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Biomedical subjects

M Bader

Publications and source records attributed to M Bader.

At least 19 recordsLinked to original sources
PubMed1992

Species specificity of renin kinetics in transgenic rats harboring the human renin and angiotensinogen genes.

The renin-angiotensin system (RAS) is the most important regulatory system of electrolyte homeostasis and blood pressure. We report here the development of transgenic rats carrying the human angiotensinogen TGR-(hAOGEN) and human renin TGR(hREN) genes. The plasma levels and tissue distribution of the transcription and translation products from both genes are described. A unique species specificity of the enzyme kinetics was observed. The human RAS components in the transgenic rats did not interact with the endogenous rat RAS in vivo. Instead, infusions of exogenous human RAS components specifically interacted with human transgene translation products. Thus, infusion of human renin in TGR(hAOGEN) led to an increase of angiotensin II and an elevation of blood pressure, which could not be antagonized by the human-specific renin enzyme inhibitor Ro 42-5892. Rat renin also elevated blood pressure and angiotensin II in TGR(hAOGEN); however, this effect was not antagonized by the human renin inhibitor. Compared to mice, rats offer the advantage of chronic instrumentation and repetitive, sophisticated, hemodynamic, and endocrinological investigations. Thus, transgenic rat models with human-specific enzyme kinetics permit primate-specific analyses in non-primate in vivo and in vitro experimental systems.

Angiotensin II↗
PubMed1992

Expression of nitric oxide synthase in kidney macula densa cells.

The distribution of nitric oxide synthase (NOS), the enzyme by which NO is generated from L-arginine, was investigated in rat kidney. The indirect immunofluorescence technique using a polyclonal antibody against type I NOS was applied, followed by the histochemical NADPH diaphorase staining technique on the same sections in order to demonstrate the enzymatic activity of NOS. Macula densa cells were strongly stained by both techniques, demonstrating abundant NOS in the cytoplasm of these cells. In addition, these findings were confirmed by nonradioactive in situ hybridization, thus demonstrating the corresponding messenger RNA in macula densa cells as well. Our findings provide the morphological basis for a possible role of NO as a mediator substance in signal transfer from distal tubular fluid to glomerular arterioles.

Amino Acid Oxidoreductases↗
PubMed1992

Basic methodology in the molecular characterization of genes.

PURPOSE: During the past two decades, molecular biology techniques have had an increasing impact upon hypertension research. This article will thus review the basic methodology in this field. CONTENTS: Protocols are described for the establishment of a genomic library and its use for the cloning of specific genes, as well as methods for the detection and sequencing of DNA. In addition, techniques to detect and quantify specific messenger RNA, such as Northern blotting, ribonuclease protection assay and in situ hybridization, and the reporter gene approach for the analysis of regulatory gene sequences, are included. The polymerase chain reaction which, as a newly established technique to detect and amplify DNA, has exerted a strong influence upon all areas of molecular biology is the subject of the concluding paragraph. CONCLUSIONS: Molecular biology techniques may be of substantial help in revealing the cause of hypertension and developing tools to prevent and treat this disorder.

Animals↗
PubMed1992

Role of tissue renin in the pathophysiology of hypertension in TGR(mREN2)27 rats.

A transgenic rat line, TGR(mREN2)27, was established by introducing the murine Ren-2 gene into the genome of rats by microinjection techniques. These rats exhibit severe hypertension, making them an interesting model in which to study the role of renin in the pathophysiology of hypertension. However, although the additional renin gene is the only genetic difference compared with control rats, the exact mechanism of hypertension in TGR(mREN2)27 rats is still unclear. It cannot be attributed to a stimulation of the endocrine renin-angiotensin system or to an overexpression of renin in the kidney, since plasma and kidney renin and renin gene expression in the kidney are low in these animals. Here we describe recent progress made toward elucidating mechanisms of hypertension in TGR(mREN2)27 rats. 1) TGR(mREN2)27 rats were bred to homozygosity. The development of high blood pressure in homozygous rats is accelerated compared with that of heterozygous rats. This is paralleled by a higher mortality rate in homozygous TGR(mREN2)27 rats. Blood pressure and mortality rate of homozygous transgenic rats were effectively reduced by 10 mg captopril per kilogram body weight. 2) Treatment of 8-week-old heterozygous TGR(mREN2)27 rats with 10 mg/kg body wt per day of the angiotensin II receptor antagonist DuP 753 for 4.5 weeks normalized blood pressure. After withdrawal of the drug, blood pressure increased rapidly, reaching control levels after 3 weeks. In another group of TGR(mREN2)27 rats treated with 0.5 mg/kg per day, there was no change in blood pressure. Plasma renin and plasma angiotensin II were significantly higher in the high-dose group compared with the low-dose group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1992

The role of the adrenal gland in hypertensive transgenic rat TGR(mREN2)27.

The TGR(mREN2)27 is a new monogenetic rat model in hypertension research. As the mouse Ren-2d renin gene is integrated into their genome, they develop fulminant hypertension between 5 and 15 weeks of age, with blood pressure maxima of 300 mm Hg. Their plasma renin-angiotensin system (RAS) is suppressed, but the transgene is highly expressed in the adrenal gland, so we investigated its possible role in steroid metabolism and the pathogenesis of hypertension. During the phase of hypertension development (between 6-18 weeks), the urinary excretion of deoxycorticosterone (DOC), corticosterone (B), 18-hydroxycorticosterone, and aldosterone is 1.5- to 2.5-fold elevated compared with that in Sprague-Dawley (SD) rats (P less than 0.0005) despite the suppressed plasma RAS. Moreover, the adrenal gland in TGR(mREN2)27 shows an increased maximal response to ACTH stimulation in regard to urinary excretion of DOC (after ACTH, 244 +/- 42 ng/24 h in TGR; 62 +/- 10 ng/24 h in SD; P less than 0.0005) and B (after ACTH, 5144 +/- 346 ng/24 h in TGR; 2607 +/- 324 ng/24 h in SD; P less than 0.0005). Additionally, plasma prorenin in TGR was stimulated more than 10-fold, indicating transgene regulation by ACTH. Since spironolactone treatment did not lower the blood pressure in TGR, hypertension solely due to hypermineralocorticoism is unlikely. Our results indicate that the adrenal steroid metabolism is markedly stimulated in young TGR, and the absolute increase in urinary DOC and B after ACTH injections is enhanced, possibly due to a stimulated local intraadrenal RAS.

18-Hydroxycorticosterone↗
PubMed1991

A 60-kDa protein from rabbit reticulocytes specifically recognizes the capped 5' end of beta-globin mRNA.

The binding of proteins from rabbit reticulocyte lysate to in-vitro-generated beta-globin mRNA and its defined segments was investigated using ultraviolet-cross-linking experiments as well as gel-retardation assays. Under stringent conditions, only three proteins (72, 60 and 50 kDa) were found associated with full-length beta-globin mRNA at different positions. The 72-kDa protein is most likely the poly(A)-binding protein and binds, as expected, to the poly(A) tail, whereas the 50-kDa protein exhibits affinity for the trailer region of beta-globin mRNA. The binding region of the 60-kDa protein is located at the 5' end of beta-globin mRNA. The interaction of this protein is dependent on the presence of the 5' cap structure, as indicated by competition experiments using an uncapped beta-globin-mRNA leader segment. Further competition experiments with beta-globin mRNA, deleted in part in the leader region, suggest that, besides the cap structure, certain sequence elements are necessary for the interaction of the 60-kDa protein and the beta-globin mRNA leader.

Animals↗
PubMed1991

Topography of event-related potentials elicited by visual emotional stimuli.

This experiment was intended to explore the effects of the emotional connotation of stimuli on the hemispheric lateralization. Ten right-handed male subjects (Ss) were presented a set of slides of faces expressing a positive emotion, a negative emotion or emotional neutrality. The ERPs elicited by the face stimuli were recorded from 16 leads and topographic maps of P3 amplitude were created. The results show that when Ss had to discriminate between emotional (target) and neutral (non-target) faces, the main differences were seen predominantly over the right centroparietal area. On the contrary, when Ss had to detect a face particularity not related to the emotional content, the differences between target and non-target faces were bilaterally distributed. The present results support the hypothesis that the perception of emotional expressions is processed mainly by the right hemisphere.

Brain↗
PubMed1990

Authoritarianism and attitudes toward AIDS victims.

This study investigated the relationship of authoritarianism and attitudes toward AIDS victims in three samples. One hundred fifty-eight students at Oregon State University participated, including 101 students from the United States, 25 from Japan, and 32 from other Asian societies. The survey instrument included the 20-item Attitudes Toward AIDS Victims (ATAV) Scale, the 18-item F Scale, the Form A, and 14-item Formal Content of Dogmatism Scale. Results showed slight but significant correlations between the ATAV and F (r = .17, p less than .044) and Formal Content of Dogmatism (r = .20, p less than .023) Scales for the United States sample. Highly significant differences were found in the predicted direction among the three samples on authoritarianism, F = 43.94, p less than .001.

Acquired Immunodeficiency Syndrome↗