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Biomedical subjects

V South

Publications and source records attributed to V South.

6 recordsLinked to original sources

A double-blind comparison of granisetron and placebo for the treatment of acute migraine in the emergency department.

Three hundred and ninety-seven patients who presented to the emergency department were screened for a randomized, double-blind, placebo-controlled study of iv granisetron (40 micrograms/kg or 80 micrograms/kg) in acute migraine. Twenty-eight patients fulfilled the stringent eligibility criteria and completed the study. Rescue medication was required 2 h post-infusion in 8 of 10 patients receiving granisetron 40 micrograms/kg, 5 of 10 patients receiving granisetron 80 micrograms/kg, and 6 of 8 patients receiving placebo. Significant improvement (p less than 0.05) in headache pain (on a visual analogue scale and categorical scale) was observed in the 80-micrograms/kg group. Headache pain evaluated with the Hunter headache scale indicated improvement for the sensory and affective components of headache pain in both granisetron groups. Except for more nausea at 30 min in the placebo group, no significant differences were noted between treatments. All three treatments were well tolerated. Granisetron may be effective for acute migraine headache; however, further studies with increased patient numbers are required.

Acute Disease

Cloning and expression of the human substance K receptor and analysis of its role in mitogenesis.

The primary structure of the human substance K receptor was established from the sequences of complementary DNA clones isolated from a human jejunal complementary DNA library. It consists of 398 amino acids, including seven putative transmembrane regions. The gene for the human substance K receptor was localized to chromosome region 10p13-10q23, a region with frequent chromosomal abnormalities. The human substance K receptor was expressed in transfected NIH-3T3 cells lacking endogenous substance K receptors, and Scatchard analysis of 125I-labeled substance K binding indicates approximately 100,000 receptors/cell with a single dissociation constant of 12 nM. Covalent cross-linking experiments utilizing 125I-substance K and three different chemical cross-linking reagents (disuccinimidyl suberate, disuccinimidyl tartrate, or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-HCl) demonstrate an apparent molecular weight of 45,000, consistent with little or no N-linked glycosylation. The binding of substance K to its receptor on transfected cells led to a rapid increase in the production of total inositol phosphates and the release of Ca2+ from internal stores. Growth of the cells transfected with the human substance K receptor is stimulated by the addition of substance K to the medium to a level similar to 10% serum. Therefore, the human substance K receptor can function as a growth factor receptor when expressed in mouse 3T3 cells.

Amino Acid Sequence

Human glioblastoma cell lines have neuropeptide receptors for bombesin/gastrin-releasing peptide.

Bombesin/gastrin-releasing peptide receptors were characterized in human glioblastoma cell lines. [125I]Gastrin-releasing peptide or ([125I]Tyr4)bombesin bound with high affinity to these cell lines. Binding to cell line U-118 was time dependent, reversible, and specific. ([125I]Tyr4)Bombesin bound with high affinity (Kd = 1.6 nM) to a single class of sites (Bmax = 30,000/cell). The C-terminal of bombesin- or gastrin-releasing peptide was essential for high-affinity binding. Bombesin- or gastrin-releasing peptide elevated the cytosolic Ca2+ levels in a dose-dependent manner. Because gastrin-releasing peptide, but not gastrin-releasing peptide, increased the cytosolic Ca2+ levels, the C-terminal but not the N-terminal of GRP is essential for biological activity. These data indicate that biologically active bombesin receptors are present in human glioblastoma cell lines.

Binding, Competitive