Biomedical subjects
Publications and source records attributed to J Hinson.
Neuropeptide Y (NPY) stimulates the hydrolysis of inositol phospholipid in rat brain miniprisms. The stimulation was two-fold in the frontal cortex and in the hippocampus, and 1.5-fold in the striatum. NPY produced no significant effects on basal inositol monophosphate levels in hypothalamic miniprisms. However, those basal levels were much higher than in the other brain regions.
Between 1976 and 1986, 64 patients with rectal adenocarcinoma who were considered unresectable or had prognostic signs suggestive of high risk for local failure received preoperative adjuvant therapy. They were treated with pelvic irradiation (40 Gy) combined with 5-fluorouracil (5-FU) and mitomycin-C, followed by surgery. All had definitive resections resulting in 12.5% of operative specimens free of tumor and only 26.5% containing nodal metastases. The projected 5-year disease-free survival rate is 64% with an actuarial survival of 68%. No mortality or severe morbidity has been observed. Combined modality therapy is a safe and effective regimen for those rectal tumors in the high risk category.
Of 43 rectal carcinomas, initially presumed to be modified Dukes' stage A or B-1, 42 were examined with computed tomography (CT) prior to endocavitary treatment or surgery in 40 cases. The CT correctly showed 28 patients to have early stages and incorrectly showed 2 to have perirectal extension. Three patients had anal neoplasms. The remaining 10 patients had disease stage B-2 or higher and CT was not good for staging them. A CT scan can fairly accurately stage rectal carcinomas stage A and B-1 grouped together, and is doing better in predicting the prognosis than digital palpation when histologic sections show well or moderately well-differentiated adenocarcinoma of the rectum.
The structural requirements in the ACTH molecule for evocation of the glycolytic response in suspensions of mouse adrenal cells were investigated by examining the effects of analogues containing modifications at positions 8, 9 and 10 and of peptides containing homologies with the amino-terminal segment of ACTH. Introduction of a nitrophenylsulphenyl (NPS) group into the tryptophan moiety at position 9 of ACTH(1-24) greatly reduced both the potency and the capacity for maximal glycolytic response. It also virtually abolished cyclic AMP formation. In contrast, the capacity for a maximal steroidogenic response remained unimpaired in the NPS derivative, although steroidogenic potency was reduced to 0.4% of that of ACTH(1-24). Replacement of the tryptophan moiety with phenylalanine had intermediate inhibitory effects on glycolysis and steroid output; replacement with alanine virtually abolished both these responses. Replacement of arginine in position 8 with lysine in the Phe9 analogue caused a fifty-fold increase in glycolytic potency, but rendered it steroidogenically inactive. Cyclic AMP production was abolished in the Ala9 analogue and greatly impaired in the Phe9 and Lys8,Phe9 analogues. Replacement of the glycine moiety in position 10 with L-alanine, D-alanine, beta-alanine or alpha-aminoisobutyric acid had little or no effect on steroidogenic or glycolytic capacity, although potency was reduced with all substitutions excepting L-alanine.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of shortening the ACTH molecule from either end of the peptide chain on adrenal glycolysis and steroidogenesis were examined in mouse adrenal cell suspensions. Shortening the (1-24) sequence to (1-17), (1-16) and (1-14), thereby interfering with the basic tetrapeptide (15-18) assigned to the address message, progressively reduced both glycolytic and steroidogenic potencies by four, six and ten orders of magnitude respectively, without impairing the capacity for maximal excitation. The glycolytic potency of the (1-18) sequence, which was amidated at the C-terminal, equalled that of ACTH (1-24), but the steroidogenic potency was reduced by an order of magnitude. The (1-13) sequence of alpha-MSH, which contains substitutions at both terminals, had glycolytic and steroidogenic potencies intermediate between those of ACTH(1-16) and ACTH(1-17). Deletion of Ser1,Tyr2 from ACTH(1-18)-NH2 reduced both potencies by an order of magnitude. ACTH(11-24) and (7-38) were inactive or inhibitory. The capacity for excitation was further examined by comparing responses to peptide fragments (1-4), (1-10), (1-13), (4-10), (4-11), (5-10), (5-14), (7-13) and (11-24) at a concentration of 1 mmol/l. All fragments, excepting (1-4), (5-10) and (11-24) were active. The activities of fragments (5-14) and (7-13), as opposed to (5-10), suggest that the requirements for methionine in position 4 may be replaced by the (11-13) tripeptide.(ABSTRACT TRUNCATED AT 250 WORDS)
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The effects of the dibutyryl derivatives of cyclic GMP and cyclic AMP on lactic acid and steroid production were compared in intact mouse adrenal glands at concentrations of 0.5-1 mmol/l and in mouse adrenal cell suspensions at concentrations of 0.01-1 mmol/l. The dibutyryl derivative of cyclic GMP had little or no effect on lactic acid production in either tissue preparation. It caused a slight stimulation of corticosteroid output in intact glands at a concentration of 1 mmol/l, amounting to one-tenth of the response observed with 1 mM-dibutyryl cyclic AMP. Dose-dependent increases in lactic acid and steroid production were obtained with dibutyryl cyclic AMP in cell suspensions. AMP and GMP increased lactic acid but not steroid production. All the substrates tested (glucose, glucose-6-phosphate, fructose, fructose-6-phosphate, fructose-1,6-diphosphate, 10 mmol/l; pyruvate and glycerol, 20 mmol/l) stimulated basal glycolysis in intact glands and cell suspensions and none affected basal steroid production significantly. By far the greatest increase in lactic acid production was noted with fructose-1,6-diphosphate. However, only glucose and, in unsectioned glands, pyruvate exerted a potentiating effect on the glycolytic response to ACTH. Glucose potentiated the steroidogenic response to ACTH also, but only in intact glands. The relative ineffectiveness of dibutyryl cyclic GMP is in accord with the species-dependent differing responses to the free form of the cyclic nucleotides noted in mouse and rat adrenal glands. The substrate requirements are in keeping with a rate-limiting role of phosphofructokinase and an action of ACTH at some site between the entry of glucose into the cell and the formation of fructose-1,6-diphosphate.
The medical problems associated with cocaine ingestion, most notably cardiovascular side effects, have become evident as its use has become epidemic in the United States. Its effects on pregnancy and the developing fetus are similarly being recognized as more women of childbearing age are abusing cocaine. A case of placental abruption at 33 weeks' gestation following cocaine use is reported. A review of the pharmacodynamics, medical complications, teratogenic potential and effects in pregnancy is included.