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Biomedical subjects

J R Turtle

Publications and source records attributed to J R Turtle.

At least 109 records · Page 6Linked to original sources

The effect of salicylates on nonenzymatic glycosylation and thermal stability of collagen in diabetic rats.

The effects of glucose on the nonenzymatic glycosylation and thermal rupture time of rat tail collagen were examined by (1) in vitro incubation of collagen fibers in glucose and (2) in vivo in diabetic rats. In vitro, glucose caused a dose-dependent rise in both nonenzymatic glycosylation and thermal rupture time and there was a good correlation between these two parameters (r = 0.68, P less than 0.0001). Aspirin, a known inhibitor of nonenzymatic glycosylation, was effective in preventing the glucose-induced rise in nonenzymatic glycosylation and thermal rupture time when present at concentrations of 0.78, 1.56, and 3.12 mM. Sodium salicylate at concentrations of 1.56 and 3.12 mM was also effective. In vivo, the nonenzymatic glycosylation and thermal rupture time of collagen fibers were both increased by 2-3-fold in rats with streptozotocin-induced diabetes of 4 wk duration. Aspirin or sodium salicylate treatment for 4 wk (240 mg/kg/day) from the onset of diabetes was able to prevent the rise in thermal rupture time without affecting nonenzymatic glycosylation of collagen or glycosylated hemoglobin levels. Aspirin or sodium salicylate treatment did not have detectable effect on properties of collagen in normal rats. The in vitro findings are consistent with the hypothesis that nonenzymatic glycosylation leads to the increased thermal stability of collagen fibers. The significance of nonenzymatic glycosylation in vivo is less certain, as thermal rupture time can be altered independently. The action of aspirin and sodium salicylate in vivo suggests new therapeutic options in the prevention and treatment of diabetic complications.

Animals↗

Testicular function after renal transplantation: comparison of Cyclosporin A with azathioprine and prednisone combination regimes.

Testicular function was assessed in 24 men after renal transplantation who were on either Cyclosporin A (CSA) (8 men) or a combination of azathioprine and prednisone (AZP) (16 men) as immunosuppressive therapy. The different regimes were not associated with any differences in clinical or hormonal (LH, FSH, prolactin, testosterone, estradiol) indices of testicular function although adrenal androgen (dehydroepiandrosterone sulphate) was suppressed in prednisone-treated men. Overall, however, poor graft function was associated with abnormal testicular function. Renal allograft function rather than immunosuppressive regime was the major determinant of gonadal function.

Adult↗

The compliance of diabetic patients: relationship between subjective assessment by physicians and objective measurement of patient performance.

During a survey period of 9 months, diabetic patients attending an outpatient clinic were asked routinely by the nursing staff to produce their home urine/glucose monitoring charts and diet charts. If they could not do so, the importance of bringing these charts was explained and they were instructed to bring their charts at subsequent visits. In addition, the individual responses of 109 consecutive patients were monitored as index cases. The physicians of these 109 patients were asked to grade each patient according to their estimate of the patient's compliance. This subjective rating was correlated with the actual performance of the patients in bringing charts. During the survey the overall number of patients attending the clinic who brought urine/blood charts increased from 31% to 59%. The corresponding figures for diet charts were 6% and 21%. Before intervention, the group rated "high compliance" was more likely than the "low compliance" rated group to bring urine/glucose charts. However, after adjustment for this baseline difference the subsequent performances of the high and low rated groups were comparable. These two groups of patients also performed similarly with respect to diet charts. It is concluded that patients judged subjectively to have poor compliance were able to modify their behaviour similarly to those assessed as having good compliance.

Adult↗

Outcome of pregnancy complicated by diabetes: experience with 232 patients in a 4 year period.

The outcome of pregnancy was reviewed in 232 women with diabetes (Group 1 = 72 Insulin Dependent Diabetes; Group 2 = 9 Non Insulin Dependent Diabetes and 151 Gestational Diabetes) seen at a major metropolitan teaching hospital in the 4 yr period 1978-1981 inclusive. The perinatal mortality was 5.6% and there was a high rate of congenital malformations (5.6% major, 7.7% minor) with no difference in incidence between the 2 groups. Infants of women whose pregnancies extended beyond 37 weeks of gestation had a reduced incidence and severity of respiratory distress syndrome. Measurement of amniotic fluid lamellar body phospholipid proved accurate in predicting this complication. Neonatal hypoglycaemia correlated with poor maternal blood glucose control in the third trimester and during parturition.

Abnormalities, Multiple↗

Calcium-dependence of insulin receptor phosphorylation.

Phosphorylation of the insulin receptor of isolated rat adipocytes in response to insulin has been studied. Immunoprecipitation of adipocyte membrane protein demonstrated increased incorporation of 32P after exposure to insulin for 15 min, but this was dependent on the presence of physiological concentrations of Ca2+ and Mg2+. Autoradiography of solubilized immunoprecipitated membrane protein after sodium dodecyl sulphate/polyacrylamide-gel electrophoresis revealed that most of the 32P incorporation occurred in a band corresponding to Mr 95 000, which has been identified previously as the beta-subunit of the insulin receptor. 32P incorporation was inhibited by 2,4-dinitrophenol and trifluoperazine. It is suggested that insulin-receptor phosphorylation is an energy-requiring process that is Ca2+-dependent and may be modulated by calmodulin. Phosphorylation may proceed independently of glucose transport.

Adipose Tissue↗

Non-enzymatic glycosylation of tissue protein in diabetes in the rat.

Non-enzymatic glycosylation of tissue and haemolysate proteins has been studied in normal and diabetic rats by reduction with tritiated sodium borohydride (NaB3H4) alone or in combination with chromatography on m-aminophenylboronic acid coupled to Biogel P-6. With NaB3H4 reduction alone, there was a linear relationship between plasma glucose and tritium incorporation into haemolysate protein. However, increased non-enzymatic glycosylation of tissue protein could not be demonstrated with NaB3H4 reduction alone. Tritiated glycosylated amino acids could be selectively removed by m-aminophenylboronic acid immobilized on Biogel P-6, then eluted by acidification and the radioactivity in the acidic peak used to estimate non-enzymatic glycosylation. Using the combined techniques, an increase in non-enzymatic glycosylation was observed in heart, kidney and liver obtained from rats with diabetes of 18 weeks duration.

Animals↗

The thermal stability of collagen in diabetic rats: correlation with severity of diabetes and non-enzymatic glycosylation.

The thermal stability of collagen fibres from rat tail tendon was studied in both normal and diabetic rats. Results were correlated with the age of the animals, glycosylated haemoglobin level and the degree of non-enzymatic glycosylation of the collagen. Age was found to be the most important single determinant of the thermal rupture time of collagen fibres (r = 0,87, p less than 0.005). Thermal rupture time was also increased in diabetes and showed good correlation with glycosylated haemoglobin (r = 0.69, p less than 0.005) and non-enzymatic glycosylation of collagen (r = 0.51, p less than 0.005). The correlation of glycosylated haemoglobin level and thermal rupture time was significant, independent of age and non-enzymatic glycosylation of collagen. Experiments in vitro showed that incubation of collagen fibres with glucose increased the thermal stability of collagen. These results demonstrated an independent effect of severity of diabetes on the physical properties of collagen. The role of non-enzymatic glycosylation in causing the changes in collagen properties in diabetes remains to be fully elucidated.

Aging↗

Hypogonadism and massive testicular infiltration due to amyloidosis.

We report a case of infertility with bilateral testicular enlargement and hypogonadism due to amyloidosis. Testicular biopsy revealed complete replacement with amyloid and subsequent investigation demonstrated primary hypogonadism with marked elevation of gonadotropins, azoospermia, mild renal failure and lack of progression of generalized amyloidosis during 2 years.

Adult↗

Testicular damage after radioactive iodine (I-131) therapy for thyroid cancer.

Testicular damage was evaluated in twelve men by determination of sperm counts, serum FSH, LH, and testosterone up to 3 1/2 years after treatment with radioactive iodine (131I) therapy for thyroid cancer. Dose-dependent spermatogenic damage with elevation of serum FSH was evident. Full recovery in one and partial recovery in another patient was documented during 2 1/2 years of follow-up. Serial study in two patients documented a small but significant effect of 50 mCi 131I on serum FSH levels and clinically important effects appear to be restricted to men having multiple doses totalling over 100 mCi.

Adult↗

Measurement of insulin binding by erythrocyte ghosts. A method that allows storage without loss of binding characteristics.

The insulin binding of red cell ghosts was studied and found to be similar to insulin binding of the original erythrocyte. Red cell ghosts were stable on storage, and serial samples can be measured in one assay, thus eliminating the problem of interassay variation. Erythrocyte ghosts may be preferable to whole red cells for long-term insulin receptor studies.

Calcium↗

Prevalence, testicular function and seminal parameters in men with sperm antibodies.

A prospective survey of 289 unselected men, attending a male infertility clinic (200 subjects) or as donors presenting for an artificial insemination programme (89 subjects) was performed. High titres of sperm agglutinating antibodies (greater than 1/32) were present only in a group of (6.5%) of infertile men but not in volunteer donors. Low titres occurred with similar frequencies (12%) in both groups. The sperm immobilizing antibody test was less sensitive and more specific but of no additional diagnostic benefit. Patients with high titres of sperm antibodies had evidence of testicular damage with decreased testicular volumes, elevated serum FSH and LH levels and reduced sperm density and motility whereas low titres were not associated with any testicular or seminal pathology. These data suggest a sub-group of infertile men have evidence of spermatogenic damage and impaired sperm function associated with high titres of sperm antibodies. Immunologic infertility in these men may reflect either an underlying autoimmune orchitis or a secondary immune reaction following testicular damage of various causes.

Adult↗

Heterozygote detection in congenital adrenal hyperplasia.

Detection of heterozygote carriers for congenital adrenal hyperplasia by use of a modified tetracosactide (a synthetic corticotropin) stimulation test with prior overnight dexamethasone suppression proved to have a diagnostic accuracy of 95%. Discrimination of heterozygotes from normals was best when we used a criterion based on the ratios of 17 alpha-hydroxyprogesterone to cortisol at baseline and at 30 min after intravenous administration of 250 micrograms of tetracosactide.

17-alpha-Hydroxyprogesterone↗

Induction of somatogenic receptors in livers of hypersomatotropic rats.

Male and female Wistar-Furth rats bearing the pituitary tumor MtT/W15 had serum GH and PRL levels several hundred-fold higher, and immunoreactive somatomedin levels 3-fold higher, than those of controls. The presence of tumor appeared to have no effect on specific binding of radioiodinated bovine GH to liver microsomal membranes in male animals, and to decrease specific binding by 78% in females. However, after desaturating receptors by treatment with 3.2 M MgCl2 for 5 min, bovine GH binding to membranes from tumor-bearing males was 3-fold higher than in normal males, while in tumor-bearing females binding was more than twice as high as in normal females. Competitive binding curves showed the induced receptors to be specific for growth hormones, and thus somatogenic in nature. This study indicates that a high degree of occupancy of GH receptors in hypersomatotropic rat liver does not cause their down-regulation. The mechanism of receptor induction is unknown.

Animals↗

The measurement of glycosylated hemoglobin in man and animals by aminophenylboronic acid affinity chromatography.

Glycosylated hemoglobin (GHb) was estimated in normal and diabetic human, rat, and dog hemolysate by m-aminophenylboronic acid (PBA) affinity chromatography and the results compared with the values determined using two ion-exchange (ION-E) methods and a colorimetric thiobarbituric acid (TBA) method. There was a good correlation between the values estimated by PBA and both ION-E chromatography methods for the human samples (r = 0.83, P less than 0.0002, r = 0.86, P less than 0.002). In diabetic rat and dog hemolysates, PBA chromatography demonstrated higher glycosylated hemoglobin than in normal hemolysate. In both species, there was an excellent correlation between the PBA-estimated GHb and plasma glucose levels (rat r = 0.79, P less than 0.001; dog r = 0.67, P less than 0.003). The ION-E and TBA methods were not as effective in separating diabetic from normal samples and correlated less well with plasma glucose levels. PBA chromatography relies on the interaction of m-amino phenylboronate with the hydroxyl groups of the glucose residues attached to hemoglobin. It is not affected by intra- or interspecies variations in the hemoglobin moiety and should be adaptable for measurement of GHb in a number of laboratory animals and in patients with hemoglobinopathy. It is not affected significantly by temperature and may offer advantages over the ION-E method in the routine determination of human glycosylated hemoglobin.

Animals↗

The effect of aldose reductase inhibition on motor nerve conduction velocity in diabetic rats.

This study examined the effects of an aldose reductase inhibitor (CP 45634, Sorbinil, Pfizer, New York, New York) on the neuropathy of streptozotocin-induced diabetic rats. Sorbinil treatment for 4 wk reduced sciatic nerve sorbitol concentration and improved motor nerve conduction velocity in diabetes of 2-9 mo duration. It remains to be determined whether Sorbinil can prevent chronic diabetic neuropathy.

Aldehyde Reductase↗

Dexamethasone suppression of adrenocortical function.

To investigate the potency of dexamethasone in suppressing adrenocortical function, we gave various evening doses to laboratory staff members. Plasma corticotropin, cortisol, and dehydroepiandrosterone sulfate concentrations were measured the following day, to quantitate the degree of suppression after both short- and long-term treatments. We found that the minimum amount for effective suppression was 1 mg for a single evening dose, 0.5 mg per day for a long-term evening dose. On these regimens plasma corticotropin and cortisol were consistently suppressed, but plasma dehydroepiandrosterone sulfate was suppressed only with long-term treatment.

Adrenal Cortex↗

Radioimmunoassay for somatomedin C: comparison with radioreceptor assay in patients with growth-hormone disorders, hypothyroidism, and renal failure.

We raised an antiserum (Tr4) in rabbits against a basic somatomedin C-like peptide preparation. Using high-immunoreactivity somatomedin C tracer, we compared the performance of radioimmunoassays in which we used the Tr4 antiserum and a well-characterized somatomedin C antiserum distributed by the National Pituitary Agency (NPA) with that of the human placental-membrane somatomedin radioreceptor assay (RRA). In their cross reactivity toward various somatomedin-like and unrelated peptides, the two radioimmunoassay methods were almost identical, although NPA antiserum, with about fourfold higher titer than Tr4 antiserum, showed a slightly greater sensitivity for most peptides tested. Radioimmunoassay of acid-ethanol-extracted plasma samples from normal persons and acromegalic, hypopituitary, hypothyroid, and renal-failure patients revealed no analytical differences between the antisera (for 122 samples, r = 0.979 between methods). Somatomedin values for acromegalic and hypopituitary samples showed no overlap with normals. Values for hypothyroid and pre-dialysis renal-failure samples were significantly lower than normal. By comparison, the RRA showed greater cross reactivity toward some somatomedin-like peptides and gave significantly lower values than radioimmunoassay for acromegalic and hypothyroid plasma extracts, and significantly higher value for hypopituitary and renal-failure samples. We conclude that the radioimmunoassay methods clearly are of greater diagnostic value than RRA for clinical somatomedin measurement.

Acromegaly↗