Fujihiko Iwata

Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter.

Maintenance of fluid and electrolyte homeostasis is critical for normal neuromuscular function. Bartters syndrome is an autosomal recessive disease characterized by diverse abnormalities in electrolyte homeostasis including hypokalaemic metabolic alkalosis; Gitelmans syndrome represents the predominant subset of Bartters patients having hypomagnesemia and hypocalciuria. We now demonstrate complete linkage of Gitelmans syndrome to the locus encoding the renal thiazide-sensitive Na–Cl cotransporter, and identify a wide variety of non-conservative mutations, consistent with loss of function alleles, in affected subjects. These findings demonstrate the molecular basis of Gitelmans syndrome. We speculate that these mutant alleles lead to reduced sodium chloride reabsorption in the more common heterozygotes, potentially protecting against development of hypertension.

Abdominal adiposity is associated with fatty acid desaturase activity in boys: Implications for C-reactive protein and insulin resistance

Fatty acid composition, which is altered in patients with abdominal obesity, is influenced not only by dietary intake but also by the desaturating enzymes stearoyl-CoA desaturase (SCD), delta-6 desaturase (D6D) and delta-5 desaturase (D5D). We investigated desaturase activities and their associations with metabolic risk factors, C-reactive protein levels (CRP) and insulin resistance in Japanese children. There were 237 school children in this study; 115 were boys. The fatty acid composition of plasma phospholipids was analyzed, and the following desaturase activities were estimated: SCD (16:1n-7/16:0 and 18:1n-9/18:0), D6D (20:3n-6/18:2n-6) and D5D (20:4n-6/20:3n-6). D6D and D5D activities, but not SCD activity, were significantly associated with triglyceride levels, high-density lipoprotein cholesterol levels and insulin resistance in both sexes, and with CRP levels in boys. In addition, increased abdominal adiposity was significantly associated with increased D6D activity, and decreased D5D activity and insulin resistance in both sexes, and with increased CRP levels in boys. The n-6 polyunsaturated fatty acid desaturation pathway may be associated with metabolic risk factors, insulin resistance and increased inflammation in children with abdominal obesity, especially in boys.

Identification of recurrent and novel mutations in the LDL receptor gene in Japanese familial hypercholesterolemia

We used the denaturing gradient gel electrophoresis (DGGE) method to investigate 120 Japanese patients with familial hypercholesterolemia (FH) for mutations in the promoter region and the 18 exons and their flanking intron sequence of the low density lipoprotein (LDL) receptor gene. Fourteen aberrant DGGE patterns were found, and the underlying mutations were characterized by DNA sequencing. Five novel missense mutations (C317S, F382L A410T, L547V, and E693K), two nonsense mutations (W512X and K790X), four frameshift mutation (355del7, 1246ins5, 1687ins1, and 2035ins1), one splicing mutation (1845+2 T→C), and two inframe mutations (661ins21 and 1115del9/ins6) were identified. Six of these mutations (L547V, E693K, W512X, 355del7, 1687ins1, and 20354ins1) have not been described before in FH. These newly identified mutations cosegregated in their family members with defective LDL receptor activity and hypercholesterolemia, and are thought to be causal for the FH phenotype. These results demonstrate that there is a broad spectrum of mutations in the LDL receptor gene in the Japanese population. Hum Mutat 14:87, 1999.

Lipoprotein (a) and apolipoprotein A‐1 and B in schoolchildren whose grandparents had coronary and cerebrovascular events: A preliminary study of 12–13 year old Japanese children

The aim of this study was to evaluate the relationship between the serum levels of lipoprotein (a) [Lp (a)] and apolipoproteins (apo A‐1 and apo B) in schoolchildren with a history of coronary and cerebrovascular events in their grandparents.

Characteristics of obese children with low content of arachidonic acid in plasma lipids

Background: Although there have been many studies on the relationship between obesity and long‐chain polyunsaturated fatty acid (LCPUFA), the results and their interpretation are controversial, especially in children. Arachidonic acid (AA), the product of n‐6 LCPUFA, is reported to be related to insulin resistance. The purpose of the present paper was to investigate the LCPUFA profile in obese children and mechanisms that contribute to reduced AA content.

Serum lipid profile in obese children in China

Abstract Background : The aim of the present study was to examine the serum lipid profile in obese Chinese children, their serum lipid and apolipoprotein A‐I (apoA‐I) and B (apoB) levels were examined.

Chronic hypomagnesemia and hypokalemia due to renal wasting in siblings

A 13 year old girl with carpopedal spasm is presented. Investigation values showed hypomagnesemia and hypokalemia. Her younger brother and sister demonstrated the same biochemical abnormalities without any symptoms. Their urinary excretion of magnesium and potassium were inappropriately high compared with their serum levels. Treatment with oral magnesium sulfate failed to correct the abnormalities, but serum levels of magnesium and potassium were just below the lower limits. This familial disease may represent congenital renal wasting of magnesium and potassium.

Abdominal adiposity is associated with high-density lipoprotein subclasses in Japanese schoolchildren.

BACKGROUND The large HDL subclass is considered to possess cardioprotective properties. The purpose of this study is to determine the relationship among abdominal adiposity, insulin resistance and HDL subclass profiles of Japanese schoolchildren. METHODS The study subjects included 164 children (79 boys and 85 girls). We obtained waist to height ratio (WHtR), lipid profile, and HOMA-IR. The HDL subclass profile was analyzed by HPLC. RESULTS Children of either sex with abdominal obesity (WHtR≥0.5) had reduced concentrations of very large, large, and medium HDLC in conjunction with elevated triglyceride (TG) concentrations and HOMA-IR. WHtR was inversely related to the concentrations of very large (boys: r=-0.5306, p<0.0001; girls: r=-0.3483, p=0.0011), large (r=-0.6168, p<0.0001; r=-0.4387, p<0.0001), and medium (r=-0.4170, p=0.0001; r=-0.4116, p<0.0001) HDLC. The multiple regression analyses revealed that WHtR was an independent factor of the concentrations of very large, large, small, and very small HDLC in boys and the concentrations of large and medium HDLC in girls. CONCLUSIONS In Japanese schoolchildren, abdominal obesity is associated with atherogenic HDL subclass profile. Abdominal obesity may be an important target for the prevention and management of HDL subclass alteration, even in children who do not suffer from insulin resistance or hypertriglyceridemia.

Age- and sex-specific body composition of Chinese children.

UNLABELLED We examined age- and sex-specific body compositions of Chinese children by the bioelectrical impedance method. The subjects were a total of 587 children aged 6-14 y who had normal relative weight. In all ages, boys had larger fat-free mass and lower percent body fat (%BF) than girls did. Even in the subjects with BMI <20 kg/m2, more than one quarter of them had high %BF. CONCLUSION Chinese children may have higher %BF than that predicted by BMI.

Magnetic resonance imaging of the cauda equina in two patients with Guillain‐Barré syndrome

The results are presented of magnetic resonance imaging (MRI) of the spine in two cases of childhood Guillain‐Barré syndrome. After injection of gadolinium‐diethylenetriamine pentaacetic acid, MRI showed enhancement of the cauda equina in these patients. These MRI observations may help confirm the diagnosis of Guillain‐Barré syndrome. The nerve root enhancement resolved as the clinical symptoms improved. Serial imaging may be useful in monitoring the response to therapy and assessing new treatment regimens. It may also yield a better understanding of the disease process.