Wolfram syndrome not HLA linked.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
C A Stanley
Publications and source records attributed to C A Stanley.
Effect of tri-iodothyronine replacement on the metabolic and pituitary responses to starvation.
To determine the implication of decreased T3 production during fasting, seven normal men were fasted for 80 hours on two occasions; they received 5 microgram of T3 every three hours durnig the second fast. The mean serum T3 concentration declined during the control fast from 120 to 73 ng per deciliter (P less than 0.01), but remained slightly above base-line values during the T3 fast. Mean serum T4 concentrations did not change, and mean serum rT3 concentrations increased, during both fasts. The peak serum TSH increment after TRH was 11.1 micromicron per milliliter before fasting, 8.9 (not significant) after the control fast and 2.2 (P less than 0.01) after the T3 fast. Urea excretion was 9.1 per cent higher during the T3 fast; there were no differences in the changes in blood glucose, plasma fatty acids or other substrates during the two fasts. Pretreatment with potassium iodide lowered serum T4 concentrations and increased the serum TSH response to TRH after fasting. We conclude that the decrease in serum T3 concentrations during fasting spares muscle protein. Fasting is accompanied by a lower set point of TSH secretion, which remains sensitive to changes in serum thyroid hormone concentrations.
Adult↗
Metabolic fuel and hormone responses to fasting in newborn infants.
To examine why newborn infants frequently cannot maintain adequate levels of plasma glucose in the interval between delivery and the time they are first fed, circulating metabolic fuel and regulatory hormone concentrations were determined in 44 healthy infants at the end of an eight-hour postnatal fast. Plasma glucose fell below 40 mg/100 ml prior to eight hours in four of 24 term-appropriate-for-gestational-age (AGA), two of nine preterm-AGA, five of six term-small-for-gestational-age (SGA), and three of five preterm-SGA infants. Fuel and hormone patterns in the premature and SGA infants were not different from those found in term-AGA infants. Results in these neonates differed in two areas from the response to fasting seen later in life. In fasted term-AGA infants, ketones were low (beta-hydroxybutyrate 0.29 +/- 0.04 mM/liter) despite elevated concentrations of fatty acid precursors (1.4 +/- 0.07 mM/liter), and the group of infants studied failed to demonstrate the increase in plasma ketones with lower glucose levels (r = ".23, P = .07) which is found in older children. Levels of glucose precursors were two to three times higher in term-AGA infants (lactate 2.9 +/- 0.2 mM/liter; alanine 0.48 +/- 0.02 mM/liter) than levels found beyond the neonatal period and, in contrast to older children and adults, were not diminished in infants with lower plasma glucose (lactate, r = -.28, P less than .035; alanine, r = -33, P less than .02). These differences between the responses to postnatal fasting and those seen beyond the neonatal period suggest that the capacity for both hepatic ketone synthesis and gluconeogenesis is not fully developed at birth.
Adaptation, Physiological↗
Pancreatic adenomas in infants and children: current surgical management.
Islet cell adenomas are an important consideration in infants and children with hypoglycemia due to hyperinsulinism. Between 1965 and 1977, 32 patients with hyperinsulinism were seen at the Children's Hospital of Philadelphia. Sixteen of these patients underwent surgery. Eight patients had single pancreatic adenomas, 5 of whom were infants under 1 yr of age. In 3 infants an adenoma was recognized and removed at the time of surgery. In 4 patients a subtotal pancreatectomy was successful in removing the adenoma. One infant is whom the adenoma was not included in the subtotal pancreatectomy died postoperatively with intractable hypoglycemia. Of the 7 patients cured by surgery, 6 are normal and 1 has brain damage due to delay in treatment of hypoglycemia. One child has mild diabetes. A combined medical and surgical protocol has been developed that permits rapid diagnosis of hyperinsulinism and selection of candidates for surgery. Infants under 1 yr of age who fail to respond to diazoxide should be explored. In children whose hyperinsulinism appears beyond 1 yr of age, surgery is indicated, since an adenoma is likely.
Adenoma, Islet Cell↗
Sex differences in binding of human growth hormone to isolated rat hepatocytes.
Since liver is a target for growth hormone action, binding of 125I-labeled human growth hormone to enzymatically isolated rat hepatocytes was studied. Specific binding was shown with hepatocytes from both male and female animals. There was a single class of receptors for human growth hormone on cells from males (affinity constant, Ka = 1.16 x 10(9) liters/mole; sites per cell, q = 6200). In males, bovine growth hormone was almost as potent as human growth hormone in displacing bound 125I-labeled human growth hormone, while ovine prolactin was about 1000 times less potent. Cells from female rats bound more 125I-labeled human growth hormone than cells from males. The cells from females contained at least two classes of receptors for human growth hormone. The receptor of highest affinity had the same affinity for human growth hormone as the single receptor found in males (Ka = 0.96 x 10(9) liters/mole). However, there were three to four times as many of these receptors per cell in females (q = 21,000). In females, bovine growth hormone and ovine prolactin were both about 20 times less potent than human growth hormone. Treatment of male rats with estrone produced cells that show the same binding characteristics as females. These results indicate that human growth hormone binds to a somatogenic receptor in hepatocytes from male rats. In females and estrogen-treated males, the receptors that bind human growth hormone recognize lactogenic as well as somatogenic properties. This suggests that the lactogenic and growth-promoting effects of human growth hormone in the rat are mediated by different receptors.
Animals↗
Characterization of somatogenic and lactogenic binding sites in isolated rat hepatocytes.
Suspensions of rat hepatocytes isolated enzymatically by the method of Berry and Friend were used to study the binding of 125I-labeled human (hGH) and bovine (bGH) growth hormones and ovine prolactin (oPRL). Displacement of these labeled hormones by their unlabeled analogues was analyzed by means of Scatchard plots and affinity constants (K) and the number of binding sites per cell (q) were calculated. Specificity of binding was studied using hGH, bGH oPRL and rat growth hormone (rGH) and rat prolactin (rPRL). Rat hepatocytes contained two types of binding sites which bound hGH. The first, somatogenic, was specific for the growth-promoting hormones bGH and rGH. The second, lactogenic, was specific for lactogenic hormones, oPRL and rPRL. Human GH, which has both lactogenic and growth-promoting properties in rodents, bound to both sites. The somatogenic binding sites were present in both males and females, and the number of sites was similar in females and in males and was not affected by hypophysectomy. The lactogenic binding sites were present only in females, and the number of lactogenic and somatogenic sites was similar (40,000/cell). The affinity of hGH for the lactogenic binding sites was less than for the somatogenic (0.37 X 10(9) vs. 1 X 10(9)M-1). The lactogenic binding sites were lost when female rats were hypophysectomized and could not be restored by estrogen treatment.
Animals↗
Hyperinsulinism in infants and children: diagnosis and therapy.
Explore the source record for details and available documents.
Adult↗
Hyperinsulinism in infancy: diagnosis by demonstration of abnormal response to fasting hypoglycemia.
The metabolic adaptation to fasting in infants with hyperinsulinism was examined to see whether a characteristic abnormality could be found that would aid in the diagnosis of this disorder. Seven infants under 1 year of age with hyperinsulinism were studied; 7 control infants of similar age and 12 children with ketotic hypoglycemia served as contrast groups. At the time of hypoglycemia, four of the seven infants with hyperinsulinism did not have elevated levels of insulin. However, levels of beta-hydroxybutyrate were significantly lower in the infants with hyperinsulinism than in the control and ketotic hypoglycemic groups. Levels of free fatty acids were also lower in the infants with hyperinsulinism. Expected levels and normal limits for beta-hydroxybutyrate, insulin, and free fatty acids when plasma glucose is below 40 mg/100 ml were estimated by combining the control and ketotic hypoglycemic groups. Using these values as standards, the diagnosis of hyperinsulinism can be made by evaluation of the response to fasting hypoglycemia. The application of this approach is illustrated by three case examples.
Blood Glucose↗
Accidental poisoning with 50 per cent glucose solution: the danger of large stock bottles.
Explore the source record for details and available documents.
Brain↗
Determination of the equilibrium constants of associating protein systems. 3. Evaluation of the weight fraction of monomer from the weight-average partition coefficient (application to bovine liver glutamate dehydrogenase).
Explore the source record for details and available documents.
Animals↗
Medium-chain and long-chain acyl CoA dehydrogenase deficiency: clinical, pathologic and ultrastructural differentiation from Reye's syndrome.
The clinical and pathologic findings in 12 patients with medium-chain acyl CoA dehydrogenase deficiency and three patients with long-chain acyl CoA dehydrogenase deficiency are summarized. Although these inborn errors of intramitochondrial beta-oxidation of fatty acids present with similar findings to Reye's syndrome, there are clinical, laboratory and hepatic histologic differences. Younger age at presentation, history of unexplained sibling death, a previous episode of lethargy, hypoglycemia or acidosis precipitated by fasting stress and only mildly elevated serum transaminases with normal or only mildly prolonged prothrombin time may all suggest an acyl CoA dehydrogenase deficiency. Long-chain acyl CoA dehydrogenase deficiency is differentiated from medium-chain acyl CoA dehydrogenase deficiency by younger age at presentation, more profound cardiorespiratory depression, evidence of cardiomyopathy, and sequelae of muscle weakness, hypotonia and developmental delay. Definitive diagnosis is made by assay of medium-chain or long-chain enzyme activity in cultured skin fibroblasts or in leukocytes. Hepatic light microscopic alterations are essentially limited to steatosis, which may be either macro- or microvesicular. The cases with microvesicular steatosis can be differentiated morphologically from Reye's syndrome by electron microscopy, showing the absence of the mitochondrial changes characteristic of Reye's. Four of seven cases of acyl CoA dehydrogenase deficiency showed some variations from normal in the appearance of the hepatocyte mitochondria. The relationship of these variations to the basic metabolic defect(s) remains to be determined.
Acyl Coenzyme A↗
Aberrant mRNA splicing associated with coding region mutations in children with carnitine-acylcarnitine translocase deficiency.
This report describes three infants with genetic defects of carnitine-acylcarnitine translocase (CACT), an inner mitochondrial membrane carrier that is essential for long-chain fatty acid oxidation. Two of the patients were of European and Chinese origin; the third was from consanguineous Turkish parents. CACT activity was totally deficient in cultured skin fibroblasts from all three patients. Patient 1 was heterozygous for a paternal frameshift mutation (120 del T in exon 1) and a maternal lariat branch point mutation (-10 T --> G in intron 2). Patient 2 was heterozygous for the same lariat branch point (-10T --> G intron 2) mutation, derived from the father, and a maternal frameshift mutation (362 del G in exon 3). Patient 3 was homozygous for a frameshift mutation (306 del C in exon 3). All of the three frameshift mutations give rise to the same stop codon at amino acid residue 127 which is predicted to cause premature protein truncation. In addition, cDNA transcript analysis showed that these coding sequence mutations also increase the amount of aberrant mRNA splicing and exon skipping at distances up to 7.7 kb nucleotides from mutation sites. The data suggest that the stability of mRNA transcripts is decreased or the frequency of aberrant splicing is increased in the presence of CACT coding sequence mutations. These results confirm that CACT is the genetic locus of the recessive mutations responsible for the fatal defects of fatty acid metabolism previously associated with deficiency of translocase activity in these three cases.
Carnitine Acyltransferases↗
Pancreatic venography and plasma ketone measurements in the diagnosis of hyperinsulinism.
Preoperative localization of an insulinoma was possible using a technique of transhepatic pancreatic venography, with measurement of insulin levels in six pancreatic veins. Surgical exploration confirmed the presence of an insulinoma at the site predicted by venography. Peripheral plasma insulin levels were only minimally elevated at the time of hypoglycemia. However, complete suppression of ketogenesis during a 74-hour fast was observed, and felt to be a biological marker for hyperinsulinism. These observations suggest that transhepatic pancreatic venography and the measurement of plasma ketones in addition to glucose and insulin during fasting, may be useful supplementary studies in the evaluation of patients with fasting hypoglycemia.
Adult↗
Postmortem recognition of fatty acid oxidation disorders.
With an appropriate protocol for collection, storage, and sample analysis, it should be possible to ensure correct diagnosis of disorders of fatty acid oxidation presenting to the pathologist. Appropriate counseling of affected families will lead to presymptomatic sibling diagnosis of these frequently treatable disorders, which, in turn, can prevent the catastrophic metabolic consequences of the disorders.
Autopsy↗