27 research outputs found
Dissection of lung parenchyma using electrocautery is a safe and acceptable method for anatomical sublobar resection
BACKGROUND: Anatomic sublobar resection is being assessed as a substitute to lobectomy for primary lung cancers. However, persistent air leak after anatomic sublobar resection is prevalent and increasing surgical morbidity and costs. The use of electrocautery is being popularized recently in anatomic sublobar resection. We have retrospectively evaluated the safety and efficacy of intersegmental plane dissection using electrocautery. METHODS: Between April 2009 to September 2010, 47 patients were treated with segmentectomy for clinical T1N0M0 non-small cell lung cancers. The intersegmental plane was dissected using electrocautery alone or in combination with staplers. We evaluated the methods of dividing intersegmental plane (electrocautery alone or combination with electrocautery and staplers), intraoperative blood loss, duration of chest tube placement, duration of surgery, preoperative FEV(1.0) %, incidence of prolonged air leak, length of postoperative hospital stay, postoperative pulmonary function at 6 months after surgery and the cost for sealing intersegmental plane. RESULTS: Among the 47 patients, 22 patients underwent intersegmental plane dissection with electrocautery alone and 25 patients did in combination with electrocautery and staplers. The mean number of stapler cartridges used was only 1.3 in electrocautery and staplers group. Mean age, gender, number of patients whose FEV(1)% < 70 % were similar between two groups. There was no statistical difference between electrocautery alone and combination with electrocautery and staplers group in duration of surgery (282 vs. 290 minutes), intraoperative blood loss (203 vs.151 ml), duration of chest tube placement (3.2 vs. 3.1 days), postoperative hospital stay (11.0 vs.10.0 days), postoperative loss of FEV(1.0) (13 vs.8 %), loss of FVC (11 vs. 6 %) or incidence of minor postoperative complications [9 % (2/22) vs. 16 % (4/25), p = 0.30)]. However, incidence of prolonged air leak was higher in electrocautery alone group than in combination with electrocautery and staplers group [14 % (3/22) vs. 4 % (1/25), p = 0.025)]. The cost of materials for sealing air leaks amounted to €964 per patient in the electrocautery alone group and €1594 per patient in combination with electrocautery and staplers group. CONCLUSIONS: The number of patients with prolonged air leak was higher in the electrocautery alone group. The use of staplers in addition to electrocautery may lead to reduced prolonged air leak. However, the use of electrocautery for intersegmental plane dissection appeared to be safe with acceptable postoperative complications and effective in reducing costs
In situ evaluation of podocin in normal and glomerular diseases
In situ evaluation of podocin in normal and glomerular diseases.BackgroundMutations of the NPHS2 gene are responsible for autosomal-recessive steroid-resistant nephrotic syndrome. Its product, podocin, faces the slit diaphragm area with its two ends in the cytoplasm of foot processes.MethodsWe generated rabbit polyclonal antibodies against conjugated peptides from human podocin N- and C-termini, and studied podocin and synaptopodin using kidney tissues of normal humans and those with glomerular diseases.ResultsAntipodocin antibodies detected the original 42 kD fragment and an extra smaller fragment by Western blot analysis using human isolated mature glomeruli. RNA analysis showed two bands, the original and the other of a decreased length. Immunohistochemically, podocin was detected in a linear pattern along the glomerular capillary loop. Antipodocin antibody (C-terminal) stained the smooth muscles of renal arterioles and aorta. Among 42 patients, podocin was normally expressed in glomeruli in purpura nephritis, IgA nephropathy (IgAN), and minimal-change disease (MCD), while it was either decreased or absent in most subjects with focal segmental glomerulosclerosis (FSGS). The expression of synaptopodin was similar to that of podocin, although some discrepancy existed.ConclusionAlthough indirect, our data suggest the existence of a vascular isoform of podocin with a different molecular mass. We propose that examination of podocin expression may help differentiate MCD from FSGS
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
Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial
Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials.
Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure.
Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen.
Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049
Stimulating Macrophage Activity in Mice and Humans by Oral Administration of Quillaja Saponin
Acute 40% exchange-transfusion with hemoglobin-vesicles in a mouse pneumonectomy model.
Hemoglobin vesicles (HbVs) function as a red blood cell (RBC) substitute and are composed of purified hemoglobin encapsulated in a phospholipid bilayer membrane. The performance of HbVs as a substitute for RBC transfusions was examined in a mouse model of pneumonectomy following acute 40% exchange-transfusion with HbVs.Before performing left pneumonectomies, 40% of the blood volume of mice was replaced with a) lactated Ringer's solution (control), b) 5% recombinant human serum albumin (rHSA), c) mouse RBCs shed in rHSA (mRBCs/rHSA), or d) HbV suspended in rHSA (HbV/rHSA). We compared postoperative a) survival, b) functional recovery, and c) histopathological, immunohistochemical, and inflammatory responses among the study groups.In the HbV/rHSA and mRBC/rHSA groups, all mice survived ≥7 days after pneumonectomy, whereas 100% of the control mice died within a few h and 50% of mice in the rHSA group died within 24 h after pneumonectomy. Immunohistochemical staining for hypoxia-inducible factor-1α showed that hepatic and renal hypoxic injuries were prominently mitigated by HbV and mRBCs.The oxygen-carrying performance of HbV was similar to that of mRBCs, even with impaired lung functions following pneumonectomy. HbV infusion did not interfere with the recovery from surgical injury. In the near future, HbVs could be used clinically as a substitute for the perioperative transfusion of RBCs, when or where donated RBCs are not immediately available
NEW INSIGHTS INTO β-ADRENOCEPTORS IN SMOOTH MUSCLE: DISTRIBUTION OF RECEPTOR SUBTYPES and MOLECULAR MECHANISMS TRIGGERING MUSCLE RELAXATION
Changes in serum concentrations of (A) TNF-α, (B) IL-6, (C) G-CSF, and (D) IFN-γ between the baseline period and the 7<sup>th</sup> postoperative day (POD), in the indicated study groups.
<p>Values are shown as the mean ± SD. n = 10 in each group. *<i>P</i> < 0.05 versus baseline (Student’s t-test).</p
Hemoglobin vesicle (HbV) solution.
<p>HbVs were developed as artificial oxygen carriers in the form of liposomes containing concentrated hemoglobin, which can be preserved for years, used regardless of the blood type, and do not pose a risk of infection.</p