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Biomedical subjects

Shigeru Kohno

Publications and source records attributed to Shigeru Kohno.

At least 199 records · Page 11Linked to original sources
PubMed2004

Azithromycin inhibits MUC5AC production induced by the Pseudomonas aeruginosa autoinducer N-(3-Oxododecanoyl) homoserine lactone in NCI-H292 Cells.

The features of chronic airway diseases, including chronic bronchitis, cystic fibrosis, bronchiectasis, and diffuse panbronchiolitis, include chronic bacterial infection and airway obstruction by mucus. Pseudomonas aeruginosa is one of the most common pathogens in chronic lung infection, and quorum-sensing systems contribute to the pathogenesis of this disease. The quorum-sensing signal molecule [N-(3-oxododecanoyl) homoserine lactone (3O-C(12)-HSL)] not only regulates bacterial virulence but also is associated with the immune response. In this study, we investigated whether 3O-C(12)-HSL could stimulate the production of a major mucin core protein, MUC5AC. The effect of a macrolide on MUC5AC production was also studied. 3O-C(12)-HSL induced NCI-H292 cells to express MUC5AC at both the mRNA and the protein levels in time- and dose-dependent manners. A 15-membered macrolide, azithromycin, inhibited MUC5AC production that was activated by 3O-C(12)-HSL. 3O-C(12)-HSL induced extracellular signal-regulated kinase (ERK) 1/2 and I-kappa B phosphorylation in cells, and this induction was suppressed by azithromycin. 3O-C(12)-HSL-induced MUC5AC production was blocked by the ERK pathway inhibitor PD98059. Our findings suggest that the P. aeruginosa autoinducer 3O-C(12)-HSL contributes to excessive mucin production in chronic bacterial infection. Azithromycin seems to reduce this mucin production by interfering with intracellular signal transduction.

4-Butyrolactone↗
PubMed2004

Pharmacodynamics and bactericidal activity of gatifloxacin in experimental pneumonia caused by penicillin-resistant Streptococcus pneumoniae.

BACKGROUND: Antimicrobial resistance rates for Streptococcus pneumoniae continue to increase worldwide, and resistance to nearly every major class of antimicrobials used to treat pneumococcal infections has been reported. Gatifloxacin (GFLX) is one of the quinolones that have strong activity against S. pneumoniae. METHODS: We compared the bacteriological, pharmacological and histopathological effects of orally administered GFLX with those of levofloxacin (LVFX) and ciprofloxacin (CPFX) in a murine model of pneumonia caused by penicillin-resistant S. pneumoniae (PRSP). RESULTS: Treatment with GFLX resulted in a significant decrease in the number of viable bacteria (control, CPFX, LVFX, and GFLX: 6.48 +/- 0.36, 6.44 +/- 0.27, 5.51 +/- 0.15, and 4.89 +/- 0.28 log10 CFU/lung, respectively, mean +/- SD). A significant decrease in mortality was observed in the GFLX-treated group in comparison with the other groups. Histopathological examination revealed that inflammatory changes in GFLX-treated mice were less marked than in the other mice. CONCLUSION: Our results suggest that orally administered GFLX is effective in PRSP pneumonia. The pharmacokinetic profiles also reflected the effectiveness of GFLX.

Administration, Oral↗
PubMed2004

Antimicrobial activity of saturated fatty acids and fatty amines against methicillin-resistant Staphylococcus aureus.

The objective of this study was to investigate the antimicrobial activities of saturated fatty acids and fatty amines against methicillin-resistant Staphylococcus aureus (MRSA). The antimicrobial activity of saturated fatty acids and fatty amines was determined by oxygen meters with multi-channels and disposable oxygen electrode sensors (DOX-96). Lauric acid, the most effective among the saturated fatty acids, showed antimicrobial activity at 400 microg/ml against methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA. The minimal inhibitory concentration (MIC) of fatty amines depended on each hydrophobic chain length. The MIC of myristylamine was 1.56 microg/ml; most effective of the fatty amines. In time-kill curves, lauric acid and myristylamine produced a bactericidal effect and a bacteriostatic effect at 4-fold the MIC, respectively. The antimicrobial activities of lauric acid and myristylamine were decreased by human plasma. Cytotoxicity of 3 saturated fatty acids and 3 fatty amines was examined in cultured endothelial cells. Although cytotoxicity of fatty amines was severer than that of saturated fatty acids, myristylamine showed the highest value of apparent therapeutic index among them. DOX-96 was useful for screening antimicrobial substances, especially in the case of insoluble substances. We found that myristylamine showed anti-MRSA activity comparable to that of vancomycin and teicoplanin.

Amines↗
PubMed2004

Low-dose combination therapy with temocapril and losartan reduces proteinuria in normotensive patients with immunoglobulin a nephropathy.

This study investigates the ability of low doses of angiotensin-converting-enzyme inhibitors, in combination with angiotensin II receptor blockers, to exert antiproteinuric effects in normotensive and proteinuric outpatients with immunoglobulin A (IgA) nephropathy confirmed by biopsy. We performed a prospective, randomized, 6-month study of the effects of temocapril 1 mg (n=10), losartan 12.5 mg (n=10), and both (n=11) on mild-to-moderate proteinuria 0.76+/-0.35 g/day (range, 0.4 to 1.6 g/day) and renal function. The study subjects comprised 31 normotensive and proteinuric outpatients with IgA nephropathy accompanied by normal, or mild-to-moderately reduced but stable renal function (glomerular filtration rate>50 ml/min) without steroid or immunosuppressive therapy. We prospectively evaluated blood pressure, proteinuria, renal function and biochemical parameters before and after 6 months of therapy. The combination therapy significantly reduced proteinuria (63.2%) compared with either temocapril or losartan alone (41.3% and 36.6%, respectively, p=0.04 and 0.01, respectively). Blood pressure was most decreased in the group that received combination therapy. The reduced proteinuria did not correlate with reduced systolic or diastolic blood pressure or mean arterial pressure in any of the groups. The glomerular filtration rate fell during the first 3 months of combined therapy, but became reversible after a further 3 months of therapy. The combination significantly decreased angiotensin II (p <0.01), and this decrease was greater than that by either drug alone. In conclusion, the effectiveness of the combined therapy may have been at least partly due to the greater inhibition of the action of angiotensin II in patients with IgA nephropathy. This strategy apparently reduced mild-to-moderate proteinuria in patients with normotensive IgA nephropathy.

Adult↗
PubMed2004

Clinical similarities and differences between human T-cell lymphotropic virus type 1-associated bronchiolitis and diffuse panbronchiolitis.

STUDY OBJECTIVES: Human T-cell lymphotropic virus type 1 (HTLV-1)-associated bronchiolitis and diffuse panbronchiolitis might overlap. We examined whether these conditions can be differentiated by comparing their clinical features and the effect of long-term macrolide treatment. PATIENTS AND METHODS: Fifty-eight Japanese patients, including 15 with HTLV-1-associated bronchiolitis and 43 with diffuse panbronchiolitis. Both conditions were clinically compared using the clinical criteria for diffuse panbronchiolitis, including findings from CT scans and BAL fluid testing. Pulmonary function, blood gas levels, and cold hemagglutinin (CHA) levels were assessed before and after long-term treatment with macrolides. Interleukin-2 receptor (IL-2R) expression in T cells obtained from the BAL fluid of patients with HTLV-1-associated bronchiolitis or diffuse panbronchiolitis was analyzed by flow cytometry. RESULTS: Clinical, laboratory, radiologic, and bacterial features were strikingly similar in both groups, except for the fact that patients with HTLV-1-associated bronchiolitis had a higher ratio of IL-2R-positive cells in the BAL fluid. The histopathologic features were also similar. Long-term treatment with macrolides improved PaO(2), FEV(1), and CHA in patients with HTLV-1-associated bronchiolitis to a lesser extent than in those with diffuse panbronchiolitis, and PaO(2) and FEV(1) in the group of patients with HTLV-1-associated bronchiolitis who had high IL-2R levels did not respond after therapy. CONCLUSIONS: These findings showed that the clinicopathologic features of the two conditions are quite similar, suggesting that diffuse panbronchiolitis is a chronic pulmonary manifestation of HTLV-1 infection. However, HTLV-1-associated bronchiolitis might be associated with conditions that are distinct from those of diffuse panbronchiolitis based on the different responses to macrolide treatment and the difference in the number of activated T cells bearing IL-2R in the lungs.

Bronchiolitis↗
PubMed2004

Membranous nephropathy after allogeneic stem cell transplantation: report of 2 cases.

Nephrotic syndrome (NS) is a rare complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The cases of 2 patients who developed NS after receiving allo-HSCT for chronic myelogenous leukemia and acute lymphoblastic leukemia are described. In both cases, renal biopsy revealed membranous nephropathy (MN), and the patients achieved remission after treatment with prednisolone. Previously reported cases and our experience suggest that most NS patients show MN in histologic tests after allo-HSCT and that its development is related to graft-versus-host disease. Early treatment with steroids seems effective for resolving symptoms of NS and improving renal function.

Adolescent↗
PubMed2004

Micafungin: a therapeutic review.

In recent decades, the incidence of aspergillosis, candidiasis and clinically important deep mycoses has been increasing, with advances in transplantation medicine and anticancer chemotherapy. Micafungin (FK463, Fujisawa Healthcare) has been developed as a novel type of antifungal agent, which inhibits 1,3-beta-D-glucan synthase in the fungal cell wall. Micafungin, one of the echinocandins, exhibits extremely high antifungal activity against Aspergillus spp. and Candida spp. in vitro. It is also characterized by a linear pharmacokinetic profile and a much lower prevalence of adverse reactions than amphotericin B. Micafungin is quite useful in the treatment of deep mycoses. In clinical studies in Japan, micafungin was found to be highly effective against aspergillosis (57.1% overall efficacy rate) and candidiasis (78.6%). Micafungin is expected to increase the efficacy rate of treatment in patients with severe aspergillosis or candidiasis when used in combination with amphotericin B or mold azoles.

Animals↗
PubMed2004

Clinical characteristics of pneumonia caused by penicillin resistant and sensitive Streptococcus pneumoniae in Japan.

BACKGROUND: S. pneumoniae is the leading cause of morbidity and mortality worldwide. P-lactam antibiotics were very effective against S. pneumoniae, however resistance to this class of antibiotic has become an increasing problem. OBJECTIVES: To assess the clinical differences between penicillin-sensitive and penicillin-resistant pneumococcal pneumonia. METHODS: The medical records of 306 patients with pneumococcal pneumonia who visited Nagasaki University Hospital or affiliated institutions between January 1997 and December 2001 were retrospectively reviewed. The Pneumonia Severity Index (PSI), sensitivity of S. pneumoniae, antibiotic choices and information on clinical outcome were evaluated. RESULTS: Penicillin sensitive and resistant organisms were responsible for 177 (57.7%) and 129 (42.0%) cases of pneumonia, respectively. The median age of patients was 65.5 years, and 72.3% (222) were males. There were no significant differences in the resistance rate between elderly (>65 years) and young patients. The median PSI score was 76. No significant association was observed between the severity of illness and sensitivities of S. pneumoniae. Previous use of beta-lactams in the last 3 months and chronic obstructive pulmonary disease were associated with penicillin resistance. The failure rate of first line antibiotics was significantly higher in the resistant group (22.5%) than in the sensitive group (9.0%). Four of 306 patients died (mortality, 1.3%). CONCLUSION: There were no significant differences clinically between the penicillin-sensitive and penicillin-resistant groups. The failure rate of first line antibiotics was higher in the resistant than in the sensitive group. Thus, the selection of antimicrobial agents should be carefully considered in the context of the patient's risk factors.

Aged↗
PubMed2004

A small outbreak of pulmonary tuberculosis in non-close contact patrons of a bar.

Four habitual drinking and smoking patients with pulmonary tuberculosis who were thought to have had no contact with one another were admitted to our hospital. During admission, we found that they were regular visitors of the same bar. To investigate the possibility of outbreak, we analyzed the tuberculosis isolates from them by restriction fragment length polymorphism. Such analysis showed identical chromosomal DNA restriction patterns of these 4 culture isolates. We concluded that these patients were considered to represent a mini-outbreak of pulmonary tuberculosis, although there was little, if any, contact among them while in or out of the bar.

Alcohol Drinking↗
PubMed2004

Nonspecific interstitial pneumonia with poor prognosis associated with amyopathic dermatomyositis.

Amyopathic dermatomyositis (ADM) is a clinical subtype of dermatomyositis, characterized by the lack of motor weakness and the presence of normal muscle enzyme levels. ADM is sometimes accompanied by interstitial pneumonia that shows a rapid progressive course associated with a poor prognosis. We report a 49-year-old patient who presented with nonspecific interstitial pneumonia (NSIP) associated with ADM. The patient failed to respond to prednisolone and immunosuppressive therapy and died. Although idiopathic NSIP is known to have a better prognosis, NSIP in ADM could be a fatal disease. Therefore, we should appropriately treat interstitial pneumonia in ADM even if it is NSIP.

Dermatomyositis↗
PubMed2004

[A rare case of marked dilatation of the pulmonary veins and emphysematous lesions in both lower lung lobes].

A 34-year-old man was admitted to our hospital because of continuous shortness of breath and abnormal chest shadows. Bronchiectasis had been suspected because of abnormal chest shadows during childhood. However, a chest CT scan obtained on admission did not show any bronchiectatic changes, but marked dilated blood vessels and emphysematous changes in the bilateral lower lobes were seen. A pulmonary angiogram showed normal pulmonary arteries in the arterial phase and diffuse dilated veins in the venous phase. Although he has been suffering also from liver cirrhosis type B with portal hypertension, we could not find any association between the liver cirrhosis and the lung lesions. This is a very rare case in which there is a possibility of congenital or idiopathic dilatation of the pulmonary veins.

Adult↗
PubMed2004

[A case of pulmonary Mycobacterium gordonae infection with pleural effusion].

A 65-year-old woman, treated with prednisolone (5 mg daily) for rheumatoid arthritis, visited our hospital because of right chest pain. Chest CT showed small nodular shadows in the right lung accompanied with right pleural effusion. A pulmonary Mycobacterium gordonae infection was diagnosed, since M. gordonae was identified twice from her sputum. She was treated with rifampicin, ethambutol and streptomycin for two months, and then streptomycin was replaced with clarithromycin. Three months after the initial treatment, M. gordonae was eradicated from her sputum. Pleural puncture revealed bloody, exudative, lymphocytotic pleural effusion, but no malignant cells were identified. Although pathological diagnosis by thoracoscopic pleural biopsy could not be performed, it is likely that the pleural effusion was associated with the pulmonary M. gordonae infection in the present case.

Aged↗
PubMed2004

[Two cases of asthmatic exacerbation caused by parainfluenza virus 3 infection].

Although viral respiratory tract infections are considered to be the most frequent causes of asthmatic exacerbation, respiratory viruses can rarely be detected in the adult population. We describe 2 cases, in a 43-yr-old man with severe atopic asthma and in a 69-yr-old man with moderate non-atopic asthma. After the onset of nasal discharge, sore throat and fever, the asthma had become exacerbated in both cases during the summer of 2002. In both cases, parainfluenza virus (PIV) 3 viral RNA could be detected from oral gargling by RT-PCR, and the serum viral antibody titer against PIV 3 increased significantly. These cases were therefore diagnosed as undergoing asthmatic exacerbation caused by PIV 3 infection and were successfully treated with systemic steroids. During summer, 2002, in our outpatient clinic, PIV 3 infection was demonstrated in approximately half of the asthmatic exacerbations associated with upper respiratory symptoms, including the present cases. Collectively, PIV 3 seems to represent an important viral cause of asthma exacerbation in summer.

Adult↗
PubMed2004

[A case of amyopathic dermatomyositis with interstitial pneumonia: successful treatment with a combination of prednisolone and cyclosporin A].

A 53-year-old woman visited our hospital in July 2002 with complaints of skin eruptions on the face and extremities, dry cough and dyspnea. A diagnosis of amyopathic dermatomyositis (ADM) was made on the basis of characteristic skin lesions and skin biopsy findings with slight muscle symptoms and mild elevation of muscle enzymes. Interstitial shadows were observed in both lower lung fields on chest radiographs, and thoracoscopic lung biopsy specimens revealed a diffuse alveolar damage (DAD) pattern. After induction of chemotherapy with prednisolone (50 mg/day) and cyclosporin A (150 mg/day), the respiratory symptoms and interstitial shadows were gradually reduced. Although it is known that interstitial pneumonia has an acute course and poor prognosis in ADM, the present case responded well to the chemotherapy with prednisolone and cyclosporin A.

Anti-Inflammatory Agents↗