Emergency Operation for Non-Hodgkin Lymphoma of the Small Intestine

We report 5 cases of non-Hodgkin lymphoma of the small intestine (S-NHL) treated with emergency operation. These cases showed three reasons for emergency operation :［1］massive hemorrhage with shock before diagnosis of S-NHL (Case 1),［2］obstruction of the small intestine before and during chemotherapeutic treatment for S-NHL (Cases 2 and 3),and［3］spontaneous perforation with peritonitis before diagnosis of SNHL or iatrogenic perforation following chemotherapy (Cases 4 and 5).For tumor discovery,double-balloon endoscopy of the small intestine was employed in 3 cases.Three tumors were histologically diagnosed before treatment,while 2 were histopathologically diagnosed using the resected specimens after emergency operation. An advanced stage of NHL was frequently observed.No surgical mortality accurred.We always consider the possibility of emergency operation before, during, and after the diagnosis and treatment of patients with SNHL. Shinshu Med J 60 : 21-25, 2012Article信州医学雑誌 60(1): 21-25(2012)departmental bulletin pape

Male Infertility and Its Causes in Human

Infertility is one of the most serious social problems facing advanced nations. In general, approximate half of all cases of infertility are caused by factors related to the male partner. To date, various treatments have been developed for male infertility and are steadily producing results. However, there is no effective treatment for patients with nonobstructive azoospermia, in which there is an absence of mature sperm in the testes. Although evidence suggests that many patients with male infertility have a genetic predisposition to the condition, the cause has not been elucidated in the vast majority of cases. This paper discusses the environmental factors considered likely to be involved in male infertility and the genes that have been clearly shown to be involved in male infertility in humans, including our recent findings

Discovery of a TEKTIN-t/TEKT2 Gene Variant Encoding Sperm Flagellar Protein in Japanese Males

ﾃｸﾁﾝは､ﾀﾞｲﾆﾝとともに精子の鞭毛や繊毛の形成に関与したﾀﾝﾊﾟｸ質である｡ﾃｸﾁﾝには､ﾋﾄにおいて少なくとも6種類の遺伝子の存在が報告されている｡ﾃｸﾁﾝ遺伝子のうち､Tektin-t/Tekt2､Tekt3､もしくは Tekt4 が欠失することによって､精子の鞭毛が機能不全を起こし､なかでも Tektin-t/Tekt2 遺伝子の欠失は､雄性不妊症になることがﾏｳｽで示されている｡男性不妊症の原因にﾃｸﾁﾝ遺伝子の機能不全が関与することが予想される｡私たちは､ﾋﾄ TETIN-t/TEKT2 遺伝子の遺伝子多型と男性不妊症との関係について調べるため､282人の原因不明の男性不妊症患者と89人の妊孕性が確認された男性ﾎﾞﾗﾝﾃｨｱの遺伝子の解析を行った｡その結果､日本人男性不妊症患者に有意に検出される TETIN-t/TEKT2 遺伝子の変化は見られなかった｡これらの結果は､TETIN-t/TEKT2 は､日本人男性不妊症の原因遺伝子となる割合は非常に低くいことを示すとともに､今後の大規模な男性不妊症の原因となる遺伝子の解析に役に立つものと考えられる｡TEKTIN proteins contribute to the formation of cilia and flagella together with dynein. At least six types of TEKTIN genes have been reported in humans. The disruption of Tektin-t/Tekt2, Tekt3, or Tekt4 in mice causes sperm flagellar dysfunction, and Tektin-t/Tekt2 null male mice are infertile. To investigate the possible association between variations in TEKTIN-t/TEKT2 and impaired spermatogenesis in Japanese males, we screened for mutations in TEKTIN-t/TEKT2 using DNA from 282 sterile male patients and 89 proven-fertile male volunteers. Six polymorphisms were found in the open reading frame of TEKTIN-t/TEKT2, but no significant differences in genotype frequency were identified in the infertile subjects(P>0.05). We also did not detect a previously reported TEKTIN-t/TEKT2 gene variant in our subjects. These data may be applied to future large-scale genetic analyses of the association between genetic background and male infertility

Genetic Variation in the Testis-Specific GSG3/CAPZA3 Gene Encoding for the Actin Regulatory Protein in Infertile Males

ｱｸﾁﾝｷｬｯﾋﾟﾝｸﾞ蛋白質 GSG3/CAPZA3 は､受精可能な精子の形態形成に重要な役割を担っている｡GSG3/CAPZA3 遺伝子は､ｲﾝﾄﾛﾝﾚｽ遺伝子として哺乳類に保存され､ﾏｳｽにおいてﾐｯｾﾝｽ変異が精子の減少と形態異常を誘導し､雄性不妊症の原因となることが知られている｡日本人において男性不妊症と GSG3/CAPZA3 遺伝子多型の関係を調べるため､261人の男性不妊症患者と139人の妊孕性が確認された男性ﾎﾞﾗﾝﾃｨｱの遺伝子多型を調べた｡その結果､妊孕性が確認された男性ﾎﾞﾗﾝﾃｨｱの一人にｱﾐﾉ酸置換を伴う一塩基多型がﾍﾃﾛ接合型として検出された｡このことから､GSG3/CAPZA3 遺伝子には､他の精子細胞特異的ｲﾝﾄﾛﾝﾚｽ遺伝子に比べて遺伝子多型が極めてわずかしか存在しないことが示唆された｡The actin capping protein GSG3/CAPZA3 plays a physiologically important role in maintaining sperm architecture for fertilization. The GSG3/CAPZA3 gene is conserved in mammals and lacks introns. A missense mutation in the CAPZA3 gene in mice causes male infertility by reducing the concentration and changing the shape of sperm. To investigate possible associations between GSG3/CAPZA3 gene variations and impaired spermatogenesis in Japanese males, we screened for mutations in GSG3/CAPZA3 using DNA from 261 sterile male patients and 139 male volunteers who were fertile. A single nucleotide polymorphism(SNP)was found in one sample in the heterozygous state in the fertile male volunteers. The results indicate that compared with other germ-cell-specific intronless genes the change was restricted in GSG3/CAPZA3 protein

Single Nucleotide Polymorphisms of the IZUMO Gene in Male Infertile Patients

IZUMOは精子頭部の膜表面に局在し、マウスの精子と卵の受精に必須なタンパク質である。日本人におけるIZUMO遺伝子の多型と精子形成の異常の関係を解析するために、我々は妊孕性の確認されたボランティアの男性１７２人と男性不妊症患者８９２人のゲノムDNAを用いてIZUMO遺伝子の多型と変異の検索を行った。ABI‐PRISM 3730xl Genetic Analyzer and SeqScape software （Applied Biosystems社）を用い解析を行った結果、妊孕性の確認されたボランティアの男性では検出されない一塩基置換を男性不妊症患者に見出した。初回の探索において、男性不妊症患者に４つの一塩基多型（４１７T>G（Cys１３９Trp），５８９A>T（Ser１９７Cys），９３９T>A（Phe３１３Leu），９４４G>A（Arg３１５Gln））が有意に検出された。これらの一塩基置換は、別のプライマーセットを用いた塩基配列解析では検出することができなかったが、一塩基多型と男性不妊症の関係の解析において重要な標的候補と考えられる。IZUMO is a surface protein on sperm and essential for egg fusion in mice. To investigate the possible association between variations in the IZUMO gene and impaired spermatogenesis in Japanese males, we screened for mutations in the human IZUMO gene using DNA from 892 sterile male patients and 172 proven-fertile male volunteers. Single Nucleotide Polymorphisms (SNPs) were identified in the heterozygous state in the infertile patients, and neither variant was identified in fertile subjects using an ABI-PRISM 3730xl Genetic Analyzer and SeqScape software (Applied Biosystems). Four single nucleotide polymorphisms (SNPs), 417 T>G (Cys 139 Trp), 589 A>T (Ser 197 Cys), 939 T>A (Phe 313 Leu), and 944 G>A (Arg 315 Gln), were found significantly more often in infertile subjects than in fertile controls in the first screening. Otherwise, the four SNPs were not detected by direct sequencing using the other primers. These results show that four SNPs exist as an analytical target of SNPs that associated with the male infertility n the IZUMO gene

SARS-CoV-2 spike receptor-binding domain is internalized and promotes protein ISGylation in human induced pluripotent stem cell-derived cardiomyocytes

Although an increased risk of myocarditis has been observed after vaccination with mRNA encoding severe acute respiratory syndrome coronavirus 2 spike protein, its underlying mechanism has not been elucidated. This study investigated the direct effects of spike receptor-binding domain (S-RBD) on human cardiomyocytes differentiated from induced pluripotent stem cells (iPSC-CMs). Immunostaining experiments using ACE2 wild-type (WT) and knockout (KO) iPSC-CMs treated with purified S-RBD demonstrated that S-RBD was bound to ACE2 and internalized into the subcellular space in the iPSC-CMs, depending on ACE2. Immunostaining combined with live cell imaging using a recombinant S-RBD fused to the superfolder GFP (S-RBD-sfGFP) demonstrated that S-RBD was bound to the cell membrane, co-localized with RAB5A, and then delivered from the endosomes to the lysosomes in iPSC-CMs. Quantitative PCR array analysis followed by single cell RNA sequence analysis clarified that S-RBD-sfGFP treatment significantly upregulated the NF-kβ pathway-related gene (CXCL1) in the differentiated non-cardiomyocytes, while upregulated interferon (IFN)-responsive genes (IFI6, ISG15, and IFITM3) in the matured cardiomyocytes. S-RBD-sfGFP treatment promoted protein ISGylation, an ISG15-mediated post-translational modification in ACE2-WT-iPSC-CMs, which was suppressed in ACE2-KO-iPSC-CMs. Our experimental study demonstrates that S-RBD is internalized through the endolysosomal pathway, which upregulates IFN-responsive genes and promotes ISGylation in the iPSC-CMs.Okuno S., Higo S., Kondo T., et al. SARS-CoV-2 spike receptor-binding domain is internalized and promotes protein ISGylation in human induced pluripotent stem cell-derived cardiomyocytes. Scientific Reports 13, 21397 (2023); https://doi.org/10.1038/s41598-023-48084-7

SNPs within the Intron-less TAF7 Gene Encoding a General Transcription Factor in Japanese Males

TAF7 は転写開始と伸長に必須な転写開始前複合体に含まれる｡精巣において､TAF7 は細胞の増殖を伴う精原細胞と第一精母細胞の核に局在し､また､TAF7 の精巣特異的ｱｲｿｻﾞｲﾑである TAF7L は､精子細胞分化過程で核に局在する｡このことから､雄性生殖細胞では､細胞増殖を伴う精原細胞では TAF7 が､その後の精子分化過程では TAF7L が転写調節に機能していることが考えられる｡今回私たちは､細胞増殖をともなう精原細胞で発現する TAF7 ｲﾝﾄﾛﾝﾚｽ遺伝子について､男性不妊症と TAF7 の遺伝子多型の関係を調べるため､282人の日本人男性不妊症患者と96人の妊孕性が確認された日本人男性ﾎﾞﾗﾝﾃｨｱの遺伝子多型を調べた｡その結果､男性不妊症性患者において､5\u27 非翻訳領域に CTC の3塩基欠失と､ｱﾐﾉ酸置換を伴う一塩基多型がそれぞれﾍﾃﾛ接合型として各々一人づつ検出された｡ The National Center for Biotechnology Information には TAF7 に関して多くの一塩基多型が登録されているが､日本人男性に関してそれらの遺伝子多型はほとんどが検出されなかった｡新たに同定されたこれらの遺伝子多型は､体質と遺伝子多型の大規模な解析に役立つものと考えられる｡TAF7 is a part of the protein complex that is indispensable for the start of transcription. In the testis, TAF7 localizes on nuclei in spermatogonia and primary spermatocytes during proliferation. To examine whether genetic polymorphisms of the intron-less TAF7 gene are associated with male infertility, we screened TAF7 for genetic polymorphisms using DNA from 282 sterile and 96 fertile male volunteers. We identified 11 genetic polymorphisms in the TAF7 region. Although many single nucleotide polymorphisms (SNPs) have been reported in the SNP database of the National Center for Biotechnology Information, we found a novel CTC deletion and one SNP with an amino acid substitution in the TAF7 genomic region in infertile patients. These genetic polymorphisms might be causes of male sterility. These results will be useful for analyzing the association of traits and genetic polymorphisms in further large-scale genetic analyses

Alterations in the steroid hormone receptor co-chaperone FKBPL are associated with male infertility: a case-control study

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Male infertility is a common cause of reproductive failure in humans. In mice, targeted deletions of the genes coding for FKBP6 or FKBP52, members of the FK506 binding protein family, can result in male infertility. In the case of FKBP52, this reflects an important role in potentiating Androgen Receptor (AR) signalling in the prostate and accessory glands, but not the testis. In infertile men, no mutations of FKBP52 or FKBP6 have been found so far, but the gene for FKBP-like (FKBPL) maps to chromosome 6p21.3, an area linked to azoospermia in a group of Japanese patients. Methods To determine whether mutations in FKBPL could contribute to the azoospermic phenotype, we examined expression in mouse and human tissues by RNA array blot, RT-PCR and immunohistochemistry and sequenced the complete gene from two azoospermic patient cohorts and matching control groups. FKBPL-AR interaction was assayed using reporter constructs in vitro. Results FKBPL is strongly expressed in mouse testis, with expression upregulated at puberty. The protein is expressed in human testis in a pattern similar to FKBP52 and also enhanced AR transcriptional activity in reporter assays. We examined sixty patients from the Japanese patient group and found one inactivating mutation and one coding change, as well as a number of non-coding changes, all absent in fifty-six controls. A second, Irish patient cohort of thirty showed another two coding changes not present in thirty proven fertile controls. Conclusions Our results describe the first alterations in the gene for FKBPL in azoospermic patients and indicate a potential role in AR-mediated signalling in the testis.Published versio