Distribution of cardiac troponin I in the Japanese general population and factors influencing its concentrations.

BACKGROUND: The 99th percentile of cardiac troponin I level in the general population is accepted as the cut-off for the diagnosis of acute myocardial infarction (AMI). However, it is not clear whether the cut-offs derived in racially and geographically different populations are applicable in Japan. METHODS: Troponin I was determined using the Abbott ARCHITECT STAT high-sensitive troponin I immunoassay in 698 apparently healthy individuals who visited the Japanese Red Cross Medical Center for a health checkup. RESULTS: The 99th percentile of the hsTnI in the overall population was 22.5 (95% confidence interval (CI), 16.8-36.6) pg/mL, 17.7 (95% CI 12.0-22.8) pg/mL for females and 30.6 (95% CI 17.1-53.4) pg/mL for males. The median of the hsTnI in the overall population was 3.2 (95% CI, 3.0-3.3) pg/mL, 2.6 (95% CI 2.4-2.8) pg/mL for females and 4.0 (95% CI 3.8-4.3) pg/mL for males. The age and gender had a significant influence on these values. The troponin I level also showed significant associations with the body mass index (BMI), the gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), estimated glomerular filtration rate (eGFR), and cardiac abnormalities by electrocardiography (ECG) but not with the high-sensitive C-reactive protein (hsCRP) level. CONCLUSIONS: The 99th percentiles of the troponin I measured in the general population in Japan were comparable as the ones derived in the US, Germany, and Singapore. The troponin I level was dependent on the gender, age, BMI, and cardiac abnormalities found by ECG but not by the hsCRP level.

Significant increase of prostaglandin E-major urinary metabolite in male smokers: a screening study of age and gender differences using a simple radioimmunoassay.

BACKGROUND: For the assessment of inflammatory status, we have developed a simple, reliable radioimmunoassay (RIA) of prostaglandin E-major urinary metabolite (PGE-MUM), which remains stable in urine after it is metabolized. Using this method, we conducted a screening study to compare standard values of PGE-MUM to serum C-reactive protein (CRP) levels in health check volunteers. METHODS: PGE-MUM (micrograms per gram creatinine) was measured in normal urine samples obtained from 797 samples in volunteers for health check, using a newly developed RIA, and analyzed in relation to age, gender, smoking, and drinking habits. Results were compared to serum CRP. RESULTS: PGE-MUM was significantly higher in males than in females. It was significantly higher in smoking males, compared to males who had never smoked (nonsmokers), particularly in those above 40 years of age. In nonsmokers, PGE-MUM declined in males with advancing age, while it rose in females. Although PGE-MUM reflected current smoking status, independent of smoking index (SI), serum CRP indicated both current and former smoking condition, rather dependent upon SI. CONCLUSIONS: PGE-MUM increases in smokers, as suggested by possible inflammatory injury of pulmonary tissue. This RIA method for PGE-MUM may be thus a sensitive and reliable biomarker for current inflammation, different from serum CRP.

Association of IFNGR2 gene polymorphisms with pulmonary tuberculosis among the Vietnamese.

Interferon-γ (IFN-γ) is a key molecule of T helper 1 (Th1)-immune response against tuberculosis (TB), and rare genetic defects of IFN-γ receptors cause disseminated mycobacterial infection. The aim of the present study was to investigate whether genetic polymorphisms found in the Th1-immune response genes play a role in TB. In our study, DNA samples were collected from two series of cases including 832 patients with new smear-positive TB and 506 unrelated individuals with no history of TB in the general population of Hanoi, Vietnam. Alleles of eight microsatellite markers located around Th1-immune response-related genes and single nucleotide polymorphisms near the promising microsatellites were genotyped. A set of polymorphisms within the interferon gamma receptor 2 gene (IFNGR2) showed a significant association with protection against TB (P = 0.00054). Resistant alleles tend to be less frequently found in younger age at diagnosis (P = 0.011). Luciferase assays revealed high transcriptional activity of the promoter segment in linkage disequilibrium with resistant alleles. We conclude that the polymorphisms of IFNGR2 may confer resistance to the TB development of newly infected individuals. Contribution of the genetic factors to TB appeared to be different depending on age at diagnosis.

Identification of MICA as a susceptibility gene for pulmonary Mycobacterium avium complex infection.

Host genetic susceptibility to adult pulmonary Mycobacterium avium complex disease remains unknown. To identify genetic loci for the disease, we prepared 3 sets of pooled DNA samples from 300 patients and 300 sex-matched control subjects and genotyped 19,651 microsatellite markers in a case-control manner. D6S0009i-located in the MICA (major histocompatibility complex class I chain-related A) gene, which encodes a ligand of the NKG2D receptor-had the lowest P value in pooled and individual DNA typing. The A6 allele of the microsatellite was significantly associated with female patients (P <. 001), whereas the classical HLA-B and HLA-DRB1 alleles did not show significant association. Functional analysis of allelic expression imbalance revealed that A6-derived messenger RNA was more highly expressed than non-A6-derived messenger RNA in human bronchial epithelial cells. MICA was expressed in bronchiolar epithelium, alveolar macrophages, and granulomatous lesions. These findings suggest that MICA might be one of the immune molecules affecting the pathogenesis of the disease.

[A case of volcanic ash lung: report of a case].

A 57-year-old woman inhaled much volcanic ash without using a mask every day during the eruption of the Miyake Volcano in August 2000. An abnormal shadow was pointed out on her chest radiography by chance, after she sought refuge in Higashimurayama city in September. She had no respiratory symptoms and her chest radiography in an annual health check in July 2000 had showed no abnormality. She was admitted to our hospital and thoracoscopic lung biopsy was performed. We diagnosed it as lung inflammation caused by volcanic ash. The reasons for diagnosis were because the abnormal shadow appeared after the inhalation of volcanic ash, chest computed tomography showed diffuse irregular shadows with air bronchogram, thoracoscopic lung biopsy showed cellular-bronchiolitis around crystals, and the results of mineralogical analysis of the particles in alveolar macrophages detected in the biopsy specimen by scanning electron microscopy (SEM) were very similar to those of volcanic ash. The shadow on her chest radiography disappeared gradually without any treatment, but she avoided further exposure to volcanic ash. It is necessary to consider volcanic ash capable of causing lung inflammation.

Variations of the CFTR gene in the Hanoi-Vietnamese.

In order to investigate polymorphic backgrounds of the cystic fibrosis transmembrane conductance regulator gene (CFTR) in the Vietnamese, we analyzed 495 blood samples of randomly selected healthy individuals in Hanoi for the delta F508 mutation and TG-repeats, poly-T, and M470V polymorphisms. We compared their distributions with those of Caucasians and other Asian populations. No delta F508 mutation was found, being consistent with the extremely low incidence of cystic fibrosis (CF) in Vietnam. Allele frequency of the T5 allele promoting exon 9 skipping was 0.037. Greater number of TG-repeats, which is known to facilitate this aberrant splicing, was a predominant trend in the Vietnamese and other Asians. A "T5-TG12-V470" haplotype was most common (29/37) among T5-bearing haplotypes. Three major haplotypes, T7-TG12-M470, T7-TG11-V470, and T7-TG12-V470, estimated by PHASE program, related to 92% of the population. This is the first study of the CFTR gene among the Vietnamese.