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Biomedical subjects

Shigeru Kohno

Publications and source records attributed to Shigeru Kohno.

At least 181 records · Page 10Linked to original sources
PubMed2004

Chronic visceral hypersensitivity renders defecation more susceptible to stress via a serotonergic pathway in rats.

Visceral hypersensitivity, intestinal dysmotility, and stress play major roles in irritable bowel syndrome. However, the significance of visceral hypersensitivity in stress-induced changes of colorectal motor function is not conclusive. A rat model of chronic visceral hypersensitivity was induced by mechanical colorectal irritation during postnatal development. Defecation and colonic transit time were not different between the visceral hypersensitivity and the control groups at baseline. Stress and a 5-hydroxytryptamine (5-HT) agonist both resulted in a significant increase in defecation in the visceral hypersensitivity group compared with the controls. Prior administration of granisetron, a 5-HT3 receptor antagonist, inhibited stress-induced changes in defecation in the visceral hypersensitivity group as well as the controls. Stress-induced acceleration of colonic transit was not significantly different between the two groups. Our results indicate that chronic visceral hypersensitivity can modulate the effect of stress on defecation via a serotonergic pathway and suggest that visceral hypersensitivity may be related to the susceptibility of the defecative response to stressful events in patients with irritable bowel syndrome.

Animals↗
PubMed2004

A multicenter, open-label clinical study of micafungin (FK463) in the treatment of deep-seated mycosis in Japan.

The efficacy and safety of micafungin (FK463), which is a new lipopeptide antifungal agent of the echinocandin class and is active against both Aspergillus and Candida species, were investigated in patients with deep-seated mycosis in this study. 70 patients were treated with micafungin 12.5-150 mg/d intravenously for up to 56 d. The overall clinical response rates were 60% (6/10) in invasive pulmonary aspergillosis, 67% (6/9) in chronic necrotizing pulmonary aspergillosis, 55% (12/22) in pulmonary aspergilloma, 100% (6/6) in candidemia, and 71% (5/7) in esophageal candidiasis. The response rates for patients with prior antifungal treatment which was considered ineffective or toxic, were similar to rates for patients without prior treatment. Mycological eradication was observed in patients infected with Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus, Aspergillus niger, Candida albicans, Candida glabrata, or Candida krusei. Adverse events related to micafungin were reported in 21 patients (30%), and there was no dose-related occurrence of any adverse event. It is concluded that treatment with micafungin as monotherapy seems to be effective and safe in patients with deep-seated mycosis.

Adult↗
PubMed2004

Clinical and immunohistochemical study of immunoglobulin A nephropathy (IgAN) before and after tonsillectomy.

Tonsillectomy often improves clinical features in immunoglobulin A nephropathy (IgAN), however, the mechanisms mediating clinical modifications are unclear. In the present study, we examined the immunohistological alterations in biopsy specimens obtained from IgAN patients before and after tonsillectomy. We investigated eight IgAN patients who underwent repeated renal biopsy in the present study. Immunohistochemistry for alpha-smooth muscle actin (alpha-SMA), CD68 and proliferating cell nuclear antigen (PCNA) were performed and histological findings were compared before and after tonsillectomy. None of the patients were treated with steroids or immunosuppressive drugs before second renal biopsy. The expression of alpha-SMA and the number of CD68 positive cells were significantly decreased in IgAN patients with improvement of proteinuria and hematuria after tonsillectomy. The degree of mesangial cell proliferation, expansion of mesangial area and the number of PCNA positive cells were not changed after tonsillectomy. These results suggest that the reduced number of activated mesangial cells and macrophages may be involved in the improvement of hematuria after tonsillectomy. They also suggest that tonsillectomy may improve proteinuria and hematuria in some patients with IgAN through reduction of mesangial cell activation and macrophage infiltration.

Actins↗
PubMed2004

Three 20-minute interspaced salbutamol inhalations as a test for the diagnosis of reversible airflow limitation in adult asthmatics.

Reversible airflow limitation represents an important parameter for the diagnosis of bronchial asthma. The aim of this study was to design a simple and useful test for the detection of reversible airflow limitation. The subjects were 29 patients with asthma and forced expiratory volume in 1 second (FEV1) < 80% predicted. Following baseline spirometry, subjects inhaled 1.5 mg of salbutamol by a nebulizer and then spirometry was performed 20 min later. The procedure was repeated three times. Subsequently, 13 patients received 30 mg of predonisolone orally once daily for 1 week. Spirometry was performed before and after the oral predonisolone therapy, and results were compared with those of salbutamol inhalation test. The mean increase in FEV1 over the baseline was 18.3% after the first salbutamol inhalation, 26.4% after the second inhalation, and 30.2% after the third inhalation. The increases in FEV1 were significant after each inhalation. The mean increases in the maximum expiratory flow rate at 50% (V50) and that at 25% (V25), measured from the flow volume loop, were 53.5% and 46.9% after the first inhalation, but there were no significant changes by repeated inhalations. A significant reversal of airflow limitation was demonstrated in 18 subjects after the first inhalation, 22 subjects after the second inhalation, and 27 subjects after the third inhalation. Improvement in FEV1 after oral predonisolone was equivalent to that after the third inhalation of salbutamol. A test composed of three 20-min interspaced salbutamol inhalations is useful for the diagnosis of asthma by demonstrating the presence of reversible airflow limitation.

Administration, Inhalation↗
PubMed2004

Hepatic mucosa-associated lymphoid tissue lymphoma and hepatocellular carcinoma in a patient with hepatitis B virus infection.

Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is an extremely rare disease. A 65-year-old female patient with chronic hepatitis B presented with multiple solid masses in segment (S) 4, S5, and S6 of the liver. The nodule in S5 was diagnosed preoperatively as hepatocellular carcinoma by computed tomography, magnetic resonance imaging, and angiography. The nodule in S4 was initially interpreted as lymphoid follicles by needle biopsy. Segmentectomy of S5 and partial resection of S6 were performed. Microscopic examination of the S5 nodule revealed moderately differentiated hepatocellular carcinoma. The nodule from S6 showed nodular proliferation of atypical intermediate to medium-sized lymphoid cells in the portal area and lymph epithelial lesions of bile ducts. The atypical lymphoid cells were positive for LCA, L-26 and bcl-2 and negative for UCHL-1. These features were consistent with the diagnosis of MALT lymphoma. This is the first case report of synchronous hepatic MALT lymphoma and hepatocellular carcinoma associated with chronic hepatitis B.

Aged↗
PubMed2004

Preliminary analysis of a newly proposed prognostic scoring system (SLiDe score) for hepatocellular carcinoma.

BACKGROUND: The long-term prognosis of hepatocellular carcinoma (HCC) remains poor and the prediction of survival is often difficult because of the limited liver function and frequent recurrence of HCC in most patients. Therefore, a prognostic classification of HCC should account for both tumor-related variables and liver function. METHODS: The value of reported prognostic factors for HCC was assessed and a new prognostic classification was established called the 'SLiDe' scoring system (S, stage; Li, liver damage; De, des-gamma-carboxy prothrombin) using 'stage' and 'liver damage' of the recently revised 4th edition of the Japanese staging system edited by the Liver Cancer Study Group of Japan, and the serum level of des-gamma-carboxy prothrombin (DCP) in 177 patients with HCC. RESULTS: Univariate analysis identified Child-Pugh stage, liver damage, tumor morphology, portal vein thrombosis, stage, serum level of alpha-fetoprotein (AFP), serum level of DCP, and initial treatment as significant prognostic factors. Of these, liver damage, stage, and serum level of DCP remained independent predictive factors of survival after multivariate prognostic analysis using the proportional hazards regression model. Therefore, a new prognostic scoring system (SLiDe scoring system) was derived that assigned a linear score (0/1/2/3) to these three covariates. This SLiDe scoring system was statistically a better model for predicting outcome in the present study population than the Cancer of the Liver Italian Program (CLIP) and the Japan Integrated Staging (JIS) scoring systems, as judged by the Akaike Information Criteria. CONCLUSION: The SLiDe scoring system is useful for the assessment of the prognosis of patients with HCC as long as the Japanese staging system is used, although this uses parameters such as the indocyanine green retention test and DCP, which are not examined routinely in every part of the world. Therefore, the proposed classification should be further validated in other large study populations.

Adolescent↗
PubMed2004

Hospital-acquired pneumonia in general wards of a Japanese tertiary hospital.

OBJECTIVE: Hospital-acquired pneumonia (HAP) is an important nosocomial disorder because both its mortality and morbidity are high. The Japanese Respiratory Society (JRS) has proposed a new guideline for the diagnosis and treatment of HAP. Clinical investigations of HAP were conducted to assess the current status of HAP in accordance with this guideline. METHODOLOGY: Inpatients who developed HAP in the Second Department of Internal Medicine, Nagasaki University Hospital, a tertiary hospital in Japan, were evaluated. The incidence of HAP was 1.86% (59 cases in 3176 admissions) from 1996 to 2000. In particular, the severity rating of HAP for 46 patients in accordance with the JRS guidelines, was assessed. RESULTS: The mortality rate was 6.5% at this hospital, which is less than that reported by other investigators in the field. The frequency of bacteria isolated from clinical specimens was as follows: Haemophilus influenzae (20%), Pseudomonas aeruginosa (16.7%), and methicillin-resistant Staphylococcus aureus (13.3%). Response rates were stratified by first-line medications and the results were as follows: penicillins (33.3%), third-generation cephems (44.4%), and carbapenems (66.7%). CONCLUSIONS: Based on the results presented here, the severity rating proposed in this guideline for HAP appears reasonable, as the response rate for the first-line antibiotic was better in Group II than in Groups III and IV. It will be important to analyse 'clinical outcome' in accordance with this guideline.

Adult↗
PubMed2004

TNP-470, an angiogenesis inhibitor, suppresses the progression of peritoneal fibrosis in mouse experimental model.

BACKGROUND: In patients on long-term peritoneal dialysis (PD), angiogenesis and vasculopathy are observed in the peritoneum, and the degree of vascularization correlates with the area of fibrotic tissue, suggesting the involvement of angiogenesis in the progression of peritoneal fibrosis. The aim of the present study was to evaluate the effect of TNP-470, an anti-angiogenic compound, on the development of peritoneal fibrosis induced by chlorhexidine gluconate (CG). METHODS: Peritoneal fibrosis was induced by injection of CG into peritoneal cavity of Institute for Cancer Research (ICR) mice. TNP-470 was injected subcutaneously with CG. Mice were sacrificed, and peritoneal tissues were dissected out at days eight and 16 after CG and TNP-470 injection. The expression patterns of CD31 (as a marker of endothelial cells), vascular endothelial cell growth factor (VEGF), alpha-smooth muscle actin (as a marker of myofibroblasts), heat shock protein 47 (HSP47), type III collagen, F4/80 (as a marker of mice macrophages), proliferating cell nuclear antigen (PCNA), and cyclin-dependent kinase 2 (Cdk2) were examined by immunohistochemistry. RESULTS: CG-injected mice showed thickening of the submesothelial zone and increased number of vessels, myofibroblasts, and infiltrating macrophages. The expression levels of VEGF, type III collagen, and HSP47 were increased, and a large number of PCNA-positive cells and Cdk2-expressing cells were observed in the thickened submesothelial area. Treatment with TNP-470 suppressed the submesothelial zone thickening and reduced collagen III expression as well as angiogenesis. TNP-470 also decreased the number of VEGF-expressing cells, myofibroblasts, macrophages, PCNA-positive cells, and Cdk2-expressing cells. CONCLUSION: Our results indicate the involvement of angiogenesis in the progression of peritoneal fibrosis, and suggest that TNP-470 may be potentially useful for the prevention of peritoneal fibrosis through inhibition of angiogenesis and suppression of myofibroblast proliferation.

Actins↗
PubMed2004

Enhanced expression of interleukin-8 and activation of nuclear factor kappa-B in endoscopy-negative gastroesophageal reflux disease.

OBJECTIVE: Interleukin-8 (IL-8) mediates neutrophil trafficking via its receptors. Recent studies have shown that IL-8 is likely involved in the development and progression of erosive reflux esophagitis (RE), yet little is known about its implication in endoscopy-negative gastroesophageal reflux disease (GERD). The purpose of this study was to determine IL-8 messenger ribonucleic acid (mRNA) expression levels in endoscopy-negative GERD, along with assessment of nuclear factor kappaB (NF-kappaB) activation, which upregulates IL-8 expression. METHODS: We studied 31 patients with endoscopy-negative GERD, 15 patients with erosive RE, and 15 asymptomatic controls. Paired biopsy samples were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap-frozen for measurement of IL-8 mRNA levels by real-time quantitative polymerase chain reaction, and another was formalin-fixed for histopathological evaluation. In nine endoscopy-negative GERD patients, the IL-8 mRNA expression levels were measured before and 8 wk after treatment with lansoprazole. We also sampled additional specimens for NF-kappaB-DNA binding assay and immunohistochemical analyses of NF-kappaB p65 and p50 subunits, IL-8 and specific IL-8 receptor, CXCR-1. RESULTS: The relative IL-8 mRNA expression levels were significantly higher in esophageal mucosa of patients with endoscopy-negative GERD than those of the controls. The presence of basal zone hyperplasia and intraepithelial neutrophils, histopathological hallmarks of GERD, were associated with higher levels of IL-8 mRNA. Lansoprazole treatment significantly reduced the IL-8 mRNA expression levels. The esophageal epithelium of patients with GERD showed intense immunoreactivity for IL-8, and expressed CXCR-1 antigen. We found NF-kappaB activation in esophageal mucosa in GERD patients and the NF-kappaB subunits were localized predominantly in the nuclei of IL-8-expressing cells. CONCLUSIONS: Our results demonstrate enhanced mucosal expression of IL-8 in incipient GERD even without mucosal breaks. NF-kappaB activation may be implicated in the pathogenesis in GERD.

Adult↗
PubMed2004

Mucosal concentrations of proinflammatory cytokines and chemokines at gastric cardia: implication of Helicobacter pylori infection and gastroesophageal reflux.

OBJECTIVES: The pathogenesis of carditis remains unclear, although gastroesophageal reflux disease (GERD) and Helicobacter pylori infection have been proposed. Little is known about the profile of proinflammatory cytokines and chemokines in the pathogenesis of carditis. METHODS: We studied 28 patients with GERD and 40 controls. Two biopsy specimens were taken endoscopically from the cardiac mucosa within 5 mm from the squamocolumnar junction; one was snap frozen for measurement of mucosal levels of interleukin 1beta (IL-1beta), tumor necrosis factor-alpha, IL-6, IL-8, monocyte chemoattractant protein 1 (MCP-1), regulated on activation normal T-cell expressed and presumably secreted (RANTES) by enzyme-linked immunosorbent assays, while another was processed for histopathology. H. pylori infection was assessed by serology, rapid urease test, and histology with Giemsa staining. Samples were taken from the cardia of 18 H. pylori-positive patients, before and after eradication treatment. RESULTS: Carditis was significantly associated with H. pylori infection, but not GERD. IL-8, MCP-1, and RANTES levels were significantly higher in cardiac mucosa of patients with carditis than in those without it and in patients with than without H. pylori infection. IL-8 concentrations were significantly associated with the degree of neutrophil infiltration within the cardiac mucosa and decreased after cure of the infection. Mucosal MCP-1 and RANTES levels correlated positively with the grades of mononuclear cell infiltration and IL-1beta concentrations. CONCLUSION: Our results indicate that chemokines produced locally in the cardiac mucosa may be involved in the development of H. pylori-associated carditis.

Adult↗
PubMed2004

Elevated concentrations of alpha-defensins in gastric juice of patients with Helicobacter pylori infection.

OBJECTIVE: Defensins (alpha- and beta-defensins) are endogenous antimicrobial peptides. Little is known about alpha-defensins during Helicobacter pylori infection. METHODS: The concentrations of human neutrophil peptides (HNP-1, -2, and -3), the major components of neutrophils-derived alpha-defensins, were measured by radioimmunoassay (RIA) in plasma and gastric juice of 61 H. pylori-infected and 33 uninfected subjects, and before and after anti-H. pylori treatment in 12 patients with H. pylori-associated gastritis. Interleukin (IL)-8 concentrations in gastric juice were measured by enzyme-linked immunosorbent assay. Histological grades of gastritis and neutrophil counts (/mm(2)) infiltrating in the gastric mucosa were determined using two biopsy specimens taken from the antrum and corpus. Immunohistochemistry and reverse-phase high performance liquid chromatography (RP-HPLC) were used to identify HNPs 1-3. RESULTS: HNP 1-3 concentrations in gastric juice were significantly higher in H. pylori-positive than in H. pylori-negative patients and significantly decreased after cure. HNP 1-3 concentrations in gastric juice correlated with IL-8 levels and neutrophil densities in the gastric mucosa and were associated with histological degree of gastritis, especially the grades of activity. Intense immunoreactivity for anti-HNPs 1-3 antiserum was noted in infiltrating neutrophils in H. pylori-infected mucosa. In RP-HPLC analysis, all of the HNP 1-3 molecules were identified as their mature forms. Plasma HNP 1-3 concentrations were similar in H. pylori-infected and non-infected groups and showed no correlations with other parameters. CONCLUSIONS: We demonstrated significantly elevated levels of HNPs 1-3 in gastric juice during H. pylori infection. The elevation of HNPs is presumably secondary to H.pylori-associated gastric inflammation involving neutrophil infiltration.

Adult↗
PubMed2004

[A case of invasive group A Streptococcus infection which was successfully treated with linezolid].

A 53-year-old male was admitted to our hospital with a high fever and pain in the right arm. He was diagnosed as toxic shock-like syndrome by Streptococcus pyogenes. His arm was amputated because of necrotizing myositis and his renal damage was severe, he was treated in the intensive care unit with continuous hemodiafiltration. Bacteria were isolated from blood, ascites, pleural effusion, skin, and muscle. He was treated with a large amount of ampicillin, clindamycin, and gammaglobulin. However, his general status became worse. His illness improved after linezolid was administered. The reason for the success in treatment with linezolid, which was the inhibitory effect on bacterial toxin and its excellent penetration into the tissue.

Acetamides↗
PubMed2004

Effect of erythromycin on chronic respiratory infection caused by Pseudomonas aeruginosa with biofilm formation in an experimental murine model.

Diffuse panbronchiolitis (DPB) is a chronic lower respiratory tract infection commonly associated with persistent late-stage Pseudomonas aeruginosa infection. However, low-dose long-term therapy with certain macrolides is effective in most patients with DPB. The present study was designed to examine the effects of long-term erythromycin (ERY) therapy by using our established murine model of chronic respiratory P. aeruginosa infection. ERY or saline was administered from day 80 after intubation with a P. aeruginosa-precoated tube for the subsequent 10, 20, 40, and 80 days. Bacteriologic and histologic analyses of the murine lungs and electron microscopy of the intubated tube were performed. In the murine model, treatment with ERY for 80 days significantly reduced the number of viable P. aeruginosa organisms in the lungs (P < 0.05). The biofilm formed in situ by P. aeruginosa on the inner wall of the inoculation tube placed into the murine bronchus became significantly thinner after 80 days of ERY treatment. We conclude that the clinical efficacy of macrolides in DPB may be due at least in part to the reduction in P. aeruginosa biofilm formation.

Animals↗