Development of alveolar and airway cells from human iPS cells: toward SARS-CoV-2 research and drug toxicity testing.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 enters host cells by binding with the receptor angiotensin-converting enzyme 2 (ACE2). While ACE2 is expressed in multiple cell types, it has been implicated in the clinical progression of COVID-19 as an entry point for SARS-CoV-2 into respiratory cells.

Phase II study of cisplatin/pemetrexed combined with bevacizumab followed by pemetrexed/bevacizumab maintenance therapy in patients with EGFR-wild advanced non-squamous non-small cell lung cancer.

Purpose: This phase II study was performed to evaluate the efficacy and safety of cisplatin/pemetrexed combined with 15 mg/kg of bevacizumab followed by pemetrexed/bevacizumab maintenance therapy as first-line chemotherapy in advanced non-squamous non-small cell lung cancer (NSCLC) limited to epidermal growth factor receptor (EGFR)-wild type.

Patients And Methods: Fifty patients with advanced or metastatic EGFR-wild type NSCLC aged < 75 years old were enrolled in the study. The patients were treated with four cycles of cisplatin (75 mg/m, day 1), pemetrexed (500 mg/m, days 1), and bevacizumab (15 mg/kg, day 1), every 3 weeks, followed by pemetrexed plus bevacizumab maintenance until progression for achieving a response over stable disease after induction chemotherapy.

A Four-Center Retrospective Study of the Efficacy and Toxicity of Low-Dose Trimethoprim-Sulfamethoxazole for the Treatment of Pneumocystis Pneumonia in Patients without HIV Infection.

The dose of trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of pneumonia (PCP) in patients without human immunodeficiency virus (HIV) infection has not been verified. The aim of this study was to investigate the efficacy and toxicity of a low-dose TMP-SMX regimen in such patients. A retrospective study was conducted in four hospitals.

Two Cases of Proteinase 3-Anti-Neutrophil Cytoplasmic Antibody (PR3-ANCA)-related Nephritis in Infectious Endocarditis.

We herein report two cases of proteinase 3-anti-neutrophil cytoplasmic antibody (PR3-ANCA)-related nephritis in infectious endocarditis. In both cases, the patients were middle-aged men with proteinuria and hematuria, hypoalbuminemia, decreased kidney function, anemia, elevated C-reactive protein (CRP) levels, and PR3-ANCA positivity. Each had bacteremia, due to Enterococcus faecium in one and Streptococcus bovis in the other.

Activation of aryl hydrocarbon receptor mediates suppression of hypoxia-inducible factor-dependent erythropoietin expression by indoxyl sulfate.

Indoxyl sulfate (IS) is a representative uremic toxin that accumulates in the blood of patients with chronic kidney disease (CKD). In addition to the involvement in the progression of CKD, a recent report indicates that IS suppresses hypoxia-inducible factor (HIF)-dependent erythropoietin (EPO) production, suggesting that IS may also contribute to the progression of renal anemia. In this report, we provide evidence that aryl hydrocarbon receptor (AhR) mediates IS-induced suppression of HIF activation and subsequent EPO production.

Indoxyl sulfate exacerbates low bone turnover induced by parathyroidectomy in young adult rats.

Low-turnover bone disease is one of the bone abnormalities observed in patients with chronic kidney disease (CKD) and is recognized to be associated with low serum parathyroid hormone (PTH) level and skeletal resistance to PTH. Indoxyl sulfate (IS) is a representative uremic toxin that accumulates in the blood as renal dysfunction progresses in CKD patients. A recent in vitro study using an osteoblastic cell culture system suggests that IS has an important role in the pathogenesis of low bone turnover through induction of skeletal resistance to PTH.

Clinical outcomes in elderly patients administered gefitinib as first-line treatment in epidermal growth factor receptor-mutated non-small-cell lung cancer: retrospective analysis in a Nagano Lung Cancer Research Group study.

The clinical efficacy and outcomes of gefitinib therapy as a first-line treatment for elderly patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations were analyzed retrospectively. We analyzed chemotherapy-naïve NSCLC patients aged 75 years or older who had EGFR mutations (exon 19 deletion mutation or L858R), who were initially treated with gefitinib (250 mg) once daily in Nagano Prefecture. A total of 55 patients (16 men, 39 women) with a median age of 81.

Phase I/II study of S-1 combined with biweekly irinotecan chemotherapy in previously treated advanced non-small cell lung cancer.

Purpose: This phase I/II study was designed to evaluate a combination of irinotecan and S-1 a new regimen for salvage chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC).

Methods: The study group comprised patients with advanced or metastatic NSCLC who had previously received at least one platinum-containing chemotherapy. Patients received irinotecan on days 1, 15 and oral S-1 (40 mg/m(2) twice daily as a fixed dose) on day 1 to 14 of a 28-day cycle.

Gefitinib as first-line treatment in elderly epidermal growth factor receptor-mutated patients with advanced lung adenocarcinoma: results of a Nagano Lung Cancer Research Group study.

Unlabelled: Efficacy of first-line gefitinib for elderly epidermal growth factor receptor mutated patients with lung adenocarcinoma is uncertain. This study was aimed to investigate efficacy of gefitinib for such population. The primary endpoint was response rate (RR) and at least 12 cases were needed.

Characterization of dense artificial connective tissues generated in a newly designed bioreactor.

Dense connective tissues were generated simultaneously by accumulating collagen fibrils and fibroblasts on stainless steel mesh using a bioreactor system that we designed. The advantage of our system is that the artificial connective tissues can be generated within 24 hr in the absence of inhibitors against matrix metalloproteinases. The fibroblasts were suspended in 200 mL of Dulbecco's modified Eagle's medium containing 10% fetal bovine serum and 0.

Clinical experience of laparoscopy-assisted proximal gastrectomy with Toupet-like partial fundoplication in early gastric cancer for preventing reflux esophagitis.

Background: Laparoscopy-assisted proximal gastrectomy (LAPG) has become prevalent for early gastric cancer in the upper stomach, but standard esophagogastrostomy is sometimes complicated with reflux esophagitis. Clinical outcomes are described here in patients with reconstruction by esophagogastrostomy with Toupet-like partial fundoplication (TPF) in LAPG.

Study Design: From November 2005 through December 2008, LAPG was performed in 36 patients with early gastric cancer, 26 (72.

Laparoscopy-assisted pancreas- and spleen-preserving total gastrectomy for gastric cancer as compared with open total gastrectomy.

Background: Laparoscopy-assisted total gastrectomy (LATG) is not widely used for the treatment of gastric cancer located in the upper or middle third of the stomach. To assess the safety and usefulness of LATG, we compared the outcomes of LATG with those of open total gastrectomy (OTG).

Methods: From July 2004 to July 2007, we performed pancreas- and spleen-preserving total gastrectomy with D1 + beta or D2 lymph-node dissection and Roux-en-Y reconstruction in 74 patients with cancer located in the upper or middle third of the stomach.

Liver metastasis of colorectal cancer by protein-tyrosine phosphatase type 4A, 3 (PRL-3) is mediated through lymph node metastasis and elevated serum tumor markers such as CEA and CA19-9.

Phosphatase of regenerating liver (PRL)-3 was identified as a molecule associated with liver metastasis in colorectal cancer (CRC), although its precise causative role in distant metastasis remains elusive from a clinical point of view. The aim of this study was to promote the mechanistic insight of PRL-3 involvement in liver metastasis in CRC. One hundred and seven CRC patients with resection of the primary lesions were studied for clinicopathological and prognostic association with PRL-3 and were evaluated by immunohistochemistry in univariate and multivariate analyses.

Silica-associated systemic lupus erythematosus in an elderly man.

The predominantly young woman-orientated systemic lupus erythematosus (SLE) is a disease that involves an extremely complicated and multifactorial interaction of various genetic and environmental factors. Crystalline silica (Si) may act as an immunoadjuvant to increase secretions of inflammatory endogenous substances and antibody production. In addition, previous studies have suggested that exposure to Si may induce SLE.

Immunohistochemical distribution of heat shock protein 47 (HSP47) in scirrhous carcinoma of the stomach.

Background: The aim of the present study was to examine the immunohistochemical distribution of the 47-kDa heat shock protein (HSP47) to enhance the understanding of the mechanisms involved in stromal fibrosis, which accompanies cancer infiltration in scirrhous carcinoma of the stomach.

Materials And Methods: In vitro gastric cancer models were prepared by collagen gel cultures using three different human gastric cancer cell lines (KATO-III, MKN-74, MKN-45) and a human fibroblast cell line (TIG-101). Tumor tissues were obtained from ten patients with early gastric cancer (5 scirrhous carcinoma; 5 non-scirrhous carcinoma) and three patients with advanced scirrhous gastric cancer.

Role of endoscopic clipping for determining the resection line for tumors located in the middle or upper corpus of the stomach: experience with 100 gastrectomies for early gastric cancer.

Background: The efficacy and limitations of preoperative endoscopic clipping for determining the resection line in patients with early gastric cancer remain unclear.

Materials And Methods: Subjects comprised 100 patients with early gastric cancer (33 females, 67 males; mean age, 60.5 years; range, 33-84 years) who underwent pre-operative endoscopic clipping for lesions located in the middle or upper corpus of the stomach.

Phase II study of weekly docetaxel combined with cisplatin in patients with advanced non-small-cell lung cancer.

Purpose: To evaluate the safety and efficacy of the combination of cisplatin on day 1 and docetaxel on days 1, 8 and 15 every 4 weeks for the treatment of previously untreated patients with non-small-cell lung cancer (NSCLC).

Patients And Methods: A group of 38 patients with advanced or metastatic NSCLC who had not received prior treatment and who were aged under 75 years were enrolled. The patients received intravenous infusions of docetaxel (25 mg/m2, days 1, 8, 15) and cisplatin (80 mg/m2, day 1), followed by a week of rest.

Thermostability gradient in the collagen triple helix reveals its multi-domain structure.

A triple-helical conformation and stability at physiological temperature are critical for the mechanical and biological functions of the fibril-forming collagens. Here, we characterized the role of consecutive domains of collagen II in stabilizing the triple helix. Analysis of melting temperatures of genetically engineered collagen-like proteins consisting of tandem repeats of the D1, D2, D3 or D4 collagen II periods revealed the presence of a gradient of thermostability along the collagen molecule with thermolabile N-terminal domains and thermostable C-terminal domains.

[Antimicrobial susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolated in major hospitals in Nagano Prefecture].

We determined the minimum inhibitory concentration (MIC) of various antimicrobial agents against 108 strains of Streptococcus pneumoniae and 144 strains of Haemophilus influenzae isolated from respiratory organs in the First Department of Internal Medicine, Shinshu University, and affiliated hospitals between January 2000 and February 2001. The following results were obtained. 1.

Pseudomembranous tracheobronchitis caused by methicillin-resistant Staphylococcus aureus.

We report a case of severe tracheobronchitis caused by methicillin-resistant Staphylococcus aureus in a man exhibiting symptoms of upper airway obstruction after infection with influenza. Bronchoscopy revealed diffuse pseudomembrane formation throughout the trachea and bilateral bronchi, which were nearly obstructed. In this case, it was helpful to perform bronchoscopy, protected brushing and tracheotomy immediately in order to avoid choking.