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Biomedical subjects

J Levin

Publications and source records attributed to J Levin.

At least 271 records · Page 15Linked to original sources

Sex differences in the twenty-four-hour mean plasma concentrations of dehydroisoandrosterone (DHA) and dehydroisoandrosterone sulfate (DHAS) and the DHA to DHAS ratio in normal adults.

The 24-h mean plasma concentrations of dehydroisoandrosterone (DHA) and dehydroisoandrosterone sulfate (DHAS) and the DHA to DHAS ratio were determined in 37 normal women, aged 21-75 yr, and 32 normal men, aged 21-72 yr. As predicted from our study of sex differences in the metabolism of DHAS, women showed a markely higher DHA to DHAS ratio than men at all ages; the geometric mean for women was 7.5 x 10(-3) and that for men was 3.9 x 10(-3) (P less than 0.0001); and the mean for premenopausal women (6.7 x 10(-3) did not differ significantly from that for postmenopausal women (8.6 x 10(-3)). The two steroids showed a clear-cut linear inverse correlation between concentration and age in both sexes, and menopause was "nonevent" in the age progression for both steroids in the women. The slopes of the concentration vs. age curves were considerably greater in the women, as a reuslt of which the sex differences in concentrations of these steroids changed with age. Under age 50 yr, the plasma DHA concentration of women was considerably higher than that of men [462 +/- 187 (mean +/- SD) vs. 336 +/- 103; P less than 0.025], while the concentrations of DHAS showed no significant sex difference ((77 +/- 38 vs. 101 +/- 67; P greater than 0.1). In persons 50 yr of age or over, plasma DHA concentrations were about the same in women and men (238 +/- 119 vs. 287 +/- 121; P greater than 0.1), but plasma DHAS concentrations were very much lower in women (31 +/- 21 vs. 83 +/- 49; P less than 0.0001).

Adult↗

Subnormal plasma adrenal androgen levels in men with uremia.

The 24-h mean plasma concentrations of 8 hormones were measured in 11 men with chronic uremia and 32 normal men. Our findings confirm previous reports of subnormal levels of testosterone, T3, and T4 and elevated levels of LH, PRL, and cortisol. In addition, we observed a new finding: markedly subnormal levels of the adrenal androgens dehydroisoandrosterone (DHA) and DHA sulfate. The mean DHA level in the patients was 164 +/- 46 (SD) ng/dl, compared with 320 +/- 124 in age-matched controls (P < 0.0001); the geometric mean DHA sulfate level was 40 micrograms/dl (95% confidence limits, 11-113) in the patients and 76 micrograms/dl (95% confidence limits, 26-214) in age-matched controls (P = 0.005). The depression of adrenal androgen levels in the face of elevated cortisol levels suggests a biosynthetic block in the adrenal cortex at the step where the C-19 and C-21 pathways diverge, namely the removal of the 2-carbon side chain by C-17, 20-lyase. If a similar defect were present in the testes, it could account for the diminished synthesis of testosterone, which is a further metabolite of DHA in the testes.

Adult↗

Gastric carcinoma and other malignancies in patients with chronic myelogenous leukemia. Case report and review of the literature, with particular reference to young adults.

generally appears to be increased in patients with this condition. Thirteen of 90 patients who had CML and were seen at The Johns Hopkins Hospital between 1967 and 1977 had a second malignancy; two were less than 35 years old. Pertinent literature on the occurrence of second malignancies in patients with CML is reviewed.

Adolescent↗

Platelet production after administration of antiplatelet serum and 5-fluorouracil.

Although 5-fluorouracil induces relatively minimal thrombocytopenia in mice compared with antiplatelet serum, the ensuing rebound thrombocytosis is much greater. It also occurs several days later. Administration of 5-fluorouracil 24 hr after antiplatelet serum suppresses the increase in platelets produced by antiplatelet serum while the subsequent thrombocytosis is indistinguishable from that produced by 5-fluorouracil alone. It is concluded that the thrombocytosis that occurs after 5-fluorouracil originates from a class of primitive stem cells, or early megakaryocyte precursors, which are not killed by the drug. Thrombocytosis occurring after antiplatelet serum is derived from more mature precursor cells, which are sensitive to 5-fluorouracil.

Animals↗

The effects of acute thrombocytopenia on megakaryocyte-CFC and granulocyte-macrophage-CFC in mice: studies of bone marrow and spleen.

The effects of acute thrombocytopenia, produced by platelet antiserum (PAS), on both megakaryocyte colony-forming cells (Meg-CFC) and granulocyte-macrophage colony-forming cells (GM-CFC) were studied. During the 1-hr to 14-day period following acute thrombocytopenia (platelet counts < 5% of normal), bone marrow and splenic cells of C57BL/6J mice were obtained and cultured for 7 days in 0.3% agar. Numbers of GM and Meg colonies were determined. At no times were alterations in frequency of GM-CFC and Meg-CFC detected in femoral bone marrow. In contrast, GM-CFC in spleen were increased from 3 to 7 days after PAS and from 4 to 7 days after normal serum (NS). Increase in Meg-CFC in the spleen occurred from 3 to 5 days after PAS with a lesser, not significant increase after NS. Alterations in white blood cells and hematocrit values were not detected. Similar responses were observed in germ-free mice and after rechallenge of animals that had received PAS or NS 14 days previously. The delayed increase in Meg-CFC indicates that they are unlikely to be responsible for the altered megakaryopoiesis previously reported in bone marrow after acute thrombocytopenia and was not due to inhibition by PAS. The increase in GM-CFC may reflect stimulation of the reticuloendothelial system by heterologous proteins.

Acute Disease↗

Comparison of 99mTc and 131I scans in thyroid function studies.

Thyroid function was studied in 170 patients, using technetium-99m (99Tc) and oral radio-iodine (131I); 110 patients had normal thyroid function, and 60 had hyperthyroidism. The 20-minute 99mTc uptake gave an accurate assessment of thyroid function in 95% of patients, and the 24-hour 131I uptake was accurate in 92%. One hundred 99mTc and 131I scintiscans were compared by 3 observers. Scans obtained with each isotope were of comparable quality, and in only 1 patient were both scans of poor quality. 99mTc is as good as 131I for assessing thyroid function and morphology, but has several advantages over 131I.

Evaluation Studies as Topic↗

Radiocolloid imaging in primary liver cancer and amoebic liver abscess. Accuracy of differential diagnosis and extent of inter-observer variability.

Radiocolloid liver scans from 58 patients with primary liver cancer and 56 patients with amoebic liver abscess were examined 'blind' and independently by three nuclear physicians and one registrar in training in order to evaluate the accuracy of the differential diagnosis between the two conditions and to assess the extent of inter-observer variability in the interpretation of these scans. Each of the observers incorrectly interpreted about 12% of scintiphotographs and at least one observer was wrong in 25% of the scans. The difference in diagnostic accuracy between individual observers was not statistically significant. Observers disagreed in 21,6% of the scans. The main reasons for misdiagnosis were failure to realize that excessive extrahepatic uptake of radiocolloid can occur with liver abscesses, and the indistinguishable appearance of the defect or defects in some cases of primary liver cancer and amoebic liver abscess. This margin of error and of inter-observer variability must be borne in mind when interpreting liver scans of patients thought to have either primary liver cancer of amoebic liver abscess.

Colloids↗

Humoral control of thrombopoiesis.

There is increasing evidence that an important mechanism by which platelet production is regulated depends upon a humoral substance (thrombopoietin) that affects the production of platelets by megakaryocytes. Plasma from thrombocytopenic donors increases the rate of appearance or concentrations of subsequently administered Na235SO4 or selenomethionine-75Se in platelets. Both isotopes are initially incorporated into the cytoplasm of megakaryocytes, and labeled platelets appear in the circulation after their production and release from megakaryocytes. Thrombopoiesis-stimulating activity also can be detected in the plasma of normal donors when endogenous thrombopoiesis has been suppressed in recipient assay animals by the hypertransfusion of platelets. Recent studies have indicated that certain fractions of plasma from throbocytopenic donors are also capable of stimulating thrombopoiesis in recipient animals. The nature of thrombopoietin(s) and its mechanism of action remain unknown. However, currently available data indicate that thrombopoiesis-stimulating factors may act both on diploid precursors and immature megakaryocytes and upon maturing megakaryocytes. The site of production of thrombopoietin also is unknown. Although the sensor that regulates thrombopoietin or other humoral mediators of thrombopoiesis has not been identified, it appears that platelet numbers, per se, are not the sole variable to which megakaryocytopoiesis eventually responds.

Ammonium Sulfate↗

Temporal gradients in the retrograde amnesia of patients with alcoholic Korsakoff's disease.

Eleven alcoholic patients with Korsakoff's disease and 15 control subjects were given three tests of retrograde amnesia. The first consisted of photographs of famous faces from the past, the second was a recall test of famous people and events, and the third was a multiple-choice questionnaire. To determine whether previously reported temporal gradients (ie, preservation of remote events) were related to item difficulty, half of the questions dealt with events of transient fame while half concerned subjects that continued to receive public attention for many years. The findings indicate that alcoholic patients with Korsakoff's disease have a marked retrograde amnesia that is characterized by a steep temporal gradient, and that this gradient is not an artifact due to the difficulty of the questions or the method of testing.

Alcohol Amnestic Disorder↗

Stem cell migration induced by erythropoietin or haemolytic anaemia: the effects of actinomycin and endotoxin contamination of erythropoietin preparations.

The injection of erythropoietin or the induction of anaemia with phenylhydrazine leads to changes in murine pluripotent and granulocyte-macrophage stem cells indicating migration from marrow to spleen. In order to evaluate the interrelationship between erythroid differentiation and stem cell migration we have selectively suppressed erythroid differentiation with actinomycin D. Anaemia or EP injection resulted in stem cell changes consistent with migration; actinomycin blocked these changes in anaemic but not EP injected mice while blocking erythropoiesis in both groups. The erythropoietin contained from 0.01 to 1000 microgram/ml of endotoxin as defined by the limulus test; it decreased marrow erythropoiesis and stimulated marrow granulopoiesis. Adsorption of the erythropoietin preparation with limulus lysate removed endotoxin without decreasing erythropoietin activity. Adsorbed erythropoietin stimulated erythropoiesis and not granulopoiesis, and stem cell changes induced by its administration were largely blocked by actinomycin, suggesting that endotoxin in the non-adsorbed erythropoietin caused the actinomycin resistant stem cell changes. The observation that actinomycin blocks both erythroid differentiation and stem cell migration suggests that these two physiologic events are closely linked. The effects of injected erythropoietin on murine haemopoietic stem cells may, to a significant extent, be secondary to the presence of endotoxin in the erythropoietin preparations.

Anemia, Hemolytic↗

The relationship between marrow iron stores, plasma ferritin concentrations and iron absorption.

The percentage absorption from a 3 mg dose of ferrous iron was measured in 50 subjects with iron stores that varied over a wide range. Iron status was assessed by a number of measurements, including the haemoglobin concentration, the plasma iron concentration, the total iron-binding capacity, the plasma ferritin concentration and the concentration of non-haem iron in the bone marrow. There were good inverse correlations between the log percentage iron absorption and both the log marrow non-haem iron concentration (r -0.94; P less than 0.001) and the log plasma ferritin concentration (r -0.78; P less than 0.001). In addition, there was a positive ferritin concentration (r +0.84; P less than 0.001). These results suggest that reticuloendothelial iron stores represent an important determinant of iron absorption and that their size can be guaged from the plasma ferritin concentration.

Anemia↗

Characteristics of lipid A-protein complex from endotoxin of Shigella dysenteriae type 1 (S and R strains).

Mild acetic acid hydrolysis of endotoxin (lipopolysaccharide-protein complex) of Shigella dysenteriae type 1 (S and R forms) yielded a lipid A-protein complex that consisted of amino acids, fatty acids, and sugar and, in terms of chemical composition, displayed no marked differences between the S and R forms. Its protein portion (53 to 56%) consisted of at least 16 amino acids. In the fatty acid portion (14 to 18%), myristic, 3-hydroxymyristic, palmitic, and stearic acids accounted for 50%. The sugar portion (10 to 12%) consisted solely of glucosamine. The remainder was unidentified substances, most of which contained phosphorus. Lipid A-protein complexes derived from both S and R forms were not toxic for mice in doses up to 1,000 microgram/mouse, but their Linulus test activity had increased considerably as compared with the starting lipopolysaccharide-protein complex material: from 10(-6) to 10(-10--10(-12) mg/ml. The lipid A-protein complexes were readily soluble in a water solution of triethylamine, in dimethyl sulfoxide, and in pyridine.

Amino Acids↗

Effect of flutamide on estradiol metabolism.

The effect of flutamide, a potent nonsteroidal antiandrogen, on the metabolism of iv tracers of [3H]estradiol was studied in five patients with advanced prostate cancer. The drug produced no change in the percentage of the injected radioactivity recovered in urine or in the glucuronide or nonglucuronide conjugate fractions. Of the five individual metabolites that were quantitated, estrone, estradiol, and estriol were unaffected by flutamide, but the drug caused striking decreases in conversion of estradiol to 2-hydroxyestrone (4.0% vs. 7.4%) (P less than 0.005) and 2-methoxyestrone (1.1% vs. 2.6%; P less than 0.05); every one of the patients showed a marked fall in recovery of both of these compounds. This depression of the formation of 2-oxygenated metabolites is reminiscent of the findings in liver disease; the same abnormality occurs regularly in cirrhosis and frequently in extrahepatic biliary obstruction. Taken together with our previous studies of the effects of flutamide on testosterone and cortisol metabolism, this study demonstrates that flutamide produces multiple functional, reversible, cirrhosis-like disturbances of steroid metabolism. Because these disturbances are universal in the patients studied regardless of whether they had clinical responses to flutamide, we doubt that the steroid metabolic changes play a role in the therapeutic effect of the drug.

Anilides↗

Plasma cortisol profiles in Cushing's syndrome.

Plasma cortisol profiles were studied by the frequent sampling method in 5 patients with Cushing's disease (CD), 7 patients with Cushing's syndrome due to adrenocortical adenoma (AA), and one patient with bronchogenic carcinoma. Plasma ACTH was measured by radioimmunoassay at 10 min intervals in 2 of the subjects. In CD, there was distinct episodic secretion of cortisol and ACTH; the coefficients of variation about the mean plasma cortisol concentration ranged from 24 to 27%; plasma ACTH ranged from zero to 455 pg/ml with a mean of 94 pg/ml. In AA, the tumour secreted cortisol at a constant rate with little fluctuation; the coefficients of variation of plasma cortisol concentration ranged from 8 to 14%; plasma concentrations of ACTH were always near zero. In the patient with bronchogenic carcinoma, the coefficient of variation of cortisol was 14%. These results were apparent even in profiles of plasma cortisol concentrations measured over only a 6 h period. It is concluded that characteristics of plasma cortisol and ACTH secretory patterns are helpful in differentiating Cushing's syndrome of differing aetiology.

Adenoma↗