Takuo Ito

A case of Kabuki make-up syndrome with central diabetes insipidus and growth hormone neurosecretory dysfunction

A case of a 6 year old boy with Kabuki make‐up syndrome with central diabetes insipidus and growth hormone neurosecretory dysfunction is reported. Magnetic resonance imaging revealed abnormal findings of the pituitary gland and stalk. Good catch‐up growth was obtained by treatment with growth hormone. These findings suggest that hypothalamic‐pituitary dysfunction might be involved in Kabuki make‐up syndrome.

Insulin-like growth factor I (IGF-I) delays the onset of diabetes in non-obese diabetic (NOD) mice

It has been shown that prophylactic exogenous insulin treatment prevents the development of insulin-dependent diabetes mellitus (IDDM) in animal models and humans. In this study, we examined whether the development of diabetes and insulitis in female non-obese diabetic (NOD) mice could be affected by prophylactic administration of insulin-like growth factor I (IGF-I), which shares structural homology with insulin and has insulin-like metabolic effects. Two experiments which differed in duration and dosage of IGF-I treatment were carried out. In the first experiment, animals were treated from 4 to 9 weeks of age with IGF-I (17.9 nmol/day at 4-5 weeks of age and 35.9 nmol/day at 6-9 weeks of age) and observed up to 34 weeks of age. In the second experiment, the animals were treated from 4 to 34 weeks of age with IGF-I (1.79 nmol/day at 4-5 weeks of age, 3.59 nmol/day at 6-9 weeks of age, and 5.38 nmol/day at 10-34 weeks of age). The former treatment could significantly delay the onset of diabetes (P < 0.05) and decrease the insulitis score at 10 weeks of age (P < 0.01). On the other hand, the latter treatment did not affect the incidence of diabetes, the age at onset or the insulitis score. Our results suggest that the IGF-I treatment at the early age may provide protection against autoimmune beta-cell destruction in NOD mice.

Urinary excretion of human growth hormone in children with short stature: Correlation with pituitary secretion of human growth hormone

Thirty-five children with short-stature underwent insulin-loading and sleep tests for assessment of secretion of human growth hormone. Correlations between the levels of human growth hormone in the serum and urine during the tests were examined to elucidate the clinical significance of urinary human growth hormone levels in short children. The concentration and total amount of human growth hormone in the urine correlated significantly with the peak concentration of serum human growth hormone (r = 0.81, p less than 0.001 and r = 0.80, p less than 0.001, respectively) and the integrated concentration of human growth hormone (r = 0.85, p less than 0.001 and r = 0.85, p less than 0.001, respectively) in the insulin-loading test. The concentration and total amount of human growth hormone in the morning urine also correlated significantly with the peak concentration of serum human growth hormone (r = 0.80, p less than 0.001 and r = 0.70, p less than 0.001, respectively) and the integrated concentration of serum human growth hormone (r = 0.80, p less than 0.001 and r = 0.72, p less than 0.001, respectively) in the sleep test. The concentration or total amount of human growth hormone in the urine differed significantly among children with human growth hormone deficiency, those with nonendocrine short stature, and those with normal stature (p less than 0.05). These data suggest that measurement of human growth hormone in the urine may be used to assess secretion of human growth hormone, serving as a screening test for human growth hormone deficiency in children.

Hypoplastic left heart syndrome with a single coronary artery originating from the pulmonary artery.

A newborn male infant with hypoplastic left heart syndrome due to mitral and aortic atresia died on the third day of life. Autopsy revealed a single coronary artery originating from the pulmonary artery, reversed coarctation of the aorta, a coronary sinus type atrial septal defect and stenosis of the left subclavian artery. To our knowledge, hypoplastic left heart syndrome associated with a single coronary artery originating from the pulmonary artery has never been reported in the English or Japanese literature. This may be the first such case.

Analysis of cytokine mRNA expression in pancreatic islets of nonobese diabetic mice.

Nonobese diabetic mice develop type 1 diabetes in an age-related and gender-dependent manner. Th1 (IFN-gamma and TNF-beta) and Th2 (IL-4 and IL-10) cytokine mRNA expression was analyzed in pancreatic islets isolated from female NOD mice with a high incidence of diabetes and male NOD mice with a low incidence of diabetes. The levels were measured at 5 time points from the onset of insulitis until the development of overt diabetes, using a semiquantitative reverse transcriptase PCR (RT-PCR) assay. IFN-gamma mRNA levels were significantly higher in the islets obtained from females than those of males, from 10 weeks of age. TNF-beta mRNA was expressed in both females and males between 5 and 15 weeks of age. However, TNF-beta mRNA levels were decreased in males at 20 weeks of age. In contrast, IL-4 mRNA levels were lower in females than in males. These results suggest that islet beta-cell destruction and diabetes in female NOD mice correlates with IFN-gamma and TNF-beta production in the islets, and that male NOD mice may be protected from autoimmune beta-cell destruction by down-regulation of these cytokines. Furthermore, our findings also suggest that insulitis and beta-cell destruction are independently regulated: TNF-beta is more important in forming and maintaining the insulitis, while IFN-gamma has a more important role in beta-cell destruction.

Inhibitory effect of amiloride on glucose transport in isolated rat adipocytes

The effect of amiloride on 3-O-methylglucose (3-O-MG) uptake was studied in isolated rat adipocytes to define to what extent amiloride inhibited the process of insulin action or glucose transport. Amiloride (1 mM), which did not change the intracellular water space of adipocytes, inhibited by 43.3% the insulin-stimulated uptake of 3-O-MG, while it did not appear to inhibit the basal uptake. To distinguish the inhibitory effect on glucose transport activity from that on the process of insulin action, the effect of amiloride was evaluated in the transport system using adipocytes deprived of ATP, in which glucose transporters were considered immobile. Amiloride (1 mM) inhibited this transport by 32.8% in an insulin-stimulated state, which was obtained using adipocytes that had been treated with 20 nM insulin and exposed to 2 mM KCN, whereas it did not inhibit the transport system at the basal state. In the inhibitory effect, 76% was thus attributable to the inhibition of glucose transport activity recruited by insulin and 24% to the inhibition of the action of 20 nM insulin itself. These results indicate that amiloride can not be used as a specific inhibitor of the insulin action itself.

An immunopotentiator of β-1,6;1,3 d-glucan prevents diabetes and insulitis in BB rats

The preventive effect of an immunopotentiator, beta-1,6;1,3 D-glucan, on the development of diabetes and insulitis was studied in BB rats. The intravenous administration of 1 mg kg-1 week-1 of beta-1,6;1,3 D-glucan from the age of 4 weeks decreased the cumulative incidence of diabetes from 43.3% (13/30) to 6.7% (2/30) (P less than 0.005) and also the incidence of insulitis from 82.4% (14/17) to 26.3% (5/19) at the age of 20 weeks (P less than 0.002). Eight of nine rats were free from diabetes for 5 weeks after stopping beta-1,6;1,3 D-glucan at the age of 20 weeks. The total numbers of leukocytes in the peripheral blood and spleen of the rats were increased by beta-1,6;1,3 D-glucan treatment (P less than 0.05), whereas their T lymphocytes subsets were not changed. These data indicate that immunopotentiators could modulate the autoimmune mechanisms directed to pancreatic islets and inhibit the development of diabetes in BB rats.

Acquired hypothyroidism in a very young infant with Omenn’s syndrome

A very young male infant with Omenns syndrome had acquired hypothyroidism that was most likely caused by autoimmune thyroiditis. The hypothyroidism appeared at 3 months of age. These 2 rare conditions have not previously been reported occurring together. This case suggests that autoimmune thyroiditis may be another abnormal finding in Omenns syndrome.

Prevention of Diabetes in Non-Obese Diabetic (NOD) Mice by Short-Term and High-Dose IGF-I Treatment

This report describes the results of IGF-I treatment in a NOD mouse colony with a high incidence of overt diabetes. The animals were treated with IGF-I 17.9 nmol/day at 28-41 days of age and 35.9 nmol/day at 42-69 days of age and observed up to 280 days of age. Three of 12 (25%) IGF-I-treated animals developed diabetes compared with 8 of 11 (73%) controls (P < 0.05). The severity of insulitis at the conclusion of the follow-up was less pronounced in non-diabetic treated animals than in non-diabetic controls. These data support previous findings that IGF-I treatment protects the pancreatic beta-cells from destruction by diabetic autoimmunity in NOD mice.

Familial Predisposition of Type 1 Diabetes Mellitus in Japan, a Country with Low Incidence

The study group of the Japan Diabetes Society (JDS) carried out nationwide hospital-based and population-based surveys of childhood type 1 diabetes mellitus (DM) in Japan. According to the nationwide population-based survey, the incidence of childhood type 1 DM in Japan was 1.5 (1.4-1.6)/10(5), which did not differ for the 5 years from 1986-1990. Predisposition for DM and autoimmunity were studied in the first-degree relatives of the patients, including older and later cohorts. The prevalence of type 1 DM was 3.3% (12/369) among siblings and 2.2% (8/369) among parents, while the prevalence of type 2 DM was 0% among siblings and 4.3% (16/369) among parents. The risk of type 1 DM among siblings of the patients was 330 times higher than that among the general population in the Japanese population. The rate of positivity for autoantibodies, including ICA, IAA, GAD and IA-2, was 1.4-2.9% in parents (n=140) and 2.0-3.9% in siblings (n=203). The genetic susceptibility for type 1 DM is far lower in Japanese children than in Caucasian children, but predisposition to the disease and positive autoimmunity are almost the same in Japanese families of patients as in Caucasian families. The quality of life of Japanese parents of children with type 1 DM was less satisfactory that that of the Caucasian parents previously reported, which might be a result of the low incidence of type 1 DM in Japan.