Cytogenetic and Dermatoglyphic Studies on Severely Hand­icapped Patients in an Institution

Cytogenetic and dermatoglyphic studies were performed on a group of 197 institutionalized patients with severe mental and physical handicaps in order to evaluate the contribution of chromosomal aberrations on the etiology of the condition, and to determine whether any association exists between the dermatoglyphics and the severe handicaps. There were 4 patients with trisomy 21 and 2 patients with a de novo balanced reciprocal translocation. In addition, 9 patients were found to have a pericentric inversion of chromosome 9 (inv (9) (p11q13)). Other chromosome variations identified included inv (1) (p11q11) (one case), elongation of 1 qh (one case), and telocentric chromosome 13 (two cases). Dermatoglyphics from the patients excluding cases with Down syndrome were compared with those from 500 normal controls. Significant differences were observed in several dermatoglyphic characteristics, including simian crease, fingertip pattern, mean a-b ridge count, thenar/first interdigital pattern, hypothenar pattern, and hallucal pattern. The present study indicated that de novo balanced translocation as well as chromosome duplication or deficiency is causally related to the severe combined handicaps. This study also showed that the incidence of inv (9) (p11q13) in the patients was 4.2 times higher than that in the general Japanese population. If a real association exists between the inv (9) (p11q13) and severe handicaps, the increase of inv (9) (p11q13) in the patients may be explained by the concept of a risk factor. Moreover, the dermatoglyphic deviations found in patients may be evidence that pathological factors had been operating during early embryonic life in some of them.</p

Gastric Endocrine Cell Carcinoma with Long-Term Survival Developing Metachronous Remnant Cancer

A rare case of primary gastric endocrine cell carcinoma in a 79-year-old man is reported. Upper gastrointestinal endoscopy showed a large Bormann's type 2 tumour located in the middle of the stomach. On computed tomography, the gastric wall was thickened by the large tumour, and there were no distant metastases. Distal gastrectomy, lymph node dissection, and partial resection of the transverse colon were performed because the tumour involved the transverse mesocolon. The final pathological diagnosis was endocrine cell carcinoma, with tumour infiltration up to the subserous layer. Adjuvant chemotherapy was given, but metachronous remnant gastric cancer developed 2 years after surgery. Endoscopic submucosal dissection was performed for the early 0-IIc type gastric cancer, and the surgical margin was preserved. The patient has survived for 5 years after the primary surgery, remaining disease-free so far

A rare case of xanthogranuloma of the stomach masquerading as an advanced stage tumor

<p>Abstract</p> <p>Background</p> <p>Xanthogranuloma of the stomach is an extremely rare disease, and this lesion has only been found to coexist with early gastric cancer in 2 cases in the literature.</p> <p>Case presentation</p> <p>We report a case of xanthogranuloma of the stomach combined with early gastric cancer that mimicked an advanced stage tumor. A 65-year-old female was referred to our hospital because of epigastralgia. During a physical examination, a defined abdominal mass was palpable in the region of the left hypochondrium. Imaging studies revealed an advanced gastric cancer, which was suspected of having infiltrated the abdominal wall. Total gastrectomy and resection of the regional lymph node and abdominal wall were performed. Histopathologic examination of the resected specimen demonstrated xanthogranuloma combined with early gastric cancer.</p> <p>Conclusion</p> <p>Xanthogranuloma presenting as a form of SMT (submucosal tumor) of the stomach is an extremely rare disease, and diagnosing it preoperatively is difficult. Further accumulation and investigation of this entity is necessary.</p

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

Drug Release Profile from Calcium-Induced Alginate-Phosphate Composite Gel Beads

Calcium-induced alginate-phosphate composite gel beads were prepared, and model drug release profiles were investigated in vitro. The formation of calcium phosphate in the alginate gel matrix was observed and did not affect the rheological properties of the hydrogel beads. X-ray diffraction patterns showed that the calcium phosphate does not exist in crystalline form in the matrix. The initial release amount and release rate of a water-soluble drug, diclofenac, from the alginate gel beads could be controlled by modifying the composition of the matrix with calcium phosphate. In contrast, the release profile was not affected by the modification for hydrocortisone, a drug only slightly soluble in water