[Cefoxitin, a new semi-synthetic cephamycin (author's transl)]. The authors review the procedure utilized for the naming of a new antibiotic. The cephamycins are taken as an example. Cefoxitin, derivative of the cephamycin C through an original chemical reaction is described. This antibiotic possesses a high degree of resistance to beta-lactamases due to the presence of a methoxy group in the 7alpha position of the beta-lactam ring. The results of extensive in-vitro trials are given, they indicate that cefoxitin has a unique antibacterial activity.


[Amyloid tumors of the lung. Apropos of a new case]. The authors report a new case of pseudo-tumoral nodular amyloidosis of the lungs. The amyloid nodules being discovered during a surgical procedure for an adenocarcinoma of the lower oesophagus. The histopathological study of the nodules confirmed their amyloid origin and allowed to precise their histochemical features.


[Long term administration of oral prednisone or prednisolone in treatment of myasthenia gravis. Report of five cases (author's transl)]. Five patients, four of them with severe or severe generalized myasthenia gravis, were treated by long term orally administrated prednisolone, with following results: one complete remission and two almost complete remissions (in three aged fernale patients), two substantial improvements (one in a male patient, one in a young adult female patient, both thymectomized). The least favourable result was observed in the male patient. Positive results of such treatment were similarly reported by several authors (with an average of 70% complete or almost complete remission, 20% substantial improvement, 7% moderate improvement). These results appear qualitatively superior to those obtained with ACTH, and may be long-lasting. Treatment with prednisolone may be applied to any form of myasthenia gravis, particularly those which do not react to anticholinesterasic agents in moderate dosages. At onset of treatment, patients should be under care of a reanimation unit. Dosage is initially high (60--100 mg daily, secondarily on alternate days), and should be reduced very slowly, once a definite improvement is achieved. The duration of this treatment depends upon the results obtained: it should not last under one year. Associated treatment with anticholinesterasic agents remains disputable, whereas associated thymectomy seems to provide best results.


[Indication and problems of radiotherapy of primary bone and cartilage tumours of the thoracic wall (author's transl)]. The authors discuss the management in radiotherapy of bony tumours of the thoracic wall: necessity of accepting the risk due to the volume of healthy tissue which is inevitably irradiated, the technics of irradiation which limit these risks. Limited hope of improvement of the still modest results with new technics of radiotherapy. They emphasize the difference which exists between the idea of radiosensitivity and radiocurability.


[Comparative clinical evaluation of two mucolytic agents: S-carboxy-methyl-cysteine and letosteine (author's transl)]. A controlled double-blind clinical trial comparing a noval medicament, letosteine, to a known bronchial fluidifier, S-carboxy-methyl-cysteine, was conducted on a total of 47 hospitalized patients suffering from various types of chronic obstructive lung disease. Daily observations were made on the patients themselves and on sputum samples obtained from them before, during and after the course of mucolytic therapy. When the code was broken at the end of the trial, there appeared no significant difference between the patient groups treated with the two drugs regarding either changes in respiratory symptoms or changes in sputum characteristics. Thus, in this study, letosteine (50 mg t.i.d.) appeared equivalent to S-carboxy-methyl-cysteine (750 mg t.i.d.) in the treatment of chronic obstructive lung disease in adults.


[Plexus lesions following radiation therapy. Report of nineteen cases (author's transl)]. Nineteen patients with plexus lesions following radiation therapy were investigated: fifteen with brachial plexus, 4 with lumbar or sacral plexus involvement. Symptoms at onset are usually sensory. Motor disturbances occur either simultaneously or after some delay, their course is generally gradual and unfavourable. Areflexia appears early and was present in every case. Important cutaneous lesions (radiodermitis) and considerable induration of soft tissues were observed in every patient. Diagnosis is a relapse of the mitotic process. Severity of prognosis makes imperative a definite technique of radiation therapy. In all the patients included in this study, dosage had exceded 1,600 rets. Patients were tentatively treated with D-penicillamine, an inhibitor of collagen synthesis.


[Cisterno-medullary anomalies. Diagnostic problems, surgical treatment (author's transl)]. Under the term cisterno-medullary anomalies are included several disorders: bony and nervous malformations, arachnoiditis of the posterior fossa. As they are frequently associated, a thorough investigation, both anatomical and dynamic, is a prerequisite to any therapeutic attempt. Along with causing damage to the neuraxis, these anomalies interfere with the dynamics of the CSF and may lead to the development of a communicating syringomyelia, whatever the theory proposed. The presenting symptoms are varied, and diagnosis should be accordingly suspected. Of fundamental importance are instrumental investigations. A complete evaluation is in most of the cases obtainable with: bone X-rays, air-myelography (or "bulle"), intrathecal ou ventricular radio-isotope scan. Surgery is the only treatment. The aim is both decompression of the neural structures and restoration of a normal CSF dynamic flow. Opening of the posterior fossa is successful in the case of developmental abnormalities, But it seems to prove a failure when the chief anomaly is arachnoiditis. In such cases, ventricular drainage alone may be followed by improvement. It appears from this that the problem is twofold: the technical problem of the drainage, and the pre-operatory diagnosis of a posterior fossa arachnoiditis.


[The induced hyperlipemia test. 10 years of experience]. The induced hyperlipemia test, which is easly to administer, yields very interesting information for the study of lipidic metabolism in arteriosclerosis patients. Its use, in both the pre- and post-operative phases, has brought out the valuable effect of ligature of the intestinal lymphatics in treating arteritis. It may also enable us to determine whether there is a hereditary factor or family predisposition to arteriosclerosis. Furthermore, the test makes it possible to confirm diagnosis of obstruction of the lymphatics of the gut in exsudative enteropathy and in various dysfunctious of the chyliferous vessels (sclerosis, rupture, tumoral invasion) without to resort to the use of radioactive substances.


[Reversible humoral alterations paralleling the course of a recurring meningioma with metastases (author's transl)]. Case report of a recurring meningioma of the posterior fossa, with pulmonary metastases. Humoral alterations (sedimentation rate, fibrinemia, alkalin phosphatases, sideremia, prothrombin, blood proteins and BSP) paralleled the course of the tumor and may be considered as a para-tumoral syndrome. Pathogenesis is unknown.


[A treatment of mild and moderate hypertension with timolol (author's transl)]. 21 patients with essential sustained mild or moderate hypertension were treated with timolol for an average of 6 months at a mean dosage of 3,14 tablets per day. The mean decreases of supine systolic and diastolic blood pressures were respectively of 17,8 and 7,3 mm Hg. The efficacy of timolol was considered excellent or good in 11 cases (52,4 p. cent) and its tolerance perfect in 15 cases (71,4 p. cent). The study was extended in 15 cases with one dose of timolol per day. Effectiveness remained excellent in 12 cases. There was neither orthostatic hypotension nor brady-cardia of less than 55 beats per minute nor water retention. Side effects appeared in 6 cases requiring discontinance of therapy in only one case (exertional dyspnea).


[Memorization and headaches (author's transl)]. The pathogenicity of headaches is still, in many cases, a mystery evoking the involvement or modification of basic algogenic processes. These types of headaches are usually resistant to true analgesics, and a medication which acts on the mesolimbic system could be effective. Tiapride, which has the characteristic of acting at this level, is not a true analgesic according to classical tests. Experimentally, however, it has been shown to inhibit the hypertensive algogenic response, which is a test of the overall response of the organism to painful stimuli. This special activity of tiapride probably accounts for its efficacy in many types of headache which are resistant to classical medication, the underlying tension, and emotional and memorization problems being due to the involvement of the mesolimbic system.


[Growth retardation in histiocytosis X. Evaluation of anterior pituitary function (author's transl)]. Among six patients with histiocytosis X of long duration and growth retardation of 3 to 4 standard deviations, three had a blunted growth hormone response to stimulation tests, associated to diabetes insipidus. In two of these three children there was a partial catchup of growth without treatment by human growth hormone. The causes and mechanisms of growth retardation in histiocytosis X, the influence of hydroelectrolytic disorders on growth in these patients and their need for treatment with human growth hormone are discussed.


[Pharmacokinetics use in anti-cancer therapy (author's transl)]. Dynamic studies of anti-neoplasic agents provide a mathematical expression of various biological steps. High specific technics of dosage make possible the measurements of the drugs and their metabolites. Pharmacokinetics provides a new approach to three fundamental aspects in oncology: drug toxicity, relationship between drug schedule and response in each individual, drug resistance to anticancer drugs. Rational therapeutic approaches are made possible, as it was shown by the use of high dose of methotrexate.


[The pulmonary aspiration-washing: new treatment of severe bacterial pneumopathies (author's transl)]. Over the last few years, the apparition of severe broncho-pulmonary suppurations in relation with an often poly-immune bacterial flora presents intricate therapeutic problems. The use of broncho-fibroscopy to enable several focussed cycles of broncho-pulmonary aspiration-washing perfusion, gave us interesting results.


[A new therapeutical approach in neurology (author's transl)]. The therapeutic action of Tiapridal appeared to the authors particularly precious and constant in delirium tremens, senile agitation and turbulence, whatever the origin, and bucco-linguo-facial dyskinesia, whether the latter were linked to age or whether they formed part of a neuroleptic syndrome. Their experience does not permit them to have any opinion concerning the use of this drug in tremor and chorea, the patients seem to respond favourably to treatment but in an erratic manner. On the other hand the drug was totally inefficacious in patients suffering from spasmodic torticollis and writer's cramp. Finally, it seemed to them useful to emphasise the improvement in comfort in patients suffering from various pains when given Tiapridal. This justifies the place given to Tiapridal among drugs necessary for the daily practice of neurology.


[Alpha chain disease. Report of a case (author's transl)]. A young patient, with alpha chain disease, is in good clinic condition, a little more than 4 years after the diagnosis. She received, during 1 year, antibiotics of tetracycline type, then antimitotics during 2 years. 9 months after antimitotics treatment was achieved, histologic signs remained unmodified, without evidence of degenerescence. Immunoelectrophoresis which was normal at the end of chemotherapy is always normal after 15 months without treatment.


[Hemangioendothelioma of bone:  A propos of an anatamo-clinical observation]. Malignant hemangioendothelioma, localised to the skeleton of the lower limbs, to the exclusion of any other bony or visceral involvement, complicated by hemolytic anemia and spontaneous fractures, edl to death in spite of bilateral amputation, less than one year after its chance discovery. The multifocal character of the bony lesions, which is common, may suggest either rapidly developing metastases, or multicentric development of the tumour. The clinical, radiological and laboratory signs--pure osteolysis of large size without condensation nor periostosis, are not specific. Pathological examination permits recognition of the vascular origin of the tumour but does not always permit one to recognize its malignant nature. Treatment, which is mainly surgical, is often ineffective.


[Constrictive pericarditis and post-radiotherapy myocarditis with mitral incompetence (author's transl)]. The cardiac complications of radiotherapy of the thorax (e.g. for Hodgkin's disease and carcinoma of the breast) are various: 1) Pleural effusions, occurring a few months to two years after radiotherapy, spontaneously curable but may give signs of tamponnade or lead to constriction. 2) Constrictive pericarditis often several years after irradiation, with a poor prognosis in spite of attempts at pericardectomy which is indicated at the stage of hemodynamic constriction. 3) Myocardial involvement with advanced fibrosis and with various clinical presentations. The failure of pericardectomy and mitral incompetence were evidence of myocarditis in the case reported here.


[Therapeutical test of Euthyral in thirty one cases of hypothyroidism (author's transl)]. Euthyral was prescribed in 31 cases of hypothyroidism. Plasma levels of T3, T4 and TSH were measured. Plasma TSH returned to normal values in all cases when daily doses of Euthyral exceeded 3/4 of a tablet. Plasma T4 returned to normal values in all cases when daily doses of Euthyral exceeded 3/4 of a tablet. Plasma T4 returned to normal values in all cases when daily doses of Euthyral exceeded half a tablet. Plasma T3 returned to normal values in all cases but was above normal values in 30 per cent of the cases when the daily doses of Euthyral exceeded 3/4 of a tablet.


[The controversy concerning whooping cough vaccination (author's transl)]. The importance of the neurological complications of whooping cough vaccination has been greatly exaggerated. Their frequency may vary tenfold, depending on the authors. Most of the latter are mainly linked to age and are thus coincidences. Other etiologies may be responsible, as also may a receptive constitutional background, the vaccine then simply reveals a preexisting condition. Present whooping cough vaccines are efficacious as shown by the fall in morbidity curves and the large number of cases in unvaccinated subjects during epidemics. Whooping cough in infants remains a problem which can only be solved by vaccination. Primary vaccination should be carried out as early as possible, while strictly observing the contraindications. The poor absorption of whooping cough vaccines is in favour of their injection by the intramuscular route which is better tolerated. Other vaccines with less reaction and more immunogenic are being sought.


Hepatoblastoma. A case report.

Hepatoblastoma. A case report. A case of hepatoblastoma in a 16-month-old Black child is described and the classification of hepatoblastoma is reviewed. Early diagnosis is important, since the prognosis is more favourable in hepatoblastoma than in hepatocellular carcinoma.


Computed axial tomography in intracranial neoplasms in children. The computed axial tomographic (CAT) findings in 22 children with intracranial neoplasms are presented. CAT offers a rapid, non-invasive method of assessing the locality and extent of these tumours, as well as the presence of calcification and hydrocephalus. CAT is of value in the follow-up treatment, but an absolute histological diagnosis is not always possible.


Cyclic nucleotides in platelet function. Inhibition of adenylate cyclase in intact platelets by addition of compounds such as 2', 5' - dideoxyadenosine prevented the inhibition of platelet aggregation by PGE1 but did not affect the responses of platelets to aggregating agents in the absence of PGE1. This confirms that cyclic AMP mediates the effects of PGE1 but indicates that the level of cyclic AMP in unstimulated platelets is too low to affect the actions of aggregating agents. Studies on the phosphorylation of proteins in intact 32P-labelled platelets showed that PGE1 increased the phosphorylation of a membrane-bound polypeptide (P24) and prevented the increased phosphorylation of other polypeptides (P47 and P20) that occurred on addition of inducers of the release reaction. It is suggested that the cyclic AMP-dependent phosphorylation of P24 stimulates the active transport of Ca(2+) out of the platelet cytosol, so preventing phosphorylation of P47 and P20, reactions which may be involved in the release mechanism. As increases in platelet cyclic GMP could be dissociated from both platelet aggregation and the release reaction, it is proposed that the bidirectional regulation of platelet function is achieved primarily by the opposing actions of increases in the concentrations of Ca(2+) and cyclic AMP.


Lesions of the caruncle: a clinicohistopathologic study. This study reports 112 caruncular lesions seen in the Eye Pathology Laboratory of the Wilmer Institute during a 52-year period (1923--1976). These uncommon lesions are analyzed with regard to their relative occurrence and their clinical and histologic features. Clinical grouping of these lesions is presented to help in the differential diagnosis of caruncular lesions. Nevi, papillomas, and sebaceous gland hyperplasia were the most commonly encountered lesions, accounting for 65% of the total.


Detection of antibody to a new antigen induced by Epstein-Barr virus in rheumatoid arthritis. A new antigen which is different from Epstein-Barr virion antigen was detected in NC-37 cells infected with Epstein-Barr virus (EBV). A significant elevation of the titer of antibody to this new antigen was observed in the sera of the patients with rheumatoid arthritis (RA), but not in the sera of controls. From the standpoint of the etiologic role of EBV in RA, it is interesting that the antibody to the new antigen is not detected in the healthy persons in contrast to other viral antibodies. Therefore, it differs from any other viral antibodies so far reported.


Prevention of tissue factor generation in mononuclear cells by agents known to increase intracellular cyclic AMP. Agents known to increase intracellular levels of cyclic 3', 5'-adenosine monophosphate (cyclic AMP) were examined for their effect on tissue factor generation by mononuclear cells cultured with E. coli endotoxin. Aminophylline, an inhibitor of phosphodiesterase, and epinephrine, a beta-adrenergic agent, showed an inhibitory effect, and these effects were reversible. Moreover, dibutyryl cyclic AMP also exhibited the effect. Dibutyryl cyclic GMP, however, did not enhance the tissue factor generation by mononuclear cells. On the basis of these observations, it was concluded that the phenomenon of tissue factor generation by mononuclear cells is a biological event, and that intracellular cyclic AMP has a possible role in modulating this phenomenon.


Machakos Project Studies: agents affecting health of mother and child in a rural area of Kenya. VII. The incidence of diarrhoeal disease in the under-five population. The outcome of three years of fortnightly diarrhoea surveillance of about 4000 children under the age of five is described. The two-weekly incidence of diarrhoea in children in the age group 0-5 months, 6-11 months and 12-23 months, who were reported and/or observed to be ill, was 3.4%, 5.6% and 3.4% respectively. A decline in the attack rates of diarrhoea not associated with measles at the end of 1975 and the beginning of 1976 corresponds with a similar decline in the incidence of measles and malnutrition. Initially diarrhoea information was only obtained from children who where reported and/or observed to be ill; later on, all mothers were questioned about their children's diarrhoea experience at the moment of the fieldworkers's visit or in the preceding two weeks. This yielded a four to sevenfold increase in diarrhoea incidence. Thus, diarrhoea appears to be a common condition among under-fives which is not necessarily considered to be an illness by the mother.


[Transformation of human embryonic cells by the Rous sarcoma virus and the polyomavirus depending on the mitotic cycle phase]. The whole cycle of skin-muscle embryonic human tissue culture is 18 hours, with phases S, G1, G2 and M being 7, 6, 4 and 1 hour, respectively. The mitotic index of this culture is 28%. The maximum sensitivity of these synchronized cell cultures to transforming activity of the Rous and Sindai viruses was observed in phase S. The infection of synchronized primary embryonic human fibroblasts in phase S with the polyoma virus together with the Sindai virus has resulted in single cases of transformation. Similar results were obtained with non-synchronized human cultures.


Comparative electron-microscopic studies of benign hepatoma and icterus in patients on oral contraceptives. The author compared the electron-microscopic picture of 6 benign hepatomas and 3 specimens of icteric liver tissue in female patients on oral contraceptives. The majority of ultrastructural changes seen were identical in the tumor and non-tumor cases. It is noteworthy that there is an accumulation of filamentous substance of unknown origin in the bile canaliculi and in the Disse's spaces associated with a damage to the cell membrane. The electron-microscopic picture of the sinusoidal endothelial cells suggested an increased protein producing activity. The most conspicuous feature of the tumours was formation of continuous capillaries at the site of the sinusoids. The importance of systematic electron-microscopic investigation in studying the effect of oral contraceptives on the liver cells is stressed by the author.


[Cyclic 3',5'-AMP metabolism in progressive muscular dystrophy patients]. Concentration of cyclic AMP was distinctly decreased in muscular tissue of patients with Dushenn's myodystrophy. Simultaneously, in patients with the myopathy basal activity of adenylate cyclase as well as activation of the enzyme by adrenaline and sodium fluoride were decreased. As a compensation, activity of phosphodiesterase was also decreased. Content of cAMP, activity and activation of adenylate cyclase were similar to normal state in patients with Erb's and Landuzi--Dejerin's myopathies; activity of phosphodiesterase was increased in the latter impairment. Dissociation constant for binding of cAMP by protein kinases was more than 10-fold decreased in patients with these types of myopathy.


[Changes in the lung tissue in bronchial adenomas]. Changes in the lung tissue in bronchial adenomas are not dependent on their histological structure, but on the anatomical form of growth, localization and duration of the existance. Both peripheral adenomas and cancer may have an asymptomatic course. In central (especially exophitic) adenomas distelectasis, atelectasis, fibrosis and vascular regeneration develop in sequence, while with the secondary infection-pneumonic foci. In relation to the mechanism of the development, lung tissue changes may arise as a result of invasive tumor growth, hypoxia, and impaired drainage function of the bronchi, toxico-immunological disturbances.


[Functioning of rat liver mitochondria in hepatitis]. Parameters of oxidative phosphorylation, the rate of respiration in various metabolic conditions as well as an activity and stability of mitochondrial polyenzyme systems were altered in rats with experimental hepatitis, treated with CCl4. Proteins and phospholipids from mitochondrial membranes proved to be more susceptible to the effect of trypsin and phospholipase D. Kinetics of cytochrome C desorption from membranes and mitochondria demonstrated that capacity of these membranes to confine the exogenous proteins was altered in hepatitis.


[Cyclic AMP system in muscle tissue during prolonged hypokinesia]. Constituents of cAMP system were studied in prolonged hypokinesia (70--75 days) and within the period of readaptation of muscular tissue in rats. Content of cAMP as well as activities of adenylate cyclase and phosphodiesterase were increased in muscles at the initial period of limited mobility (especially, within the first 5 days). Within the period of so-called "adaptation" (during the first 24--37 days) content of cAMP and activity of both enzymes were practically similar to control values. Distinct decrease in cAMP content, activation of phosphodiesterase and decrease in stimulating effect of adrenaline on adenylate cyclase activity were observed within the first 70 days of the experiment. Pronounced normalization of the patterns studied occurred within the period of readaptation.


[Hypolipidemic activity of substances structurally close to penphenone in rats and mice]. Effect of substances, structurally related to penphenone (2-phenyl-3-methyl-3-hydroxypentanic acid sodium salt), was studied on the main patterns of lipid metabolism in blood of rats and mice, as well as on lipoprotein spectra of rat blood serum. All the compounds studied exhibited hypolipidemic effect, decreasing concentration of total cholesterol, cholesterol of alpha-lipoproteins and triglycerides in rat blood. The effect was less distinct in mice. 2-phenyl-3,4-dimethyl-3-hydroxypentanic acid sodium salt possessed the most pronounced hypolipidemic effect. A decrease in content of beta-and pre-beta-lipoproteins as well as of alpha-lipoproteins was observed after electrophoretic separation of blood serum lipoproteins in polyacrylamide gel in animals treated with the compound.


[Antibody formation in type A viral hepatitis]. Immune response to hepatitis type A antigen (HAAg) was measured by the passive hemagglutination test (PHA) and by the immune adherence test (IAHA). Specific antibodies found by PHA are of the IgM class which indicates a recent exposure to hepatitis A virus. The antibodies found by IAHA reflect the level of postinfectious immune status. The antibody curve is highest in the age group of 30--49 years (95%). The above-mentioned serological tests were carried out with purified by gel filtration in Sepharose 6B Botevgrad faecal morphologically consisting of 27 nm particles with the buoyant density in CcCl of 1.40 g/ml. The same particles were aggregated with sera positive for antibody to hepatitis type A antigen in immune electron microscopy (IEM).


[Detection of an agent similar to rotavirus in infantile gastroenteritis]. The etiology of nonbacterial enterovirus infections in children was studied in autumn and winter under conditions of focal outbreaks in Moscow hospitals. Electron microscopy revealed a reovirus-like agent in concentrated suspensions of feces collected in the acute period of the disease from children suffering from diarrhea. Examinations of paired sera from the patients by the CF test with the antigen of Nebraska calf disease virus established significant rises in antibody titers in 68.3% of cases. The results permit a conclusion that in this country a virus of acute gastroenteritis of children (viral gastroenteritis A) is circulating, causing outbreaks of the disease. The virus belongs to the genus Rotavirus of the Reoviridae family.


[Activity of lactate dehydrogenase and its isofractions in experimental asymptomatic adenovirus infections]. Experimentally in 147 dog puppies an asymptomatic infection caused by adenovirus of human origin was produced and the process was caused to become manifest by administration of the same virus against the background of the effect of antilymphocyte serum. The activity of LDG in asymptomatic adenovirus infection was found to decrease in the cytoplasmic fraction of hepatocytes and to increase in the blood serum. An increase in the content of the "hepatic" complex of LDG in the blood serum and its decrease in the cytoplasmic fraction of hepatocytes was established indicating disorders in the liver function. It is concluded that asymptomatic adenovirus infection leads to the formation of the state of pre-pathology. Manifestation of the infection enhances the quantitative aspect of the changes.


[Several characteristics of new strains of diploid green marmoset fibroblasts]. Two strains of diploid fibroblasts were derived from green monkey fetal lungs and their main properties were studied. These strains were shown not to differ principally from the well studied human diploid fibroblasts. The derived cultures are free from contaminating viruses. The titers of attenuated poliomyelitis virus strains achieved in green monkey diploid cells are comparable to those in primary cultures of green monkey kidneys. The possiblity of using green monkey diploid fibroblasts in virological practice is discussed.


[Development of a method of concentrating enteroviruses for virologic studies of meat]. A method for concentration of enteroviruses in meat extracts was developed using polyvinylpyrrolidone (molecular mass 10,000), polyethylene glycol (molecular mass 15,000), both in 10% concentration, silicagel with a granule size of 200 mesh in a concentration of 5%, aluminum hydroxide in an amount of centrifuged pellet of 5 ml of original suspension per 10 ml meat extract. When the optimal conditions of meat extract preparation (meat mass: Hanks' solution ration 1: 10) were observed, followed by virus concentration in polymers of silicagel 2--4 PFU of enteroviruses in 1 g of meat could be determined in all the experiments. Virus doses of 0.2--0.5 PFU per 1 g of meat could be detected in some experiments.


[Isolation of type 71 enterovirus from patients with a poliomyelitis-like disease during an outbreak in Bulgaria]. Virological examinations of 72 specimens obtained during an outbreak of a poliomyelitis-like disease in Bulgaria, 1975, yielded 23 strains of enterovirus type 71 (E71) and 5 strains of enteroviruses of other types. The viruses were isolated in green monkey kidney cell cultures, in newborn cotton rats, newborn white mice and in monkeys. Most of E71 strains (16 out of 23) were isolated from the autopsy materials (brains and spinal cords) from 9 children dying of poliomyelitis, meningoencephalitis, and encephalitis. The remaining E71 strains and all the strains of other enterovirus serotypes, with the exception of ECHO7, were isolated from stool specimens of children with aseptic meningitis and their contacts. The antigenic similarity of the group of Bulgarian strains and their relationship with the prototype BrCr strain of E71 was established. The conclusion is that E71 was the causative agent of an outbreak of a poliomyelitis-like disease in Bulgaria.


[Steroid-examinations in serum of old men as a functional testing of the suprarenal glands (author's transl)]. A surgical intervention is dangerous for the old patient awing to the reduced reactiveness and polymorbity. The knowledge of the function of the suprarenal glands in stress (operation) is important. The latent insufficiency of the suprarenal glands is determined with the ACTH-stimulations test. 136 patients from 60 to 100 years were proved. In the case of a latent insufficiency of the suprarenal glands the substitution of glucocorticoids and ACTH is necessary.


Potassium adaptation after reduction of nephron population. Two weeks after 75 percent nephrectomy in rats fed a normal diet glomerular filtration rate was found to be reduced by 2/3 and there was no hyperkalemia. Normal K balance was maintained by a threefold increase of fractional urinary potassium excretion. When infused with 0.5 M KCl solution, both normal and 75 percent nephrectomized rats increased their fractional excretion, while normal rats kept on a very high K-diet did not further increase their fractional potassium excretion. Adaptation of fractional excretion to infused KCl was blunted in 75 percent nephrectomized rats given a low K diet.Addition of 0.1 M KCl to the drinking water resulted in a three- to fourfold increase of potassium intake in normal rats: within 7 days, the Na-K-ATPase in the outer medulla of the kidney rose by 30 percent but no change occurred in the cortex. Further increases in dietary K load induced an increase of Na-K-ATPase activity, both in outer medulla and cortex, but not in other tissues. After 75 percent nephrectomy, specific Na-K-ATPase activity increased by 20-25 percent in the outer medulla and in the cortex.Dietary K loading, in normal rats, also resulted in a large increase of net potassium secretion into the perfused colon and of specific Na-K-ATPase activity of the colonic mucosa. These effects of potassium loading were not abolished by adrenalectomy and were accompanied by an increase of transmural PD. It was concluded that chronic potassium loading may enhance secretion of potassium into lower nephron tubular fluid and into colonic contents by primarily stimulating the synthesis of Na-K-ATPase and the resulting increase of the number of pumping sites. 75 percent nephrectomy may induce similar changes in the remaining nephrons.


Factors influencing the increase in Na-K-ATPase in compensatory renal hypertrophy. An increase in Na-K-ATPase in kidney homogenates usually accompanies compensatory renal hypertrophy. While it may be evident in both the cortex and medulla of the kidney, it is most marked in the outer medulla and may be present only in that region. The increase in enzyme activity does not depend on an intact adrenal cortex and can be elicited in the absence of adrenal glucocorticoids. It is not seen in the form of renal hypertrophy produced by potassium depletion, in which the transport of sodium and potassium by the kidney is not increased. When present in compensatory renal growth, the enzyme change is correlated with an increase in the reabsorption of sodium, or the excretion of potassium, or both, per unit of renal tissue. It proceeds in the presence of either, but not in the absence of both.


Cyclic nucleotide concentrations in relation to renal growth and hypertrophy. In rats no consistent change in the concentration of cyclic GMP or cyclic AMP concentration was found in the renal cortex between 2 hours and seven days after unilateral nephrectomy. In regenerating liver tissue, between 2 hours and seven days after removal of one-third of the liver, there were no consistent changes in cyclic GMP concentrations, but cyclic AMP concentrations were higher than in controls. During postnatal growth, no consistent changes occurred in the cyclic GMP concentration of the spleen, the testes, the kidney cortex, the renal papilla, the liver or the ventricle between two and sixty days after birth. Cyclic AMP concentration on the other hand, in all these tissues with the exception of the spleen, was depressed between the twenty-first and fortieth day after birth, i.e., at a period of rapid growth. In the spleen, the concentration of cyclic AMP increased continuously from the second to the fifth day after birth. During renal parenchymal hyperplasia induced by a large intravenous dose of folic acid two days before sacrifice, the concentration of cyclic GMP in renal cortical tissue increased consistently. A model is proposed to explain the different patterns of changes in the cyclic nucleotide concentrations found.


[The abdominal tuberculoses].

[The abdominal tuberculoses]. In a report on the extrapulmonary tuberculosis the abdominal forms are once more emphasized and analysed on the basis of a number of patients. There are no more any actual references to this picture of a disease in the modern general situation of tuberculosis, as by abolition of the bovine tuberculosis the prerequisites could be removed. There is no decisive symptomatology which leads to an abdominal tuberculosis. With the help of 89 clinically treated cases certain problems could be elaborated with regard to the diagnostics and therapy. The inclination to recidivation is not unconsiderable (8.9%), which is due to a disappointing bacteriological diagnostics and the false chemotherapeutic treatments resulting from this. With 34 cases in the GDR in 1976 this tuberculous disease is at present scarcely still of any significance. It must also in future be reckoned with sporadic new diseases which appear due to an intermittent lympho-haematogenic dissemination from tuberculous lung, pleura or lymph node processes and which may be treated with success by a modern multiple chemotherapy in a tuberculosis institution. The severe courses accompanied by complications which gave rise to surgical emergency measures might finally belong to the past.


[Results of islet transplantation in diabetic dogs]. The influence of histocompatibility on islet transplantation in dogs was studied. Donors and hosts were chosen by help of the macrophage-electrophoresis-mobility test. By subtotal pancreatectomy and twice applying streptocotocin diabetes was successfully induced in recipient animals. Isolation of pancreating islets from the donor was done by means of the collagenase method combined with the Ficoll-gradient-separating technique. The grafting occurred via portal vein into the liver. Significant decrease of blood sugar during 10 weeks was observed in animals with good compatibility. This effect lasted only 14 days in cases of bad compatibility. Concentrations of insulin in the portal vein and superior caval vein 4 weeks after grafting was lower in cases with high-grade histoincompatibility. The duration of functioning of transplanted islets depends on the histocompatibility.


[Effect of Collins' solution the kidney concentrating gradient and the Na+ and K+-ATPase of the kidney]. Canine kidneys were preserved under hypothermia in Collins' standard solution and the contents of sodium, potassium, and Na+ and K+-ATPase in several parts of these kidneys were followed. Hypothermic preservation in combination with single perfusion by means of Collins' solution without thermic ischemia caused loss of sodium, increase of potassium, and decrease of the total osmotic cortico-papillary gradient of the kidney. No loss of Na+ and K+-ATPase activity occurred under these conditions. The determination of Na+ and K+-ATPase level in the renal tissue turns out to be a rational method to assess the vitality of an organ to be transplanted.


[Enzymatic and morphologic studies on long-term perfused dog kidneys]. 21 canine and 12 human kidneys were submitted to long-term perfusion for 24 hours. During that time LDH-activity, histologic, enzyme-histochemic, and ultrastructural examinations were carried out. The findings proved that kidneys with lesser damage from ischemia showed lower activities during the first 4 to 6 hours than kidneys which were more injured before. The latter showed the same ultrastructural alterations as kidneys after perfusion for 24 hours, which suggests an irreversible partial damage of the organ.


[In-vitro inhibition of collagenase activity in epidermolysis bullosa hereditaria dystrophica]. By means of a biological collagenase assay we estimated collagenolytic activity of the vesicular fluid of patients with epidermolysis bullosa hereditaria dystrophica. All the 5 examined patients showed increased collagenolysis. Inhibition studies were performed applying ethylendiaminetetraacetate inhibition 11,15%, normal human serum in 12.15% (means). o-Phenanthroline as well as erythromycine in an aequimolar ratio stopped the collagenolytic activity completely in the 5 specimen. It was the aim of our study to indicate that erythromycine, in contrast to other collagenase inhibitors relatively atoxic, is able to inhibit collagenase activity which is suggested to play a pathogenetic role in that disease.


[Prognostic significance of follow-up scintigraphy with 99m Tc-pyrophosphate in myocardial infarction (author's transl)]. Using 99m Tc-pyrophosphate there is a positive visualization of a transmural myocardial infarction by a localized tracer activity outside of the skeletal system. The uptake of the tracer in the infarcted area is expressed as percentage of the accumulation over the sternum. It reaches a maximum 48-60 hours after infarct onset and then recedes gradually but not strictly linearly. On the occasion of a control scintigraphy 3-4 weeks after the myocardial infarction and after full mobilization 56 per cent of the investigated patients showed a variable decrease of the tracer activity. On 44 per cent the tracer activity in the infarcted area remained unchanged or even increased slightly, though the infarction could be excluded. At the same time performed haemodynamic investigations with measuring the pulmonary artery pressure at rest and under stress conditions showed a good correlation between the persistence of the tracer activity in the infarcted area and the amount of the pulmonary pressure at rest and during stress, manifesting left ventricular function. So the result of a control scintigraphy 3-4 weeks after myocardial infarction allows to draw prognostic inferences about the further course of the disease.


Ultrastructural alterations and peroxide formation induced by naphthoquinones in different stages of Trypanosoma cruzi. Addition of beta-lapachone, an o-naphthoquinone with bactericidal, cytotoxic, and trypanocidal activities, to Trypanosoma cruzi epimastigote and amastigote stages induced the release of O2- and H2O2 from the whole cells into the suspending medium. In the presence of reduced nicotinamide adenine dinucleotide as reductant beta-lapachone was also able to stimulate O2- and H2O2 production by homogenates of these stages. Electron micrographs showed that in beta-lapachone-treated amastigotes and trypomastigotes, the chromatin is arranged in patches, clearly differing from the normal pattern of chromatin distribution. Alterations of the nuclear, mitochondrial, and cytoplasmic membranes, as well as swelling of the mitochondria were also observed.


Dependence of cellular surface area on growth density of 3T3 and SV40-3T3 cells. The cell surface areas of 3T3 and SV40-3T3 cells both for suspended and for flat cells growing on the culture substrate have been determined in dependence on growth density. The surface areas of flat 3T3 and SV40-3T3 cells turn out to be independent of growth density over a wide range. For 3T3 cells the surface area of flat cells compares well with that determined by Collard and Temmink for suspended 3T3 cells taking the surface area of their coverlayer of microvilli into account. This indicates that upon suspension of flat 3T3 cells the surplus surface area is disposed of in the form of microvilli. For SV40-3T3 cells we obtained a surface area of flat cells which differs by a factor of about two from that of suspended cells as determined by Collard and Temmink including the surface area of microvilli. Microscopical diameters and electrical ("Coulter") volumina of suspended 3T3 and SV40-3T3 cells depend only little on cell density in the range investigated.


[Benign and malignant synovialoma (author's transl)]. Synovialomas are rare tumorus. Their histology is as difficult as assessing their prognosis. Benign synovialomas should be extirpated radically. In case of malignancy amputation should be performed immediately, because amputation not until the first recurrence will often come too late. Only this treatment plan offers at present a chance to lower the otherwise high mortality rate.


[Characterization of plasmid DNA in a lecithinase-positive and in a lecithinase-negative strain of Clostridium perfringens (author's transl)]. A non pathogenic variant of Clostridium perfringens and the wild type strain were characterized. The strains agreed in most of the biochemical properties, in susceptibility against antibiotics and in bacteriocin production. Contrary to the wild type the variant did not produce lecithinase and gelatinase. In deoxyribonucleic acid (DNA) of both strains centrifuged in cesiumchlorid-ethidiumbromide equilibrium there was found a satellite peak containing three distinct, covalently closed circular (CCC) DNA elements. The sum of the average molecular weight or contour length of the two small circular molecules was equal to the average molecular weight or contour length of the third. The presence of the plasmids in the variant indicated that the synthesis of lecithinase might not be coded by a plasmid.


Phosphatase activity of aerobic and facultative anaerobic bacteria. 1115 strains of aerobic and facultatively anaerobic bacteria were tested for phosphatase activity by a conventional plate method and a microtest. The microtest was devised to allow results to be read after 4 h cultivation. Phosphatase activity was found in wide range of species and strains. Besides staphylococci, where the test for phosphatase is successfully used, it may be applied as one of the valuable tests for the differentiation of the following species: Bacillus cereus, B. licheniformis, Aeromonas spp., Vibrio parahaemolyticus, Actinobacillus spp., Pasteurella spp., Xanthomonas spp., Flavobacterium spp., Alteromonas putrefaciens, Pseudomonas maltophilia, Ps. cepacia, and some other species of Pseudomonas. The species which gave uniformly negative phosphatase reaction were as follows: Staph. saprophyticus, Acinetobacter calcoaceticus, Alcaligenes faecalis, and Bordetella bronchiseptica.


Purification and some properties of collagenase proenzyme activator from rheumatoid synovial fluid. 1. An activator of leucocyte latent collagenase has been extracted from rheumatoid synovial fluid by a preparative method consisting of six steps including precipitation by ammonium sulphate and chromatography on Sephadex G-100, QAE-Sephadex and SP-Sephadex C-50. The purification factor was nearly 1000 and the activator isolated could be shown to have a high degree of homogeneity.--2. Gel chromatography indicated a molecular weight of ca. 60 000.--3. Kinetic studies of the activation and inactivation of the activator during incubation at higher temperatures demonstrated its enzymic nature.--4. Activation of latent collagenase was partially inhibited by iPr2P-F and KCN. Soybean trypsin inhibitor, iodoacetamide, TosLysCH2Cl and TosPheCH2Cl had no effect.--5. Leucocyte latent collagenase was also activated by an excess of trypsin and p-hydroxymercuribenzenesulphonic acid, but only to the extent of about 40% of its activation capacity. Purified neutral protease from human leucocyte granules had no effect on latent collagenase.--6. Several typical substrates for proteases, peptidases, esterases and glycosidases were not attacked by the activator. The possibility that the activator is a known enzyme, such as kallikrein, urokinase or cathepsin B1, could be excluded.


Morphological and physical characteristics of an antigen associated with viral hepatitis type A (Botevgrad antigen). Immune electron microscopy (IEM) was employed in studying faecal samples of viral hepatitis type A patients and their contacts, in whom the presence of an antigen, differing from the HBsAg, designated as Botevgrad antigen (BA) was proved by the CFT. Particles 25--28 nm in diameter, aggregated by sera positive for the anti-HAAg were established in the faecal samples. The buoyant density of these particles in CsCl was found to be 1.40 g/ml. Particles of the same buoyant density were established also in sera positive for BA which were aggregated in large masses with antiserum against BA obtained from rabbits. The associations between BA and HAAg are discussed.


Cyclic AMP and its functional relationship in Tetrahymena: a comparison between phagocytosis and glucose uptake. In Tetrahymena, an increase in the level of cAMP is accompanied by an increased phagocytotic rate, whereas increased sugar uptake is parallelled by a decreased cAMP level. The increase in cAMP level seems to be decisive with respect to phagocytosis as a basic phenomenon of life. In the action of epinephrine, however, some mechanism other than cAMP mediation may be involved. Depending on concentration, one hormone may provoke either an increase or a decrease in cAMP level, and this in turn triggers the corresponding function.


[Comparative study of the fatty acid composition of glycerophosphatides from whole vertebrate brain and portions of it]. Fatty acids of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and monophosphoinositide were studied in the whole brain, in the forebrain and the brain stem in the frog Rana temporaria, tortoise Emys orbicularis, hen and cat. Every family of phospholipids (PL) possesses a characteristic fatty acid pattern irrespectively of the brain part. There are regular topologic differences in the fatty acid composition of PL, namely the relative amount of saturated and polyenoic acids is higher and that of monoenoic acids lower in the forebrain as compared to the brain stem. The increase in the relative size of the forebrain, occurring in the evolution of vertebrate brain, exerts a definite influence on the fatty acid composition of the total brain. Nevertheless this increase in the size of the forebrain does not solely determine the fatty acid composition of the total brain. Similar changes are occurring in all brain parts: the relative amount of saturated fatty acids of PL is increasing and that of unsaturated acids decreasing. The evolutionary deductions derived from the biochemical study of the total brain find confirmation in the investigation of the brain parts.


[Clinical forms of glomus tumors of the temporal bone and base of the skull]. On the basis of the clinical examination of 99 patients, researchers distinguished the clinical forms of the glomus tumour of the temporal bone and of the base of the skull: glomus jugulare tumour, tympanic glomus, glomus of the pyramid of the temporal bone, glomus of the vagus nerve. Every clinical form is characterized both by general symptoms and by signs which appear only with the given form. The peculiarity of the clinical course of glomus tumours is due to intracranial growth, malignization and also by recurrence and prolonged growth.


The cytologic diagnosis of breast aspirations. A series of 1,792 breast cytology specimens were evaluated from the Boston Hospital for Women for the years 1970-1974. The majority (1,684) were needle aspiration smears, the remainder (108) were nipple secretion smears. The cytologic criteria for diagnosing breast specimens were presented. Of the 1,792 breast specimens examined cytologically, 48 cases were histologically proven cancers with 33 smears containing malignant or suspicious cells, indicating 92% accuracy (after correction for unsatisfactory smears). A suspicious or positive interpretation of the smears prompted a biopsy and led to early diagnosis. Although needle aspiration cytology is not a new technique, it is one which is economical, easy, accurate and lacking in complications to the patient. Hopefully in the near future, it will be a more widely accepted procedure for the early detection of breast cancer.


Cytopathology of Paget's disease of the vulva. Diagnostic abrasive cytology. The cytologic appearance of Paget's disease of the vulva is described, noting the similarity in appearance of the cells to those seen in Paget's disease of the nipple. The relation of this disease state to mammary involvement is emphasized by the fact that three of the five cases presenting had either a current or past history of breast ductal carcinoma or hyperplasia.


Cytologic findings in a case of malignant fibrous histiocytoma. Morphologic changes in malignant cells obtained by needle aspiration of a recurrent malignant fibrous histiocytoma of the left axilla in a 61 year old male are reported. Basically, two types of cells are described: pleomorphic malignant histiocytic cells with marked phagocytic activity and sarcomatous spindle cells. Intermediate forms with features of both types are identified.


Nuclear DNA content of trophoblastic tumors. The nuclear DNA content of trophoblasts was measured in 25 cases of normal pregnancy, 46 cases with hydatidiform mole, ten cases with destructive mole and six cases of chorionepithelioma (choriocarcinoma). In normal pregnancy, DNA distribution in syncytiotrophoblasts and cytotrophoblasts showed a sharp peak at the diploid region, although a few cytotrophoblasts with increased DNA content were observed in the first trimester. In chorionepithelioma the DNA content of the trophoblastic cells showed extremely wide distribution without any special peak. In destructive mole, although a wide distribution was observed, the sharp peak was usually noted at the diploid range. Cases with hydatidiform mole were divided into two categories according to the DNA distribution patterns. Type I showed the patterns similar to the first trimester of normal pregnancy and type II resembled the patterns of destructive mole. In hydatidiform mole of type II, subsequent progress towards destructive mole was frequently encountered.


Corpora amylacea in cerebrospinal fluid. A source of possible diagnostic error. Corpora amylacea in the central and peripheral nervous system are round, amorphous intracellular bodies which are frequently found in large numbers around the ventricles of elderly individuals. These bodies were recently identified in a cytologic preparation of ventricular fluid. Although they have no known diagnostic significance, their possible confusion with yeast forms makes recognition of these structures important.


Studies on cyclic nucleotides in the adrenal gland. IX. Effects of ACTH on cyclic AMP and steroid production by the zona fasciculata-reticularis of the adrenal cortex. Effects of ACTH and calcium on cyclic AMP and steroid production by the zona fasciculata-reticularis (the decapsulated fraction) from the rat adrenal cortex have been studied. Increasing concentrations of extracellular calcium enhanced the action of ACTH on cyclic AMP and steroid production. These effects of ACTH with calcium were prevented by lanthanum, but not by tetracaine or verapamil, suggesting that ACTH stimulation may be mediated by calcium through a process not involving the tetracaine- or verapamil-vulnerable step(s) of the calcium current. High concentrations of external calcium itself increased cyclic AMP accumulation without any increase in steroidogenesis. A calcium ionophore, X537A was stimulatory for steroidogenesis but inhibitory with respect to cyclic AMP accumulation. Considered together with the findings of AMP increase, these results suggest that ACTH primarily increases intracellular calcium mobilization thus stimulating directly the steroidogenesis, which is independent of the cyclic AMP system. Relatively high concentrations of ACTH activate the adenylate cyclase, which depends on extracellular calcium to increase cyclic AMP levels and stimulation of steroidogenesis by the decapsulated fractions of the adrenal cortex.


The cell concentration method using acetylcysteine for sputum cytology. In order to improve the results of cytologic diagnosis of pulmonary carcinoma, a technique for concentrating cells from sputum using acetylcysteine was developed. Using the same sputum specimens, the rate of positive cytologic diagnosis of pulmonary carcinoma by this method was increased by 22.6% over the level achieved by the direct smear method. This cell concentration method improved the rate of positive diagnosis in peripheral type pulmonary carcinoma and particularly in adenocarcinoma. The cell concentration method using acetylcysteine shows great promise in the cytologic diagnosis of sputum specimens.


Synovial sarcoma diagnosed by fine-needle aspiration biopsy. A case report. The cytologic findings of a synovial sarcoma are described. A 60 year old male had felt a slowly growing tumor in his right sole for three years. From the first fine-needle aspiration biopsy a fibrosarcoma or other mesenchymal tumor was suggested; but the second biopsy showed both fibrosarcoma and mesothelial-like cells in contact with each other, and the diagnosis of synovial sarcoma was made. Histologic and electron microscopic sections confirmed the diagnosis. In the differential diagnosis of this case, fibrosarcoma and other malignant mesenchymal tumors were considered. The applicability of fine-needle aspiration biopsy in mesenchymal lesions is discussed.


Plasma cyclic nucleotide levels in hyperthyroidism. Plasma cyclic AMP and cyclic GMP levels were studied in a group of normal subjects and 10 subjects with hyperthyroidism. In the control group, mean plasma cyclic AMP levels were 15.3 +/- 1.3 nmol/l (SEM), and plasma cyclic GMP levels were 9.4 +/- 0.58 nmol/l (SEM). In untreated hyperthyroid subjects, both plasma cyclic AMP and cyclic GMP levels were significantly elevated above normal with mean values of 35.0 +/- 2.4 nmol/l (SEM) (P less than 0.001) and 14.7 +/- 0.2 nmol/l (SEM), (P less than 0.001), respectively. Six of the hyperthyroid subjects were re-studied when they became euthyroid; plasma cyclic nucleotide concentrations all fell within the normal range. To evaluate the relative contribution of triiodothyronine and thyroxine to elevated plasma cyclic nucleotide levels, two hyperthyroid subjects were treated with propylthiouracil and iodide. Plasma cyclic nucleotide levels were normalized when plasma triiodothyronine levels declined to normal range, at the time when plasma thyroxine levels were still elevated. These preliminary data suggest that increased triiodothyronine production is responsible for the increased cyclic nucleotide levels in hyperthyroidism.


Immunoreactive beta-MSH in human plasma and in a corticotrophic adenoma culture medium. Its relation to the lipotrophins. In order to characterize more accurately the relationship between immunoreactive beta-MSH ("BETA-MSH") and the lipotrophins (LPH) we attempted to investigate the gel filtration and the immunological characteristics of "beta-MSH" in the plasma of patients with Nelson's syndrome and Addison's disease as well as in the culture medium from a human corticotrophic adenoma using a sensitive radioimmunoassay from human beta-MSH. When added either to hormone free plasma or to a plasma from a patient with Nelson's syndrome all the human beta-MSH (hbeta-MSH) elutes from a Sephadex G-50 column as a single peak in a volume corresponding to its molecular weight. In contrast plasma "beta-MSH" in 3 patients with Nelson's syndrome and one patient with Addison's disease almost completely elutes in a volume corresponding to a molecular weight range of 6000-10 000; no "beta-MSH" can be detected in its normal elution volume. Drastic pH change (8.2 to 2.3) does not significantly alter the elution pattern. Chromatography of a corticotrophic adenoma culture medium gave a similar pattern of "beta-MSH" with a main peak in the molecular weight range of 6000-10 000. In our radioimmunoassay the culture medium and purified hbeta-LPH gave parallel displacement curves for [125I]hbeta-MSH. It is suggested that hbeta-LPH or a closely related substance is the main material responsible for "beta-MSH" immunoactivity.


Spontaneous rosette formation in vitro under the effect of agents affecting the cyclic nucleotide system of circulating lymphocytes of normal subjects. Aminophylline was found to effect the early and total rosette-forming capacity of human thymus-dependent lymphocytes. This may be connected with an increase in the intracellular cyclic adenosine 3',5'-monophosphate level. Acetylcholine increases the proportion of early spontaneous rosettes, a phenomenon suggestive of a shift within the lymphocyte population toward a subpopulation of higher activity. The effect of acetylcholine is possibly mediated by an increase in the intracellular cyclic guanosine 3'-, 5'-monophosphate level. Aminophylline affects only the early rosette-forming capacity of thymus-derived lymphocytes. Levamisole has no influence on either early or total rosette-forming capacity of normal lymphocytes. The results are suggestive of definite relationships between the functional state, activity and cyclic nucleotide system of thymus-dependent lymphocytes.


Effect of changes in cyclic nucleotide levels on human antibody-dependent cellular cytotoxicity. The effect of agents influencing intracellular cyclic nucleotide levels and that of exogenous cAMP was studied on the cytotoxicity of normal human peripheral blood mononuclear cells on antibody coated human and chicken erythrocytes. Elevation of the cAMP level resulted in a marked decrease in cytotoxicity, while basically similar in the allogeneic and the xenogeneic test systems, but more expressed in the allogeneic system.


In vitro effect of transfer factor on the cyclic nucleotide level of human lymphocytes in chronic lymphocytic leukaemia and of mouse lymphocytes. In the present study transfer factor (TF) failed to produce any change in the cAMP- and cGMP-levels of lymphocytes of patients with chronic lymphoid leukaemia (CLL). This is attributed to the malignant transformation of the lymphocytes or to a changed proportion of different lymphocyte populations in CLL. Human TF leaves the cyclic nucleotide levels of splenic lymphocytes of BALB/c mice unaffected.


Influence of measles virus antigen on leukocyte migration in multiple sclerosis and controls. The leukocyte migration inhibiton test was used in multiple sclerosis patients and in healthy controls for investigation of sensitization of blood lymphocytes against preparations of measles virus, mumps, NDV virus, and PPD. Regardless of antigen used, no significant differences were found between the groups. There was a strong correlation between the leukocyte migration inhibition obtained with measles virus antigen and with PPD. The leukocytes from MS patients as well as from healthy controls showed a significantly more pronounced inhibiton when a Tween 80 and ether-treated preparation of measles virus was used, compared with the whole measles virus antigen. No correlations were found between the degree of leukocyte migration inhibition and the antibody titers against different components of measles virus in individual samples.


A sporadic juvenile case of the amyotrophic lateral sclerosis with neuronal intracytoplasmic inclusions. In an autopsy case of the sporadic juvenile ALS (a 17-year-old girl) intracytoplasmic inclusions are found in the upper and lower motor neurons and in nerve cells of the dentate nucleus, pontine nucleus, brain stem reticular formation, substantia nigra, thalamus, globus pallidus and others. Histochemically they contain RNA-Protein compounds. Electron microscopically, they consist of randomly interwoven tubules with granular endoplasmic reticulums and free ribosomes in the margin. Each tubule measures 90--150 A in diameter and shows no distinct periodic constiction. Amorphous substances as well as ribosome granules are scattered and associated with those tubules. The inclusion-bearing cells are usually swollen and chromatolytic and have a large hydropic nucleus, suggesting a close relation between the development of the inclusion and chromatolysis. Clinically, a rapid progress of the symptoms (total duration: about 12 months) and conspicuous disturbances of the autonomic nerve, such as sinus tachycardia and bladder sphincter dysfunction, should be noticed.


Lafora-like inclusion bodies in the CNS of aged dogs. Forty randomly selected dogs, arranged into three groups according to age, were examined light and electron microscopically. Lafora-like inclusion bodies were found in all cases of aged dogs without neurological signs. They appeared as PAS positive, round bodies measuring up to 15 mu in diameter. Typically they had central cores and radiating peripheral lines. Electronmicroscopically, the inclusions consisted of irregularly clustered, short branching filaments measuring about 80--120 A in diameter or of electron-dense homogeneous or granular central cores with filamentous peripheral areas and located both in the perikarya and neuronal processes. The inclusions were disseminated all over the brain and spinal cord. The thalamic nuclei, a circumscribed area dorsal to the aqueduct, and the molecular layer of the superior colliculus were the most severely affected. The frequency of the inclusions showed age-dependency; the inclusions were not found in dogs younger than 2 years, but were extensive in all dogs of more than 8 years of age. The occurrence of the inclusions may therefore represent an age-dependent phenomenon. The relationship between the present findings and Lafora's disease is discussed.


Ultrastructural study of a patient with progressive dementia showing special intraplasmic inclusions in diffuse cerebral cortex. Mechanism of inclusions production. Numerous inclusions were diffusely observed in the neurons and glial cells in the cerebral cortex of a patient with progressive dementia. These inclusions were initially produced by rough ER in the cells and gradually enlarged destroying the rough ER membranes. The nature of these inclusions was neutral mucopolysaccaride including protein histochemically. In the nuclei of the nerve cells and glial cells, some types of intranuclear virus-like inclusions were found. The first type was papova virus-like structure with high electron density measured 30--35 nm in diameter. The second type was paramyxovirus-like structure with granulo-fibrilar shape. The third type was large hexogonal core with high electron density measured 100 nm in diameter. These intranuclear virus-like bodies were not specific in the present case; however, it was speculated that intranuclear virus-like inclusions might have a deep relation to change the function of the nuclei and produced large intraplasmic inclusion bodies.


Choroid plexus papilloma: light and electron microscopic study of three cases. Three cases of choroid plexus papilloma were studied by light and electron microscopy. All had the typical papillary pattern, and, in addition, two exhibited solid areas of tumor growth which predominated in one case. PAS positive (diastase resistant) and argyrophilic cytoplasmic inclusions were present in all three tumors but were particularly abundant in the predominantly solid one. Ultrastructurally, the inclusions appeared as irregularly shaped structures containing lipid droplets, filamentous material and microtubules, and resembled the "silver bodies" of Biondi found in normal choroid plexus. Along with other ultrastructural features of normal choroid plexus, these cytoplasmic inclusions may be helpful in the differential diagnosis of papillary tumors involving the ventricular system.


Somatic unmyelinated fibre degeneration in rabbits with granulomatous hypersensitivity produced by a non-myelin antigen in sensory peripheral nerve. Rabbits previously sensitised by injection of human sensory peripheral nerve showed degeneration of somatic unmyelinated fibres at skin test sites when challenged by sensory nerve or certain non-myelin fractions prepared from human sensory nerve. Epithelioid cells were found in the endoneurium and may mediate the nerve damage. The degeneration was consistently found and lasted for at least 58 days. Phagocytosing macrophages were absent. Differences in the pattern of nerve damage to that of EAN and EAE are discussed.


Wolman's disease: ultrastructural evidence of lipid accumulation in central and peripheral nervous systems. We report the first case of Wolman's disease in which the fine structure of either the peripheral or the central nervous system has been examined. We confirm ultrastructurally the presence of lipid within endothelial and pericytic cells. Several cell types previously believed to be uninvolved in this storage process demonstrate lipid inclusions characteristic of Wolman's disease: perineural, endoneurial and Schwann cells of peripheral nerve, and oligodendrocytes and astrocytes of the central nervous system.


[Peripheral nerve changes in Tangier disease. Comparative light-, electron-microscopic and cytometric studies (author's transl)]. A sural nerve biopsy was performed in a 55-year-old male patient with Tangier disease (familial-lipoprotein deficiency). Light-microscopy showed an increase in the endoneural connective tissue and a loss of nerve fibers indicating a chronic peripheral neuropathy. Electron-microscopy revealed an accumulation of lipid droplets within Schwann cells of myelinated and unmyelinated nerve fibers. When compared with age-matched controls the myelinated fiber density was reduced with a relative preponderance of small myelinated fibers. In addition, distributional cytometric studies of nerve fibers in relation to the perineurium and endoneurial capillaries showed: Contrary to 4.6-7.5 micron thick nerve fibers, which accumulated in the center of the nerve fascicle, small (0.5-4.5 micron) and large (7.6-10.0 micron) fibers lay nearby the perineurium. The measured increase in small myelinated nerve fibers around endoneurial capillaries may be explained as a sign of regeneration.


Joint changes after overuse and peak overloading of rabbit knees in vivo. The effect of overuse and overuse combined with axial peak overloading on the knee joints of living rabbits has been investigated. A specially constructed apparatus was used for this purpose. Physical and biochemical changes are reported and include: 1. Early and progressive damage to the articular cartilage surface shown by the scanning electron microscope. 2. The presence of an increased amount of prostaglandin E in the synovial fluid. 3. A reduction of cyclic 3'--5' monophosphate in the subchondral bone. 4. Late changes which were consistent with osteoarthritis. These changes were found only in the joints subjected to simultaneous overuse and peak overloading. The results suggest that: 1. Cartilage damage and chemical changes in the subchondral bone are simultaneous and are both responsible for eventual degenerative changes. 2. Frictional overuse alone does not seem to be responsible for the production of oesteoarthritis.


Liver cell dysplasia and hepatitis B surface and core antigens in cirrhosis and hepatocellular carcinoma of autopsy cases. Liver tissues of 180 autopsy cases of cirrhosis and hepatoma and 285 consecutive autopsy cases of other diseases were studied for liver cell dysplasia correlated with hepatitis B surface and core antigens (HBsAg and HBcAg) in liver cells and sera, and antibody to HBsAg (anti-HBs) in sera. Liver cell dysplasia was characteristic in cirrhotic livers, particularly with hepatoma. No significant difference was found in age and sex between cirrhotic cases with and without dysplasia. Rate of positive HBsAg in liver cells and sera was significantly high in cirrhotic cases with dysplasia with or without hepatoma. Massive pattern distribution of orcein-positive liver cells was statistically significant in cirrhotic livers with or without hepatoma, but morphological characteristics of orcein-positive liver cells could not be correlated in significance with dysplasia and hepatoma. HBcAg showed neither correlation with liver cell dysplasia nor hepatoma. It appears to correlate with active cirrhosis, marked liver cell degeneration and necrosis, and membranous diffuse type HBsAg in liver cells.


Beta-adrenoceptors in the pregnant and non-pregnant myometrium of the goat and cow. The muscle relaxing effect of beta-adrenoceptor agonists was examined without and with the presence of beta-adrenoceptor antagonists in strips from the pregnant and non-pregnant myometrium of the goat and from the pregnant myometrium of the cow. Isoprenaline, salbutamol and ritodrine caused a dose-dependent reduction of the spontaneous contractions of the pregnant myometrium and a dose-related and parallel shift to the right of the isoprenaline dose-response curve was obtained with butoxamine but not with practolol. Isoprenaline but neither salbutamol nor ritodrine caused a dose-related reduction of the spontaneous contractions in the non-pregnant myometrium and a dose-related and parallel shift to the right of the dose-response curve of isoprenaline was brought about with propranolol but not with either butoxamine or practolol. The muscle relaxing effect of ritodrine on the pregnant myometrium of the goat and cow shown in vitro was also demonstrated in vivo in the same species within eight hours of delivery. It is concluded that the beta-adrenoceptors in the pregnant myometrium of the goat and cow belong to the beta2-group whereas those in the non-pregnant myometrium cannot be classified as either beta1- or beta2-adrenoceptors.


Ectopic ACTH-MSH producing carcinoid tumor with multiple endocrine hyperplasia in a child. An autopsy case of a 9-year-old Japanese girl revealed a carcinoid tumor originating in the duodenum and hyperplasia of the multiple endocrine organs as manifested by ectopic ACTH syndrome, carcinoid syndrome and giantism. The tumor cells were positive for histochemical argyrophile reaction and two types of secretory granules were identified by electron microscopy. Biochemical assay revealed the production of ACTH and beta-MSH by the tumor cells. Other changes of multiple endocrine organs included acidophil dominant hyperplasia of the pituitary, diffuse hyperplasia of the thyroid, chief cell hyperplasia of the parathyroid, hyperplasia of the islets of Langerhans and the adrenal cortex. This case was considered to be a type of multiple endocrine adenomatosis including carcinoid tumor. The relationship between the carcinoid tumor and multiple endocrine adenomatosis was discussed.


Decorporation of copper from liver subcellular fractions after alimentary loading of rats. Subcellular copper distribution was studied after single alimentary loading of rats with copper sulfate and after 2- and 4-day spontaneous decorporation of the metal. Copper content in mitochondria and in the soluble fraction was found to rise as early as the 1st day. Then it decreased reaching the normal values after 2-day and 4-day autodecorporation for cytosol and mitochondria, respectively. The activities of rotenone-sensitive NADH-cytochrome c reductase, succinate-cytochrome c reductase and cytochrome oxidase were inhibited by copper treatment but after a 4-day decorporation they became normal. On the contrary, rotenone-insensitive NADH-cytochrome c reductase was activated. Single alimentary copper treatment induced changes in electron transport and oxidative phosphorylation with succinate and glutamate as substrates. The changes established were in accordance with the decreased enzyme activities. After chronic copper loading (7-8 weeks) the interruption of copper-enriched diet for 5 days led to restoration of the copper content in the subcellular fractions. Treatment with unitiol did not change the spontaneous decorporation.


Bell's palsy-beneficial effect of treatment with adrenocorticotrophic hormone (ACTH) in patients with a poor prognosis. In 111 patients with idiopathic peripheral facial paralysis (Bell's palsy) the prognosis was established during the first days of the disease, using sialometry and the stapedius reflex test in 102 patients. A poor prognosis was indicated in 36 patients. Treatment with adrenocorticotrophic hormone (ACTH) was commenced within 10 days (in the majority within 5 days) of the onset of the paresis in 31 of those patients with a poor prognosis. The recovery rate in the ACTH-treated group was superior compared with the untreated control group of patients with a poor prognosis. The difference is statistically significant. Those patients with a good prognosis were not treated but merely followed up. Some factors which could influence the result of the treatment are considered.


The effect of exhaustive swimming and chloramphenicol on the content of mitochondrial protein and cytochromes in rat liver and myocardium. The content of mitochondrial protein and cytochromes aa3, b, c1 and c in rat liver and heart was determined in four groups of rats: controls, CAP-treated rats, exercised rats and CAP-treated exercised rats. Single swimming does not change the amount of mitochondrial protein in liver and myocardium as well as the content of cytochromes aa3, b, c1 and c in liver mitochondria. The content of cyt. c is lowered in heart mitochondria. CAP treatment of rats for three days decreases the amount of mitochondrial proteins and cyt. aa3, and b whereas no such changes are observed in heart mitochondria. The subsequent swimming on the background of the inhibitor does not affect additionally liver mitochondria, but lowers significantly the mitochondrial protein and the content of cyt. aa3, b, c1 and c in the myocardium. These data show that exhaustive muscular work alters the effect of CAP in heart mitochondria. Three hours of exhaustive swimming are not sufficient to change neither the amount of total mitochondrial protein, nor the cytochrome content. The lowered cyt. c content in heart mitochondria after swimming is explained by an intensified permeability of the outer membrane. Thus, the changes in the activity of some enzymes and the oxidative phosphorylation previously reported by us, are not due to alterations in the protein synthesis.


Mechanism of action of benzodiazepines - the GABA hypothesis. Benzodiazepines influence on a number of neurotransmitters such as acetylcholine, catecholamines, serotonin, glycine and gamma-aminobutyric acid (GABA), but during recent years the major interest has been focused on the inhibitory transmitter GABA. This paper reviews the hypothesis that benzodiazepines act via GABA-ergic mechanisms in the central nervous system. At NIMH in Washington D.C. a novel method to measure the turnover rate of GABA in rat brain nuclei has been developed (Bertilsson et al., J. Pharmacol. Exp. Therap. 200: 277, 1977). The incorporation of 13C from glucose into glutamic acid and GABA was quantitated in stereomicroscopically isolated nuclei. Using this technique it was shown that the GABA agonist muscimol and diazepam have a similar action. Both drugs decreased the turnover rate of GABA in N. caudatus and accumbens, but not in globus pallidus (Mao et al., Biol. Psychiatry 12: 395, 1977). This gives further support to the theory that diazepam acts as a GABA-mimetic drug.


The effect of oxazepam on sleep in normal human volunteers. The effects of 25 mg of oxazepam, a benzodiazepine with a short half-life and no active metabolites, were compared with placebo in two healthy volunteers in a single-blind polygraphically recorded sleep study. The experiment lasted for 24 nights and recordings were made for 11 nights. It was found that 25 mg oxazepam induced sleep faster than placebo, and that the subjects awoke less often during the treatment period. The total amount of REM-sleep was not affected. However, REM-sleep was shortened during the first part of the night and extended during the latter part of the night. Slow-wave sleep diminished differently in the two subjects, possibly due to interindividual differences in the rate of elimination of oxazepam. The effect on blood pressure was small, and the normal physiological difference between bedtime and morning blood pressure was preserved.


Stereotactic computer tomography for biopsy of gliomas. A technique is introduced enabling automatic transfer of coordinates obtained at computer tomography into a stereotactic system previously applied in biopsies of brain lesions. Four to five biopsies from different parts of gliomas were taken to compare the structures demonstrated on computer tomography with the microscopic appearances. Of 45 biopsies in 13 patients, 36 were predicted correctly. This also served as an attempt to classify gliomas on the basis of their appearance in the CT image.


En-bloc irradiation of unresectable bronchogenic carcinomas and their regional lymphatics. Patients with unresectable or inoperable bronchial carcinoma were treated with en-bloc irradiation of the tumour and the mediastinal lymph nodes to a total target absorbed dose of 40 Gy in 20 fractions. The first 52 patients were treated in one series and the last 45 patients in two series (split-course). Radiation adverse effects were only mild. The two regimens gave the same palliative results. The median survival was the same for the 2 groups (8 months). Most patients died in disseminated disease.


Postoperative irradiation of glioblastomas. Results in a randomized series. A material of 108 patients with glioblastoma is presented. The series was randomized in two groups: cases only operated upon and cases with postoperative irradiation in addition. Patients dead within 2 months after operation were excluded in estimating the real value of the postoperative irradiation. The irradiated cases had a 6-month survival rate of 64 per cent and a one-year survival rate of 19 per cent; the non-irradiated cases a 6-month survival rate of 28 per cent and a one-year survival rate of 0 per cent.


Combination chemotherapy in the management of superior vena caval obstruction in small-cell anaplastic carcinoma of the lung. Among 225 consecutive patients with small-cell anaplastic bronchogenic carcinoma, 26 (11.5%) had superior vena caval obstruction when the malignancy was diagnosed. Of these 26 patients, a consecutive series of 22 were treated initially with combination chemotherapy (cyclophosphamide, methotrexate and CCNU, in some cases combined with vincristine) alone, and in all these cases resolution of the syndrome was prompt within a median of 7 days. In no case were symptoms increased transiently by the treatment. No difference in response rate was observed between the histologic subtypes of small-cell anaplastic bronchogenic carcinoma according to the WHO classification. Combination chemotherapy alone is an effective treatment of superior vena caval obstruction in patients with small-cell anaplastic bronchogenic carcinoma.


Elevation of high-density lipoprotein in epileptic patients treated with phenytoin. Previous observations have shown that serum alpha (high-density) lipoprotein (HDL) cholesterol is increased by some agents which also act as liver microsomal inducers. Against this background we measured the serum HDL and other lipoprotein and apolipoprotein A levels in 28 epileptic patients who received phenytoin as the only medication. In comparison with healthy controls of similar age and sex, the phenytoin users had significantly higher HDL cholesterol (p less than 0.001) and apolipoprotein A-I (p less than 0.01) levels. Highest values of both parameters were found in patients whose serum phenytoin concentration was within the therapeutic range. HDL cholesterol levels were above the control mean +2 S.D. in 43% of the phenytoin users. Hypertriglyceridemia was more common among male phenytoin users than in control males (33 vs. 16%). It is suggested that phenytoin increases the secretion of nascent HDL particles (and probably also that of VLDL) by the liver and that this could be associated with the induction of hepatic microsomes. Since HDL is inversely reversely related to risk of coronary heart disease, the observed increase of this lipoprotein may be an example of a beneficial side-effect of a drug.


Air pollution exposures to five target health hazards. The Occupational Safety and Health Administration (OSHA) initiated a Target Health Hazards Program (THHP) in January 1972. The five substances singled out as target health hazards (asbestos, cotton dust, carbon monoxide, lead and silica) are discussed. Outlines are given of the pertinent points of the present and proposed OSHA standards for each substance as well as data of OSHA inspection efforts with regard to the THHP. A summary statement is made of the National Emphasis Program and of OSHA efforts to upgrade standard setting and compliance activities.


Regression of the larval opisthonephros during metamorphosis of the sea lamprey, Petromyzon marinus L. The opisthonephric kidney of larval anadromous sea lamprey, Petromyzon marinus L., undergoes a programmed regression during metamorphosis. Degeneration is initiated in the anterior end of each kidney and progresses posteriorly until the kidneys are reduced to short, pigmented strands by the end of metamorphosis. The first sign of degeneration in both the epithelium of the renal corpuscles and the tubules is a folding of the basal lamina. Autolysis then occurs throughout the entire epithelium of the nephron with the gradual accumulation of larger and greater numbers of acid phosphatase-containing autophagic vacuoles, cytosomes, and myelin figures. Cytoplasmic debris and electron-dense material accumulates in the tubular lumina and in the urinary space. Although no definitive evidence is provided for the method of removal of the tubular epithelium, macrophages play a large part in the phagocytosis of the components of the renal corpuscle. Mesangial cells appear to engulf debris from the capillaries while a second type of macrophage is involved in the destruction of podocytes and parietal epithelial cells. The method of programmed degeneration of the renal corpuscle closely resembles descriptions of the mammalian renal corpuscle in diseased conditions. The sole surviving element of the degeneration of the entire nephron epithelium is a pleated basal lamina. The regressing larval opisthonephros has potential as an alternative system for studying a normal developmental pattern such as tissue regression.


Immunoreactive beta-endorphin and ACTH in the same neurons of the hypothalamic arcuate nucleus in the rat. Immunoreactive ACTH and beta-endorphin (beta-End) were localized in the brain and pituitaries of normal and colchicine-treated rats, using the immunoperoxidase method at the light microscopic level. On adjacent serial 5-micron paraffin sections of anterior pituitaries, both ACTH and beta-End could be found in the same cells. On adjacent 5-micron paraffin sections of brains of colchicine-treated rats, both ACTH and beta-End could be found in the same perikarya of hypothalamic arcuate nucleus neurons. It appeared that all perikarya containing beta-End contained ACTH as well, suggesting that neurons producing beta-End also produce ACTH. Pathways of ACTH fibers corresponded to pathways of beta-End fibers. These findings suggest that the synthesis, and transport, of ACTH and beta-End are linked in the brain as well as in the pituitary, possibly through a common precursor.


Dietary fiber and blood lipids: reduction of serum cholesterol in type II hyperlipidemia by guar gum. Guar gum, a storage polysaccharide galactomannan and a form of dietary fiber, was administered to 10 patients with type II a or b hyperlipidemia for 2 weeks. Five grams of gum was given before each of three meals daily, either in a specially prepared soup or mixed with fruit juice or milk. No other deliberate change of diet was made. Three patients had been taking 12 to 16 g/day of cholestyramine for more than 2 years and one had been taking 1000 mg of clofibrate daily. These drugs were continued throughout the trial. Serum cholesterol levels of all 10 patients had been stable for 6 to 18 months before the trial at the start of which the mean level was 345 +/- 15 mg/dl. After 2 weeks of guar gum the mean was 308 +/- 16 mg/dl, a fall of 10.6% (P less than 0.01). Serum triglyceride was not changed significantly. Guar gum, which can be incorporated into foods, merits further study as a potential hypocholesterolemic agent.


The molecular mode of action of Clostridium perfringens enterotoxin. While certain strains of Clostridium perfringens have been associated with food poisoning outbreaks for the past 30 years, it has been only during the past 10 years that progress has been made in describing the disease process. And only within the past 5 years has meaningful progress been made in understanding the mechanism by which the disease is caused. Early observations, that the protein enterotoxin can cause erythema, increase capillary permeability, and exhibit parasympathomimetic properties, have been greatly added to in more recent studies. It is now believed tht the enterotoxin can alter intestinal transport of fluid, ions, and glucose, cause tissue damage in the gut and inhibit metabolic processes in intestinal tissue. Furthermore, the enterotoxin is thought to act very quickly (in a matter of minutes, compared to hours for other known enteropathogenic factors) and to affect basic function (macromolecular synthesis) and structure (membrane damage to microvillus brush borders) of individual cells. These findings have opened up many new questions that hopefully, when answered, will further the understanding of how this enterotoxin acts, as well as other enterotoxins being studied today.


Nutrition imbalance and angiotoxins as dietary risk factors in coronary heart disease. Imbalancing nutritionally adequate diets with an excessive amount of fat calories and cholesterol has obscured the fact that intimal thickening occurs spontaneously in time on low-fat cholesterol-free diets during the aging process, and that intimal thickening can be accelerated by dietary angiotoxic "risk factors." Electron microscopy of arterial tissue from animal models identified degenerated smooth muscle cells in the fetus from sows kept on low-fat cholesterol-free diets. After birth, the degenerated smooth muscle cells increased in number with age. The presence of angiotoxic "risk factors" such as oxidized cholesterol and vitamin D3 (cholecalciferol) in the diet of such animal models increased the frequency of smooth muscle cell death in their arteries. Two types of pathology could be developed in the thoracic aorta by continuous or short term feeding of 12.5 times more vitamin D than normally present in commercial rations: 1) a diffuse fibroelastic intimal thickening in the thoracic aorta (arteriosclerosis) with no evidence of lipid deposition by continuous feeding of vitamin D or 2) an initimal thickening in the thoracic aorta and intimal thickening with foam cells and extracellular lipid deposits (atherosclerosis) in the coronary arteries after a short period of supplemental vitamin D followed by 3 to 4 months of supplement-free diets. These two types of arterial damage were identical to that in the plugs of thoracic aorta obtained as a by-product of elective coronary bypass surgery. Although all of the possible sources of oxidized cholesterol in the diet have as yet not been identified, laboratory studies have identified oxidized cholesterol as an angiotoxic factor. Since population groups that consume less vitamin D-supplemented foods, less deep fat fried cholesterol-containing foods, and less hydrogenated fats have a lower incidence of coronary heart disease than Americans, it seems judicious for food processors to reduce these previously unconsidered risk factors to a minimum. This could be done by eliminating vitamin D2 and D3 from all vitamin supplements, from all food and cereal products and from the diet of livestock 1 month before they were killed so that the intake of vitamin D is no larger than the 400 IU/quart in milk which is necessary to prevent rickets in children. Deep fat fryers, which are kept at almost 200 C for 24 hr/day, could perhaps be replaced with microwave ovens in fast food chain outlets. Processors could hydrogenate vegetable oils to a minimum trans fatty acid content and rearrange this fat with polyunsaturated fats to produce high polyunsaturated fats trans-free margarines and shortenings.


Relation of serum lipids and lipoproteins to obesity and sexual maturity in white and black children. The interrelationships of serum lipids and lipoproteins with measures of body habitus and maturation stages were analyzed in a biracial population of 3151 children, ages 5--14 years. In general, triglycerides, pre-beta-lipoprotein, and beta-lipoprotein were positively correlated with body habitus and maturation while alpha-lipoprotein was negatively correlated. The relationships in most instances were more apparent in whites than in blacks, with the highest correlations observed in white boys. No significant correlations were observed between serum cholesterol and the anthropometric variables except in white boys. The most obese children tended to have higher levels of triglycerides, pre-beta-lipoprotein, and beta-lipoprotein, and lower levels of alpha-lipoprotein than the remaining population. In the total population, the multiple correlation coefficients with the children's age, race, sex weight-height index, triceps skinfold and maturation stage as the independent variables and the concentrations of the different serum variables as the dependent variables ranged from 0.04 to 0.11.


Treatment of genital herpes simplex virus infection with photodynamic inactivation. A double-blind randomized study to evaluate the effect of proflavine in the treatment of genital herpesvirus infection was conducted. One hundred fifty-seven women were studied, of whom 75 were treated with proflavine (treated women) and 82 were treated with placebo (control group). There were 62 women with primary disease and 95 with recurrent infection. Under the conditions by which this study was conducted, there was no apparent difference in the time of healing of lesions, development of recurrences, or virus isolation following treatment in the proflavine-treated and control groups.


Retinal aneurysms in adult cytomegalovirus retinitis. We observed aneurysms of the retinal arteries, capillaries, and venules occurring in a patient with cytomegalovirus retinitis. These aneurysms were caused by involvement of the retinal vascular endothelium resulting in focal weaknesses in the vascular walls. The clinical appearance of this retinitis superficially resembled retinal branch vein occlusion.


A myofibroblastic tumor. Infantile digital fibroma (recurrent digital fibrous tumor of childhood). Infantile digital fibromas are distinctive tumors both clinically and morphologically. A unique light microscopic features in the presence of intracytoplasmic, spherical, eosinophilic inclusion bodies. Previous electron microscopic studies have shown these bodies to consist of fibrils; bundles of fibrils have also been described in the cytoplasm. We have examined one such tumor, confirmed earlier findings, and established that the component cells are typical myofibroblasts. The latter are a variety of fibroblasts first described in granulation tissue; they are endowed with contractile properties and are characterized ultrastructurally by bundles of fibrils containing "dense bodies" such as are found in smooth muscle cells. Since our case is identical to those previously described, we propose that this tumor be called infantile digital myofibroblastoma.


Revisions in the microscopic method of estimating age at death in human cortical bone. Problems recently discovered in the Kerley method of estimating age at death from cortical microstructure are discussed. Kerley's original data have been re-analyzed to produce new regression equations and to document the original field size.


Involvement of cGMP in LHRH-stimulated gonadotropin release. Anterior pituitary content of cyclic AMP (cAMP) and cyclic GMP (cGMP) has been measured during stimulation of gonadotropin release by luteinizing-hormone-releasing hormone (LHRH) in vitro to gain more information concerning the relationship between the mechanism of action of LHRH and cyclic nucleotides. During the increased gonadotropin release obtained by incubation by hemipituitaries with LHRH (0.25--25 X 10(-9) M) for 180 min, the glands taken from both male and female rats exhibited increased cGMP content, whereas cAMP content rose only in those taken from male rats. The increase in cGMP content was observed after only 2 min in the presence of LHRH (5 X 10(-9) M) and prior to augmented gonadotropin release. The increase in cAMP content in the male glands was detectable only after 60 min of incubation. These results suggest that cGMP might be involved in the mechanism of action of LHRH.


Arginine vasopressin metabolism in dogs. I. Evidence for a receptor-mediated mechanism. The plasma clearance rates (PCR) of arginine vasopressin (AVP), and iodinated AVP (125I-AVP) were determined after pulse injection in conscious water-loaded dogs. Both the PCR and the apparent initial volume of distribution were significantly greater for AVP than for the biologically inactive iodinated AVP 37.4 +/- 4.8 ml/kg per min vs. 6.7 +/- 0.8 ml/kg per min (P less than 0.001) and 12.7 +/- 0.9% body wt vs. 7.1 +/- 0.4% body wt (P less than 0.001). AVP clearance was then determined by the constant-infusion technique at doses that produced equilibrium AVP concentrations within and above the physiological range. AVP-PCR was 37.4 +/- 7.1 ml/kg per min at 34 microU/kg per min, which was comparable to that after pulse injection (P less than 0.9). AVP clearance fell progressively, and urine osmolality progressively increased with increasing AVP infusion rates to plateau values at 136 microU/kg per min; a strong negative correlation was observed between mean AVP-PCR and urine osmolality (r = -0.993). The data suggest a relationship between the biological activity of AVP and its clearance. It is proposed that plasma membrane receptors may mediate a portion of the metabolic clearance of AVP.


Arginine vasopressin metabolism in dogs. II. Modeling and system analysis. System modeling and analysis methods were applied to interpret data regarding arginine vasopressin (AVP) metabolism in dogs. Based on this analysis a new nonlinear 3-pool model of AVP distribution and disposal was proposed and quantified; the model pools included the plasma, a receptor pool, and an extravascular nonreceptor pool. The receptor pool mediated a portion of the rapid flux of hormone between the plasma and the extravascular pool. Mathematical analysis indicated that the plasma AVP impulse response (bolus) data would be insufficient to uniquely estimate all the model constants, but additional plasma impulse data using 125I-labeled AVP, which does not bind to physiologic hormone receptors, would allow unique model quantification. Other required measurements were the urinary excretion of intact hormone, and plasma AVP degradation. The model was successfully fitted to the data from 10 dogs. The results suggest that, in the normal dogs studied, plasma contained 25% of the total AVP, 19% was bound to receptors, and the remaining 56% was in the extravascular pool. Eighty percent of the flux of AVP from the vascular compartment was mediated by the receptor pool; 98% of AVP degradation occurred in the extravascular pool; and urine excretion and plasma degradation made up the remainder.