Estimation of the frequency of the recessive gene of acatalasemia in Japan

The frequency of recessive gene, heterozygotes and homozygotes in Japanese acatalasemia were estimated as 0.0038, 7.5 X 10-3 and 3.0 X 10-5 by DAHLBERG'S formula, and estimated as 0.00087, 1.73 xl 0-3 and 4.23 X 10-6 by KIMURA'S formula. The frequency of recessive gene was calcu. lated from the frequency of hypocatalasemia obtained by the screening method as 0.00083, and it was almost identical with that calculated 1:'&#62;y KIMURA'S formula. The number of acatalasemia was estimated as about 423 by KIMURA'S formula.</p

Epidemiological studies on subacute myelo-optico-neuropathy with abdominal symptoms (SMON) in epidemic area of Okayama Prefecture, Japan. XI. Epidemiological studies on SMON

Epidemiological study on the prevalence of SMON III Ibara City, Yoshii Town and Yubara Town in Okayama Prefecture was conducted and the following results were obtained. &#34;Epidemization precession&#34; (Die Prazession der Durchseuchung), described by Rudder which shows that ages common to this disease is shifting to younger generation as incidence rate increases, in the endemic regions was recognized in Ibara City and Yubara Town. The mode of the distribution of the interval between the primary and secondary patients in a family suggests that it corresponds to the incubation period. Distribution of the patients to the size of family is not adaptable to binomial model, but adaptable to chain binomial model, and the intra-household transmitted rate is 5 per cent, and the true intra-household transmitted rate is about two times as high as extra-household transmitted rate by the modified chain binomial model. Intra-hospital incidence among SMON patients and non-SMON patients as well as medical workers were observed at the time when the number of new patients increased in a hospital. In SMON patients, the rate of appendectomized ones was higher than that of non-SMON patients, suggesting that gastrointestinal tract has some relationship to the development of SMON disease.</p

A case of congenital unilateral partial absence of fallopian tube

Congenital partial absence of a fallopian tube has rarely been reported in the literature. A 29-year-old nulligravida woman presented with a two-year history of infertility. Hysterosalpingography revealed an obstructed left fallopian tube with a normal uterine cavity and right fallopian tube. After several AIH treatments, diagnostic laparoscopy was performed, revealing segmental absence of the mid portion of the left fallopian tube. Only a 1-cm stump of the left fallopian tube remained, the majority of the isthmic portion was absent. A 3-cm distal ampullary portion with normal-appearing fimbria was attached to the left pelvic sidewall near the pelvic brim. No other abnormal findings were observed for the uterus, right fallopian tube, and ligaments surrounding the uterus. There are two possible etiologies of partial absence of the fallopian tube:congenital absence associated with developmental alterations of the Müllerian ducts or asymptomatic torsion followed by autoamputation and reabsorption

Salivary Effects of Facial Vibrotactile Stimulation in Patients with Sjogren’s Syndrome and Poor Salivation

We examined the effect of vibrotactile apparatus in patients with Sjögren’s syndrome and others with reduced salivation in comparison to normal subjects. The most effective salivation in normal subjects was produced by 89 Hz vibrotactile stimulation with 9.8 μm amplitude on the parotid or submandibular glands vibrotactile stimuli. First, we examined by measuring the weight of dental cotton rolls positioned at the opening of the secretory duct for total salivation 3 min during resting, and then after 5-min intervals, the weights were measured every 3 min of vibrotactile stimulation on salivary glands. Furthermore, we measured facial temperature around vibrators after 2 min of vibration. We investigated 10 poor salivation patients with Sjögren’s syndrome (8 patients) defined by examinations (contrast study or scintigraphic test) and others (2 patients). About 50% of patients with poor salivation gained recognition for good results, although they had periods of short-term (3 months) and long-term effects (6–7 years) during recuperation. Furthermore, facial skin temperatures on both sides of parotid glands were decreased in Sjogren’s syndrome after vibration, although their temperatures were increased following recovery. Although the mechanism is not clear, we think that vibrotactile stimulation gives activation to salivary glands under the rising facial temperature

Current Performance and On-Going Improvements of the 8.2 m Subaru Telescope

An overview of the current status of the 8.2 m Subaru Telescope constructed and operated at Mauna Kea, Hawaii, by the National Astronomical Observatory of Japan is presented. The basic design concept and the verified performance of the telescope system are described. Also given are the status of the instrument package offered to the astronomical community, the status of operation, and some of the future plans. The status of the telescope reported in a number of SPIE papers as of the summer of 2002 are incorporated with some updates included as of 2004 February. However, readers are encouraged to check the most updated status of the telescope through the home page, http://subarutelescope.org/index.html, and/or the direct contact with the observatory staff.Comment: 18 pages (17 pages in published version), 29 figures (GIF format), This is the version before the galley proo

Effective impairment of myeloma cells and their progenitors by hyperthermia

Multiple myeloma (MM) remains incurable, and MM-initiating cells or MM progenitors are considered to contribute to disease relapse through their drug-resistant nature. In order to improve the therapeutic efficacy for MM, we recently developed novel superparamagnetic nanoparticles which selectively accumulate in MM tumors and extirpate them by heat generated with magnetic resonance. We here aimed to clarify the therapeutic effects on MM cells and their progenitors by hyperthermia. Heat treatment at 43°C time-dependently induced MM cell death. The treatment upregulated endoplasmic reticulum (ER) stress mediators, ATF4 and CHOP, while reducing the protein levels of Pim-2, IRF4, c-Myc and Mcl-1. Combination with the proteasome inhibitor bortezomib further enhanced ER stress to potentiate MM cell death. The Pim inhibitor SMI-16a also enhanced the reduction of the Pim-2-driven survival factors, IRF4 and c-Myc, in combination with the heat treatment. The heat treatment almost completely eradicated “side population” fractions in RPMI8226 and KMS-11 cells and suppressed their clonogenic capacity as determined by in vitro colony formation and tumorigenic capacity in SCID mice. These results collectively demonstrated that hyperthermia is able to impair clonogenic drug-resistant fractions of MM cells and enhance their susceptibility to chemotherapeutic drugs

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection