Expression and Localization of the Cell Adhesion Molecule SgIGSF during Regeneration of the Olfactory Epithelium in Mice

Spermatogenic immunoglobulin superfamily (SgIGSF) is a cell adhesion molecule originally discovered in mouse testis. SgIGSF is expressed not only in spermatogenic cells but also in lung and liver epithelial cells and in neurons and glia of the central and peripheral nervous systems. In the present study, we examined the expression and localization of SgIGSF in mouse olfactory epithelium before and after transection of the olfactory nerves, by RT-PCR, Western blotting and immunohistochemistry. In normal olfactory mucosa, SgIGSF showed 100 kDa in molecular weight, which was identical with that in the lung but different from that in the brain. SgIGSF was expressed on the membrane of all olfactory, sustentacular and basal cells, but more abundantly in the apical portions of the olfactory epithelium where the dendrites of olfactory cells are in contact with sustentacular cells. After olfactory nerve transection, mature olfactory cells disappeared in 4 days but were regenerated around 7–15 days by proliferation and differentiation of basal cells into mature olfactory cells through the step of immature olfactory cells. During this period, both the mRNA and protein for SgIGSF showed a transient increase, with peak levels at 7 days and 11 days, respectively, after the transection. Immunohistochemistry showed that the enriched immunoreactivity for SgIGSF at 7–11 days was localized primarily to the membrane of immature olfactory cells. These results suggested that, during regeneration of the olfactory epithelium, the adhesion molecule SgIGSF plays physiological roles in differentiation, migration, and maturation of immature olfactory cells

Thymus and Activation-regulated Chemokine as a Biomarker for IgG4-related Disease

High serum concentrations of thymus and activation-regulated chemokine (TARC) are observed in allergic diseases such as atopic dermatitis and bronchial asthma. Frequent allergic symptoms have been reported in patients with IgG4-related disease (IgG4-RD). We investigated the pathogenic role of TARC as a biomarker in IgG4-RD patients. We evaluated the serum concentrations of TARC from 29 IgG4-RD patients, 28 primary Sjogren syndrome (pSS) patients, and 23 healthy controls (HCs) by enzyme-linked immunosorbent assay (ELISA). We analyzed the correlations between the TARC concentrations and the subjects’ clinical parameters. To investigate the biological effect of TARC on the pathogenesis of IgG4-RD, we evaluated the in vitro induction of plasmablasts from IgG4-RD patients by TARC. The serum concentrations of TARC in the IgG4-RD patients were significantly higher than those of the pSS patients and HCs. The serum TARC concentration of the IgG4-RD group was positively correlated with the IgG4-RD responder index (IgG4-RD RI) score and with the number of organs involved, but it was not correlated with the serum IgG4 level or eosinophil number in the IgG4-RD patients’ peripheral blood. The patients who had lung involvement had higher serum TARC concentrations. In vitro, TARC clearly induced the formation of plasmablasts from the IgG4-RD patients’ peripheral blood mononuclear cells. Collectively, our data suggest that a systemic increment of TARC may contribute to the development of IgG4-RD through an aberrant induction of plasmablasts

Granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α in combination is a useful diagnostic biomarker to distinguish familial Mediterranean fever from sepsis

Objective: To identify potential biomarkers to distinguish familial Mediterranean fever (FMF) from sepsis.Method: We recruited 28 patients diagnosed with typical FMF (according to the Tel Hashomer criteria), 22 patients with sepsis, and 118 age-matched controls. Serum levels of 40 cytokines were analyzed using multi-suspension cytokine array. We performed a cluster analysis of each cytokine in the FMF and sepsis groups in order to identify specific molecular networks. Multivariate classification (random forest analysis) and logistic regression analysis were used to rank the cytokines by importance and determine specific biomarkers for distinguishing FMF from sepsis.Results: Fifteen of the 40 cytokines were found to be suitable for further analysis. Levels of serum granulocyte-macrophage colony-stimulating factor (GM-CSF), fibroblast growth factor 2, vascular endothelial growth factor, macrophage inflammatory protein-1b, and interleukin-17 were significantly elevated, whereas tumor necrosis factor-α (TNF-α) was significantly lower in patients with FMF compared with those with sepsis. Cytokine clustering patterns differed between the two groups. Multivariate classification followed by logistic regression analysis revealed that measurement of both GM-CSF and TNF-α could distinguish FMF from sepsis with high accuracy (cut-off values for GM-CSF = 8.3 pg/mL; TNF-α = 16.3 pg/mL; sensitivity, 92.9%; specificity, 94.4%; accuracy, 93.4%).Conclusion: Determination of GM-CSF and TNF-α levels in combination may represent a biomarker for the differential diagnosis of FMF from sepsis, based on measurement of multiple cytokines

Pengaruh Komunikasi Terapeutik Perawat Terhadap Kepuasan Pasien Di Rawat Jalan RSUD Jogja

The Objective of this study is to know influence of nurse therapeutic communication to satisfaction of patients satisfaction in RSUD Yogyakarta. The study was a quantitative research methods such as surveys of descriptive inferential research with cross sectional approach. Number of samples in this research is 285 sample in inpatient and 140 in emergency room. The instrument used a questionnaire. Analysis of data using multiple linear regression. This study show that there is the influence of therapeutic communication nurse to satisfaction of outpatients and Emergency room in RSUD Yogyakarta, and orientation phase is a phase that most influence on patient satisfaction. The most influential to therapeutic communication is termination stage

Upper abdominal body shape is the risk factor for postoperative pancreatic fistula after splenectomy for advanced gastric cancer: A retrospective study

<p>Abstract</p> <p>Background</p> <p>Postoperative pancreas fistula (POPF) is a major complication after total gastrectomy with splenectomy. We retrospectively studied the effects of upper abdominal shape on the development of POPF after gastrectomy.</p> <p>Methods</p> <p>Fifty patients who underwent total gastrectomy with splenectomy were studied. The maximum vertical distance measured by computed tomography (CT) between the anterior abdominal skin and the back skin (U-APD) and the maximum horizontal distance of a plane at a right angle to U-APD (U-TD) were measured at the umbilicus. The distance between the anterior abdominal skin and the root of the celiac artery (CAD) and the distance of a horizontal plane at a right angle to CAD (CATD) were measured at the root of the celiac artery. The CA depth ratio (CAD/CATD) was calculated.</p> <p>Results</p> <p>POPF occurred in 7 patients (14.0%) and was associated with a higher BMI, longer CAD, and higher CA depth ratio. However, CATD, U-APD, and U-TD did not differ significantly between patients with and those without POPF. Logistic-regression analysis revealed that a high BMI (≥25) and a high CA depth ratio (≥0.370) independently predicted the occurrence of POPF (odds ratio = 19.007, p = 0.002; odds ratio = 13.656, p = 0.038, respectively).</p> <p>Conclusion</p> <p>Surgical procedures such as total gastrectomy with splenectomy should be very carefully executed in obese patients or patients with a deep abdominal cavity to decrease the risk of postoperative pancreatic fistula. BMI and body shape can predict the risk of POPF simply by CT.</p

Protective Role of HLA-DRB1*13:02 against Microscopic Polyangiitis and MPO-ANCA-Positive Vasculitides in a Japanese Population: A Case-Control Study

Among antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), granulomatosis with polyangiitis (GPA) and proteinase 3-ANCA-positive AAV (PR3-AAV) are prevalent in European populations, while microscopic polyangiitis (MPA) and myeloperoxidase-ANCA-positive AAV (MPO-AAV) are predominant in the Japanese. We previously demonstrated association of DRB1*09:01-DQB1*03:03 haplotype, a haplotype common in East Asians but rare in the European populations, with MPA/MPO-AAV, suggesting that a population difference in HLA-class II plays a role in the epidemiology of this disease. To gain further insights, we increased the sample size and performed an extended association study of DRB1 and DPB1 with AAV subsets in 468 Japanese patients with AAV classified according to the European Medicines Agency algorithm (MPA: 285, GPA: 92, eosinophilic GPA [EGPA]: 56, unclassifiable: 35) and 596 healthy controls. Among these patients, 377 were positive for MPO-ANCA and 62 for PR3-ANCA. The significance level was set at α = 3.3x10-4 by applying Bonferroni correction. The association of DRB1*09:01 with MPO-AAV was confirmed (allele model, P = 2.1x10-4, odds ratio [OR] = 1.57). Protective association of DRB1*13:02 was detected against MPO-AAV (allele model, P = 2.3x10-5, OR = 0.42) and MPA (dominant model, P = 2.7x10-4, OR = 0.43). A trend toward increased frequency of DPB1*04:01, the risk allele for GPA in European populations, was observed among Japanese patients with PR3-AAV when conditioned on DRB1*13:02 (Padjusted = 0.0021, ORadjusted = 3.48). In contrast, the frequency of DPB1*04:01 was decreased among Japanese patients with MPO-AAV, and this effect lost significance when conditioned on DRB1*13:02 (Padjusted = 0.16), suggesting that DRB1*13:02 or other allele(s) in linkage disequilibrium may be responsible for the protection. The differential association of DPB1*04:01 with PR3-AAV and MPO-AAV and difference in DPB1*04:01 allele frequencies between populations supported the hypothesis that the HLA-class II population difference may account in part for these epidemiologic characteristics. Furthermore, taken together with our previous observations, the haplotype carrying DRB1*13:02 was suggested to be a shared protective factor against multiple autoimmune diseases

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

Increased E-selectin in hepatic ischemia-reperfusion injury mediates liver metastasis of pancreatic cancer

金沢大学医薬保健研究域医学系Several recent studies have reported that selectins are produced during ischemia-reperfusion injury, and that selectin ligands play an important role in cell binding to the endothelium and in liver metastasis. Portal clamping during pancreaticoduodenectomy with vessel resection for pancreatic head cancer causes hepatic ischemia-reperfusion injury, which might promote liver metastasis. We investigated the liver colonization of pancreatic cancer cells under hepatic ischemia-reperfusion and examined the involvement of E-selectin and its ligands. A human pancreatic cancer cell line (Capan-1) was injected into the spleen of mice after hepatic ischemia-reperfusion (I/R group). In addition, to investigate the effect of an anti-E-selectin antibody on liver colonization in the IR group, mice received an intraperitoneal injection of the anti-E-selectin antibody following hepatic ischemia-reperfusion and tumor inoculation (IR+Ab group). Four weeks later, mice were sacrificed and the number of tumor nodules on the liver was compared to mice without hepatic ischemia-reperfusion (control group). The incidence of liver metastasis in the I/R group was significantly higher (16 of 20, 80%) than that in the control group (6 of 20, 30%) (P<0.01). Moreover, mice in the I/R group had significantly more tumor nodules compared to those in the control group (median, 9.9 vs. 2.7 nodules) (P<0.01). In the I/R+Ab group, only 2 of 5 (40%) mice developed liver metastases. RT-PCR and southern blotting of the liver extracts showed that the expression of IL-1 and E-selectin mRNA after hepatic ischemia-reperfusion was significantly higher than the basal levels. Hepatic ischemia-reperfusion increases liver metastases and E-selectin expression in pancreatic cancer. These results suggest that E-selectin produced due to hepatic ischemia-reperfusion is involved in liver metastasis.Embargo Period 6 month