Hypoxic Ventilatory Response to Acute and Prolonged Hypoxic Exposures in Subjects Susceptible to High-altitude Pulmonary Edema

Article信州医学雑誌 69(4) : 179-187(2021)departmental bulletin pape

Myeloperoxidase (MPO) Gene Polymorphisms are not Associated with Japanese Patients with COPD

Article信州医学雑誌 68(1): 41-48(2020)journal articl

Gene-gene Interaction Between EPAS1 and EGLN1 in Patients with High-Altitude Pulmonary Edema

Article信州医学雑誌 63(3):157-165 (2015)journal articl

Electron Microscopy Observation of Human Pulmonary Ultrastructure in Two Patients with High-Altitude Pulmonary Edema

We examined the pulmonary ultrastructure in tissue from two patients with high-altitude pulmonary edema (HAPE) by electron microscopy. In one case, we found that neutrophils were trapped in pulmonary capillary lumen of alveolar-capillary wall and part of the cytoplasm of a neutrophil protruded and adhered to the capillary endothelium. There were several degranulated vacuoles in the cytoplasm of the neutrophil. The pulmonary capillary wall was deformed, thickened, and swollen and there was evidence of degeneration. In another case, infiltration of neutrophils and macrophages, proliferation of type II pneumocytes, and numerous red blood cells were also observed in alveolar air space. These electron microscopic ultrastructural observations illustrate for the first time damage to the pulmonary alveolar-capillary barrier in lung tissue of humans with advanced HAPE.ArticleHIGH ALTITUDE MEDICINE & BIOLOGY.18(3):288-291(2017)journal articl

Lack of Association of Serotonin 2A Receptor Gene in Japanese Patients with Obstructive Sleep Apnea Syndrome

Article信州医学雑誌 65(3): 153-162(2017)journal articl

The association of Toll-like receptor 4 gene polymorphisms with the development of emphysema in Japanese subjects: a case control study

<p>Abstract</p> <p>Background</p> <p>The principal role of Toll-like receptor 4 (TLR4) is the induction of immune responses to lipopolysaccharides. Previously, mice deficient in the <it>TLR4 </it>gene exhibited up-regulation of the NADPH oxidase system in the lungs. This resulted in increased oxidant generation and elastolytic activity, which led to pulmonary emphysema. It was suggested that TLR4 might maintain constitutive lung integrity by modulating oxidant generation. We investigated whether single nucleotide polymorphisms (SNPs) in the <it>TLR4 </it>gene were associated with the emphysema phenotype in Japanese subjects with chronic obstructive pulmonary disease (COPD).</p> <p>Results</p> <p>Seven SNPs in the <it>TLR4 </it>gene (<it>rs10759930</it>, <it>rs1927914</it>, <it>rs12377632</it>, <it>rs2149356, rs11536889</it>, <it>rs7037117</it>, and <it>rs7045953</it>) were genotyped with allelic discrimination assays. The frequencies of SNPs were compared between 106 patients with the emphysema phenotype of COPD and 137 healthy smokers. We found that the positivity of the individuals with the major G allele of <it>rs11536889 </it>was significantly less in the emphysema group than the control group (<it>p </it>= 0.019). The frequencies of the minor C allele and the distribution of the CC genotype as well as the frequency of the major haplotype that carried the minor C allele of <it>rs11536889 </it>were all significantly higher in the emphysema group than the control group (<it>p </it>= 0.0083, 0.019, and 0.004, respectively). Furthermore, the strength of the association of the CC genotype with the emphysema phenotype was in an odds ratio of 2.60 with 95% confidence intervals from 1.17 to 5.78. However, these significances were not apparent after adjust for age and smoking history by logistic regression. No associations were observed between the <it>rs11536889 </it>and the low attenuation area score, the forced expiratory volume, and the carbon monoxide diffusion capacity in the emphysema group.</p> <p>Conclusions</p> <p>The minor C allele of the <it>rs11536889 </it>SNP in the <it>TLR4 </it>gene is likely associated with the risk of developing emphysema in the Japanese population.</p

Myocardial Performance Index in Subjects Susceptible to High-Altitude Pulmonary Edema

Objective A recent study concerning high-altitude pulmonary edema (HAPE), a non-cardiogenic pulmonary edema, suggested that it is initially a hydrostatic-type pulmonary edema. We suspect that some extent of cardiac insufficiency may likely relate to the mechanism of the development of this disease. Methods By Doppler echocardiography, the Tei index (a new quantitative index proposed for the evaluation of global myocardial performance) and the systolic pulmonary artery pressure (sPAP) were measured before and after 30 minutes of hypoxic breathing. Patients Eleven HAPE-susceptible subjects (HAPE-s) and nine HAPE-resistant subjects (HAPE-r). Results The results of Tei index indicated an enhanced left myocardial performance but an impaired right performance in HAPE-s during hypoxic breathing. The sPAP of HAPE-s was significantly increased after hypoxic breathing, which was not correlated with the heart functions such as right ventricular (RV) Tei index, cardiac index (CI), percent ejection fraction (EF%) and percent fractional shortening (FS%) under hypoxic condition. Comparatively, the HAPE-r subjects did not show such significant changes of Tei index after hypoxic breathing. The results suggested that a paradoxical myocardial performance, in a format of an augmented left ventricular (LV) in contrast to an attenuated RV, was observed in the HAPE-s exposed to acute hypoxia. Conclusion The responses of the left and right myocardial performances to hypoxia may be involved in the pathogenesis of HAPE.ArticleINTERNAL MEDICINE. 50(24):2967-2973 (2011)journal articl