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Biomedical subjects

S Land

Publications and source records attributed to S Land.

26 records · Page 2Linked to original sources

Endothelin receptors in rat renal papilla with a high affinity for endothelin-3.

A high density of binding sites for endothelin has been described in rat renal papilla but the nature and significance of papillary endothelin receptors have not yet been evaluated. In the current study, the effect of endothelin peptides on phosphatidylinositol turnover in papillary tubules has been investigated. Endothelin-1, endothelin-3 and the endothelin-related peptide sarafatoxin S6b all stimulated the accumulation of inositol phosphates in [3H]inositol-labelled papillary tubule preparations. However, at these papillary receptors endothelin-3 was more potent than endothelin-1. In other tissues, endothelin-1 is more potent than endothelin-3 at endothelin receptors coupled to phosphatidylinositol turnover. The EC50 value for endothelin-3 expressed as the negative logarithm was 9.3 +/- 0.13 compared with 8.42 +/- 0.11 for endothelin-1 (mean +/- S.E.M., n = 5 in each case, P less than 0.01). The affinity of sarafatoxin S6b was similar to that for endothelin-3 (9.2 +/- 0.15, n = 3). These findings raise the possibility of a direct tubular function of endothelin and suggest that endothelin-3 rather than endothelin-1 may be the natural agonist for these papillary receptors.

Animals↗

Culturing rat neonatal myocytes causes changes in the phosphatidylinositol turnover pathway.

1. Cultured neonatal myocytes are commonly used as a model system for the study of cardiac phosphatidylinositol (PI) turnover. 2. In neonatal myocytes stimulation with noradrenaline causes the release of the Ca2(+)-releasing compound inositol-1,4,5-trisphosphate and the generation of the Ca2(+)-regulatory compound inositol-1,3,4,5-tetrakisphosphate. 3. Addition of noradrenaline to intact, neonatal rat hearts stimulates the release of inositol-1,4,5-trisphosphate, but not inositol-1,3,4,5-tetrakisphosphate. 4. These findings show that the isolation and culture of the neonatal myocyte causes changes in the PI turnover pathway so that it becomes similar to that described in other cell types and different from that in intact myocardial tissue. 5. The neonatal myocyte is not a useful model for the study of cardiac PI turnover.

Animals↗

Decreased in vitro susceptibility to zidovudine of HIV isolates obtained from patients with AIDS.

This study tested isolates of human immunodeficiency virus, obtained before and after zidovudine therapy from 10 patients, for susceptibility to the drug in vitro. The isolates collected after therapy were less susceptible to zidovudine as assessed by replication in MT-2 cells and production of reverse transcriptase activity by infected mononuclear leucocytes in the presence of the drug. Furthermore, pretherapy isolates were sensitive to a range of zidovudine concentrations when 100% inhibition was used as the end point. The loss of zidovudine susceptibility did not correlate with any clinical or virologic consequences in this small group of patients.

Acquired Immunodeficiency Syndrome↗

Comparison of core antigen (p24) assay and reverse transcriptase activity for detection of human immunodeficiency virus type 1 replication.

This report compares two assay systems for monitoring human immunodeficiency virus (HIV) replication in peripheral blood leukocyte cultures. A commercial enzyme-linked immunoassay detected core antigen (p24) in 80% of cell cultures from HIV-seropositive individuals, whereas 67% of the cell cultures produced detectable levels of reverse transcriptase activity. There were clearly three patterns of reverse transcriptase activity produced, two of which may evade detection without regular sampling and maintaining cell cultures for more than 4 weeks. Once established, core antigen levels remained high so that cell cultures could be confidently monitored by an intermittent screening regimen.

Cells, Cultured↗

Purification and biochemical characterization of hepatic arylamine N-acetyltransferase from rapid and slow acetylator mice: identity with arylhydroxamic acid N,O-acyltransferase and N-hydroxyarylamine O-acetyltransferase.

An inbred mouse model for the human N-acetylation polymorphism has been used to investigate the biochemical basis for the arylamine N-acetylation polymorphism and the relationship between the cytosolic enzymes arylamine N-acetyltransferase (NAT), arylhydroxamic acid N,O-acyltransferase, and N-hydroxyarylamine O-acetyltransferase. Biochemical studies of partially purified NAT from rapid and slow acetylator mice revealed identical molecular weights of 31,500, activation energies of 21,000 cal/mol, equivalent affinities for acetyl coenzyme A, broad pH optima, the presence of an active site sulfhydryl group, and similar behavior during purification with anion exchange, gel filtration, and hydrophobic interaction chromatography. The enzymes differed in inhibition by hydrogen peroxide and dithiobis(2-nitrobenzoic acid). These observations taken in conjunction with previous investigations indicate that the rapid and slow mouse NAT enzymes are isozymes with minimal structural differences. NATs from rapid and slow acetylator mice were purified more than 10,000-fold by the following sequence of methods: homogenization and fractional centrifugation, protamine sulfate precipitation, and chromatography on DEAE-Trisacryl M, Sephadex G-100, Amethopterin-AH-Sepharose 4B, butyl agarose, and Sephacryl S-200, with a 15-25% recovery. NAT from B6 mice was purified to greater than 95% purity, as judged by silver staining of sodium dodecyl sulfate-polyacrylamide gels. Although only NAT appeared to be subject to a genetic polymorphism as evidenced by N-acetylation activities in liver cytosol, the purified NAT protein possessed arylhydroxamic acid N,O-acyltransferase, N-hydroxyarylamine O-acetyltransferase, and NAT activities. Thus, the cytosolic N-acetyltransferase of mouse liver may catalyze N-, O-, and N,O-acetyltransfer reactions through a common acetylated intermediate of a single protein.

Acetylation↗

Trauma center and the OR. A cooperative approach to caring for the massively injured.

Communication must be established between the operating room and trauma center. At SNJRTC, perioperative nurses rotate through the trauma center and are part of nursing grand rounds on trauma patients. This system has improved interdepartmental relations, educational development, and most importantly, established a system in which patients have the best chance of survival as a result of the cooperative approach to the care of the massively injured.

Communication↗

The aging thyroid. Relationship between elevated serum thyrotropin level and thyroid antibodies in elderly patients.

The relationship of thyroid antibodies and the serum level of thyrotropin in older adults (over age 60) was studied to determine whether thyroid antibodies were a good clue to thyroid failure in elderly persons. Of those with thyroid failure, evidenced by clearly elevated serum thyrotropin values (more than 10 microU/ml), 67 percent had positive antimicrosomal antibody levels, a prevalence much greater (p less than 0.001) than that among those of comparable age with normal thyroid function (18 percent). Nevertheless, one third (33 percent) had thyroid failure without positive antimicrosomal antibody levels; this was true whether or not a low serum thyroxine value was present. Furthermore, of those with positive antimicrosomal antibody levels, most (68 percent) did not have thyroid failure. Thus, although positive antimicrosomal antibody levels occurred more often in elderly patients with thyroid failure than in those with normal thyroid function, a sizable fraction of those with thyroid failure did not have positive antimicrosomal antibody levels. Hence, measurement of thyroid antimicrosomal antibodies is not a good test of early thyroid failure in older patients; direct demonstration of a clearly elevated serum thyrotropin value is a better approach.

Adult↗