High prevalence of wild-type transthyretin deposition in patients with idiopathic carpal tunnel syndrome: a common cause of carpal tunnel syndrome in the elderly

Carpal tunnel syndrome is the most common type of entrapment neuropathy. However, the cause of carpal tunnel syndrome remains unclear in most cases. Senile systemic amyloidosis, induced by wild-type transthyretin deposition, is a prevalent aging-related disorder and often accompanied by carpal tunnel syndrome. In this study, we measured the frequency of unrecognized wild-type transthyretin deposition in patients with idiopathic carpal tunnel syndrome. One hundred twenty-three patients with carnal tunnel syndrome, including 100 idiopathic patients, treated by carpal tunnel release surgery were analyzed. Tenosynovial tissues obtained at surgery were analyzed by Congo red and immunohistochemical staining. If staining for transthyretin was positive, the entire transthyretin gene was analyzed by direct DNA sequencing. We also analyzed tenosynovial tissues from 32 autopsy cases as controls. Thirty-four patients (34.0%) with idiopathic carpal tunnel syndrome showed amyloid deposition in the tenosynovial tissue, and all amyloid showed specific immunolabeling with antitransthyretin antibody. Direct DNA sequencing of the entire transthyretin gene did not reveal any mutations, indicating that all amyloid deposits were derived form wild-type transthyretin. Statistical analysis using logistic regression showed that the prevalence of transthyretin deposition in the idiopathic carpal tunnel syndrome group was significantly higher than that in controls (odds ratio, 15.8; 95% confidence interval, 3.3-75.7), and age and male sex were independent risk factors for transthyretin amyloid deposition. Our results demonstrate that wild-type transthyretin deposition is a common cause of carpal tunnel syndrome in elderly men. It is likely that many patients develop carpal tunnel syndrome as an initial symptom of senile systemic amyloidosis.ArticleHUMAN PATHOLOGY. 42(11):1785-1791 (2011)journal articl

High prevalence of wild-type transthyretin deposition in patients with idiopathic carpal tunnel syndrome: a common cause of carpal tunnel syndrome in the elderly

Carpal tunnel syndrome is the most common type of entrapment neuropathy. However, the cause of carpal tunnel syndrome remains unclear in most cases. Senile systemic amyloidosis, induced by wild-type transthyretin deposition, is a prevalent aging-related disorder and often accompanied by carpal tunnel syndrome. In this study, we measured the frequency of unrecognized wild-type transthyretin deposition in patients with idiopathic carpal tunnel syndrome. One hundred twenty-three patients with carnal tunnel syndrome, including 100 idiopathic patients, treated by carpal tunnel release surgery were analyzed. Tenosynovial tissues obtained at surgery were analyzed by Congo red and immunohistochemical staining. If staining for transthyretin was positive, the entire transthyretin gene was analyzed by direct DNA sequencing. We also analyzed tenosynovial tissues from 32 autopsy cases as controls. Thirty-four patients (34.0%) with idiopathic carpal tunnel syndrome showed amyloid deposition in the tenosynovial tissue, and all amyloid showed specific immunolabeling with antitransthyretin antibody. Direct DNA sequencing of the entire transthyretin gene did not reveal any mutations, indicating that all amyloid deposits were derived form wild-type transthyretin. Statistical analysis using logistic regression showed that the prevalence of transthyretin deposition in the idiopathic carpal tunnel syndrome group was significantly higher than that in controls (odds ratio, 15.8; 95% confidence interval, 3.3-75.7), and age and male sex were independent risk factors for transthyretin amyloid deposition. Our results demonstrate that wild-type transthyretin deposition is a common cause of carpal tunnel syndrome in elderly men. It is likely that many patients develop carpal tunnel syndrome as an initial symptom of senile systemic amyloidosis.ArticleHUMAN PATHOLOGY. 42(11):1785-1791 (2011)journal articl

有限要素法を用いた中小病院の「Clean Hospital化」に関する実測および解析

In recent years, the increase of nosocomical infections caused by droplet infection, airborne infection or contact infection has been a social problem, and preventive countermeasures are being discussed. For SARS (Severe Acute Respiratory Syndrome) for example, it has been argued that the delay of action to prevent it has caused a global problem. For the purpose of seeking data concerning hospital sanitization, from the perspective of preventive medicine, this paper examined the real condition of a certain small-to-medium sized hospital for a year. Measurements focused on microbes (staphylococci and fungi), the most serious sources of infections in hospitals, including common bacteria (total count), staphylococcus , aureus, and multidrug-resistant staphylococcus aureus. We measured air cleanliness and airborne microbes at principal spots in the hospital 12 times during the year; after culturing, colony count was done to each microbe. Also, we measured the surface-adherent microbes taken from walls or fixtures (work tables, handrails, bed sheets, etc.) 6 times during the year. Multivariate analysis was done on the data. The results show the changes in the number of microbes depending on temperature and humidity throughout a 12-month period. Compared effects of different cleaning methods are also shown

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

Effect of Apple Consumption on Postprandial Blood Glucose Levels in Normal Glucose Tolerance People versus Those with Impaired Glucose Tolerance

The present study investigated the effect of apple consumption on postprandial blood glucose and insulin levels in subjects with normal versus impaired glucose tolerance. The study participants were ten healthy subjects with no glucose intolerance (normal subjects) (mean, 24.4 ± 4.8 years) and nine subjects with impaired glucose tolerance (mean, 45.2 ± 11.1 years, including 2 on insulin therapy). The test meal included white rice (148 g) and a Fuji apple (150 g). The normal subjects were randomly divided into two groups: the apple-first group, wherein the subjects consumed white rice 5 min after consuming the apple, and the rice-first group, wherein the subjects consumed an apple 5 min after consuming the white rice. Blood samples were then taken from both groups for 3 h. In addition, the subjects with impaired glucose tolerance received the same treatment as the normal subjects, with the difference being glucose level monitoring according to the order in which the apples were consumed. In the normal subjects, the Cmax of Δblood glucose and Δinsulin levels were 54.0 ± 5.0 mg/dL and 61.9 ± 7.2 µU/dL versus 46.2 ± 5.9 mg/dL and 49.8 ± 8.5 µU/dL in the rice-first and apple-first groups, respectively. The incremental area under the curve (iAUC) of insulin tended to decrease in the apple-first group. In the impaired glucose tolerance subjects, the Cmax of Δblood glucose was 75.2 ± 7.2 mg/dL in the apple-first group compared to 90.0 ± 10.0 mg/dL in the rice-first group, which was a significant difference (p < 0.05). The iAUC of blood glucose was lower in the apple-first group. Eating an apple before a meal may be a simple and effective strategy for managing the glycaemic response in individuals with impaired glucose tolerance

Two different types of giant bleb formation following Ahmed Glaucoma valve implantation

Purpose: This study aims to present two different types of giant bleb formation following Ahmed Glaucoma Valve (AGV) implantation: an anterior enlarged giant bleb and a posterior enlarged giant bleb. Observations: In Case 1, a 70-year-old Japanese male underwent AGV implantation for neovascular glaucoma in his right eye (OD). Preoperatively, the patient's intraocular pressure (IOP) and best corrected visual acuity (BCVA) were 23 mmHg and 0.6, respectively, OD, while using 3 antiglaucoma topical medications. Two months post-surgery, the patient began experiencing double vision. Slit lamp evaluation revealed no abnormalities, IOP and BCVA were 24.0 mmHg and 0.8, respectively, OD. A posteriorly enlarged bleb in the superotemporal quadrant OD was found to be causing displacement on T2-weighted orbital MRI. The patient underwent surgical excision of the anterior bleb wall. By three weeks post-surgery, the double vision resolved; IOP and BCVA were 17 mmHg and 0.7, respectively, and a normal bleb in the slit lamp evaluation was identified OD. In Case 2, a 10-year-old Japanese female underwent AGV implantation for childhood glaucoma associated with congenital cataract OD. Preoperatively, IOP and BCVA were 30 mmHg and 0.5, respectively, OD, while using 3 antiglaucoma topical medications. She underwent pars plana vitrectomy (PPV) in addition to AGV implantation. Seven months post-surgery, slip lamp evaluation revealed an anteriorly enlarged giant bleb that only cause her a cosmetic concern. Conclusions and Importance: There are two types of giant bleb formation following AGV implantation based on the direction of the enlargement: an anterior enlarged giant bleb and a posterior enlarged giant bleb. The introduction of this classification contribute to better understanding and management of this unusual surgical complication

A fatal septic shock caused by Capnocytophaga gingivalis potentially associated with COVID-19: A case report

Background: Capnocytophaga spp. is associated with fulminant sepsis, particularly in those with immunosuppression. We here report a rare case of fatal fulminant septic shock caused by C. gingivalis, concurrent with COVID-19. Case Presentation: A Japanese woman developed septic shock, which led to her death. Polymerase chain reaction (PCR) testing of the respiratory specimen was positive for SARS-CoV-2, and a CT scan of the chests revealed bilateral ground glass opacities. The blood cultures identified C. gingivalis. The patient had rheumatoid arthritis and was taking prednisone orally. There were no splenic abnormalities shown on the CT scan. Conclusion: A rare case of fulminant septic shock caused by C. gingivalis, together with COVID-19 was identified. The precise pathogenesis of this combination, together with the best treatment option should be sought by further studies