PubMed Health⌕ Search

Biomedical subjects

J R Turtle

Publications and source records attributed to J R Turtle.

At least 91 records · Page 5Linked to original sources
PubMed1985

Familial hyperinsulinemia complicated by extreme insulin resistance during pregnancy: a probable postreceptor defect.

Detailed studies of a family with hyperinsulinemia are reported. The index patient, a 30-yr-old woman with polycystic ovary syndrome, presented with gestational diabetes which was completely resistant to insulin in the presence of severe endogenous hyperinsulinemia. Sensitivity to insulin was regained after delivery. Therapy with cyproterone acetate and ethinyl estradiol for hirsutism exacerbated the hyperinsulinemia toward the levels occurring in pregnancy, with a concomitant deterioration of glucose tolerance. Five other members of her family also were found to have hyperinsulinemia together with high concentrations of circulating C-peptide. Antibodies to insulin and to insulin receptors were not detected, insulin antagonists were not increased, and insulin degradation in the circulation was normal. Insulin extracted from the patient's serum was identical to normal insulin by the criteria of Sephadex chromatography, placental membrane insulin receptor binding, and stimulation of 2-deoxyglucose uptake in isolated rat adipocytes. Although [125I]insulin binding to erythrocytes of all family members and to the patient's placental membranes was markedly reduced, binding to fibroblast cultures from the patient was normal. Insulin-stimulated glucose transport in these fibroblasts also was normal, but there was a mild (20%) reduction in the concentration of cytochalasin B-binding sites in erythrocyte ghosts. Insulin resistance in this family may be due to a partial defect distal to the insulin receptor. This is asymptomatic unless metabolic stresses (pregnancy or steroid administration) are superimposed.

Adult↗
PubMed1985

Organ culture of human foetal pancreas: conditions which affect basal and stimulated insulin release.

Human foetal pancreas has been maintained in organ culture with net synthesis and release of insulin for up to 60 days. The age of the donor foetus affected the basal insulin release rate. A plateau of secretion was reached with foetuses of greater than or equal to 16 weeks of gestation. Explants cultured within 2 h of expulsion following prostaglandin induced termination secreted 3.0 times more insulin after 20 days of culture than those cultured within 2-4 h and 8.1 times more than those cultured more than 4 h post-termination. A high oxygen environment was toxic to the explants during culture. Fresh tissue responded to a high concentration of glucose (19.3 mM) with a small but significant increase in insulin secretion. The addition of 10 mM theophylline caused a major increase in insulin release. Cultured tissue did not respond to glucose alone but did not show increased insulin release following stimulation with glucose (22 mM) together with theophylline (10 mM) in static incubation. The culture of human foetal pancreatic tissue may be useful in maintaining responsive beta cells and may help to ensure an adequate amount of donor tissue for future transplantation into diabetic patients.

Carbon Dioxide↗
PubMed1985

The effects of cyclooxygenase and lipoxygenase inhibitors on the collagen abnormalities of diabetic rats.

The importance of cyclooxygenase and lipoxygenase pathways in the determination of collagen abnormalities in diabetes was investigated. Pharmacological agents with antiprostaglandin activity, such as indomethacin, naproxen, and aspirin, were able to prevent the rise in thermal rupture time of tail collagen in diabetic rats. Paracetamol was without effect. The action of indomethacin on diabetic collagen was abolished by concurrent administration of sodium benoxaprofen, an inhibitor of lipoxygenase, to the diabetic rats. Collagen abnormalities in diabetes may be regulated by a balance of the cyclooxygenase and lipoxygenase pathways. Antiprostaglandin agents may have a role in the prevention of some diabetic complications.

Acetaminophen↗
PubMed1985

Typing of human fetal organs for the histocompatibility antigens A, B and DR.

In the transplantation of human fetal pancreatic explants into diabetic man, the importance of matching the histocompatibility antigens of donor and recipient to decrease the chances of rejection is unknown. Before this question can be answered human fetuses must be tissue typed. We have shown that lymphocytes harvested from fetal liver, thymus, bone marrow and spleen can be successfully HLA DR typed in 64% and A and B typed in 57% of 58 fetuses aged 15 wk or more. Typing should ideally be carried out on unseparated T and B cells. Best results were achieved if all four of the above organs were available and more than one million viable cells were able to be harvested for typing. Whilst the DR antigens could be typed from all tissues, the A and B antigens could be typed, with few exceptions only from thymus, spleen and bone marrow. The efficacy of matching the histocompatibility antigens of recipient and donor fetuses, especially the DR antigens can now be tested in the human diabetic being transplanted with pancreatic explants.

Diabetes Mellitus↗
PubMed1984

The effect of body weight and the fatty acid-oxidation inhibitor 2-tetradecylglycidic acid on pyruvate dehydrogenase complex activity in mouse heart.

The proportion of pyruvate dehydrogenase complex in the active, dephosphorylated form was decreased (compared with lean controls) in heart muscle in gold thioglucose-treated obese hyperinsulinaemic mice, and the extent of enzyme inactivation was significantly linearly correlated with both body weight and body fat content. A single oral dose (25 mg/kg body wt.) of the beta-oxidation inhibitor 2-tetradecylglycidic acid to obese animals restored pyruvate dehydrogenase complex activity to that of lean controls. It is suggested that increased fatty acid oxidation may be a major factor in mediating the phosphorylation and inactivation of pyruvate dehydrogenase complex in mouse heart muscle in obesity, and this may represent an important mechanism in the development and/or expression of insulin resistance in respect of abnormalities of cellular glucose homoeostasis in these animals.

Adipose Tissue↗
PubMed1984

Control of insulin receptor affinity by a Ca2+-sensitive binding site.

Calcium (Ca2+) increased insulin-receptor binding in both membrane and solubilised receptor preparations. Ca2+ increased both receptor affinity and initial rate of association of [125I]insulin to the receptor preparations. Ca2+ had no effect on insulin receptor number in either receptor preparation. The effect of Ca2+ on affinity could be mimicked by ions with similar ionic radii and properties (e.g., Ba2+, Mg2+ and Sr2+). EDTA and oleic acid reduced insulin binding and receptor affinity and these effects were reversed by the addition of Ca2+. These studies suggest that Ca2+ and Ca2+-like ions may bind to a site on or near the receptor and may be responsible for a conformational change with a consequent increase in receptor affinity.

Calcium↗
PubMed1984

Young's syndrome. Obstructive azoospermia and chronic sinopulmonary infections.

We studied 29 men with Young's syndrome, a combination of obstructive azoospermia and chronic sinopulmonary infections. Men with this syndrome have only mildly impaired respiratory function and normal spermatogenesis; the azoospermia is due to obstruction of the epididymis by inspissated secretions. The diagnosis is based on the occurrence of chronic sinopulmonary infections, persistent azoospermia, normal spermatogenesis, and characteristic epididymal findings, as well as exclusion of cystic fibrosis and the immotile-cilia syndrome. The sperm themselves appear to be normal in Young's syndrome. Pregnancies had occurred in five couples; in three paternity was documented by genotyping. Thus, improved microsurgical and medical therapy might restore fertility. We suggest that Young's syndrome has a prevalence comparable to that of Klinefelter's syndrome and is a common cause of both chronic sinopulmonary infection and azoospermia.

Adult↗
PubMed1984

Proportion of active dephosphorylated pyruvate dehydrogenase complex in heart and isolated heart mitochondria is decreased in obese hyperinsulinaemic mice.

The proportion of active, dephosphorylated, pyruvate dehydrogenase complex was decreased in the mouse heart by obesity (by 56%), and this decrease in enzyme activity persisted during preparation and extraction of heart mitochondria. Phosphorylation and inactivation of pyruvate dehydrogenase may be a major factor in mediating the inhibitory effects of obesity on glucose oxidation in muscle, and this may represent an important mechanism in the development and/or expression of cellular insulin-resistance.

Animals↗
PubMed1984

The effects of aldose reductase inhibition on nerve sorbitol and myoinositol concentrations in diabetic and galactosemic rats.

The interrelationship between sorbitol excess and myoinositol deficiency in the peripheral nerve was examined in acutely diabetic rats. Nerve myoinositol concentration was also studied in galactosemic rats. Polyol pathway blockade with Sorbinil (Pfizer, Connecticut) prevented nerve myoinositol reduction in both groups of animals. This conclusion was independent of alteration in the fluid content of the peripheral nerve. It is likely that myoinositol loss from nerves is causally related to the sorbitol and galactitol accumulation.

Aldehyde Reductase↗
PubMed1984

Testicular function in potential sperm donors: normal ranges and the effects of smoking and varicocele.

Testicular exocrine (semen analysis) and endocrine (plasma LH, FSH, prolactin and testosterone) function was assessed in 119 consecutive healthy men presenting for screening as potential sperm donors. Since these volunteers were unbiased with respect to their fertility status, this sample of the general male population was suitable to determine normal ranges and the influence of a variety of physical (height, weight, standardized body weight, varicocele) and demographic (age, marital and fertility status, tobacco and alcohol consumption) factors on normal human testicular endocrine and exocrine function, without the confounding effects of bias in selection of subjects. The statistical distribution of all seminal parameters was non-gaussian, but cube-root transformation of the data normalized the distribution, allowing for parametric statistical analysis. The median (and 95% confidence limits) for the various semen parameters was 73.0 (10.6-235.3) million sperm per ml; 189.0 (12.6-868) million sperm per ejaculate; 50.4 (5.9-181.9) million motile sperm per ml; 133.0 (6.9-661.7) million motile sperm per ejaculate; 54.0 (7.0-172.9) million morphologically normal sperm per ml and 138.5 (7.5-672) million morphologically normal sperm per ejaculate. Testicular volume was correlated positively with measures of physique such as standardized body weight (r = 0.25, P less than 0.01) and body surface area (r = 0.30, P less than 0.002), and negatively with plasma levels of FSH (r = -0.31), P less than 0.002) but not LH. Sperm output was positively correlated with testicular volume (r = 0.28, P less than 0.005) and negatively correlated with plasma FSH (r = -0.31, P less than 0.002) and plasma LH (r = -0.31, P less than 0.002). Smoking was associated with a highly significant reduction in sperm output and motility. Men with varicocele (25%) were significantly taller, had slightly lower haemoglobin levels and moderate left (but not right) testicular atrophy, but neither seminal nor hormonal parameters were different from men without varicocele. There was no difference in any markers of human testicular function between men according to marital or fertility status, grades of moderate alcohol consumption or the presence of low titres of sperm antibodies.

Adult↗
PubMed1984

Ovarian function after renal transplantation: comparison of cyclosporin A with azathioprine and prednisone combination regimens.

Ovarian function was assessed in 24 women after renal transplantation who were treated either with cyclosporin A (10 patients) or with a combination of azathioprine and prednisone (14 patients) as immunosuppressive therapy. The different regimens were not associated with any differences in clinical or endocrine indices of ovarian function (LH, FSH, prolactin, testosterone, oestradiol, dehydroepiandrosterone sulphate). Excessive hair growth was common in both treatment groups. Levels of testosterone and dehydroepiandrosterone were higher in cyclosporin-treated women but this was due to prednisone-induced suppression of adrenal androgen output in the azathioprine- and prednisone-treated women. Excessive hair growth was present in postmenopausal women on both treatments suggesting that hypertrichosis is a consequence of renal transplantation and is not a specific side-effect of cyclosporin A therapy.

Adult↗
PubMed1984

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

Two hundred and thirty two women with diabetes complicating pregnancy were seen at a metropolitan teaching hospital during a 4-year period. Management during pregnancy in insulin dependent diabetics was directed towards strict metabolic control using conventional insulin regimens and diet. A similar programme was followed for women in whom screening revealed glucose intolerance. Control of maternal blood glucose levels, assessment of fetal maturity and modes of delivery were reviewed in an attempt to define factors which could predict optimal neonatal outcome. Patients with insulin dependent diabetes were less likely to have optimal metabolic control both during pregnancy and parturition than patients with gestational diabetes. Women with gestational, but not preexisting diabetes, demonstrated a close correlation between gestational age and parameters of fetal pulmonary maturity. A high rate of intervention to deliver infants in both groups (50%) was noted. These data indicate the need for meticulous care of women with insulin dependent diabetes during pregnancy.

Adolescent↗
PubMed1984

Rat growth hormone (GH) but not prolactin (PRL) induces both GH and PRL receptors in female rat liver.

This study was designed to elucidate which hormone is responsible for the induction of GH and PRL receptors in rat liver. Intact female rats were implanted with osmotic minipumps delivering rat GH (rGH) or ovine GH (oGH) or PRL at various rates from 75 to 800 micrograms/day for 7 days, and binding of radioiodinated bovine GH or ovine PRL (oPRL) tracer was measured on liver microsomal membranes. MgCl2 treatment was used to remove bound hormones from receptors before tracer binding. Infusion of rGH resulted in a significant increase (P less than 0.001) in both GH and PRL binding, the effect being maximal (2.5- to 3-fold for both ligands) at rGH infusion rates from 150 to 400 micrograms/day. Serum rGH levels were elevated 3- to 5-fold in these animals, but somatomedin-C concentrations were not higher than in controls. MgCl2 treatment showed that GH, but not PRL, binding sites in rGH-treated animals were significantly occupied by administered hormone. Analysis of competitive binding curves indicated that receptors for both GH and PRL increased in concentration without changes in binding affinity. In contrast to the rGH effect, oGH infusion from 75 to 400 micrograms/day failed in two experiments to consistently alter either bovine GH or oPRL binding sites. This was not explained by the potency of the preparation at the somatogenic receptor; oGH was in fact more potent than rGH. The effects of rat PRL and oPRL infusion on receptor levels were also assessed. In contrast to previous reports, neither preparation caused induction of either PRL or GH binding sites. oPRL decreased PRL binding by 30-40% when infused between 200 and 400 micrograms/day, whereas rat PRL had a less consistent effect. MgCl2 stripping of membranes suggested that administered PRL preparations did not significantly occupy PRL receptors. GH receptors were unaffected in any PRL-treated group. It is concluded that in intact female rats, rGH regulates the concentration of both GH and PRL receptors. The slight down-regulation of PRL receptors resulting from PRL infusion casts further doubt on the concept that PRL induces its own hepatic receptors.

Animals↗
PubMed1984

Immunoreactive somatomedin-C/insulin-like growth factor I and its binding protein in human milk.

Milk contains cell growth factors, but somatomedin-C/insulin-like growth factor I has not previously been identified. Acid-ethanol extracts of fresh human milk samples displaced somatomedin-C tracer from the specific somatomedin-C antiserum Tr4 parallel to standard. In samples obtained between days 1 and 9 postpartum, highest levels [17.6 +/- 10.4 (+/- SD) ng/ml; n = 7) were found in day 1 samples; these fell to stable levels of 6-8 ng/ml over the next several days. Sephadex G-200 chromatography of fresh 1- to 2-day-postpartum milk samples revealed immunoreactive peaks of approximately 150,000 and 40,000 mol wt, accounting for about 80% of the immunoreactivity; the remainder corresponded in elution volume to free somatomedin-C. On chromatography of the high molecular weight fractions in 1 M acetic acid, most of the immunoreactivity shifted to the position of somatomedin-C. Milk samples stripped of their endogenous somatomedins by ion exchange chromatography at low pH specifically bound somatomedin-C tracer in proportion to the amount of added protein up to 20% binding. Displacement of tracer by unlabeled somatomedin-C indicated an association constant of about 1 X 10(10) liter/mol. Fresh milk incubated with somatomedin-C tracer and fractionated by neutral gel chromatography bound the tracer predominantly in the 40,000 mol wt region, which was abolished when excess unlabeled peptide was included in the incubation. These results indicate that fresh human milk contains immunoreactive somatomedin-C, of which a significant proportion is not protein bound at neutral pH. Somatomedin-C may account for some of the mitogenic activity of milk reported by others. The role of this activity in neonatal growth is unknown.

Carrier Proteins↗
PubMed1984

Pharmacokinetics of gonadotropin-releasing hormone: comparison of subcutaneous and intravenous routes.

Pulsatile administration of GnRH has been used to stimulate gonadal function in both hypogonadotropic men and women; however, deficient responses were observed with the sc in contrast to the iv route of hormone delivery. To clarify whether this was due to altered bioavailability, we compared the pharmacokinetics of these two routes of GnRH administration by bolus injection and steady state continuous infusion methods. Synthetic GnRH was administered by both sc and iv routes to 14 hypogonadotropic patients (11 women and 3 men) as a bolus (5 micrograms in 25, 100, or 250 microliters, sc, and 250 microliters, iv; n = 6) or by continuous iv or sc infusion (3.17 micrograms/h for 6 h; n = 11). In single dose studies, plasma immunoreactive GnRH (IR-GnRH) peaks were earlier and higher (400 vs. 93.5 pg/ml) and returned to baseline sooner (less than 60 vs. greater than 120 min) after iv than after sc bolus injection. Plasma IR-GnRH levels were lower between 1 and 5 min, but higher between 30-90 min after sc injection compared with iv bolus injection. During the continuous infusions, plateau levels of IR-GnRH between 2 and 6 h were 34% lower with sc delivery (67.5 vs. 102.4 pg/ml), indicating irreversible losses of about one third of GnRH injected sc. In patients undergoing pulsatile GnRH therapy delivered by programmed portable minipumps, plasma IR-GnRH profiles were highly damped after sc administration, but retained an intermittent pulse wave form with the iv route. These data suggest that pharmacokinetic differences in the sc and iv routes of GnRH administration are due to a combination of prolonged and delayed absorption with reduced bioavailability of GnRH via the sc route. The consequent damping of the plasma GnRH profiles with sc administration may contribute to differences in the clinical efficacy of pulsatile GnRH regimens, and specific modifications of pulsatile regimens may be required to adapt the physiological requirements of an intermittent plasma GnRH wave form to the damped and reduced bioavailability of sc GnRH therapy.

Adult↗
PubMed1984

Terbium, a fluorescent probe for insulin receptor binding. Evidence for a conformational change in the receptor protein due to insulin binding.

Terbium (Tb3+), an ion of the lanthanide series that has been used as a fluorescent probe for calcium (Ca2+) binding sites in proteins, binds to the proteins in both solubilized and purified human placental insulin receptor preparations. Tb3+ fluorescence was determined directly and the effect of insulin binding on Tb3+-enhanced fluorescence was studied without the need to separate bound and free ligands. Tb3+ behaved similarly to, but was more potent (50-fold) than, Ca2+ in increasing the insulin bound to its receptor. When insulin bound to its receptor, the Tb3+ fluorescence of the receptor preparation decreased. When various insulin analogues were tested, the decrease in Tb3+ fluorescence was proportional to the biologic activity of the insulin analogues. In addition, Tb3+ could be displaced from insulin-sensitive sites by Ca2+, indicating that there were Ca2+ (and Tb3+) binding sites on or near the insulin receptor. These sites, when filled, were responsible for the increased insulin receptor affinity. The decrease in Tb3+ fluorescence after insulin binding may be indicative of a conformational change in the insulin receptor precipitated by the binding of insulin. This conformational change may be related to the release of Ca2+ by insulin binding, is associated with a decrease in insulin receptor affinity, and suggests that an allosteric mechanism involving both Ca2+ and insulin binding sites may be responsible for the observed changes in insulin receptor affinity.

Binding, Competitive↗
PubMed1984

Histologic differentiation of human fetal pancreatic explants transplanted into nude mice.

The transplantation of human fetal pancreas has been suggested as a means of treatment of insulin-dependent diabetes in man. We have obtained human fetal pancreata during the second trimester of pregnancy and transplanted 1-mm3 explants subcutaneously (s.c.) into both diabetic and nondiabetic nude mice, some of the tissue being cultured in vitro before implantation. These implants coalesced and grew. They were removed at intervals up to 37 wk later and showed selective differentiation of endocrine tissue that normally occurs in the fetus and neonate, with formation of bipolar, mantle, and mature islets. There was growth of this endocrine tissue with significantly more islets than in the freshly stained fetal pancreas assuming an average dimension larger than 150 micron, which is the reported mean diameter of a neonatal islet. Duct and fibrous tissue remained viable, but there was no definitive acinar tissue seen. The pancreata uncultured before implantation reached a larger size than that attained by those implants cultured before being transplanted, the difference probably being the amount of ductular and mesenchymal tissue still present. Of those glands cultured before transplantation, the longer the period of culture, the smaller the size the implants reached. Culture beyond 3 wk in vitro made it difficult to macroscopically locate the implant. These data show that, in human fetal pancreas removed from its usual environment, both selective differentiation of the endocrine component and growth of the islets can occur.

Animals↗