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Biomedical subjects

H Bryan

Publications and source records attributed to H Bryan.

9 recordsLinked to original sources

The selective endothelin ETA receptor antagonist BQ123 antagonizes endothelin-1-mediated mitogenesis.

The mitogenic effects of endothelin isopeptides and the selective ETA receptor antagonist BQ123 were evaluated in rat aortic vascular smooth muscle cells. Endothelin-1 (ET-1) and endothelin-3 (ET-3) produced concentration-dependent increases in [3H]thymidine incorporation (EC50 = 0.1 and 25 nM, respectively). The ETB-selective agonist sarafotoxin 6c did not produce significant effects on [3H]thymidine incorporation. BQ123 produced selective and concentration-dependent inhibition of ET-1-mediated [3H]thymidine incorporation. These data demonstrate that ET-1-mediated mitogenesis in vascular smooth muscle is mediated by ETA receptors.

Animals

Identification of endothelin receptor subtypes in rat kidney cortex using subtype-selective ligands.

125I-Endothelin (ET)-1 and 125I-ET-3 displayed specific, saturable, and high affinity binding to membranes prepared from rat kidney cortex. Saturation binding experiments using 125I-ET-1 and 125I-ET-3 revealed that 125I-ET-3 binding sites were 40-50% less abundant than 125I-ET-1 binding sites. The dissociation constants (Kd) and maximum binding (Bmax) for 125I-ET-1 and 125I-ET-3 with these membranes were 218 +/- 23 pM and 275 +/- 20 fmol/mg of protein and 207 +/- 19 pM and 113 +/- 17 fmol/mg of protein, respectively. In the presence of 10 nM sarafotoxin 6c, a selective agonist for ETb receptors, 125I-ET-1 binding was decreased by 45-50% and 125I-ET-3 binding was totally abolished, suggesting that approximately 40-50% of kidney cortex ET receptors are of the ETB subtype and that 125I-ET-1 binds to both ETA and ETB receptors with the same high affinity, whereas 125I-ET-3 binds to only ETB receptors with high affinity. In addition, in the presence of BQ123 [cyclo(D-Trp,D-Asp,L-Pro,D-Val,L-Leu)], a selective antagonist for ETA receptors, 125I-ET-1 binding was decreased by 50%, whereas 125I-ET-3 binding was unaffected. Our results strongly suggest that rat kidney cortex contains ETA and ETB receptors in a 50:50 ratio and that sarafotoxin 6c and BQ123 are valuable tools in identifying the subtypes of ET receptors in various tissues.

Amino Acid Sequence

Postnatal lung growth after repair of diaphragmatic hernia.

The lungs of two patients who died eight months and 64 months after repair of a left-sided diaphragmatic hernia on the first day of life were examined. Lung volumes were appropriate for the size of the children, and the ratio of right lung volume to left lung volume was also normal in both patients. The lungs, however, were grossly abnormal with evidence of enlargement and destruction of respiratory tissue. The left lung was affected more than the right in both subjects. In one patient the total number of alveoli in the lungs was similar to that of normal children of the same age, but this was because the right lung had more than twice as many alveoli as the left lung. It appears that alveolar multiplication is impaired after repair of diaphragmatic hernia. The number of bronchioles was reduced in the infant with very few alveoli, and there may have been too few bronchioles in the other patient.

Child, Preschool

Cis-diamminedichloroplatinum (NSC-119875) in childhood malignancies: a Southwest Oncology Group study.

Children with malignancies resistant to conventional therapy were treated with cis-diamminedichloroplatinum (PDD), 15 to 20 mg/m2, given daily by rapid intravenous infusion for 5 days at 3-wk intervals. Eleven of 24 children with acute lymphocytic leukemia (ALL) received two or more courses; among these no remissions occurred. Fifty-four children with solid tumors were treated: 25 neuroblastoma, 9 rhabdomyosarcoma, 4 Ewing sarcoma, 2 testicular embryonal carcinoma, 2 retinoblastoma, and 12 miscellaneous tumors. One complete remission, 3 partial remissions, and 2 improvements were observed in children with neuroblastoma. One girl with metastatic osteogenic sarcoma achieved a partial remission. One child with metastatic testicular embryonal carcinoma showed improvement. The side effects were vomiting controlled by antiemetics in 26 children and transient elevations of serum creatinine and BUN in 14 children. Nineteen of 39 children with solid tumors, who received more than one course of PDD, had moderately severe myelosuppression caused by PDD. In summary, PDD is a promising agent in neuroblastoma, osteogenic sarcoma, and testicular embryonal carcinoma, and an ineffective agent in ALL. The effect of PDD on other types of solid tumors should be evaluated in the future.

Adolescent

Dose-response relationships between amino acid intake and blood levels in newborn infants.

The objective of the present investigation was to investigate the nature of the blood amino acid response with amino acid intake in newborn infants. Forty-nine newborn infants of 640 to 4020 g birth weight and 26 to 40 weeks gestational age were placed on one of the following regimes within 48 hr of birth: intravenous dextrose with intravenous feeding of three levels of crystalline amino acid mixture, or of one level of casein hydrolysate, or with oral feeding of two levels of milk formula. Blood amino acid levels at 132 hr after feeding of graded levels of the intravenous amino acid solution were evaluated by regression analyses and compared to blood levels when casein hydrolysate was fed intravenously or milk formula was fed orally. At low levels of amino acid intake, such as were achieved with formula feeding, blood levels were relatively unchanged. However, with higher intakes, as were obtained with intravenous feedings, blood levels increased at rates which could be defined for each amino acid. This observation suggests that if the composition and rate of delivery of an amino acid solution is known, blood levels may be predicted.

Age Factors

Mutilating lawn mower injuries in children.

Serious injuries from riding power mowers were sustained by 18 children. Eleven children were passangers on the mower and fell into its path. The injuries required an extensive number of hospitalizations and reconstructive procedures. Fifteen patients suffered considerable residual deformities. Operating riding power mowers in the vicinity of children must be actively discouraged.

Accidents, Home