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Biomedical subjects

J Levin

Publications and source records attributed to J Levin.

At least 217 records · Page 12Linked to original sources
PubMed1983

Interactions of lipid a and liposome-associated lipid A with Limulus polyphemus amoebocytes.

Lipid A or lipid A fractions and liposomes containing lipid A were tested for the ability to gel Limulus amoebocyte lysates and for effects on intact Limulus amoebocytes. Liposomes having a relatively low concentration of lipid A did not produce coagulation of lysate and were designated as Limulus-negative, but liposomes having a high concentration of lipid A were Limulus-positive. Limulus-negative liposomes had no effect on intact amoebocytes. Limulus-positive liposomes caused a striking transformation in the appearance of amoebocytes in that the cells sent out long filamentous extensions that formed a tangled network of processes between cells. The filamentous projections were similar to those that have been previously observed in the presence of gram-negative bacteria. We conclude that amoebocytes have the ability to recognize Limulus-positive liposomes, but the lack of activation of Limulus lysate or the absence of amoebocyte recognition does not prove the absence of liposomal lipid A. We also found that individual lipid A fractions were heterogeneous in their ability to gel lysate. Of eight fractions tested, one (fraction 1) had no detectable activity above the background, and the seven others had activity that ranged from 10-fold to 10,000-fold above the background. The heterogeneity of lipid A fractions detected in assays with amoebocyte lysate was consistent with the finding of heterogeneity in other functional assays of lipid A fractions.

Animals↗
PubMed1983

Effects of obesity on estradiol metabolism: decreased formation of nonuterotropic metabolites.

Obesity is associated with an increased incidence of reproductive dysfunction and estrogen-linked diseases. In the present study, we have examined the principal oxidative biotransformations of estradiol in 13 obese premenopausal females and 10 obese males compared to those in 9 premenopausal female and 15 male controls. These studies were carried out using a recently devised, sensitive radiometric method which permits the assessment of the total in vivo oxidative metabolism of estradiol at specific sites (i.e. 17 alpha, 16 alpha, or C-2) on the steroid molecule. Our results indicate that obesity (greater than 60% above ideal body weight) is associated with significant decreases in hydroxylation at C-2 in both sexes (P less than 0.001 for females and P less than 0.02 for males) and in oxidation at 17 alpha in premenopausal females (P less than 0.05) compared to that in age-matched, normal weight controls. Analysis of the plasma 3H2O specific activity curves suggested a slight decrease in the rate of 17-oxidation in obese subjects. The extent of hydroxylation at 16 alpha was not significantly affected by obesity. These metabolic alterations documented in obesity could result in a relative hyperestrogenic state, since, unlike the other estrogen metabolites, the 2-hydroxyestrogen compounds display relatively little peripheral estrogenic activity. This metabolic alteration on a prolonged basis might be contributory to the prevalence of certain hormonally related diseases in obese individuals.

Adult↗
PubMed1983

Lack of endotoxin in Borrelia hispanica and Treponema pallidum.

Borrelia hispanica from infected guinea pigs and Treponema pallidum from testicular syphilomas of rabbits were assayed for the presence of endotoxin with the Limulus lysate test. A suspension of Borrelia, containing 1.3 X 10(8) spirochetes/ml, was nonreactive both when it was tested as intact organisms, and when tested after disruption of the spirochetes by sonication. Eight different suspensions of treponemes, ranging from 0.6 X 10(9) to 3 X 10(9) treponemes/ml, were negative at a 1:10 dilution and were no more active than control suspensions of normal rabbit testes. Therefore, it was concluded that T. pallidum, as well as the Borrelia, possessed no endotoxin.

Animals↗
PubMed1983

Uptake of Tc-99m di-isopropyliminodiacetic acid by hepatocellular carcinoma: concise communication.

Uptake of Tc-99m di-isopropyliminodiacetic acid (DISIDA) by hepatocellular carcinoma was assessed in 30 patients showing obvious liver defects on a Tc-99m tin colloid image. In none of these patients was there complete "filling in" of the defects, and even partial "filling in" occurred in only 11 (36.7%). There was no uptake of Tc-99m DISIDA by the primary tumor in the remaining 19 patients (63.3%). In 19 of the 30 patients an attempt was made to correlate the degree of histologic differentiation of the tumor with the uptake of DISIDA by the tumor. No difference in uptake could be demonstrated between well, moderately, and poorly differentiated tumors. Tc-99m DISIDA was not taken up by pulmonary metastases in the only two patients tested. We conclude that imaging with Tc-99m DISIDA in conjunction with Tc-99m colloid is of no value in the specific diagnosis of hepatocellular carcinoma.

Adult↗
PubMed1983

Subnormal 24-hour mean plasma LH concentration and elevated plasma FSH/LH ratio in obese premenopausal women. A possible human counterpart of the slow-GnRH-pulsing model in primates.

The 24-hour mean plasma concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured during the follicular phase of the menstrual cycle in 15 healthy, regularly cycling obese women (59-218% above desirable weight) and 9 healthy, regularly cycling nonobese women (14% below to 14% above desirable weight). The obese women showed slightly but not significantly higher FSH values (12.5 vs. 9.6 mIU/ml), definitely and significantly lower LH values (11 vs. 17 mIU/ml; p less than 0.005) and markedly and very significantly higher FSH/LH ratios (1.2 vs. 0.62; p less than 0.0005). These abnormalities may represent a human counterpart of the slow-GnRH-pulsing model of primates: monkeys in which the GnRH secretory centers have been ablated and that receive GnRH infusions at subnormal pulsing rates show slightly elevated FSH levels, markedly decreased LH levels, greatly elevated FSH/LH ratios and anovulation.

Adult↗
PubMed1983

The effects of 5-fluorouracil on hematopoiesis: studies of murine megakaryocyte-CFC, granulocyte-macrophage-CFC, and peripheral blood cell levels.

the effect of 5-fluorouracil (5-FU) on megakaryocytopoiesis in mice was studied with assays of megakaryocyte colony-forming cells (Meg-CFC) in bone marrow and spleen and simultaneous determinations of peripheral blood counts, after a single intraperitoneal dose (150 mg/kg) of 5-FU. Although only moderate thrombocytopenia (platelet count 40% of control values) occurred at 7 days following administration of 5-FU, sustained rebound thrombocytosis (platelets 200-250% of control values) was observed from days 11 to 17. No rebound leukocytosis was detected despite comparable initial leukopenia. Megakaryocyte colony-forming cells (Meg-CFC) in bone marrow and spleen were decreased for 2 and 5 days, respectively, after administration of 5-FU. Subsequently, there was a prolonged rebound increase in the total number of Meg-CFC in the spleen from days 11 to 17 after 5-FU, a phenomenon which did not occur with Meg-CFC derived from the bone marrow. Granulocyte-macrophage colony-forming cells (GM-CFC) in bone marrow and spleen exhibited alterations which were similar to those of Meg-CFC, indicating similar sensitivities of GM-CFC and Meg-CFC to 5-FU. Normal feedback mechanisms which control platelet levels are perturbed for almost 3 wk after administration of 5-FU. The simultaneous occurrence of maximal thrombocytosis and increased splenic Meg-CFC suggests that increased platelet production after 5-FU is associated with concomitant stimulation of the megakaryocyte progenitor compartment in the mouse spleen. However, the concurrence of thrombocytosis and increased splenic Meg-CFC indicates that elevated levels of Meg-CFC did not initiate the period of thrombocytosis.

Animals↗
PubMed1983

The inverse relation between platelet volume and platelet number. Abnormalities in hematologic disease and evidence that platelet size does not correlate with platelet age.

We determined the platelet count and MPV in 100 normal subjects, in 147 subjects with thrombocytopenia or thrombocytosis due to other than primary hematologic disorders, and in smaller groups with immune or septic thrombocytopenia or iron deficiency. In these groups, the inverse, nonlinear relation between MPV and platelet count was the same as in a previous study of normal subjects. The same relation between platelet volume and count was found in individual patients as platelet counts rose during recovery from immune or septic thrombocytopenia. The concomitant progressive fall in MPV during recovery from thrombocytopenia, at which times rapidly rising platelets counts were necessarily associated with a population of young platelets, suggests that magnitude of stimulation of thrombopoiesis, not platelet age, is the major determinant of platelet volume. In contrast, as compared to normal persons with similar platelet counts, MPV was increased in subjects with heterozygous thalassemia but decreased in patients receiving chemotherapy for malignancy or renal transplantation. The undefined mechanism of regulation of platelet formation from megakaryocytes, reflected by the inverse relation of platelet size and count, thus seems altered in these disorders. Platelet volume is an easily obtained variable that appears to be useful in the evaluation of abnormal platelet production.

Anemia, Hypochromic↗
PubMed1982

Treatment of metastatic breast cancer in estrogen receptor positive patients. A randomized trial comparing tamoxifen alone versus tamoxifen plus CMF.

In a controlled clinical trial, 52 patients with ER positive metastatic breast cancer were randomly assigned to receive initial treatment with either tamoxifen alone followed by sequential cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) after tumour progression of concurrent tamoxifen plus CMF, All 52 patients entered are eligible and 50 patients were currently assessable. Response rates (CR + PR) were similar for the two treatment groups (15/24 tamoxifen alone, 17/26 tamoxifen + CMF). The median durations of survival for the two treatment groups 17.7 months and 17.1 months were also not significantly different. Significant correlations were found between level of ER and response rate and also between level of ER and response duration. From the result of this investigation it would appear that there is no advantage to the addition of chemotherapy prior to an adequate trial of hormone therapy in patients with metastatic ER positive breast cancer.

Adult↗
PubMed1982

Fractionation of Limulus amebocyte lysate. Characterization of activation of the proclotting enzyme by an endotoxin-mediated activator.

Limulus amebocyte lysate was fractionated by heparin-Sepharose chromatography into four components (fractions A, B, C and D). Major coagulation factors, i.e., proclotting enzyme, coagulogen, and proclotting enzyme activating factor precursor (proactivator) in the lysate were eluted, respectively, in fraction A, fraction B and fraction C. Clotting enzyme activity was detected only following recombination of fraction A and fraction C in the presence of endotoxin. The conversion of proactivator to its active form (activator) was an endotoxin-dependent reaction and was inhibited by polymyxin B. Either proactivator is an endotoxin-sensitive factor or another endotoxin-sensitive factor, which activates proactivator, is present in fraction C. Optimal pH for proclotting enzyme activation by activator was broad and ranged from pH 6.0 to 8.0, while that for the endotoxin-mediated activation of proactivator was pH 7.0. No initial latent period was observed during activation of the proactivator or proenzyme. The activator was inhibited by benzamidine, leupeptin, soybean trypsin inhibitor and diisopropyl fluorophosphate, suggesting that the activator is a trypsin-type serine protease. Trypsin, but not thrombin, urokinase, plasmin, papain or alpha-chymotrypsin activated the proclotting enzyme. Therefore, limited proteolysis, i.e., of an arginyl- or lysyl-X bond(s), of the proenzyme molecule is probably involved in its activation.

Animals↗
PubMed1982

Serum immunoreactive calcitonin concentrations in hepatocellular carcinoma.

Having found raised serum calcitonin concentrations in 94% of patients with hepatocellular carcinoma when using a dextran-coated-charcoal radio-immunoassay, we have now repeated the study, using a double-antibody radio-immunoassay, in 102 further patients with hepatocellular carcinoma and 35 matched controls. Serum immunoreactive calcitonin concentrations (iCT) in the controls ranged from 10 to 310 pg/ml (mean 154.6 pg/ml). Values in the tumour patients ranged from 10 to 1,650 pg/ml (mean 302.6 pg/ml). The mean figures were significantly higher in the tumour patients (P less than 0.001), 35.5% of them having values above 310 pg/ml. In 65 of the patients serum iCT concentrations were also determined by dextran-coated-charcoal radio-immunoassay. Values ranged from 10 to 10,780 pg/ml (mean 2,179 pg/ml). If 1,000 pg/ml is taken as the upper limit of normal, 69% of the patients had raised iCT concentrations. There was a good correlation (r = 0.67; P less than 0.001) between serum iCT values measured with both methods in 50 patients. If measured by the double-antibody radio-immunoassay method, the serum calcitonin value is not useful as a marker for hepatocellular carcinoma.

Adolescent↗
PubMed1982

The pathological basis of end-stage renal disease in blacks.

In a series of 115 black patients admitted to a chronic haemodialysis programme over a 4-year period, a definitive pathological diagnosis was made in 70 cases. Of these, 5 were made anatomically while in 65 the diagnosis was histological. The commonest single cause of end-stage renal disease was essential malignant hypertension which showed a peak incidence in males aged 40 - 50 years. Chronic pyelonephritis and other diseases prominent in series of White patients were conspicuously absent. The prevalence of malignant hypertension presents a challenge for the detection and treatment of such cases by the community health services.

Adolescent↗
PubMed1982

Effects of cyclophosphamide on murine bone marrow and splenic megakaryocyte-CFC, granulocyte-macrophage-CFC, and peripheral blood cell levels.

The effect of cyclophosphamide (CY) on megakaryocytopoiesis in mice was examined with assays of megakaryocyte colony-forming cells (Meg-CFC) in bone marrow and spleen and simultaneous determinations of peripheral blood counts, after a single intraperitoneal dose (200 mg/kg) of CY. Significant rebound thrombocytosis (170% of normal) occurred at day 11 after injection with CY, although only modest preceding thrombocytopenia (70% of normal) was observed. After an initial 3-5 day period of suppression, total megakaryocyte colony-forming cells (Meg-CFC) in both bone marrow and spleen of CY-treated mice demonstrated rebound increases at 5 and 7 days, respectively, after administration of the drug. Granulocyte-macrophage colony-forming cells (GM-CFC) exhibited alterations which were similar to those of Meg-CFC, suggesting similar sensitivities of Meg-CFC and GM-CFC to CY. The increase in Meg-CFC in both bone marrow and spleen preceded development of thrombocytosis by 4-6 days. This suggests that increased platelet counts in CY-treated mice are attributable, at least in part, to alterations in feedback mechanisms which control megakaryocytopoiesis, with resultant stimulation of the megakaryocyte progenitor compartment.

Animals↗
PubMed1982

Abnormal levels of plasma hormones in men with prostate cancer: evidence toward a "two-disease" theory.

The 24-hr mean plasma concentrations of 13 hormones or hormone metabolites (cortisol, testosterone, dihydrotestosterone, dehydroisoandrosterone, dehydroisoandrosterone sulfate, androsterone, androsterone sulfate, estrone, thyroxine, triiodothyronine, LH, FSH, and prolactin) were measured in 16 rigorously screened patients (aged 55-80) with stage C or D prostate cancer and 36 normal men. Nine of the hormones showed no abnormalities in the patients but four (testosterone, dihydrotestosterone, cortisol, and estrone) showed abnormalities. Testosterone and dihydrotestosterone, which, respectively, decreased with age and showed no change with age in the normal men, rose sharply with age in the patients. The patients' curves crossed the normal curves at about age 65; patients 65 or above showed normal values while patients under age 65 showed significantly subnormal levels of both hormones: testosterone averaged 282 ng/dl in patients vs 434 ng/dl in controls (P less than 0.0001) and dihydrotestosterone averaged 70 ng/dl in patients vs 99 ng/dl in controls (P less than 0.01). Cortisol, which was age invariant in the normal men, fell sharply with age in the patients; patients under 65 had significantly elevated levels (10.1 vs 6.9 micrograms/dl; P less than 0.0001), while patients 65 or older had normal levels. Estrone levels were age invariant in both patients and controls, but the mean level in patients was markedly elevated (81 vs 47 pg/ml in controls; P less than 0.001). The cortisol/testosterone ratio almost completely separated prostate cancer patients under 65 from normal men, but did not discriminate patients 65 or older from normal. The findings indicate that prostate cancer patients under 65 differ markedly in their endogenous hormonal pattern from patients 65 or older. This leads us to propose a "two-disease" theory of prostate cancer, with possible differences in genetic factors and prognosis.

Age Factors↗