Soroku Nishiyama

Mild to moderate zinc deficiency in short children: Effect of zinc supplementation on linear growth velocity

Twenty-one prepubertal, short Japanese children (11 boys) without endocrine abnormalities were identified as having mild-to-moderate zinc deficiency by zinc kinetics studies (zinc body clearance > or = 20 ml/kg per hour). Only one child had a serum zinc level < 65 micrograms/dl (cutoff level). A total of 10 children (5 boys) received 5 mg/kg per day of zinc sulfate for 6 months; 11 untreated children (6 boys) served as control subjects. During treatment, calorie intake (p < 0.01), growth velocity (p < 0.01), serum zinc, calcium, and phosphorus concentrations, alkaline phosphatase activity (p < 0.001), percentage of tubular reabsorption of phosphorus (p < 0.05), ratio of maximal tubular reabsorption rate for phosphorus to the glomerular filtration rate (p < 0.05), serum osteocalcin level (p < 0.01), and plasma insulin-like growth factor 1 (p < 0.05) were significantly increased, but urinary excretion of growth hormone was unchanged in the zinc-supplemented group. All these values were unchanged in the untreated children. We conclude that zinc supplementation is effective for inducing growth in short children with zinc deficiency, and that body zinc clearance tests facilitate detection of marginal zinc deficiency.

Differences in basal and postexercise osteocalcin levels in athletic and nonathletic humans

SummaryThe levels of serum osteocalcin, in addition to other parameters, were monitored in athletic (N=9) and nonathletic (N=10) university male students before, immediately after, and 60 min after 30 min of exercise on a running ergometer and at a constant workload of approximately 50% of their maximum capacity; there was adequate replenishment of drinking water. In both groups, the increase in serum parathyroid hormone levels observed immediately after exercise correlated well with a decrease in ionized calcium as well as the total calcium, and also with an increase in serum phosphorus, whereas the concentration of serum albumin remained stable. The response of serum osteocalcin differed between the two groups, in that (1) the concentration before exercise was significantly higher in athletic than in nonathletic students (P<0.001), and (2) the maximum level was evident in the former group 60 min after exercise, whereas it was present in the latter group immediately after exercise. We speculate that athletic subjects have a higher turnover of bone status compared with nonathletic subjects.

Characterization of self-glutamic acid decarboxylase 65-reactive CD4+ T-cell clones established from Japanese patients with insulin-dependent diabetes mellitus

To investigate autoimmunity to glutamic acid decarboxylase (GAD) 65 in Japanese patients with insulin-dependent diabetes mellitus (IDDM, type I diabetes), we established seven CD4+ T-cell clones, by stimulating peripheral blood mononuclear cells (PBMC) of six IDDM patients, using a mixture of overlapping human GAD65 peptides. No GAD65 autoreactive T-cell clones were evidenced in four healthy controls. Specificities of T-cell clones were as follows: (a) two clones specific to GAD65 p111-131 (residue 111 to 131) + DR53 (DRB4*0103); (b) one clone specific to GAD65 p413-433 + DR1 (DRB1*0101); (c) two clones specific to GAD65 p200-217 + either DR9 (DRB1*0901) or DR8 (DRB1*0802); and (d) two clones specific to GAD65 p368-388 + DP2 (DPA1*01 or 0201-DPB1*0201). Two DR53-restricted and one DR1-restricted T-cell clones, responded to a recombinant human GAD65 protein, and showed cytotoxicity against B lymphoblastoid cell lines pre-pulsed with the peptides. Six T-cell clones exhibited the Th1-like phenotype. Interestingly, two DR53-restricted T-cell clones killed a Fas-deficient B lymphoblastoid cell line, thereby indicating that cytotoxicity was not completely dependent on a Fas-Fas ligand interaction. Thus, the T-cell epitopes were mapped in a limited portion of GAD65 protein, with a tendency to be restricted by disease-associated HLA-DR, but not DQ molecules.

Decreased bone density in severely handicapped children and adults, with reference to the influence of limited mobility and anticonvulsant medication.

Bone density and related biochemical parameters were investigatd in institutionalised children and adults with severe handicaps, who were classified according to the degree of limited mobility (group 1, bed-ridden; group 2, capable of crawling; group 3, capable of walking) and according to whether or not they were receiving anticonvulsants. As determined by microdensitometric analysis of radiograms of the second metacarpal bone, bone width (D), bone pattern area (ΣGS) and bone salt density (ΣGS/D) were decreased in the patients, the decreases being most prominent in group 1, followed by groups 2 and 3, in that order. Significant decreases of ΣGS and ΣGS/D, but not of D, were found in patients on anticonvulsant treatment in comparison to patients without therapy. Serum alkaline phosphatase (Al-p) and parathyroid hormone (iPTH) as well as urinary calcium and cyclic adenosine-3′,5′-monophosphate (cAMP) excretion were significantly increased in group 1. In comparison to patients without therapy, anticonvulsant-treated children showed significantly decreased levels of serum calcium (Ca), ionised Ca (Ca2-), 25-hydroxy vitamin D3 and urinary phosphate (PO4) excretion, and elevated levels of Al-p, iPTH and calcitonin (iCT). It is suggested that limited physical activity results in a mild hyperparathyroid state, which is aggravated in patients on anticonvulsant treatment.

Age- and sex-related differences in lipoproteins containing apoprotein A-I.

We Investigated ageand sex-related differences In the structure and composition of two species of lipoproteins that contain apoprotein (apo) A-I (A-I Lp): lipoproteins containing apo A-I and apo A-II (Lp A-l/A-ll), and Iipoprotein containing apo A-I but no apo A-II (Lp A-I), which were isolated by immunoaffinlty chromatography. Sixty normollpidemlc volunteers were assigned to one of three groups based on their ages and sexual maturation (Group A, prepubertal; Group B, puberty; and Group C, postpuberty). In A-I Lp, the levels of total cholesterol, choiesteryi ester, phosphoiipid, and apo A-I were lower In males during puberty and then remained stable. In Lp A-I/ A-II, there were no ageor sex-related changes In llpids or In apo A-II. Levels of apo A-I in the females were lower with advance in age, although significant differences were observed only between preand postpubertal subjects. In Lp A-I, the levels of total cholesterol, choiesteryi ester, phosphoiipid, and apo A-I were lower In males during puberty and remained stable thereafter, as in the case of A-I Lp. Therefore, the ageand sex-related differences observed in A-I Lp appear to be primarily due to the differences In Lp A-I. When we take Into account the constancy of Lp A-l/A-ll levels In all groups, the physiological function of A-I Lp (high density Iipoprotein) In each Individual may be limited by the Lp A-I levels.

The polymorphic 43Thr bcl-2 protein confers relative resistance to autoimmunity: an analytical evaluation

We have found a novel polymorphic (Ala43Thr; ACC→GCC) bcl-2 allele in a Japanese population. An in vitro expression study with a mouse IL-7-dependent pre-B cell line has revealed that inhibition of the programmed cell death function of 43Thr bcl-2 protein is suppressed compared with that of normal 43Ala bcl-2 protein. Since bcl-2 expression in B-lymphoid cells elicits autoimmune disease in mice, we have investigated the possibility of whether a bcl-2 polymorphism has a different susceptibility to autoimmune disease. To evaluate the clinical impact of this polymorphism, the frequency of bcl-2 polymorphism was investigated in 221 children with insulin-dependent diabetes mellitus (IDDM), 237 adults with autoimmune disease (105 with rheumatoid arthritis, 57 with systemic lupus erythematosus, 55 with Sjögren’s syndrome, and 20 others), and 290 healthy Japanese children and adults. The frequency of the 43Thr bcl-2 allele, either homozygous or heterozygous, was 14.5% in normal controls, 6.8% (P<0.01) in children with IDDM, and 8.0% (P<0.025) in adults with autoimmune disease. These results suggest that the 43Thr allele of bcl-2 confers resistance to autoimmune disease. The different anti-apoptotic function resulting from the different expression of bcl-2 protein in lymphocytes seems to be associated with the development of autoimmune disease, indicating that the bcl-2 gene affects human autoimmune disease.

Kinetics of Zinc Status in Children With IDDM

Objective To ascertain zinc deficiency in patients with insulin-dependent diabetes mellitus (IDDM) and evaluate the relationship between zinc clearance and body height velocity. Research Design and Methods Six boys and 11 girls with IDDM and zincuria and glycosuria were studied. Study quality and specific descriptive information concerning relationship and outcome measurement were assessed. Results The values of total-body zinc clearance in IDDM patients were higher than in the control subjects (24.6 ± 1.8 vs. 15.1 ± 0.6 ml · kg−1.h−1, P < 0.01). There was a negative correlation between body zinc clearance values and height velocity in IDDM patients. Conclusions Patients with IDDM have a secondary zinc deficiency, and normal growth may be stunted.

Zinc and IGF-I concentrations in pregnant women with anemia before and after supplementation with iron and/or zinc.

OBJECTIVE The objective of our study was to investigate zinc (Zn) status and effects of Zn supplementation in relation to insulin-like growth factor-I (IGF-I) and iron deficiency anemia in pregnant women. The role of Zn and IGF-I in hematologic abnormalities has remained unclear. METHODS Thirty-eight Japanese women, when examined at the second trimester of pregnancy, had hemoglobin concentrations below 11.0 g/dL and 32 of 38 had normocytic erythrocytes. These 38 women were divided into three groups, and we compared the hematological status and serum IGF-I levels before and after iron (Group A) or Zn (Group B) or iron plus Zn (Group C) supplementation. RESULTS The concentrations of hemoglobin (Hb) did not change in groups A and B. In group C, Hb levels were significantly increased from 10.3+/-0.3 to 11.0+/-0.6 g/dL. Furthermore, numbers of RBC and reticulocytes also increased significantly. Concentrations of iron, IGF-I and total iron binding capacity (TIBC) were increased, and concentrations of erythropoietin were decreased, but not statistically. There were significant positive correlations between increases in IGF-I and increases in Hb and RBC in the Zn administered groups. CONCLUSION Zn status to some extent can account for hematological abnormalities in pregnant women. Zn derived IGF-I has a role in the regulation of hematopoiesis in pregnant women.

Predominance of large low density lipoprotein particles and lower fractional esterification rate of cholesterol in high density lipoprotein in children with insulin-dependent diabetes mellitus

Abstract Coronary artery disease (CAD) is a major cause of death in patients with insulin-dependent diabetes mellitus. Qualitative changes in low density lipoprotein (LDL) and high density lipoprotein (HDL) are thought to be important for evaluating the risk for CAD. In the present study, we evaluated LDL particle size (LDL-size) by 2%–16% gradient gel electrophoresis, along with conventional lipids and apolipoproteins, in 23 children with IDDM (10 males and 13 females) and 27 nondiabetic controls (12 males and 15 females). The fractional and molar esterification rates (FER and MER) of cholesterol in plasma and HDL were also determined. Plasma levels of triglyceride were significantly lower in diabetic children than in controls. Plasma apoA-I and apoA-II levels in female diabetic children were significantly higher and lower than those in controls respectively. Plasma levels of HDL-cholesterol and the ratio of apoA-I to apoA-II were significantly higher in diabetic children than in controls. Other lipid and apolipoprotein parameters in diabetic children were similar to those in controls. LDL-size in diabetic children was significantly greater than that in controls. FERHDL, which reflects the particle size distribution of HDL, was significantly lower in diabetic children than in controls, which suggests that diabetic children had larger HDL particles. Conclusion The qualitative and quantitative changes in LDL and HDL in diabetic children are similar to those associated with a reduced risk for CAD. Intensive insulin therapy in children may help preventing coronary heart disease in adulthood.

Zinc Status Relates to Hematological Deficits in Middle-Aged Women

OBJECTIVE The objective of our study was to investigate zinc (Zn) status and the effects of Zn supplementation in relation to iron deficiency anemia in middle-aged women. It is important to define the role of Zn in hematologic abnormalities and to determine the frequency of Zn deficiency. METHODS Fifty-two Japanese women, selected from a health examination survey on 6200 women, had hemoglobin concentrations below 12.0 g/dl, total iron binding capacity (TIBC) below 390 micrograms/dl and fairly normocytemia. These 52 were divided into three groups and we then compared the hematological status before and after iron (group A) or Zn (group B) or iron plus Zn (group C) supplementation. RESULTS After treatment, concentrations of hemoglobin (Hb) increased slightly in groups A and B, but not statistically significant. In group C, Hb levels were significantly increased from 10.8 +/- 1.1 to 12.8 +/- 1.1 g/dl. Furthermore, numbers of RBC and reticulocytes, and concentrations of albumin were also increased significantly. Increased values over 1.0 g/dl of hemoglobin levels were noted in four women (26.6%) in group A, three women (14.2%) in group B and 13 women (81.2%) in group C. CONCLUSION Zn status to some extent can account for hematological abnormalities in middle-aged women. At least 5.0% of middle-aged Japanese women may have Zn deficiency. Normocytic anemia with low TIBC levels may serve as a good indicator of a marginal Zn deficiency.