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Biomedical subjects

W H Daughaday

Publications and source records attributed to W H Daughaday.

At least 91 records · Page 5Linked to original sources
PubMed1981

Angiomatous lymphoid hamartoma: inhibitory effects on erythropoiesis, growth, and primary hemostasis.

An 11-year-old boy was noted to have microcytic anemia, growth retardation, polyclonal hypergammaglobulinemia, and abnormal platelet function. An angiomatous lymphoid hamartoma was removed from the retroperitoneal space. Postoperatively the child exhibited a dramatic growth spurt and complete resolution of the abnormal laboratory measurements. Studies were performed before and after tumor removal to investigate the nature of the associated anemia, growth retardation, and altered hemostasis. There was no evidence of iron deficiency, thalassemia, or an antierythropoietin factor. Prolonged bleeding time and impaired ristocetin-induced platelet aggregation normalized following tumor resection. Serum obtained before surgery inhibited lymphocyte proliferation in mixed lymphocyte culture as well as fibroblast growth in vitro. Detailed study of growth regulatory hormones failed to reveal significant alterations except for significantly reduced somatomedin which normalized after surgery. The factor(s) which inhibit in vitro cellular growth and lower in vivo plasma somatomedin concentration remain unknown.

Adolescent↗
PubMed1981

Plasma somatomedins, endogenous insulin secretion, and growth in transient neonatal diabetes mellitus.

Infants with transient neonatal diabetes mellitus are small for gestational age and fail to thrive postnatally unless insulin is administered. We have measured the concentrations of insulin-related growth factors in an infant girl with this condition to learn if deficiencies in one or more of these factors could be responsible for the impaired growth. Cord blood serum radioimmunoassayable insulin and somatomedin C/insulin-like growth factor I (SMC/IGF-I) were low, but insulin-like growth factor II (IGF-II) measured by a specific radioreceptor assay was normal. Insulin therapy begun on the fourth day of life resulted in a prompt increase in weight and a delayed rise in SMC/IFG-I. No significant changes in IGF-II were observed. After 2.5 months, insulin treatment was discontinued. At that time, endogenous insulin secretion was documented by increased urinary C-peptide. Normal growth and SMC/IFG-I levels persisted. We conclude that growth failure in this condition may be related not only to a lack of insulin but also to SMC/IGF-I deficiency. A deficiency in IGF-II is not involved.

Adult↗
PubMed1981

Plasma somatomedins in children with hyperinsulinism.

Hyperinsulinism has been postulated as a possible stimulus to somatomedin (SM) synthesis by the perfused rat liver and in man. Seven children who presented with severe fasting hypoglycemia and who had documented hyperinsulinism were studied to explore the effect of excessive endogenous insulin secretion on plasma levels of the SMs. Neither the concentration of somatomedin C/insulin-like growth factor-I (SMC/IGF-I) (mean +/- SD, 0.53 +/- 0.37 U/ml) nor that of IGF-II (1.10 +/- 0.58 microgram/ml) was significantly different from values observed in normal children. SMC/IGF-I and IGF-II were inversely correlated. There was a positive correlation between SMC/IGF-I and body weight, and an inverse correlation among IGF-II, body weight, and length. These results suggest that in children with normal GH secretion, hyperinsulinism sufficient to cause severe recurrent hypoglycemia does not result in an increase in either SMC/IGF-I or IGF-II concentrations in plasma.

Child, Preschool↗
PubMed1981

Measurement of insulin-like growth factor II by a specific radioreceptor assay in serum of normal individuals, patients with abnormal growth hormone secretion, and patients with tumor-associated hypoglycemia.

A radioreceptor assay for insulin-like growth factor II (IGF-II) is described in which [125I]IGF-II is bound by rat placental membranes. IGF-I and other insulin-related peptides have less than 1% of the potency of IGF-II in displacing [125I]-IGF-II. IGF-II is extracted from its serum binding protein with a simple acid-ethanol step. After neutralization with Tris base, the extract is introduced directly into the radioreceptor assay. Results are expressed in terms of a reference serum with an assigned potency of 1 U/ml. By this method, serum from normal adults, 20-69 yr of age, had a mean (+/-SE)IGF-II activity of 0.73 +/- 0.03; higher concentrations were noted in adults more than 70 years of age (1.05 +/- 0.05), in cord serum (1.55 +/- 0.24), and in short children with normal GH secretion (0.88 +/- 0.42). In hypopituitary dwarfism, serum IGF-II activity was reduced (0.50 +/- 0.05), but in acromegaly, it was not increased (0.77 +/- 0.06). In 10 of 14 serum samples from patients with tumor-related hypoglycemia, the IGF-II exceeded the normal 95.5% confidence limits. In 8 of these sera, IGF-I by RIA was low, and in 5, it was essentially unmeasurable. These results with a new radioreceptor assay for IGF-II provide additional evidence that the regulation of this serum peptide differs from that of IGF-I.

Acromegaly↗
PubMed1981

Acromegaly and Cushing's syndrome associated with a foregut carcinoid tumor.

We report an 18-yr-old youth with a metastatic foregut carcinoid tumor, Cushing's syndrome, and hypersomatotropic gigantism. Administration of cyproheptadine caused a dramatic fall in urinary cortisol excretion and plasma ACTH levels associated with clinical remission of the Cushing's syndrome. GH secretion was not affected by cyproheptadine administration. Ectopic ACTH secretion was confirmed by RIA of tumor extracts and immunohistochemical demonstration of ACTH-containing cells in hepatic metastases. There were two sources of GH production demonstrated in this patient. Ectopic secretion of GH by the carcinoid hepatic metastases was documented by both RIA and immunohistochemical techniques. A somatotrophic pituitary tumor was also present. The histological characteristics of this tumor suggest adenomatous hyperplasia rather than de novo neoplastic change as the likely mechanism of its pathogenesis. GH releasing factor-like activity was demonstrated in extracts of plasma and in extracts of the carcinoid tumor. We conclude that cyproheptadine exerted an effect on the ectopic ACTH-producing cells but not on the ectopic GH-producing cells or on adenohypophyseal GH secretion. Production of a GH releasing factor-like activity by the carcinoid tumor may have caused the pituitary somatotrophic tumor.

Abdominal Neoplasms↗
PubMed1980

myo-Inositol transport in renal brush border vesicles and it inhibition by D-glucose.

We examined the mechanism of myo-inositol uptake by rabbit renal proximal tubule brush border membrane vesicles and characterized the relationship between the transports of myo-inositol and D-glucose. A 100 mM Na+ electrochemical gradient (extravesicular medium > intravesicular medium) stimulated the initial rate of myo-inositol uptake 20- to 60-fold. Other cation gradients were ineffective. The Na+ myo-inositol co-transport system was shown to be electrogenic. The Na+ electrochemical gradient-dependent uptake of myo-inositol saturated at about 1 mM myo-inositol, with an apparent Km of 94 micro M at an initial 100 mM Na+ gradient. D-Glucose was an inhibitor of the Na+ gradient-dependent uptake of myo-inositol. D-Glucose, but not L-glucose, elicited accelerative exchange diffusion of myo-inositol. myo-Inositol did not significantly inhibit the Na+ gradient-dependent transport of D-glucose. We suggest that D-glucose inhibits myo-inositol uptake by dissipating the membrane potential and sharing the myo-inositol carrier. The inhibition of myo-inositol transport across the brush border membrane by D-glucose explains how glycosuria could produce inosituria in patients with diabetes mellitus.

Animals↗
PubMed1980

Concentration of myo-inositol in skeletal muscle of the rat occurs without active transport.

The cellular uptake of nonphosphorylated myo-inositol (MI) and its incorporation into phosphoinositide in the rat epitrochlearis muscle was measured. Cellular uptake of [2-(3)H]MI was determined by the difference between total uptake and [2-(3)H]MI present in the extracellular fluid determined with [1-(14)C]mannitol. Cellular uptake was parabolic and directly proportional to medium MI concentrations between 25 and 3,200 muM. Saturation of a MI carrier was not evident. Moreover, uptake was not inhibited by 2 mM ouabain, 0.3 mM 2,4-dinitrophenol, or 22 mM glucose. Insulin, 100 mU/ml, was without effect on either cellular uptake of [2-(3)H]MI or its incorporation into phosphoinositides. In muscles that were preloaded with [2-(3)H]MI and then incubated in media that contained a constant amount of MI but no [2-(3)H]MI, 44.3% of the [2-(3)H]MI was released after 10 min increasing to 62.5% by 120 min. Cellular MI concentrations were 0.18 mumol/g wet tissue (four times plasma levels) in rapidly isolated and frozen epitrochlearis muscle. When muscle was incubated without MI, 48% of endogenous MI was lost rapidly. Restoration of cellular MI in 50 muM MI media occurred in two phases, a rapid uptake phase lasting 10 min and a subsequent slow phase of MI uptake. It is concluded that MI enters and leaves skeletal muscle cells freely by a process that does not involve active transport. Neither insulin nor hyperglycemia affected MI transport nor its incorporation into phosphoinositides. The intracellular to medium concentration gradient may be dependent on reversible binding to tubulin and possibly to other intracellular components.

Adenosine Triphosphate↗
PubMed1979

Demonstration and partial characterization of insulin receptors in human platelets.

Recently, evidence has been reported to suggest that human platelets like several other circulating blood cells may bind insulin. To examine whether human platelets contain specific insulin receptors, washed human platelets suspended in Hepes buffer were incubated at 24 degrees C with 125I-insulin in the presence and absence of unlabeled insulin and specific insulin binding was determined. Insulin binding by platelets increased progressively with time of incubation to reach a maximum at 3 h and was proportional to the number of platelets in the incubation mixture. Maximum insulin binding was observed at pH 8. Insulin degradation by platelets as assessed by TCA precipitability and reincubation studies was minimal. Scatchard analysis of the binding data and dissociation studies revealed evidence of negative cooperativity of the platelet insulin receptor. A high affinity dissociation constant of approximately equal to 3 X 10(9) M-1 was determined and the concentration of platelet insulin receptors was estimated as 25 binding sites/micron2 platelet surface area. Binding of 125I-insulin by platelets was inhibited by unlabeled porcine insulin and to a lesser extent by catfish insulin and porcine proinsulin but not by glucagon, prolactin, growth hormone, and thrombin. The findings indicate that human platelets contain specific insulin receptors. The significance of the platelet insulin receptor, particularly with respect to altered platelet function in diabetes mellitus, remains to be determined.

Blood Platelets↗
PubMed1979

Effects of glucose and parathyroid hormone on the renal handling of myoinositol by isolated perfused dog kidneys.

The effects of glucose and parathyroid hormone (PTH) on the transport and metabolism of myoinositol (MI) and [2-(3)H]MI were studied in isolated perfused dog kidneys. Studies during perfusion of kidneys with normal and elevated glucose concentrations demonstrated that under normal conditions the isolated kidney reabsorbed 94.7+/-0.2% of the filtered MI, and the renal production of (3)H-metabolities of MI was 117.9+/-6% of the filtered MI load. This indicated that entry of MI into tubular cells by reabsorption was not the sole pathway for entry into the pool of MI within the kidney undergoing catabolism. High glucose perfusate decreased MI reabsorption to 68.6+/-4.7% and thus decreased delivery of [2-(3)H]MI into the catabolic pool from the reabsorptive pathway. In the high glucose experiments, the rate of [2-(3)H]MI catabolism exceeded [2-(3)H]MI reabsorption by the same fraction as in normal glucose experiments, which indicates that high glucose did not affect nonreabsorptive access of MI to the catabolic site. In contrast to the effects of glucose, PTH administration resulted in an increase in perfusate MI concentration and a decrease in the perfusate [2-(3)H]MI specific activity. Concomitantly, urinary MI and [2-(3)H]MI concentrations were increased, again with a decrease in [2-(3)H]MI specific activity. These results indicate that PTH caused a release of MI into the urine (not the same as decreased MI reabsorption, which would not affect urinary [(3)H]MI specific activity) and into the perfusate of the isolated kidneys. These effects on MI release were about coincidental with the increase in urinary cyclic 3',5'-AMP after PTH and preceded the peak phosphaturic effect of PTH. There was no detectable effect of PTH on MI synthesis from glucose as a source of the MI released into the urine and perfusate. However, PTH temporarily halted accumulation of tritiated MI catabolites. There was no effect of inactivated PTH on urinary cyclic 3',5'-AMP or on MI transport, which indicates that the PTH effect on MI handling was a specific hormonal effect. These studies clarify the renal metabolism of MI, and they demonstrate heretofore unknown effects of PTH on the renal handling and metabolism of MI. The effects of PTH on renal MI metabolism have important implications in renal carbohydrate metabolism and phospholipid turnover.

Animals↗
PubMed1979

The effect of hypophysectomy on rat chorionic somatomammotropin as measured by prolactin and growth hormone radioreceptor assays: possible significance in maintenance of somatomedin generation.

We have previously reported that serum somatomedin concentrations are maintained in pregnant rats after hypophysectomy. Because rat chorionic somatomammotropin (rCS) might replace pituitary GH during pregnancy, the concentration of rCS was measured at intervals after hypophysectomy on day of pregnancy. By day 16 of pregnancy, the serum rCS of hypophysectomized (hypox) rats was actually higher than that of normal pregnant rats when measured by a lactogenic radioreceptor assay. Increased levels of lactogenic radioreceptor activity (L-RRA) were maintained in the serum of hypox rats throughout the remainder of pregnancy. The GH radioreceptor activity (GH-RRA) of serum of hypox pregnant rats was also greater than that of normal rats during the last days of pregnancy, but the activity was only about 1/20th that of the L-RRA with the assays employed. There was no significant difference between placental L-RRA and GH-RRA of normal and hypox pregnant rats. The difference in concentration could not be attributed to differences in the number of fetuses. We conclude that the high levels of rCS were sufficient to maintain serum somatomedin concentration in hypox pregnant rats. This effect of rCS could have been due to binding by GH or PRL receptors of the maternal liver.

Animals↗
PubMed1978

Purification, characterization, and amino acid sequence of rat anaphylatoxin (C3a).

C3a anaphylatoxin derived from the third component of complement has been isolated from rat serum and its complete amino acid seuqence determined. A three-step purification procedure was employed that consisted of gel filtration on Sephadex G-100, followed by chromatography of the anaphylatoxin-containing pool on carboxymethylcellulose. A subsequent separation on DEAE-Sephadex resolved C3a from minor contaminating peptides. Biological studies have shown that purified rat anaphylatoxin is approximately twice as active as human or porcine C3a when tested for smooth-muscle contraction. In addition to the active form of rat anaphylatoxin, a serum carboxypeptidase B inactivated form of C3a (C3ades-Arg) was purified from rat serum and utilized in subsequent structural studies. Sequence analysis of rat C3a was facilitated by a long automated Edman degradation which established the first 55 residues of the anaphylatoxin. Overlapping peptides were generated by cyanogen bromide and trypsin, and the resultant fragments were sequenced by either automated or manual Edman procedures. The primary structure of rat C3a is 70% identical to the previously determined structures of human and porcine anaphylatoxin. Antisera raised to the purified rat peptide do not cross-react immunologically by Ouchterlony analysis with either human or porcine C3a.

Amino Acid Sequence↗