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Biomedical subjects

M C Shah

Publications and source records attributed to M C Shah.

11 recordsLinked to original sources
PubMed2000

Human skeletal myosin heavy chain genes are tightly linked in the order embryonic-IIa-IId/x-ILb-perinatal-extraocular.

Myosin heavy chain (MyHC) is the major contractile protein of muscle. We report the first complete cosmid cloning and definitive physical map of the tandemly linked human skeletal MyHC genes at 17p13.1. The map provides new information on the order, size, and relative spacing of the genes. and it resolves uncertainties about the two fastest twitch isoforms. The physical order of the genes is demonstrated to contrast with the temporal order of their developmental expression. Furthermore, nucleotide sequence comparisons allow an approximation of the relative timing of five ancestral duplications that created distinct genes for the six isoforms. A firm foundation is provided for molecular analysis in patients with suspected primary skeletal myosinopathies and for detailed modelling of the hypervariable surface loops which dictate myosin's kinetic properties.

3' Untranslated Regions↗
PubMed1996

Rapid agonist-induced internalization of the 5-hydroxytryptamine2A receptor occurs via the endosome pathway in vitro.

The mechanism by which agonists induce 5-hydroxytryptamine2A (5-HT2A) receptor internalization was investigated in a clonal cell line stably transfected with the 5-HT2A receptor cDNA. Confocal laser microscopy of immunolabeled 5-HT2A receptors in control (untreated) cells demonstrated that most of the immunoreactivity was associated with the cell surface. After quipazine administration, a significant increase in intracellular immunofluorescence was measured. Time course studies demonstrated rapid agonist-dependent internalization of 5-HT2A receptors, with significant internalization occurring as early as 5 min after agonist administration at 37 degrees. In GF-62 cells, agonist-induced internalization was blocked by preincubation with the 5-HT2A receptor antagonist ketanserin. Internalization was also temperature sensitive because agonist-induced internalization did not occur at 4 degrees. Dual-label experiments disclosed that 5-HT2A and transferrin receptors were internalized via the same endocytotic vesicles. These results suggest that 5-HT2A receptors and transferrin receptors are internalized via the endosomal pathway in GF-62 cells. Although 5-HT2A receptors were internalized, down-regulation, or loss of radioligand binding sites, did not occur. Our results demonstrate that agonists rapidly induce 5-HT2A receptor internalization via the endosomal pathway and that internalization can be dissociated from down-regulation.

3T3 Cells↗
PubMed1994

Use of supercritical fluid extraction for sample preparation of sustained-release felodipine tablets.

Supercritical fluid extraction (SFE) was shown to be an accurate and precise alternative to liquid extraction for sample preparation of sustained-release felodipine tablets (5 mg potency) while realizing an 80% reduction in solvent consumption. Extractions of felodipine spiked on an inert support were used to evaluate the solubility of felodipine in CO2 as well as analyte trapping after SFE. Even though the pure drug was found to be soluble in pure CO2, extractions of felodipine from the tablet matrix required moderate modifier concentrations [8.7% (v/v) methanol in CO2] in order to overcome strong matrix-drug interactions. Sequential static/dynamic extraction steps were also required to quantitatively recover the drug from the tablet matrix, indicating that the drug extraction was diffusion-limited. Average recoveries (n = 5) for the optimized SFE method were determined to be 4.93 mg felodipine tablet (98.6% claim) with an RSD of 1.2% versus those for the liquid extraction procedure (n = 5, 4.98 mg/tablet, 99.6% claim, 2.4% RSD). Similar levels of drug degradation (0.12% expressed as felodipine) were also obtained with both the traditional liquid extraction and with the SFE method.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Hazards of small amounts of heparin in a patient with subclinical vitamin K deficiency.

The use of small amounts of a dilute solution of heparin (less than or equal to 100 IU) to keep indwelling intravenous needles or catheters patent for intermittent venous access either for intravenous therapy or timed blood sampling is a common clinical practice. It is considered safe since the amount of heparin required is much less than that required for heparinization. Herein, we describe a 13-yr-old patient with malabsorption who developed clinically significant bleeding shortly after a diagnostic test which required multiple small injections of heparin for intermittent venous access (total amount of heparin administered was 600 units over 5 hr). The coagulopathy was corrected by a single dose (10 mg) of parenteral vitamin K. As our patient had multiple risk factors for the development of vitamin K deficiency including malabsorption, decreased food intake, and antibiotic use, we postulate that the small amount of heparin precipitated the coagulopathy by increasing the antiprotease activity of antithrombin III on abnormal factors X and II formed in the vitamin K deficient state. We would therefore recommend administration of vitamin K to patients who are at risk of developing vitamin K deficiency before using even small amounts of heparin.

Adolescent↗