原発性副甲状腺機能亢進症, 尿管ポリープおよび腎盂結石を伴ったKlinefelter症候群の1例

副甲状腺機能亢進症, 右尿管ポリープ, および右腎盂結石を合併したKlinefelter症候群の1例を経験し, その臨床経過を報告するとともに文献的考察を加えた。〔症例〕 55歳男性で右側腹部痛を主訴として来院した。理学的所見で外陰部は男性型であるが発育不良で両側睾丸は小さくeunuchoidal habitusを呈した。既往歴に右尿管結石で5回自然排石が認められたほかに, 16年前gynecomastiaのためmastectomyを受けた事がある。身長171 cm, arm span 177.8 cmで体毛は少なく染色体検査は47XXYでKlinefelter症候群と診断した。血清LH, FSHは高値でテストステロン値は低値を示した。排泄性腎盂造影で右水腎症と右腎孟結石が認められ, 逆行性腎盂造影により右尿管上部に水腎症の原因となる腫瘍による多発性陰影欠損がみられ, 尿細胞診も悪性腫瘍を疑わせたため, 右腎尿管全摘術を施行した。尿管腫瘍は組織学的には多発性の尿管ポリープであった。血清Ca, Pは正常範囲内であるがhypercalciuriaがみられ, %TRPも54%と低値で副甲状腺ホルモン値も高いため, 原発性副甲状腺機能亢進症を疑いcervical explorationを施行した。副甲状腺は, diffuse hyperplasiaを呈し3/4副甲状腺亜全摘術と胸腺摘出術を行った。摘出した胸腺内には異所性副甲状腺組織は認められなかった。文献的に本症候群には糖尿病, 甲状腺機能不全, 下垂体牲腺機能不全などのいくつかの内分泌機能障害が報告されている。しかし本症候群に副甲状腺機能充進を合併した報告は過去に1例をみるにすぎない。副甲状腺機能亢進症の診断上, %TRPと静脈カテーテルによる頸部静脈血のmultiple samplingによる副甲状腺ホルモン測定の意義について言及した。Herein is reported a case of 47 XXV-Klinefelter's syndrome associated with ureteral polyps, renal pelvic stone and primary hyperparathyroidism. To the best of our knowledge, this is the second patient reported to have Klinefelter's syndrome coexisting with primary hyperparathyroidism. Frequent endocrinological disorders in the patients with Klinefelter's syndrome and diagnostic problems for hyperparathyroidism and ureteral polyps are discussed

Nationwide retrospective observational study of idiopathic dendriform pulmonary ossification : clinical features with a progressive phenotype

Background: Diffuse pulmonary ossification is a specific lung condition that is accompanied by underlying diseases. However, idiopathic dendriform pulmonary ossification (IDPO) is extremely rare, and the clinical features remain unclear. In this study, we aimed to report the clinical characteristics of IDPO. Methods: We conducted a nationwide survey of patients with IDPO from 2017 to 2019 in Japan and evaluated the clinical, radiological, and histopathological findings of patients diagnosed with IDPO. Results: Twenty-two cases of IDPO were identified. Most subjects (82%) were male, aged 22-56 years (mean (SD), 37.9 (9.1)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1s). Two cases with rapid decline of 10% /year in %FVC predicted were observed.)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1s). Two cases with rapid decline of 10% /year in %FVC predicted were observed. )) at diagnosis. Nearly 80% of the subjects wereasymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1s). Two cases with rapid decline of 10% /year in %FVC predicted were observed. Conclusions: IDPO develops at a young age with gradually progressive phenotype. Further research and long-term (>20 years) follow-up are required to clarify the pathogenesis and clinical findings in IDPO

Abnormal spermatogenesis and male infertility in testicular zinc finger protein Zfp318-knockout mice

Zfp318, a mouse gene with a Cys2/His2 zinc finger motif, is mainly expressed in germ cells in the testis. It encodes two alternative transcripts, which regulate androgen receptor-mediated transcriptional activation or repression by overexpression of them. However, the role of Zfp318 is still obscure in vivo, especially in spermatogenesis. To elucidate the role of Zfp318 during gamete production, we established a knockout mouse line. Zfp318-null male mice exhibited infertility, whereas Zfp318-null female mice displayed normal fertility. ZFP318 was expressed during multiple stages of spermatogenesis, from spermatocytes to round spermatids. The nuclei of secondary spermatocytes showed high levels of expression. Histological analysis and quantitative analysis of DNA content showed decreased numbers of both spermatids in the seminiferous tubules and mature spermatozoa in the epididymides of Zfp318-null mice. These results suggest that Zfp318 is expressed as a functional protein in testicular germ cells and plays an important role in meiosis during spermatogenesis

CIN85 drives B cell responses by linking BCR signals to the canonical NF-κB pathway

CIN85 transduces B cell receptor signals to IKK-β, and its expression in B cells is essential for T cell–independent type II antibody responses in mice

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

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

Pulmonary Pleomorphic Carcinoma Detected as a Result of Pneumothorax and the Subsequent Occurrence of Multiple Cystic Metastases

A 39-year-old man was admitted for spontaneous pneumothorax. He underwent pulmonary resection to correct the lesion causing the air leakage, and a pathological diagnosis of pulmonary pleomorphic carcinoma was made because we thought that the pneumothorax developed due to the direct rupture of necrotic neoplastic tissue into the pleural cavity. After the operation, the patient received chemotherapy, during which multiple cystic metastases gradually developed in the lung that caused repeated occurrences of pneumothorax. Clinicians must be careful to recognize that pneumothorax can also be a complication of primary and various metastatic pulmonary malignancies