Molecular analysis of cystinosis: probable Irish origin of the most common French Canadian mutation.

Infantile nephropathic cystinosis, an autosomal recessive disease characterized by a lysosomal accumulation of cystine, presents as failure to thrive, rickets and proximal renal tubular acidosis. The cystinosis gene, CTNS, which maps to chromosome 17p13, encodes a predicted 55 kDa protein with characteristics of a lysosomal membrane protein. We have conducted extensive linkage analysis in a French Canadian cystinosis cohort identifying a founding haplotype present in approximately half (21/40) of the chromosomes studied.

The influence of K(+)-induced membrane depolarization on insulin secretion in islets of lean and obese (ob/ob) mice.

The present study was undertaken to determine whether factors that affect K+ permeability produce differences in insulin secretion in the islets of obese versus lean mice. At basal glucose (3 mM), the obese islets secreted more insulin for a given increment in depolarizing K+ concentration and responded to a wider range of K+ concentrations (5-45 mM) than the lean islets (5-25 mM). In contrast, the membrane potential changes induced by increments in pK+ were not significantly different in the two types of islets.

Infant feeding practices and socio-demographic factors in Ottawa-Carleton.

Parents of 320 infants 6-18 months of age were interviewed to determine infant feeding practices and socio-demographic factors contributing to parental choices. 76% of women breastfed initially. Social class was directly related to the incidence of breastfeeding.

Abnormal regulation of cAMP accumulation in pancreatic islets of obese mice.

The present study was undertaken 1) to determine whether a defect in the regulation of adenosine 3',5'-cyclic monophosphate (cAMP) accumulation was present in the beta-cell of the ob/ob mouse, 2) to determine how such a defect, if present, would alter the regulation of insulin secretion in these islets, and 3) to find out if epinephrine had similar effects on insulin secretion and cAMP production in islets of lean and obese mice. In the obese mouse, inhibitory modulators neither inhibited cAMP accumulation in intact islets nor adenylate cyclase activity in islet homogenates. These anomalies in the modulation of cAMP accumulation were not correlated with a failure to inhibit insulin secretion.

Insect repellent, N,N-diethyl-m-toluamide, effect on ammonia metabolism.

There appear to be at least three mechanisms for systemic reactions to diethyltoluamide. As with most substances, allergy is possible. The ingestion of large doses can produce seizures and coma by a direct action on the CNS.

Different insulin-secretory responses to calcium-channel blockers in islets of lean and obese (ob/ob) mice.

The purpose of these experiments was to determine whether the activity of the voltage-dependent Ca2+ channel was modulated in the same manner in islets of the ob/ob mouse as in islets of homozygous lean mice of the same strain. The effect of agents that are known to alter the concentrations and movements of intracellular Ca2+ were investigated in relation to glucose-stimulated insulin secretion and in relation to the effect of forskolin. In islets of obese mice, verapamil and nifedipine both inhibited glucose-induced insulin release, nifedipine being the more potent inhibitor.

Abnormal regulation of insulin secretion in the genetically obese (ob/ob) mouse.

To determine whether the abnormal insulin-secretory activity encountered in obese mice is due to an anomaly in the production of cyclic AMP, islets of lean and obese mice were incubated with forskolin under various conditions. Our data show that, in addition to the well-known quantitative differences in insulin-secretory activity between islets of lean and obese mice, there are important qualitative differences. The islets of obese mice accumulated less cyclic AMP than did those of lean mice in response to given doses of forskolin, yet their insulin secretion was enhanced to much higher values.

The occult insulinoma operative localization by quick insulin radioimmunoassay.

Hypoglycemia secondary to organic hyperinsulinism in children can be caused by diffuse or localized pancreatic lesions. Differentiation between these two types of lesions is of utmost importance since the surgical approach will be different. Some tumors escape detection by all preoperative investigations including ultrasound, scintiscan, arteriography, and computerized tomography.

Zinc supplementation attenuates insulin secretory activity in pancreatic islets of the ob/ob mouse.

The purpose of this study was to establish whether a relationship may exist between the hyperinsulinemia, the exaggerated insulin secretion, and the resistance to insulin characteristic of the obese-hyperglycemic syndrome and the zinc status of the ob/ob mouse. To this end, mice were given control and zinc-supplemented diets, and the effects of zinc supplementation on insulin secretion in vivo and in vitro as well as on glucose tolerance were studied. These data were compared with those obtained with oxytetracycline treatment, which is known to ameliorate the insulin sensitivity and glucose tolerance of these animals.

Serum enzymes in the BB rat before and after onset of the overt diabetic syndrome.

As part of a six-month prospective study of the effects of neonatal thymectomy in the spontaneously diabetic BB Wistar rat, activities of the following enzymes were determined: alkaline phosphatase (AP), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and UDP-galactosyltransferase (UDPG). In prediabetics, AP and LDH levels were higher than in sham-operated, non-diabetic controls; however, this increase was seen in nearly all diabetes-prone BB rats, diminishing the usefulness of these changes in discerning potential diabetics from asymptomatic, diabetes-prone rats. After onset of the syndrome, there was a striking elevation of AP values in all diabetics with no similar alteration in asymptomatic, diabetes-prone rats suggesting this was a diabetes-related phenomenon.

Control mechanisms in brown adipose tissue plasma membrane.

It is generally agreed that the site of heat production during nonshivering thermogenesis is the brown adipose tissue (BAT) and that the triggering event for heat production is the interaction of noradrenaline (NA) with its receptor on the plasma membrane. Following this initial event, several changes occur which result in increased rates of cAMP synthesis, redistribution of ions across the membrane, enhanced rates of lipolysis, and increased mitochondrial oxidation of substrates. BAT is also a target for the anabolic effect of insulin.

The effects of anxiety management training on the control of juvenile diabetes mellitus.

The present study was designed to determine whether diabetic control could be improved through the direct psychological management of stress and anxiety. Five poorly controlled female adolescent diabetics ranging in age from 15 to 18 years were used as subjects. All were seen on an outpatient basis over a 6-month period.

Insulin secretion in the obese (ob/ob) mouse. The effect of oxytetracycline on insulin release.

The effect of oxytetracycline (OTC) pretreatment on the response of the ob/ob mouse to insulin secretagogues in vivo and in vitro was investigated. With glucose loading in vivo, the peak glucose was twofold greater and the insulin levels threefold greater in obese than in lean mice. After OTC treatment, there was no significant difference an insulin levels between lean and obese mice although the peak glucose level was still obese mice although the peak glucose level was still 1.

Adenylate cyclase activity in brown adipose tissue of the genetically obese (ob/ob) mouse.

The activation of brown adipose tissue adenylate cyclase by catecholamines was studied in genetically obese (ob/ob) and lean mice. In obese mice, the maximum activation of the enzyme by several beta-adrenergic agonists was only two-thirds that in lean mice and, as an activator, noradrenaline was only one-eighth as potent. The adenylate cyclase was also less responsive to guanine nucleotides.

Enzyme immunoassay of gentamicin with the Abbott ABA-100 analyzer.

The enzyme immunoassay of gentamicin using "EMIT" reagents was adapted to take advantage of the small reagent volume required by the Abbott ABA-100. The method increases fourfold the maximum number of tests per kit. The correlation with the bacterial inhibition method was 98%.

A case of accidental inorganic mercury poisoning.

Mercuric chloride was accidentally ingested by a nineteen-month old boy. He exhibited severe symptoms of inorganic mercury poisoning including acute renal failure. The blood mercury level at the time of admission to hospital was 1920 ng/mL.

An improved double antibody radioimmunoassay for the determination of insulin in serum, plasma, and tissue incubation media.

We have modified the double antibody method of insulin radioimmunoassay to allow relatively short incubation periods and the use of centrifugation to separate bound from free insulin. This was achieved by altering the order of addition of reagents and by adding normal guinea-pig serum to reduce nonspecific interactions. The method allows for precise measurements in the range of 0-3.

Oxytetracycline treatment improves the response to insulin in the spontaneously diabetic (BB) rat.

Chronic oxytetracycline treatment was found to alter the diabetic status of the spontaneously diabetic rat (BB rat). The treatment led to lowered plasma glucose levels in the fed as well as in the fasted state. These results indicate that the oxytetracycline treatment was effective in lowering the insulin requirements as well as in improving the handling of glucose.

Autosomal dominant hypoparathyroidism: a proband with concurrent nephrogenic diabetes insipidus.

In this paper we report an extended family with well documented autosomal dominant hypoparathyroidism which was ascertained through a proband with coincident nephrogenic diabetes insipidus. Clinical findings were limited to a slight decrease in overall stature and to clinical signs of hypocalcaemia. Intelligence was normal and two patients were asymptomatic.