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Biomedical subjects

J Levin

Publications and source records attributed to J Levin.

At least 307 records · Page 17Linked to original sources
PubMed1978

Extraadrenal effects of metyrapone in man.

[14C]Cortisol was injected iv into three subjects during a control period and while receiving metyrapone. The plasma kinetics of the tracer cortisol and the patterns of its urinary metabolites were measured. Metyrapone caused an increase in the volume of distribution of cortisol (34%) and in the MCR (75%); the half-life was decreased by 25%. There were marked changes in the urinary metabolite pattern: 3 alpha,11 beta,17,21-tetrahydroxy-5 alpha-pregnan-20-one, 3 alpha,17,21-trihydroxy-pregnane-11,20-dione(THE), pregnane-3 alpha,11 beta,17,20 alpha,21-pentol, plus pregnane-3 alpha,11 beta,17,20 beta-21-pentol (cortol), and 3 alpha,17,20 alpha,21-tetrahydroxypregnan-11-one (cortolone) all decreased by an average of 62%, 44%, 38%, 45%, and 25% respectively. In contrast, there was an increase of 296% in 3 alpha,17,20 beta,21-tetrahydroxypregnan-11-one (beta-cortolone). To account for these effects it is postulated that metyrapone has the following extraadrenal actions: 1) it inhibits the back reduction of cortisone to cortisol and 2) it stimulates the 20-ketosteroid reductase that converts THE to beta-cortolone.

Adult↗
PubMed1978

Investigation of hormone-receptor interactions by means of fluorescence labeling.

Fluorescent-labeled hormones can be used to study hormone-receptor interactions by means of fluorescence polarization, visualization by fluorescence microscopy, or separation methods, e.g., dextran-coated charcoal. Subcellular fragments, single cells, and tissue preparations are amenable to study; in this work rat uterine cytosol was used unless otherwise noted. Estrone labeled with fluorescein at position 17 gives 50% inhibition in the radiometric dextran-coated charcoal assay at 8.3 X 10(-7) M as compared to 3.4 and 3.5 X 10(-8) M for diethylstilbestrol and estradiol, respectively. Scatchard plots from fluorescence polarization are hyperbolic and consistent with two classes of binding sites having association constants 5.6 X 10(10) and 6.4 X 10(7) M-1. Binding by high-affinity sites, which were present at about 3 times the concentraion of "specific" sites (radiometric dextran-coated charcoal assay), was abrogated by estradiol or diethylstilbestrol. Kinetic measurements showed that binding sites that can be blocked by excess estradiol or diethylstilbestrol are those that are both slowly associating and slowly dissociating. Staining of tissues by estrone labeled with fluorescein at position 17 as seen in the fluorescence microscope showed specificity. In normal rat uterus only epithelial cells were stained. In one human infiltrating ductal carcinoma only the malignant ductoid elements stained, while in another there was essentially no staining.

Animals↗
PubMed1978

Preparation of [24,25-3H] cholesterol. Oxidation in man as a measure of bile acid formation.

In order to devise a convenient method for measuring the rate of formation of bile acids from cholesterol in man, [24,25-3H] cholesterol was prepared by catalytic tritiation of desmosterol where the delta5-unsaturation was protected by conversion to the 3 alpha, 5 alpha-cyclosterol-6-methyl ether. It was shown that tritium in the purified labeled sterol was located exclusively in the side chain. Measurements of 3H2O and the specific activity of plasma cholesterol at timed intervals up to 96 hours after administration of the tracer to three subjects afforded values for cholesterol oxidation (equals bile acid formation) in good agreement with accepted figures for bile acid formation determined by other techniques.

Adult↗
PubMed1977

Endocrine studies on the San ('bushmen') of Botswana.

Gonadal and gonadotrophic hormones were assayed in members of !Kung population who live in north-western Ngamiland, Botswana, and who are true San ('Bushmen') hunter-gatherers. An attempt was made to correlate their hormonal secretion and morphology. Peripheral serum levels of gonadotrophins and gonadal steroids were measured by means of radio-immune methods. Female San appear to have suppressed circulating levels of gonadal steroids, while gonadotrophins were in the normal range. No evidence for elevated circulating levels of oestrogen could be found. Male San showed hormone levels similar to Caucasoid and Negro ('Bantu') values.

Adult↗
PubMed1977

Activation of protein mediators of inflammation and evidence for endotoxemia in Borrelia recurrentis infection.

Fifteen patients with Borrelia recurrentis infection were studied to evaluate the role of certain plasma proteins and endotoxin in the pathophysiology of both the acute illness and the Jarisch-Herxheimer-like reaction. The causative spirochetes disappeared from the blood during the Jarisch-Herxheimer-like reaction, which occurred about 2 hours after antibiotic therapy. The mean titers of Hageman factor, plasma prekallikrein and serum hemolytic complement activity were decreased at the time of admission and 2 hours after treatment, and rose to normal values during convalescence. Serum properdin titers were decreased in 14 patients at the time of admission, in 12 patients 2 hours after treatment, and in none during convalescence. The frequency of elevated levels of fibrinogen-related antigens increased from three patients at the time of admission to 12 patients 2 hours after treatment. Results of plasma limulus tests for endotoxin-like material were positive in 11 patients at the time of admission and in 13 patients 2 hours after treatment. These findings demonstrated that Hageman factor, prekallikrein and proteins of the complement system are activated in B. recurrentis infection and that endotoxin may play a role in both the acute illness and in the development of the Jarisch-Herxheimer-like reaction after treatment.

Adolescent↗
PubMed1977

Factor IX levels in patients with hemophilia B (Christmas disease) following transfusion with concentrates of factor IX or fresh frozen plasma (FFP).

There has been no systematic re-examination of variables that may affect the level and duration of response of patients with hemophilia B (Christmas disease) to transfusion. Therefore, 49 of our transfusion episodes and 171 previously reported transfusions were evaluated. Mean calculated initial increase of Factor IX levels (delta %/unit (U) of procoagulant activity infused/kg) was 0.82 +/- 0.09% (mean +/-S.E.) in previously reported cases and 1.01 +/- 0.13% in our patients, after transfusion of concentrate; but only 0.05 +/- 0.11% after fresh frozen plasma (FFP). Response was not altered by acute hemorrhage, baseline Factor IX levels, or body weight. Proplex (Hyland) and Konyne (Cutter) produced similar responses. Following transfusion, the disappearance curve was biphasic. The mean T1/2 for the second component was 27.5 hrs, but the direct T1/2 was only 6.4 +/- 1.0 hr. Regardless of common clinical variables, increase of Factor IX following transfusion of American concentrates is 1.0% (or 0.01 U)/1 administered/kg. Appropriate frequency of transfusion depends upon an understanding of the biphasic disappearance of Factor IX. Importantly, the initial frequency of transfusion therapy should be based on a direct T1/2 of only 6 to 8 hrs.

Blood Transfusion↗
PubMed1977

Haemophilia, hepatitis and porphyria.

A patient with haemophilia A developed hepatitis B, seemingly as a consequence of treatment with blood products. Six years later, bullae, photosensitivity, and the biochemical findings of porphyria cutanea tarda developed.

Hemophilia A↗
PubMed1977

The effect of 7beta, 17alpha-dimethyltestosterone (calusteron) on testosterone metabolism in women with advanced breast cancer.

Calusterone (7beta, 17alpha-dimethyltestosterone) is a 17-alkylated, orally active androgenic steroid used in the treatment of breast cancer. The effect of this steroid on the metabolism of 14C-testosterone and the excretion of endogenous urinary androgen metabolites has been studied in four patients with breast cancer. Total glucuronide metabolites of the tracer decreased significantly, the andorsterone/etiocholanolone ratio rose by a factor of 2-4, and there was increased formation of uncharacterized polar metabolites. There was no significant change in either the sum of the excretion of endogenous androgen metabolites or the androsterone/etiocholanolone ratio. The changes resemble those we have seen in cirrhosis of the liver. It is concluded that the effects of Calusterone on testosterone metabolism, like its effects on cortisol or estradiol metabolism, represent nonspecific effects of an orally administered 17-alkylated steroid on hepatic structure and function, and probably bear no relationship to its therapeutic effect in breast cancer.

Androsterone↗
PubMed1977

The effect of flutamide on testosterone metabolism and the plasma levels of androgens and gonadotropins.

Flutamide, a nonsteroidal antiandrogen, was given to 11 men with prostate cancer, in doses of 750 to 1500 mg daily for 0.5--7 months. Four patients had a clinical remission and seven showed no response. All the patients showed a profound change in the peripheral metabolism of testosterone: markedly increased conversion to androsterone (A) and correspondingly decreased conversion to etiocholanolone (E); the A/E ratio rose to levels never before observed consistently in any group of healthy or diseased humans. This change was probably due to alteration by flutamide of the relative activities of steroid 5alpha and 5beta reductase in favor of the former. 24-Hour mean plasma testosterone was increased in five of the six patients studied for this parameter, for the group as a whole, testosterone rose from 279 ng/dl to 484 ng/dl (P less than .05). 24-Hour mean values for plasma dihydrotestosterone, dehydroisoandrosterone, LH and FSH showed no significant change, for the group as a whole, in the same six patients. Since flutamide did not change the metabolic clearance rate or volume of distribution of testosterone tracers, the increased plasma levels of the hormone were probably due to increased production.

Aged↗
PubMed1977

Biological activities of tritiated endotoxins: correlation of the Limulus lysate assay with rabbit pyrogen and complement-activation assays for endotoxin.

Tritiated endotoxins were prepared by three different methods. The biological activities of the tritiated endotoxins were determined by the Limulus amebocyte lysate assay, a rabbit pyrogen assay, and a complement-activation assay and were compared to native, unlabeled endotoxin. All three tritiated endotoxin preparations manifested adequate biological activity in each of the three assay systems, and all three assays ranked the biological activity of the different endotoxin preparations in the same order. Endotoxin tritiated by the Wilzbach procedure retained most of its biological activity and also had the highest specific radioactivity. The good correlation between the Limulus lysate, rabbit pyrogen, and complement-activation assays suggests that the same active site of the endotoxin molecule is identified by the three different assays.

Animals↗
PubMed1977

Tissue factor generation by human mononuclear cells: effects of endotoxin and dissociation of tissue factor generation from mitogenic response.

The effects of the presence of endotoxin in a mononuclear cell culture system have been assessed. Endotoxin was shown to be mitogenic for human peripheral blood lymphocytes and capable of stimulating the generation of tissue factor. Concentrations of endotoxin, found to contaminate many commercial mitogens and antigens, activated mononuclear cells in a time-dependent manner. Generation of tissue factor was detected in cultures harvested from 2 to 72 hours following stimulation with endotoxin. Dose-response curves relating concentrations of endotoxin to mononuclear cell stimulation were determined; as little as 0.001 microng/ml. of E. coli endotoxin was capable of stimulating the generation of tissue factor in the cell cultures. The mitogenic effect of endotoxin was modest, however, and appeared to be unrelated to the ability of endotoxin to active tissue factor. Inhibition of DNA synthesis in the cell cultures by cytosine arabinoside or nonlethal irradiation failed to impair the generation of tissue factor. Endotoxin contamination of various reagents used in cell culture was evaluated with the Limulus assay, which detected as little as 1 X 10(-4) microng/ml. of endotoxin. Endotoxin was detected in preparations of phytohemagglutinin, purified protein derivative of the tubercle bacillus, mumps vaccine, tetanus toxoid, concanavalin A, and pokeweed mitogen. Because of the broad implications of contamination by endotoxin of various reagents, we assessed the specificity of the Limulus assay for the detection of endotoxin in the lectin, concanavalin A, and determined that the reaction was specific for endotoxin. Contamination by endotoxin of mononuclear cell culture systems should be considered as a possible factor in the production of various biological effects attributed to some commonly used mitogens and antigens.

Cytarabine↗
PubMed1977

Trousseau's syndrome and other manifestations of chronic disseminated coagulopathy in patients with neoplasms: clinical, pathophysiologic, and therapeutic features.

Analysis of 182 patients with chronic disseminated intravascular coagulopathy and malignancy shows common features. Migratory thrombophlebitis occurred in 96 patients while at least a single episode of thrombophlebitis was noted in 113. Seventy-five of the patients bled and 45 had arterial emboli in various organs. Twelve patients had the triad of thrombophlebitis, hemorrhage, and arterial emboli, often sequentially. Hematologic data showed derangements associated with intravascular coagulation, the most prominent of which were hypofibrinogenemia and thrombocytopenia. Other abnormalities included prolonged prothrombin time, increased fibrinogen-fibrin degradation products, decreased levels of factors V and VIII, cryofibrinogenemia, and microangiopathic hemolytic anemia. Forty-one patients had lesions of non-bacterial thrombotic endocarditis at autopsy; 31 of these had arterial emboli during life. None of the lesions were infected. Mitral and aortic valves were most frequently involved. No single mechanism that causes the disseminated intravascular coagulopathy has been identified. However, cell products--secretions and enzymes--and the cells themselves have been proposed as the procoagulant(s) responsible for the syndrome. In addition to treatment of the underlying neoplasm, symptomatic disseminated intravascular coagulopathy should be controlled. Heparin is the drug of choice for treatment of this problem, very little benefit having been observed with warfarin therapy. Long-term use of anticoagulants is potentially feasible for control of chronic disseminated intravascular coagulopathy, but without effective control of the underlying tumor ultimately will be unsuccessful.

Adult↗
PubMed1976

57-cobalt-bleomycin as a tumor scanning agent in primary hepatocellular cancer.

57Co-bleomycin and 99mTc-sulfur colloid scans were performed in 13 southern African black patients with primary hepatocellular cancer (PHC) and 3 patients with other space-occupying hepatic lesions. Selective concentration of 57Co-bleomycin in the defect or defects seen on the 99mTc-sulfur colloid scan occurred in only 4 of the 13 (31%) patients with PHC. In the remaining PHC patients, as well as in the 2 patients with metastatic liver disease and the 1 patient with an amebic liver abscess, the 57 Co-bleomycin and 99mTc-sulfur colloid scans were identical. 57Co-bleomycin appears to have only a limited place as a tumor-seeking agent in the diagnosis of PHC in southern African blacks.

Bleomycin↗
PubMed1976

Alteration of colony-stimulating factor output, endotoxemia, and granulopoiesis in cyclic neutropenia.

Cellular and humoral factors involved in the regulation of granulopoiesis were evaluated in two patients with cyclic neutropenia by utilizing the agar-gel marrow culture technique to serially study marrow granulocytic colony-forming capacity (CFC) and the urinary output of colony-stimulating factor (CSF). CSF output varied inversely with peripheral neutrophil counts and directly with monocyte counts and evidence for infection (endotoxemia and/or staphylococcal abscesses). Following autologous infusion of one patient's plasma obtained during a period of neutropenia, increased urinary excretion of CSF occurred concomitant with increments in both marrow CFC and the proportion of granulocytic progenitor cells in DNA synthesis. Neutrophil periodicity was not altered by the administration of the neutropenic plasma. These findings are consistent with the hypothesis that cyclic neutropenia is caused by a quantitatively decreased entry of stem cells or granulocytic progenitor cells into granulopoiesis.

Abscess↗
PubMed1976

Hemorrhagic diathesis in a carrier of hemophilia B.

A carrier of hemophilia B was found to have an unusually low factor IX level of 13 per cent. Her history of previous bleeding and the hospital course following elective dental extractions were consistent with a mild hemorrhagic diathesis. The patient is a member of a rare kindred of hemophiliacs. The mean level of factor IX in 12 carriers in this kindred was 42 per cent, with a range of 13 to 100 per cent. This patient represents the sixth reported case in which a female carrier of factor IX deficiency was symptomatic.

Adult↗
PubMed1976

Yersinia pestis infection in Vietnam. II. Quantiative blood cultures and detection of endotoxin in the cerebrospinal fluid of patients with meningitis.

Quantitative blood cultures were obtained from 42 patients with acute Yersinia pestis infection to determine whether the concentration of bacteria in blood influenced the clinical severity and outcome of illness. In 17 bacteremic patients, colony counts in blood cultures ranged from less than 10 to 4 X 10(7)/ml. Three of five patients with colony counts of greater than 10(2)/ml died, and two patients survived episodes of hypotension. Results from plasma limulus tests were positive at the time of admission in three of 10 patients tested, and these three patients had bacteremia with colony counts of greater than 10(2)/ml. Meningitis developed in three patients and pneumonia in two patients; these five patients a-l had buboes in the axillary region. Endotoxin was detected with the limulus test in the cerebrospinal fluid in the three patients with meningitis. Ten patients randomly assigned to receive streptomycin or trimethoprim-sulfamethoxazole survived. Those treated with streptomycin had a shorter median duration of fever and a lower incidence of complications than did the patients treated with trimethoprim-sulfamethoxazole.

Adolescent↗
PubMed1976

The effect of medroxyprogesterone acetate on the pituitary-adrenal axis.

Twelve cancer patients and one patient with diabetes mellitus were treated with medroxyprogesterone acetate (MPA) by intramuscular injection in a total weekly dose of 400, 700, or 1200 mg. The treatment reduced the plasma cortisol concentration by 76% in the AM hours (21 leads to 5.0 mug/dl) and by 75% in the PM hours (12.8 leads to 3.2 mug/dl). Cortisol production rate decreased by 67% (19 leads to 6.2 mg/24 hrs). The 24 hour profile of plasma cortisol concentration measured in 3 patients showed zero secretion over this period. Low plasma ACTH values prevailed during treatment, and a blunted response to maximal ACTH stimulation was found. No evidence of adrenal insufficiency was observed in any patient, even though in some patients the plasma cortisol concentration remained at zero for many weeks. MPA has cortisol-like effects and the suppression of adrenal function is probably mediated by a negative feedback action on the hypothalamus or pituitary.

Adrenocorticotropic Hormone↗