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Biomedical subjects

M Weiss

Publications and source records attributed to M Weiss.

At least 559 records · Page 31Linked to original sources

cDNA cloning of alkaline phosphatase from rat osteosarcoma (ROS 17/2.8) cells.

Two cDNA clones of rat alkaline phosphatase (AP) were isolated from a rat osteosarcoma lambda gt 11 cDNA library (ROS 17/2.8) utilizing a human bone-liver-kidney (BLK) type AP cDNA. These clones contain overlapping DNA sequences of 597 and 520 bp, respectively, corresponding to the 3' noncoding region of AP mRNA. The sequence homology with the human BLK AP cDNA is 61%. In Northern blot analysis the rat cDNA hybridizes to a single band of 2.5 kb mRNA from ROS 17/2.8 and rat liver, under highly stringent conditions. Steady state levels of AP mRNAs measured in several rat osteosarcoma cell lines (ROS 17/2.8, ROS 2/3, ROS 25/1, UMR 106) correlate with the level of AP enzymatic activity in these cells. Dexamethasone, which stimulates AP enzymatic activity in ROS 17/2.8 cells, increases the relative abundance of AP mRNA in a dose-dependent manner. This probe can be used to study AP expression in rat tissues and cells.

Alkaline Phosphatase↗

Reduced excitatory effect of kainic acid on rat CA3 hippocampal pyramidal neurons following destruction of the mossy projection with colchicine.

Rats were injected unilaterally with colchicine in the dentate gyrus of the dorsal hippocampus. Two weeks later, under urethane anesthesia, extracellular recordings were obtained on both sides from pyramidal neurons of the CA1 and of the CA3 regions of the dorsal hippocampus. Microiontophoresis was used to assess the responsiveness of these neurons to kainate, glutamate and ibotenate. The colchicine injection produced a nearly complete destruction of the granule cells of the ipsilateral dentate gyrus and of their mossy fiber projections to CA3 without apparently affecting other hippocampal neurons. On the lesioned side, the potency of kainate in activating CA3 pyramidal neurons was reduced by 94% compared to the same neurons on the intact side. However, the excitatory effect of glutamate was unchanged and that of ibotenate only slightly reduced. Kainate was 80 times more potent in activating CA3 than CA1 pyramidal neurons on the intact side, whereas this ratio had dropped to 2.6 on the lesioned side. The selective decrease of the effectiveness of kainate in activating CA3 pyramidal neurons following the colchicine lesion suggests that this amino acid, but not glutamate and ibotenate, produces most of its excitatory effect in the intact CA3 region by releasing (an) excitatory neurotransmitter(s) from mossy fibers terminals, the nature of which remains to be identified.

Animals↗

Fatal copper storage disease of the liver in a German infant resembling Indian childhood cirrhosis.

A female child of non-consanguineous, healthy German parents fell ill at the age of 7 months with a progressive liver disease leading to irreversible hepatic failure 3 months later. Histological examination revealed severe liver cell necrosis, excessive Mallory body formation and veno-occlusive-like changes associated with massive storage of copper, similar to Indian childhood cirrhosis (ICC). Chronic copper contamination of drinking water was the only detectable aetiological factor. The study illustrates that ICC most probably is an environmental disease, also occurring outside the Indian subcontinent, and is likely to be underdiagnosed in the Western world.

Child↗

Generalizations in linear pharmacokinetics using properties of certain classes of residence time distributions. II. Log-concave concentration-time curves following oral administration.

The present approach enables a noncompartmental assessment of log-concave plasma concentration-time profiles following oral drug administration. Observed log-concavity corresponds to a nonparametric class of residence time distributions with the following properties: (1) The fractional rate of elimination kB(t) (failure rate of the distribution) increases monotonically until reaching the terminal exponential coefficient kB,Z. (2) The relative dispersion of body residence times CVB2 (ratio of variance to the squared mean, VBRT/MBRT2) acts as a shape parameter of the curve. The role of the input process in determining the shape of the concentration profile is discussed. In this connection evidence is provided for the importance of log-concave percent undissolved versus time plots, introducing the general concept of a time-varying fractional rate of dissolution. The governing factor for the appearance of log-concavity is the ratio of mean absorption time to mean disposition residence time (MAT/MDRT); this factor exceeds a particular threshold value which depends on the distributional properties of the drug. Generalizing previous approaches which are valid for first-order input processes, the "flip-flop" phenomenon and the problem of "vanishing of exponential terms" are explained using fewer assumptions. Upper bounds for the elimination time (more than 90% eliminated) and the cutoff error in AUC determination are presented. The concept of log-concavity reveals general features of the pharmacokinetic behavior of oral dosage forms exhibiting a dominating influence of the absorption/dissolution process.

Administration, Oral↗

A low protein-high linoleate diet increases glomerular PGE2 and protects renal function in rats with reduced renal mass.

Renal function deteriorates progressively in partially nephrectomized rats. This deterioration of renal function may be ameliorated by a diet either low in protein or high in linoleic acid. In the present experiment, partially nephrectomized rats were pair fed diets low in protein, high in linoleic acid or both low in protein and high in linoleic acid. Survival of renal function was most prolonged in rats fed a diet with both a low protein and high linoleic acid content; glomeruli from these animals demonstrated increased glomerular PGE2 production. This additive effect may be mediated by increased production of the vasodilatory PGE2 by glomeruli.

Animals↗

Induction of adrenocortical special zone in the male possum (Trichosurus vulpecula).

The induction of adrenocortical special zone (S.Z.) by gonadotrophin administration was studied in male brush tailed possums. Castrated males injected with porcine FSH (NIH-FSH-P2) formed well developed S.Z.s, varying in sizes from 5-20% of the gland's volume. Pregnant mare serum gonadotrophin (PMSG) was ineffective. From adrenal homogenates of FSH treated possums incubated with [3H]-progesterone the major conversion products were 5 beta-reduced steroid metabolites (72%) and cortisol (4%). The conversion products from adrenals of saline and PMSG treated males were cortisol and corticosterone (65%). Of the ten untreated castrates, one had a well developed S.Z. and two had S.Z.s at an early stage of development. Significant 5 beta-reduction of [3H]progesterone was only found in one animal. The plasma FSH concentrations were in intact males 317 +/- 41 ng rat FSH ml-1 (mean +/- SEM) and in castrates 769 +/- 64. The possible reasons for the lack of spontaneous S.Z. formation in intact males are discussed.

Adrenal Cortex↗

Life stress and hypertension.

Based on psycho-physiological, clinical and epidemiological studies, essential arterial hypertension is considered to be a consequence of an inadequate 'person-environment fit', objectively, subjectively or both. Besides genetic predisposition, salt intake, obesity and physical inactivity, psychological factors--among them 'hyper-reactivity' of the sympathetic nervous system, predisposing behaviour patterns and stressful life-events--should be taken into account in reaching a better understanding of the causes, prediction and prevention of hypertension. It was demonstrated that a maladaptation in various functional systems, even to minor psycho-emotional stress, is an important pathogenetic link between environment, objectively defined stressors and blood pressure regulation from the earliest phases of the disease. Implications for further research and behavioural interventions, together with other lifestyle-related factors, are discussed for improving the population-based health care in cardiovascular disease in the G.D.R.

Adolescent↗

Determinants of rat albumin promoter tissue specificity analyzed by an improved transient expression system.

The 150-base-pairs region located upstream of the transcriptional start site of the rat albumin gene contains all of the critical sequences necessary for this gene's tissue-specific expression in rat hepatoma cells. In transient expression assays using an improved CAT system or direct mRNA analysis we were able to detect a faithful transcription from the albumin promoter in albumin-negative dedifferentiated H5 hepatoma cells which was 250-fold weaker than in differentiated H4II hepatoma cells producing albumin. This strong tissue specificity could be completely overcome through the cis action of a non-tissue-specific enhancer. Two upstream regions from nucleotides -151 to -119 and from -118 to -94, were required for efficient transcription in H4II cells. Each region contained a sequence motif highly conserved among different species. The effect of the -151/-119 region was strictly tissue specific, while the -118/-94 region was also involved in the low level of transcription observed in H5 cells. Finally, sequences between the CCAAT box and the TATA box also contributed to the overall tissue specificity of rat albumin gene transcription.

Acetyltransferases↗

A new family of vertebrate viruses: Toroviridae.

The proposed family Toroviridae is characterized by eveloped, peplomer-bearing particles containing an elongated tubular nucleocapsid with helical symmetry. The capsid may bend into an open torus, conferring a biconcave disk or kidney-shaped morphology to the virion (largest diameter 120-140 nm) or the capsid may be straight, resulting in a rod-shaped particle (35 X 170 nm). Morphogenesis is by budding of preformed nucleocapsids through membranes mainly of the Golgi system and of the rough endoplasmic reticulum. Berne virus, which is proposed as the family prototype, contains a single strand of infectious positive-sense RNA, Mr about 6.5 X 10(6), which is polyadenylated. The RNA is surrounded by the major nucleocapsid phosphoprotein (Mr about 20,000) which, in turn, is enveloped by a membrane containing one major protein (Mr 22,000) and a phosphoprotein (Mr 37,000). The viral peplomers, about 20 nm long, carry determinants for neutralization and hemagglutination; they are formed by a polydisperse N-glycosylated protein (Mr 75,000-100,000). Four major subgenomic polyadenylated RNAs have been identified in infected cells, with Mrs of 3.0, 0.71, 0.46 and 0.26 X 10(6). Torovirus replication is inhibited by actinomycin D, alpha-amanitin and pre-irradiation of the host cell with UV light. All toroviruses identified so far cause enteric infections and are probably transmitted by the fecal-oral route. Serologic relationships between equine, bovine and human toroviruses have been demonstrated.

Animals↗

Identification of human growth hormone messenger ribonucleic acid in pituitary adenoma cells by in situ hybridization.

The technique of in situ hybridization was used to examine human GH gene expression in human GH-secreting pituitary adenoma cells. Five somatotroph adenoma specimens obtained at surgery were dispersed into single cell suspensions. Hybridization experiments were performed on cells immediately after dispersal or on cells cultured for 48-72 h in a defined serum-free medium. Tritiated GH cDNA was used to probe fixed cells, and hybridization was determined by liquid autoradiography. Of the freshly dispersed adenoma cells probed with GH cDNA, more than 70% contained GH mRNA, as determined by counting silver grains per cell. Significant cellular grain counts were obtained for GH cDNA-probed cells from all five tumors, while negative controls showed negligible silver grain counts. In cultured cells derived from three of five tumors, an average of 40% contained detectable GH mRNA. Therefore, quantitative in situ hybridization is a useful technique to demonstrate the expression of GH mRNA in human pituitary adenoma cells.

Adenoma↗

A model clinical neuroscience curriculum.

We have attempted to identify those attitudes, skills, and competencies in the clinical neurosciences that every graduating medical student should possess. Curricular guidelines are provided that may act as a model educational outline, to be adapted and utilized as individual circumstances dictate and resources permit. A universal, although not lockstep, curriculum emerges from these considerations.

Curriculum↗

Trapidil does not affect serum levels and cardiotonic action of digoxin in healthy humans.

The influence of trapidil on serum levels and cardiac effects of digoxin was investigated in 10 healthy men, intraindividually compared with placebo. Each subject took digoxin orally for 9 days (0.375 mg daily on days 1 to 8, 0.25 mg on day 9) either combined with trapidil (400 mg daily on days 1 to 8, 200 mg on day 9) or combined with placebo in a cross-over design. Trapidil failed to change significantly the steady-state serum digoxin concentrations on day 9 of treatment. It did also not alter significantly the following digoxin effects: shortening in QS2c time indicating the cardiotonic digoxin effect, shortening in QTc time, increase in PTQ index. But trapidil prevented the negative chronotropic digoxin effect.

Adult↗