Angiotensin-converting enzyme. II. Serum activity in early and newly diagnosed sarcoidosis.

Serum angiotensin-converting enzyme (ACE) was studied in 51 patients with early or newly diagnosed sarcoidosis. Only 45% of these patients had increased ACE activity when their diagnosis was established, which diminishes the diagnostic value of this enzyme measurement. On the other hand, ACE accurately reflected disease activity, and it proved a useful tool for assessing of need for corticosteroid treatment. Patients with acute sarcoidosis associated with erythema nodosum (EN) had low ACE activity compared with the other patients with active, but less acute disease. Serum ACE was not significantly correlated with blood lymphocytes or the immunoglobulins, but there was a positive correlation between the enzyme and serum lysozyme, which strengthens the hypothesis of both enzymes being produced by the epithelioid cells of sarcoid granulomas.


Space-filling models of kinase clefts and conformation changes.

Space-filling models of yeast hexokinase, adenylate kinase, and phosphoglycerate kinase drawn by computer clearly portray the bilobal character of these phosphoryl transfer enzymes, and the deep cleft which is formed between the lobes. A dramatic conformational change occurs in hexokinase as glucose binds to the bottom of the cleft, which causes the two lobes of hexokinase to come together. A substrate-induced closing of the active site cleft is postulated to occur in other kinases as well. This change may provide a mechanism by which some of these enzymes reduce their inherent adenosine triphosphatase activity and could be a general requirement of the kinase reaction.


Beta-adrenergic-sensitive adenylate cyclase in secretory cells of choroid plexus.

Biochemical evidence supporting the sympathetic control of cerebrospinal fluid production has been obtained through identification of a specific beta-adrenergic-sensitive adenylate cyclase in the choroid plexus. The enzyme, which is localized in the secretory epithelium, is activated by low concentrations of isoproterenol and norepinephrine and appears separate from beta-adrenergic-sensitive adenylate cyclase present in cerebral blood vessels.


Prolactin receptors in Rana catesbeiana during development and metamorphosis.

Specific binding of ovine prolactin was found in microsomal preparations of tail, gill, and kidney of the bullfrog Ran catesbeiana. Binding by larval and adult liver and by kidney before larval stage XVII was low or nondetectable. Renal binding increased during metamorphic climax and in response to treatment with thyroid hormone. The emergence of renal binding of prolactin may signify a shift in the hormone's participation in the control of hydromineral homeostasis from the gill, which is resorbed, to the kidney. A renal action of prolactin during climax may facilitate metamorphosis.


Testosterone reduces refractory period of stria terminalis neurons in the rat brain.

The absolute refractory period of neurons projecting from the corticomedial amygdala to the medial preoptic-anterior hypothalamic junction in rats was significantly increased by castration (from 1.01 to 1.61 milliseconds) and decreased again by testosterone (from 1.48 to 0.97 millisecond). Corticomedial amygdala neurons which projected to the capsule of the ventromedial nucleus of the hypothalamus were unaffected. These results demonstrate a specific, direct neuronal effect of testosterone.


[Hematological manifestations and complications in Sjögren's syndrome (author's transl)].

The main hematological manifestations and complications seen in 18 cases of Sjögren's syndrome are described: a slight anemia of the inflammatory type, a leucopenia, and/or an eosinophilia occur in about half of the patients. One case of auto-immune hemolytic anemia, one of pernicious anemia, 3 of hypoplastic anemia--one of them drug-induced--, and one of thrombocytopenic purpura have also occurred. The clinical and biological manifestations related to the disturbed immunologic status are also frequent: hyperglobulinemic purpura. Raynaud's syndrome due to cryoglobulinemia, rheumatoid factor, anti-nuclear factor. In 4 patients, the disease presented with or evolved into lymphadenopathy and/or splenomegaly; the initial "pseudo-lymphoma" diagnosis corresponded to different aspects or courses: in one cases, malignancy appeared soon, another has evolved in a chronic lympho-proliferative disease, a third one had the histologic features of angio-immunoblastic lymphadenopathy. These various manifestations, which may reveal the Sjögren's syndrome, are discussed in the light of the litterature data.


[Diagnosis methods in Sjögren's syndrome (author's transl)].

The diagnosis value of various methods used to detect or confirm a Sjögren's syndrome are discussed. The Schirmer's test, generally abnormal, is a good test for detection, although not specific. A subnormal concentration of tears lysozyme is seen in about half of the patients, as so as the presence of anti-salivary ducts antibodies, or significant aspects in lip biopsy. The tests that are most frequently disturbed are the salivary immunoglobulin assay and the fonctionnal study of salivary glands with 99m technetium tracer but they are not specific. These abnormalities are neither constant, not specific: for this reason, there are frequently some problems in the diagnosis or the nosologic definition of Sjögren's syndrome. The occurrence in the same subject of many of these abnormalities makes however this diagnosis highly probable even in patients without functionnal troubles.


[Systematic screening for Sjögren's syndrome in patients with various blood diseases].

A Sjögren's syndrom was looked for systematically in 154 hematological patients, half of them with lymphoproliferative disorders, by means of three current diagnosis methods: the Schirmer's test, the tear lysozyme assay, and the salivary immunoglobulin assay. These tests, poorly specific, are frequently abnormal, but the coexistence of the three abnormalities in the same patient makes the diagnosis highly probable. This corresponded to 4 patients. Taking into account the other diagnostic methods, the diagnosis was considered as possible or probable in 7 patients, and certain in 3 of them. This rate of 2% is discussed but the frequency of latent Sjögren's syndrome in hematologic patients and mainly in lymphoproliferative disease cannot be considered as high.


[Pseudolymphoma and lymphoproliferative syndromes in Gougerot-Sjögren syndrome (author's transl)].

Five cases of pseudolymphoma in Sjögren's syndrome were reported. Pseudolymphoma's pathological aspects described by Rothman then Talal are discussed. After recognition of the Sjögren's syndrome and a pseudolymphoma appearance, the risk of lymphomatous evolution enjoin a clinical close attention. Among our five cases, three had a peculiar evolution: one has presented and immunoblastic lymphoma (case 2). In an other case (case 3) the pathological aspect was very near to the angioimmunoblastic lymphadenopathy features. Waldenström's macroglobulinemia was cause of death of the last one (case 5).


[Pernicious anaemia associated with Hashimoto's thyroiditis, Sjögren's syndrome and chondrocalcinosis (author's transl)].

An association of pernicious anaemia. Hashimoto's thyroiditis, Sjögren's syndrome and chondrocalcinosis in a 68 years old women is described. Such an observation, does not seem to have been reported previously; the frequency of the different associations and the specificity of the antibodies observed in each cases are discussed.


[The use of tobramycin in severe infections (author's transl)].

The interest of tobramycin, studied here in 63 cases of severe infection, is due to several factors: --its ease of use including in cases of renal insufficiency; --the efficiency of subcutaneous administration, of particular interest to patients on anticoagulants; --its action on multi-resistant Enterobacteria and those not responding to gentamicin. Antibiotherapy is however only one of the elements of success in the treatment of severe infections, beside two factors which are often linked and determining: early treatment and the development of foci resistant to antibiotics.


[Attacks of acute headache (author's transl)].

Acute headaches are in most cases significant symptoms or premonitary signs of a neurological condition. From a semiological point of view, they may be: (i) isolated, (ii) associated with neurological symptoms (ophtalmoplegia, hemiplegia, hemianesthesia...). From an etiological point of view, the haemorragic conditions are predominant (30%): encephalic vascular malformation with or without subarachnoidal haemorragia (21%), subarachnoidal haemorragia without malformation (6%) and subdural haematoma (3%). Two types of conditions are also frequently observed: ischemic attacks (22,3%) and inflammatory meningeal syndromes (12%). Rare cases with hypophyseal adenomas, ischemic attacks under oestro-progestative treatment, accidents of mono-amine-oxydase inhibitors and multiple sclerosis are observed. 23,8% of the cases remained without any precise diagnosis. One of the interesting points in the acute headache issue is the possibility of discovering an encephalic vascular malformation without any important bleeding and, therefore, good conditions for surgery.


[Acquired idoxuridine resistance of herpes simplex virus. Clinical data (author's transl)].

The authors report two cases of severe herpetic keratitis and briefly discuss the possible mechanism of acquired idoxuridine resistance of herpes simplex virus. They believe that acquired resistance to IDU may be due to the treatment itself because of activity site of the inhibitor, i.e. the viral DNA.


[Role of hormonal receptors in the regulation of the corpus luteum (author's transl)].

Recent publications dealing with the hormonal regulation of the corpus luteum function have been reviewed. Hormones involved in this regulation are: LH and placental analogue hCG, FSH, prolactin and placental analogue hPL, prostaglandins, oestradiol and androgens. The hormone receptor interaction in the luteal cells and the role of each hormone in the modulation of the cell responsiveness has been reviewed.


[Abrikossof tumor in the esophagus].

Among the benign tumours of the oesophagus, the discovery of an Abrikossof tumour is exceptional. Although modern methods of investigation now permit recognition of this tumour and suspect its benign nature, only histology permits one to determine its precise nature, either by biopsy or by frozen section. Histogenetically, the schwann cell and histiocytic theories are not completely incompatible to the extent that they are considered from the point of view of general pathology, where there is evidence in favour of the mesoectodermic origin of the granular cell myoblastomas. In all cases, surgical excision is necessary. This resection of the myoblastoma permits a permanent cure.


[Use of Celestene by ionization in the treatment of rheumatic diseases].

The authors report a series of 154 cases reports of 89 female and 65 men who were treated by dielectrolysis using a corticosteroid, bethamethasone phosphate (Celestene injectable). The ionization technique is recalled as: nature of the current, generator, electrodes, methods, as well as the protocol. Patients suffered mostly from rheumatologic diseases in particular scapulohumeral periarthritis, arthrosis, epicondylitis and abarticular syndromes, often long-standing and resistant to current therapeutics. This serie also comprises 15 Dupuytren's contractures and La Peyronie's diseases. The very favorable results state as good and very good in 82%. The authors emphasize the excellent tolerance of this therapeutic method which allows a profitable utilization of corticotherapy without any risk.


[Current research in therapy of postmenopausal osteoporosis (author's transl)].

The goals of osteoporosis treatment are not only to decrease bone resorption, but also and mainly to increase bone formation. Present research is based on bone histomorphometry and prospective double blind therapeutic studies. Physical exercise, adequate calcium intake oestrogen therapy in postmenopausal or oophorectomized women have been shown to be effective in prevention of the disease. A moderate beneficial effect of the association of synthetic anabolic steroids with oral calcium has been recognized. Better results are expected from combined treatments such as low doses of calcitonin and oral calcium, or vitamin D metabolites and sodium fluoride, and from stimulating bone formation by low doses of parat-hormone.


[Non cardiogenic pulmonary edema (author's transl)].

Non cardiogenic pulmonary edema is caused by an increase of alveolocapillary permeability, due to different etiologies: fat embolism, multiple trauma, septic shock, influenza pneumonia, aspiration syndrome... Chest radiographs exhibit interstitial and/or alveolar pattern, severity of injury is assessed by the magnitude of intra-pulmonary shunting. Pulmonary wedge pressure is normal, and increased pulmonary vascular resistance is sometimes evidence in prolonged evolutions, especially in fatal cases. Treatment consists in the suppression of hypervolemia, and ventilation with positive and expiratory pressure (PEEP). Extra-corporeal membrane lung oxygenation remains since now rather unsuccessful.


[Cardiogenic shock in acute myocardial infarction (author's transl)].

To date, pump failure and its extreme manifestation, cardiogenic shock are the most common cause of death in patients with acute myocardial infarction. Post-mortem studies have shown that primary (myocardial) cardiogenic shock does not occur until some 40 to 50% of the myocardium has been rendered nonfunctional. Not infrequently, cardiogenic shock is mainly the result of a mechanical lesion (mitral regurgitation secondary to papillary muscle dysfonction or rupture, or ventricular septal defect) superimposed upon an ischemic and infarcted ventricle. In both situations medical therapy usually produces only a limited effect. Numerous physiological studies have shown that balloon pumping can reduce the workload and oxygen demands of the heart while increasing coronary blood flow and cardiac output. Most patients with cardiogenic shock can be at least temporarily stabilized, but many patients are balloon-dependent in the sense that when circulatory support is temporarily discontinued, shock or severe heart failure recurs. In these patients, some attempt to correct the underlying anatomic abnormalities appears necessary if they are to survive. Early intra-aortic balloon pumping (IABP) and surgery is much more effective in patients with cardiogenic shock secondary to mechanical complications. Finally, the combination of IABP and surgery has resulted in survival of approximately 50% of patients with cardiogenic shock either primary or secondary.


[Remission of diabetes during conventional insulin therapy or therapy controlled by use of an artificial pancreas].

12 recent acute-onset ketotic juvenile diabetics were optimally treated during 5 +/- days by means of an external artificial pancreas. Remission of diabetes occurred in 9 patients (75%). In a comparative group of 28 patients treated by conventional subcutaneous insulin, only 3 (11%) steady remissions were obtained. In a third group of 6 patients treated by insulin infusion without feed-back control, only 1 remission (17%) was obtained. The difference between these two groups and the first group (patients treated by the artificial pancreas) is significant (p less than 0.01). Urinary C-peptide/blood glucose ratio showed a steady improvement of insulin secretion during the remission period. At this time, actuarial analysis shows that the number of patients still in remission decreases during the first 10 months but seems to stabilize after this period. Duration of our remissions is equal to the duration of the "spontaneous" remissions taken from the literature. New treatment able to sustain the residual insulinsecretion during the remission phase (with presently can be induced frequently with our technique) are still to be found.


[T-lymphocyte diseases. Physiopathological and nosologic concepts (excluding cancer and graft rejection)].

The T-lymphocyte is at the heart of the physiopathological mechanism of most dysimmunity affections. Furthermore, some cases of granulomatosis, the immediate consequence of macrophagic disorder, come within the framework of T-lymphocyte diseases, épicritical centre of the complex process of cellular immunity. By reference to new knowledges about various actions of T-lymphocytes and their interactions with lymphocytes B and macrophages, and by reference to classic pathologic findings of diseases of immunity, the author's propose a new classification of these diseases, suggesting therapeutic reasearch in consideration of effect of drugs, especially immunostimulant treatments, on the immune system.


[A clinical survey on 17 cases of cholelithiasis in childhood (author's transl)].

A series of 17 cases of gallstones in children observed over a period of 10 years in the area of Marseilles is described and the literature reviewed. The majority of children were girls over 10 years old. Symptoms were constantly present and the disease revealed nine times by acute "mechanical" cholecystitis, compared to 16 infectious cholecystitis followed during the same period, three times by an accident of migration (cholangitis in a 14 years old girl, bile ascitis in two infants). A cholecystography should be performed in acute recurrent abdominal pain of unknown origin in children, gallstones appearing to be radiotransparent in six patients. Among causes of gallstone formation, the authors dig out only 6 hemolytic anemias, related to hemoglobinopathies in three patients, and they emphasize the frequency of idiopathic cholelithiasis which should lead to a more complete investigation of the enterohepatic cycle and chemical constitution of bile in such patients.


[Long-term therapy of osteoarthritis of the hip and the knee by sulindac (a cooperative trial in general practice) (author's transl)].

Long-term trial of sulindac (in general practice): 2,040 patients with osteoarthritis of the hip or of the knee been treated, 86,5% of them have been following the treatment for one year. This trial let us pointing out the non-improverishment of effectiveness of sulindac and the keepint of its good tolerance for long term. Some epidemiological data have been collected, among which: the importance of ponderal overload in patients studied and the prevalence of the right joints diseases on the left one's.


[Oral oestro-progestative contraception and cervical and vaginal cytology (author's transl)].

The cytological study of 1,685 smears belonging to women taking an oral contraception treatment, compared to 1,000 normal smears, shows that oestroprogestative drugs may be responsible for a certain number of more or less serious morphological disturbances in cervical and vaginal epithelial cells. These cell abnormalities, which correspond to inflammary of to slight dysphasia changes, are mostly spontaneously reversible or regress after cessation of the treatment. There does not seem to be a greater number of cervical cancers.


[Cytological diagnosis by punction of thyroid lesions. Histopathological correlations. Benign lesions (600 cases) (author's transl)].

Because of its important and its soft consistency, the thyroid is not always convenient for punction. Many smears cannot be classified, others are disappointing. The analysis of 2,300 punctions of thyroid lesions, allowed the authors to realise 900 comparisons between histopathological and cytological results. Among 300 histological malignant lesions, 89 unknown cancers were found, 40 of which gave haemorragic smears. The real false diagnosis were especially linked to vesicular and papillary carcinomas. On the other hand, undifferentiated carcinomas and lymphomas usually led to a correct interpretation. A correct diagnosis was made in 70% of all smears and in 81% of interpretable smears. The best results are found in benign lesions. The interpretation is correct in 94% of 600 punctions. A false diagnosis of malignancy is made in 6.1% of cases. So, this method fails to recognize an important number of cancers. It is not sufficient to assert the diagnosis and must be followed by an histopathological per-operatoire study. On the other hand a cytological diagnosis of cancer is reliable as long as the cytologist is not impressed by some cellular changes which are not so significant, as far as thyroid lesions are concerned, as in other fields of cytology.


Endometrial hyperplasia: a five-year study.

Because of the recent controversy concerning estrogen and endometrial cancer, we studied the possible potential precursor lesions of the endometrium, reviewing 263 patients hospitalized in a community teaching hospital. The estrogen hormonal status, either exogenously or endogenously produced, plays a large role in the histologic structure of the uterine endometrium and may lead to difficulty in determining the exact histologic diagnosis or its potential to progress to endometrial adenocarcinoma.


[Statistical studies on hand accidents (author's transl)].

Statistics furnished by the French Social Security System covering 18 years (1957-1975) show not only the  marked frequency of injuries of the hand their financial, economic and social importance, but also an astonishing consistency of numbers over the years. This lack of improvement shows that (except in certain rare specialized centers) in general the treatment of hand injuries has minimally improved over the course of the last few decades while the rest of traumatology has made spectacular progress. This disastrous state of affairs should be addressed by medical and administrative authorities by improving the education and organizing the treatment of hand injuries.


Metastatic carcinoma with carcinocythemia mimicking leukemia.

Carcinoma metastatic to the bone marrow may present with peripheral blood and bone marrow changes and a clinical picture difficult to distinguish from leukemia. It is important to make an accurate diagnosis since the management is different. We have described a patient with circulating primitive cells and diffuse marrow involvement by similar cells. The pathologic process may be identified without cell markers by careful attention to the pattern of distribution, as well as the cytologic features of the neoplastic cells in the bone marrow biopsy.


[Parathyroid adenoma induced by cervical radiotherapy].

The authors report one case of parathyroid adenoma in a 59 years old woman having received a cervical radiation therapy 38 years previously for suspected Basedow's disease. The cause and effect relationship between the cervical radiation and the appearance of the parathyroid adenoma seems to be established in the light of animal experimentation on one hand, and identical results found in the medical litterature on the other hand.


Ultrastructure of cholangiocarcinoma associated with opisthorchiasis.

An electron microscopic study was carried out on eleven surgical liver biopsy specimens obtained from patients with cholangiocarcinoma associated with opisthorchiasis. The tumor cells of histologically well differentiated cholangiocarcinoma had few cytoplasmic organelles. They contained relatively large nuclei, abundant free ribosomes and numerous groups of fine fibrils. Each cell was surrounded by a basement membrane. Numerous long microvilli were seen projecting into the glandular lumen. The moderately differentiated cholangiocarcinomatous cells exhibited increased organelle content, marked variation in the shape of the nuclei with deep cytoplasmic invagination into the nuclear membrane; there were small intranuclear pseudoinclusions, and shorter microvilli. The tumor cells showed intracellular microvillus-lined spaces, abundant free ribosomes, many fine fibrils and their surrounding basement membranes were incomplete. The ultrastructure of the poorly differentiated cholangiocarcinoma was similar to that of the moderately differentiated tumor, except for fewer microvilli, abundant cytoplasmic organelles, and ill-defined or absent basement membrane.


Colloid adenocarcinoma of the caecum in a 13-year-old. A case report.

A 13-year-old Coloured girl presented with an abdominal mass and a small-bowel obstruction. At operation a constricting carcinoma of the caecum which had spread to the regional lymph nodes was found. Histological examination revealed that it was a mucinous adenocarcinoma.


Surgical treatment of ulnar neuropathy.

Ulnar neuropathy is a well recognized clinical entity caused by a variety of pathological lesions around the elbow. The characteristic features include paresthesia and numbness in the little finger and medial half of the fourth digit, weakness of the small muscles of the hand innervated by the ulnar nerve, and a positive Tinel's sign. The diagnosis is confirmed by electrophysiological studies. Current methods of treatment are anterior transposition, neurolysis and medial epicondylectomy of the humerus. Forty-four patients with ulnar neuropathy are described in the present report. Most were males with a median age of 45. The left side was involved more frequently. Results of subcutaneous anterior transposition and medial epicondylectomy are presented along with a review of the literature.


Respiratory viral infection and wheezy bronchitis in childhood.

The role of respiratory viral infection in wheezy bronchitis was studied in 163 children, aged 0-12 years, in a London general practice. Virological investigations were also performed when these same children had acute upper respiratory illness without wheeze. A virus was isolated in 146 (26.4%) of 554 episodes of wheezy bronchitis, rhinoviruses accounting for almost half of the isolations. The relative frequency with which individual viruses were isolated in wheezy bronchitis was similar to that in acute upper respiratory illness in 180 other children who had never had wheezy bronchitis. The large number of isolations of rhinoviruses in wheezy bronchitis is probably due to their numerous serotypes and the absence of cross-immunity between them. Our findings have confirmed that infection by respiratory viruses can provoke wheezy bronchitis in certain children, in whom host factors are an important predeterminant. In children with a previous history of wheezy bronchitis infection by rhinoviruses was associated significantly more often with such an episode than with upper respiratory illness. The maturation of protective mechanisms, including the acquisition of specific immunity to a progressively larger number of viruses, could explain the fall in the age-incidence of wheezy bronchitis.


Value of measuring serum angiotensin I converting enzyme and serum lysozyme in the management of sarcoidosis.

Serum angiotensin I converting enzyme (ACE) and lysozyme have been measured in 23 controls, 115 patients with sarcoidosis, and 64 with other chest diseases. Both enzymes were significantly raised in sarcoidosis. ACE was raised above the normal range in 21 of 72 (29%) patients with definite sarcoidosis and in 17 of 38 (45%) of those who were untreated and seen within one year of presentation. The rise discriminated usefully between those with stable and progressive disease (5% and 62% respectively). Lysozyme was raised in 50 of 72 (69%) patients with sarcoidosis but also in 11 of 54 (20%) patients with other chest diseases. Discrimination between stable and progressive disease was useful only if very high levels were considered. Five patients had serial measurements after treatment with oral steroids and showed a progressive fall in levals of both enzymes, but patients with other diseases also showed a significant fall within the normal range when so treated. Measurement of these enzymes may help in the management of some cases of sarcoidosis, but results require critical interpretation.


An out-break of acute gastroenteritis due to rotavirus in an infant home.

In December 1976, an outbreak of acute infectious diarrhea occurred among infants who resided in an infant home in the city of Sapporo. Rotavirus infection was proved in 42 (90%) of 47 infants by serologic and/or electron microscopic examinations. Out of 42 infected infants 38(90%) were clinically affected; diarrhea with or without vomiting in 27 (64%), vomiting without diarrhea in 6 (14%) and only febrile episode in 5 (12%). The remaining 4(10%) infants showed no symptoms. Clinical manifestations seemed to differ depending on age. Diarrhea without vomiting was more common in the patients younger than 6 months of age, and vomiting or fever was more common in the groups of older age. Possible reasons for such an age dependency were discussed on the basis of complement-fixation tests using human and calf strains of rotavirus.


Electron microscopic studies on transplantable mucus-secreting and tubular adenocarcinomas of colo-rectal origin in ACI/N rats.

Two transplantable, one mucus-producing (R-1) and the other tubular but less mucinous (R-2), adenocarcinomas were investigated electron microscopically. The R-1 tumor was composed of a large number of intermediate cells and mucus-producing cells, incompletely differentiated goblet-like cells and absorptive-like cells, and a small number of undifferentiated cells. The electron microscopic features of the mucus-producing cells exhibited distinctive features different from those of the epithelium of normal colon. They had highly electron-dense granules, expanded rER, well-developed mitochondria and Golgi apparatus. The R-1 tumor was found to be a well-differentiated adenocarcinoma in agreement with observations by light microscopy, while the R-2 tumor exhibited more malignant features than R-1.


An improved procedure for the preparation of rat uterine cell suspensions.

In the present paper we report on an improved procedure for the preparation of free uterine cells which avoids the use of trypsin and employs very low concentration of collagenase. The cells released mechanically from the digested tissue are constantly removed from the enzyme containing medium, thus minimizing exposure to collagenase. 60%-70% of the cells which make up the intact uterus are obtained as free cells and 95% of these cells are viable for at least 15 hours at 37 degrees. Metabolic integrity was assessed by measuring the cell's ability to oxidize glucose and synthesize proteins over extended periods of time. The membrane leucine carrier protein and the membrane Na+/K+ ATPase were found to be fully functional. Electron microscopic analysis of the cells confirmed their structural integrity. Data are presented illustrating that with this system the estrogen binding protein is stable at physiological temperatures. The cells contain approximately 30,000 specific estrogen binding sites, with an apparent KA of 5--6 x 10(9) M-1. At 37 degrees 80% of the hormone receptor complexes were in the nuclear fraction, 20% in the cytoplasm. The similarity of the estrogen receptor binding parameters with those measured in the intact tissue after in vivo hormone adminsistration, together with the cells' structural and metabolic integrity make this procedure for the preparation of uterine cell suspensions in high yields particularly suitable for studies in which minimal cell injury is an essential prerequisite.


Adrenergic control of cerebral blood flow and energy metabolism in the rat.

Studies in rats were designed to separate and define the roles of the intrinsic and extrinsic adrenergic neurons in the control of cerebral blood flow (CBF) and cerebral energy metabolism. The data suggest several conclusions: 1. Arterial sympathetic innervation plays a role in the autoregulation of cerebral circulation. 2. The central adrenergic neurons have several functions: a) they enhance cerebral vascular tone by action on alpha receptor sites. b) They play an important role in the metabolic control of CBF. The proton-sensitive receptor sites on blood vessel walls require beta-adrenergic input in order to function. c) They influence metabolic rate of brain tissue by acting on beta-receptor sites on the cell membrane.


Evaluation of parasitological and serological techniques in diagnosis of amoebiasis.

Parasitological investigations carried out on 324 subjects of symptomatic and asymptomatic amoebiasis showed that formol-ether concentration was a superior technique than examination of 3 consecutive stool specimens by direct microscopy in cases of colitis, hepatitis and cyst passers. Culture of pus yielded better results than the other techniques for examination of stool in cases of liver abscess. Indirect haemagglutination test carried out with 238 sera from cases confirmed to be either positive or negative for Entamoeba histolytica revealed good correlation of its results with parasitological investigations in cases of dysentery and hepatitis. This test proved to be much superior to parasitological investigations in diagnosis of liver abscess. A close correlation between the results of gel-diffusion and I.H.A. was observed in dysentery and liver abscess groups, although I.H.A. was more sensitive. Precipitin band appeared in gel-diffusion test only when the I.H.A. titre was 1: 486 and the number of bands increased with rise in the titre.


Bluetongue antibody in Botswana's domestic and game animals.

Bluetongue precipitating antibody was demonstrated in sera of cattle, camels, sheep, goats and seven game species. Of the domestic species the percentage of sera positive were; cattle 92%, camels 81%, goats 83% and sheep 36%. Sheep sera, unlike those of other domestic species, varied greatly from area to area in the percentage positive. Seroconversions were recorded in adult sheep between September and April. In adult cattle there was a gradual decline in the percentage positive with increasing age. Positive reactions were recorded in the following game species: impala (Aepyceros melampus), lechwe (Kobus leche), kudu (Tragelaphus strepsiceros), blue wildebeest (Connochaetes taurinus), gemsbok (Oryx gazella), springbok (Antidorcas marsupialis) and tsessebe (Damaliscus lunatus).


Evolution of primary tumors induced in adult mice by MSV-H and MSV-H producer tumor cells.

The oncogenic activity of both MSV-H and MSV-H-producer tumor cells (3T3 + MSV-H) in adult mice was investigated and compared. A higher incidence of tumors was observed with MSV-H tumor cells, especially with very small tumor cell doses. No regression was observed in any of the induced tumors.


Analysis of some factors effecting survival in malignant gliomas.

Many factors, including the histological aspect, are known to effect the survival of patients with malignant gliomas. The relation between survival and diagnoses such as primary and secondary glioblastoma, anaplastic astrocytoma, etc., is not definitely clear. In 324 malignant gliomas the relationship between survival and age, sex, tumor pathology, occurrence of lymphoplasmacytic infiltrations, and size of the examined specimen was studied. Preoperative intervals of primary and secondary glioblastomas do not differ; anaplastic astrocytomas show definitely longer preoperative intervals and slightly but not significantly longer postoperative patient survival. The correlations are discussed, focusing on importance of knowing the survival times of untreated cases in order to evaluate the efficacy of chemotherapeutic drugs in malignant gliomas.


On the relation between peripheral atherosclerosis and serum lipoproteins.

The occurrence and degree of peripheral atherosclerosis in 30 male patients with symptoms of intermittent claudication were studied by arteriography. The changes observed in the angiograms were codified. In all patients the concentrations of triglycerides and cholesterol were determined in whole serum and in the three major lipoprotein classes--very low density, low density and high density lipoproteins. These data were compared with those of a control material and were also correlated to the codified angiographic findings in each individual patient. Positive significant correlation was not found between the arteriographic changes and the serum concentrations of lipids and lipoproteins, which might be explained by an advanced stage of the disease where such relationships might not appear.


Management of neurogenic bladder in infancy and childhood.

Sixty-two patients, age twelve years and under, were treated for incontinence due to neurogenic bladder secondary to spina bifida (58) or trauma (4) with a follow-up period of three to thirty-two months (mean, ten months). In early life, patients were managed with the Credé maneuver (18 patients). Older children were managed with intermittent clean catheterization (44 patients) with or without pharmacologic agents. Continence was achieved with intermittent clean catheterization in 77 per cent, thus enabling these children to be more acceptable to their peers and in many cases attend schools from which they had previously been excluded because of urinary incontinence. With the Credé maneuver, renal deterioration was noted in 11 per cent on follow-up IVP, and in 2 per cent of the patients on intermittent clean catheterization. Recurrent asymptomatic bacteriuria occurred in 33 per cent of those with the Credé maneuver and in 55 per cent of the patients using intermittent clean catheterization. The use of antibiotic bladder irrigations reduced this incidence to 5 per cent. All patients with renal deterioration except one responded to intermittent clean catheterization; this patient was treated with cutaneous vesicostomy. Urodynamic assessment was performed in 15 patients, and this diagnostic tool assisted in the therapeutic management of these children.


[Effect of dibazol on the state of the hypophyseal-adrenal system in patients operated on under thiopental anesthesia].

In the observations over the patients subjected to operations on the limbs under thiopental narcosis and in the experiments on white rats exposed to a shockogenic trauma (by Kennon's method) it has been found that the prophylactic injection of 1--2 mg/kg dose of dibazol rises the non-specific resistance of the body. The hormones of the pituitary-adrenal system have been found to hold an important place in the mechanism of the effect of dibazol.


Immunologic methods for the detection of humoral and cellular immunity.

A variety of immunologic techniques have been introduced during the past few years. Many of these techniques are being applied to clinical specimens in an attempt to help the practicing veterinarian make a diagnosis. The introduction of new techniques requires extensive testing with clinically normal and diseased patients. It is essential for the practicing veterinarian to understand that the techniques available for the detection of immunologic disorders in the dog and cat are not routine diagnostic procedures and that adequate information has not been developed for any of the techniques described to assure the clinical significance of either positive or negative results (Table 3). This should not discourage the practitioner from submitting samples, but should encourage him or her to question the significance of those results and to attempt to correlate them with history and clinical signs before arriving at a final diagnosis.


Frequency of canine and feline tumors in a defined population.

The Tulsa Registry of Canine and Feline Neoplasms was the second animal tumor registry in the United States concerned with a defined population in a delimited geographic area. Only tumors histologically confirmed by registry pathologists were included in frequency statistics based on the annual dog and cat population presented to veterinarians. During the first registry year, about 1% of the 63,504 dogs and 0.5% of the 11,909 cats had one or more primary tumors. While the incidence rate for malignant tumors in dogs was similar to that in cats, the incidence of benign tumors of dogs was over 10 times that of cats. The most common tumors were sebaceous adenoma in dogs and lymphosarcoma in cats. Mammary cancer was the most common malignant tumor in dogs. Mammary tumors of female dogs were significantly more frequent in Pointers, Poodles and Boston Terriers, in that order, than in other breeds. A greater incidence of mammary tumors among intact compared to spayed female dogs was seen for virtually every age group except in the Pointer breed.


Granular cell variants in a rat schwannoma. Evidence of neurogenic origin of granular cell tumor (myoblastoma).

A large, intraabdominal rat schwannoma had numerous granule-containing cells cytologically identical to cells of granular cell tumor (myoblastoma). The small eosinophilic granules stained positively by the periodic acid-Schiff (PAS) reaction, with intensity not reduced by diastase pretreatment. Granules stained positively with the Tibor Pap silver impregnation for reticulin and by electron microscopy were identical to myoblastoma cell granules. The nuclei of granular cells were morphologically identical to those of the neoplastic Schwann cells. The granular cells were in numerous foci within the tumor, frequently were seen in mitosis, and possessed an extremely variable volume of cytoplasm. They seemed to evolve from neoplastic Schwann cells. Cells with only a narrow perinuclear rim of granular cytoplasm were of the same size and general configuration as adjacent neoplastic Schwann cells, while cells with increasing volumes of granular cytoplasm were increasingly swollen and round. One area of the tumor was composed almost entirely of such large cells and was histologically identical to classic granular cell tumor.


Effects of anabolic steroids on liver cell ultrastructure in sheep.

Castrated male sheep were sham inplanted or implanted with estradiol, trenbolone acetate or trenbolone acetate in combination with estradiol, and slaughtered after 56 days. Ultrastructural and morphometric examination of the livers of steroid-treated sheep showed an increase in the volume density of the cell occupied by rough endoplasmic reticulum and microbodies. In four of the eight sheep treated with trenbolone acetate, either alone or in combination with estradiol, enlarged mitochondria with crystalline inclusions were seen. The increase in hepatic rough endoplasmic reticulum may be of benefit to the sheep whereas the mitochondrial changes after anabolic steroid use indicate a cellular lesion of unknown significance for health.


Malignant fibrous histiocytoma in dogs and cats.

Five soft tissue tumors of varied morphology in dogs and cats were classified as malignant fibrous histiocytomas on the basis of their histologic composition. All were composed of varying mixtures of histiocytes and fibroblasts and three contained large multinucleated cells. This giant cell variant of malignant fibrous histiocytoma was seen only in cats. These tumors are comparable to those described in man as malignant fibrous histiocytoma on the basis of the malignant histiocyte and its varied morphology and function.


Ultrastructural and histological study of 11 bronchial carcinoids. Evidence for different types.

Seven of eleven bronchial carcinoids investigated showed cells with small granules resembling P cells which have already been described in human fetal and adult lung; two of these P cell tumours showed distinctive paraganglioid features. One tumour showed peculiar ultrastructural findings resembling closely those previously reported by Black (1969) in a so called "pulmonary oncocytoma". Three remaining cases showed large secretory granules resembling those of type 3 cells already described by Hage (1973b) in bronchial carcinoids; one of these tumours produced large amounts of 5-hydroxytryptamine (5HT). It is concluded that, on cytological grounds, at least two types of tumours can be distinguished among bronchial carcinoids, i.e. P cell and type 3 cell tumours. Moreover, two varieties of P cell carcinoids have been recognized, showing either the less frequent and more distinctive paraganglioid structure or the more common trabecular structure.


[Isolation and properties of myeloperoxidase from human bone marrow].

A preparation of myeloperoxidase was isolated from human bone marrow by column chromatography on DEAE-Sephadex, CM cellulose and gel filtration on Sephadex G-100. The enzyme was purified to 0.76 purity with a 16% yield. The repeated gel filtration, E430/E280 ratio and immunochemical study confirm the high degree of purification. Molecular weight of the enzyme, determined by gel filtration on Sephadex G-100, was 150000.


[Effect of oxythiamine on pyruvate and lactate metabolism in rat tissues].

The ratio of two substrates (pyruvate and lactate), activity of enzymes, responsible for their turnover in liver tissue, sceletal muscles and blood, were studied simultaneously in experiments on the effect of hydroxythiamin, which was administered at doses, causing a state of hypovitaminosis B1. Hydroxythiamin was shown to inhibit specifically the activity of thiamin-dependent enzymes (transketolase and pyruvate dehydrogenase). It affected also the metabolism of triose phosphates, pyruvate and lactate. At the same time, hydroxythiamin was responsible for changes in activities of other enzymes, participating in turnover of the substrates studied.


[Relation of urinary excretion of cholesterol in cancer patients to certain hormonal-metabolic parameters and the effect of drugs on this relation].

Excretion of cholesterol with urine was studied using gas chromatography in healthy persons, in patients with cancer of mammary glands, fibroadenoma, lung carcinoma and in patients with beningn processes in lungs. Cholesterol excretion was not increased in patients with the malignant tumors studied. In patients with the cancer of mammary glands and lung carcinoma normal correlation was altered between excretion of cholesterol with urine and content of lipoproteins, protein-bound iodine, 11-hydroxycorticosteroids in blood as well as excretion of cyclic AMP with urine. Treatment with euphylline was accompanied by a decrease in cholesteroluria in patients with fibroadenoma but the drug had no comparable effect on patients with the cancer of mammary glands. In patients with the cancer of mammary glands phenphormine caused distinct decrease and misclerone--moderate increase in excretion of cholesterol with urine.


[Study of lipoprotein changes in the vessel wall by ultracentrifugation of aortic extracts in discontinuous density gradients].

As shown by stepwise density gradient ultracentrifugation, atherogenic lipoproteins pentrating into aorta wall, underwent conversions, which were accompanied by alterations in their hydratation density. The data obtained suggest that complex formation of lipoproteins with components of connective tissue matrix is one of important steps responsible for conversion of atherogenic lipoproteins in vessel wall.


[Change in the apoproteins of very low density lipoproteins in the blood in hypertriglyceridemia].

Some properties of very low density lipoproteins were studied under conditions causing an increase of their concentration in blood plasma. Content of high molecular apolipoprotein B and low molecular lipoproteins were estimated after fractionation using column chromatography and selective precipitation with tetramethylurea. In 216 men (40-59 years old) with hypertriglyceridemia the increase in content of particles of very low density lipoproteins was accompanied by simultaneous alteration in their composition in blood plasma: content of low molecular polypeptides, triglycerides and cholesterol was increased per a weight unit of apoprotein B. At the same time, the absolute concent of apoprotein B and of low molecular apoproteins of very low density lipoproteins was increased in blood plasma. The most distinct alteration in the ratio of apolipoproteins to very low density lipoproteins was observed, if content of testosterone--activator of lipoprotein lipase--was decreased in blood plasma.


[Hydrocyanic acid content in cerals and cereal products].

In the above paper for the first time a systematic study of the amount of hydrocyanic acid in grains and cereal products is reported. Among 24 analysed wheat, rye, maize and oats types, the presence of hydrocyanic acid could be identified in 19 cases in their Karyopses. Similar is the result with 28 among 31 analysed cereal products. The content of hydrocyanic acid lies between 0.1 and 45 microgram/100 gr dried mass.


[Hemodynamics in patients suffering from hyperkinetic cardiac syndromes and in normal persons under psychological stress before and after treatment with propranolol (author's transl)].

In patients with hyperkinetic heart syndrome we found at rest a higher heart rate, a higher stroke volume and a higher cardiac output than in normal volunteers. Therefore blood pressure is high although peripheral resistance is lower than in normals. Similar circulatory differences were found under conditions of mental stress. After beta-adrenergic blockade with 15 mg Propranolol heart rate and cardiac output decrease, whereas peripheral resistance increases. Mean blood pressure thus remains unchanged. Even after beta-adrenergic blockade circulatory differences between normals and patients with hyperkinetic heart syndrome are seen. The possible causes of these differences are discussed.


Feline preleukemia: an animal model of human disease.

In man, hematologic abnormalities precede the development of acute myeloblastic leukemia in about one-third of individuals. This preleukemic state may represent a stage of adult leukemia wherein small numbers of leukemic cells are present and the normal marrow stem cell compartment has not been seriously compromised. A syndrome resembling human preleukemia occurs in cats infected with feline leukemia virus (FeLV). This disorder is characterized by anemia, leukopenia or thrombocytopenia occurring weeks or months prior to the development of feline acute leukemia. The natural occurrence of this syndrome in this domestic animal population makes it a potential model of human preleukemia. Initial poor results of therapy of human preleukemia presently prohibit one from carrying out controlled trials with chemotherapeutic agents in such a group of patients. Preliminary trials with chemo- and/or immunotherapy may be more easily attempted with FeLV infected preleukemic cats.


[Attempts to enrich and to solubilize the muscarinic acetylcholinereceptor from bovine caudate nucleus (author's transl)].

Neuronal membranes of postsynaptic origin twofold enriched in acetylcholinesterase, muscarinic acetylcholinereceptor and (Na+/K+)-ATP-Phosphohydrolase, proteins associated with cholinergic nerve excitability, were prepared with yields between 60 and 75% from bovine caudate nucleus. On subfractionation of these membranes an additional twofold enrichment of the mentioned proteins is achieved in different subfractions. SDS-gradient gel electrophoresis shows that these subfractions have slightly different polypeptide compositions. Neuronal membranes of presynaptic origin on the other hand, prepared from purified synaptosomes, possess only small amounts of the mentioned proteins, showing no enrichment with respect to the homogenate. Solubilization of acetylcholinesterase with 1 M NaC1 as well as of muscarinic acetylcholinreceptor with 2 M NaC1 does not succeed. These proteins are therefore not solely bound by ionic forces to the isolated membranes from bovine caudate nucleus.


Antibody studies in the Kuru region. Immunological epidemiology of population groups in and adjacent to the Kuru region in Papua New Guinea. I. Enteroviruses.

A serological survey is reported for antibodies to Coxsackie, ECHO and polioviruses on sera collected in the kuru region of Papua New Guinea during earliest European contacts with kuru-affected and control populations through the period of highest kuru incidence. The results are discussed in the light of increasing European contact over the period of investigation. Suggestions are made concerning possible immunization programs with polioviruses.


[Pathogenesis of several forms of progressive muscular dystrophy].

The level of cyclic 3,5-adenosine monophosphate (cAMP), the activity of adenylate cyclase (AC) and phosphodiesterase (PDE) were studied in bioptates of the muscles of 17 patients with different forms of myopathy. The cAMP level and AC activity were decreased while that of PDE was increased. These changes are particularly demonstrative in patients with Erba type of myopathy. It is recommended that beta-adrenomimetic drugs and PDE inhibitors may be tried in pathogenetic therapy.


[Pathogenetic therapy of nervous system and muscular diseases using large doses of prednisolone on alternate days].

A total of 230 patients with myasthenia, polymositis, disseminated sclerosis and myeloradiculopolyneuronitis were administered high doses of prednisolone (up to 100 mg) every other day. The treatment efficacy and low incidence of side effects and complications are emphasized. High doses of prednisolone given every other day do not inhibit secretions of endogenic ACTH and cortisol. The immunodepressant effect of the drug remains unchanged.


[Clinical value of studying strength-duration curves using intramuscular (needle) electrodes in patients with lumbosacral radicular syndromes].

The paper deals with the results of a force-duration curve comparative study which was accomplished-in 20 patients with the aid of usual skin and acupunctural point electrodes. The spicular needle introduced painlessly into the muscles studied, served as an active electrode connected by a fine cord to a clamp of the electric pulser. In order to determine the force-duration curve, 10 rectangular impulses of a different length at a constant frequency of 1 hz were used. The results demonstrated that the determination of the force-duration curve with the aid of acupuncture is a more sensitive and precise method of study inasmuch as it permits to receive genuine values of the current in the test area.


[Facial autonomic and trophic disorders].

The paper is concerned with the results of a clinical electrophysiological, biochemical, histochemical, X-ray and morphological study of 289 patients with different vegetovascular and trophical disturbances, mainly of a regional character, in the facial area. Some clinical aspects and questions of the pathogenesis of these disturbances are discussed which are not sufficiently reflected in the literature. It is suggested that the form of the pterygopalatine ganglion is related to the incidence of the pathological process and the traits of vegetative and pain phenomena, accompanying the Sluder syndrome. Vegetovascular changes were revealed in the skin of the face and enzymatic changes in mucous membrane of the nose on the homolateral to the paresis side of the face in lesions of the facial nerve. Specific vegetative trophical changes were also found in a progressive hemiatrophy of the face, Barrakera-Simons disease, in the syndrome of facial hemistrophy due to lesions of the different vegetative and somatic structures of the nervous system.


Interaction of metal ions with nucleic acids. Interaction of copper(II) with adenosine and its derivatives.

The interaction of copper(II) with adenosine, 2'-deoxyadenosine, 1-methyladenosine, 7-deazaadenosine and AMP was studied by spectroscopic and magnetochemical methods. In non-aqueous medium, copper(II) interacts with adenosine and AMP at N-7 and N-1, and with 1-methyladenosine at N-7 and N-3. The copper ion is not bound to the NH2 group. In aqueous solution, copper(II) interacts both with N-7 and N-1 of adenosine, and in AMP additionally with the phosphate group. The interaction of copper(II) with the heterocyclic part, but not withthe phosphate group, is dependent on the extent of protonation of the molecular. A crystalline AMP-copper(II) complex [Cu(C10H12N5O7P).(H2O)2] was obtained; the phosphate group and probably N-7 are involved in the complex formation.


Studies on the structure of haptoglobin and the haptoglobin-haemoglobin complex by spin and fluorescence labelling.

Human haptoglobin (Hp) of the 1-1 type incorporated one spin or fluorescence marker per molecule; the markers were found in the beta chain. Formation of the complex between spin-labelled Hp and haemoglobin or antibody caused conformational changes in the Hp molecular, evidenced by increased participation in the electron paramagnetic resonance spectrum of the component bound with the slowly rotating marker. From fluorescence-labelled Hp, the beta chain was isolated and cleaved by CNBr; only in one of the obtained peptides, one out of 4 histidine residues was modified with the marker.


The effect of sialic acid on adenylate cyclase activity and thyrotropin-receptor binding in human thyroid membranes.

Exogenous sialic acid at 3 mM and higher concentrations inhibits the basal adenylate cyclase activity and the activity stimulated by thyrotropin (TSH) and fluoride in the human thyroid membrane fraction; 30 mM-sialic acid acts as an inhibitor of TSH binding. The decrease of these activities at high sialic acid concentrations might be ascribed to changes in membrane conformation caused by acidic character of this sugar.


[Role of the pituitary-adrenal system in the pathogenesis of severe closed craniocerebral injuries].

In patients with severe contusion of the brain, the concentration of ACTH in blood increases from the 2nd and to the 10th day after the trauma whereas the level of 11-OCS remains on a significantly high level during the entire period of treatment. The potential reserves of the adrenal cortex are reduced on the 5th day. The ACTH level returns to normal by the end of the 3rd week. Neurohormonal shifts play an important role in the pathogenesis of the trauma and cause the development of its clinical manifestations.


Effects of soluble fractions from untreated and SiO2-treated subcellular particles of macrophages on nucleic acid metabolism in isolated nuclei of experimental granulation tissue.

Nuclei isolated from proliferating granulation tissue were incubated with 20 000 g supernatants from untreated and SiO2-treated subcellular particles of rat peritoneal macrophages in the presence of radioactive nucleic acid precursors. The supernatant from SiO2-treated subcellular particles increased the incorporation of [3H]CTP into nuclear RNA maximally by 26% at 5 min, and that of [methyl-3H]dTTP into DNA by 16% at 20 min. The release of radioactivity from labeled DNA was suppressed simultaneously. An RNase preparation from rat peritoneal macrophages enhanced the release of radioactivity from labeled DNA similarly as the soluble fraction from untreated subcellular particles of macrophages. The results suggest that the effects of the soluble fractions upon DNA metabolism of granuloma cells are at least partly independent of the effects on RNA metabolism and that the soluble fraction from SiO2-treated subcellular particles of macrophages stabilizes DNA through inhibition of nuclease activity.


Demyelinating encephalomyelitis induced by a long-term corona virus infection in rats. A preliminary report.

About 30% of weanling rats inoculated with JHM virus developed a subacute demyelinating encephalomyelitis (SDE) 3 weeks after inoculation (a.i.). From the remaining animals, 5% displayed overt neurological signs 3, 6, and 8 months a.i. Animals with and without clinical signs 6-8 months a.i. were morphologically examined. Fresh demyelinating lesions could be demonstrated in paralyzed animals. Viral antigen was demonstrated and infectious JHM virus could be recovered from one animal which developed clinical signs at 3 months a.i. In one animal with clinical onset of 8 months a.i. completely remyelinated areas as well as recent demyelinating lesions were observed, suggesting a recurrence of the disease process. Remyelinated areas were also found in 40% of clinically silent animals. The morphology of the late onset of the demyelination was similar to that occurring in SDE. Remyelination consisted of both CNS and PNS-type. This animal model offers the possibility to investigate the virus-host relationship which is responsible for the induction of a demyelinating process after a long incubation period.


Experimental aggression and bruxism in rats.

Aggression has been suggested as one of the etiologic factors in bruxism. Experimental bruxism, audible, nonfunctional grinding or clenching of the teeth, was provoked in aggressive animals by drugs affecting central dopaminergic systems. Electric foot-stimulation was used to induce aggression, evident as the threatening or fighting position, in paired male Wistar rats. After initial stimulation, shocks were given only to maintain the characteristic fighting pose. Apomorphine facilitated induction of aggressive behaviour by electric shocks, and the rats receiving both treatments showed bruxism more frequently than controls subjected to shocks alone: up to 95 bruxism periods registered by a tape recorder during 30 min, as opposed to a few sporadic periods in the controls. Without shocks, apomorphine-treated rats displayed stereotypy with locomotion and biting of various objects. Aggression and bruxism were not equally successfully induced after L-dopa given with a peripheral inhibitor of aromatic amino acid decarboxylase (benserazide) or when L-dopa treatment was modified with the inhibitor of dopamine-beta-hydroxylase (diethyldithiocarbamate) or monoamine oxidase inhibitor (iproniazid). However, all the present drug combinations known to enhance central dopaminergic function seemed to increase irritability and disposition to experimental oral dyskinesias. This was observed especially when a sensory stimulus was applied at the same time or the drug had an amine-releasing effect (pheniprazine).


A prospective study on the incidence and significance of congenital cytomegalovirus infection.

Screening of 3060 neonates for congenital cytomegalovirus (CMV) infection by virus excretion in the urine showed an overall incidence of 0.4%. The incidence was about 1% for mothers between 16 and 25 years and only 0.2% for mothers between 25 and 35. No mothers over 35 years of age gave birth to congenitally infected infants. The percentage of women in the child-bearing age susceptible to CMV infection was estimated by the absence of CMV complement-fixing antibodies in cord sera and ranged from 48% to 33% with increasing age. None of the infected infants showed obvious signs of congenital CMV infection at birth. At follow-up, two infants showed slight, but transient symptoms compatible with a foetal infection; a pair of premature twins exhibited retarded physical and psychomotor development, but this could just as well be ascribed to the prematurity itself. None of the infants had detectable CMV--IgM antibodies in cord sera, but a trend towards elevated total IgM concentration in cord sera and elevated virus excretion titres appeared in the infants with symptoms. With the very low incidence and no signs of sensomotor sequelae the preliminary conclusion is that foetal CMV infection in our population by no means has a significance to deserve screening or a vaccination programme.


Screening of cord blood low-density-lipoprotein cholesterol in the diagnosis of familial hypercholesterolaemia: a study of 2000 infants.

A prospective follow-up study of infants selected by cord blood total cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C) levels from 2000 consecutive live births was undertaken to reassess the role of cord blood screening in the diagnosis of familial hypercholesterolaemia (FH). Mean values for serum cholesterol were (mmol/l +/- S.D.): TC, 1.83 +/- 0.56; LDL-C, 0.90 +/- 0.49; HDL-C, 0.70 +/- 0.33; TG, 0.38 +/- 0.16. Seventy-three of 117 infants who had had a cord TC and/or LDL-C greater than 95th percentile, and 373 control group children (cord TC and/or LDL-C less than 95th percentile) were followed up at age 3--12 months. Six of the 117 were hypercholesterolaemic (HC), and one child had an HC parent: positive detection rate greater than or equal to 0.05%; false positive rate greater than or equal to 3.7%. Four control-group children were HC and had an HC parent; false negative rate greater than or equal to 1.1%. With the possible exception of detecting FH in a child with a known affected parent, cord blood screening appears to be unreliable for the diagnosis of FH.


Multiple pituitary hormone deficiencies in eight siblings of one Jewish Moroccan family.

In a Jewish Moroccan inbred family, 8 of 12 siblings were found to have multiple deficiencies of pituitary hormones, including GH, TSH and gonadotrophins. The parents showed no deficiency and are in good health, as are the other 4 siblings. The investigations carried out indicate that in this family the etiology is hereditary in nature, probably being autosomal recessive, with the defect located in the pituitary gland.


Distribution of cyclic nucleotides in the organ of Corti.

Recent developments in radioimmunoassay technology have made possible measurements of cyclic nucleotides in individual specimens of the organ of Corti and its subdivisions. Steep longitudinal and transverse gradients of glycogen are known to exist in the organ of Corti of the guinea pig, with preferential accumulation in the outer hair cells of the apical turns. However, no significant longitudinal gradient of cyclic AMP was detectable in the organ of Corti, and the concentration of the compound was found to be nearly equal in the inner and outer hair cell layers. This is indirect evidence against the concept that cyclic AMP plays a role as "second messenger" in the control of glycogen metabolism of the organ of Corti. By contrast, the concentration of cyclic GMP was found to be consistently higher in the inner layer than in the outer layer of the organ of Corti, and to increase significantly in basal direction. This trend is remarkably similar to the distribution patterns of acetylcholinesterase, which may be considered as indirect evidence in favor of a possible role of cyclic GMP in the mediation of cholinergic effects.


Lymphocyte blast transformation response of seropositive and seronegative subjects to herpes simplex, rubella, mumps and measles virus antigens.

Lymphocytes from seronegative and seropositive subjects were stimulated in vitro with herpes simplex, rubella, mumps and measles viral antigens. Viral antigens were beta-propiolactone inactivated crude material (containing cell-membrane fragments) grown in Vero cells and prepared identically. Lymphocytes from seropositive subjects responded specifically to herpes virus antigen, and most rubella and mumps seropositive subjects responded to the respective antigens. Measles antigen, however, did not stimulate lymphocytes from seropositive or seronegative subjects. The responses of three subjects studied repeatedly over a period of several weeks were reproducible. The results of the study support the usefulness of the blast transformation test as a measure of sensitization to viruses.


Apomorphine stereotypies and transmitter mechanisms in the striatum. I. Changes in the apomorphine stereotypies caused by drugs acting on the GABA-ergic, dopaminergic and cholinergic transmission.

Experiments on male albino mice were carried out in order to determine the effects of drugs connecting with the GABA-ergic, dopaminergic and cholinergic transmission, on apomorphine stereotypies. The agents acting on GABA-ergic transmission are found to reduce the intensity of apomorphine stereotypies in the following order (arranged from strongest to weakest effect and expressed in doses of microgram per mouse: GABA (100), aminooxyacetic acid (5), diazepam (20), picrotoxin (1), GABA (10), semicarbazide (30), picrotoxin (0.1). The agents acting on the dopaminergic transmission also reduce apomorphine stereotypies in the following order: haloperidol (20;2), L-DOPA (500 mg/kg, i. p.), alpha-methylparatyrosine (150 mg/kg, i. p.) diethyldithiocarbamate (200). The strongest antagonistic effect in the two groups of agents studied was found for haloperidol. The agents acting on the cholinergic transmission (agonists and antagonists of muscarinic and nicotinic cholinoreceptors) have no significant effect on apomorphine stereotypies. It is assumed that the striatum is not the only brain structure responsible for apomorphine stereotypies.


Apomorphine stereotypies and transmitter mechanisms in the striatum. II. Interactions between GABA-ergic and cholinergic transmission.

The interactions between the GABA-ergic and cholinergic transmissions in the striatum of male mice are determined through microinjection in the striatum of agents influencing these types of transmission in cases of apomorphine stereotypies. It is found that the agents acting on the cholinergic transmission (agonists and antagonists of the muscarinic and nicotinic cholinoreceptors), antagonize considerably the reducing effect on apomorphine stereotypies of the agents acting on GABA-ergic transmission. Conversely, the agents acting on GABA-ergic transmission (pre- and post-synaptic) intensify or weaken the effects of the agents acting on the cholinergic transmission with respect to apomorphine stereotypies, though the difference is not entirely significant. The influence of the effects of the agents acting on the GABA-ergic transmission in cases of apomorphine stereotypies is thought to be due to the antagonistic action of the striatal cholinergic neurones on the GABA-ergic neurones, while the latter interact with the striatal dopaminergic neurones either directly or through the mediation of substantia nigra. The lack of direct interactions between the GABA-ergic and the cholinergic neurones in the striatum explains the weak influence on cholinergic transmission exerted by the agents acting on the GABA-ergic transmission with respect to apomorphine stereotypies.


Uptake and release of adenosine in isolated rat fat cells.

Radioactively labelled adenosine and adenine were rapidly taken up by isolated rat fat cells, and incorporated into nucleotides, of which ATP dominated. The overall process had an apparent Km of 1--5 micrometers. During incubation, especially in the presence of lipolytic agents, there was a reduction in labelled ATP with a compensatory increase in ADP, AMP, cAMP and nucleosides. The build-up of adenosine during incubation was inhibited by theophylline, which inhibits 5'-nucleotidase. Radioactivity released from perifused fat cells consisted mainly of nucleoside material, of which adenosine predominated. Lipolytic stimulation caused no significant increase in nucleoside outflow from perifused cells, whereas oxygenation was capable of reducing this outflow. It is concluded that adenosine is formed by fat cells as a consequence of ATP breakdown. Stimulation of lipolysis during activation of the sympathetic nerves leads to reversible ATP breakdown and adenosine release. Adenosine might therefore act as a modulator of lipolysis in vivo under these conditions, even though it does not serve as a feed back regulator in the proper sense.


Biochemical and morphological study on hepatotoxicity of azathioprine in rat.

Sprague-Dawley rats given azathioprine in the diet for 3 to 4 weeks developed severe liver damage. Elevations of serum alkaline phosphatase and gamma-glutamyl transpeptidase activities were associated with increased hepatic glucose 6-phosphate dehydrogenase levels and decreased liver glucose 6-phosphatase activities, i.e., conditions which were commonly observed in various hepatotoxin-induced liver injuries. Light and electron microscopic observations revealed centrolobular necrosis with large scars and the proliferation of the mitochondria and rough endoplasmic reticulum. This model could be used to study the mechanisms of azathioprine-induced liver damage and its prevention.


A case of mesenchymoma in the oral cavity clinically resembling a large pleomorphic adenoma.

A report is made of a 52-year-old male whose main complaint was a painless tumor at the right side of the palate resulting in speech disturbance. He was diagnosed as a case of what Stout called benign mesenchymoma. Some discussion is also made of the tumor pathology in terms of genetic factors, predirective sites, age range, sex differences and therapy.


Detection and characterization of antibody to liver cell membrane in sera from patients with chronic active liver diseases.

Sera from 84 patients with chronic liver disease [CLD] (74 chronic active) and from 53 blood donors were tested immunochemically for anti-liver cell membrane antibody (LMAb). LMAb to rat liver tested by an indirect immunofluorescent technique was positive in 53.3% of CLD patients with positive HB surface antibody (HBsAb) and 40.0% of HBsAb positive blood donors. Pepsin digestion of the sera indicated that the binding between liver cell membrane and IgG was at the Fc site on the immunoglobulin. The sera with positive LMAb from HBsAb positive blood donors had elevated Clq-binding activity (Clq-BA). The LMAb to rat liver was a macro-molecular IgG (19-22S IgG) when assayed by Sephadex G-200 column chromatography and 5-40% sucrose density gradient ultracentrifugation. The results suggest that the LMAb in serum from a patient with chronic active liver disease may be an immune complex which consists of various antigens such as HB virus and its antibodies in serum.


Sarcoidosis presenting with diabetes insipidus followed by acute cranial nerve syndrome. A case report.

Diabetes insipidus in a previously healthy 16-year-old girl led to surgical exploration of a pituitary stalk intumescence detected by oxygen cisternography with the use of tomography. Biopsy of the pituitary stalk contained chronically inflamed brain tissue. Subsequent liver and bone biopsies showed characteristic granulomata, confirming the diagnosis of sarcoidosis. Subfrontal craniotomy was followed by a rapidly progressive basal meningoencephalitis with multiple cranial nerve involvement. The need to establish a causal diagnosis in diabetes insipidus is stressed. The rarity of the disorder and the presumed role of subfrontal craniotomy with regard to the flare-up of the sarcoidosis of the brain are discussed.


'Not Cushing's syndrome'.

Cushing's syndrome is characterized by protein wasting secondary to hypergluconeogenesis, which produces thin skin, poor muscle tone, osteoporosis and capillary fragility. These features distinguish patients with true Cushing's syndrome from those who have some of the clinical findings often associated with the syndrome, such as obesity, hypertension, striae and hirsutism. The dexamethasone suppression test helps identify patients with pseudo-Cushing's syndrome.


Altered adrenergic activity in coronary arterial spasm: insight into mechanism based on study of coronary hemodynamics and the electrocardiogram.

To elucidate the pathophysiologic mechanism of coronary arterial spasm, the hypothesis was examined that underlying alterations in sympathetic activity may account for this syndrome in some patients. Observations were directed to alterations in coronary arterial hemodynamics and the electrocardiogram. Spasm of the left anterior descending coronary artery produced a mean increase in coronary vascular resistance of 107 percent (P less than 0.05) in four patients in whom coronary sinus blood flow was measured with the thermodilution technique. The alpha adrenergic blocking agent phentolamine, given intravenously, acutely reversed coronary spasm and its clinical manifestations in eight patients and reduced coronary resistance. In four patients, administration of the long-acting oral alpha blocking agent phenoxybenzamine (20 to 80 mg/day) caused disappearance of symptoms during a follow-up period of 3 to 12 months. Transient prolongation of the corrected Q-T interval preceded spontaneous or ergonovine maleate-provoked coronary spasm in 11 patients with variant angina pectoris, whereas no significant change in the Q-T interval followed ergonovine administration in 27 control patients with atypical chest pain who did not have coronary spasm. T wave inversions in the resting electrocardiogram were normalized by isoproterenol infusion in one patient and by long-term phenoxybenzamine treatment in four patients with variant angina pectoris. These Q-T and T wave changes are analogous to those described with unilateral or asymmetric stellate ganglion stimulation in animals. These observations suggest that alterations in the sympathetic nervous system that are consistent with asymmetric stellate ganglion activity and transient alpha adrenergic receptor stimulation can presage the development of coronary arterial spasm in some patients with variant angina pectoris.


Serum lipid response to a high-caloric, high-fat diet in agricultural workers during 12 months.

The effect of a gluttony diet in healthy subjects was studied over an observation period of 12 months. Twenty-six agricultural workers, all of them Yemenite Jews, received a high-caloric, high-fat diet, and the changes in serum cholesterol (CH), high-density-lipoprotein-cholesterol, triglycerides, and body weight were assessed. Yemenite Jews as a group are characterized by low serum CH levels and by a low incidence of coronary artery disease. For a period of 7 months the subjects received a diet of 4553 cal/day, more than double their original "Yemenite diet". After this time they resumed their customary low-caloric diet for 3 months, and thereafter for another 2 months they continued with the high-caloric food regimen. The high-caloric, high-fat diet resulted in the expected increase of serum CH. A similar increase of high-density lipoprotein-CH was found. Serum triglyceride levels changed inversely to those of CH. It is suggested that the altered relation of calories derived from carbohydrates to those derived from fats brought about the decrease of triglycerides, and this irrespective of the increased intake of carbohydrates and fats. The rather small gain of body weight over the trial period--despite the doubled caloric intake--is similar to other studies that showed that the ability of normal individuals to gain weight through overeating varies considerably.


Lymphosarcoma of the duodenum associated with carcinoma of the lung. Five-year survival.

The case presented describes a patient with lymphosarcoma of the duodenum associated with carcinoma of the lung. This emphasizes the basic problems which lymphosarcoma of the duodenum presents. They are vague symptoms until late in the course of the disease, the absence of early physical findings, the difficulty in interpretation of radiological studies and the frequent association with other primary malignancies elsewhere.


Metastatic carcinoma simulating linitis plastica of the colon. A case report.

Reported herein is the case of a 70-year old woman with metastatic breast carcinoma presenting as linitis plastica of the ascending colon. The breast tumor was diagnosed nine years previously. The clinical, roentgenographic and pathologic features of colonic linitis plastica and the preoperative diagnostic difficulties are discussed. There is no difference in the morphologic features of primary and secondary linitis plastica. The latter may result from anaplastic carcinoma of the stomach, gallbladder or breast.


Induced abortion and congenital malformations in offspring of subsequent pregnancies.

A case-control (n = 1427 and 3001, respectively) study in Connecticut found no relationship between delivery of an infant with congenital malformations and overall previous experience of induced abortion (odds ratio (o) = 0.9, 95% CL = 0.7, 1.1). Delivery of a congenitally malformed infant was also unrelated to: 1)abortion of penultimate pregnancy, 2) abortion of first pregnancy when index pregnancy is second, and 3) multiple previous abortions. Non-white women aged 25-29 who delivered a malformed child were significantly more likely to have aborted ( o = 2.6,95% CL = 1.2, 5.8, p less than 0.05). This may be due to more frequent histories of illegal and septic abortion, or to other characteristics of these women. Legal abortion performed under safe clinical conditions appears to impose no increased risk for subsequent delivery of a malformed infant.


ProACTH: use for early detection of lung cancer.

ProACTH was identified by radioimmunoassay and column chromatography in extracts of 38 lung carcinomas. One hundred patients were evaluated because of abnormalities on chest roentgenograms; 53 (72 per cent) of 74 with lung cancers had increased plasma ACTH immunoreactivity; all 26 with benign abnormalities had normal ACTH. Of 101 patients with obstructive lung disease, five of 20 with elevated plasma ACTH levels and two of 81 with normal plasma ACTH levels had lung cancer within two years. In three of 31 patients with granulomatous lung disease plasma ACTH levels were elevated during acute exacerbation of the disease, but they returned to normal after recovery. We conclude that plasma ACTH immunoreactivity is frequently increased early in the course of lung carcinoma.


Fulminating hypercalcemia and markedly increased nephrogenous cyclic AMP in a patient with transitional cell carcinoma of the bladder.

Refractory hypercalcemia developed suddenly in a patient who had undergone a radical cystectomy for an anaplastic transitional cell carcinoma of the bladder. A normal serum parathyroid hormone (PTH) value was obtained by immunoassay while the patient had hypercalcemia and unimpaired renal function. This normal PTH value in the presence of hypercalcemia was consistent with his hypercalcemia being secondary to excessive amounts of circulating PTH. The finding of increased nephrogenous cyclic AMP, however, provided the definitive diagnosis of hyyperparathyroidism. Since autopsy revealed that there was no residual tumor in the bladder area, only evidence of metastatic disease, and since the parathyroid glands were not hyperplastic or adenomatous, we attributed this patient's hypercalcemia to hyperparathyroidism due to the ectopic production of PTH by a metastasis from the transitional cell carcinoma of the bladder.


Effects of long-term estrogen replacement therapy. II. Neoplasia.

Two groups of hypoestrogenic women are analyzed by retrospective comparison. Patients were observed by a single group of physicians for at least five years -- 301 patients treated with replacement estrogen and 309 untreated patients. Of each group, 207 women had uteri in situ. Incidence figures for neoplasia (gynecologic, breast, and all sites) were compared between the two groups and with the Third National Cancer Survey, yielding a risk ratio for the development of adenocarcinoma of the endometrium among estrogen-treated women of 3.8 and 9.3, respectively. There was no increase among any other malignancies. The addition of synthetic progestin to estrogen therapy provided significant protection against the likelihood of developing endometrial cancer and did not reduce previously reported metabolic benefits of estrogen treatment. Data pertaining to estrogen use and details of the patients with endometrial carcinoma are presented.


Endocrine studies of normal and polycystic ovarian tissues in vitro.

The purpose of this study was to compare the steroidogenic potential of the granulosa, theca, and medullary tissues from polycystic and normal ovaries. These ovarian endocrine compartments were isolated from appropriate ovaries and were cultured in vitro for three days in the absence (control) and presence of follicle-stimulating hormone (FSH)/luteinizing hormone (LH) (1 lU/ml), N6,O2-dibutyryladenosine-3':5''-cyclic monophosphoric acid (Bu2cAMP) (10(-2)M), and adrenocorticotropic hormone (ACTH) (1.3 U/ml). After the incubation, steroids in the media were measured by radioimmunoassay. Granulosa cells (10(5) cells per dish) from 4 to 7 mm follicles of normal and polycystic ovaries secreted progesterone spontaneously during the culture period and the production of progesterone was markedly stimulated (between tenfold and thirtyfold) by gonadotropins and Bu2cAMP but not by ACTH. Little, if any, androgen (androstenedione, dehydroepiandrosterone, and testosterone) or estrogen (estrone and estradiol) accumulated in the media of any granulosa cell culture. The control cultures of theca tissue from normal and polycystic ovaries secreted large amounts of androstenedione and progesterone and the production of these steroids by normal and polycystic ovary theca was stimulated in most cases by LH/FSH and Bu2cAMP but not by ACTH. Both normal and polycystic ovary theca secreted some testosterone and dehydroepiandrosterone but little, if any, estrone or estradiol accumulated in any theca culture. The medullary tissue of normal and polycystic ovaries produced only trace amounts of steroids in vitro except for the results from one polycystic ovary with hyperthecosis in which case significant quantities of C19 and C18 steroids were secreted. These experiments have demonstrated that isolated granulosa and theca cells from midantral follicles of normal and polycystic ovaries have a similar capacity to secrete C21 and C19 steroids in the absence and presence of trophic agents. Therefore, it seems probable that chronic anovulation in patients with polycystic ovaries is not caused by an obvious deficiency in the de novo steroidogenic potential of the multiple midantral follicles of the polycystic ovaries or by the absence of gonadotropin receptors on the polycystic ovary follicular cells.


Peripheral rheumatoid ulceration and evidence for conjunctival collagenase production.

Two patients with rheumatoid arthritis and peripheral corneal ulcerations were successfully treated by conjunctival resection. The tissues removed were assayed by a variation of the radial diffusion method for tissue collagenases. We used an agarose matrix containing lathyritic rat skin collagen. Wells 3 mm deep were punched in the agarose-collagen and surgical specimens were placed in the wells. Spaces remaining in the wells were filled with balanced salt solution. The assay dishes were incubated for four days at 32 degrees C near 100% humidity. Under these conditions release of collagenase was detected by the clearing of diffuse zones in the gel surrounding the well. Conjunctiva proximal to the ulcer produced definite zones of lysis, whereas control specimens taken remote to the ulceration produced no lysis. This direct evidence for collagenase involvement offers an exploration for the beneficial effects of conjunctival resection.


Application of the likelihood ratio test to age estimation using the infant and child temporal bone.

Several developmental changes in the skull of infants and children are well documented and have been used in the estimation of age at death of infants and children. This paper will present a feature of the infant and child temporal bone, the development of the tympanic plate (floor) of the external auditory meatus, which has recently proven useful in age estimation. Through the use of the Likelihood Ratio Test (Sprott, '73), a six-stage developmental sequence for the tympanic plate has been evaluated. Analysis of tthe tympanic plate developmental sequence has produced the following age categories: fetal, newborn, six months, one to two and one-half years. A general discussion of the basis and potential applications of the Likelihood Ratio Test for analysis of stages and other ordinal data is offered.


Correlated release of acetylcholine and protein from the neuromuscular junction.

Transmitter release at adrenergic synapses is accompanied by release of chromogranin proteins, which are contained in synaptic vesicles. To determine if a similar phenomenon occurs at the neuromuscular junction, correlated release of acetylcholine (ACh) and protein was investigated using in vitro neuromuscular preparations (phrenic nerve-diaphragm muscle of the rat and mouse, sciatic nerve-sartorius muscle of Rana pipiens and R. catesbeiana). Nerve stimulation of curare-paralyzed preparations increased the rate of efflux of Lowry-reactive material relative to control values. Stimulus-specific responses outlasted the period of neural stimulation. Stimulus-induced release of Lowry-reactive material was correlated with ACh release since it was Ca2+ dependent and Mg2+ antagonized. Conditions that potentiate spontaneous ACh release also significantly increased the rate of efflux of Lowry-reactive material. Most of the Lowry-reactive material released with ACh is not a secretory product of synaptic vesicles because the amount released exceeds the contents of synaptic vesicles that undergo exocytosis. It is concluded that ACh release from the neuromuscular junction is accompanied by release of proteinaceous material that is not entirely derived from synaptic vesicles.


Is the function of the renal papilla coupled exclusively to an anaerobic pattern of metabolism?

It is widely accepted that in vivo the function of the papilla of the mammalian kidney is supported primarily by anaerobic metabolism. As a result, the major source of energy for support of function in the papilla is considered to be derived from glycolysis. This orientation originates from two concepts: 1) that in vivo the gaseous environment of the papilla has such a low PO2 that O2 availability limits O2 consumption, and 2) that papillary tissue has a high rate of glycolysis when compared with either cortical tissue or extrarenal tissues. It has also been tacitly assumed that papillary tissue has a "low" O2 uptake. Review of the measurements of PO2 of papillary tissue and of urine PO2 indicates that the PO2 of papillary tissue should not limit its aerobic mitochondrial oxidative metabolism. While the rate of aerobic glycolysis in papillary tissue is high, simultaneously papillary tissue has a rate of O2 uptake similar to that of liver and higher than that of muscle. The major (two-thirds) source of energy for papillary tissue in vitro is from O2 uptake. That papillary tissue is not exclusively dependent on glucose for its energy requirements is indicated by the greater stimulation of papillary tissue QO2 by succinate than by glucose. Thus, papillary tissue has both a high aerobic mitochondrial oxidative metabolism and a high aerobic glycolytic metabolism. It is suggested that the mechanism for the high rate of aerobic glycolysis in the presence of an adequate O2 supply is due to the relatively small mass of mitochondria in papillary tissue in relation to the amount of work done by the tissue. As a result of the limited rate of ATP production by the mitochondrial electron transport chain, the phosphorylation state ([ATP]/[ADP][Pi]) is reduced and the cytoplasmic redox state ([NAD+]/[NADH]) of the papillary collecting duct cells also becomes more reduced; changes in both ratios enhance the rate of glycolysis. This limited metabolic capacity of the collecting duct cells may permit an excess volume of solute and water to be excreted during volume expansion diuresis. The metabolic characteristics of the papilla, when compared to cortex, also provide a basis for the observed differences in substrate selectivity of cortex and medulla with respect to utilization of glucose and lactate. The experimental approaches that may provide information bearing on the suggested mechanisms for regulation of papillary metabolism in relation to tubular work functions are indicated.


Evidence for existence of cortical androgen-stimulating hormone.

An animal model using dexamethosone-suppressed, castrated dogs was developed to test the hypothesis that a pituitary hormone other than ACTH modulates adrenal androgen (AA) secretion. Plasma samples were obtained every 15 min during infusions of saline, synthetic alpha 1-24 corticotropin, porcine 1-39 corticotropin (ACTH), or bovine pituitary gland extract (PE) in a wide range of doses. Androstenedione (A), dehydroepiandrosterone (DHA), and cortisol (F) were quantified by radioimmunoassay. When the ratio of AA levels was related to those of F, in order to correct for ACTH content in the PE, the slopes of the dose-response curves for corticotropin and PE were different at the 0.01 level. For A the dose-response slope for the PE was 0.18 +/- 0.5 SE, whereas that of ACTH was 0.02 +/- 0.01. For the DHA response the slopes were 0.17 +/- 0.04 for the PE and 0.04 +/- 0.03 for ACTH. Related studies showed no increase in AA levels in response to luteinizing hormone-releasing hormone, bovine growth hormone (GH), bovine prolactin, ovine thyroid-stimulating hormone (TSH), or synthetic aqueous arginine vasopressin (AVP). We conclude that a pituitary factor other than ACTH, prolactin, GH, luteinizing hormone, follicle-stimulating hormone, TSH, or AVP may be responsible for the observed increase in AA concentrations.


Insulin inhibition of hormone-stimulated protein kinase systems of rat renal cortex.

Parathyroid hormone (PTH) and glucagon increase the urinary fractional excretion of phosphate, but insulin administration is associated with a decreased fractional excretion of phosphate. It was the purpose of this study to determine whether insulin will antagonize the effects of PTH and glucagon on cAMP levels and protein kinase activation of rat renal cortex. In situ incubation studies were performed on rat renal cortical slices exposed to insulin, PTH, and glucagon. Insulin alone did not affect the tissue cAMP and cGMP levels or the state of protein kinase activation. Preincubation of slices with insulin, however, did significantly inhibit increases in protein kinase activation induced by both PTH and glucagon. Insulin also significantly inhibited PTH-stimulated increases in tissue cAMP levels, but did not blunt the elevations of cAMP levels induced by glucagon. Insulin (10(-9) M) had no effect on either the in vitro activity of adenylate cyclase, basal or PTH-stimulated, or on the activities of low Km cytosolic or membrane-bound cAMP phosphodiesterase. The data show that insulin antagonizes activation of protein kinase by both PTH and glucagon in renal cortex. Separate mechanisms are probably involved for PTH and glucagon interaction. The antiphosphaturic effect of insulin in vivo may result in part from this antagonism at the cellular level.


Inhibition of H+ secretion in frog gastric mucosa by somatostatin.

Somatostatin added to the serosal bathing solution of the isolated gastric mucosa of Rana pipiens significantly inhibited pentagastrin- and histamine-stimulated H+ secretion. The decrease in H+ secretion rate was accompanied by an increase in the transmucosal potential difference and resistance. Somatostatin (10(-5) M) had no effect on the N6,O2-dibutyryl adenosine 3'-5'-cyclic monophosphate (DBcAMP)-stimulated H+ secretion rate. The mucosa exposed to somatostatin secreted H+ on stimulation by DBcAMP or histamine, but did not respond to 2.8 X 10(-7) M pentagastrin. However, pentagastrin added to the serosal solution stimulated H+ secretion after the somatostatin was washed away. Calcium inophore (3 X 10(-5) M) alone or 10(-2) M Ca2+ plus calcium ionophore temporarily increased the H+ secretion rate inhibited by somatostatin. The data suggest that somatostatin has a direct effect on the oxyntic cells in the gastric mucosa.


Uric acid transport in brush border membrane vesicles isolated from rabbit kidney.

The transport of uric acid was studied in brush border membrane vesicles isolated from rabbit kidney. The uptake of uric acid by the vesicles was osmotically sensitive and occurred in the absence of significant uric acid degradation. Under the conditions used to evaluate transport, urate binding to the membranes represented only 10--15% of the total uptake. The initial rate of uptake was linear over the concentration range 0.04--8 mM urate. Uptake of urage was Na+ gradient independent. It was dependent on external pH and temperature with Q10 near 3. The urate uptake was inhibited reversibly by p-chloromercuribenzoate. Probenecid, ouabain, cyclic adenosine 3',5'--monophosphate, and its dibutyryl derivative had no appreciable effects. Pyrazinoic acid and pyrazinamide stimulated urate uptake. Experiments performed with osmotically shocked vesicles demonstrated that this stimulatory effect resulted from increased binding of urate to the membranes. These results indicate that in several ways urate transport in vesicles resembles that observed with more physiologically intact preparations.


Effects of the oral converting enzyme inhibitor SQ 14225 in experimental high output failure.

The relation of the renin-angiotensin-aldosterone system to sodium retention was studied in dogs with an aortic-caval fistula and high output failure by administering orally the new converting enzyme inhibitor SQ 14225. The acute response to an initial oral dose of SQ 14225 (10 mg/kg) consisted in a fall in arterial pressure (BP) from 97 to 67 mmHg, plasma aldosterone concentration (PAC) from 21.7 to 11.3 ng/100 ml, creatinine clearance (CCr) from 89 to 44 ml/min, and filtration fraction (FF) from 39 to 18%, whereas plasma renin activity (PRA) increases from 12.7 to 36.1 ng angiotensin I.ml-1.h-1 and renal sodium excretion was unchanged. It is suggested that the marked fall in BP and CCr offset the drop in PAC and FF which favored a natriuresis. The daily responses to SQ 14225 for 3 days also showed a fall in BP and PAC but sodium excretion increased. In the animal with the best response, a striking natriuresis occurred. These findings demonstrate an important role for the renin-angiotensin-aldosterone system in experimental high output failure.


beta-Endorphin and naloxone in psychiatric patients: clinical and biological effects.

The authors conducted single- and double-blind studies of the responses of 7 chronic male schizophrenic patients to 10 mg of naloxone. BPRS ratings were made before and 6 hours after the injection; ACTH blood levels were determined before and 1 1/2 and 6 hours after injection. Statistically significant improvement of psychotic behavior occurred after 6 hours. The greatest improvement occurred in the patient who showed the most pronounced diurnal variation of ACTH levels, and there was no improvement in the patient who had no diurnal changes. Prolactin plasma levels following endorphin injections were apparently dose-dependent and peaked at approximately 30 minutes. The mean half-life of elimination of exogenous beta-endorphin was between 12 and 35 minutes. The authors theorize that positive and negative behavioral responses to naloxone depend--as possibly do many placebo responses in general--on the relative stress produced by experimental or therapeutic interventions.