Search PubMed⌕ Search

Biomedical subjects

Shigeru Kohno

Publications and source records attributed to Shigeru Kohno.

At least 37 records · Page 2Linked to original sources
PubMed2006

Positive correlations between cerebral choline and renal dysfunction in chronic renal failure.

INTRODUCTION: Cerebral metabolism in chronic renal failure (CRF) patients has not been fully evaluated. This study examined cerebral metabolites in CRF, using proton magnetic resonance spectroscopy (MRS). METHODS: Subjects comprised 19 CRF patients and 21 healthy volunteers. Spectra were acquired from voxels of interest positioned in the parietal gray and white matter, and concentrations of the following cerebral metabolites were measured: N-acetyl group (NA), creatine + phosphocreatine (Cr), choline-containing compounds (Cho), myo-inositol and glutamate + glutamine. Among the 19 CRF patients, 9 who were started on hemodialysis (HD) underwent careful follow-up. Proton MRS was performed before and about 2 weeks after starting HD. In six patients in whom follow-up was possible, a third MRS was performed after about 18 months. RESULTS: The NA/Cr ratio was not significantly changed in CRF. However, elevations in the Cho/Cr ratio were found in both gray and white matter compared with controls. To the best of our knowledge, this is the first report of positive correlations between the Cho/Cr ratio in both regions and serum osmotic pressure. Compared with baseline data, no significant changes in cerebral metabolite ratios were found about 2 weeks after starting HD. About 18 months after starting HD, however, the elevated Cho/Cr ratio was significantly reduced in the gray matter and tended to be reduced in the white matter. CONCLUSIONS: Cho appear to play an important role in the regulation of cerebral metabolism to compensate for alterations in serum osmotic pressure in CRF, and HD may correct this abnormal cerebral metabolism.

Adult↗
PubMed2006

The expression of pro- and anti-apoptotic Bcl-2 family proteins in peribronchiolar lymphocytes from patients with diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is a distinctive form of small airway disease, which is characterized by chronic inflammation with lymphocyte infiltration around bronchioles. The aim of this study was to evaluate the importance of factors related to apoptosis in peribronchiolar lymphocytes of DPB. We employed immunohistochemical methods for the localization of Bax (a promoter of apoptosis), Bcl-2 (an inhibitor of apoptosis), and caspase-3 (a key executioner molecule of apoptosis) in lung tissues of five patients with DPB. In all patients, immunostaining for Bax was almost completely absent in accumulated lymphocytes around the bronchioles and in lymphocytes of the parafollicular area that correspond to a zone populated by T cells. In contrast to the reaction for Bax, Bcl-2 immunoreactivity was uniformly strong in all of the patients. The pattern of staining for caspase-3 was similar to that for Bax in all of the patients. In normal lung tissue, a few lymphocytes showed negative immunostaining for Bcl-2 and a positive reaction for caspase-3. Our results suggest that Bcl-2 protein may provide T-lymphocyte survival and hypercellularity in the bronchioles, thereby contributing to the progression of DPB.

Adolescent↗
PubMed2006

Long-term survival in three patients with metastatic non-small cell lung cancer treated with gefitinib.

Gefitinib, a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), produces radiographic regression and symptom relief in patients with refractory advanced non-small cell lung cancer. However, it remains controversial whether gefitinib improves patient survival. We report three cases of refractory metastatic non-small cell lung cancer who have survived approximately 3 years since they first started gefitinib. These long-term survivors were Japanese female non-smokers with adenocarcinoma, who often had multiple lung metastases and were effectively re-treated with gefitinib. One patient had a surgical specimen available for DNA extraction and showed deletions in exon 19 of EGFR. Our experience suggests that gefitinib may improve long-term survival in selected patients. Further studies are required to identify biomarkers downstream of the EGFR mutations that are involved in multiple lung metastases and which could identify those patients who may benefit from gefitinib re-treatment.

Aged↗
PubMed2006

BCRP/ABCG2 levels account for the resistance to topoisomerase I inhibitors and reversal effects by gefitinib in non-small cell lung cancer.

PURPOSE: Breast cancer resistance protein (BCRP) confers resistance against topoisomerase I inhibitors in cancer cells. Very recently, we reported that gefitinib reverses BCRP-mediated drug resistance by direct inhibition. However, it remains undetermined how much BCRP contributes to the resistance to topoisomerase I inhibitors in non-small cell lung cancer (NSCLC). The present study was designed to examine whether BCRP levels in NSCLC cells are correlated with the resistance to topoisomerase I inhibitors and the reversal effect by gefitinib. METHODS: BCRP levels and its function were evaluated by Western blotting and flowcytometry, respectively. Gefitinib-insensitive NSCLC cells expressed various levels of BCRP, which were closely correlated not only with the IC50 values of SN-38 (r=0.874, P<0.05) and those of topotecan (r=0.968, P<0.001), but also with the reversal effects of 1 microM gefitinib on SN-38 resistance (r=0.956, P<0.001) and topotecan resistance (r=0.977, P=0.0001). RESULTS: BCRP levels accounted for between 80 and 90% of the variation in the resistance to topoisomerase I inhibitors and the reversal effects by gefitinib. Also, gefitinib increased intracellular topotecan accumulation in proportion to the BCRP levels. CONCLUSIONS: These findings suggest that BCRP is the most important molecule responsible for topoisomerase I inhibitor resistance, and that the development of BCRP inhibitors is an effective approach for overcoming this resistance. In addition, the examination of BCRP levels in NSCLC tissues may identify an optimal patient population for treatment with topoisomerase I inhibitors alone or in combination with BCRP inhibitors.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2006

A case of Mycobacterium nonchromogenicum pulmonary infection showing multiple nodular shadows in an immunocompetent patient.

Mycobacterium nonchromogenicum is generally considered nonpathogenic. However, M. nonchromogenicum rarely causes human disease; particularly, pulmonary disease is extremely rare. The common finding of M. nonchromogenicum pulmonary infection on chest X-ray is a solitary cavity. The present report describes an unusual case of M. nonchromogenicum primary pulmonary infection showing multiple nodular shadows.

Adult↗
PubMed2006

A phase I trial of carboplatin and etoposide for elderly (>or=75 year-old) patients with small-cell lung cancer.

PURPOSE: The combination of carboplatin and etoposide is currently considered the most appropriate regimen for treating elderly patients with small-cell lung cancer (SCLC). Previous reports on elderly patients, 70 years or older, found that the recommended dose was close to that of younger patients. Then, we conducted a phase I study of carboplatin and etoposide in elderly patients, 75 years or older, with SCLC. This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). METHODS: Twenty-six patients fulfilling the eligibility criteria, chemotherapy-naive, performance status (PS) of 0-2, age>or=75, and adequate organ functions were enrolled. Patients' characteristics were: male/female=21/5; PS 0/1/2=9/11/6; median age (range)=78 (75-82); and limited/extensive stage=16/10. The patients intravenously received carboplatin with a target AUC of 4 or 5 mg min/ml (Chatelut formula) on day 1 and etoposide at 80-120 mg/m2 on days 1, 2 and 3. Therapy was repeated four times in every 4 weeks. RESULTS: The MTD of carboplatin/etoposide was AUC=5/80, 4/110, and 4/120. The DLTs were thrombocytopenia, neutropenia, leukopenia, and febrile neutropenia. Overall, grade 4 thrombocytopenia, neutropenia (>or=4 days), leukopenia (>or=4 days), and febrile neutropenia occurred in 27, 20, 7, and 13% of cases at MTD levels, respectively, and 0% at other levels. Twenty of 26 patients showed objective responses (2CR, 18PR; RR=77%). CONCLUSION: A dose of carboplatin of AUC=4 and etoposide of 100 mg/m2 was recommended in this regimen.

Aged↗
PubMed2006

Comparison of the grade evaluated by "Liver damage" of Liver Cancer Study Group of Japan and Child-Pugh classification in patients with hepatocellular carcinoma.

BACKGROUND: The "Liver damage" classification proposed by the Liver Cancer Study Group of Japan and Child-Pugh classification are both useful classifications for hepatic function. However, the factors responsible for the difference between the two classifications have not been fully investigated. METHODS: The medical records of 594 admissions of 220 patients with hepatocellular carcinoma (HCC) were retrospectively analyzed for encephalopathy, ascites, serum bilirubin and albumin, plasma retention rate (%) at 15min after injection of 0.5mg/kg of indocyanine green (ICG R15), and prothrombin time. RESULTS: Of 594 admissions, ICG R15 was tested in 337 (56.7%). The Child-Pugh classification was evaluated in all 594 admissions, but the "Liver damage" could be evaluated in 510 (85.9%) due to the lack of ICG R15 results. Of the 594 admissions, 372 (62.6%), 162 (27.3%), and 60 (10.1%) were Child-Pugh grade A, B, and C, respectively. Of the 510 admissions, 219 (42.9%), 202 (39.6%), and 89 (17.5%) were "Liver damage" grade A, B, and C, respectively. The grade of "Liver damage" was similar to that of Child-Pugh classification in 369 (72.4%), under-evaluated in 138 (27.1%), and over-evaluated in 3 (0.6%). The Child-Pugh classification was statistically a better classification for predicting outcome than "Liver damage", but the "Liver damage" had better stratification ability than Child-Pugh classification in patients with relatively good liver function. CONCLUSIONS: Although the "Liver damage" could not be evaluated in some cases due to the lack of ICG R15 results, this classification system is useful in the evaluation and prediction of outcome of patients with early-stage liver diseases.

Journal Article↗
PubMed2006

Antimicrobial susceptibility of respiratory tract pathogens in Japan during PROTEKT years 1-3 (1999-2002).

Data are presented on antimicrobial resistance among isolates of Streptococcus pneumoniae, Streptoco-ccus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis collected in Japan during years 1-3 (1999-2002) of the Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin (PROTEKT) surveillance study. In addition to the standard panel of PROTEKT antimicrobial agents, eight other agents often used in Japan also were tested against these isolates. The majority (30%-55%) of S. pneumoniae and H. influenzae isolates were collected from patients with community-acquired pneumonia, whereas most (>70%) S. pyogenes isolates came from patients with tonsillitis/pharyngitis. Penicillin and macrolide resistance were high among isolates of S. pneumoniae, averaging 30.9%-44.5% and 77.2%-79.9%, respectively, across all centers over the 3 study years; the highest occurrences were reported among pediatric patients aged 0-2 years. The erm(B) genotype accounted for >50% of all erythromycin-resistant isolates each study year. S. pyogenes isolates were highly susceptible to most antimicrobial agents except the macrolides and tetracycline. beta-Lactamase production among H. influenzae isolates range was 8.5%-9.7% per annum. A total of 9 beta-lactamase-negative, ampicillin-resistant isolates were collected during the study. Almost all (>95%) M. catarrhalis isolates were beta-lactamase positive each year. Telithromycin was highly active against all pathogens examined in this study during all 3 years.

Adolescent↗
PubMed2006

Prospective multicenter study of the causative organisms of community-acquired pneumonia in adults in Japan.

Although a wide variety of recognized pathogens causes community-acquired pneumonia, the precise etiology in Japan remains unknown. We prospectively investigated the etiology in 232 patients with community-acquired pneumonia who visited 20 community-general hospitals. New diagnostic methods, using polymerase chain reaction (PCR) assays and urinary antigen tests were employed, in addition to conventional methods. The frequency of identification of causative pathogens was high (73.3%), and the leading organism was Streptococcus pneumoniae (24.6%), followed by Haemophilus influenzae (18.5%), viruses (16.4%), Chlamydia pneumoniae (6.5%), Mycoplasma pneumoniae (5.2%), and Legionella spp. (3.9%). S. pneumoniae and M. pneumoniae were the most prevalent pathogens in younger patients, and S. pneumoniae and H. influenzae were the most prevalent in elderly patients. Multiple or mixed infections were found in 25.9% of all patients and in 35.3% with a causal diagnosis. The results have important practical implications for the initial treatment of adult patients with community-acquired pneumonia.

Adolescent↗
PubMed2006

Study of upper respiratory tract bacterial flora: first report. Variations in upper respiratory tract bacterial flora in patients with acute upper respiratory tract infection and healthy subjects and variations by subject age.

With the appearance of penicillin-resistant Streptococcus pneumoniae, there has been increasing debate concerning antimicrobial treatments for acute upper respiratory tract infection (AURTI) and acute otitis media in children. This study compares the nasopharyngeal bacterial flora in patients with AURTI (AURTI group; 710 subjects) and healthy subjects (HS group; 380 subjects). The comparisons were made between subjects aged 6 years or younger (0-6 subgroup: 330 subjects), between 7 and 74 years (7-74 subgroup: 668 subjects), and 75 years and older (92 subjects), because the subjects were subgrouped as described above dependent on the maturity of the protective immunity. In the HS group 7-74 subgroup, viridans group streptococci, Staphylococcus aureus, coagulase-negative staphylococci, and Corynebacterium sp. with a detection rate of 10% or more were classified as normal nasal flora (NNF), and Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were classified as drum cavity pathogens (DCP). In the 0-6 subgroup, although the detection rate for DCP bacteria in the AURTI group tended to be high, it did not reach a significant difference, whereas the detection rate for NNF bacteria was significantly lower. This trend was also observed to some degree in the other age subgroup. In the 0-6 subgroup, leukocyte infiltration observed with a microscope indicated the closest relationship between S. pneumoniae detection rate and detection quantity. These results suggest that in the 0-6 subgroup the tendency for patients with AURTI to have NNF bacteria as well as DCP bacteria should be taken into consideration.

Acute Disease↗
PubMed2006

Flow cytometric analysis of expression of transforming growth factor-beta and glucocorticoid-induced tumor necrosis factor receptor on CD4(+) CD25(+) T cells of patients with inflammatory bowel disease.

To determine whether human CD4(+)CD25(+) cells express glucocorticoid-induced tumor necrosis factor receptor (GITR) and transforming growth factor-beta (TGF-beta) and the difference in CD4(+)CD25(+) cells between patients with inflammatory bowel diseases and healthy subjects, peripheral blood lymphocytes were obtained from patients with ulcerative colitis (UC; n = 50), Crohn's disease (CD; n = 49), and healthy volunteers (control; n = 50) and flow cytometric analysis was performed. In control subjects, the expression of GITR on CD4(+)CD25(+) cells (41.8 +/- 10.5%) was significantly higher than on CD4(+)CD25(-) cells (11.1 +/- 7.4%). Similarly, TGF-beta expression on CD4(+)CD25(+) cells (5.3 +/- 4.6%) was higher than on CD4(+)CD25(-) cells (1.2 +/- 1.4%). There were no significant differences among UC, CD, and control in CD4(+)CD25(+)/CD4(+) ratio. However, there was a significant difference in the CD4(+)CD25(+) TGF-beta+/CD4(+)CD25(+) ratio between active UC and inactive UC (2.7 +/- 2.6 and 7.2 +/- 3.9%, respectively). The results suggest that TGF-beta is involved in the induction or sustained remission of UC.

Adolescent↗
PubMed2006

Renal circulatory effects of acetazolamide in patients with essential hypertension.

BACKGROUND: Reports indicate that acetazolamide (ACZ) induces the vasodilation of all vessels in animal models, as well as in small and medium kidney vessels in animal models. However, the effect of ACZ on the renal circulation of patients with essential hypertension remains unknown. In this study we examined the effects of a carbonic anhydrase inhibitor, acetazolamide (ACZ), on the renal circulation of patients with essential hypertension. METHODS: We directly infused 1000 mg of ACZ into the main renal arteries of 10 patients with essential hypertension who had undergone cardiac catheterization. We then evaluated the effects of ACZ upon heart rate, renal artery blood pressure (BP), renal artery cross-sectional area, renal Doppler blood flow velocity, renal blood flow (RBF), and renal vascular resistance (RVR). RESULTS: The infusion of ACZ was not associated with any significant changes in heart rate or in systolic or diastolic BP. However, the velocity-time integral was increased by 11.1% +/- 7.2%, from 17.6 +/- 1.8 to 20.0 +/- 3.7 cm (P = .009); RBF was increased by 39% +/- 21%, from 300 +/- 43 to 422 +/- 96 mL/min/m(2) (P = .002); and RVR was reduced by 38% +/- 20% from 24,351 +/- 2,291 to 17,651 +/- 2,731 dynes.sec.cm(-5) (P < .01). In contrast the cross-sectional area of the renal artery did not change. CONCLUSIONS: The results of the present study demonstrated that ACZ has a potent vasodilatory effect on the renal circulation of patients with essential hypertension, leading to an obvious decrease in RVR and an increase in RBF.

Acetazolamide↗
PubMed2006

Effects of anti-inflammatory therapies on recurrent and low-grade respiratory syncytial virus infections in a murine model of asthma.

BACKGROUND: Recurrent and subclinical viral respiratory tract infections could immunologically exacerbate allergic airway inflammation. However, the most appropriate treatment for virus-induced asthma exacerbation is yet to be established. The effects of glucocorticoids in virus-induced acute asthma are controversial. OBJECTIVE: To determine the effects of representative anti-inflammatory therapies for asthma--glucocorticoids and leukotriene receptor antagonists (LTRAs)--in mite allergen-sensitized and repeatedly low-grade respiratory syncytial virus (RSV)--infected mice. METHODS: Dermatophagoides farinae-sensitized mice were inoculated twice with low-grade RSV and subcutaneously injected with either a glucocorticoid or an LTRA for 4 consecutive days. Lung inflammation, cytokine profiles, LT production, and viral RNA in lung tissues were compared in 5 groups of 8 mice each: controls, D farinae allergen sensitized, D farinae sensitized and RSV infected, D farinae sensitized and RSV infected with dexamethasone, and D farinae sensitized and RSV infected with pranlukast, an LTRA. RESULTS: Allergic airway inflammation in D farinae mice was significantly enhanced by recurrent and low-grade RSV infections (RLRIs). The glucocorticoid attenuated allergic airway inflammation, which was associated with interleukin 5 (IL-5) and interferon-gamma (IFN-gamma) suppression in lung-draining lymph nodes without affecting viral quantity. The LTRA also attenuated allergic airway inflammation in D farinae-RSV mice with concomitant inhibition of IL-5 but not IFN-gamma. Dermatophagoides farinae allergen sensitization significantly increased LTs in the airway, whereas RLRIs did not further enhance LT production. CONCLUSIONS: Glucocorticoids and LTRAs significantly inhibit RLRI-induced exacerbation of allergic airway inflammation by distinct pathways. Dexamethasone suppressed nonspecific cytokines, whereas viral RNA did not increase via suppression of immunity. In contrast, pranlukast specifically inhibited IL-5 but not IFN-gamma.

Acute Disease↗
PubMed2006

IgA class antibodies to 2-oxo-acid dehydrogenase complex are not predictive markers of histopathological progression in primary biliary cirrhosis.

Although antimitochondrial antibody (AMA) is the characteristic serological feature of primary biliary cirrhosis (PBC), its pathogenic role remains unclear. In our previous study, we reported a positive correlation between immunoglobulin (Ig) A class anti-2-oxo-acid dehydrogenase complex (2-OADC) and histopathological stage. To determine whether the appearance of IgA class anti-2-OADC by immunoblotting represents an early marker of more aggressive disease or whether it is late finding during the disease course of PBC, we tested not only the entire IgA class but also IgA1, IgA2 and secretory IgA class anti-2-OADC in serial serum samples from 15 patients with PBC. During the median observation period of 51 months, four cases showed histopathological progression (from stage 1 to 2, stage 1 to 3, stage 1 to 4 and stage 2 to 4). There was no statistically significant correlation between the above IgA class anti-2-OADCs and histopathological progression. There was no significant correlation between histopathological stages and IgA2 class anti-2-OADC or secretory IgA class anti-2-OADC by immunoblotting. IgA class anti-2-OADC was more frequent in stages 3-4 than in stages 1-2 (p = 0.0049), but IgA1 class anti-2-OADC was more frequent in stages 1-2 than in stages 3-4 (p = 0.0232). Our present study demonstrated that serum IgA class 2-OADC was not a predictive marker of histopathological progression but was associated with the histopathological stage of PBC. Although the IgA class AMA may have a specific pathogenic role for PBC, the discrepant results between IgA and IgA1 class anti-2-OADC should be further assessed to investigate different functional activities depending on their molecular form.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed2006

Quorum sensing system lactones do not increase invasiveness of a MexAB-OprM efflux mutant but do play a partial role in Pseudomonas aeruginosa invasion.

We studied the quorum sensing (QS) system and the related homoserine lactones (HSLs) observing Pseudomonas aeruginosa invasion using the epithelial cell monolayer penetration assay model. Compared to the PAO1 wild-type, the QS mutants, DeltalasI and DeltarhlI, were compromised in their capacity to invade. The decreased invasiveness of DeltarhlI was restored by adding 100 microM exogenous C(4)-HSL. However, the decreased invasiveness of an efflux mutant, DeltamexAB-oprM, was not restored in the presence of exogenous HSLs. The QS system partially plays a role in P. aeruginosa invasion; however, C(4)-HSL and 3-O-C(12)-HSL are not the essential determinants for invasiveness for P. aeruginosa.

4-Butyrolactone↗
PubMed2006

Aldosterone breakthrough during therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in proteinuric patients with immunoglobulin A nephropathy.

BACKGROUND: We are investigating whether aldosterone breakthrough negatively impacts on the antiproteinuric effects of angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin II receptor blockers (ARB). METHODS: We examine the role of aldosterone breakthrough in 43 normotensive, proteinuric (0.7 +/- 0.3 g/day) outpatients (aged 41.5 +/- 10.9 years) with immunoglobulin A nephropathy (IgAN) accompanied by stable renal function (creatinine clearance >50 mL/min). The patients were treated with temocapril (1 mg; n = 14), losartan (12.5 mg; n = 16), or a combination therapy (n = 13) for 12 months. We prospectively evaluated blood pressure (BP), urinary protein excretion (UPE), biochemical parameters and the renin-angiotensin-aldosterone system before and after 12 months of treatment. RESULTS: Although the overall plasma aldosterone concentrations values did not change after any of the treatments administered for 12 months, they eventually increased in 23 (temocapril, seven patients; losartan, eight patients; combination, seven patients) of the 43 patients (53.4%; aldosterone breakthrough), and fell in the remainder (46.6%). Blood pressure and renal function did not differ among the three groups at 12 months. In contrast, UPE was significantly higher in patients with, than without aldosterone breakthrough during temocapril and losartan administration. However, combination therapy induced a more remarkable reduction in UPE regardless of aldosterone breakthrough. CONCLUSIONS: A combination of ACE inhibitors and ARB in normotensive patients with IgAN produces a more profound decrease in proteinuria than either monotherapy. This additive antiproteinuric effect is not dependent on aldosterone breakthrough. Additional larger, prospective, randomized studies will be needed for general acceptance of this strategy.

Adult↗