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Biomedical subjects

J Levy

Publications and source records attributed to J Levy.

At least 433 records · Page 24Linked to original sources
PubMed1984

cAMP-independent protein kinase activity is correlated with growth of rat mammary tumors.

An important portion of the protein kinase activity in the 7,12-dimethylbenz(a)anthracene (DMBA) induced rat mammary tumour is inhibited by the bioflavonoid quercetin (10(-4) M). By partial purification on a DEAE Cellulose column it was shown that the quercetin-inhibitable enzyme activity can be eluted in a separate peak which contains markedly reduced cAMP-dependent protein kinase activity. Since quercetin does not affect the cAMP-dependent protein kinase activity, this drug becomes a potent tool for the quantitation of this special activity in the tumor. By hormonal manipulation, namely ovariectomy and estrogen treatment, it was shown that changes in the growth rate of the tumour were closely correlated with the magnitude of these special protein kinase activities. These results suggest a possible cause-and-effect relationship between cyclic AMP-independent protein kinase activity and tumour malignancy in this chemically induced tumor. These data are similar to recent findings in viral-induced malignant transformation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

A review, analysis, and some new data on hand-posture distributions in left-handers.

Different methods have been employed to assess handwriting posture in left-handers, and different dimensions of hand posture have been used for categorization. Within North American samples, there is a remarkable consistency between studies in the distributions when the same assessment method is used, but there are very large and highly significant differences for different methods of assessment. The various methods and dimensions of categorization evidently index different variables, and these are likely to have different relations with neuropsychological factors. It is possible, however, to gather questionnaire data on handwriting posture that closely resemble direct experimenter observation, as a brief report on left-handed males shows.

Female↗
PubMed1984

Disposition of tobramycin in patients with cystic fibrosis: a prospective controlled study.

The pharmacokinetics of tobramycin in adolescents or young adults with cystic fibrosis and in age-matched controls were prospectively compared. Patients with CF had a higher tobramycin total body clearance (121.2 +/- 14.2 ml/min/1.73 m2) than did controls (102.2 +/- 18.9 ml/min/1.73 m2, P less than 0.05). This was not associated with a higher glomerular filtration rate (iothalamate total body clearance 147.5 +/- 29.2 ml/min/1.73 m2 in patients vs 142.9 +/- 33.3 ml/min/1.73 m2 in controls) or a lower binding of gentamicin to serum proteins (14.3% +/- 2.6% in patients vs 17.4% +/- 3.8% in controls). Tobramycin renal clearance was not significantly different in the two groups (89.5 +/- 17.9 ml/min/1.73 m2 in patients vs 81.0 +/- 15.8 ml/min/1.73 m2 in controls). In the control group, tobramycin total body and renal clearances were highly correlated with iothalamate total body clearance (r = +0.95 and +0.88, P less than 0.01). In patients with cystic fibrosis, the correlation was not significant (r = +0.56, P greater than 0.05 for total body clearance, and r = 0.32, P greater than 0.1 for renal clearance). There was no significant difference in volume of distribution normalized to body surface area or in half-life of elimination. The higher tobramycin total body clearance without an increase in renal clearance, and the lower correlation with glomerular filtration rate indicate that an extrarenal clearance pathway might play a significant role in the elimination of tobramycin from the serum of patients with cystic fibrosis.

Adolescent↗
PubMed1984

Dysphagia as a primary manifestation of hyperthyroidism.

A 69-year old woman suffered from severe dysphagia, abdominal pain, and weight loss. The dysphagia was accompanied by nasal speech, nasal regurgitation of food, weakness, and wasting of the proximal muscles of the upper and lower girdles. Laboratory data revealed T3 sephadex uptake 65.2%; T4 15.1 mcg%; and T3 250 ng%. Treatment with antithyroid medication reversed the manifestation of all the symptoms, including dysphagia. Cine-studies revealed esophageal motor dysfunction as the cause of the dysphagia. Hyperthyroidism is a rare, but treatable cause of unexplained dysphagia.

Aged↗
PubMed1984

Systemic carnitine deficiency exacerbated by a strict vegetarian diet.

A 12-year old boy suffered episodes of vomiting, lethargy, and hypoglycaemia from the age of 1 year. Adhering to a vegetarian diet caused an increase in frequency and severity of the attacks. It was found that he was suffering from systemic carnitine deficiency that responded promptly to treatment with L-carnitine.

Carnitine↗
PubMed1984

Protein kinase activity in the rat mammary gland during pregnancy, lactation, and weaning: a correlation with growth but not with progesterone receptor levels.

A protein kinase activity fraction was defined in cytosols and membranes of mammary tissue isolated from rats during pregnancy lactation, and weaning. By partial purification on DEAE-cellulose columns, it was shown that this protein kinase activity is cAMP independent and that its preferential substrate is casein and not histone. This protein kinase activity is inhibited by the bioflavonoid quercetin at doses that do not inhibit cAMP-dependent protein kinase activity. The enzyme requires Mg2+ and is inactive in the presence of 10 mM Ca+2; these properties distinguish this activity from casein kinase activity found in the Golgi fraction and involved in milk protein processing. By following the physiological cycle of mammary gland development during pregnancy, lactation, and weaning, we found a close correlation between proliferation, expressed as the DNA content per gland, and quercetin-inhibited cytosolic protein kinase activity. Moreover, changes in this phosphorylating activity preceded the glandular growth changes. There was a less significant correlation between the growth process and protein kinase activity in the membrane fraction. The cytosolic cAMP-dependent protein kinase activity showed (only partial) correlation with growth only during pregnancy. Cytosolic progesterone receptor levels in mammary tissue were used as an estrogenic marker. Tissue growth correlated with progesterone receptor levels during pregnancy, where estrogens are the predominant hormones affecting tissue proliferation. However, no such correlation was found during lactation and weaning, when PRL is the major hormone affecting mammary gland growth. These results suggest that quercetin-inhibitable protein kinase activity is not merely another estrogenic marker, but represents more general regulatory activity which might be connected to growth processes of breast tissue.

Animals↗
PubMed1984

Cyclic changes in rat uterine proliferation during the estrous cycle are preceded by changes in protein kinase activity.

A protein kinase activity was defined in cytosols and membranes of rat uterus by using two types of enzyme inhibitors. The heat stable protein kinase inhibitor inhibited the cAMP-stimulated protein kinase but not the basal activity measured in the absence of the cyclic nucleotide. However, this basal activity was inhibited by quercetin in a dose-dependent manner, whereas the cAMP-stimulated protein kinase was not inhibited by this bioflavonoid. Thus, quercetin can be used as a tool to define a specific fraction of cAMP-independent protein kinase activity in rat uterine cytosols and membranes. The mature rat uterus is characterized by short (4 days) cyclic changes in tissue growth. Cell proliferation expressed as total uterine DNA content is observed on proestrus, reaches its peak at estrus, and declines sharply during metestrus and diestrus. The quercetin-inhibited protein kinase activity in the membranes of this tissue also changes cyclically and precedes by one phase the cyclic change in tissue proliferation. The clearest effect was seen when the protein substrates for this protein kinase activity were endogenous membrane proteins partially solubilized by Triton X-100 treatment. In contrast no change was observed in cytosolic, quercetin-inhibited protein kinase activity. The cAMP-stimulated protein kinase activity decreased slightly on diestrus. These results support our working hypothesis that tissue proliferation in the uterus and other tissues such as rat mammary gland and mammary tumors, correlates with cAMP-independent, quercetin-inhibited, protein kinase activity in these tissues.

Animals↗
PubMed1984

Induction of cytosolic receptors for 1 alpha, 25-dihydroxyvitamin D3 in the immature rat uterus by oestradiol.

The role of oestradiol-17 beta in the induction of specific cytosolic receptors for 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) was examined in the immature rat uterus. An acrylamide gel electrophoretic analysis was developed to separate the specific receptor for 1,25(OH)2D3 from the plasma binding protein for vitamin D3 metabolites. Employing this sensitive method the presence of receptors for 1,25(OH)2D3 in the mature rat uterus was evident. Such receptors were not found in the uterus of saline-treated immature rats. However, oestradiol administration caused an induction of these receptors in the immature rat uterus, together with a significant increase in the uterine weight, progesterone receptor level and peroxidase activity. These results suggest a mechanism for oestradiol regulation of calcium metabolism in the uterus at times of high demand for this cation during the gestation period.

Animals↗
PubMed1984

Impaired insulin action in rats with non-insulin-dependent diabetes.

Studies were performed to test the hypothesis that impaired insulin action occurs as an acquired phenomenon in the streptozocin (STZ)-treated, non-insulin-dependent (NIDDM) diabetic rat model. A number of methods were used to evaluate impaired carbohydrate tolerance in these animals. Plasma glucose and insulin levels were measured at 6 and 14 wk of age, and insulin glucose tolerance tests were performed at 4 and 5 wk of age (before overt hyperglycemia ensues), and at 8 and 14 wk of age (after the animals manifest overt diabetes). The STZ-treated rats had higher plasma glucose levels than those of control animals (P less than 0.001) at 6 and 14 wk of age, while their plasma insulin values were decreased to levels 73% of the controls (1.7 ng/ml versus 2.3 ng/ml, P less than 0.04). Glucose disappearance rates after high (0.35 U/kg) and low (0.175 U/kg) insulin challenge were reduced in the experimental diabetic animals at all ages with both insulin doses. The data suggest that these animals have an early and progressive acquired impairment in insulin action, most compatible with a defect in cellular biologic response to insulin. The possibility that this abnormality is secondary to insulin deficiency is raised.

Animals↗
PubMed1984

Handwriting posture, visuomotor integration, and lateralized reaction-time parameters.

On a simple manual reaction-time (RT) task to lateralized visual signals, right-handers and left-handers with the noninverted handwriting posture (RN and LN subjects, respectively) were faster and more consistent when the signal and response hand were homolateral as compared to heterolateral, but left-handers with the inverted handwriting posture (LI subjects) were not. For LI subjects, there was no speed difference for homolateral and heterolateral hand-signal combinations, and there was a clear and significant heterolateral superiority for response consistency. In agreement with suggestions of others, we believe that the anomalous response pattern of LI subjects is likely to be due to a disorder of visuomotor integration and cannot be attributed to reliance on uncrossed motor pathways.

Adolescent↗
PubMed1983

Tissue- and cell-specific casein gene expression. II. Relationship to site-specific DNA methylation.

The relationship between DNA methylation and the expression of the gamma- and beta-casein genes was investigated in both expressing and nonexpressing tissues and in isolated tumor cell subpopulations displaying differential casein gene expression. MspI/HpaII digestions of DNA isolated from liver, a totally nonexpressing tissue, indicated that specific sites of hypermethylation existed in these genes as compared to the DNA isolated from casein-producing lactating mammary gland. The positions of these sites were mapped in the gamma-casein gene by comparing total genomic DNA Southern blots to the restriction digests of several overlapping phage clones constituting the gamma-casein gene. In contrast, the methylation status of the HhaI sites in the gamma-casein gene was found to be invariant regardless of the expression status of the gene. The inverse correlation between the hypermethylation of certain MspI/HpaII restriction sites in the casein genes and their potential expressibility was further substantiated by studies in 7,12-dimethylbenz(a)anthracene- and N-nitrosomethylurea-induced mammary carcinomas, which have an attenuated casein gene expression, and in cell subpopulations isolated from the 7,12-dimethylbenz(a)-anthracene tumor which were either depleted or enriched in casein-producing cells. Analysis of total tumor DNAs indicated that the casein genes were hypermethylated at the same sites observed in liver. However, a very faint hybridization signal was observed in the HpaII digests, suggesting cell-specific methylation differences. We have confirmed the hypomethylation of at least two of these MspI/HpaII sites within the subpopulation containing the casein-producing cells at a level consistent with the relative enrichment in that fraction. These results demonstrate differential site-specific casein gene methylation not only between tissues but also between cell subpopulations within a single tissue.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Enhancement of deficient T-cell function in rheumatoid arthritis by tolmetin sodium.

The in vitro effect of tolmetin on deficient T-lymphocytes from patients with autoimmune diseases was tested using a mitogen-stimulation assay. For comparison, levamisole was also tested on T-cells in the same assay system in this group of patients. Tolmetin and levamisole both showed enhancement of T-cell function and normalization of mitogenesis in vitro. To evaluate the relevance of these in vitro findings to treatment of disease, four patients who had active rheumatoid arthritis and who had displayed repeated deficiency in vitro of T-cell mitogenesis were studied. After baseline studies, the patients were started on tolmetin at an oral dose of 800 mg/day in divided doses. If no significant enhancement of T-cell function was observed by four weeks, the dose of tolmetin was increased to 1600 mg/day. The results of the clinical study confirmed that tolmetin enhanced T-cell function in vivo as well as in vitro in a manner similar to that which has been reported for levamisole. This normalization of T-cell function by tolmetin was associated with clinical improvement.

Arthritis, Rheumatoid↗
PubMed1983

Growth enhancement induced by prolonged L-dopa administration in rats.

To follow growth of rats, in which growth hormone secretion has been chronically stimulated, L-Dopa (5 mg/kg) was injected subcutaneously twice daily for 70 days to growing rats. A control group, matched for sex and sibship, pair fed with the treatment group was given saline injections. At 10-day intervals, the rats were weighed and measured. At 90 days of age the rats were ether anesthesized, bled for growth hormone determination, and internal viscera weighed. Weight gain and length in the L-Dopa-treated group was found to be significantly greater. A mean weight gain of 6% and 12% in the male and female rats, respectively, and a mean length gain of 5% in both male and female rats was observed at 90 days of age. The thymus, thyroid, adrenals, uterus, and gonads all tended to be heavier in the L-Dopa-treated group. Significantly heavier kidneys were found in the L-Dopa group. Serum growth hormone was found to be 8.44 +/- 1.4(SE) ng/ml in the L-Dopa group and 4.6 +/- 0.9 ng/ml in the control group. It is concluded that the continuous administration of L-Dopa produces an increase of circulating serum growth hormone levels, and this in turn enhances growth.

Animals↗
PubMed1983

Is cerebral asymmetry of function a dynamic process? Implications for specifying degree of lateral differentiation.

It is proposed that the product-moment correlation between a subject's trial-to-trial performance and sensory half-field in which a stimulus appears be employed as an index of functional differentiation of the cerebral hemispheres, both when reaction time is the dependent variable and when accuracy is the dependent variable. This proposal is based on a model of hemispheric functioning in which the difference in competencies of the two sides of the brain, rather than being a static and unchanging dimension of an individual subject, is seen to vary from moment to moment, a variability that is just as characteristic of the cerebral hemispheres and their relationship as is the mean level of performance for each side. The relative degrees of asymmetry inferred for different subjects differ for laterality indices based on the static assumption verus correlational indices based on the dynamic assumption.

Brain↗