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Biomedical subjects

Shigeru Kohno

Publications and source records attributed to Shigeru Kohno.

At least 109 records · Page 6Linked to original sources
PubMed2005

Nephronophthisis in two siblings.

We describe here two sisters with nephronophthisis, which was not detected until the development of endstage renal failure. Twenty- and 15-year-old female siblings were admitted to our hospital for further examination of renal dysfunction. No urinalysis abnormalities had been found in yearly health checks in either patient. The serum creatinine level was 7.2 mg/dl in case 1 (the 20-year-old) and 6.4 mg/dl in case 2. Medical history, physical findings, and laboratory tests showed no evidence of urinary tract infection, use of any drugs, arthritis, or skin eruptions. To identify the cause of the renal failure, open left renal biopsies were performed in both patients. Histopathological findings were very similar in the two patients and included marked tubular and interstitial changes (tubular dilatation, focal tubular atrophy, interstitial fibrosis, and infiltration of mononuclear cells). The glomeruli were devoid of mesangial proliferation, mesangial expansion, and adhesion of Bowman's capsule. Based on the clinical and pathological findings, the final diagnosis was nephronophthisis in both patients. It is important to remember that some progressive renal diseases, including nephronophthisis, cannot be detected even by annual urinary screening tests, which are widely performed in Japan.

Adolescent↗
PubMed2005

Circulating ghrelin levels in patients with various upper gastrointestinal diseases.

The stomach is the main source of circulating ghrelin. Plasma concentrations of this hormone in patients with various upper gastrointestinal diseases remain undetermined. Thus we measured plasma ghrelin levels by radioimmunoassay in 225 subjects, including 134 Helicobacter pylori-infected and 91 uninfected subjects. They included 67 patients with chronic gastritis (CG), 26 with benign gastric polyp (BGP), 24 with gastric ulcer (GU), 24 with reflux esophagitis (RE), 18 with duodenal ulcer (DU), 28 with acute gastritis (AG), 23 with gastric cancer (GC), and 39 who had normal mucosa on upper endoscopy (N). Plasma pepsinogen I and II levels were also measured. The extent of gastritis was assessed endoscopically. Ghrelin levels differed significantly among the different disease groups. Plasma ghrelin concentrations were lowest in the CG group, followed by the GU group, and highest in the AG patients. There was a significant difference in the levels between differentiated and undifferentiated GC. Ghrelin concentrations in BGP, RE, and DU patients were comparable to those in the N group. Ghrelin circulating levels were lower in H. pylori-positive than -negative individuals, but the significant differences among disease groups were still observed in H. pylori-infected and uninfected populations. Ghrelin concentrations correlated positively with plasma pepsinogen I levels and I/II ratios and inversely with the extent of H. pylori-related gastritis. Plasma ghrelin levels varied widely in diverse conditions of the upper digestive tract, reflecting the inflammatory and atrophic events of the background gastric mucosa. Further investigation is warranted to unravel the mechanisms of the high circulating ghrelin levels in certain upper gastrointestinal diseases.

Adult↗
PubMed2005

The sperm mitochondria-specific translocator has a key role in maternal mitochondrial inheritance.

The mechanism of maternal mitochondrial inheritance in animals involves the selective elimination of sperm mitochondria by the elimination factor of the egg and the sperm mitochondria-specific factor. In vitro fertilization using sperm from isogenic mice incorporating heterospecific mitochondrial DNA (mtDNA) showed that the number of PCR positives of sperm mtDNA in two-cell embryos was significantly increased following sperm incubation with anti-tetratricopeptide repeat-containing protein involved in spermatogenesis (tpis) protein, anti-translocator of mitochondrial outer membrane (Tom) 22 and anti-Tom40 antibodies. The treatment of fertilized eggs with EGTA and other endonuclease inhibitors increased the sperm mtDNA levels. We conclude that the elimination factor, which is probably an endonuclease, is selectively received by the tpis protein of the sperm mitochondrial outer membrane within the egg. It is then transported into the sperm mitochondria by Tom22 and Tom40, where it destroys the sperm mtDNA, establishing the maternal inheritance of mtDNA.

Animals↗
PubMed2005

Antimicrobial susceptibilities of potential bacterial pathogens in adults with acute respiratory tract infections Prospective Epidemiological Network Investigating Community-acquired Infection SurveiLLance In Nagasaki (PENICILLIN) Study.

The prevalence and the antimicrobial susceptibilities of bacterial pathogens in acute upper respiratory tract infections (AURTIs) is not clear. We conducted a prospective community-based multicenter study in 45 centers across Nagasaki, Japan, between December 2001 and April 2002. We examined the nasopharyngeal or throat isolates in 930 adult outpatients with AURTIs. Potential bacterial pathogens, including Streptococcus pyogenes (from 6.8% patients), S. pneumoniae (5.3%), S. milleri group (2.0%), Staphylococcus aureus (26.0%), Moraxella catarrhalis (7.4%), Haemophilus influenzae (17.6%), and Klebsiella pneumoniae (1.2%), were isolated from 51.8% of the patients. Penicillin nonsusceptible phenotype accounted for 44.9% of S. pneumoniae isolates. Among Staphylococcus aureus isolates, 9.1% were methicillin-resistant. In H. influenzae isolates, 6.7% produced beta-lactamase and 23.2% were beta-lactamase-negative ampicillin-resistant. The results indicated that the potential bacterial pathogens were detected in the remarkable population of the adults with AURTIs and the current antimicrobial susceptibilities of such pathogens.

Acute Disease↗
PubMed2005

Regional variation in the prevalence of extended-spectrum beta-lactamase-producing clinical isolates in the Asia-Pacific region (SENTRY 1998-2002).

We examined the prevalence of extended-spectrum beta-lactamase (ESBL)-producing strains of Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Proteus mirabilis, Citrobacter koseri, and Salmonella spp. that were isolated as part of the SENTRY Asia-Pacific Surveillance Program between 1998 and 2002. During the study period, a total of 6,388 strains were gathered from 17 medical centers in 7 countries and examined for ESBL production and hyperproduction of K. oxytoca chromosomal K1 beta-lactamase enzyme. High rates of confirmed ESBL-producing isolates were found in K. pneumoniae strains from Singapore (35.6%), followed by those from mainland China (30.7%), South Africa (28.1%), and the Philippines (21.9%), whereas the rates were less than 10% in Japan and Australia. ESBL-producing E. coli strains were also prominent in mainland China (24.5%), Hong Kong (14.3%), and Singapore (11.3%). ESBL-producing K. oxytoca were common in the Philippines (38.5%), Singapore (33.3%), and China (30.0%). Hyperproduction of K. oxytoca chromosomal K1 beta-lactamase enzyme was common in Australia and Japan. P. mirabilis strains from Singapore produced ESBL (17.9%) despite the low prevalence (0-8.1%) in other countries. Few ESBL-producing C. koseri and Salmonella spp. strains were found in Japan, Singapore, Taiwan, and South Africa. Although there was variation among countries in substrate preference, ceftazidime was more likely to detect presumptive ESBL phenotype in K. pneumoniae and aztreonam more likely in E. coli, whereas ceftriaxone was the best substrate for the confirmation of ESBL production. ESBL-producing strains showed high levels of co-resistance to aminoglycosides, tetracycline, trimethoprim-sulfamethoxazole, and ciprofloxacin. Imipenem retained activity against all ESBL-producing strains. Organisms expressing ESBLs are widely distributed in the Asia-Pacific region, although prevalence rates vary significantly.

Anti-Bacterial Agents↗
PubMed2005

PROTEKT 1999-2000: a multicentre study of the antimicrobial susceptibility of respiratory tract pathogens in Japan.

DESIGN: A six-centre study in Japan during the winter of 1999-2000 assessed the in vitro activity of >20 antimicrobial agents against the common respiratory pathogens Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis. The minimum inhibitory concentrations (MIC) of each antimicrobial was determined against these isolates using National Committee for Clinical Laboratory Standards (NCCLS) methodology. RESULTS: Among S. pneumoniae isolates, 44.5% were penicillin resistant. The macrolide resistance rate was 77.9% with 90.5% of penicillin-resistant strains also being macrolide resistant. Resistance mechanisms in macrolide-resistant isolates were identified as mef(A) or erm(B) in 42.5% and 52.5%, respectively. Of the fluoroquinolone-resistant isolates (1.3%), most were also penicillin and macrolide resistant. All strains were inhibited by telithromycin at <or=1mg/L. Among S. pyogenes isolates, erythromycin resistance was 17.5% overall but showed considerable variation among the six centres. For H. influenzae, 8.5% produced beta-lactamase and a single beta-lactamase-negative, ampicillin-resistant isolate (0.36%) was obtained, and there was no fluoroquinolone resistance. All isolates were susceptible to telithromycin. Most antimicrobials showed good activity against M. catarrhalis, although 96.7% were beta-lactamase positive. CONCLUSION: The prevalence of antimicrobial resistance to macrolides, penicillin and the fluoroquinolones among the common respiratory pathogens is high in Japan.

Anti-Bacterial Agents↗
PubMed2005

Placental and intestinal alkaline phosphatases are receptors for Aeromonas sobria hemolysin.

The Aeromonas sobria hemolysin causes diarrhea following infection by this enteropathogenic bacterium. We previously identified the putative receptor for A. sobria hemolysin as a p66 protein on Intestine 407 cells (Microb. Pathog. 27 (1999) 215-221). Here, we have partially purified and obtained a peptide mass fingerprint of p66 which revealed its identity with placental alkaline phosphatase (PLAP). Recombinant PLAP expressed in 293T cells was also found to bind to hemolysin and the binding was found not to be dependent on the N-linked glycosylation of PLAP. By immunohistochemical analysis, PLAP expression was detected in human intestinal mucosa, the target tissue in disease. In addition to PLAP, hemolysin also binds to intestinal alkaline phosphatase (IAP), an enzyme that is also abundantly expressed in intestine. Thus, both PLAP and IAP are very likely involved in the pathogenesis of diarrhea caused by this bacterial toxin.

Aeromonas↗
PubMed2005

Novel effects of gefitinib on mucin production in bronchioloalveolar carcinoma; two case reports.

Two Japanese females complained of cough and bronchorrhea for which chest radiographs showed infiltrate in the lungs. The patients were subsequently diagnosed as having bronchioloalveolar carcinoma by transbronchial lung biopsy. After receiving systemic chemotherapy, their symptoms were slightly improved. A few months later, their bronchorrhea and dyspnea worsened, and they were then treated with gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor. Bronchorrhea and dyspnea were improved within 24 h after treatment with gefitinib where the improvement was evident after 6 h for one patient and 24 h for the other patient. Thereafter, their radiological findings showed gradual improvement. Rapid relief of bronchorrhea preceded the improvement seen by the radiological findings. These observations suggest that gefitinib may inhibit mucin production as well as exert anti-proliferative activity against bronchioloalveolar carcinoma.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2005

Gefitinib, an EGFR tyrosine kinase inhibitor, directly inhibits the function of P-glycoprotein in multidrug resistant cancer cells.

Gefitinib (Iressa) is a selective epidermal growth factor receptor tyrosine kinase inhibitor and is used for the treatment of lung cancer. Recently, we discovered that it inhibits the breast cancer resistance protein, which is an ATP-binding cassette transporter. P-glycoprotein (Pgp) also pumps multiple types of drugs out of the cell using energy generated from ATP, and confers multidrug resistance on cancer cells. This study was designed to examine whether gefitinib inhibits the function of Pgp. We used multidrug resistant PC-6/PTX lung cancer and MCF-7/Adr breast cancer cells which overexpress Pgp and measured their drug sensitivity and drug-efflux function by tetrazolium assay and flowcytometry, respectively. In addition, the drug-stimulated ATPase activity of Pgp was measured using insect membranes that express human Pgp. Epidermal growth factor receptor was expressed in MCF-7/Adr, but not in PC-6/PTX cells, and the overexpression of Pgp did not confer resistance to gefitinib to both cell types. However, clinically achievable levels of gefitinib moderately reversed the Pgp-mediated resistance to paclitaxel and docetaxel in Pgp overexpressing cells. In addition, gefitinib increased the intracellular accumulation of the Pgp substrate rhodamine-123 in resistant cells, and activated ATPase in a preparation of pure Pgp-expressing membrane. These findings suggest that gefitinib directly interacts with Pgp and inhibits its function. Gefitinib may clinically inhibit the excretion of Pgp substrate drugs including anticancer agents, and its drug-interaction should therefore be considered.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Gefitinib inhibits MUC5AC synthesis in mucin-secreting non-small cell lung cancer cells.

Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is an active agent in non-small cell lung cancer, and rapidly relieves bronchorrhea in patients with bronchioloalveolar carcinoma before the improvement of radiological findings. In addition, epidermal growth factor regulates mucin secretion in normal airway goblet cells. The present study was designed to clarify whether gefitinib modifies mucin production in lung cancer cell lines apart from its anti-proliferative effects, using A549 adenocarcinoma and NCI-H292 mucoepidermoid carcinoma cells expressing EGFR and MUC5AC mRNA. Mucin synthesis was measured by RT-PCR and ELISA, and MAPK and Akt, the downstream targets of EGFR, were examined by Western blotting assay. The clinically-achievable concentration of 1muM gefitinib inhibited the growth of both cells by only 10%, but gefitinib suppressed MUC5AC mRNA levels subsequent to a decrease in intracellular and secreted MUC5AC protein. Gefitinib also inhibited the phosphorylation of MAPK and Akt, and the selective inhibitors PD98059 and LY294002 also suppressed MUC5AC protein synthesis. These findings suggest that gefitinib may inhibits MUC5AC synthesis, at least in part, through MAPK and Akt signaling pathways. Thus, gefitinib inhibits mucin production, which is encouraging for trials involving its use against bronchorrhea in patients with lung cancer.

Adenocarcinoma↗
PubMed2005

Better choice of fixatives provides better histological details of the alveolar-capillary interface.

AIMS: To evaluate lung disease, pulmonary tissues should be fixed by inflation. However, many histological sections prepared after inflation fixation show wire-like alveolar septa with capillary collapse. We investigated the reason for this artefact. METHODS: To evaluate the effect of fixatives, we used the following commercially available solutions: regular 10% neutral buffered formalin (NBF), 20% NBF, 10% and 5% formalin prepared by diluting the 20% NBF, modified formalin solution as a substitute for 10% NBF, and 10% formalin prepared by diluting the 100% formalin without any buffers. RESULTS: The osmolarity of the fixative was found to be responsible for the collapse artefact. Ten per cent formalin, prepared by diluting 100% formalin, the commercially available substitute for 10% NBF, and 5% formalin prepared by diluting 20% NBF, yielded the best pulmonary tissue morphology, including that of the alveolar-capillary interface. CONCLUSIONS: Pulmonary physicians and pulmonary pathologists should use a suitable fixative solution for obtaining a better pulmonary architecture as well as to preserve the tissue block in optimal condition for future assessment of pulmonary diseases.

Artifacts↗
PubMed2005

Community acquired pneumonia (CAP) caused by Cryptococcus neoformans in a healthy individual.

A 41-y-old male had been diagnosed as having community acquired pneumonia (CAP) with consolidations in the chest radiograph, fever and cough. Since clarithromycin and ss-lactam agents were not effective, bronchoscopic examination was performed. Indian ink staining of bronchial wash smears revealed yeast-like cells with a thick capsule, and Cryptococcus neoformans was isolated several d later. Serum glucuronoxylomannan antigen was > or = x 1024. The patient was treated with itraconazole for 16 weeks.

Adult↗
PubMed2005

Chronic necrotizing pulmonary aspergillosis following cryptococcal infection of the lung.

A 64-y-old male with steroid-induced diabetes mellitus was admitted to our hospital because of a nodular shadow found by chest radiography. Pathological examination revealed pulmonary cryptococcosis, and he was positive for serum Cryptococcus antigen. After oral treatment with fluconazole, he experienced clinical and radiographic improvement, but during ensuing observation without antifungal treatment his respiratory symptoms gradually worsened. Chest radiography showed progressive infiltration around the cavity, and Aspergillus mold was isolated by transbronchial lung biopsy from the lesion where previous cryptococcal infection was present. In addition, serum antibodies to Aspergillus antigens were demonstrated by immunodiffusion. Thus, pulmonary aspergillosis was found to complicate a case of pulmonary cryptococcal infection.

Aspergillosis↗
PubMed2005

Salivary IgA and oral candidiasis in asthmatic patients treated with inhaled corticosteroid.

BACKGROUND: Inhaled corticosteroids are used for the treatment of bronchial asthma. Systemic side effects are rare, but local problems, such as oral candidiasis, can occur. Only a proportion of patients encounter this problem, and the mechanism of oral candidiasis induced by inhaled corticosteroids remains obscure. According to reports in immunodeficient patients, oral candidiasis is related to deficiencies in topical immunity, such as salivary IgA. OBJECTIVES: We evaluated differences in salivary IgA between asthmatics in whom Candida was detected or not detected from the pharynges, respectively. METHODS: Saliva was collected from 18 healthy controls and 37 asthmatic patients treated with inhaled corticosteroids. The amounts of total IgA and the Candida-specific IgA of the saliva were measured. Fungal culture of the pharyngeal wall was also performed. RESULTS: There were no differences in salivary total IgA and Candida-specific IgA between healthy controls and culture-negative asthmatic patients. Salivary total IgA of Candida-positive asthmatic patients was significantly lower than that of Candida-negative patients. However, there was no difference in Candida-specific IgA levels between these two groups. CONCLUSIONS: Our results suggest that inhaled corticosteroids can potentially decrease salivary total IgA but that host factors are also important in the development of oral candidiasis.

Administration, Inhalation↗
PubMed2005

Role of Pseudomonas aeruginosa quorum-sensing systems in a mouse model of chronic respiratory infection.

The role of quorum-sensing systems in a mouse model of chronic Pseudomonas aeruginosa infection was studied. A chronic P. aeruginosa respiratory infection model was established by placement of a tube pre-coated with strain PAO1 (wild-type) or a quorum-sensing mutant, namely PAO-JP1 (Delta lasI), PDO100 (Delta rhlI) or PAO-JP2 (Delta lasI/Delta rhlI), in the bronchus. At day 14 after infection, the numbers of viable bacteria in the quorum-sensing-mutant groups were lower than in the wild-type group. Histopathological examination showed milder inflammatory changes in the lungs infected with the mutant groups compared with the wild-type group. In the bronchoalveolar lavage fluid from the quorum-sensing-system-mutant groups the proportion of neutrophils was lower than in wild-type group. These findings indicate that the quorum-sensing system plays an important role in chronic P. aeruginosa respiratory infection.

Animals↗