The Levels of Serum Low-Density Lipoprotein Cholesterol Using Direct Measurement in Healthy Japanese School Children

This study aimed to investigate the levels of serum low-density lipoprotein cholesterol (LDLC) using direct measurement in healthy Japanese school children. The subjects were 621 children (325 boys and 296 girls) aged 9 to 10 in the 4th grade, and 688 children (334 boys and 354 girls) aged 12 to 13 in the 7th grade. The levels of serum LDLC and high-density lipoprotein cholesterol were measured by direct determination (Cholestest LDL and Cholestest NHDL; Daiichi Pure Chemicals Co., Ltd., Tokyo, Japan). In boys in the 4th grade, the mean, the 75th, the 90th and the 95th percentiles of LDLC levels (mg/dl) were 91.6, 104, 124 and 134, respectively. In girls in the 4th grade, they were 92.8, 108, 122 and 130. In boys in the 7th grade, they were 83.4, 96, 113 and 123. In girls in the 7th grade, they were 93.0, 106, 126 and 137. Serum LDLC levels in boys in the 7th grade were lower than those of other groups. The direct measurement of serum LDLC level is useful for evaluation of dyslipidemia in healthy school children, because the method is applicable to non-fasting serum.     

Comparison of clinical efficacy and cost-quality of antihistamines in early treatment for Japanese cedar pollinosis]

BACKGROUND: Japanese cedar pollinosis (JCP) affects more than 16% of the Japanese population. The estimated direct and indirect costs for this disease totaled 286 billion yen in 1998. In JCP therapy, antihistamines are first line agents. It is well known that starting treatment for JCP with antihistamines before initial day of the pollen scattering can relieve nasal symptom severity during pollen season. The aim of this study is to assess the clinical efficacy and cost-quality of 7 major second-generation antihistamines in early treatment for Japanese cedar pollinosis (JCP). METHODS: Patients were randomly selected from 16 ENT clinical sites in Osaka and Wakayama between February 24 and March 8, 2003 (peak pollen season). Effectiveness was assessed using patient'ratings of nasal and ocular symptoms and overall assessment in their condition compared to previous season ones. Costs include direct costs of the drugs used for treatment to JCP from January to March. RESULTS: One hundred seventy-five patients who were treated with antihistamine monotherapy (azelastine: n=15, cetirizine: n=15, ebastine: n=36, epinastine: n=16, fexofenadine: n=16, loratadine: n=60, oxatomide: n=17) and 510 non-treatment patients were evaluated. Among 8 groups, there were significant differences in sneezing, rhinorrhea, ocular itching and overall health condition. However, among 7 monotherapy groups, there were no differences in each symptom or the overall assessment. In cost-quality analysis, there were significant differences in a cost for each effective patient (defined as those with improvement in their overall condition) among 7 drugs. The top three cost-efficacious drugs resulted in azelastine, loratadine and fexofenadine. CONCLUSION: These results show that there were no significant differences in clinical efficacy in early treatment for JCP among 7 antihistamines. But Japanese National Health Insurance drug price scheme led to significant differences in cost-quality.     

Gastrointestinal stromal tumor arising from anorectum: correlation of imprint cytology and radiologic imaging

The diagnosis of gastrointestinal stromal tumor (GIST) is generally established on histopathologic examination of surgical specimens. Gastrointestinal stromal tumor comprises a heterogenous group of neoplasms of the gastrointestinal tract previously referred to as leiomyomas, leiomyosarcomas, or schwannomas. Gastrointestinal stromal tumor arising from anorectum is a rare instance. We report a case of GIST for the correlation of imaging and cytologic features with immunocytochemical staining. A computed tomography and magnetic resonance imaging confirmed a 2-cm tumor growing into the rectal lumen. The central portion of the tumor showed T1-weighted imaging of low signal and suspected central necrosis by the T2-weighted imaging of high signal. Imprint cytology from excised tumors showed isolated or loosely aggregated spindle cells with scanty and fibrillary cytoplasmic processes, nuclear pleomorphism, fine granular chromatin, and irregular nuclear margins. Epithelioid tumor cells showed grooves with abundant cytoplasm and several round nucleoli. Both c-kit and CD34 antigen were positive with strong and diffuse stainability in smears as well as paraffin sections by immunoperoxidase staining. We suggest that the combined use of imaging diagnosis and cytology with immunocytochemical staining are useful initial diagnosis of GIST.     

Autosomal linkage analysis of a Japanese single multiplex schizophrenia pedigree reveals two candidate loci on chromosomes 4q and 3q.

We analyzed a large multiplex schizophrenia pedigree collected in mid-eastern Japan using 322 microsatellite markers distributed throughout the whole autosome. Under an autosomal-dominant inheritance model, the highest pairwise LOD score (LOD = 1.69) was found at 4q (D4S2431: theta = 0.0), and LOD scores at two other loci 3q (ATA34G06) and 8q (D8S1128) were 1.62 and 1.46, respectively. In multipoint analysis, LOD scores of the regions on 4q and 3q remained at a similar level; however, the LOD score of the region on 8q apparently decreased. Additional dense map analysis revealed haplotypes on 4q and 3q regions shared by affected individuals. On chromosome 4q, the haplotype spanning about 8 centiMorgans (cM) was shared by four of six genotyped individuals with schizophrenia and one affected individual whose haplotype was estimated. On 3q, the haplotype spanning about 20 cM was shared by five genotyped individuals with schizophrenia. We obtained two candidate regions of major susceptibility loci for schizophrenia on chromosomes 3q and 4q.     

Mutation analysis of the retinoid X receptor beta, nuclear-related receptor 1, and peroxisome proliferator-activated receptor alpha genes in schizophrenia and alcohol dependence: possible haplotype association of nuclear-related receptor 1 gene to alcohol dependence

Because retinoid cascades are involved in the regulation and development of the central nervous system, including dopaminergic neurons, retinoic acid signaling defects may contribute to schizophrenia and substances dependence. Retinoid X receptors (RXRs) form heterodimer complexes with nuclear-related receptor 1 (NURR1) or with peroxisome proliferator-activated receptors (PPARs). We examined 48 Japanese patients with schizophrenia and 32 patients with alcohol dependence to detect mutations in the retinoid X receptor beta gene (RXRB) on chromosome 6p21.3, the NURR1 gene (NR4A2) on chromosome 2q22-q23, and the PPAR alpha gene (PPARA) on chromosome 22q12.2-13.1. A Val95Ala polymorphism of the RXRB gene, a Val227Ala polymorphism in the PPARA gene, and two synonymous single-nucleotide and CA repeat polymorphisms in the 5' region and 3' untranslated region of the NR4A2 gene were identified. Extended case control samples did not suggest an association between the diseases and the RXRB or PPARA polymorphisms. However, they revealed a significant association between the NR4A2 gene haplotype and alcohol dependence, indicating that 2q22-q23 including the NR4A2 gene locus is a possible genomic region contributing to genetic susceptibility to alcohol dependence.     

Mutation analysis of the calpastatin gene (CAST) in patients with Alzheimer's disease

The calpains, a family of calcium-dependent cysteine proteinases, and calpastatin, their endogenous inhibitor protein, are involved in the proteolysis of amyloid precursor protein, which is thought to be abnormal in patients with Alzheimer's disease (AD). Specific inhibitors of calpains attenuate amyloid beta peptide-induced neuronal death. We hypothesized that some AD patients have functionally deficient mutation(s) of the CAST gene encoding calpastatin, and we screened 40 Japanese patients with AD for mutations in the coding region of CAST. Nine polymorphisms, -82A/G, IVS7-96A/G, 669A/G, 1223C/G (Ser408Cys), IVS20-10C/T, IVS21-65G/A, IVS22+31T/C, IVS24+38Ins/DelA, and IVS25-32A/G, were identified. The 669A allele causes skipping of exon 11, leading to the loss of 13 residues. Comparisons between 101 patients and 90 controls revealed no significant association between CAST polymorphisms and risk for AD, indicating that genomic variations of CAST are not likely to be substantially involved in the etiology of AD.     

Diagnostic significance of serum soluble transferrin receptors in various anemic diseases: the first multi-institutional joint study in Japan

Serum soluble transferrin receptor (sTfR) has been reported to be higher in patients with iron deficiency or with elevated erythropoiesis. In the present study, serum sTfR was measured in various anemic diseases and their clinical significance was examined in a multi-institutional joint study. Serum sTfRs in patients with the following anemic diseases were markedly higher than those in normal healthy adults: non-treated iron deficiency anemia (IDA) (9.13 +/- 7.04 mg/l, n = 52, p < 0.0001), anemia of chronic disorders (ACD) (3.45 +/- 1.38 mg/l, n = 20, p < 0.0001), hemolytic anemia (HA) (5.57 +/- 3.26 mg/l, n = 17, p < 0.0001), and myelodysplastic syndrome (MDS) (4.03 +/- 2.83 mg/l, n = 20, p < 0.0001). There were significant differences between IDA and ACD (p < 0.0001), between aplastic anemia (AA) (1.58 +/- 1.26 mg/l, n = 16) and MDS (p < 0.001), and between AA and MDS with refractory anemia (MDS-RA) (4.16 +/- 3.40 mg/l, n = 9) (p < 0.02). In patients with chronic renal failure (CRF), serum sTfR levels and serum sTfR/log serum ferritin ratios (sTfR/F index) were compared in the two classified groups according to Muirhead's criteria, as IDA and non-IDA groups with or without recombinant human erythropoietin (rHuEPO) treatment. Significantly high levels of both serum sTfR (p < 0.0001) and the sTfR/F index (p < 0.0001) were observed in IDA without rHuEPO treatment. Especially in CRF with rHuEPO treatment, the sTfR/F index showed marked elevation in the IDA group (p < 0.0001) compared with serum sTfR (p < 0.001), indicating more diagnostic efficacy of the sTfR/F index for CRF with IDA. In conclusion, the serum sTfR concentration is a useful diagnostic tool for discrimination between IDA and ACD, and between AA and MDS-RA, and for the detection of iron deficiency in CRF patients in the Japanese population.     

Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension

Adipocyte-derived leucine aminopeptidase (ALAP) inactivates angiotensin II and/or generates bradykinin in the kidney, suggesting a possible role for ALAP in the regulation of blood pressure. We considered the hypothesis that genomic variants of the ALAP gene are associated with hypertension or individual variations in blood pressure. We screened for mutations in the ALAP gene in 48 unrelated Japanese individuals and identified 33 polymorphisms including 15 novel polymorphisms. We then performed a two-stage analysis. In the first stage, the eight missense polymorphisms were evaluated for associations with blood pressure in 96 apparently healthy individuals. In the second stage, only the most promising polymorphisms were evaluated for association with essential hypertension in 143 hypertensive and 348 normotensive subjects. Among the eight missense polymorphisms, the Ile276Met and Lys528Arg polymorphisms showed significant association with blood pressure. Subsequent analysis confirmed association between the Lys528Arg polymorphism and essential hypertension. The estimated odds ratio for essential hypertension was 2.3 for presence of the Arg allele at codon 528, in comparison with presence of the Lys/Lys genotype (P = 0.004). These findings support involvement of ALAP in the regulation of blood pressure.     

Mutation analysis of the retinoid X receptor beta,nuclear‐related receptor 1, and peroxisome proliferator‐activated receptor alpha genes in schizophrenia and alcohol dependence: Possible haplotype association of nuclear‐related receptor 1 gene to alcohol dependence

Because retinoid cascades are involved in the regulation and development of the central nervous system, including dopaminergic neurons, retinoic acid signaling defects may contribute to schizophrenia and substances dependence. Retinoid X receptors (RXRs) form heterodimer complexes with nuclear‐related receptor 1 (NURR1) or with peroxisome proliferator‐activated receptors (PPARs). We examined 48 Japanese patients with schizophrenia and 32 patients with alcohol dependence to detect mutations in the retinoid X receptor beta gene (RXRB) on chromosome 6p21.3, the NURR1 gene (NR4A2) on chromosome 2q22–q23, and the PPAR alpha gene (PPARA) on chromosome 22q12.2–13.1. A Val95Ala polymorphism of the RXRB gene, a Val227Ala polymorphism in the PPARA gene, and two synonymous single‐nucleotide and CA repeat polymorphisms in the 5′ region and 3′ untranslated region of the NR4A2 gene were identified. Extended case control samples did not suggest an association between the diseases and the RXRB or PPARA polymorphisms. However, they revealed a significant association between the NR4A2 gene haplotype and alcohol dependence, indicating that 2q22–q23 including the NR4A2 gene locus is a possible genomic region contributing to genetic susceptibility to alcohol dependence. © 2001 Wiley‐Liss, Inc.