Biomedical subjects

S Kosowski

Publications and source records attributed to S Kosowski.

5 recordsLinked to original sources

PubMed1994

beta ig-h3: a transforming growth factor-beta-responsive gene encoding a secreted protein that inhibits cell attachment in vitro and suppresses the growth of CHO cells in nude mice.

beta ig-h3 is a novel gene first discovered by differential screening of a cDNA library made from A549 human lung adenocarcinoma cells treated with transforming growth factor-beta 1 (TGF-beta 1). It encodes a 683-amino-acid protein containing a secretory signal sequence and four homologous internal domains. Here we show that treatment of several types of cells, including human melanoma cells, human mammary epithelial cells, human keratinocytes, and human fibroblasts, with TGF-beta resulted in a significant increase in beta ig-h3 RNA. A portion of the beta ig-h3 coding sequence was expressed in bacteria, and antisera against the bacterially produced protein was raised in rabbits. This antisera was used to demonstrate that several cell lines secreted a 68-kD beta IG-H3 protein after treatment with TGF-beta. Transfection of beta IG-H3 expression plasmids into Chinese hamster ovary (CHO) cells led to a marked decrease in the ability of these cells to form tumors in nude mice. The beta IG-H3 protein was purified from media conditioned by recombinant CHO cells, characterized by immunoblotting and protein sequencing and shown to function in an anti-adhesion assay in that it inhibited the attachment of A549, HeLa, and WI-38 cells to plastic in serum-free media. Sequencing of cDNA clones encoding murine beta ig-H3 indicated 90.6% conservation at the amino acid level between the murine and human proteins. Finally, the beta ig-h3 gene was localized to human chromosome 5q31, a region frequently deleted in preleukemic myelodysplasia and leukemia. The corresponding mouse beta ig-h3 gene was mapped to mouse chromosome 13 region B to C1, which confirms a region of conservation on human chromosome 5 and mouse chromosome 13. We suggest that this protein be named p68 beta ig-h3.

Amino Acid Sequence↗

PubMed1993

Glycosylation of active human renin is necessary for secretion: effect of targeted modifications of Asn-5 and Asn-75.

Renin is a mammalian aspartic protease that is rate-limiting in the renin-angiotensin cascade. Preprorenin is the translational product of the human renin gene and is secreted as prorenin, an inactive zymogen, primarily from the juxtaglomerular cells of the kidney. It has previously been shown that the 46-amino-acid pro domain is not necessary for the secretion of fully active or mature renin from mammalian cells. Additionally, previous reports indicated that glycosylation of Asn-5 and Asn-75, the two potential sites of N-glycosylation in renin, is not necessary for the secretion of prorenin from mammalian cells. In the present study, the role of N-glycosylation in the secretion of mature renin was examined. Asn to Ser mutations at one or both of the glycosylation sites of mature renin were made and the expression of these constructs was examined in COS, CHO, and Sf9 insect cells. In the absence of the pro sequence, N-glycoylation at Asn-75 was essential for the secretion of active renin protein from all three cell types. The mutation at Asn-75 caused a more dramatic reduction in renin secretion than the mutation at Asn-5. This is in contrast to results previously reported for prorenin.

Animals↗

PubMed1979

Inhibition of osmotic thirst by electric stimulation of the basal forebrain in dogs.

The effect of electrical brain stimulation (ESB; 50 Hz, 50-150 microA sine wave, 5 s on/5 s off) on osmotic thirst was examined in 10 conscious dogs chronically implanted with electrodes aimed at the anteromedial part of the basal forebrain. Suppression of osmotic thirst (SOT) was observed during stimulation through 18 of 41 electrodes located in the olfactory tubercle, the nucleus accumbens, the caudate nucleus, the medial septum, and the lateral preoptic-anterolateral hypothalamic area (PrA/ALH). Mean increment in plasma osmolality necessary to cause drinking rose from 9.0 +/- 1.5 mosmol (X +/- SE; n = 15) under control conditions to 15.8 +/- 2.6 mosmol (n = 18) during ESB in SOT placements. Threshold cellular dehydration eliciting drinking increased from 2.70 +/- 0.50% of intracellular water (ICW;n = 16) to 4.77 +/- 0.68% of ICW (n = 18), respectively. The strongest SOT was found during ESB in the nucleus accumbens, and the PrA/ALH. The same stimulation failed to inhibit feeding, support self-stimulation or produce appreciable changes of dog's gross behavior. The results give evidence for the existence in the basal forebrain of the dog a widely distributed neural system suppressing osmotic thirst. The nucleus accumbens and the PrA/ALH seem to play an important role in this system.

Animals↗

PubMed1978

Osmotic thirst suppression elicited by electrical stimulation of the basal forebrain in the dog.

Reactivity of the thirst mechanism to osmotic stimuli was measured in conscious dogs chronically implanted with electrodes in the basal forebrain. It was found that the thirst threshold to the osmotic stimulus increases markedly during electrical stimulation of the preoptic area, septum, nucleus accumbens septi, and to smaller degree during stimulation of the nucleus caudatus. The possibility of existence of some inhibitory components in the neural system controlling thirst in the dog is suggested.

Animals↗

PubMed1975

[Not Available].

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History, Ancient↗