Dynamics of beta adrenoceptor induced amylase release and cyclic AMP accumulation in the guinea pig submandibular gland. The dynamics of amylase release from the guinea pig submandibular gland were studied in vitro by applying a multi-channel microperfusion set. This technique makes it possible to measure time related enzyme release more accurately and to take samples of perifused tissue at short intervals. Stimulation of the beta-adrenoceptor with norepinephrine gives rise to a rapid initial enzyme discharge, detectable within 15 s. Administration of propranolol inhibits enzyme release, which is not restored after removal of the agent. Simultaneous measurements of tissue cyclic AMP during norepinephrine stimulation at various time intervals display a significant increase of cAMP as early as 15 s after stimulation of secretion. This increase of cAMP thus coincides with the discharge of amylase. In addition, cAMP continuously accumulates during 30 min of norepinephrine perifusion of the slices. The present study describes a valuable tool with high sensitivity for visualizing the relations between enzyme secretion from the salivary gland and the intracellular biochemical processes. The data obtained further indicate a close correlation between amylase and cAMP during the initial phase of enzyme discharge.


The gliovascular interphase in irradiated brain tissue. Electron microscopic investigations on location of specific phosphatases. In the brains of rats exposed to a dose of 800 rads of gammma radiation the location of phosphatases hydrolysing the following phosphate esters: adenosinetriphosphate (ATP), cytidinetriphosphate (CTP), guanosinetriphosphate (GTP) and inosinediphosphate (IDP) was determined in the ultramicroscopic structures. Changes were observed in their location in the gliovascular interphase. Early after the exposure (6 hours) the activity of specific phosphatases decreased in brain capillaries, then (48 hours) the reaction product disappeared from the basal membrane of the capillaries and appeared in the endothelium. Later (72 hours -- 7 days) the intensity of the reaction increased in the processes of the astrocytes adhering to the capillary. These changes took place concomitantly with an increase in the permeability of the blood-brain barrier and suggested that specific phosphatases participate in the barrier mechanisms.


Abdominal CT in the evaluation of small cell carcinoma of the lung. Upper abdominal CT scans were performed on 45 consecutive patients with biopsy proven but previously untreated small cell carcinoma of the lung. Evidence of metastases was found in 16 (36%) patients. The most common site of metastases was the liver (27%). CT had a sensitivity of 88% and specificity of 94% as compared with biopsy results. Evidence of retroperitoneal metastases was found in seven (16%) patients.


Expression of monocytic--histiocytic cytochemical markers in epithelial neoplasia. The diagnosis of malignant histiocytosis is usually based upon typical light microscopic features of the neoplasm. Supplementary cytochemical and immunologic features have been suggested as typical of malignant histiocytosis. The present study was prompted by an unusual erythropagocytic hepatocellular carcinoma having immunologic and cytochemical markers suggesting mononuclear phagocytic origin. Twenty-four neoplasms of unquestionable epithelial origin were prospectively evaluated for activity of alpha-naphthyl acetate esterase, a cytochemical marker useful in distinguishing between the non-Hodgkin's lymphomas and malignant histiocytosis. The epithelial tumors represented a broad spectrum of tissue origins and consistently demonstrated alpha-naphthyl acetate esterase activity. Thus, erythrophagocytosis and alpha-naphthyl acetate esterase positivity may be misleading in the unusual instance in which the histopathologic differential diagnosis includes malignant histiocytosis and epithelial neoplasia. Ultrastructural assessment is useful in the exclusion of poorly differentiated carcinoma.


Persistent falsely positive rapid tests for infectious mononucleosis. Report of five cases with four--six-year follow-up data. In many laboratories, rapid slide tests incorporating differential absorption have replaced heterophil antibody tube tests in the investigation of suspect infectious mononucleosis. The present report describes serologic data from five individuals whose Monospot tests remained falsely positive for four years or more without other evidence of infectious mononucleosis or underlying disease states. Three of the five had never been infected with the Epstein-Barr virus. All five had negative results when studied with the ox cell hemolysin and the horse cell differential absorption tube tests. False-positive test results have also been encountered in healthy controls, as frequently as in patients with underlying disease states. The authors are unable to attach any clinical significance to the findings of an isolated falsely positive Monospot test even when it persists for many months or years.


The effect of tocopherol on high-density lipoprotein cholesterol. A clinical observation. A significant redistribution of cholesterol in lipoproteins following ingestion of large doses of D,L-alpha tocopherol (vitamin E) is documented. In persons with decreased high-density lipoprotein (HDL) cholesterol a complex response occurs, which includes cholesterol redistribution in favor of the HDL fraction, with decreases in very-low-density lipoprotein (VLDL) levels and total triglycerides. The response was studied in five persons with average cholestrol distributions and five persons with cholesterol distributions associated with high risk of coronary heart disease. The mean elevation of the HDL cholesterol concentration in the former group was 168% of the initial value, while the latter group experienced post-therapy levels 375% of initial levels.


Pulmonary silicatosis. A case diagnosed by needle-aspiration biopsy and energy-dispersive x-ray analysis. The diagnosis of silicatosis was made by observing birefringent crystals in needle-aspiration biopsy specimens of bilateral basilar pulmonary masses in a clay worker, initially suspected of having metastatic neoplasm. Subsequently the crystals were examined by scanning electron microscopy and energy-dispersive x-ray analysis, which gave supportive evidence for their silicate composition. This experience indicates that needle-aspiration biopsy in conjunction with scanning electron microscopy and energy-dispersive x-ray analysis may be used in the diagnosis of benign pulmonary diseases, especially those of the inhalational fibrogenic variety.


Extrarenal Wilms' tumor.

Extrarenal Wilms' tumor. Extrarenal Wilms' tumor is a rare entity usually seen as a mass in the retroperitoneal area. It may surround and distort otherwise normal kidneys and ureters. Like many other abdominal masses, its true nature remains uncertain until microscopic examination has been performed after surgery. The tumors appear to behave clinically like intrarenal Wilms' tumors, though in the cases reviewed there was a relatively higher incidence in older patients. The prognosis of extrarenal Wilms' tumor is difficult to evaluate due to the small numbers of cases reported and the differing tumor therapy used. However, those cases treated most recently appear to have a good response to therapy.


Fabry's disease in a black kindred.

Fabry's disease in a black kindred. In a 16-member black kindred with Fabry's disease, four hemizygous males had plasma alpha-galactosidase levels less than 6% and seven heterozygous females had plasma alpha-galactosidase levels between 10% and 50% of normal. A 16-year-old index male had hypertension with left ventricular hypertrophy, abnormal renal function, tortuous retinal veins, "myelin" inclusions in bone marrow macrophages, and intraepithelial inclusion bodies in the kidney. Scrotal angiectasia developed a year after diagnosis. The three other affected males had left ventricular hypertrophy and retinal vein tortuosity. Of the seven carrier females, five had frequent headaches, four had retinal vessel changes, three had proteinuria with normal renal function, and two had bundle-branch blocks on ECGs. There was no deuteranomalopia in this family, although the inheritance pattern of the Fabry gene is X-linked recessive.


Amebic liver abscess. Report of a case presenting with nonreactive serologic tests for Entamoeba histolytica. We present a patient with an acute amebic liver abscess with nonreactive serologic tests. Motile hematophagous trophozoites of Entamoeba histolytica were seen microscopically in scrapings from the wall of the abscess. Postoperative serologies revealed rapidly rising then falling titers by SAFA and IHA antibody assays. Serologic tests for amebiasis may be reative in greater than 95% of patients with invasive amebiasis. Nevertheless, a reactive serologic test should not be relied upon exclusively to establish the diagnosis. Sequential serologic testing and surgical intervention to obtain material for microscopic examination, gram stain and bacteriologic culture are warranted in patients with hepatic abscess and nonreactive serologic tests for antibodies to E. histolytica.


Autoimmune hemolytic anemia and carcinoma: an unusual association. Four patients with Coombs'-positive hemolytic anemia associated with carcinoma are presented and compared to 12 previously described patients. These patients commonly seek medical attention for symptoms of anemia rather than for complaints due to the tumor mass. The physician should particularly evaluate for an underlying carcinoma when a patient over the age of 60 years presents with autoimmune hemolytic anemia. Autoimmune hemolytic disease has been demonstrated in patients with a wide variety of tumors, including squamous cell carcinomas, adenocarcinomas, hypernephromas, oat cell carcinomas and a seminoma. Corticosteroid treatment is less effective in autoimmune hemolytic disease associated with carcinoma than in idiopathic autoimmune hemolysis. Tumor extirpation in patients with localized neoplastic disease may abolish the autoimmune hemolytic anemia. Control of the carcinoma through irradiation and chemotherapy together with corticosteroid therapy and/or splenectomy lessened the anemia in some patients. The positive Coombs' test may revert to negative with tumor excision or control. Subsequently, the positivity of the Coombs' reaction may provide a clue to recurrent neoplastic activity. The pathogenic mechanism underlying the association between carcinoma and autoimmune hemolytic disease is poorly understood.


Angiotensin-converting enzyme: serum levels during normal pregnancy. ACE activity of the serum of 52 normal pregnant women was measured in vitro under conditions of substrate saturation with Hip-His-Leu as substrate. The product His-Leu was measured by fluorimetry after reaction with o-phthaldehyde. ACE activity (nmol/min/ml serum) was 30.6 +/- 7.8, 28.8 +/- 7.4, and 30.9 +/- 8.2 for the first, second, and third trimester of pregnancy, respectively. No statistically significant differences (p greater than 0.05) in ACE activity were detected among the three trimesters of normal pregnancy with either serum volume or serum protein as reference value. These values are within the range reported by Friedland and Silverstein13 for 51 male and seven female healthy blood bank donors. We conclude that the evolution of normal pregnancy does not significantly modify the levels of ACE in peripheral blood serum.


Establishment and characterization of a new endometrial cancer cell line (SCRC-1). A new human endometrial cell line, SCRC-1, has been established from a uterine adenocarcinoma. During a period of 57 weeks in culture, the SCRC-1 cells have been passaged over 100 times. Cultures have an epitheloid morphology, high mitotic activity, and a tendency to form multiple cell layers. The cells are polygonal and are arranged in pavement-like fashion. Most have multiple nucleoli, some are multinucleated, and all have heavily vacuolated cytoplasm. Pretreatment with iododeoxyuridine did not reveal viral markers by cocultivation or immunofluorescence techniques. Karyologic studies indicate that the SCRC11 cell line is essentially diploid with a small subpopulation of tetraploid cells. Over a period of 20 weeks, 1 of 14 athymic nude mice inoculated with SCRC-1 cells developed a tumor which histologically closely resembled the original human tumor. Cells were subsequently propagated from this tumor and the resulting epitheloid-like cell line was designated SCRC-1, Tu 1.


Necrotizing retinitis caused by opportunistic virus infection in a patient with Hodgkin's disease. A 33-year-old woman with Hodgkin's disease developed a painless progressive loss of vision in both eyes. Despite an ophthalmoscopic appearance of white-yellow retinal necrosis and retinal hemorrhage similar to that described with Hodgkin's disease, no sign of the disorder was found at autopsy. Instead, widespread evidence of Herpesviridae family virus infection was present in several organs, including the retinas. Opportunistic infection, including herpes simplex and cytomegalovirus, should be considered when retinitis complicates Hodgkin's disease.


Chronic keratoconjunctivitis associated with ocular adenovirus infection. Adenovirus (types 3, 4, 5) was implicated as the etiologic agent in three cases of persistent keratoconjunctivitis. In two, virus was isolated 25 and 29 months after the onset of symptoms; the third patient has suffered intermittent flares of kerato-conjunctivitis since the initial isolation of virus 13 weeks after the onset of the disease. Such patients may represent a previously unsuspected source of adenovirus in the population. All were given corticosteroids topically. This treatment may have prolonged the adenoviral disease.


Predictors of community tenure of discharged state hospital patients. Community treatment of formerly hospitalized patients is in need of evaluation. The authors evaluated an aftercare program by examining its effect on the amount of time spent in the community by patients discharged from a state mental hospital. They assessed the impact of specific intervention in the areas of housing, employment, finances, psychiatric treatment, medication, and leisure. They conclude that assistance during the transition from the hospital to the community prolonged community tenure, that intervention in the areas of housing, finances, and medication was especially important, and that treatment in the community increased the amount of time spent in the community during the first 6 months after discharge.


Failure of indicator bacteria to reflect the occurrence of enteroviruses in marine waters. The results of several studies conducted along the upper Texas Gulf coast, where a substantial amount of quantitative virological data were collected, are compared to bacteriological indicators and other environmental factors on a statistical basis. Variables common to all these studies were anlayzed by multivariate regression. Although multivariate analysis indicated that the number of viruses detected in water was related to rainfall, salinity, and total coliforms in the water, the amount of variation in the number of viruses accounted for by these factors was not large enough to make them good predictors. Enteroviruses were detected 43 per cent of the time in recreational waters considered acceptable as judged by coliform standards, and 44 per cent of the time when judged by fecal coliform standards. Enteroviruses were detected 35 per cent of the time in waters which met acceptable standards for shellfish-harvesting. Our failure to correlate the occurrence of enteroviruses in marine waters with indicator bacteria, and the frequent occurrence of enteroviruses in water which met current bacteriological standards, indicates that these standards do not reflect the occurrence of enteroviruses, and perhaps other human pathogenic viruses, in marine waters.


Serological markers for hepatitis types A and B among U.S. Arym soldiers, Germany. Viral hepatitis rates among U.S. Army soldiers in Europe have been found to be two to three times higher than corresponding rates for soldiers stationed in the U.S. Sera from 89 per cent of a representative Army unit with 865 members and a known hepatitis problem were tested for HBsAg, anti-HBs, anti-HBc, and anti-HA. The prevalence of HB markers was 20 per cent, and hepatitis A antibody was present in 25 per cent. A six-month follow-up, conducted on 260 individuals initially negative for all four tests, revealed that 11 of these were now HB seropositive, whereas none had seroconverted to anti-HA positive. The HB virus was the principal agent responsible for hepatitis in the unit surveyed.


Milk lipid absorption and chylomicron production in the suckling rat. Structural correlates of milk lipid absorption and chylomicron production were studied in 10-day-old suckled rats. The gastric and duodenal contents and duodenal mucosae were examined with the light and electron microscopes. In the gastric lumen the milk lipid globule cores were smooth, circular and uniformly electron opaque. Many membranes and lamellar structures with a trilaminar and multilamellar appearance were adherent to the peripheries of the cores. In the central duodenal lumen the milk lipid globule cores were also smooth, circular and uniformly electron opaque. Very few milk lipid globules in the duodenal lumen showed adherent membranes or lamellae. Membrane fragments and lamellae were present in the lumen separate from the milk lipid globules. In the duodenal lumen between villi the milk lipid globules had multiple electron lucent indentations of the core. It is believed that the irregular peripheries of the milk lipid globule cores are the result of lipolysis within the duodenal lumen acting at the milk lipid globule surface. This lipolysis of triacylglycerol would produce amphiphilic lipids which may result in the electron lucent spaces at the milk lipid globule periphery. The absorptive epithelial cells along the length of the duodenal villus varied in structure relative to their position at the tip, middle, or base of the villus. Typical mid-villus epithelial cells contained lipid droplets averaging 0.3-micrometer diameter in the smooth and rough endoplasmic reticulum and in Golgi complexes in the apical cytoplasm. Villus tip and villus base cells contained large lipid droplets between 7-16 micrometers. Only a few 0.3-micrometer lipid droplets were present within these cells. These large lipid droplets appeared to be accumulations of triacylglycerol present in the apical cytoplasm associated with lamellar and membranous structures. Numerous chylomicrons were present between epithelial cells located in the middle region of the villus while significantly fewer chylomicrons were seen between epithelial cells at the tip and base of the villus. These observations suggest that the cells at the middle of the duodenal villus of suckling rats were more efficient in the production of chylomicron triacylglycerol derived from incoming milk triacylglycerol than cells at the tip and base of the villus.


Ultrastructural changes in Leydig cells of streptozotocin-induced diabetic rats. Hyperglycemia (experimental diabetes) was induced in adult male rats by destruction of the pancreatic beta cells with a single intravenous injection of streptozotocin (STZ). Testes from diabetic, from insulin-treated diabetic, and from sham-injected normal rats were fxed by vascular perfusion. The fine structure of Leydig cells was examined at two, three, and four weeks after the STZ injection in the untreated diabetic animals, and at four weeks in the controls and insulin-treated diabetic rats. A number of morphological changes was observed in Leydig cells of untreated diabetic animals. Most obvious of these was an accumulation of lipid droplets, not normally present in Leydig cells in adults of this species. Smooth endoplasmic reticulum (SER) was markedly reduced in Leydig cells of the hyperglycemic rats. Several types of intracellular bodies were seen exclusively in Leydig cells of the untreated diabetic animals. Many resembled secondary lysosomes or dense bodies, while others appeared to be autophagic vacuoles. In addition, a small, granule-containing lamellar structure was seen either within a typical dense body or free in the cytoplasm. Myelin-like structures were commonly observed within the cytoplasm of the Leydig cell or within mitochondria. The appearance of the mitochondria in diabetic rats was otherwise normal. The extracellular spaces surrounding Leydig cells from untreated hyperglycemic rats also contained large accumulations of myelin-like material. These structural changes appear to be direct consequences of the diabetic state of the animals, since the ultrastructure of insulin-treated diabetic rats did not differ from that of the controls. These findings may reflect an alteration or breakdown of Leydig cell components normally involved in the synthesis of androgen, and correlate with previous reports of lowered circulating levels of testosterone in diabetic rats.


Influence of environment on adrenal cortical response to ACTH stimulation in clinically normal dogs. Effect of testing environment on adrenal cortical responses to an injection of ACTH in clinically normal dogs was examined in three locations, presumably of increasing order of stress elicitation: in a home; veterinary hospital (VH), 4 hours in a cage; and VH, overnight in a cage. Basal cortisol (hydrocortisone) values for plasma were significantly lower (P less than 0.001) for the home group (1.8 microgram/dl) when compared with values for the VH, 4-hour cage (3.8 microgram/dl) or the VH, overnight cage (3.9 microgram/dl) groups. However, significant differences (P greater than 0.05) were not observed 2 hours after ACTH admininstration for the home group (13.7 microgram/dl); VH, 4-hour cage group (14.8 microgram/dl); or VH, overnight cage group (16.0 microgram/dl). Responses of individual dogs were consistent (P less than 0.005). The testing environment did not markedly affect results of adrenal cortical function tests for dogs when ACTH stimulation was utilized. The response of dogs to ACTH, as monitored by immunologic assay techniques (competitive protein-binding assay or radioimmunoassay), was consistent and was useful as a diagnostic aid for adrenal malfunction.


Failure of neuromuscular transmission after complete nerve section in the dog. After the ulnar nerve was surgically transected, nerve conduction velocity in the distal segment and the evoked motor unit potential (EMUP) from the interosseous muscle were recorded until neuromuscular transmission failed. In five of the six dogs in the experiment, functional conduction ceased by 4.8 days, as determined by failure of both proximal and distal stimulation of the distal segment to evoke a muscle response. From the time of section until neuromuscular failure, the nerve conduction velocity remained unchanged. The amplitude of the EMUP from the interosseous muscle, however, decreased markedly during this time. Changes in other features of the EMUP are also presented. Fibrillation (denervation) potentials did not appear until the first day that muscle response could not be detected by stimulating the nerve. These data present a principle which would enable a determination of relative extent and progression of peripheral nerve damage.


Adenocarcinoma of the lung: recent results from the Veterans Administration Lung Group. Adenocarcinoma has become the most common type of cancer of the lung. Its distinct natural history necessitates separation from the other cell types. Results from recent Veterans Administration Lung Group studies show that local-regional failure occurred in 59% of patients after irradiation for adenocarcinoma limited to the thorax. Data from 300 consecutive autopsies reveal that death was caused by intrathoracic complications of the tumor in 38%, and by metastases in 57% of patients. Adenocarcinoma has an intermediate risk of local and distant failure when compared to squamous and small-cell carcinoma. However, brain metastases are most frequent with adenocarcinoma. Preliminary results suggest that prophylactic brain irradiation decreases the frequency of brain metastases. Patients with adenocarcinoma are more likely than those with other cell types to have metastases only in the brain. Prophylactic brain irradiation may make the greatest contribution to improved survival in pateints with adenocarcinoma of the lung.


Lung cancer in chloromethyl ether workers. During the period from 1948 to 71, some workers in a chemical plant were exposed to chloromethyl ethers in varying degrees and for varying durations. A historical cohort study of 1,446 male production employees from 1960 through 1975 showed both an increased risk of lung cancer as compared to that in the general population among 465 exposed workers and a dose-response relationship. Significantly increased risk occurred only among men with moderate and heavy chemical exposure. Smoking habit could account for some of the cases of lung cancer that developed in men with light chemical exposure and for cases among unexposed workers. Microscopic sections of most of the lung cancers were reviewed, and the results suggested that small-cell carcinoma was a specific response to inhalation of chloromethyl ethers.


[Presence of antibodies in human colostral secretory IgA against enteric commensal bacteria: biological implications (author's transl)]. Antisecretory component, anti-alpha, anti-mu and anti-Fc (gamma) fluorescent antibodies were used to detect the presence of immunoglobulins with antibody activity against enteric commensal bacteria in human colostrum and serum. Forty nine colostrum samples were studied; all of them displayed secretory IgA (sIgA) antibodies reacting with Bacteroides thetaiotaomicron, Clostridium perfringens and Escherichia coli serotype O141:H32 without any K antigen. The amount of sIgA antibodies was always related to the sIgA colostral concentration varying greatly from one patient to another. For the 3 lactating women studied, the colostrum sIgA antibodies were largely predominant as compared to the antibodies of other classes; in their sera, no antibody having the same anticommensal specificity was detected in the IgA fraction while these antibodies were found in IgM and IgG. Our results are incompatible with the existence of local antigenic stimulation, and the IgA transfer from serum into mammary secretion appears unlikely, but these results are perfectly compatible with the antigenic stimulation of gut associated lymphoid tissue and subsequent migration in mammary tissue.


[Attachment of a collagenolytic strain to its substrate (author's transl)]. The bacterial collagenolytic strain Acinetobacter sp. CRZV2 adheres to insoluble collagen fibers when this substrate is introduced into the growth medium. This attachment occurs during the exponential growth. Proteolytic enzymes such as pronase and trypsine activate the adherence of bacterial cells to collagen fibers.


The natural history of peripheral neuropathy in primary systemic amyloidosis. The records of 31 patients with primary systemic amyloidosis and peripheral neuropathy seen during a 17-year period were analyzed to define the natural history of the neuropathy. Patients tended to be older men with a painful, distal, symmetrical sensorimotor neuropathy and prominent autonomic features. Loss of pain and temperature sensation was frequently more striking than loss of mechanoreception. Renal, cardiac, hematological, and gastrointestinal dysfunction often overshadowed the neuropathy. Clinical, neurophysiological, and histopathological studies pointed to axonal degeneration with predominant but not exclusive involvement of small myelinated and unmyelinated fibers. The neuropathy was progressive in all patients with or without treatment, but death was typically due to supervening medical complications.


The TO strains of Theiler's viruses cause "slow virus-like" infections in mice. Intracerebral inoculation of mice with tissue culture-adapted TO strains of Theiler's mouse encephalomyelitis viruses results in a clinical disease consisting of spastic paralysis due to demyelination after a lengthy incubation period. Thus, in effect, these ordinary picornaviruses are capable of causing a slow infection in their natural host, the mouse. In addition, through the use of tissue culture-adapted virus stocks, virus content in mouse tissues now can be accurately quantified by standard plaque assay.


Pupillary dysfunction in myasthenia gravis. The constriction-dilation cycles of pupils exposed to a stationary, discrete slit-lamp beam were significantly prolonged in 25 myasthenic patients (1,060.4 +/- 45.8 msec) undergoing therapy with steroids, anticholinesterases, or both, compared to normal controls (801.9 +/- 8.6 msec) or subjects receiving steroids for nonneurological disease (860.9 +/- 14.9 msec). The duration of myasthenia correlated with the slowing of the cycle time. Myasthenia gravis may affect ectodermally derived smooth muscle or the autonomic neuromuscular junction or both, and not be restricted to the well-demonstrated alterations of neuromuscular junction in striated muscle of mesodermal origin. Alternatively, prolonged pupillary cycles could be attributed to dysfunction of central pathways of the pupillary light reflex.


Enhancement of post-ultraviolet killing in Escherichia coli K-12 through the action of gyrase inhibitors: evidence for associated gyrase-recBC deoxyribonuclease function. This work in conjunction with the results presented in an earlier report (M. A. Purdy and K. L. Yielding, Antimicrob. Agents Chemother. 10:182--184, 1976) showed the following. (i) Nalidixic acid and novobiocin could inhibit post-ultraviolet and post-X-ray survival, implicating gyrase function in deoxyribonucleic acid repair. (ii) The inhibition of post-ultraviolet survival requires the action of functional recBC deoxyribonuclease. (iii) Structural changes in the gyrase could (a) cause recBC mutants to exhibit enhancement of post-ultraviolet killing in the presence of novobiocin, (b) increase the ultraviolet sensitivity of recBC mutants, and (c) enhance the thermal lability of a recBCts mutant.


Mecillinam-ampicillin synergism in experimental Enterobacteriaceae meningitis. The in vitro activities of mecillinam, a new beta-amidinopenicillin, and ampicillin, alone and in combination, against an Escherichia coli strain and a Klebsiella pneumoniae strain were compared, and these results were correlated with their respective activities in vivo in experimental meningitis. The mecillinam-ampicillin combination was synergistic in vitro against both strains when tested by a modified checkerboard technique (bacteriostatic synergy). However when quantitative bactericidal synergy studies were made, the relative bactericidal rate of the combination was more rapid than that of either drug alone ("bactericidal synergy") against the Escherichia coli isolate only. In a rabbit model of Enterobacteriaceae meningitis, in vivo bactericidal activity correlated with results obtained in vitro. Both drugs were administered by continuous intravenous infusion for 8 h. Serum and cerebrospinal fluid antibiotic levels were similar to those achieved in humans. Cerebrospinal fluid bacterial concentrations (colony-forming units [CFU] per milliliter) were quantitatively titrated at 2-h intervals. Both drugs, alone or the combination, were ineffective against the K. pneumoniae strain in vivo (change in titer <1 log in 8 h). In contrast, the combination produced a markedly enhanced bactericidal effect against the E. coli strain (mean +/- standard deviation, decrease of log(10) CFU per milliliter of 3.65 +/- 1.02) compared with those of ampicillin alone (decrease of log(10) CFU per milliter of 0.07 +/- 0.8) and mecillinam alone (decrease of log(10) CFU per milliliter of 1.6 +/- 0.05) (P < 0.001). When bactericidal synergism can be demonstrated for mecillinam-ampicillin in vitro in a case of gram-negative-bacillary meningitis this combination may be useful in the therapy of the illness.


Aflatoxin inhibition of viral interferon induction. The inhibitory effect of four basic aflatoxins on interferon induction by influenza virus in LLC-MK2 cell monolayers follows a structure-activity series with decreasing potency in the order aflatoxin B1 greater than G1 greater than B2 approximately G2. Of the four aflatoxins, B1 was the most deleterious to both cell growth and the viability of cells in confluent cultures. The fact that higher levels of influenza virus growth were attained in aflatoxin-treated cells than in normal cell monolayers was related to increased aflatoxin concentration in association with decreased interferon production. The ability of interferon to confer cellular resistance against viral infection, however, was not altered by aflatoxin. The inhibitory activity of aflatoxin on interferon production may be a factor contributing to impairment of host resistance to viral infections.


Activity of semisynthetic penicillins and synergism with mecillinam against Bacteroides species. The minimal inhibitory concentrations (MIC) of six penicillins (ampicillin, carbenicillin, ticarcillin, piperacillin, mezlocillin, and Bay k 4999) against 29 clinical isolates of Bacteriodes spp. (including Bacteroides fragilis, Bacteroides thetaiotaomicron, and Bacteroides vulgatus) were determined by an agar dilution method. Bay k 4999 was most active, followed in descending order by ampicillin, piperacillin, mezlocillin, ticarcillin, and carbenicillin. Mecillinam, a 6 beta-amidino-penicillanic acid, inhibited no strains at 50 micrograms/ml, but when compared with ampicillin, a fourfold or greater increase in MIC for ampicillin (antagonism) was noted in 3 of 29 strains, with no effect on MIC for 26 strains, whereas when combined with carbenicillin, a fourfold or greater decrease in MIC for both antibiotics (synergism) was noted in 12 strains, 4 of which had an MIC of greater than or equal to 250 micrograms/ml for carbenicillin alone. These studies demonstrate the increased activity of some newer semisynthetic penicillins and the potential synergy obtained with mecillinam and carbenicillin against Bacteroides sp.


RMI 15,731 (1-[5-tetradecyloxy-2-furanyl]-ethanone), a new antirhinovirus compound. RMI 15,731 (1-[5-tetradecyloxy-2-furanyl]-ethanone) is a new antiviral compound with activity specific for rhinoviruses. Virus synthesis in R-HeLa cells was susceptible to low concentrations (0.25 micrograms/ml) of the compound. RMI 15,731 was effective if added for 1 h before infection and removed or if added as late as 6 h postinfection. Low concentrations of the compound directly inactivated infectious rhinovirus in a time- and temperature-dependent fashion. RMI 15,731 appears to be a promising new antirhinovirus compound for clinical evaluation since it (i) blocks intracellular virus synthesis (without cellular toxicity), and (ii) directly inactivates virions. The last property may be important in limiting virus shedding from an infected host.


N-alpha-Cocoyl-L-arginine ethyl ester, DL-pyroglutamic acid salt, as an inactivator of hepatitis B surface antigen. N-alpha-Cocoyl-L-arginine ethyl ester, DL-pyroglutamic acid salt (CAE), exhibited a strong inactivating effect on hepatitis B surface antigen. Concentrations of CAE required for 50 and 100% inactivation of the antigen were 0.01 to 0.025% and 0.025 to 0.05% respectively. CAE completely inactivated hepatitis B surface antigen at the lowest concentration compared with various compounds including about 500 amino acid derivatives, sodium hypochlorite, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, and some detergents. Furthermore, CAE inactivated vaccinia virus, herpes simplex virus, and influenza virus, whereas poliovirus was not inactivated at all. The results suggest that the inactivating effects of CAE are related to interaction with lipid-containing viral envelopes.


Virucidal activity of retinal.

Virucidal activity of retinal. Herpes simplex virus type 2 and simian virus 40 were rapidly inactivated by retinal at micromolar concentrations. Other fat-soluble vitamins, particularly vitamin A derivatives, were also active against herpes simplex virus type 2 and several lipid-containing bacteriophages.


Cystosarcoma phylloides. A steroid receptor and ultrastructure analysis. Six cases of cystosarcoma phylloides were evaluated by ultrastructure and steroid receptor analysis. Electron microscopy of the lesions supported previous reports of a heterogeneous tumor consisting of pleomorphic mesenchyme and normal or proliferative epithelium. In each case estrogen and progesterone receptor analysis indicated the presence of a nonsaturable estrogen and progesterone 4S binding protein rather than a specific steroid receptor as suggested by previous studies.


The pathologic assessment of primary hyperparathyroidism and its impact on therapy. A prospective evaluation of 50 cases with oil-red-O stain. Normal and abnormal parathyroid glands removed surgically from 50 consecutive patients with primary hyperparathyroidism were studied by means of hematoxylin and eosin and oil-red-O stains. This was done to establish the incidence of the different pathological entities in our patient material, and to evaluate the role of the oil-red-O stain in the diagnostic histopathological process. The oil-red-O stain distinctly separates abnormally hyperfunctioning from normal or suppressed parathyroid tissue. Therefore, it is a valuable tool in the pathologic evaluation of patients with hyperparathyroidism. Chief cell adenomas were the most frequent lesions (88%), while diffuse hyperplasia was seen less commonly (10%) and carcinoma infrequently (2%). These findings justify a surgically conservative approach as the most desirable in managing patients with primary hyperparathyroidism.


[Preliminary note on the circulation of some human respiratory viruses by wild birds]. With a view to detecting infections and carriage of human respiratory viruses in wild birds, 349 serum samples collected from 21 bird species -- sedentary ones and birds with large or limited migration areas -- were investigated. The following antigens were used: influenza virus A/Hong Kong 1/68 (H3N2)), A2 England 42/73 (H3N2), A2 Victoria 3/75 (H3N2), A/New Jersey 8/76 (HswN1), B/Hong Kong 5/72; parainfluenza virus type I Sendai and type II, coronavirus OC/43. An elevated incidence of antibodies to A2 Victoria 3/75 (H3N2) and parainfluenza type I virus was detected in herons (Ardea cinerea, Nyctycorax myctycorax). The high incidence of antibodies to B/Hong Kong 5/72 (30.7% of the samples exhibited significant titers) found in the crow (Corvus corone sardonius) is ascribed to the fact that this bird is carnivorus, feeding on corpses of mammals.


Effect of guanethidine on collagen biosynthesis in blood vessels of hypertensive rats. The effect of guanethidine on collagen biosynthesis in the aorta and mesenteric artery was investigated in desoxycorticosterone acetate (DOCA)-salt hypertensive rats. Prolyl hydroxylase activity (EC 1.14.11.2; proline, 2-oxoglutarate dioxygenase) and 14C-proline incorporation into collagen, two markers of collagen biosynthesis, were significantly increased in blood vessels of hypertensive rats compared with those of controls. When guanethidine (5 mg/kg, i.p.) was given daily to the hypertensive rats for 4 weeks, the blood pressure was decreased to 150 +/- 7 mm Hg, whereas the blood pressure of the untreated hypertensive rats was 218 +/- 10 mm Hg. Prolyl hydroxylase activity in the aorta and mesenteric artery and 14C-proline incorporation into aortic collagen were significantly reduced concomitant with the decrease in blood pressure. These results suggest that the decrease in vascular collagen biosynthesis in hypertensive rats treated with guanethidine is related to the lowering of their blood pressure.


[Activity of delta-aminolevulinic synthetase, cytochrome oxidase and levels of the mixed function oxidase system during experimental protein malnutrition. Response to re-alimentation]. Activities of delta amino levulinic synthetase (DALS), cytochrome oxidase (E. C. 1.9.3.1.), NADH cytochrome b5 reductase (NADH red.), NADPH cytochrome P450 reductase (NADPH red.), contents of cytochrome P450 (cyt. P450) and cytochrome b5 (cyt. b5), and levels of hemoglobin and hematocrit were studied in three groups of rats: a) malnourished, b) during recovery from malnutrition, and c) controls. During severe protein malnutrition blood levels of hemoglobin and hematocrit were found to be decreased as well as DALS's activity in homogenized bone marrow and liver. The activity of NADH red, and contents of cyt. P.450 and cyt. b5 in hepatic microsomes were also found significantly depressed. The microsomal activity of NADPH red. as well as mitochondrial cytochrome oxidase did not present significant changes, since values obtained in malnourished rats were similar to those found for the control group. While recovering from malnutrition, when rats were fed a casein based diet (10 NDpCalo/o) supplemented with Fe and Cu, the hepatic enzymatic activities, the cytochrome contents of P450 and b5, and hematocrit experienced a spectacular increase, reaching towards the end of the refeeding period values which could be compared to those found in the control group. Nevertheless, DALS' activity in homogenized bone marrow and hemoglobin levels remained low. Results are discussed in relation to depressed activities and contents of enzymes, coenzymes, metabolites and subtrates involved in the hemoglobin synthesis in the rat bone marrow, during recovery from malnutrition.


[Enzyme arrangement of various tissues in swine. 1. Studies of the effect of 32 hours of fasting, administration of actinomycin D, and fasting in combination with administration of actinomycin D on crude protein level, activities of GOT, GTP, fructose-1,6-diphoaphatase as well as ATPase of liver, kidneys and semitendinous muscle in newborn piglets]. The effects of sufficient milk intake as well as of 32 hours of fasting after birth, administration of actinomycin D (intraperitoneal application of 1 mg/kg five weight), and fasting in combination with actinomycin D on the development of body and liver weights, crude protein levels in homogenate and supernatant of liver, kidneys, and M. semitendinosus as well as on the activities of certain tissue enzymes were analysed with four groups of piglets (n = 4). Fasting, administration of actinomycin, and fasting in combination with actinomycin D resulted in rapid reduction in body and liver weights, while the crude protein levels in those tissues were not affected with significance. GOT and fructose-1,6-diphosphatase activities in supernatant from liver tended to decline under fasting conditions. The ATPase activity in the homogenate of the above tissues did not change in response to differentiated treatment.


[Enzyme arrangement of various tissues in swine. 2. Studies of postpartum development of crude protein levels as well as activities of various enzymes (GOT, GPT, serine dehydratase, xanthine oxidase, fructose-1,6-diphosphatase) in liver, kidneys and muscle of piglets]. Twenty-eight piglets from three litters were analysed for postnatal development (0 to 6 days of age) of the crude protein levels and activities of various enzymes (GOT, GPT, serine dehydratase, xanthinoxidase, fructose-1,6-diphosphatase) in the supernatant of liver, kidneys, and muscles. Both the weight and crude protein levels of the liver increased after birth, which improved the capability of metabolic regulation. GOT and fructose 1,6-diphosphatase activities in the liver tissue increased over the first days after birth. Serine dehydratase activity was not detectable with regularity. GPT activity in the tissues concerned was low by comparison to GOT and underwent little postnatal change. The activity of xanthinoxidase in the liver tissue tended to go up after birth. ACTH (3 IU/kg live weight) was administered to piglets aged five days and did not increase the activity of GOT and fructose-1,6-diphosphatase in the liver after five hours.


[Enzyme arrangement of various tissues in swine. 3. Studies of pre- and postnatal activities of various enzymes (ATPase, GOT, GPT, leucine aminopeptidase, acid and alkaline phosphatases, aldose reductase, glucuronate reductase, sorbitol dehydrogenase) in various tissues]. The crude protein levels as well as the activities of various enzymes were studied in certain tissues of fetuses (80th through 114th days of development), piglets of different age groups, and pigs for slaughter. In most of the tissues tested the postnatal activities of Na-K-ATPase were beyond those recorded from fetuses. The highest GOT activities were recorded from the liver, myocardium, and kidneys. Activities were found to rise sizeably in some tissues after birth. The activity of GPT, too, exhibited age-dependent variations. The activity of leucine-aminopeptidase increased strongly after birth in liver and kidneys. Acid phosphatase activity was less markedly influenced by development phases. Those enzymes which are involved in the formation of fructose and glucose (aldolreductase, glucuronate-reductase, and sorbite-dehydrogenase) had their highest activities, all age-dependent, in liver and kidneys.


[Histopathological pattern of adenovirus infection in the calf]. Pneumo-enteritis is the clinical manifestation of adenovirus infection in calf. Proliferative alveolitis, endobronchitis, and peribronchitis with intranuclear inclusions in the epithelial cells, histiocytes, and macrophages were histologically recorded. Proliferative changes with minor pleomorphism of cells were recorded from lymph nodes and lymph follicles of spleen and intestines. The epithelial cells of the renal tubules and liver exhibited degenerative changes, while the endothelium of the capillaries was activated. Five Serotype-1 adenoviruses were isolated from the lung, liver, and kidneys of the foetuses. IE were recordable from the epithelial cells of kidneys and lung. Other calves were examined following natural infection with adenovirus and virus of the mucosa disease. Dystrophic and necrotic changes were recorded from their digestive organs, lymphocytolysis from spleen and lymph nodes (a characteristic change related to mucosa disease), and nephrosis with adenovirus inclusions from the epithelial cells of the renal tubules.


[Studies of necrotizing enteritis of suckling piglets (Cl. perfringens typc C enterotoxemia) in industrialized sow breeding units. 3. Experimental reproduction of the disease]. Experimental reproduction of necrotising enteritis of sucking pigs was successfully achieved by using both Clostridium perfringens Type C strains, which had been isolated from sucking pigs with necrotising enteritis, and Type C strain 3628 of A.T.C.C. (sub-type C1). The lethal dose for sucking pigs was between 20 X 10(6) and 12 X 10(7) pathogens per animal. The disease could not even be induced by repeated application of no-bacterial toxin of Cl. perfringens Type C nor by administration of Cl. perfringens Type A strains which had been cultured from broilers with necrotising enteritis. Necrotising enteritis was found to develop in two phases in sucking pigs. First, the pathogen will deposit to the villous epithelium and then penetrate the superficial strata of the mocous membrane. In the second phase, the villous structure will be destroyed by the lethal, haemolysing, and necrotising toxins of Cl. perfringens. The role played by individual toxin fractions is discussed together with the importance of humoral and localised infection defence. Sucking pigs may be sufficiently protected against infection based on single or ten-fold lethal infectious dosage by two vaccinations of the mother animal, five and three weeks prior to parturition, using "Enterotoxaemia Vaccine Dessau bivalent". Infection then would not occur unless a hundredfold lethal dose was applied. Characteristics include diarrhoea, apathy, exhaustion, and death.


Human adenohypophyseal quantitative histochemical cell classification. II. Evaluation of the effects of two fixatives and postmortem intervals. Quantitative cell counts on specific pituitary areas were done on differentially stained adenohypophyseal sections obtained at autopsy (four to 22 hours postmortem). We used specific criteria formulated from studies by previous authors to identify functional classes of secretory cells. We compared the effects of two fixatives, calcium acetate-buffered formaldehyde solution (CAF) and formol sublimate (FS), on morphologic identification. Calcium acetate-buffered formaldehyde solution is superior in identifying gonadotrophs and prolactin cells morphologically. Formol sublimate is superior in identifying the other cell types morphologically. Approximately 10% to 15% more cells could be classified by fixing with FS rather than CAF. The effect of postmortem autolysis was minimal. The only statistically significant (P less than .025) effect was the presence of a higher percentage of disrupted unclassifiable cells in CAF-fixed basophil areas at 12 to 24 hours than was present at 0 to 12 hours.


Ultrastructure of psammoma bodies of meningioma in tissue culture. An 8-day-old tissue culture of a human meningioma was studied by electron microscopy. Psammoma bodies were detected in all stages of evolution, affording a unique opportunity for observing the genesis of these structures. Matrix vesicles appeared instrumental in the calcification of a granular extracellular material. Although matrix vesicles are described in both physiologic and pathologic calcification, they have not been previously reported in the very few ultrastructural studies of psammoma bodies in meningiomas.


Malakoplakia of the brain. A report of two cases occurring in childhood. Malakoplakia was found in the brain biopsy specimens of two children with meningoencephalitis probably due to herpes simplex. Histologically, there was extensive parenchymal destruction and cellular infiltration. Numerous von Hansemann histiocytes and typical Michaelis-Gutmann bodies were present. Ultrastructurally these bodies had a dense central core and concentric alternating rings. Large intracytoplasmic phagolysosomes were present. Malakoplakia most frequently involves the urinary tract of adults. Only a few children with malakoplakia have been described. There are two previous reports of cerebral malakoplakia associated with neonatal herpes simplex. The pathogenesis is obscure. Several reports suggest an altered histiocytic response to a bacterial agent as the pathogenetic mechanism. Our findings raise the possibility of an etiologic role of a virus, such as herpes simplex.


Induction of virus specific and H-2 restricted cytotoxic T cells by UV inactivated murine cytomegalovirus. Infection of C3H mice with live or UV-inactivated murine cytomegalovirus (MCMV) was able to generate population(s) of lymphocytes in the spleen (CTL) which could exert a lytic effect against L cells infected with MCMV but not against uninfected or those infected with HSV-1. The effector cells proved to be theta-bearing T cells and the lysis of target cells was H-2 restricted. Data presented show that early viral protein synthesis but not viral DNA synthesis was necessary for the appearance of relevant antigenic determinant(s) on target cells. The results of co-capping experiments suggest that H-2 molecules may have close association with MCMV induced product(s) as also with murine leukemia virus glycoprotein (gp70) which is carried by normal L cells. Despite this observation, anti-H-2 serum effectively blocked the cytolysis whereas anti-gp70 and anti-MCMV sera failed. Anti-MCMV serum was effective in blocking cytolysis, only if the L cells were infected for 24 hours and then used as targets. MCMV infected L cells which were coated externally with inactivated Sendai virus could be effectively recognised by MCMV as also by sendai specific CTL. That the cytotoxicity exerted on such targets was of specific nature was revealed by the results of competitive blocking experiments with unlabelled targets.


Studies on avian infectious bronchitis virus (IBV). III. Interferon induction by and sensitivity to interferon of IBV. The induction of interferon by avian infectious bronchitis virus (IBV) and the sensitivity of IBV to interferon were studied. The results of experiments with ten IBV strains are summarized as follows. 1. All the IBV strains tested induced interferon in chick embryo (CE) cells, chicken kidney (CK) cells and embryonated eggs. The Iowa-609 strain induced about 1000 units of interferon in CE cells while the Beaudette-42 strain induced about 200 units of interferon in embryonated eggs; the interferon titers induced by other strains usually ranged from 5 to 60 units. No IBV strain induced interferon in HeLa or BHK-21 cells. 2. IBV particles inactivated by ultraviolet irradiation or by heating lost their ability to induce interferon. 3. The properties of the interferon produced in the present study are similar to those of other interferons produced in chicken cells. 4. HeLa or BHK-21 cells did not acquire resistance to virus infection, after incubation with interferon produced in CE cells. On the other hand, CK cells acquired the same degree of resistance to virus infection as CE cells after incubation with interferon produced in CE cells. 5. All the IBV strains tested were sensitive to interferon in CK cells. The sensitivities of Massachusetts-41 and Holte strains to interferon were similar to that of vesicular stomatitis virus.


[Na K ATPase changes in the erythrocyte membrane in subjects treated with inosine]. The effect of inosine on red cell membrane Na+K+ATPase in lead poisoning was studied in 13 subjects. In addition to enzyme damage, an appreciable increase in enzyme level was noted after 100 mg inosine i.m. for 20 days. It is felt that this form of management is useful in lead poisoning as a means of treating and preventing anaemia.


Biochemical studies with infectious bursal disease virus: comparison of some of its properties with infectious pancreatic necrosis virus. Infectious bursal disease (IBD) virus was purified from the bursae of infected chickens. Two morphologically indistinguishable populations of virus particles were separated in sucrose gradients and possessed sedimentation coefficients of 295S and 460S. Both populations contained RNA and had identical polypeptide compositions. IBD virus banded at a density of 1.31 g/ml in CsCl and at 1.24 g/ml in sodium potassium tartrate. IBD virus contained two RNA segments with mol. wts. of 2.4X10(6) and 2.2X10(6) as estimated by polyacrylamide-agarose gel electrophoresis, but sedimented in sucrose gradients at 15S. Virus RNA was resistant to 0.1 micrograms/ml ribonuclease treatment under conditions in which ribosomal RNA was completely hydrolysed, but was sensitive to 1.0 and 10 micrograms/ml treatments. These results suggest that the RNA consists of either double-stranded or highly ordered single-stranded molecules. IBD virus contained seven polypeptides with mol. wts. in the range 97,000 to 24,000. Two polypeptides were absent in empty particles of IBD virus. IBD and infectious pancreatic necrosis (IPN) viruses were morphologically indistinguishable. IPN virus possessed a sedimentation coefficient of 440S and banded at a density of 1.32 g/ml in CsCl. In addition the electrophoretic mobilities of IBD and IPN virus RNAs were almost identical. Polyacrylamide slab gel electrophoresis showed that while the number and size of the polypeptides were different for each virus there were similarities in the overall pattern.


Characterization of the infection of equine fibroblasts by equine infectious anemia virus. Equine dermal fibroblasts persistently infected with equine infectious anemia virus (EIAV) show no alterations in cell morphology or growth kinetics when compared to uninfected cells. The percentage of cells immunofluorescent positive for viral proteins fluctuated, depending upon the stage of the cell cycle, while production of extracellular virus was uniform throughout the cell cycle, increasing only as the cell number increased. This was shown in log versus stationary phase cultures as well as in cultures synchronized by sterum starvation. The establishment of productive infection did not require host cell DNA synthesis. Normal levels of progeny virus were produced in cultures pretreated with mitomycin C and placed in serum-containing medium. Serum-starved cultures, however, did not support EIAV replication as well as other cultures, presumably because synthesis of provirus was inhibited.


Enterovirus 71 isolated from cases of epidemic poliomyelitis-like disease in Bulgaria. Virological and serological studies of an epidemic disease in Bulgaria, 1975, were carried out. Epidemiologically, clinically and pathomorphologically, the disease simulated almost all known forms of poliomyelitis, acute stem encephalitis, encephalomyocarditis and aseptic meningitis. The studies completely rules out the participation of polioviruses and provided comprehensive evidence for the etiological role of a peculiar enterovirus subsequently identified as enterovirus (EV) type 71 known in the literature since 1974. Altogether, in 1975 and 1976 from 65 cases of poliomyelitis-like disease (PLD) 92 strains of EV71 were isolated, including 37 strains from the brain and medulla, 1 from the cerebrospinal fluid, 10 from mesenterial lymph nodes and tonsils and 44 from faeces. In addition, in 282 convalescent cases of the disease, diagnostic seroconversion or high titers of antibody to this virus were demonstrated. The most successful virus isolation was achieved by inoculation of green monkey kidney cell cultures and newborn white mice. Bulgarian strains of enterovirus 71 regularly caused paralysis in monkeys and morphological poliomyelitis-like lesions in their CNS, and paralysis and myositis with Zenker necrosis in newborn white mice, cotton rats, Syrian hamsters, and 3-week-old cotton rats. The diseased rodents had much more virus in their mucles than in brains.


Cytogenetic analysis of the sensitivity to anti-viral and anti-cell growth activities of human fibroblast interferon in aneuploid human tumor cell lines. Brief report. The ability of human fibroblast interferon to suppress colony formation and papovavirus T-antigen expression in six human tumor cell lines did not appear to correlate with their content of chromosomes 16 and 21. Additional factors or chromosomes may be involved in the manifestation of interferon action in aneuploid cells.


Investigation of physicochemical properties of Bulgarian strain 258 of enterovirus type 71. Brief report. In the present report some general physicochemical properties and RNA characteristics of strain 258 of enterovirus (EV) 71, isolated in 1975 from cases of poliomyelitis-like disease in Bulgaria (1), are described. It is concluded, that the features of the virus are consistent with the previous identification, based on biological studies, of this virus strain as a member of enterovirus subgroup of picornaviridae family.


Candida pachymeningitis with multiple cranial nerve pareses. A 66-year-old woman complained of right-sided headache and was found to have progressive dysfunction of cranial nerves V and VIII through XII on the right side. At autopsy, there was a granulomatous pachymengitis involving the floor of the right middle and posterior cranial fossae due to Candida tropicalis infection. Inflammatory tissue compressed the clinically affected cranial nerves.


Nucleic acid homology studies of viral nucleic acids in idiopathic Parkinson's disease. Reassociation kinetics analyses with radioiodinated herpes simplex type 1 DNA and influenza A/NWS RNA were performed in the presence of tissue nucleic acids from defined loci of the brains of nine patients with idiopathic Parkinson's disease, one normal control brain, and the brains of uninfected mice or mice infected with either herpes simplex type 1 virus or influenza A/NWS virus. Herpes simplex type 1 DNA was detected by an increased reassociation rate in the herpes simplex type 1 virus-infected mouse brains. Influenza A/NWS RNA was detected by reassociation in the influenza A/NWS virus-infected mouse brains. Experimental limits for the detection of homologous nucleic acids are given for each separate experiment with human or mouse tissue. Within these detection limits, nucleic acids complementary to herpes simplex type 1 DNA or influenza A/NWS RNA were not detected in any of the brains of patients with idiopathic Parkinson's disease.


Dibutyryl cyclic adenosine 3',5'-monophosphate: its role in regulation of cat brain extracellular fluid. The role of dibutyryl cyclic adenosine 3',5'-monophosphate (db cAMP) in influencing the water content of the cat's gray and white matter was evaluated by intracoritcal injection of 20 micrio L of 2 x 10(-1) to 2 x 10(-6)M solution of db cAMP. Cholera toxin, a stimulator of adenylate cyclase, also was tested. Concentrations of db cAMP less than 10(-3)M failed to produce significant change in brain water content, while concentrations greater than 10(-2)M produced 31.5% +/- 8% and 17.3% +/- 3.6% increases in white matter volume, respectively (P less than .05). Cholera toxin did not increase brain water levels. These results are discussed in relation to the pathophysiology of brain edema.


Aspirin, cyclophosphamide, and dexamethasone effects on experimental secondary herpes simplex uveitis. The effects of aspirin, cyclophosphamide, and dexamethasone on secondary herpes simplex uveitis were studied in rabbits. Neither daily treatment with aspirin (rectal suppositories, 650 mg begun 24 hours before challenge) nor cyclophosphamide injections every two days (80 mg begun eight days before challenge) had any effect on the severity of the uveitis, on the rise in intraocular pressure (IOP), or on the host's immune responses. As in the control animals, infectious herpes simplex virus (HSV) could not be isolated from iris tissues of either aspirin- or cyclophosphamide-treated rabbits. On the other hand, twice-daily treatment with topical dexamethasone (0.1% drops begun 24 hours before challenge) lessened the severity of the uveitis appreciably and suppressed the rise in IOP, but iris tissues yielded infectious HSV in two of ten eyes. Although the dexamethasone had no effect on the neutralizing-antibody or macrophage migration inhibition factor, it markedly suppressed the chemotactic activity of the aqueous humor for both polymorphonuclear leukocytes and macrophages.


Emerging patterns of hepatitis B chronic liver disease in Australia. Until now, the hepatitis B virus has been thought to play a minor role in the aetiology of chronic liver disease in Australia. This is a report of 21 patients with cirrhosis and/or primary hepatocellular carcinoma with hepatitis B antigenaemia. Primary hepatocellular carcinoma occurred in six patients, five of whom had underlying cirrhosis. The disease occurred mainly in non-Australian born males, and was not often associated with a previous history of hepatitis. The death of 16 patients within 12 months of presentation is in contrast to previous concepts of the benign nature of hepatitis B associated cirrhosis.


Maternal immunosuppression and cytomegalovirus infection of the fetus. Prenatal cytomegalovirus (CMV) infection associated with severe brain damage was detected in an infant whose mother had been treated with prednisolone and azathioprine for systemic lupus erythematosus (SLE). Serology showed that maternal CMV infection had been acquired at least four months before pregnancy. Screening for CMV infection in pregnant women receiving immunosuppressive drugs is recommended.


Autoradiographic localization of binding sites for follicle stimulating hormone (FSH) in the boar testis. The tubular localization of binding sites for 125I-FSH is demonstrated in vitro by the autoradiography on frozen sections of boar-testis. The uniform distribution of silver grains throughout the seminiferous epithelium suggests the presence of receptors for FSH also in the adluminal compartment. Similar results have been obtained using rat testis.


Studies on enzymes of collagen biosynthesis and the synthesis of hydroxyproline in macrophages and mast cells. The activities of four intracellular enzymes of collagen biosynthesis were assayed in freshly isolated rat peritoneal macrophages and mast cells and compared with the same enzymes in freshly isolated chick-embryo tendon cells. The macrophages were found to contain activities of all four enzymes, those of prolyl and lysyl hydroxylase being 7 and 12% respectively of those in the tendon cells when expressed per cell or 3 and 4% when expressed per unit of soluble cell protein. The corresponding values for hydroxylysyl galactosyltransferase and galactosylhydroxylysyl glucosyltransferase activities were about 82 and 68% or 32 and 24% respectively. When the macrophages were incubated in suspension with [(14)C]proline, they synthesized a small but significant amount of non-diffusible hydroxy[(14)C]proline. The synthesis per cell was only about 0.1% of that formed by the tendon cells, and its distribution between the cells and the medium also differed from that in the tendon cells. The hydroxy[(14)C]proline synthesized by the macrophages may be present in the Clq subcomponent of the complement, but its amount was too small to allow any characterization of the protein. All four enzyme activities, and in particular the two hydroxylysyl glycosyltransferase activities, seem to be present in macrophages in a large excess compared with the very low rate of synthesis of hydroxy-proline-containing polypeptide chains. The mast cell extract was found to inhibit all four enzyme activities, but even when corrected for this inhibition, prolyl and lysyl hydroxylase activities in the mast cells were less than 0.08% and the two hydroxylysyl glycosyltransferase activities less than 1% of those in the tendon cells. The intracellular enzyme pattern of collagen biosynthesis in the mast cells is thus completely or virtually completely repressed.


Tri-iodothyronine-induced increase in rat liver nuclear thyroid-hormone receptors associated with increased mitochondrial alpha-glycerophosphate dehydrogenase activity. The effect of tri-iodothyronine injection on the nuclear tri-iodothyronine receptor (putative thyroid-hormone receptor) was examined in rat liver. Nuclear receptors were extracted from isolated nuclei with 0.4 M-KCl, and their association constants (Ka) and maximal binding capacities (Cmax.) were determined by Scatchard analyses with and without correction for the endogenous hormone. The amount of endogenous tri-iodothyronine bound to non-histone protein was estimated on the basis of the specific radio-activity of [125I]tri-iodothyronine injected 2 h before the rats were killed. It was demonstrated that Cmax. of the nuclear receptors was 2.5-fold higher in severely hyperthyroid than in hypothyroid rats. However, irrespective of the thyroid status, the Ka of the receptors remained unchanged when corrected for endogenous tri-iodothyronine bound to non-histone protein. The validity of the correction was supported by experiments in vitro in which nuclear receptors were preincubated with unlabelled tri-iodothyronine. The increase in Cmax. of nuclear receptors was directly related to mitochondrial alpha-glycerophosphate dehydrogenase activity. These results suggest a hormonal modulation of the nuclear receptors which is associated with hormonal action.


Sequential changes in rat liver nuclear tri-iodothyronine receptors and mitochondrial alpha-glycerophosphate dehydrogenase activity after administration of tri-iodothyronine. The dynamics of the induction of nuclear tri-iodothyronine receptors and mitochondrial alpha-glycerophosphate dehydrogenase were studied in rat liver after a single injection of tri-iodothyronine. The maximal binding capacity (C(max.)) and association constant (K(a)) of the nuclear receptors were determined by Scatchard analyses with and without correction for the endogenous tri-iodothyronine measured by radioimmunoassay. The administration of tri-iodothyronine induced sequential increases in the concentration of nuclear receptors and alpha-glycerophosphate dehydrogenase activity in the liver. The nuclear-receptor concentration was increased to 2.5 times that in the hypothyroid rat 1 day after the administration of hormone, and then decreased, with a half-life of about 2 days. alpha-Glycerophosphate dehydrogenase activity changed in parallel with the nuclear-receptor concentration, showing a delayed response. The total amount of non-histone protein in the liver was significantly increased 3 days after the administration. It seems likely therefore that the tri-iodothyronine-induced increase in nuclear-receptor concentration is responsible, at least in part, for the induction of this enzyme. The possibility is also suggested that nuclear receptors may be one of the non-histone proteins selectively synthesized at an early stage of the hormonal stimulation. Throughout the time course, the K(a) values of the nuclear receptors for tri-iodothyronine remained unchanged, when corrected for endogenous tri-iodothyronine bound to the non-histone proteins, although they were apparently changed when the correction was not made. The results obtained provide further evidence for hormonal modulation of the nuclear receptors which is closely linked with the hormonal effect.


Effect of vitamin D deficiency on bone formation in the chick. 1. The process of diaphyseal bone formation can be investigated by studying the rate of incorporation of radioactive precursors, administered in vivo into bone fractions of increasing density. 2. In the 4-week-old vitamin D-treated chick most of the osteoid becomes calcified within 12h and almost all within 2 days. The low-density calcified phase that is formed is converted into a higher density form and within 7 days the greater proportion of the calcified tissue is in the higher density form. 3. In the vitamin D-deficient chick of similar age the rate of calcification of osteoid is decreased, as is the rate of conversion into the higher density phase with the resultant accumulation of the lower density calcified form. 4. The higher density phase probably corresponds to hydroxyapatite and the lower density one to the ACP-pase described by Termine & Posner [(1967) Calcif. Tissue Res. 1, 8--23]. 5. The disorder in the process of calcification seems to be unrelated to the alteration in blood Ca2+ and phosphate concentrations, but related to the presence or absence of cholecalciferol.


Characterization of cyanide-insensitive respiration in mitochondria and submitochondrial particles of Moniliella tomentosa. Mitochondria and submitochondrial particles of the osmophilic yeast-like fungus Moniliella tomentosa may respire by means of two pathways: a normal cytochrome pathway, sensitive to cyanide and antimycin A, and an alternative pathway, which is insensitive to these inhibitors but is specifically inhibited by salicylhydroxamic acid. The affinities of both oxidases for succinate and NADH as substrates, for O(2) as terminal electron acceptor, and for AMP as stimulator of the alternative oxidase were determined. 1. Submitochondrial particles of M. tomentosa may also respire by means of a cyanide-sensitive and/or cyanide-insensitive system. 2. The activities of both oxidases as compared with the total activity are roughly the same in submitochondrial particles as in the original mitochondria. 3. The terminal oxidase of the cyanide-insensitive pathway requires a 10-fold higher O(2) concentration for saturation than does cytochrome c oxidase. 4. The apparent K(m) for succinate is about 3 times higher for the alternative than for the normal oxidase when measured in mitochondria, and 4-10 times higher when measured in submitochondrial particles. The apparent K(m) for NADH is roughly the same for both oxidases. 5. The apparent K(m) values of both oxidases for succinate are always lower in submitochondrial particles than in mitochondria. 6. The apparent K(m) for AMP, acting as a stimulator of the alternative oxidase, is the same (25mum) in mitochondria as in sub-mitochondrial particles. These results are discussed in the light of the structure and localization of the components of the alternative oxidase.


Electron-paramagnetic-resonance measurements of the electron-transfer components of the reaction centre of Rhodopseudomonas viridis. Oxidation--reduction potentials and interactions of the electron acceptors. Oxidation-reduction potentiometry was carried out on Rhodopseudomonas viridis chromatophores. Measurements of e.p.r. signals of the semiquinone-iron type at g=1.82 have revealed a more complex situation than previously reported. The presence of three different components is indicated. The midpoint potential (E(m)) of the primary acceptor quinone/semiquinone couple was found to be approx. -165mV at pH10, with a pK being reached at around pH7.5. The primary acceptor also accepts a second electron with an E(m) of -525mV, but this redox transition exhibits a hysteresis effect. Interaction effects indicate the presence of another component with E(m) values at pH10 of approx. -165mV (pK reached at around pH7.5) for single reduction and -350mV (pK at pH10 or greater) for double reduction. It is suggested that this component is the secondary acceptor. Another semiquinone-iron-type component which gives a g=1.82 signal is also present. This component is distinguishable from the primary acceptor by its e.p.r. spectrum, which shows a double peak at g=1.82 and a g(x) line at g=1.76. This component has E(m) values at pH10 for single and double reduction of -15mV and approx. -150mV respectively. Both of these E(m) values are pH-dependent. The presence of an interaction between this component and the photoreduced primary acceptor indicates the close proximity of these components. However, the midpoint potential of this component indicates a function as a secondary electron-transport component rather than an electron acceptor in the reaction centre. The dependence of the bacteriopheophytin intermediate (I) doublet e.p.r. signal on the presence of the semiquinone-iron form of the primary acceptor is demonstrated. The midpoint potential of the I/I(-) couple is estimated to be lower than -600mV.


Protein phosphorylation in human peripheral blood lymphocytes. Subcellular distribution and partial characterization of adenosine 3':5'-cyclic monophosphate-dependent protein kinase. Cytoplasmic and membrane fractions prepared from human peripheral-blood lymphocytes both contained cyclic AMP-dependent protein kinase activity and endogenous protein kinase substrates. Protein kinase activity in the particulate fractions was not eluted with 0.25 M-NaCl, suggesting that it was not derived from non-specifically absorbed soluble cytoplasmic protein kinase. Nor was the particulate protein kinase activity eluted by treatment with cyclic AMP, suggesting that the catalytic subunit is membrane-bound and arguing against cyclic AMP-induced translocation of particulate activity. Cyclic AMP-dependent protein-phosphorylating activity in the cytoplasmic fraction was highly sensitive to inhibition by Mn2+, and was co-eluted from DEAE-cellulose primarily with type-I rabbit skeletal-muscle kinase. Cyclic AMP-dependent phosphorylating activity in the plasma-membrane fractions was stimulated at low [Mn2+] and inhibited only at high [Mn2+]. When solubilized with Nonidet P-40, plasma-membrane protein kinase was co-eluted from DEAE-cellulose with type-II rabbit muscle kinase. These differences, together with the strong association of the particulate kinases with the particulate fraction, suggest the possibility of compartmentalized protein phosphorylation in intact lymphocytes.


Protein phosphorlyation in human peripheral blood lymphocytes. Phosphorylation of endogenous plasma membrane and cytoplasmic proteins. Phosphorylation of endogenous proteins in subcellular fractions of human peripheral-blood lymphocytes was studied by one- and two-dimensional polyacrylamide-gel electrophoresis. Studies using extensively purified subcellular fractions indicated that the endogenous phosphorylating activity in the particulate fractions was derived primarily from the plasma membrane. Electrophoresis of (32)P-labelled subcellular fractions in two dimensions [O'Farrell (1975) J. Biol. Chem.250, 4007-4021] provided much greater resolution of the endogenous phosphoproteins than electrophoresis in one dimension, facilitating their excision from gels for quantification of (32)P content. More than 100 cytoplasmic and 20 plasma-membrane phosphorylated species were observed. Phosphorylation of more than 10 cytoplasmic proteins was absolutely dependent on cyclic AMP. In the plasma membrane, cyclic AMP-dependent phosphoproteins were observed with mol.wts. of 42000, 42000, 80000 and 90000 and pI values of 6.1, 6.3, 6.25 and 6.5 respectively. Phosphorylation of endogenous cytoplasmic and plasma-membrane proteins was rapid with t((1/2))=5-12s at 25 degrees C. Between 40 and 70% of the (32)P was recovered as phosphoserine and phosphothreonine when acid hydrolysates of isolated plasma-membrane phosphoproteins were analysed by high-voltage paper electrophoresis. The presence of cyclic AMP-dependent protein kinase and endogenous phosphate-acceptor proteins in the plasma membranes of lymphocytes provides a mechanism by which these cells might respond to plasma-membrane pools of cyclic AMP generated in response to stimulation by mitogens or physiological modulators of lymphocyte function.


Changing pattern of cyclic AMP-binding proteins during germination of Mucor racemosus sporangiospores. Interation of cyclic AMP with a profoundly changing pattern of specific binding proteins was shown during aerobic germination of sporangiospores from the fungus Mucor racemosus. 32P-labeled 8-azido-cycli AMP, an analogue of cyclic AMP that forms a covalent linkage with the binding proteins under u.v. light, was used as the ligand. Binding proteins carrying this photoaffinity label were separated by polyacrylamide-gel electrophoresis and identified by radioautography. Equibiltrium dissociation constants (Kd) and binding-response curves in the presence of competing nucleotides were identical for both 8-azido-cyclic [32P]AMP and cyclic [3H]AMP. A quantitative binding assay with both 8-azido-cyclic [32P]AMP and cyclic [3H]AMP over the time course of sporangiospore germination indicated a parallel relationship between cyclic AMP-binding capacity and the intracellular concentrations of cyclic AMP reported in a previous study [Paznokas & Sypherd (1975) J. Bacteriol. 124, 134--139]. Both of these parameters attained transient high values at a time of development when addition of exogenous cyclic AMP prevents hyphal-germ-tube emergence. The measured Kd values did not change during sport germination.


Lipid environment of gastric potassium ion-stimulated adenosine triphosphatase. The K+-stimulated ATPase associated with the purified gastric microsomal fraction can be completely inactivated by treatment with 15% (v/v) ethanol for 60s at 37 degrees C, but not at 25 degrees C. Sequential exposure of the microsomal fraction to 15% ethanol at 25 degrees C and 37 degrees C caused release of 2.5% and 2.9% of the total membrane phospholipids respectively. Restoration of the enzyme activity was achieved by sonication with phosphatidylcholine in the presence of Mg2+, K+ and ATP, which were essential for the reconstitution. Our data suggest that the phospholipids extracted by 15% ethanol at 37 degrees C are derived primarily from the immediate lipid environment of the enzyme, and ATP, together with the metal ions, helps the partially delipidated enzyme to retain the appropriate configuration for the subsequent reconstitution.


Sex hormone production and action.

Sex hormone production and action. The mechanisms of the production of estrogens and androgens in women and men are reviewed. Extraglandular estrogen formation from circulating androgens is the principal source of estrogen in men and postmenopausal women. The amount of estrogen formed is dependent upon precursor availability and metabolic factors, such as obesity and hepatic disease. Both androgens and estrogens in the circulation of humans are bound to sex hormone binding globulin which limits their availability to target cell receptors.


Increased collagen prolyl hydroxylase activity in the aortic wall of rabbits exposed to chronic hypoxia. The activity of collagen prolyl hydroxylase in aortic wall was studied in rabbits exposed to chronic 10% ambient oxygen tension for 30 days. Prolyl hydroxylase in rabbit aorta was shown to be similar to the enzyme from other sources in that it required molecular oxygen, alpha-ketoglutarate, ferrous iron and ascorbate for its activity. The activity of prolyl hydroxylase was increased to 180% of controls in the intima-media samples from rabbits exposed to hypoxia. No atherosclerotic lesions could be seen in arteries of animals kept in chronic hypoxia. If the arteries of rabbits were injured with a single mechanical dilatation, the activity of prolyl hydroxylase increased more than 2-fold, as reported previously. The exposure of these animals to chronic hypoxia further elevated the prolyl hydroxylase activity.


Short-term egg yolk feeding in humans. Increase in apolipoprotein B and low density lipoprotein cholesterol. In animal studies, hypercholesterolemia induced by cholesterol feeding results in the plasma cholesterol being transported by lipoproteins of lower densities. Little information is available for humans. To determine the specific lipoprotein responses to dietary cholesterol challenge in humans, four volunteer subjects ingested a liquid formula diet containing 5000 mg of egg yolk cholesterol per day for 30 days and the changes in their lipoprotein fractions were examined. The high dietary cholesterol (above the range of normal diet) was associated with marked increases in apolipoprotein B and low density lipoprotein (LDL) cholesterol levels. An elevated cholesterol : triglyceride ratio in the LDL fraction indicated that the diet altered both LDL level and composition. High density lipoprotein cholesterol and apolipoprotein AI increased slightly. Very low and intermediate density lipoprotein cholesterol and apolipoprotein E levels did not increase during the diet. Thus, high dietary cholesterol was associated with major changes in LDL level and composition, but only minor changes in the other lipoprotein fractions and suggested only minor accumulation of remnant particles.


Protein content and composition of human high density lipoprotein subfractions. High density lipoprotein (HDL) was fractionated by ion exchange column chromatography using a continuous NaCl gradient of 0.06--0.13 M. It was found that, on the basic C apoprotein content, HDL is comprised of 3 subfractions. All 3 subfractions contain apo A-I and apo A-II but the apo A-I/apo A-II ratio is different in each subfraction and in the case of subfraction c, that fraction which eluted at highest NaCl concentrations, the A-I/A-II ratio varied even within this subfraction. Subfraction a contained no C apoprotein, subfraction b contained apo C-II and apo C-III-1 but no apo C-III-2 while subfraction c contained apo C-III-2 and trace amounts of apo C-II and C-III-1. Analysis of HDL2 and HDL3 shows that both contain all 3 lipoprotein subfractions, but in differing quantities.


Uptake and degradation of low density lipoproteins (LDL) by confluent, contact-inhibited bovine and human endothelial cells exposed to physiological concentrations of LDL. Metabolism of low density lipoproteins (LDL) was studied in cultures of endothelial cells derived from bovine aorta or heart and from human umbilical veins. At low LDL concentrations nonconfluent cultures of bovine endothelial cells catabolized more LDL protein than contact-inhibited confluent cultures but this difference was reduced at high LDL concentrations. Nonconfluent human endothelial cells displayed also a higher rate of LDL degradation than their contact-inhibited counterparts, but this difference was less pronounced than in the bovine cells. Bovine endothelial cells grown in the presence of fibroblast growth factor metabolized less LDL than those cultured without fibroblast growth factor (FGF), but this difference was not consistent in the human endothelial cells. The data presented provide evidence that contact-inhibited confluent human endothelial cells are capable of catabolizing LDL when exposed to physiological concentrations of this lipoprotein.


The effects of cholestyramine on high density lipoprotein metabolism. This study on 4 type II hyperlipoproteinaemic subjects examines the effects of pharmacologic doses (8 g twice daily) of the bile acid sequestrant cholestyramine on the plasma distribution and chemical composition of the high density lipoprotein subfractions, HDL2 and HDL3, and describes the influence of the drug on the metabolism of the major HDL aporoteins, apolipoprotein A-I and A-II. Cholestyramine lowered plasma low density lipoprotein cholesterol (32%; P less than 0.05) without affecting the level of that lipid in very low density or high density lipoproteins. However, the plasma HDL2/HDL3 ratio and apolipoprotein A-I concentration rose significantly on treatment, while apolipoprotein A-II remained unchanged. The rise in apolipoprotein A-I derived from an increase in its synthetic rate and produced a relative enrichment of the protein with respect to apolipoprotein A-II in both HDL subfractions. These results demonstrate the cholestyramine treatment affects HDL metabolism in a way which, according to current concepts, may prove beneficial to the recipient.


Changes in plasma lipoproteins accompanying diet therapy in obese diabetics. Plasma lipoprotein cholesterol and triglyceride levels were measured in 24 obese not-insulin dependent Pima Indian diabetics and 9 obese nondiabetic controls before and after 1-8 months on a 500 calorie diet. The diabetics were divided into 3 groups--severe, recent onset (n = 10), severe long-term (n = 6), and borderline (n = 8). The diet regimen resulted in weight loss and improved glucose tolerance in all of the diabetics, and insulin secretion increased in the 2 groups of severe diabetics. After the period of weight loss, total plasma cholesterol had declined greater than 20%, and LDL cholesterol decreased 25% in all diabetic groups and in the controls. In all diabetic groups, HDL cholesterol did not decline; therefore the ratio of HDL/LDL cholesterol after diet therapy was significantly increased. In the controls HDL cholesterol declined with weight loss, and the distribution of HDL/LDL cholesterol remained constant. Plasma and VLDL triglyceride levels decreased in all groups in those with initial triglyceride levels greater than 150 mg/dl. The results indicate that weight loss in not-insulin dependent diabetics not only improves glucose tolerance, but also lowerss plasma lipids and reverses the dyslipoproteinemia often associated with this disorder. This may influence the risk of arteriosclerotic heart disease in these individuals.


Pronounced lipoprotein lipid reduction obtained by combined lipid-lowering treatment in patients with atherosclerotic disease. The feasibility of reducing serum lipoprotein levels in patients with atherosclerotic disease by combining diet, clofibrate and nicotinic acid (niceritrol) has been investigated. An additive lipid-lowering effect of diet and the two drugs was demonstrated. It was possible to reduce the serum triglycerides (TG) in hypertriglyceridaemic patients by 50-60%. This corresponded to a reduction of very low density lipoprotein (VLDL) TG by 73 and 66% in patients with hyperlipoproteinaemia (HLP) type IIB and IV, respectively. In normotriglyceridaemic patients the serum TG concentration decreased by 30-40%. The serum cholesterol (Chol) concentration was reduced by 33% and the low density lipoprotein (LDL) Chol by 37% in HLP type IIA and IIB. The LDL Chol decreased by 32% in normolipoproteinaemic patients and by 21% in HLP type IV. The mean value for serum cholesterol after therapy was in all groups close to 200 mg/100 ml. In hypertriglyceridaemic patients high density lipoprotein (HDL) Chol increased by 18%. Clofibrate and niceritrol differed with regard to the effect on serum lipoprotein concentrations as well as on other metabolic parameters. Niceritrol was significantly more effective than clofibrate in lowering LDL Chol and in increasing HDL Chol. Niceritrol treatment significantly reduced the Chol/TG ratio in VLDL while no such effect was seen during clofibrate administration. The two drugs also showed significantly different effects on the fractional removal rate (K2) of triglyceride-rich lipoproteins as measured by the intravenous fat tolerance test (IVFTT). The K2 was significantly increased by clofibrate but was not affected by niceritrol treatment. The two drugs differed also with regard to the effects on serum uric acid concentration and the liver function tests. The plasma fibrinogen levels and the erythrocyte sedimentation rates were reduced during treatment with both niceritrol and clofibrate. The present study demonstrates that it is possible to obtain substantial reductions of serum lipoprotein concentrations by combining lipid-lowering diet, clofibrate and niceritrol treatment. There was an additive lipid-lowering effect of this treatment and the combination of the two drugs seemed beneficial in regard to certain possible side effects. The impact of a lipid reduction within this range on cardiovascular morbidity and mortality remains to be evaluated.


[Lipid aspects in subjects with glucose-6-phosphate dehydrogenase deficiency]. To control some aspects of Lipid metabolism in G-6-PD defective subjects, are evaluated the haematic levels of Cholesterol, Tri glycerides, total Lipids and Lipoproteins. There is no significative difference between enzymopathic and normal control subjects.


[Effects of calcium, ethanol and hyperosmolarity on the distribution of intervals between MEPP's]. Distributions of intervals between MEPP's, recorded from the frog sartorius muscle in various experimental conditions, were compared, graphically and by X2, with the exponential distributions expected for a Poisson process. For each experiment, 200 intervals were measured. In isotonic Ringer solutions containing no Ca++, MEPP's fitted an exponential distribution; by adding Ca++ (1 mM, 2,5 MM, 15 mM), the fit between empirical and expected distributions became poorer, with an excess of short intervals. MEPP's showed the tendency to occur in bursts, and this was particularly evident at 15 mM Ca++. In the presence of 0,5% ethanol, also at high Ca++ the intervals between MEPP's showed a fair fit to the exponential distribution. In Ringer solutions made hypertonic by the addition of 50 mM sucrose, the fit was poor and there was a relative lack of short intervals. These different patterns of MEPP distribution could be explained by supposing that Ca++, ethanol and hypertonicity activate different mechanisms of transmitter release.


[Glioma in the aged (author's transl)].

[Glioma in the aged (author's transl)]. Glioma is the most frequent primary brain tumor in the aged which is originally much less frequent comparing that of younger generations. A large majority of gliomas in the aged is malignant. Besides the result of operation and follow-up result have been heretofore reported as more unfavorable. Fourteen cases of glioma in the aged, over 60 years of age, including 7 glioblastomas, 6 anaplastic astrocytomas and one unspecified malignant glioma, have been reported. Preoperative period varied from one month to 15 years and in 6 cases the period was less than 3 months. Poor preoperative state especially disturbance of consciousness mostly due to a markedly increased intracranial pressure, observed in 71% of the cases. The malignant gliomas which were frequently seen among the aged might be transformed tumors of more benign gliomas which originated in the younger generations and developed slowly and silently. Unfavorable prognosis of glioma in the aged might be closely related to the histological nature and poor preoperative state. However, delay of making correct diagnosis and rapidly progressive onset both of which have been mentioned as the speciality of brain tumor in the aged, were not closely related to the unfavorable prognosis.


Evaluation of leucocyte adherence inhibition in hepatocellular carcinoma. The value of the leucocyte adherence inhibition (LAI) test in the diagnosis of hepatocellular carcinoma (HCG) was investigated in 36 patients with this tumour. The sensitivity and specificity of the tube LAI test was assessed in 21 patients with HCC, 15 apparently healthy individuals, 9 patients with various forms of benign liver disease and 5 patients with non-hepatic neoplasms. In only 42% of the HCC patients tested was leucocyte adherence to glass reduced to a greater extent than in the healthy controls and in the patients with non-hepatic neoplasms, and the differences were not statistically significant. Moreover, positive results were obtained in 6/9 patients with benign hepatic disease. A further 15 patients were tested against extracts of HCC tissue using the haemacytometer LAI method. Of these, 53% gave positive results. In all, only 17/36 patients (47%) gave positive LAI responses. The test is thus of limited value in the diagnosis of HCC. The high false-negative result rate may be due either to abrogation of the immune response in HCC patients with large tumour burdens or to antigenic heterogeneity in HCC.


The antitumour agent 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide (DTIC) inhibits rat liver cAMP phosphodiesterase and amplifies hormone effects in hepatocytes and hepatoma cells. The antitumour agent 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) was found to inhibit competitively the low-Km cyclic AMP phosphodiesterase activity in an ammonium-sulphate-precipitable fraction of the 2,000g supernatant of rat liver. With substrate concentration at 0.25 microM, I50 was 790 microM for DTIC and 350 microM for theophylline. DTIC at 2 mM more than doubled the cAMP response to glucagon in hepatocytes and to adrenaline in MH1C1 hepatoma cells, indicating that it also exerts its inhibitory effect on the phosphodiesterase in intact cells. The possible contribution of the phosphodiesterase inhibition to the growth-inhibitory and cytotoxic effects of DTIC is discussed.


Focal epithelial hyperplasia of the oral mucosa. A case report from the United Kingdom. A case of focal epithelial hyperplasia of the oral mucosa (Heck's disease) is presented, which appears to be the first to be described in the United Kingdom. Virus particles were found in tissue from the lesions studied by electron microscopy, and identified as belonging to the papilloma virus sub-group of the family of papovaviruses.


Studies on the plasma membrane of normal and psoriatic keratinocytes. 2. Cyclic AMP and its response to hormonal stimulation. Cyclic AMP levels have been determined for the first time in isolated keratinocytes. Values were more reproducible than those reported using epidermal slices. Evidence is presented to show that damage to hormone receptors is minimal. Other observations include the following: (1) Keratinocytes from psoriatic lesions showed reduced 'resting' levels of cyclic AMP as well as a diminished response to adrenaline. (2) Cyclic AMP levels were maximal in the basal cells, falling dramatically in fully differentiated keratinocytes. (3) The topical application of a corticosteroid (fluocinolone acetonide) did not modulate the response of adenyl cyclase to hormonal stimulation.


Hand grip forces during chain saw operation and vibration white finger in lumberjacks. The hand grip forces at the front and rear handles of a chain saw were measured during work, in 89 professional lumberjacks. The symptoms caused by vibration to the upper limbs were compared with the hand grip force (HGF) during work. To allow better comparison between subjects we used the ratio of hand grip force (HGF) to the maximal voluntary compression force (MVC), HGF/MVC expressed as a percentage. The mean HGF during sawing varied from 5 to 12 N in all subjects. The variation in HGF was greater at the front handle than at the rear handle, during sawing. The lumberjacks who had vibration-induced white fingers (VWF), had a higher HGF/MVC in both hands than the lumberjacks without VWF. Those lumberjacks affected by VWF used over 12% of their MVC at work. Subjects without HGF/MVC ratio. The lumberjacks with and without numbness in their hands had equal HGF/MVC ratios.


An analysis of the influences of maternal age, gestational age, contraceptive method, and the mode of primary treatment of patients with hydatidiform moles on the incidence of subsequent chemotherapy. In relation to the total number of births in the United Kingdom there was an excess of hydatidiform moles arising in women over 34 years of age and possibly also under 15. The incidence of trophoblastic tumour requiring chemotherapy after hydatidiform mole was greatest in the 30 to 34 years age group and it was also high in the 20 to 24 years age group. This distribution appears to be influenced by the morphology of the moles, the mode of their removal and the use of oestrogens and progestogens in the post-evacuation period. The need for chemotherapy for trophoblastic tumour after evacuation of a hydatidiform mole was found to be two- to three-fold greater in patients who had undergone a medical induction, hysterectomy or hysterotomy compared with those whose hydatidiform moles had been evacuated by vacuum or surgical curettage, or who had aborted spontaneously. The increased risk of chemotherapy was most marked in the earlier weeks of gestation.