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Biomedical subjects

A Bennett

Publications and source records attributed to A Bennett.

At least 181 records · Page 10Linked to original sources

Biosynthetic methionyl human growth hormones is biologically active in adult man.

The acute effects of synthetic methionyl human growth hormone produced by recombinant DNA technology were compared with those of pituitary human growth hormone in 22 healthy male volunteers. Both caused increases in somatomedin and triglycerides and decreases in blood urea nitrogen and cholesterol. By all indices measured, synthetic methionyl human growth hormone was equipotent with pituitary human growth hormone. The ability to make biologically active synthetic human growth hormone creates an essentially unlimited supply of growth hormone for the treatment of hypopituitarism and for the study of additional therapeutic indications.

Blood Urea Nitrogen↗

Increased survival of cancer-bearing mice treated with inhibitors of prostaglandin synthesis alone or with chemotherapy.

In mice with a transplantable mammary carcinoma, treatment with the prostaglandin-synthesis inhibitors flurbiprofen or indomethacin produced various beneficial effects. Survival time after excision of the transplanted tumour was increase, particularly when the drugs were given with the chemotherapeutic agents methrotrexate and melphalan, and there were more disease-free survivors. The combined treatment with flurbiprofen also gave less tumour recurrence at the excision site. Flurbiprofen did not seem to alter the bioavailability of the chemotherapeutic agents.

Adenocarcinoma↗

Prostaglandins and human lung carcinomas.

Lung primary carcinomas and normal tissue from 136 patients have been extracted for prostaglandins, and the findings examined in relation to histology. In most cases, tumours yielded more prostaglandin-like material (PG-lm), as judged by bioassay, than did normal tissue from the same lungs. Amounts varied with tumour types, in the following ascending order: small-cell carcinomas, large-cell undifferentiated carcinomas, well-differentiated squamous carcinomas, poorly-differentiated adenocarcinomas, poorly differentiated squamous carcinomas, and well-differentiated adenocarcinomas. Tumour PG-lm was highest when necrosis or the neutrophil content of the tumours were moderate, whereas PG-lm from normal lung tissue correlated with the number of macrophages. Chromatography indicated the presence of various prostaglandins, in agreement with our recent findings using gas chromatography--mass spectrometry.

Adenocarcinoma↗

Pinane thromboxane A2 analogues are non-selective prostanoid antagonists in rat and human stomach muscle.

1 Pinane thromboxane A2 (PTxA2) and its epi-OH isomer were studied on rat and human stomach longitudinal muscle. 2 PTxA2 (0.5 micrograms/ml) usually caused a slight contraction of rat gastric fundus. Contractions to PGE2, PGF2 alpha, PGI2 and epoxymethano analogues of PGH2 (U-46619 and U-44069) were substantially inhibited, whereas those to PGD2 and acetylcholine were only slightly reduced. 3 In human stomach, PTxA2 0.5 micrograms/ml rarely stimulated the muscle. Contractions to PGE2, PGF2 alpha and U-46619 were antagonized, with little effect on those to acetylcholine. 4 epi-PTxA2 (0.5 micrograms/ml) did not affect rat gastric tone. It was moderately potent against PGI2 on rat gastric fundus, but was less effective than PTxA2 against U-44069.

Acetylcholine↗

Both human pituitary growth hormone and recombinant DNA-derived human growth hormone cause insulin resistance at a postreceptor site.

We have investigated the effects on carbohydrate metabolism of human GH produced by recombinant DNA technology (methionyl-hGH) compared with pituitary hGH. Twelve normal adult male subjects received four daily im injections of either methionyl-hGH or pituitary hGH in a double blind, crossover study. Oral glucose tolerance tests and assays of insulin binding to peripheral monocytes were performed before th initial administration and 12 h after the fourth injection of both hGH preparations. Both methionyl-hGH and pituitary hGH resulted in significant carbohydrate intolerance, with a rise in fasting plasma glucose from 96.6 +/- 2.9 to 105.9 +/- 3.0 mg/ml (mean +/- SEM) after pituitary hGH and from 96.2 +/- 1.5 to 107.5 +/- 3.3 mg/dl after methionyl-hGH (P less than 0.01). The area under the glucose tolerance curve increased by 34% after pituitary hGH and by 37% after methionyl-hGH. With both hGH preparations, carbohydrate intolerance was associated with marked hyperinsulinemia, with a rise in fasting plasma insulin levels from 9.4 +/- 1.2 to 33.2 +/- 7.8 microU/ml after pituitary hGH and from 7.4 +/- 1.1 to 45.8 +/- 11.1 microU/ml after methionyl-hGH (P less than 0.01). The integrated plasma insulin levels during the oral glucose tolerance test tripled after both hGH preparations. The pronounced insulin resistance could not be attributed to an alteration in insulin receptor concentrations. Both hGH preparations were associated with small reductions in insulin binding to monocytes at tracer concentrations, but the decline in binding was not statistically significant. The calculated binding sites per cell and Ke were not significantly altered by hGH administration. We conclude that methionyl-hGH and pituitary hGH are indistinguishable in their ability to induce insulin-resistant carbohydrate intolerance. This decrease in insulin sensitivity cannot be attributed to an alteration in insulin binding, and presumably represents a postreceptor defect in insulin action.

Adult↗

Somatomedins in pregnancy: a cross-sectional study of insulin-like growth factors I and II and somatomedin peptide content in normal human pregnancies.

To explore the role of the somatomedins (SM) during human pregnancy, we have measured plasma levels of insulin-like growth factor I (IGF-I), IGF-II, and SM peptide content (SMPC) in 79 women in various stages of normal pregnancies. IGF-I and IGF-II were measured by specific RIAs, and SMPC was measured by a radioreceptor assay using human placental membranes. IGF-I and SMPC rose during pregnancy, showing a significant positive correlation with the length of gestation. Plasma levels of IGF-I in the third trimester averaged 324 ng/ml, a 33% increase over the first trimester average of 243 ng/ml (P less than 0.05). Although IGF-II did not correlate with the length of gestation, the third trimester average was significantly higher than the first trimester average (780 vs. 630 ng/ml; P less than 0.05). After delivery, both IGF-I and IGF-II levels rapidly dropped to levels significantly below those seen in the third trimester. The gestational rise in SMPC and plasma levels of both IGF-I and IGF-II supports the hypothesis that SM play a role in the regulation of fetal growth.

Adolescent↗

Reactions of women to intrapartum fetal monitoring.

The present study examined the reactions of women to routine intrapartum fetal monitoring at a medical center and at a community hospital. Positive responses were found in an interview and on a questionnaire developed from interviews reported in prior studies. Women believed they understood the purpose of the monitor and used it for various purposes in labor. Some differences in reactions to intrapartum fetal monitoring were found to be based on particular characteristics of the women in each setting.

Adolescent↗

Plasma prostaglandins in mucositis due to radiotherapy and chemotherapy for head and neck cancer.

Patients with head and neck cancer were treated with synchronous radiotherapy and chemotherapy (vincristine, bleomycin and methotrexate). Before treatment, mucositis was absent and low amounts of prostaglandin-like material were extracted from peripheral plasma. As treatment proceeded mucositis occurred, and its degree correlated with the amount of prostaglandin-like material extracted from the plasma. Some patients were given moderate doses of drugs which inhibit prostaglandin synthesis, but mucositis still occurred.

Adult↗

Vocational disability and rehabilitation in multiple sclerosis.

Multiple sclerosis represents a significant cause of vocational disability among young and middle age adults. As a group, M.S. patients are frequently well educated, highly trained and possess intact families but have had to leave their former occupations. While many unemployed M.S. patients are willing and able to work, they are not now receiving the vocational rehabilitation services they need to reenter the work force. Physicians frequently see M.S. patients, but they do not often refer those patients for vocational rehabilitation services. Unemployment associated with multiple sclerosis is a significant social complication of the disease. While the physician cannot cure or halt the progress of the disease, he or she can assist the M.S. patient in obtaining the specialized help necessary to re-enter the job market.

Adolescent↗

Metabolites of arachidonic acid formed by human gastrointestinal tissues and their actions on the muscle layers.

1. Gas chromatography-mass spectrometry demonstrated the presence of arachidonic acid (AA), 6-keto-prostaglandin F1 alpha and thromboxane B2 (TxB2) in all extracts of homogenized muscle or mucosa from human stomach, terminal ileum or sigmoid colon. Prostaglandin D2 (PGD2), PGE2 or PGF2 alpha were usually found more often in the mucosal extracts. The 12-hydroxy-derivative of AA (12-HETE) was detected in all extracts of the colon but in only some of the other tissues. 2. Most prostanoids tested contracted the longitudinal muscle, the order of potency being U-46619 (an epoxymethano analogue of PGH2) greater than PGE2 greater than PGF2 alpha greater than PGD2; PGI2 usually caused relaxation, whereas its breakdown products or TxB2 had weak and variable effects. 3. U-46619 or, less potently, PGF2 alpha contracted the circular muscle, whereas PGI2 and usually PGE2 caused relaxation. PGD2, 6-keto-PGF1 alpha, 6,15-diketo-PGF1 alpha or TxB2 usually had little or no effect. 4. PGI2 antagonized contractions to some excitatory prostanoids, without greatly affecting contractions to acetylcholine. 5. For both muscle layers there was a gradient in sensitivity to prostanoids along the gastrointestinal tract. The sensitivities were stomach greater than distal ileum greater than sigmoid colon. 6. The results are discussed in relation to gastrointestinal physiology and pathophysiology.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗