Biomedical subjects

T Honda

Publications and source records attributed to T Honda.

At least 145 records · Page 8Linked to original sources

PubMed2000

Long-term follow-up of sustained responders to interferon therapy, in patients with chronic hepatitis C.

Interferon (IFN) therapy has been proven to induce the normalization of serum alanine aminotransferase (ALT) levels and to eradicate the hepatitis C virus (HCV) in some patients with chronic hepatitis C, and these patients are usually defined as 'sustained responders'. However, there have been some reports of hepatocellular carcinoma (HCC) in these patients, and the development of HCC remains life-threatening in patients who clear HCV. We analysed the long-term prognoses of patients with chronic hepatitis C in whom HCV was eradicated with IFN. We investigated 392 sustained responders to IFN therapy, from 1,277 patients with chronic HCV infection who received IFN treatment at one of our institutions between April 1989 and March 1999. We analysed the medical records and looked for the development of HCC. About 30% of the sustained responders had been lost to follow-up 3 years after the end of IFN therapy, and the follow-up rate of sustained responders was significantly lower than that of non-sustained responders (P < 0.0001). HCC were found in eight patients: in seven patients HCC developed within 5 years after completion of IFN therapy; but in one patient, a single HCC less than 3 cm in diameter was detected between 7 and 8 years after completion of IFN. Of the five patients who had regular medical follow-up, the HCC was solitary, and the patients survived without any evidence of recurrence. Of the three patients who had not been followed-up, two died from HCC and HCC recurred in the third. These results suggest that HCC can develop in sustained responders and that sustained responders should be followed-up closely after completion of IFN so that HCC may be detected at an early stage. The optimal duration of the follow-up period of the sustained responders remains unclear. Additional prospective studies are required in order to establish an appropriate follow-up protocol for sustained responders to IFN.

Adolescent↗

PubMed2000

The effects of nicardipine on dynamic cerebral autoregulation in patients anesthetized with propofol and fentanyl.

UNLABELLED: We investigated the effects of nicardipine on dynamic cerebral pressure autoregulation in 13 normal adult patients undergoing gynecologic or orthopedic surgery. Anesthesia was induced and maintained with propofol and fentanyl. Hypotension to a mean arterial pressure of 60-65 mm Hg was induced and maintained with a continuous infusion of nicardipine. Time-averaged mean blood flow velocity in the right middle cerebral artery was measured continuously by using transcranial Doppler ultrasonography. The cerebral autoregulatory responses were activated by releasing thigh cuffs. The actual blood flow velocity in the right middle cerebral artery response to acute change in mean arterial pressure was fitted to 1 of 10 computer-generated curves to determine the dynamic rate of cerebral autoregulation (dRoR), and the best fitting curve was used. The autoregulation test was repeated until two values of dRoR were obtained at baseline and during induced hypotension. Nicardipine significantly reduced dRoR values of 13.1% +/- 3.6%/s at baseline to 8.3% +/- 2.6%/s during hypotension (P: < 0.01). During deliberate hypotension induced by nicardipine, the cerebral dynamic autoregulatory response is impaired in normal adult patients. IMPLICATIONS: During deliberate hypotension induced by nicardipine, the cerebral dynamic autoregulatory response is impaired in normal adult patients.

Adjuvants, Anesthesia↗

PubMed2000

Increased circulating soluble intercellular adhesion molecule-1 in acute myocardial infarction: a possible predictor of reperfusion ventricular arrhythmias.

OBJECTIVES: Myocardial ischemia/reperfusion induces ventricular reperfusion arrhythmias (RAs). Significant parts of RAs are considered to be evoked by oxygen free radicals. Inasmuch as activated leukocytes release oxygen free radicals, and as the intercellular adhesion molecule-1 (ICAM-1) plays a major role in leukocyte infiltration, we examined whether there may be a relationship between plasma levels of soluble ICAM-1 (sICAM-1) and frequency of RAs in patients with acute myocardial infarction (AMI). DESIGN: Prospective study comparing the two AMI patient groups with or without RAs. SETTING: Coronary care unit and cardiac catheterization laboratories in a general hospital. PATIENTS: Twenty-three AMI patients (eight women and 15 men, aged 32 to 79 yrs). INTERVENTIONS: All patients received percutaneous balloon angioplasty with or without previous intracoronary thrombolysis. Significant RAs were defined as at least one of nonsustained ventricular tachycardia, multifocal premature ventricular contraction, and frequent premature ventricular contraction occurring >15 times/min, which were not observed before reperfusion. MEASUREMENTS AND MAIN RESULTS: Plasma sICAM-1 levels were measured using an enzyme-linked immunosorbent assay. The plasma sICAM-1 levels at admission were significantly greater in RA(+) (243 +/- 60 ng/mL) than RA(-) group (192 +/- 44 ng/mL) (p < .05). We followed plasma sICAM-1 levels up to 3 wks, and found that sICAM-1 levels were consistently higher in the RA(+) than the RA(-) group. Simple regression analysis showed no significant relationship between plasma sICAM-1 levels and age, systolic and diastolic blood pressures, or serum creatine kinase activity. The two AMI groups showed no differences in age, gender, events of major coronary risk factors, preinfarction angina, and medication. CONCLUSIONS: The increase in the plasma levels of sICAM-1 was observed in patients manifesting ventricular RAs. This increase in sICAM-1 levels was observed as early as at admission. The increased plasma sICAM-1 levels may be a useful biochemical marker for predicting myocardial reperfusion injury such as RAs in AMI.

Adult↗

PubMed2000

Mechanisms of chloride secretion induced by thermostable direct haemolysin of Vibrio parahaemolyticus in human colonic tissue and a human intestinal epithelial cell line.

Thermostable direct haemolysin (TDH) produced by Vibrio parahaemolyticus is thought to play an important role in the severe diarrhoea caused by this organism. This study investigated the enterotoxicity of TDH for human intestinal cells. Addition of TDH to the mucosal side of human colonic tissue in Ussing chambers caused increased short circuit currents (Isc), a process that was inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS), an inhibitor of Ca2+ -activated chloride (Cl-) channels. With human colonic epithelial (Caco-2) cells, high Isc and intracellular Ca2+ concentrations ([Ca2+]in) were detected after the addition of TDH to the apical side of the cell monolayer. The Isc decreased with the addition of DIDS, but not with glybenclamide, 5-nitro-2-(3-phenylpropylamino) benzoic acid, or gadolinium chloride. No Isc increase with TDH was observed when the Cl- in the medium was replaced by gluconate or when Ca2+ was depleted. Similarly, TDH did not raise [Ca2+]in after depletion of extracellular Ca2+. R7, a mutant form of TDH, reduced the effects of TDH on Isc and [Ca2+]in, as did protein kinase C (PKC) inhibitors. Thus, TDH increases Cl- secretion in human colonic epithelial cells, apparently through mechanisms involving cell binding and Ca2+ influx, followed by elevation of [Ca2+]in associated with PKC phosphorylation.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2000

Interaction of enteropathogenic or enterohemorrhagic Escherichia coli with HeLa cells results in translocation of cortactin to the bacterial adherence site.

Infection of cultured HeLa epithelial cells with enteropathogenic Escherichia coli (EPEC) or enterohemorrhagic E. coli (EHEC) O157:H7 results in accumulation of cortactin under the adherent bacteria. Tyrosine phosphorylation of cortactin is not induced following HeLa cell infection with EHEC or EPEC, contrary to what has been reported to occur with Shigella flexneri.

Actins↗

PubMed2000

Genetic characterization of DNA region containing the trh and ure genes of Vibrio parahaemolyticus.

We have demonstrated that possession of the gene for thermostable direct hemolysin-related hemolysin (trh) coincides with the presence of the urease gene among clinical Vibrio parahaemolyticus strains and that the location of the two genes are in close proximity on the chromosome. Here, we cloned and sequenced the 15,754-bp DNA region containing the trh gene and the gene cluster for urease production from the chromosome of clinical V. parahaemolyticus (TH3996). We found 16 open reading frames (ORFs) and a lower G+C content (41%) compared with the total genome of this bacterium (46 to 47%). The ure cluster consisted of eight genes, namely, ureDABCEFG and ureR. ureR was located 5.2 kb upstream of the other seven genes in the opposite direction. The genetic organization and sequences of the ure genes resembled those found in Proteus mirabilis. Between ureR and the other ure genes, there were five ORFs, which are homologous with the nickel transport operon (nik) of Escherichia coli. We disrupted each of the ureR, ureC, and nikD genes in TH3996 by homologous recombination and analyzed the phenotype of the mutants. In the presence of urea these mutant strains had dramatically less urease activity than the strain they were derived from. Disruption of ureR, nikD, or ureC, however, had no effect on TRH production. The DNA region containing the trh, nik, and ure genes was found in only trh-positive strains and not in Kanagawa phenomenon-positive and environmental V. parahaemolyticus strains. At the end of the region, an insertion sequence-like element existed. These results suggest that the DNA region was introduced into V. parahaemolyticus in the past through a mechanism mediated by insertion sequences. This is the first reported case that the genes for an ATP-binding cassette-type nickel transport system, which may play a role in nickel transport through bacterial cytoplasmic membrane, are located adjacent to the ure cluster on the genome of an organism.

ATP-Binding Cassette Transporters↗

PubMed2000

mkp-1 encoding mitogen-activated protein kinase phosphatase 1, a verotoxin 1 responsive gene, detected by differential display reverse transcription-PCR in Caco-2 cells.

The major cytotoxic effect of the verotoxins (VTs) produced by strains of VT-producing Escherichia coli is the inhibition of host-cell protein synthesis, but VTs are also suspected to play a role in apoptotic cell signaling and cytokine release. Four differentially expressed genes, including mkp-1 (encoding mitogen-activated protein kinase phospatase 1), were detected by differential display reverse transcription-PCR (DD RT-PCR) stimulated by VT1 in Caco-2 cells. Northern blot analysis showed the induction of mkp-1 mRNA 6 h after VT1 stimulation. Neither mutant VT1 (mutVT1), harboring two mutations in the A subunit (E167Q-R170L), nor cycloheximide induced mkp-1 mRNA, but mkp-1 mRNA was detected with both wild-type VT1 (wtVT1) and anisomycin, a 28S rRNA inhibitor. Therefore, we concluded that the A subunit of VT1 was essential for mkp-1 induction. Increased amounts of phosphorylated c-Jun protein were also found with wtVT1 and anisomycin. Although the precise mechanism of induction of MKP-1 is unknown, we hypothesized that 28S rRNA not only was a sensor for ribotoxic stress, but also was involved in the signal cascade of MKP-1. This is the first report of detection by DD RT-PCR of cellular genes induced by bacterial toxins.

Animals↗

PubMed2000

Cl(-) secretion in colonic epithelial cells induced by the vibrio parahaemolyticus hemolytic toxin related to thermostable direct hemolysin.

A hemolytic toxin related to thermostable direct hemolysin (TDH), TDH-related hemolysin (TRH), produced by Kanagawa-phenomenon-negative Vibrio parahaemolyticus is suspected of playing an important, but yet-to-be-elucidated role in diarrhea caused by this organism. In cultured human colonic epithelial cells, TRH increases Cl(-) secretion, followed by elevation of intracellular calcium.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2000

A filamentous phage associated with recent pandemic Vibrio parahaemolyticus O3:K6 strains.

A specific serotype, O3:K6, of Vibrio parahaemolyticus has recently been causing epidemics of gastroenteritis in Southeast Asia, Japan, and North America. To examine whether the new O3:K6 strains possess characteristics that may exacerbate outbreaks, we compared V. parahaemolyticus O3:K6 strains with non-O3:K6 strains using strains isolated from individuals with traveler's diarrhea at Kansai Airport Quarantine Station, Osaka, Japan. All 24 O3:K6 strains possessed a common plasmid, pO3K6 (DNA size, 8,782 bp, with 10 open reading frames [ORFs]). The gene organization of pO3K6 was similar to that of Vf33, a filamentous phage previously described in V. parahaemolyticus. We isolated a phage (phage f237) from the culture supernatant of V. parahaemolyticus O3:K6 strain KXV237, which formed a turbid plaque on an indicator strain. The genome of f237 was single-stranded DNA, and the double-stranded DNA obtained by treatment of the genome with DNA polymerase was identical to that of pO3K6 when analyzed by agarose gel electrophoresis after HindIII digestion. Furthermore, the N-terminal amino acid sequence of the f237 major coat protein was found in ORF4 of pO3K6. Our results showed that pO3K6 is a replicative form of f237. Among the ORFs found in the f237 genome, the sequence of ORF8 had no significant homology to those of any proteins in databases. ORF8 was located on a region corresponding to the distinctive region of Vf33, and its G+C content was apparently lower than that of the remaining DNA sequence of f237. By colony hybridization, ORF8 was detected only in O3:K6 strains isolated since 1996 and was not found in O3:K6 strains isolated before 1996 and clinical V. parahaemolyticus strains other than those of serotype O3:K6. Thus, this study shows that f237 is exclusively associated with recent V. parahaemolyticus O3:K6 strains. The ORF8 gene can be a useful genetic marker for the identification of the recently widespread O3:K6 strains of V. parahaemolyticus.

Diarrhea↗

PubMed2000

Limitations of vitek GPS-418 cards in exact detection of vancomycin-resistant enterococci with the vanB genotype.

The susceptibilities of 20 strains of vancomycin-resistant enterococci (VRE) with the vanB genotype obtained by using Vitek GPS-418 cards were compared with those obtained by the broth dilution method of the National Committee for Clinical Laboratory Standards (NCCLS) (approved standard M7-A4) and with those obtained by the agar screen method using bile esculin azide agar containing 6 microgram of vancomycin per ml. Although both the broth dilution and agar screen methods disclosed no discordance, Vitek GPS-418 cards yielded a very major error compared with the results obtained by the reference broth dilution method of the NCCLS. Vitek GPS-418 cards were therefore found to have considerable room for improvement for the accurate detection of vanB VRE strains.

Bacterial Proteins↗

PubMed2000

Pulmonary function tests of Mycobacterium avium-intracellulare infection: correlation with bronchoalveolar lavage fluid findings.

BACKGROUND: The pulmonary Mycobacterium avium-intracellulare (MAI) infection in patients with neither predisposing lung disease nor immunodeficiency is recognized to occur predominantly in older or middle-aged and thin females, and has characteristic chest computed tomography (CT) findings with multiple nodules and bronchiectasis. OBJECTIVE: To investigate the pathophysiology with and individual of MAI infection with neither predisposing lung disease nor immunodeficiency. The bronchoalveolar lavage (BAL) fluid (BALF) was recovered directly from the affected segments identified by the chest CT. METHODS: We performed a pulmonary function test (PFT) and BAL in 15 patients (all females) with MAI infection and 5 normal female volunteers. RESULTS: The residual volume and the slope of phase III (DeltaN(2)) were significantly increased and V(25) was significantly decreased in the 15 patients compared with the normal control subjects. The patients' BALF showed significant increases in neutrophils and activated CD4 lymphocytes, proinflammatory cytokines, and neutrophil elastase (NE) compared to those in the controls. We analyzed the PFT and BALF findings, and observed a significant correlation between the DeltaN(2) and interleukin (IL)-8 concentration (r = 0.65, p < 0.01), IL-8/albumin ratio (r = 0.51, p < 0.05) and NE/albumin ratio (r = 0.57, p < 0.05) in the BALF and DeltaN(2), respectively. CONCLUSIONS: These findings suggest that small airway dysfunction in MAI infection without predisposing lung disease is related to the inflammation probably related to the neutrophil.

Aged↗

PubMed2000

Unilateral hilar lymphadenopathy of sarcoidosis or sarcoid reaction compressing the trunk of the right pulmonary artery.

A case of sarcoidosis or sarcoid reaction with a rare manifestation of unilateral lymphadenopathy compressing the trunk of the right pulmonary artery is presented. A 71-year-old woman was admitted for evaluation of a left hilar mass. Chest CT scans showed a mass invading the right pulmonary artery. A frozen section obtained following open lung biopsy showed lymph node tissue largely replaced by noncaseous granulomas indicating sarcoidosis or sarcoid reaction. Old uveitis was compatible with sarcoidosis, and no malignancy was evident. These findings suggested sarcoidosis, however, other evidence of sarcoidosis was not obtained.

Aged↗

PubMed2000

Increased serum IL-10 and endothelin levels in hemolytic uremic syndrome caused by Escherichia coli O157.

BACKGROUND: Shiga toxin, produced by Escherichia coli O157:H7, is important for the pathogenicity of the epidemic form of hemolytic uremic syndrome (HUS). This toxin has recently been found to stimulate endothelin-1 synthesis in cultured endothelial cells in vitro. METHODS: We investigated endothelin and cytokine levels in sera during a large outbreak of E. coli O157:H7 infection in Osaka, Japan, in 1996. Eleven patients with HUS and 9 patients with hemorrhagic colitis at the onset of E. coli O157:H7 infection were studied. RESULTS: Serum IL-6 (p < 0.01), IL-8 (p < 0.05), IL-10 (p < 0.001) and endothelin (p < 0.001) levels were significantly increased in patients with HUS compared to those with colitis only. The serum thrombomodulin level, a molecular marker of endothelial damage, also showed a significant positive correlation with serum IL-6 (p < 0.01), IL-8 (p < 0.01), IL-10 (p < 0.01) and endothelin (p < 0.001) levels. In a HUS patient, the increase in serum IL-10 and endothelin levels reached a plateau prior to the peak of serum creatinine levels. CONCLUSION: Increased serum endothelin synthesis by Shiga toxin in vivo was proven in HUS secondary to E. coli O157:H7 infection. Increased serum endothelin and IL-10 levels were speculated to be associated with the development of HUS through vascular endothelial damage caused by E. coli O157:H7 infection.

Case-Control Studies↗

PubMed2000

Sensitive identification of mycobacterial species using PCR-RFLP on bronchial washings.

In 98 patients (24 with active pulmonary tuberculosis [TB] lesions, 28 with cured TB lesions, and 46 with nontuberculous opacities [control group] in chest CT scans), we examined whether washing the bronchus after brushing the lesion, then applying polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to the bronchial washings might be useful for diagnosing TB and nontuberculous mycobacteriosis (NTMosis). After biopsy and brushing with a bronchoscope, the bronchus connecting to the lesion was washed with 20 ml saline. The saline used for washing the brushes (5 ml; brushing sample), and 3 to 10 ml saline aspirated through the forceps channel (washing sample) were examined by PCR-RFLP, which proved able to identify Mycobacterium tuberculosis and seven species of nontuberculous mycobacteria (NTM). The values obtained for the sensitivity of the PCR-RFLP with respect to the brushing sample, the washing sample, and both samples mixed together were 70, 76, and 91%, respectively, when only patients who were culture-positive or radiologically improved after antituberculous therapy were considered as showing true infection. A mixture of brushing and washing samples provides useful material for PCR and culture, and the PCR-RFLP used here is a good method for the simultaneous identification of several species of mycobacterium (including M. tuberculosis).

Adult↗

PubMed2000

Analysis of HLA antigens in Mycobacterium avium-intracellulare pulmonary infection.

Mycobacterium avium-intracellulare (MAI) pulmonary infection may occur in subjects with no preexisting lung disease and no known immunodeficiency, showing radiologically nodular bronchiectasis. There have remained some unresolved problems in the pathogenesis of the disorder, including the predominance in elderly women and the presence of not deteriorated or deteriorated disease. In the present study, we examined whether immunogenetic susceptibility is present in the disorder. We evaluated 64 cases of MAI disease and analyzed their short-term natural history by assessing symptoms, sputum bacteriology, and chest computed tomographic findings. The frequencies of human leukocyte antigen (HLA) alleles in patients were compared with those in 100 healthy Japanese control subjects. We assayed the HLA-A, -B, -C, -DR, and -DQ antigens serologically. Among 64 patients, 37 (35 females) did not show deterioration, whereas 27 (24 females) showed deterioration after an interval of 30 +/- 15 mo. There was no significant frequency of HLA-B and -C alleles in either group. In 37 not deteriorated patients, DR-6 was positive in 14 (37.8%) patients but in only 16 (16%) control subjects (p = 0.0061, odds ratio [OR] = 3.20). DQ-4 was positive in 10 (27.0%) patients but in only 10 (10%) control subjects (p = 0. 0122, OR = 3.33). In 27 deteriorated patients, HLA-A26 was positive in 14 (51.9%) patients but in only 21 (21.0%) control subjects (p = 0.0015, OR = 4.05). MAI pulmonary infection with nodular bronchiectasis shows two types of outcome, deteriorated and not deteriorated. The subjects with A-26 antigen might indicate the deterioration of MAI infection.

Aged↗

PubMed2000

A synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), is a ligand for the peroxisome proliferator-activated receptor gamma.

A novel synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), previously reported to have potent differentiating, antiproliferative, and antiinflammatory activities, has been identified as a ligand for the peroxisome proliferator-activated receptor gamma (PPARgamma). CDDO induces adipocytic differentiation in 3T3-L1 cells, although it is not as potent as the full agonist of PPARgamma, rosiglitazone. Binding studies of CDDO to PPARgamma using a scintillation proximity assay give a Ki between 10(-8) to 10(-7) M. In transactivation assays, CDDO is a partial agonist for PPARgamma. The methyl ester of CDDO, CDDO-Me, binds to PPARgamma with similar affinity, but is an antagonist. Like other PPARgamma ligands, CDDO synergizes with a retinoid X receptor (RXR)-specific ligand to induce 3T3-L1 differentiation, while CDDO-Me is an antagonist in this assay. The partial agonism of CDDO and the antagonism of CDDO-Me reflect the differences in their capacity to recruit or displace cofactors of transcriptional regulation; CDDO and rosiglitazone both release the nuclear receptor corepressor, NCoR, from PPARgamma, while CDDO-Me does not. The differences between CDDO and rosiglitazone as either partial or full agonists, respectively, are seen in the weaker ability of CDDO to recruit the coactivator CREB-binding protein, CBP, to PPARgamma. Our results establish the triterpenoid CDDO as a member of a new class of PPARgamma ligands.

3T3 Cells↗

PubMed2000

Construction of an enantiomerically pure 6-substituted 3,5-syn-dihydroxyhexanoic acid system by an enantioselective deprotonation strategy: formal synthesis of an antiobesity agent, (-)-tetrahydrolipstatin.

Preparation of 6-substituted 4-hydroxytetrahydro-2H-pyran-2-one (12), a key intermediate for the synthesis of (-)-tetrahydrolipstatin, was achieved in an optically pure form by employing an enantioselective deprotonation reaction of the prochiral bicyclic derivative (5) as a key step.

Anti-Obesity Agents↗

PubMed2000

Long-term low-dose cibenzoline in patients with chronic renal failure undergoing hemodialysis.

Because most anti-arrhythmic drugs are eliminated from the kidney, anti-arrhythmic drug therapy is largely restricted in patients undergoing hemodialysis (HD). Cibenzoline is a widely used antiarrhythmic drug excreted mainly from the kidney. The present study evaluated the safety and efficacy of reduced doses of cibenzoline (25 and 50 mg/day chronically) in 8 patients with maintenance HD. Cibenzoline was administered for more than 3 months without any problems in 7 of the 8 patients, although the medication was discontinued in 1 patient due to nausea and anorexia. With cibenzoline administration, the incidence and duration of atrial fibrillation decreased or disappeared in 6 of 7 patients and the frequency of complex ventricular arrhythmias was also reduced in 3 of 4 patients. No adverse side effects were noted. Plasma concentration of cibenzoline ranged from 169 to 220 ng/ml with the 25-mg/day dosage, and from 408 to 500 ng/ml with the 50-mg/day dosage. The concentrations remained stable during the study. In conclusion, low doses of cibenzoline are safe and effective in patients undergoing maintenance HD. However, intermittent monitoring is essential to ensure therapeutic drug concentrations.

Aged↗