HLA‐C*12:02 is a susceptibility factor in late‐onset type of psoriasis in Japanese

Psoriasis is thought to be a multifactorial disease triggered by both genetic and environmental factors. The HLA‐C locus on chromosome 6p21.33 remains the strongest susceptibility candidate locus in psoriasis. The strong association between psoriasis and the HLA‐Cw6 allele has been well documented in various races. It is known that psoriatic patients with early onset are more likely to be familial and associated with HLA‐Cw6. Familial occurrence of Japanese psoriasis is smaller than other populations. Furthermore, males are predominant over females in Japanese psoriasis. We investigated the relation between HLA‐C alleles and age of onset, and in each gender for Japanese psoriasis, and discuss male predominance in the incidence of psoriasis in Japan. Four hundred forty six unrelated Japanese patients with psoriasis vulgaris and 557 sex‐ and age‐matched unrelated Japanese healthy controls were investigated by genotyping. We confirmed the association between early‐onset type of psoriasis with HLA‐C*06:02 allele in Japanese. In addition, we detected the association between the late‐onset type of psoriasis and the HLA‐C*12:02 allele in Japanese. No significant differences in allele frequency were observed between females and males. Our results suggest that there is no genetic factor effect on male predominance in Japanese. In contract, the effect of environmental risk factors on the onset of Japanese psoriatic patients is stronger in males than in females. As a result, male predominant in psoriasis may occur in Japan.     

HLA typing and transplantation

Clinical trial of organ transplantation was renal transplantation by Voronoy at 1936. The discovery of HLA in the 1950s was one of the most important new findings in the area of transplantation. Nowadays, developing HLA genotyping methods, the serum analysis does not use for donor and recipient HLA typing but for cross-matching test. Because each of HLA genotyping methods has its merits and demerits, it is important to choice right methods for avoiding type error. PCR-Luminex method using fluorescence microsphere was developed for high-resolution HLA-A, HLA-B and HLA-DRB1 genotyping in the Japanese population. This genotyping method allows to define all the possible combinations of alleles at each loci existing in Japanese at the four-digital level. In hematopoietic stem cell transplantation, to match high resolution level of HLA between donor and recipient lead an improvement of recipient's survival. In organ transplantation, removed organ has to be so immediately transplanted into recipient that no time is left for HLA genotyping. In order to have good survival of transplanted organ, HLA, cytokine promoter lesion and immunoglobulin like receptor genotyping might be helpful. We focused on this review at HLA genotyping, especially new SSO methods.     

Successful allogeneic bone marrow transplantation for acute myelogenous leukemia after drug-induced cardiomyopathy

Anthracycline derivatives often induce cardiomyopathy. Patients with seriously decreased cardiac function due to chemotherapeutic drugs cannot usually receive allogeneic hematopoietic stem cell transplantation (SCT) for hematologic disorders. We successfully performed allogeneic bone marrow transplantation (BMT) in a patient with severe cardiomyopathy. An 18-year-old woman with relapsed acute myelogenous leukemia had cardiomyopathy due to previous anthracycline administration. She underwent allogeneic BMT from her HLA-identical brother. Her preconditioning regimen was cytosine arabinoside, etoposide, total body irradiation, and high-dose cyclophosphamide. Congestive heart failure (CHF) was not present before BMT. Right heart pressures were monitored by a pulmonary arterial balloon catheter system (Swan-Ganz catheter). After BMT, she had severe CHF, which was controlled using pimobendan and amrinone. Patients with cardiomyopathy can receive allogeneic SCT under strict hemodynamic management.     

HLA and hepatitis C virus positive cardiomyopathy

The relationship between HCV (hepatitis C virus) and the susceptibility of cardiomyopathy has been indicated, but the detailed mechanism for close association is still unknown. It is well known that the human leukocyte antigen (HLA) may regulate the development of chronic hepatitis in HCV positive patients. We have analyzed the distribution of HLA class II alleles in Japanese patients with HCV antibody positive dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), and HLA-DPB1*0901 was significantly increased in HCV Ab positive DCM, and the HLA-DRB1*0901-DQB1*0303 haplotype was in HCV Ab positive HCM. These results suggested that molecular mechanism for the development of cardiomyopathy mediated by HCV is different between DCM and HCM.     

Failure to detect significant association between estrogen receptor-alpha gene polymorphisms and endometriosis in Japanese women

Objectives

The aim of the study was to test whether estrogen receptor 1 (ESR1) gene polymorphisms are correlated with the risk of the development of endometriosis in Japanese women, as a preliminary study.

Methods

To compare allelic frequencies and genotype distributions, a case-control study of 100 affected women and 143 women with no evidence of disease was performed using 10 microsatellite repeat markers and 66 single-nucleotide polymorphisms (SNPs) in the ESR1 gene region.

Results

Although our results might be insufficient to detect genetic susceptibility, owing to the small sample size and low genetic power, statistical analysis of the differences in allelic frequency between the cases and controls at each microsatellite locus demonstrated that no microsatellite locus in the ESR1 gene displayed a significant association with the disease when multiple testing was taken into account. Also, there were no statistically significant differences in the SNP allele frequencies and genotypes between the cases and controls when multiple testing was taken into account.

Conclusion

The findings in our pilot study suggest that ESR1 polymorphisms do not contribute to endometriosis susceptibility.     

Coronary flow after successful angioplasty in patients with acute myocardial infarction: comparison between coronary flow reserve by nicorandil and papaverine

In order to evaluate coronary flow response to 2 different vasodilators, nicorandil and papaverine, in patients with myocardial infarction, we measured coronary flow reserve using a Doppler guide wire in infarct-related and non infarct-related arteries. The study group consisted of 28 patients with first acute myocardial infarction 3 weeks after successful coronary angioplasty within 6 hr after symptom onset. Twelve patients with atypical chest pain served as the control group. Coronary flow reserve induced by intracoronary papaverine(12 mg) was lower in infarct-related arteries than in non infarct-related arteries, but there were no differences in coronary flow reserve induced by intracoronary nicorandil(1 mg) between infarct-related and non infarct-related arteries. Coronary flow reserve induced by nicorandil was lower than that by papaverine in non infarct-related arteries and the control group. However, there were no differences between coronary flow reserve induced by nicorandil and papaverine in infarct-related arteries. Vasodilatory response induced by nicorandil was relatively preserved in infarct-related arteries compared with papaverine. These results suggest that impairment of coronary microvascular response in infarct myocardium varies in the different sites acted on by different vasodilator agents.     

Clinical characteristics of patients with fresh left ventricular thrombus

The present study analyzed the clinical backgrounds of 9 patients with fresh left ventricular thrombus (LVT) detected by two-dimensional echocardiography during the past 5 years. Patients with acute myocardial infarction were excluded. Left ventricular systolic function was disturbed either diffusely or segmentally in all patients with a mean ejection fraction of 33%. In 7 patients, echocardiography was performed shortly after furosemide therapy for New York Heart Association class IV congestive heart failure; echocardiography was also performed just before treatment in 4 of the 7 patients and LVT was not detected in any of them. Two patients died of underlying disorders within 2 months of detection of the thrombus. However, the LVT disappeared in the other 7 patients without any thromboembolic episodes during the 6 months after starting anticoagulant therapy. As fresh LVT developed shortly after diuretic therapy in patients with severe congestive heart failure associated with left ventricular systolic dysfunction, concomitant anticoagulant therapy is recommended.     

Risk factors of thrombotic recurrence and major bleeding in patients with intermediate-risk for recurrence of venous thromboembolism

Journal of Thrombosis and Thrombolysis - Prolonged anticoagulation therapy is recommended for patients with intermediate-risk for recurrence of venous thromboembolism (VTE). The current study aimed...     

Association of sick building syndrome with neuropathy target esterase (NTE) activity in Japanese

Sick building syndrome (SBS) is a set of several clinically recognizable symptoms reported by occupants of a building without a clear cause. Neuropathy target esterase (NTE) is a membrane bound serine esterase and its reaction with organophosphates (OPs) can lead to OP‐induced delayed neuropathy (OPIDN) and nerve axon degeneration. The aim of our study was to determine whether there was a difference in NTE activity in the peripheral blood mononuclear cells (PBMCs) of Japanese patients with SBS and healthy controls and whether PNPLA6 (alias NTE) gene polymorphisms were associated with SBS. We found that the enzymatic activity of NTE was significantly higher (P < 0.0005) in SBS patients compared with controls. Moreover, population with an AA genotype of a single nucleotide polymorphism (SNP), rs480208, in intron 21 of the PNPLA6 gene strongly reduced the activity of NTE. Fifty‐eight SNP markers within the PNPLA6 gene were tested for association in a case–control study of 188 affected individuals and 401 age‐matched controls. Only one SNP, rs480208, was statistically different in genotype distribution (P = 0.005) and allele frequency (P = 0.006) between the cases and controls (uncorrected for testing multiple SNP sites), but these were not significant by multiple corrections. The findings of the association between the enzymatic activity of NTE and SBS in Japanese show for the first time that NTE activity might be involved with SBS. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1217–1226, 2014.     

Sodium/calcium exchange modulates intracellular calcium overload during posthypoxic reoxygenation in mammalian working myocardium. Evidence from aequorin-loaded ferret ventricular muscles.

We tested the hypothesis that the intracellular Ca2+ overload of ventricular myocardium during the period of posthypoxic reoxygenation is mediated by transsarcolemmal Ca2+ influx via Na+/Ca2+ exchange. In aequorin-loaded, ferret right ventricular papillary muscles, blockers of the sarcolemmal and the sarcoplasmic reticulum Ca2+ channels, slowed the Cai2+ transient, producing a convex ascent during membrane depolarization, followed by a concave descent during repolarization. The magnitude of the Cai2+ transient was affected by changes in the membrane potential, Nai+, Nao+, and Cao2+, and was blocked by Ni2+, or dichlorbenzamil. The calculated Na+/Ca2+ exchange current was in the reverse mode (Ca2+ influx) during the ascending phase of the Cai2+ transient, and was abruptly switched to the forward mode (Ca2+ efflux) at repolarization, matching the time course of the Cai2+ transient. During hypoxic superfusion, the Cai2+ transient was abbreviated, which was associated with a shorter action potential duration. In contrast, immediately after reoxygenation, the Cai2+ transient increased to a level greater than that of the control, even though the action potential remained abbreviated. This is the first demonstration on a beat-to-beat basis that, during reoxygenation, Ca2+ influx via Na+/Ca2+ exchange is augmented and transports a significant amount of Ca2+ into the ventricular myocardial cell. The activation of the exchanger at the time of reoxygenation appears to be mediated by Nai+ accumulation, which occurs during hypoxia.