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Biomedical subjects

A Saltiel

Publications and source records attributed to A Saltiel.

9 recordsLinked to original sources
PubMed1996

Involvement of ErbB2 in the signaling pathway leading to cell cycle progression from a truncated epidermal growth factor receptor lacking the C-terminal autophosphorylation sites.

To investigate the mechanisms underlying the enhanced mitogenic activity of the truncated epidermal growth factor receptor (EGFR) lacking the C-terminal autophosphorylation sites (Delta973-EGFR), we studied the intracellular signaling pathways in NR6 cells expressing human wild type EGFR and Delta973-EGFR. Microinjection of dominant/negative p21ras(N17) completely inhibited EGF-induced DNA synthesis in both cell types. EGF stimulated Shc phosphorylation as well as the formation of wild type EGFR.Shc complexes. In contrast, EGF stimulated Shc phosphorylation without formation of Delta973-EGFR.Shc complexes. Tyrosine-phosphorylated Shc formed complexes with Grb2.Sos, and microinjection of anti-Shc antibody and Shc-SH2 GST fusion protein inhibited EGF stimulation of DNA synthesis in both cell lines. EGF markedly increased ErbB2 tyrosine phosphorylation in wild type EGFR cells. In Delta973-EGFR cells, ErbB2 was tyrosine phosphorylated in the basal state and EGFR stimulated further phosphorylation of ErbB2. In addition to ErbB2, additional proteins were tyrosine phosphorylated in Delta973-EGFR cells, mostly in the molecular mass range of 120 170 kDa. Taken together with our findings indicating coupling of ErbB2 to Shc, these data suggest the importance of an alternative signaling pathway in Delta973-EGFR cells mediated by the formation of heterodimeric structures between the truncated EGFR and ErbB2, followed by coupling through Shc to Grb2.Sos and the p21ras pathway, ultimately leading to mitogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Developmentally regulated testicular galactolipid sulfotransferase inhibitor is a phosphoinositol glycerolipid and insulin-mimetic.

The synthesis of sulfogalactosylglycerolipid (SGG) is a differentiation marker in spermatogenesis restricted to the zygotene and early pachytene spermatocytes. The galactolipid sulfotransferase responsible for the synthesis of SGG is regulated by a phosphorylation mechanism. The activity of this enzyme is reduced in cells later in spermatogenesis by a low molecular weight inhibitor, which can be extracted in organic solvents and purified by reverse phase high pressure liquid chromatography (HPLC). This purified inhibitor is a potent postreceptor insulin-mimetic, which stimulates adipocyte lipogenesis more effectively than does insulin. Phosphoinositol (PI) glycolipids have been proposed as second messengers of the insulin phosphorylation cascade. These species contain a nonacetylated glucosamine, which renders them liable to cleavage by deamidation. The activity of the sulfotransferase inhibitor was lost following nitrous acid deamidation and was labile to PI specific phospholipase C digestion. Insulin and insulin-like growth factor I were found to inhibit germ cell synthesis of SGG in vitro to some degree but had no direct effect on the testicular galactolipid sulfotransferase assay. These results indicate that the sulfotransferase inhibitor is a glycosyl phosphoinositide similar to the lipid species, which mediate insulin signal transduction and suggest that germ cell SGG biosynthesis may be regulated by a receptor-mediated phosphorylation pathway.

Adipose Tissue↗
PubMed1992

Oxygen transport during anemic hypoxia in pigs: effects of digoxin on metabolism.

We tested whether digoxin would limit tissue hypoxia during severe anemia by improving peripheral O2 distribution or decreasing O2 demands. Hematocrit (Hct) was reduced in eight control and eight digoxin-treated pigs from 27-28% to 17-18, 11-12, and 7-8%. Whole body and hindlimb blood flow, O2 transport, O2 extraction, and O2 consumption and serum catecholamines (epinephrine and norepinephrine) were determined at each Hct. Arterial and femoral venous lactate and O2 deficit were obtained to reflect tissue hypoxia. Cardiac output was significantly greater (P less than 0.05) with digoxin, as expected, but there were no differences in hindlimb blood flow. Also, whole body and hindlimb O2 extractions were equal in both groups for similar levels of O2 transport, suggesting that digoxin did not alter the relationship of O2 flow to metabolism in regional circulations. As whole body O2 consumption fell, controls accumulated more (P less than 0.05) O2 deficit and arterial lactate than the digoxin group. Furthermore, the slope demonstrating the linear increase of lactate with respect to O2 deficit was much steeper in controls (y = 1.11 + 0.06x) than in digoxin (y = 1.36 + 0.02x), suggesting that there were differences in the degree of tissue hypoxia for comparable O2 deficit. This may be attributed to the marked differences in catecholamine response: epinephrine was higher in controls at Hct of 7-8% and norepinephrine was higher at Hcts of 11-12 and 7-8%. Digoxin may have inhibited the release of catecholamine or reduced the stimulus for catecholamine secretion during anemia. We speculate that digoxin markedly improved the balance between peripheral O2 supply and demand during anemia by inhibiting catecholamine thermogenesis, thereby decreasing O2 demands. This may explain some of the salutary effects of glycosides in high-output cardiac failure with normal ventricular function.

Anemia↗
PubMed1987

Cervico-endometrial cytology and physiological aspects of the post-partum mare.

After parturition, Thoroughbred mares were mated at the first post-partum oestrus (N = 24) or at a subsequent oestrus (N = 12). All mares were examined daily for: oestrous detection, palpation per rectum of the genital tract, vaginoscopic examination and cervico-endometrial cytology. Pregnancy diagnosis was carried out at Days 18, 35 and 45 after mating. An identical first service conception rate of 50% was found in both groups. The number of neutrophils followed a descending profile to only scattered cells at the first post-partum oestrus and in Group II mares remained at this very low level during the period of study. The percentage of histiocytes and eosinophils increased on Days 10 and 17, and 5 and 6 post partum, respectively. The percentage of lymphocytes remained low and constant during the period of study. Bacterial flora decreased from Days 2 to 9 and increased from Days 13 to 17 post partum. Cellular necrosis and erythrocytes decreased and ciliocytopholia increased as mares approached the first post-partum oestrus. A positive correlation was found between amount, colour, viscosity and turbidity of secretions and all cellular types, ciliocytopholia, cellular necrosis and bacterial flora. The number of neutrophils was positively correlated with the percentage of eosinophils, bacterial flora and cellular necrosis but had a negative association with the presence of ciliocytopholia. Two mares that did not re-establish cyclic ovarian activity after parturition had delayed uterine involution. Mares not conceiving at the first post-partum oestrus exhibited a more prolonged presence of cellular necrosis and erythrocytes and an increased presence of bacterial flora and lymphocytes as compared to mares conceiving at this period.

Animals↗
PubMed1986

Pathologic findings in the oviducts of mares.

Oviducts from 325 mares were evaluated macroscopically, and oviducts from 124 mares were evaluated microscopically. Two hundred and eighty-five (87.69%) of the mares had at least 1 macroscopic lesion and 116 (93.54%) had at least 1 microscopic lesion. The most frequently seen macroscopic lesions were adhesions, paraovarian cysts, and thick fibrous bands. Microscopically, intraepithelial cysts, slight, focal lymphocytic infiltration in the infundibular-ampullary region, and proteinoid material in the oviductal lumen were the most common findings. In general, the proximal segments of the oviduct were more affected than were the distal segments. Forty-nine (90.74%) of the 54 pairs of oviducts collected from pregnant mares had at least 1 macroscopic or microscopic lesion.

Animals↗
PubMed1982

Ovarian activity in the mare between latitude 15 degrees and 22 degrees N.

Ovarian activity, as measured by the presence of small (10-15 mm diam.), medium (15-30 mm) and large (greater than 30 mm) follicles, corpora haemorrhagica and corpora lutea (CL), was determined in a total of 3584 ovaries during 1 year using post-mortem specimens. There were significant correlations of the incidence of ovulated follicles (ovulations), large and medium follicles (P less than 0 . 001) and of the mean number of small follicles (P less than 0 . 05) per mare with respect to season. The yearly averages of ovulated, large and medium follicles were 30 . 1, 13 . 9 and 73 . 9%, respectively, and the mean number of small follicles per mare was 2 . 0. The mean incidence of inactive ovaries throughout the year was 21 . 2%. The adjusted sinusoidal curves remained above their own yearly average from April to October (ovulations), March to September (large follicles), February to September (medium follicles) and January to July (small follicles), and below its yearly average from March to September (inactive ovaries). The mean incidence of multiple ovulations was 11 . 9%. No significant differences were found between the activities of the right and left ovaries. It was concluded that the mare shows a seasonal reproductive pattern near the equator in the northern tropical zone.

Animals↗