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Biomedical subjects

C A Stuart

Publications and source records attributed to C A Stuart.

At least 73 records · Page 4Linked to original sources
PubMed1985

Obesity, acanthosis nigricans, insulin resistance, and hyperandrogenemia: pediatric perspective and natural history.

We studied the syndrome of acanthosis nigricans, obesity, insulin resistance, and hyperandrogenemia in 22 patients. Although isolated case reports in adolescents have appeared, this syndrome has not received full recognition as a pediatric entity. Our patients (17 girls, five boys) had a mean weight 5.7 SD above the mean for age, although mean height was only 0.5 SD above the mean for age. All patients had acanthosis nigricans. Their insulin resistance was significantly greater than that in a control group with comparable obesity. Fasting insulin concentration was 5.25 microU/ml in lean controls, 19.6 microU/ml in obese controls, and 49.8 microU/ml in study patients (P less than 0.002). Mean glucose disappearance rate during an insulin tolerance test was 6.7%/min in lean controls, 5.19%/min in obese controls, and 2.35%/min in study patients (P less than 0.02). After menarche, mean plasma testosterone concentration was 106 ng/dl, compared with less than 50 ng/dl in all lean and obese control patients. Data derived from our series of patients lead us to conclude that (1) this is a genetic syndrome, although the exact mode of inheritance is unclear; (2) the natural history of the syndrome invariably begins with the onset of obesity, followed by acanthosis nigricans that worsens with progressive weight gain; (3) acanthosis nigricans is thus a marker for hyperinsulinemia, which occurs before hyperandrogenemia; (4) hyperandrogenemia occurs only after menarche. Identification of this syndrome should permit monitoring for the development of hyperandrogenemia during puberty and determination of other affected family members.

Acanthosis Nigricans↗
PubMed1984

The somatomedin-C receptor of human placenta.

The binding and physical characteristics of the human placenta somatomedin-C (Sm-C) receptor were investigated and compared with those of the placental insulin receptor. These receptors were found to have many similar properties, but several distinctions exist between them. The two receptors have similar binding properties. Although distinct receptors, as evidenced by specificity studies, the Sm-C and insulin receptors possess similar affinities (10 X 10(9) L/mol and 3 X 10(9) L/mol, respectively) and receptor concentrations (0.4 pm/mg and 0.2 pm/mg) in placental membranes. There is also a low-affinity, high-capacity receptor for each hormone. The intact receptors are indistinguishable in size by three methods. The Stokes radius is 7.2 nm by gel filtration, the sedimentation coefficient is 11S, and the SDS polyacrylamide gel apparent molecular weight is approximately 350,000 daltons. The two receptors differ in their pH optimum for ligand binding, their isoelectric points, and their subunit size. The pH optimum for Sm-C binding is 8.2, and for insulin binding the optimum is 7.9. The isoelectric point for the Sm-C receptor is 4.6, whereas the isoelectric point for the insulin receptor is 4.2. Although the whole receptor and the half receptors for Sm-C and insulin cannot be distinguished by size on SDS gels, the binding subunit for the Sm-C receptor appears to be 8000 daltons smaller than that of the insulin receptor (134,000 v 142,000 daltons). We conclude from these studies that the insulin and Sm-C receptors of human placenta are similar in structure but are distinct entities.

Animals↗
PubMed1984

Passage of cows' milk protein in breast milk.

An enzyme-linked immunosorbent assay has been used to search for lactoglobulin and bovine casein in breast milk. Initial results suggest this may be a simple and useful method for such studies. Detection and prevention of antigen passage could influence the prevalence of atopic disease.

Animals↗
PubMed1984

Size discrepancy between somatomedin-C and insulin receptors.

Somatomedin-C (Sm-C) and insulin receptors have similar size and structure. Each receptor is a heterotetramer composed two alpha- and two beta-subunits. Sodium dodecyl sulfate (SDS)-polyacrylamide gel autoradiographic studies of affinity labeled receptor preparations demonstrated that each has a whole receptor of greater than 350,000 daltons, a half-receptor of 220,000 daltons, and binding subunit (alpha-subunit) of about 140,000 daltons. Using SDS-polyacrylamide disc gels and double labeling techniques, we demonstrated that the 125I affinity labeled alpha-subunit of the Sm-C receptor from human placenta was 8,000 daltons smaller than the 131I affinity labeled insulin receptor alpha-subunit. Further double label studies demonstrated that [125I]insulin and [131I]insulin cross-linked to placental insulin receptors precisely comigrated on SDS-disc gels, indicating that the difference between insulin and Sm-C alpha-subunits is not an artifact of the system. The difference in ligand size (Sm-C, 7,500 daltons; insulin, 5,700 daltons) would minimize the observed difference and is clearly not the cause of the difference in size observed. These studies provide further evidence in support of two functionally and physically distinct receptor molecules for insulin and Sm-C in human placenta.

Affinity Labels↗
PubMed1983

Insulin resistance in patients with myotonic dystrophy.

Evaluation of insulin sensitivity in 12 patients with myotonic dystrophy gave results different from those found in other insulin-resistant conditions. Nine of our subjects were insensitive to exogenous insulin, but only three had elevated fasting insulin concentrations. Eight had an excessive insulin response to a glucose challenge. Monocyte insulin receptor affinity was decreased (myotonics, 1.21 +/- 0.74 X 10(9) liters per mole; controls, 2.62 +/- 1.28 X 10(9)), and this parameter correlated best with the insulin resistance. No circulating receptor antibody or insulin binding inhibitor was found. Our studies suggest that the insulin resistance seen in patients with myotonic dystrophy is related to decreased insulin receptor affinity.

Adult↗
PubMed1982

Cyclic nucleotides and somatomedin action in cartilage.

The role of cyclic nucleotides was evaluated in the stimulation of cartilage metabolism by somatomedin-C (Sm-C). The effects of cAMP and cyclic guanosine monophosphate (cGMP) analogs on matrix synthesis were evaluated. The effects of Sm-C on tissue concentrations of these cyclic nucleotides were investigated. Likewise, the direct effects of Sm-C on the activities of cartilage adenylate cyclase, guanylate cyclase, and phosphodiesterase were determined. We found that tissue concentrations of cAMP in cartilage declined rapidly during organ culture, despite the presence of serum or Sm-C, cGMP concentrations in cartilage declined rapidly during control incubations but were augmented significantly at 30 and 60 min of incubation with the addition of serum or Sm-C. Thereafter, cGMP concentrations declined toward the levels of incubated control cartilages. Sm-C had no effect on phosphodiesterase activity. N6-Monobutyryl cAMP stimulated sulfate uptake, but dibutyryl cGMP did not. Sm-C did not stimulate adenylate cyclase in purified plasma membranes from chondrocytes, whereas it stimulated both plasma membrane and cytosol guanylate cyclase at concentrations of Sm-C as low as 10(-12) M. These data would indicate that cAMP is not the intracellular second messenger for Sm-C in cartilage. The data for cGMP are provocative and suggest it as a candidate for a second messenger mediating a portion of Sm's stimulation of cartilage metabolism.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1981

Physical and hormonal evaluation of transsexual patients during hormonal therapy.

The optimal hormonal therapy for transsexual patients is not known. The physical and hormonal characteristics of 38 noncastrate male-to-female transsexuals and 14 noncastrate female-to-male transsexuals have been measured before and/or during therapy with various forms and dosages of hormonal therapy. All patients were hormonally and physically normal prior to therapy. Ethinyl estradiol was superior to conjugated estrogen in suppression of testosterone and gonadotropins but equal in effecting breast growth. The changes in physical and hormonal characteristics were the same for 0.1 mg/d and 0.5 mg/d of ethinyl estradiol. The female-to-male transsexuals were well managed with a dose of intramuscular testosterone cypionate of 400 mg/month, usually given 200 mg every two weeks. The maximal clitoral length reached was usually 4 cm. Higher doses of testosterone did not further increase clitoral length or suppression of gonadotropins; lower doses did not suppress the gonadotropins. Based on the information found in this study, we recommend 0.1 mg/d of ethinyl estradiol for the noncastrate male-to-female transsexual and 200 mg of intramuscular testosterone cypionate every two weeks for the noncastrate female-to-male transsexual.

Adolescent↗
PubMed1980

Disordered control of thirst in hypothalamic-pituitary sarcoidosis.

We evaluated water metabolism in 11 patients with hypothalamic-pituitary sarcoidosis. Seven patients had abnormal water metabolism: one had partial antidiuretic hormone (ADH) deficiency, one had severe ADH deficiency, one had severe ADH deficiency and deficient thirst, one had only deficient thirst, and three had excessive thirst. In four of the five with thirst disturbances, there was loss of congruence of osmotic thresholds for thirst and ADH release. Five of our patients presented with polyuria and polydipsia, but only two had true diabetes insipidus, whereas three had organic primary polydipsia with adequate endogenous ADH. That disordered thirst resulting in polydipsia was more common than true diabetes insipidus is at odds with previously held views on the prevalence of ADH deficiency in this condition.

Adolescent↗
PubMed1979

The insulin receptor of embryonic chicken cartilage.

Highly purified plasma membranes have been obtained from embryonic chicken cartilage by physical means rather than enzymatic digestion. Rapid and reversible binding of [125I]iodoinsulin to these membranes is demonstrated. Similar to the insulin-binding properties of rat liver and adipocytes and human mononuclear cells, optimal specific binding of insulin to chondrocyte plasma membranes has a sharp pH optimum at 8.0, and maximal binding occurs at 2--4 C. Analysis of equilibrium binding reveals a curvilinear Scatchard plot, whose high affinity segment generates a maximum affinity of 1.0 X 10(9) M-1, and a receptor concentration of 0.4 pmol/mg membrane protein. This affinity constant is similar to those generated for insulin binding to membranes prepared from embryonic chicken liver (2.5 X 10(9) M-1), rat liver (1.4 X 10(9) M-1), and mouse liver (0.6 X 10(9) M-1), whereas the receptor concentration is less than that of embryonic chicken liver membranes (1.1 pmol/mg), which in turn was less than those of rat liver membranes (2.8 pmol/mg) and mouse liver membranes (3.5 pmol/mg). Kinetic studies show augmentation of insulin-receptor dissociation by excess insulin when initial receptor occupancy, is low, suggesting that negative cooperativity is present. There is little or no interaction of other hormones with the chondrocyte insulin receptor, with the exception of proinsulin and the insulin-like growth factors. Porcine proinsulin, bovine proinsulin, somatomedin C, and nonsuppressible insulin-like protein prevent [125I]iodoinsulin binding to chondrocyte plasma membranes with dose-response curves which are parallel to that of unlabeled porcine insulin itself, but with molar potencies relative to porcine insulin of 15%, 9%, 2.5%, and 1.4%, respectively. Porcine insulin and proinsulin both prevent binding of [125I]iodosomatomedin C to chondrocyte plasma membranes but with molar potencies less than 1% that of unlabeled somatomedin C. These observations are consistent with the presence of a specific independent insulin receptor in embryonic chicken cartilage which is similar in its characteristics to the insulin receptor in previously described tissues. Insulin has a weak interaction with the chondrocyte receptor for somatomedin C. Interaction with the somatomedin receptor may be the mechanism by which insulin exerts anabolic effects on cartilage when used in pharmacological amounts.

Animals↗
PubMed1978

Hypothalamic insufficiency: the cause of hypopituitarism in sarcoidosis.

Ten patients with generalized sarcoidosis and hypopituitarism were studied. Six of these 10 patients presented with sarcoid involvement of the optic nerves resulting in asymmetric visual field defects. All patients had deficiencies of two or more anterior pituitary hormones and seven had abnormalities of water metabolism. Despite hypopituitarism, nine patients had a pituitary responsive to the synthetic hypothalamic releasing factors, thyrotropin releasing hormone and gonadotropin releasing hormone, and the tenth patient had a partially responsive pituitary. The demonstration of pituitary responsiveness allows us to infer hypothalamic insufficiency as the major cause for hypopituitarism in these patients. The combination of visual field defects and hypopituitarism in sarcoidosis is a medically treatable condition that simulates the clinical presentation of a pituitary tumor.

Adolescent↗