were then applied without occlusion once daily for four days, with readings of the therapeutic effect taken on the fifth day. Only potent steroids provided unequivocal suppression in this severe test. The rank order of efficacy corresponded to clinical experience. Cream and ointment formulations of the same steroid at the same strength did not differ. High strength preparations were more effective than regular strengths. Relief of pruritus was an important early effect of efficaceous steroids.


Acne in retarded boy with autosomal chromosomal abnormality. The frequency of acne appears to be increased in boys and men of the XYY genotype. This report describes severe acne in a retarded man in whom chromosomal analysis with differential banding suggested duplication of the distal portion of the long arm of a number 13 chromosome, a partial trisomy 13. In addition to retardation and seizures, his malformations, which included narrowed temples, ear anomalies, hexadactyly, and hernias, were consistent with those reported previously in patients with partial trisomy for the distal segment of chromosome 13. This patient and one recently reported retarded boy with chronic acne and trisomy 8 mosaicism suggest that the association of acne and chromosomal abnormality may not be limited to Y chromosome excess.


Cardiopulmonary complications in multicentric reticulohistiocytosis. Report of a case. Multicentric reticulohistiocytosis (MR) is a rare disease. Only recently was its systemic nature appreciated. It affects the skin, mucous membranes, joints, muscles, tendon sheaths, synovial membranes, bones, liver, kidney, lymph nodes, heart, and lungs. Our patient, a 50-year-old woman, had life-threatening cardiopulmonary complications of MR. The connection between the skin lesions, the arthritis, and the pathologic changes in the heart and lungs is still obscure.


Fulminant diphtheritic mitral valve endocarditis. Fulminant endocarditis affecting the mitral valve in an 11-year-old boy was caused by a nontoxogenic strain of Corynebacterium diphtheriae.


Search for antigen in rheumatoid synovial macrophages. Peripheral blood monocytes and synovial macrophages obtained from 21 patients with rheumatoid arthritis and from 13 controls were cultured with autologous peripheral blood lymphocytes and stimulation measured by thymidine uptake. Rheumatoid macrophages and monocytes induced a small but significant degree of lymphocyte transformation, and those from the controls did not. The degree of stimulation appears to be more consistent with the nonspecific effect of lymphocyte activating factor, rather than with the presence of a specific synovial antigen.


The sutureless aortic valve prosthesis: experience with and technical considerations for replacement of the early model. Reoperation was performed in seven (16%) of 43 patients with early models of Magovern sutureless aortic valve prostheses, because of thromboembolism and ball variance. All patients survived reoperation with no major complications. Removal of the sutureless prosthesis was not difficult when an insertion tool of proper size was used. A scarred annulus remained which was favorable for the suturing of a new prosthesis. The incidence of disabling thromboembolism (42%) and poppet failure (21%) is high with these early models. When these complications occur, replacement of the prosthesis is recommended to prevent death or recurrent embolic episodes.


[The effect of oxyfedrine, prenylamine and dipyridamole on heart hypertrophy and collagen concentration of pressure loaded rat hearts]. Rats were subjected to constriction of the abdominal aorta and two days later to nephrectomy. The maximum left ventricular hypertrophy was reached on the seventh day following the nephrectomy. During one month the animals were treated, six days per week with i.p. dipyridamole, prenylamine or oxyphedrine. The drugs studied suppressed the increase in hydroxyproline concentration of the left ventricle whereas the development of heart hypertrophy was not influenced.


Studies on calcium transport system in cardiac sarcoplasmic vesicles and its inhibition by dl-propranolol. Fragmented sarcoplasmic reticulum was prepared from the rabbit heart. The function of vesicles was characterized by the activities of Mg++ and ATP-dependent 'Calcium-Binding' and Ca-ATPase. A fluorescence probe, 1-anilino-8-naphthalene sulfonate (ANS) was employed to examine the physicochemical changes in vesicular membranes. Chlorpromazine, dl-propranolol and lidocaine inhibited Calcium-Binding activity and increased ANS-fluorescence. There was a good correlation between the changes in two parameters. The potency of three drugs on both parameters decreased in the above-mentioned order. These drugs, however, induced no change in the ANS-fluorescence associated by serum albumin or lecithin. The drugs would act presumably at lipid-protein interfaces in vesicles to increase ANS-fluorescence. Both Ca-ATPase and Basic-ATPase were inhibited by dl-propranolol. These results suggest that the inhibitory action of dl-propranolol on the calcium transport system is ascribable to direct physicochemical effects on vesicular membranes.


Analgesic and anti-inflammatory activity of 6-chloro-alpha-methyl-carbazole-2-acetic acid (C-5720). The carbazole, C-5720, has the same order of analgesic, antipyretic and anti-inflammatory activity as indomethacin and is more potent than phenylbutazone and acetylsalicylic acid in the yeast inflamed paw, the carrageenin foot edema, the Mycobacterium butyricum-induced pyrexia, and the acute and chronic adjuvant arthritis tests. In chronic adjuvant arthritis in rats, C-5720 lowers the elevated serum mucopolysaccharide and plasma fibrinogen levels, and partially restores the depressed liver N-demethylase activity. C-5720 is 16 times less active than indomethacin in the production of gastric ulcers in rats and is about 70 times less active than indomethacin in blocking arachidonic acid-induced diarrhea in mice. C-5720 has a greater safety margin than indomethacin with respect to the production of gastric ulcers or the blockade of diarrhea and the reduction of inflammation in adjuvant-induced polyarthritis.


[Relationships between pheochromocytoma and obstructive myocardiopathy. Apropos of a case]. The authors report the case of a 45 year old man who presented with a combination of a phaechromocytoma and obstructive cardiomyopathy. They discuss the possible inter-relationships between hypertension, catecholamines, phaeochromocytoma, and outflow stenosis.


[Surgical correction of ventricular septal defects treated by banding the pulmonary artery. Apropos of 38 cases]. The authors report their experience with two-stage surgical treatment of severe ventricular septal defects in babies: initial banding of the pulmonary artery, followed by closure of the ventricular septal defect and removal of the band by an open-heart technique. Out of 162 operations to band the pulmonary artery, 90 were for cases of ventricular septal defect. The mortality was low (9.1%) when there was a ventricular septal defect with or without a patent ductus. It is considerably higher (31.4%) when there is a coincident coarctation of the aortic isthmus. So far 38 children have had the second operation, with 2 deaths. The authors have studied the surgical problems and the long-term results (6 months to 3 years follow-up) in the first 29 patients undergoing surgery. Although the results from this two-stage operation are good, when the authors take into account their current experience with one-stage closure of ventricular septal defects in the babies, they feel that this latter technique is to be preferred. Reservations must, however, be expressed when the child is very young (Weighing  3.5 kg or less), when there are multiple defects between the ventricles, and when the defect is severe, with a combination of VSD, patent ductus and coarctation of the aorta, and sometimes when the opertion must be carried out as an emergency.


[Problems posed by professional rehabilitation of cardiac patients]. The authors have followed up children with cardiac defects over almost a twenty year period. During the 1960's most of their patients had come of age, and they conclude that despite the enthusiasm of these young people and their potential, they have the greatest difficulties in finding work. This seems regrettable from the human as well as the socio-economic point of view. They propose that the law should be changed as, indeed, should the spirit of the law, so that; a subject with heart disease should no longer be considered as incapable of useful work, and that each person should be assessed according to his potential. They envisage the setting up of medico-administrative cardiological centres. Thus, in addition to the purely medical cardiological consultation, three additional persons would add their expertise: a social worker, an industrial medicine inspector, and an employment officer. These centres could be instituted easily, without making the existing system too unworkable.


Changes of some enzymatic activities in iodoacetate-treated microconidiating cultures of Neurospora crassa. In iodoacetate-treated microconidating cultures of Neurospora crassa, mycelial yield, sucrose consumption and ethanol production are reduced. The specific activity of glyceraldehyde-3-phosphate dehydrogenase is sharply decreased while the specific activities of glucose-6-phosphate dehydrogenase and of 6-phosphogluconate dehydrogenase are stimulated. A polyphenoloxidase is induced in the microconidiating cultures.


Parachlorophenylalanine reversal of tranylcypromine effects in depressed patients. Hospitalized bipolar and unipolar endogenously depressed patients who showed an antidepressant response to the monoamine oxidase (MAO) inhibitor, tranylcypromine sulfate, relapsed (ie, depression returned) when relatively small doses of parachlorophenylalanine (PCPA) were added for brief periods. Considered together with our findings that PCPA similarly reversed the antidepressant effects of the tricyclic drug, imipramine hydrochloride, implications are (1) serotonergic mechanisms are likely involved in the antidepressant effects of both the tricyclic drugs and MAO inhibitors in man and (2) this indolamine may also play a role in the endogenous clinical state of depression.


Acute immune complex disease associated with hepatitis. Etiopathogenic and immunopathologic studies of the renal lesion. Immune deposit glomerulonephritis has been associated with hepatitis B antigenemia. Immune complexes of this antigen and its antibody have been implicated in the pathogenesis of the renal disease. A boy had acute immune complex disease with glomerulitis in which cryoprecipitable complexes of HbsAg and its antibody were isolated from serum. HbsAg was concentrated in the cryoprecipitate and localized in a granular pattern along the glomerular basement membrane in association with immunoglobulins. Glomerular fixed antibody was eluted and shown to be directed against HbsAg. The level of antibody activity to HbsAg was higher in the eluate than the serum, suggesting immunopathogenic specificity of the antibody. The study demonstrates that the nephritis was mediated by immune complexes of HbsAg and its antibody, and the presence of immunoglobulin on the kidney did not represent trapping from the circulation.


Pseudo-radiculopathy in subacute trochanteric bursitis of the subgluteus maximus bursa. Seventy patients, averaging 82 years of age, were referred for low back pain and/or a suspected herniated disk. Objective neurological deficits consistent with L5 or S1 root involvement were identified in 5 of the 70 patients. Trochanteric bursitis (TB), often mimicking radiculitis, was diagnosed in 31 patients. Trochanteric bursitis was associated with lumbosacral strain and lumbar osteoarthrosis in 21 of 31 patients and with an S1 disk in 1 of those 31 patients. Degenerative joint disease of the ipsilateral hip was present in 4 of 20 of these patients with TB. Six patients with low back pain had both hip and knee arthritis (including two patients with rheumatoid arthritis). Three patients had degenerative hip disease without low back complaints. The remaining patient had TB associated with left hemiparesis. All patients had limitation of lumbosacral motion. Patients with arthritic hips had apparent shortening of the affected leg of one-half inch or greater. Trochanteric bursitis is a common complication of lumbosacral strain, frequently mimicking radiculopathy. Gait alteration associated with back pain or static traction on gluteal musculature during rest therapy may be predisposing factors. The association of TB with hip disease and/or leg length discrepancies was again confirmed.


[Treatment of serous central chorio-retinopathy using an argon laser]. After a short survey of the symptoms of the serous central retinopathy, the authors describe its treatment by argon laser. Almost all their results have been good in so short a time that they think the best way to manage the disease is to photocoagulate the leakage point as soon as it is discovered. In this manner a long course will be prevented, which disables the patient and is not harmless for the retina.


[Argon laser in the prevention of retinal detachment]. The prevention of retinal detachment by the argon laser photocoagulation of the peripheral degenerations of the retina was unsuccessful in 6 p. 100 of the cases. The proportion of failures is about the same as that of xenon photocoagulation. It is much more important than that of cryocoagulation. In the contrary the results are better in the management of macular holes without detachment.


[The argon laser and diabetic retinopathy]. The authors give their opinion about the treatment of the Diabetic Retinopathy by the argon laser. They made use successively of xenon, then argon laser photocoagulation and they prefer the latter. They present 15 cases of patients treated by photocoagulation and watched during an average period of 4 years. The results are plainly favourable to the photocoagulation.


[Results of 35 keratoplasties following corneal injuries]. We have performed 40 keratoplasties in 35 eyes presenting with corneal wounds. These injuries follow accidents of which the most frequent are:--metallic foreign bodies;--windscreen. The following results have been obtained after these grafts;--49 p. 100 success;--51 p. 100 failure. In fact 51 p. 100 of the eyes did not benefit from a satisfactory functional result despite the fact that the graft remained clear in 63 p. 100. Our failures are due to two principle complications: cataract and its subsequent surgical management in 28 out of 35 cases, and detachment of the retina in 3 out of 35 cases. The remaining failures are related to the usual complications of other keratoplasties. These keratoplasties are special since a contussion of the posterior pole is often associated with the corneal wound. The indications for these grafts cannot wait until an accurate assessment of the state of the posterior segment is possible, and this is why these grafts are special and why there should be reservations on the prediction of the final visual result. Keratoplasty however remains the only hope for visual recovery and in children the only means of preventing the development of definite amblyopia. Nevertheless in children the prognosis remains the most pessmistic (4 failures out of 5 cases in children under 10).


[Myeloid bodies of the retinal pigment epithelium in vertebrates]. After the hypothesis of Porter and Yamada about the photoreceptive role of myeloid bodies of the vertebrate pigment epithelium, we have pointed out the fine ultrastructure of these organelles: they consist of piles of flattened saccules, with a lipidic content, and linked together by an inter-saccular cement. They are not like Golgi bodies: they do not content glycoprotein. They must be discarded from phagosomes, which are membrane-bounded and content acid phosphatase activity. An oxido-reductive activity cannot been demonstrated at their level, similar to that observed on the rod outer segments. Freeze-etching does not show peculair organization on their fracture faces. They represent a special organization of the endoplasmic reticulum which seems to have a function in the metabolism of visual pigments in certain species of animals, the retina of which is avascular.


Isolated islet transplantation in experimental diabetes. Pancreatic islets have been isolated from the exocrine pancreas of inbred rats by the collagenase digestion method. Transplantation of isolated islets into the portal venous system of streptozotocin diabetic recipients resulted in complete abrogation of the diabetic state as measured by non-fasting serum glucose level, 24 h urinary output, rate of weight gain and glucose tolerance test. Transplantation to other sites resulted in less than optimal survival and function of islets. Allogeneic islets, transplanted across weak histocompatibility barriers, can survive and function for prolonged periods of time when transplanted recipients are immunosuppressed with antilymphocyte serum (ALS). Recipients of allogeneic islets, after a period of immunosuppression with ALS, become permanently tolerant to the allografted islets and to subsequent skin grafts from similar allogeneic donors. Allografted islets are able to prevent the occurrence of diabetic renal and ophthalmic changes that occur in control diabetic animals which had not undergone transplantation.


Lichen ruber planus in occupational groups in total populations. Distributed on 66 occupational groups (and 170 individual occupations) the prevalence of lichen ruber planus within the groups was determined by examining nearly every person in the total populations of 39,418 persons in five different areas in Sweden. The prevalence of l.r.p. in the total population was 0.3 per cent for males and 0.1 per cent for females. When l.r.p. prevalences were compared between different occupational groups, disturbing influences from age differences between the groups were eliminated by the standard population method. The indices calculated by aid of computer were used for direct ranking of the occupational groups from those with the highest to those with the lowest prevalences. In 33 of the 66 occupational groups (and in 129 of 170 individual occupations) no l.r.p. was found. In 24 male and 6 female occupational groups an overaverage high prevalence of l.r.p. was found. In two occupational branches, i.e. agriculture and forestry work (male agricultural workers, farmers, gardeners, garden workers and forest workers) and engineering and building metal work (steel-workers, plate-workers, machine and engine repairers, machine and engine mechanics, engineering workers, plumbers, metal workers) an overaverage high prevalence of l.r.p. was found in nearly all occupational groups. The results indicate that l.r.p. is more prevalent in occupational groups, in which the work dirties the skin (with i.e. soil, oil, cement dust), while in occupational groups with "clean work" the disease was less prevalent. However, there were exceptions. 67.7% of the males, 55.5% of the females had their debute lesions on the lower legs; in 21% of the males and 22.2% of the females the l.r.p. lesions debuted on the wrists. These are areas liable to exposure for different chemical substances and trauma.


[Peripheral circulatory disorders and acrocyanosis in arsenic exposed Moselle wine-growers]. Peripheric circulatory disturbances and acrocyanosis in Moselle vinedressers injured by arsenic. During the years 1972--1975 a total number of 100 vine-dressers came for medical treatment because of late injures caused by arsenic intoxication. That is an average of 400 examinations per year 1600 control examinations within four years. These patients belonged to the age-classes 1890--1923, and the average time of exposure to arsenic was 20 years. After years of being exposed to arsenic, and even years after the exposure to it has stopped, there are those so-called late injures caused by arsenic. There are typical arsenic melanisms on the forehad-temple-rim where the hair begins to grow, on the nape of the neck, on the shoulders, chest, arms, and on the back of the hands which pass into precanceroses and carcinomas. The average time until the first late injuries caused by arsenic occur is 26 years. However, there have been latence periods of up to 50 years. This depends mainly on the amount of arsenic absorbed during the time. There are skin alterations which resemble very much an acrodermatitis chronica atrophicans Herxheimer. Histological examinations rather showed the symptoms of an endangiitis obliterans with atrophy of the cutis. These symptoms were found in 60--70% of the 50--60 years old patients, in 80--90% of the 60--70 years old patients, and in 90--95% of the 70--80 years old patients. Simultaneously there are distinct peripheric circulatory disturbances, cyanosis of the lips, dyspnoea, and an emphysema together with typical cardiac insufficiency. Foot and finger pulse are distinctly slower, and the temperature of the skin is remarkably lower. While people grow older the cyanosis gets worse. With a control group of patients who hadn't been exposed to arsenic these symptoms had only been found on 1--2%.


The regulation of phenylalanine hydroxylase in rat tissues in vivo. The maintenance of high plasma phenylalanine concentrations in suckling rats: a model for phenylketonuria. Maximum inhibition of phenylalanine hydroxylase activity in the liver (85%) and in the kidney (50%) of suckling rats required the administration of over 9 mumol of p-chlorophenylalanine/10g body weight. Despite the decrease in the total activity from 184 to 34 units per 10g body weight, the injection of as much as 26 mumol of phenylalanine was required for its concentration in plasma to be still considerably elevated 12h later. In rats injected with p-chlorophenylalanine every 48h and with phenylalanine every 24h from 3 to 18 days of age, the hepatic and renal phenylalanine hydroxylase remained inhibited, whereas the activities of three other hepatic enzymes were unchanged. There was about 20% inhibition of brain and body growth, but no interference with the developmental formation of several cerebral enzymes (four dehydrogenases, hexokinase and glutaminase) was detected. In the course of this prolonged treatment, the phenylalanine concentrations in plasma increased gradually; on day 2 and day 8 (measured 12h after the last injection) they were 800 and 1395 nmol/ml respectively; on day 15, 12 and 18h after the usual injection, the values were 2030 and 1030 respectively as opposed to the 96 nmol in untreated rats. This degree of hyperphenylalaninaemia, persisting for 18h per day throughout a critical period of development, fulfils the primary criterion of a suitable animal model for phenylketonuria.


The regulation of phenylalanine hydroxylase in rat tissues in vivo. Substrate- and cortisol-induced elevations in phenylalanine hydroxylase activity. Injections of phenylalanine increased a 2.5-fold in 9 h the hepatic phenylalanine hydroxylase activity of 6-day-old or adult rats that had been pretreated (24h earlier) with p-chlorophenylalanine; without such pretreatment, phenylalanine did not raise the enzyme concentration. This difference is paralleled by the much greater extent to which the injected phenylalanine accumulated in livers of the pretreated compared with the normal animals. The hormonal induction of hepatic phenylalanine hydroxylase activity obeyed different rules: an injection of cortisol was without effect on adult livers but caused a threefold rise in phenylalanine hydroxylase activity of immature ones, both without and after pretreatment with p-chlorophenylalanine. In the latter instance, the effects of cortisol, and of phenylalanine were additive. Actinomycin inhibited the cortisol- but not the substrate-induced increase of phenylalanine hydroxylase, whereas puromycin inhibited both. The results indicate that substrate and hormone, two potential positive regulators of the amount of the hepatic (but not the renal) phenylalanine hydroxylase, act independently by two different mechanisms. The negative effector, p-chlorophenylalanine, also appears to interact with the synthetic (or degradative) machinery rather than with the existing phenylalanine hydroxylase molecules: 24h were required in vivo for an 85% decrease to ensue, and no inhibition occurred in vitro when incubating the enzyme with p-chlorophenylalanine or with liver extracts from p-chlorophenylalanine-treated rats.


Partial purification of a dicyclohexylcarbodi-imide-sensitive membrane adenosine triphosphatase complex from the obligately anaerobic bacterium Clostridium Pasteurianum. The membrane adenosine triphosphatase complex of vegetatively growing Clostridium pasteurianum, solublized with Triton X-100, has been recovered as a significantly purified particulate preparation that is still sensitive to inhibition by dicyclohexylcarbodiimide and butyricin 7423.


Energy coupling to active transport in anaerobically grown mutants of Escherichia Coli K12. 1. Anaerobic uptake of proline requires either the presence of a coupled Mg2+-stimulated adenosine triphosphatase or anaerobic electron transport. 2. Anaerobic uptake of glutamine does not require anaerobic electron transport even in the absence of a coupled Mg+2-stimulated adenosine triphosphatase. 3. These results support previous suggestions [Berger (1973) Proc. Natl. Acad. Sci. U.S.A. 70, 1514--1518; Berger & Heppel (1974) J. Biol. Chem. 249, 7747-7755; Kobayashi, Kin & Anraku (1974) J. Biochem. (Tokyo) 76, 251-261] that two distinct mechanisms of energy coupling to active transport exist in Escherichia coli in that energization of anaerobic proline uptake requires the 'high-energy membrane state', whereas the energization of anaerobic glutamine uptake does not.


Distribution of membranes, especially of plasma-membrane fragments, during zonal centrifugations of homogenates from glucose-repressed Saccharomyces Cerevisiae. 1. The distributions of several enzymes and other marker components were examined after zonal centrifugations of whole homogenates from glucose-repressed Saccharomyces cerevisiae on sucrose and iso-osmotic Ficoll, and the composition and morphology of the fractions were investigated. 2. After high-speed zonal centrifugation most of the protein, acid and alkaline phosphatases, alkaline pyrophosphatase, adenosine monophosphatase, beta-fructofuranosidase, alpha-mannosidase, NADPH-cytochrome c oxidoreductase and an appreciable amount of phospholipid and sterol were non-sedimentable, i.e. were at densities below 1.09 (g/cm3). Most of the RNA was at p=1.06-1.08 in Ficoll and at p=1.09-1.11 in sucrose. 3. The bulk of the Mg2+-dependent adenosine triphosphatase (Mg-ATPase) was coincident with the main peak of phospholipid and sterol, at median density 1.10, which was also rich in smooth-membrane vesicles. In Ficoll, a minor peak of phospholipid and sterol at p-1.12-1.15 contained a smaller part of the oligomycin-insensitive Mg-ATPase and heavy membrane fragments. In sucrose, several minor peaks of Mg-ATPase were in the mitochondrial density range, and a peak of oligomycin-insensitive Mg-ATPase coincident with a minor peak of phospholipid and sterol at around p-1.25 contained heavy membrane fragments of high carbohydrate content, especially mannose. 4. Further purification of the oligomycin-insensitive Mg-ATPase containing membrane preparations was performed on Urografin gradients. 5. It is argued that the oligomycin-insensitive Mg-ATPase containing membranes are fragments of the plasma membrane, but have different densities because they contain different amounts of glycoprotein particles.


Effect of heart work and insulin on the incorporation of [14C]glucose into hexose phosphates, uridine diphosphate glucose and glycogen in the normal and insulin-deficient perfused rat heart under working and non-working conditions. 1. The specific radioactivities of glucose 1-phosphate, glucose 6-phosphate, fructose 6-phosphate, UDP-glucose and glycogen, derived from [14C]gluocose, were determined in the normal and insulin-deficient (streptozotocin-diabetic and anti-insulin-serum-treated) perfused non-working and working rat heart. 2. The specific radioactivities of all glucose metabolities reached a plateau after about 10 min, except that for glycogen, which increased slightly but steadily over the whole observation period of 30min. 3. The specific radio-activities of fructose 6-phosphate, UDP-glucose and glycogen were slignificantly lower in the streptozotocin-diabetic heart than in the normal heart. 4. Mechanical work in the normal rat heart increased the specific radioactivities of glucose 1-phosphate, UDP-glucose and glycogen, but had little or no effect on those of gluose 6-phosphate and fructose 6-phosphate. 5. In the normal heart insulin strongly increased the specific radioactivities of all gluocse metabolites under all conditions tested. The maximum values achieved in the normal working heart in the presence of insulin were only about 15-20% above those in the normal non-working heart in the presence of insulin for the phosphorylated intermediates and about 40% above for glycogen. 6. In the streptozotocin-diabetic heart, work restored the specific radioactivities of all glucose metabolities to about normal values. 7. In the streptozotocin-diabetic heart insulin strongly increased the specific radioactivities of the direct glycogen precursors glucose 1-phosphate and UDP-glucose; the effect of insulin on glucose 6-phosphate and fructose 6-phosphate was less marked. These results confirm previous findings that the primary metabolic lesion in diabetic heart muscle is a defect of glycogen synthesis. The specific radioactivity of glycogen itself was increased sixfold. 8. Under all conditions tested the specific radioactivity of glucose 1-phosphate was always found to be higher than that of glucose 6-phosphate. This indicated either compartmentation of a small but metabolically very active pool of glucose 6-phosphate, or the existence of a hitherto unknown pathway of metabolism in which glucose 1-phosphate is the primary reaction product. For a number of reasons the authors prefer the first explanation, which could also account for the observation that in the perfused normal working and non-working heart the specific radioactivity of fructose 6-phosphate was always found to be higher than that of glucose 6-phosphate. This difference disappeared or was reversed in the rat hearts rendered insulin-insufficent by either streptozotocin or anti-insulin treatment.


Differences in the degradation of yeast phosphofructokinase by proteinases A and B from yeast. Proteinase A from yeast causes a stepwise degradation of yeast phosphofructokinase, resembling the action of subtilisin on this enzyme. Proteinase B, however, exhibits a limited proteolysis similar to the action of alpha-chymotrypsin.


The relative importance of muscle protein synthesis and breakdown in the regulation of muscle mass. The effects of growth-suppressing and muscle-wasting treatments on muscle protein turnover and amino acid concentrations were determined in vivo. All treatments depressed protein synthesis and some treatments depressed protein breakdown. Only prolonged starvation increased protein breakdown. Muscle protein mass is regulated primarily through alterations in protein synthesis in all except emergency conditions. The increased concentrations of the branched-chain amino acids indicate that they are unlikely to be involved in this regulation.


Phosphorylation state of cytosolic and mitochondrial adenine nucleotides and of pyruvate dehydrogenase in isolated rat liver cells. 1. Cytosolic and mitochondrial ATP and ADP concentrations of liver cells isolated from normal fed, starved and diabetic rats were determined. 2. The cytosolic ATP/ADP ratio was 6,9 and 10 in normal fed, starved and diabetic rats respectively. 3. The mitochondrial ATP/ADP ratio was 2 in normal and diabetic rats and 1.6 in starved rats. 4. Adenosine increased the cytosolic and lowered the mitochondrial ATP/ADP ratio, whereas atractyloside had the opposite effect. 5. Incubation of the hepatocytes with fructose, glycerol or sorbitol led to a fall in the ATP/ADP ratio in both the cytosolic and the mitochondrial compartment. 6. The interrelationship between the mitochondrial ATP/ADP ratio and the phosphorylation state of pyruvate dehydrogenase in intact cells was studied. 7. In hepatocytes isolated from fed rats an inverse correlation between the mitochondrial ATP/ADP ratio and the active form of pyruvate dehydrogenase (pyruvate dehydrogenase a) was demonstrable on loading with fructose, glycerol or sorbitol. 8. No such correlation was obtained with pyruvate or dihydroxyacetone. For pyruvate, this can be explained by inhibition of pyruvate dehydrogenase kinase. 9. Liver cells isolated from fed animals displayed pyruvate dehydrogenase a activity twice that found in vivo. Physiological values were obtained when the hepatocytes were incubated with albumin-oleate, which also yielded the highest mitochondrial ATP/ADP ratio.


Effects of triphenylsulphonium ions on mitochondria. Inhibition of adenosine triphosphatase activity. Triphenylsulphonium ions inhibit mitochondrial oxidative phosphorylation and adenosine triphosphatase activity. The site of action is on the soluble F1 adenosine triphosphatase component. Triphenylsylphonium ions also inhibit electron transfer in the NAD-cytochrome b region of the respiratory chain. In both types of inhibition, triphenylsulphonium ions are effective at low concentrations, half-maximal inhibition being produced by a concentration of about 20-30 muM. These effects resemble the effects of alkylguanidines on mitochondria and are discussed in relation to the effects of alkylguanidines and other lipophilic cations such as ethidium and dibenzyldimethylammonium ions. A modification of the purification procedure for the soluble mitochondrial adenosine triphosphatase [Beechey, Hubbard, Linnett, Mitchell & Munn (1975) Biochem. J. 148, 533-537] IS DESCRIBED, WHICH YIELDS A PREPARATION WITH A HIGHER SPECIFIC ACTIVITY AND SHOWING FEWER BANDS IN GEL ELECTROPHORESIS.


Control of rat mammary-gland pyruvate dehydrogenase by insulin and prolactin. Withdrawal of prolactin or of insulin from the circulation of lactating rats leads, within 3h, to increased inactivation by phosphorylation of mammary-gland pyruvate dehydrogenase. Prolactin may act by priming the tissue to respond directly to normal concentrations of circulating insulin and by this means be responsible for the increased activation of the enzyme during the course of normal lactation.


16Beta-hydroxylation of dehydroepiandrosterone sulphate by homogenates of human foetal liver. The chemical syntheses of the 3-sulphates of 16 alpha-acetoxy-, 16 alpha-hydroxy- and 16 beta-hydroxy-dehydroepiandrosterone as their triethylammonium salts are described preparatory to studies of the metabolism of [7 alpha-3 H]dehydroepiandrosterone sulphate by homogenates of human foetal liver. Five main radioactive products of the incubation were separated by partition chromatography on a Celite column. Two were identified  as 16 alpha-and 16 beta-hydroxydehydroepiandrosterone 3-sulphates by crystallization to constant specific radioactivity before and after solvolysis. The yields of the conversion to the two epimers were 24.4% (16 alpha) and 1.8% (16 beta).


Characterization of calcium-ion-activated adenosine triphosphatase in the plasma membrane of rat mast cells. The properties of a Ca2+ activated adenosine triphosphatase shown to be present in homogenates of purified rat peritoneal mast cells were investigated. The enzyme was activated by Ca2+, Mg2+, and to a lesser extent by Mn2+ and Co2+. Ca2+ alone was necessary for full activity and the further addition of Mg2+ did not have any effect. The chelating agents EGTA (ethanedioxybis(ethylamine)tetra-acetate) and EDTA completely inhibited the reaction. The pH optimum was 7.8. Reduced glutathione, cysteine, dithiothreitol, N-ethylmaleimide, urea, ADP, NaF, increasing ionic strength and Triton X-100 all inhibited the reaction. On subcellular fractionation of mast-cell homogenates by density-gradient centrifugation, the distribution of Ca2+ activated adenosine triphosphatase resembled that of 5'-nucleotidase, but differed from that of the other markers used, suggesting localization in the plasma membrane. Further experiments indicated that the enzyme is present on the external surface of the plasma membrane.


[Inhibition of the exchange of Na+ for K+ and and H+ by triamterene (in epithelia)(author's transl)]. The salivary duct epithelium, which actively transports Na+, K+ and H+/HCO3/- similarly to renal distal tubules, was used as a model tissue to study the mechanism of action of triamterene (Jatropus, Dyrenium) on electrolyte transport. Triamterene was only effective when administered from the luminal side of the duct, not from the interstitial side. 10-4 M triamterene completely blocked Na+-reabsorption. At the same time K+ secretion dropped to half of control, whereas HCO-/3 accumulated in the duct lumen following reduced H+ secretion. These changes in electrolyte transport are caused by an inhibition of Na+-entry by triamterene as suggested by measurements of ion permeability of the cell membrane. Triamterene has no specific effect on the membrane-bound ATPase. Since Na+-entry is functionally coupled with exit of K+ and H+ from cell to lumen, impairment of Na+-entry by triamterene necessarily causes reduction of K+ and H+ secretion into lumen.


Influence of anti-inflammatory agents on rat liver mitochondrial ATPase. Several classes of anti-inflammatory agents including acetyl-salicylic acid, salicylic acid, flufenamic acid, phenyl-butazone, indometacin, oxyphenyl-butazone, and mefenamic acid were found to be inhibitors of rat liver mitochondrial ATPase in both intact and freeze-ruptured mitochondria. The freeze-ruptured mitochondrial ATPase was found to be Mg2+- and ATP-concentration dependent. The standard uncoupler, 2,4-dinitrophenol, not possessing anti-inflammatory activity, activates the enzyme in both preparations. A number of compounds of various structural classes possessing no anti-inflammatory property in vivo were found to have no inhibitory effect on the enzyme. This inhibition of ATPase by anti-inflammatory agents could be used as an in vitro test method for the primary screening of potential anti-inflammatory agents.


Seasonal variations in the susceptibility of the aortic wall to atherosclerosis. Biochemical studies of glycosaminoglycans and collagen of rabbit atherosclerosis. The aortic content of glycosaminoglycans and collagen as well as the uptake of [125 I] albumin were studied in 53 male albino rabbits during hair-shedding and outside the period of hair-shedding to elucidate the previously reported resistance to experimental arteriosclerosis during the shedding period [1]. The concentration of hyaluronic acid was highest during hair shedding, decreasing towards the non-shedding period. The content of dermatan sulphate, chondroitin-4, 6-sulphate and hydroxyproline was lowest during sheeding and highest outside the sheeding period. Accordingly, the incorportation of [35 S] sulphate in chondroitin -4, 6-sulphate and the dermatan plus heparan sulphate fraction was increased outside shedding, consistent with a stimulated synthesis. The concentration of hyaluronic acid was negatively correlated to the uptake of [125I] albumin, and the dermatan sulphate content was positively  correlated to the content of hydroxyproline. The higher concentration of hyaluronic acid during the period of shedding may improve the elastic properties as well as the ability of the aortic wall to absorbe the haemodynamic strain involved in the vascular injury of this type of experimental arteriosclerosis [2]. The decrease in the concentration of hyaluronic acid simultaneously with an increase in the aortic content of collagen as well as of chondroitin-4, 6-sulphate and dermatan sulphate may imply a greater stiffness of the aorta resulting in a higher susceptibility to injury. The relationship between hyaluronic acid and [125 I] albumin is consistent with an importance of hyaluronic acid to the susceptibility of the arterial wall to deposition of macromolecules such as the lipids. Our observations represent an example of endogenous conditioned variations in the aortic content of glycosaminoglycans and hydroxyproline accompanied by a variation in the susceptibility to experimental arteriosclerosis.


The ground substance of the arterial wall. Part 2. Electron-microscopic studies. Electron microscopy of ruthenium red stained bovine aorta before and after chondroitinase digestion demonstrates proteoglycans on and between collagen fibrils. The collagen-associated proteoglycans include a proteoglycan previously purified from this tissue as demonstrated by immunocytochemistry and are extractable with high molar guanidine HC1. In loci rich in proteoglycans such as areas of turbulent flow in calves, more proteoglycan can be demonstrated morphologically, and these molecules also coat elastin.


Sarcoidosis in a child, presenting as an erythroderma with keratotic spines and palmar pits. A case of sarcoidosis with generalized erythroderma, exfoliation and micropapule formation in a 6-year-old boy is presented. Follicular spiny keratoses, resembling those seen in pityriasis rubra pilaris, and palmo-plantar pitting were among the other extraordinary features in this case. The epidermis overlying the widespread sarcoid granulomata showed parakeratosis, lymphocytic infiltration and degeneration of the basal layer.


Study of an inhibiting factor of epidermal proliferation in plucked skin and various tumours of mice. The aim of our research was to investigate, by autoradiographic methods, the presence of an inhibitory factor (IF) in normal skin, in plucked skin and in five experimental skin tumors of the mouse, capable of inhibiting epidermal proliferation. The experimental model used was that of Bullough & Laurence (1960), i.e. a wound in the ear of a mouse. After tritiated thymidine administration the measurement of the labelling index confirmed the existence of an inhibitory substance in normal skin. The plucked skin had no inhibitory effect when it was taken 24 h after plucking, but after 4 days its effect had returned to normal. The skin tumours, whether epithelial or mesenchymal, showed the same inhibitory effect as normal skin whereas a non-cutaneous tumour tested had no inhibitory effect.


Pilo-sebaceous duct physiology. III. Observations on the number and size of pilo-sebaceous ducts in acne vulgaris. We have used surface microscopy to measure the pil-sebaceous duct orifices at different sites in 150 subjects. Our data have shown that there are more pilo-sebaceous units on the face compared to the back and that these exists are smaller on the face. Despite the small exit the sebum excretion rate per gland on the forehead was not significantly different from that on the back. Thus the number of pilo-sebaceous duct units and the pilo-sebaceous canal exit size are possible factors in the localization of acne.


Polycystic ovarian disease.

Polycystic ovarian disease. Sex hormone binding globulin (SHBG) capacity was reduced in 9 of 31 patients with polycystic ovarian (PCO) disease and the mean level in PCO patients was significantly less (p less than 0.001) than normal. Serum testosterone levels were elevated in 21 of 32 PCO patients and the mean level was significantly elevated (p less than 0.001). Serum androstenedione values were raised in 17 of 31 patients and the mean value was also significantly raised (p less than 0.001). Serum dehydroepiandrosterone sulphate (DHAS) concentrations were elevated in only 2 of 14 patients. Urinary 17-oxo and 17-oxogenic steroids were normal in all patients studied. Basal follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were normal but LH release following injection of luteinizing hormone-releasing hormone (LH-RH) was enhanced. A highly significant negative correlation (r=--0.449; p less than 0.01) was found between the logarithm of testosterone and the logarithm of LH levels. Serum prolactin concentrations were elevated in 4 of 21 PCO patients. Thyroid-stimulating hormone (TSH) values were normal. Eighteen of 20 patients ovulated following treatment with clomiphene and nine became pregnant. Five of 12 of patients treated with oestrogen/progesterone preparations noticed an improvement in their hirsutism. It is suggested that the normal cyclical release of LH is inhibited in PCO disease by a negative feedback by androgens to the hypothalamus or the pituitary, and that wedge resection should be reserved for patients in whom other forms of treatment have failed.


Down's syndrome and oral contraceptive usage. We examined the history of oral contraceptive usage in a group of 103 mothers of infants with Down's syndrome and an equal number of matched normal controls. We found no evidence of increased pill use among mothers of the abnormal infants either during the pregnancy or in the year before pregnancy.


The effect of an unsaturated-fat diet on cataract formation in streptozotocin-induced diabetic rats. 1. Cataract formation in streptozotocin-induced diabetes in rats was reduced by approximately 85% when a diet rich in maize oil (300 g/kg diet) (fat diet) was given, thus confirming results of earlier studies. However, the concentration of sorbitol in the lens of diabetic animals remained high, the values for diabetic rats given the standard diet and the fat died being 65 and 40 mumol/g protein respectively. 2. With the standard diet, the fatty acid profile of the triglycerides of the epididymal fat pads was characterized by a greater relative proportion of saturated fatty acids for the diabetic animals compared to that for the normal animals. The fat diet moderated the tendency towards saturation in the diabetic animals. 3. The fat diet had other effects on the diabetic animals; these included a reduced mortality rate, increased body-weight, a decrease in the daily water intake, and in the daily urinary excretion of glucose and urea. 4. In the diabetic animals the fat diet had no effect on the specific activities in the liver of hexokinase (EC 2.7.1.1), glucokinase (EC 2.7.1.2), phosphofructokinase (EC 2.7.1.11) and pyruvate kinase (EC 2.7.1.40). However, the specific activity of glucose-6-phosphatase (EC 3.1.3.9) was reduced, while that of malate dehydrogenase (decarboxylating) (NADP) (EC 1.1.1.40) was increased. The NAD+:NADH ratio, as calculated from liver pyruvate and lactate concentrations, tended to increase. 5. The results suggested that the fat diet moderated the long-term metabolic effects of diabetes.


The relative effects of a low-protein-high-carbohydrate diet on the free amino acid composition of liver and muscle. 1. Free amino acid concentrations in the plasma have been compared with those in liver and quadriceps muscle, in rats fed on diets containing 209 (control) and 31 (low-protein) g protein/kg. The effects of the low-protein diet on diurnal variations in these values were also measured. 2. In the plasma, the total amino acid concentration was significantly lower in animals given the low-protein diet, at all times of day except 12.00 hours. In the liver, and to a lesser extent the muscle, total amino acid concentration was maintained. 3. In the control animals, diurnal variation in the concentrations of both essential and nonessential amino acids was very similar in plasma, liver and muscle. In animals given the low-protein diet, although the same diurnal pattern was maintained for non-essential amino acids, that occurring among the essential amino acids had virtually disappeared 4. In plasma, the mean 24 h concentration of essential amino acids decreased from 2-43 mmol/l in control animals to only 1-29 mmol/l in the low-protein-fed animals. Concentrations in muscle and liver were reduced by a similar proportion (from 8-60 to 5-56 mumol/g and from 8-67 to 5-05 mumol/g respectively). Conversely the concentrations of non-essential amino acids in animals given the low-protein diet were increased in plasma (from 1-53 to 2-00 mmol/l), muscle (from 12-5 to 14-3 mumol/g), and liver (from 16-8 to 20-5 mumol/g), muscle showing the lowest increase. 5. With the exceptions of lysine, threonine, cystine and tyrosine, the concentrations of all other essential amino acids were reduced more in liver than in muscle. The relationship between this and the failure to maintain plasma albumin concentations is discussed.


Enzymatic determination of nonrandom incorporation of 5-bromodeoxyuridine in rat DNA. Secondary cultures of normal rat embryo cells were synchronized by a double thymidine block and pulsed with 10(-7) M 5-[3H]bromodeoxyuridine (BrdUrd) OR 10(-7) M[3H]thymidine during an entire S phase (7.5 h). To examine the pattern of [3H]thymidine, DNA was immediately extracted and purified at the completion of the S phase, CsCl density gradient centrifugation revealed that substitution for thymine by bromouracil was less than 7%. Single-strand specific nucleases obtained from Aspergillus oryzae and Neurospora crassa were allowed to react with native and partially depurinated (24-29%) [3H]BrdUrd-labeled rat DNA samples, and the products were assayed by hydroxylapatite column chromatography. Approximately 4-6% of the native, nondepurinated rat DNA was hydrolyzed by both nucleases. However, 24-28% of the partially depurinated, [3H] thymidine-labeled rat DNA was hydrolyzed by both enzymes as determined by loss of mass as well as radioactivity. Whereas comparable levels of depurinated, [3H]BrdUrd-labeled DNA were physically hydrolyzed by both nucleases, nearly 65% of the radioactivity was not recovered. Native, as well as depurinated, enzyme-treated DNA samples were sequentially and preparatively reassociated into highly repetitive, middle repetitive, and nonrepetitive nucleotide sequence components. The absolute and relative specific activities of each subfraction of native [3H]thymidine-labeled DNA were comparable. [3H]BrdUrd was differentially concentrated in the middle repetitive sequences as compared to other reiteration frequency types. When depurinated, nuclease-treated DNA samples were similarly fractionated, [3H]thymine moieties were uniformly distributed thoughout all sequences. However, a differential loss of [3H]BrdUrd moieties was detected predominantly from the middle repetitive nucleotide fraction. Melting profiles of the renatured DNA samples were characteristic of each respective DNA subfraction regardless of isotopic precursor. These results suggest that [3H]BrdUrd may be differentially incorporated into A + T rich clusters of rat DNA, especially in the moderately repeated chromosomal elements.


Pre-steady-state kinetic evidence for a cyclic interaction of myosin subfragment one with actin during the hydrolysis of adenosine 5'-triphosphate. A single cycle of adenosine 5'-triphosphate (ATP) hydrolysis by a complex of actin and myosin subfragment one (acto-S-1) was studied in a stopped-flow apparatus at low temperature and low ionic strength, using light scattering to monitor the interaction of S-1 with actin and fluorescence to detect the formation of fluorescent intermediates. Our results show that the addition of a stoichiometric concentration of ATP to the acto-S-1 causes a cycle consisting of first, a rapid dissociation of the S-1 from actin by ATP; second, a slower fluorescence change in the S-1 that may be related to the initial phosphate burst; and third, a much slower rate limiting recombination of the S-1 with actin. This latter step equals the acto-S-1 steady-state adenosine 5'-triphosphatase (ATPase) rate at both low and high actin concentrations, and like the steady-state ATPase levels off at a V max of 0.9s-1 at high actin concentration. Therefore, the release of adenosine 5'-diphosphate and inorganic phosphate is not the rate-limiting step in the acto-S-1 ATPase. Rather, a slow first-order step corresponding to the previously postulated transition from the refractory to the nonrefractory state precedes the rebinding of the S-1 to the actin during each cycle of ATP hydrolysis.


Molecular weights and hydrophobicity of the polypeptide chain of sarcoplasmic reticulum calcium(II) adenosine triphosphatase and of its primary tryptic fragments. The polypeptide chain of the Ca2+-stimulated adenosine triphosphatase from sarcoplasmic reticulum has a molecular weight of 119 000+/-6500 on the basis of sedimentation equilibrium measurements in sodium dodecyl sulfate. The two primary fragments obtained by limited proteolysis each have within experimental error the same molecular weight, corresponding to one-half the molecular weight of the whole chain. Both fragments are eqaully resistant to complete denaturation by guanidine hydrochloride, a property characteristic of many intrinsic membrane proteins. This suggests that the native enzyme has two membrane-embedded halves, with an externally accessible link between them.


The structure and stability of trypsin-resistant segments from rabbit tropomyosin. Tropomyosin was found to undergo only limited digestion by trypsin at 0 degrees C and the two segments that accumulated amounted to two-thirds of the original protein. They are referred to as segments A and B. These segments were not resistant to trypsin digestion at 20 degrees C and at the latter temperature no large fragments remained as judged by disc gel electrophoresis. Segments A and B were separated from each other on the basis of solubility differences and were found to have molecular weights of 24600 and 21900 respectively. Each of the segments appeared to retain about 70-75% of the helical conformation as judged by circular dichroism at 20 degrees C. However, the segments did not show any of the inhibitory activity of the parent tropomyosin molecule when mixed with troponin in the Mg2+-actomyosin ATPase system. Amino acid analysis showed that the portion of tropomyosin that was digested by trypsin (EC 3.4.21.4) had a lower content of the helix stabilizing residues Glu and Leu and a higher content of the helix-destabilizing residues Arg and Lys. These differences indicate that the digested portion should be less stable in the helical conformation than the two trypsin-resistant segments. End group determinations along with the results of the amino acid analysis indicated that segment A was probably derived from the central one-third of tropomyosin and segment B from the C-terminal one-third. By the process of elimination the N-terminal third appears to have been more liable region that was digested by trypsin. The segments A and B were shown to differ in their stability to denaturation by guanidine-HCl and elevated temperature. All of these observations indicate that tropomyosin is not a uniform structure and is composed of regions of different stability.


A water-soluble Mg2+-ATPase from erythrocyte membranes. A ouabain-insensitive ATPase activity associated with the water-soluble proteins of the human and bovine erythrocyte membrane is demonstrated by means of activity-staining in polyacrylamide gels. The ATPase activity from both sources had an absolute requirement  for Mg2+, activity becoming easily detectable at 0.2 mM Mg2+. At low Mg2+ concentrations added Ca2+ appeared to decrease the intensity of the ATPase stain. The activity is unaffected by monovalent cations, does not hydrolyse p-nitrophenyl phosphate and is not inhibited by 2 : 4 dinitrophenol. The ATPase has an apparent molecular weight of approximately 100 000 as determined by electrophoresis in acrylamide gels containing dodecyl sulphate.


The effect of phospholipases and proteases on the binding of gamma-aminobutyric acid to junctional complexes of rat cerebellum. A preparation enriched in junctional complexes, as judged by marker enzymes and electron microscopy, was prepared from rat cerebellum. The junctional complexes were incubated with gamma-amino [14C]butyric acid at 25degreesC for 10 min, using [3H]sucrose as a marker for entrapped space, Total binding was determined in the absence of, and non-specific binding in the presence of, and excess of unlabelled gamma-aminobutyric acid. The difference bewteen the two binding values, i.e. the specific binding, was saturable and reversible, and showed positive cooperativity with a Hill number of about 2. The specific binding was inhibited by N-methylbicuculline, picrotoxinine and imidazole-4-acetic acid, but not by curare, strychnine or L-2,4-diaminobutyric acid. The above compounds had little effect on the non-specipic binding, but addition of ethylenediaminetetraacetic acid decreased non-specific binding by 80%. Trypsin, pronase, phospholipase A2 (EC 3.1.1.4), lysolecithin and sodium dodecyl sulfate decreased binding. Phospholipase C (EC 3.1.4.3) increased the specific binding by 260%. Phospholipids competed with gamma-aminobutyric acid for binding, with phosphatidylethanolamine being more potent than phosphatidylcholine. These results lend support for Watkins' hypothesis that phosphatidylethanolamine competes with gamma-aminobutyric acid for binding to the receptor protein.


Mutations in Neurospora crassa which affect multiple amino acid transport systems. Characterization of a double mutant, his-6: hgu-4, which is unable to utilize L-histidyl-glycine as a source of histidine has revealed a new locus on linkage group V. The hgu-4 genotype results in a generalized reduced transport activity for amino acids, with a concomitant increased resistance to amino acid analogs. Transport rates and analog resistance for amino acids by this mutant are compared to the previously reported transport deficient mutants fpr-1, nap and un-3. Transport of L-aspartate as a function of temperature is examined in a variety of transport deficient strains in an attempt to explain the mode of action of mutation which pleiotropically affect several genetically and biochemically distinct amino acid transport systems.


Properties of a bicarbonate-stimulated ATPase from rat uterus. Crude subcellular fractions from rat uterus contain a HCO-3 -stimulated Mg2+ -ATPase with properties analogous to those previously reported for the enzyme in gastric mucosa, pancreas, salivary gland and liver lyosome. Estradiol-17 beta treatment of ovariectomized rats resulted in an increase in uterine mitochondrial (HCO-3 +Mg2+)-ATPase and Mg2+ -ATPase activity. In an early response (105 min) to estradiol-17 beta treatment of ovariectomized rats, the lysosomal enzyme, beta-N-acetylglucosaminidase increased in the nuclear and mitochondrial fractions and decreased in the microsomal and supernatant fractions.


Effects of medium composition and metabolic inhibitors on glycosaminoglycan synthesis in chick embryo cartilage and its stimulation by serum and triiodothyronine. Incorporation of inorganic sulfate into glycosaminoglycans of chick embryo sternum is stimulated by serum and triiodothyronine. Variations in the amino acid content of the medium, and in particular in the concentration of glutamine, changed the incorportion in control and stimulated sterna to the same degree. Omission of Na+ from the medium greatly reduced incorporation in both control and stimulated sterna; incorporation, and its stimulation by triiodothyronine, was restored by raising the concentration of Na+. Ouabain and valinomycin inhibited incorporation more than 90%, and triiodothyronine did not stimulate under these conditions. Puromycin and cycloheximide also inhibited incorporation almost completely, and abolished the stimulation by triiodothyronine and serum. Addition of p-nitrophenyl-beta-xyloside, in the presence of of puromycin ir cycloheximide, restored sulfation to a level of 5-10% of the control value; however, this level of incorporation was not increased by addition of serum or triiodothyronine. Actinomycin D, colchicine and vinblastine inhibited incorporation by 40% or less at the highest concentrations tested; however, these three agents completely abolished the ability of triiodothyronine to stimulate incorporation. Lumicolchicine and cytochalasin B decreased incorporation in controls slightly but did not affect the stimulation by serum or triiodothyronine. The results indicate that thyroid hormones stimulate glycosaminoglycan synthesis only under conditions which support efficient synthesis in control incubations, and suggest that microtubule formation may be essential to the mode of action of thyroid hormones in this system.


Presence of sulfated proteoglycans in prolactin secretory granules isolated from the rat pituitary gland. The composition of the segregated content of rat prolactin granules was investigated taking advantage of the fact that these organelles, isolated as a pure fraction, retain their structural organization after solubilization of their limiting membrane by mild detergent treatment. We found that these membraneless granules contain not only the hormone, but also a number of minor macromolecular components including sulfated glycosaminoglycans, which are labeled when pituitary slices are incubated in vitro with [35S] sulfate. In order to characterize the latter components, the isolated radioactive granules were solubilized (by treatment with either a high ionic strength solution orNaOH) and 35S-labeled acidic glycosaminoglycans precipitated by complexing with cetylpirydinium chloride. A high degree of heterogeneity was observed when the ensuing precipitates were analyzed by cellulose acetate electrophoresis: different components were found to co-migrate with authentic heparin and chondroitin sulfate A and C standards. Another component, which accounts for approx. 50% of the glycosaminoglycan-bound radioactivity, might be heparin sulfate. These acidic glycosaminoglycans are linked to peptide moieties to form proteoglycans.


The mitochondrial ribosomes of Neurospora crassa. II. Comparison of the proteins from Neurospora crassa mitochondrial ribosomes with ribosomal proteins from Neurospora cytoplasm, from rat liver mitochondria and from bacteria. 1. It has been shown by Datema et al. (Datema, R., Agsteribbe, E. and Kroon, A.M. (1974) Biochim. Biophys. Acta 335, 386--395) that Neurospora mitochondria isolated in a Mg2+-containing medium (or after homogenization of the mycelium in this medium and subsequent washing of the mitochondria in EDTA-containing medium) possess 80-S ribosomes; mitochondria homogenized and isolated in EDTA medium yield 73-S ribosomes. The ribosomal proteins of the subunits of 80-S and 73-S ribosomes were compared by two-dimensional electrophoresis. The protein patterns of the large, as well as of the small subunits are very similar but not completely identical; the most conspicuous difference is that the large subunit of 80 S contains about eight more proteins than the large subunit of 73 S. 2. The contamination by Neurospora cytoplasmic 77-S ribosomes in the 80-S preparations, if present, is only minor. 3. Neurospora cytoplasmic ribosomes contain 31 proteins in the large, and 21 proteins in the small subunit. 4. Neurospora 80-  mitochondrial ribosomes contain 39 proteins in the large, and 30 proteins in the small subunit 30 proteins. 5. Rat liver mitochondrial ribosomes contain 40 proteins in the large and at least 30 proteins in the small subunit. About 50% of these proteins has an isoelectric point below pH 8.6. 6. The pattern of Paracoccus denitrificans is very similar to that of other bacterial ribosomes, the large subunit contains 29, the small subunit 18 proteins.


Effect of insulin to decrease glucose transport in dissociated cells from the R3230AC mammary adenocarcinoma of diabetic rats. Dissociated cells of the R3230AC mammary tumor were found to take up glucose by diffusion and by a passive carrier system. Using labeled 3-O-methylglucose as the probe, the following properties of the passive carrier were identified: (1) specificity for glucose, (2) competition by galactose and mannose but not by mannitol and fructose, (3) inhibition by phloretin but not by phloridzin, (4) temperature sensitivity, and (5) a Km for transport of 3-4 mM. The effects of insulin in vitro on carrier-mediated glucose transport were investigated in tumor cells from diabetic rats. At 10-9 M insulin, a time-related decrease in v for transport was observed resulting in an increased calculated Km (2- to 3-fold increase after 60-90 min incubation with insulin); only slight effects on V were obtained. This unusual response in v to insulin was observed when glucose was present in the medium at 2 mM and 5 mM, but not at 20 mM glucose. The effect of insulin to decrease the v was dose-related, with the major effects seen between 10-10M and 10-8M. The apparent decrease in glucose entry in vitro may in part explain the ability of insulin to inhibit growth of this tumor in vivo.


The polypeptide and the phospholipid components of axon plasma membranes. The axon plasma membrane fraction isolated from garfish olfactory nerve was analyzed for its polypeptide composition by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. There were present over 20 well-resolved polypeptide components in this membrane, and eleven of them, with an apparent molecular weight range of 22,000-130,000, accounted for most of the membrane proteins. None of the major polypeptide species present in the membrane appeared to be glycoprotein. Based on electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gel, eight of the major polypeptides found in garfish nerve membrane appeared to be also present in the axon plasma membrane isolated from lobster walking leg nerve. Both garfish and lobster nerve membranes contained high concentration of lipids (66-76%) which were essentially cholesterol and phospholipids. The classes of phospholipids present were phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, phosphatidylinositol and sphingomyelin. Lobster nerve membrane also contained about 3% phosphatidic acid. Assays for acetylcholinesterase in axon plasma membrane fractions isolated from different nerve sources showed a wide variation, ranging from a specific activity of 2.4 for garfish nerve to 312.5 for lobster nerve membrane.


Investigations on the sodium dependence of bile acid fluxes in the isolated perfused rat liver. At [Na+]o = 118 mM the concentrative transfer of cholic and taurocholic acid from the perfusate into the isolated rat liver displays saturation kinetics (taurocholate: V = 299 nmol-min-1-g-1, Km = 61 muM; Cholate: V=327 nmol-min-1-g-1, Km = 436 muM). Perfusion with an isotonic sodium-free medium did not change the feature of a carrier-mediated transport but did markedly reduce V without affecting Km (taurocholate: V = 65 nmol-min-1-g-1, Km = 78 muM; cholate: V = 104 nmol-min-1-g-1, Km = 354 muM). It was experimentally assured that the observed reduction of bile salt uptake was not a consequence of regurgitation of bile salts or due to an excessive intracellular accumulation during cholestasis in the sodium-free state. The rate of taurocholate efflux is very low when compared with the rapid rate of the uptake. A stimulatory action of extracellular sodium on this pathway was also observed. Inhibition of the (Na+ + K+)-ATPase by 1 mM ouabain resulted in a decrease of bile salt uptake. Activation of the enzyme by potassium readmission to a K+-deprived liver enhanced bile salt uptake. The immediate response to alteration of the enzyme activity suggests a close association of a fraction of bile acid active transport with the sodium pump.


Ca2+ activation of membrane-bound (Ca2++Mg2+)-dependent ATPase from human erythrocytes prepared in the presence or absence of Ca2+. The kinetics of Ca2+ activation of membrane-bound (Ca2+ + Mg2+)-dependent ATPase (ATP phosphohydrolase EC 3.6.1.3) from human erythrocytes was studied. The ATPase from membrane prepared in the presence of 0.7-500muM Ca2+ showed positively cooperative behaviour and a Km for Ca2+ of between 1 and 4 muM. If the membranes were prepared in the absence of Ca2+ the Km increased, and an enzyme model with at least four calcium-binding sites accounted for the kinetic change assuming that one calcium-binding site decreased its affinity. Mg2+ or Mg-ATP could not replace Ca2+. Continuous-flow centrifugation involving a shear stress on membranes was necessary to obtain the high affinity ATPase activity. Using ordinary centrifugation the Ca2+-prepared membranes behaved as membranes prepared in the absence of Ca2+. The Ca2+-stimulated ATPase from membranes prepared without Ca2+ showed reduced maximum activity, but dialyzed, membrane-free hemolysates, whether prepared with Ca2+ present or not, recovered the activity when the hemolysate was present during the ATPase assay. It is suggested that the different Ca2+-affinities of the Ca2+-stimulated ATPase correspond to two different states of the calcium-pump.


Temperature dependence of membrane function. Disparity between active potassium transport and (Na+ & K+)ATPase activity. Ouabain-sensitive K+ influx in mammalian erythrocytes exhibits far less temperature sensitivity than the ((Na+ & K+)ATPase prepared by hypotonic lysis from the same population of cells. The results are not in accord with lipid phase change as the critical mechanism of cold inhibition of intact pumps.