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Biomedical subjects

T Itoh

Publications and source records attributed to T Itoh.

At least 325 records · Page 18Linked to original sources

Effects of a new orally active dopamine prodrug, docarpamine, on refractory ascites: a pilot study.

OBJECTIVE: Refractory ascites is a debilitating condition in patients with cirrhosis. Recently, docarpamine, an orally active dopamine prodrug, was reported to increase renal blood flow, glomerular filtration, and sodium excretion. This suggests docarpamine may be useful for the treatment of refractory ascites. METHODS: In this study, we investigated docarpamine metabolism in cirrhotic patients and its effect on refractory ascites. RESULTS: Blood samples were obtained from seven cirrhotic patients and six healthy subjects after administration of 750 mg docarpamine, and plasma levels of free dopamine were measured. In healthy subjects, maximum plasma concentration (Cmax), time taken to reach Cmax (Tmax), elimination half-life (T(1/2)), and area under the plasma concentration-time curve (AUC) of plasma free dopamine were 76.8 +/- 24.1 ng/ml, 1.3 +/- 0.2 h, 0.8 +/- 0.1 h, and 97.5 +/- 21.1 ng x h/ml, respectively. In patients with cirrhosis, Cmax (53.1 +/- 24.9 ng/ml), T(1/2) (0.8 +/- 0.1 h), and AUC (100.6 +/- 45.6 ng x h/ml) were no different from healthy subjects when comparing each parameter, whereas Tmax (2.7 +/- 0.2) was significantly longer than that of healthy subjects. We treated 10 cirrhotic patients with refractory ascites with docarpamine or placebo and the same dose of diuretics used before hospitalization. After 8 wk of docarpamine treatment, ascites disappeared completely in three of the five patients and decreased in the remainder. However, in five patients treated with placebo, ascites was not changed or increased. Side effects were not observed in any case. CONCLUSIONS: Docarpamine was found to metabolize in cirrhotic patients as well as in normal subjects and may be an effective treatment for refractory ascites.

Administration, Oral↗

The role of volume-weighted mean nuclear volume in predicting disease outcome in patients with prostate cancer treated with radical prostatectomy.

BACKGROUND: Estimates of volume-weighted mean nuclear volume (MNV) are the only means by which unbiased estimates of three-dimensional parameters can be obtained from single two-dimensional sections without any assumptions. We have reported that for prostate cancer estimates of MNV are prognostically equal or superior to morphological grading of malignancy, such as Gleason score (GS), and in particular, that MNV proved to be a meaningful predictor of prognosis for patients with clinically localized tumors. However, all previous studies were conducted on patients treated conservatively, and no authors have tested whether estimates of MNV can predict the prognosis of patients treated with radical prostatectomy. MATERIALS AND METHODS: A retrospective prognostic study of 52 patients with clinically localized prostate cancer diagnosed at three Hospitals in Shizuoka Prefecture, Japan (Shizuoka City Hospital, Shizuoka Prefectural Hospital and Shimada Municipal Hospital) and treated by radical prostatectomy was performed. Twenty of these patients were treated with hormone therapy before radical prostatectomy. Unbiased estimates of MNV were compared with clinical stage, histological grading according to GS and neo-adjuvant hormone therapy with regard to the prognostic value. RESULTS: MNV was significantly correlated with pathological T stage, but was not significantly correlated with the presence or absence of lymph node metastasis. Univariate analysis revealed that MNV correlated significantly with progression-free survival (p = 0.0116). Multivariate analysis revealed that MNV (p = 0.0115) and GS (p = 0.0275) were two significant independent predictors of progression-free survival. CONCLUSIONS: The results of the present study suggest that MNV and GS are powerful independent predictors of prognosis for prostate cancer treated with radical prostatectomy. We recommend estimates of MNV as a supportive method to the histological grading for patients with prostate cancer.

Antineoplastic Agents↗

The role of volume-weighted mean nuclear volume in predicting disease outcome in patients with stage M1 prostate cancer.

BACKGROUND: Various factors have been reported to be of value in predicting the prognosis of prostate cancer. Gleason score (GS) and prostate-specific antigen (PSA) are the two most powerful prognosticators among them. We previously reported that estimation of volume-weighted mean nuclear volume (MNV) was a more useful prognosticator for prostate cancer than subjective histologic grading. In this study, we compared estimates of MNV with PSA and GS for predicting the prognosis of stage M1 prostate cancer. EXPERIMENTAL DESIGN: A retrospective prognostic study of 66 patients with stage M1 prostate cancer diagnosed between January 1989 and December 1996 at Shizuoka City Hospital and Shizuoka Prefectural Hospital was performed. The prognostic value of unbiased estimates of MNV were compared with PSA and histologic grading according to GS. RESULTS: Univariate analysis revealed that estimates of MNV (p=0.0136) and post-treatment nadir PSA level (p<0.0001) correlated significantly with the prognosis of stage M1 prostate cancer, whilst GS (p=0.9377), pre-treatment PSA level (p=0.7377) and rate of decrease in PSA level within 1 month after the beginning of therapy (p=0.8999) had no prognostic value. Multivariate analysis revealed that post-treatment PSA level and estimates of MNV were the two most powerful prognosticators. CONCLUSIONS: This study indicates that estimation of MNV is an important prognosticator, in conjunction with post-treatment nadir PSA level, in stage M1 prostate cancer.

Aged↗

[Study on the verotoxin-producing Escherichia coli--isolation of the bacteria from deer dung].

To identify the source and route of verotoxin-producing Escherichia coli (VTEC) infection in humans, we tried to isolate VTEC from fresh deer dung collected from free-range animals in two parks during the period from August 1997 to January 1998. The results are presented below. 1) VTEC were isolated from 21 of 200 deer dung samples (10.5%), consisting of 15 of 100 samples (15.0%) collected in park A and 6 of 100 samples (6.0%) collected in park B, suggesting that the incidence of VTEC isolation differs depending on location. 2) With respect to typing of verotoxin, the 21 isolated VTEC strains consisted of 10 strains (47.6%) as VT1 producer, 5 strains (23.8%) as VT2 producer, and 6 strains (28.6%) as double producer of both types. 3) With respect to serogroup of the isolated VTEC strains, 2 strains belonged to O128:H2.1 strain each belonged to the O8:H10, O128:H12, and O169:HUT groups. The remaining 16 strains failed to be identified as particular serotypes. Regarding local distribution of the serotype, in park A, 1 strain each belonged to the O128:H2, O8:H10, and O169:HUT groups. The remaining 12 strains did not clearly show particular serotypes. In park B, 2 strains belonged to O128:H2, and 4 strains failed to show particular serotypes. The remaining 1 strains showed autoagglutination. In conclusion, we isolated VTEC strains from deer that showed types of toxin and serogroups identical to those of human VTEC. Therefore, VTEC found in deer dung could well be a source of VTEC-infectious diseases in humans.

Animals↗

[Biochemical and molecular characterization of Salmonella ser. enteritidis phage type 1 isolated from food poisoning outbreaks in Tokyo].

Since the first outbreak in 1990, the incidence of Salmonella ser. Enteritidis (S. Enteritidis) phage type (PT) 1 food poisoning has gradually increased in Tokyo and has reached approximately 30% of the total S. Enteritidis outbreaks reported. To characterise these S. Enteritidis PT1 food poisoning, a total of 198 strains obtained from 44 outbreaks between 1990 and 1996 were examined for antimicrobial resistance, acid producibility from glycols (propylene and ethylene glycol) and plasmid DNA profiles. The 44 PT1 outbreaks analysed were further subdivided into 11 types by epidemiological markers. The most common patterns were type A (plasmid profile carrying only one plasmid (60 kb). SM and TC resistance and non producibility from glycols), and type B (plasmid profile carrying two plasmids (60 and 20 kb), SM resistance and no producibility from glycols) and were responsible for 21 (47.7%) and 15 (34.1%) outbreaks, respectively. In 11 of 44 outbreaks, strains carrying identical epidemiological markers were isolated both from patients and vehicle foods, environments, and/or food-handlers. Similar to PT4 and PT34 outbreaks reported in Japan, egg and egg-related foods were also suspected in 8 of these 11 outbreaks. Of interest, chicken which were not pointed out in PT4 and PT 34 outbreaks was also suspected as a vehicle of transmission in two outbreaks.

Bacteriophage Typing↗

[Prevalence and serotypes of verocytotoxin-producing Escherichia coli (VTEC) isolates from dairy cattle].

To clarify the source of infection and route of transmission of Verocytotoxin-producing Escherichia coli (VTEC) in humans, we collected fresh feces from healthy dairy cattle reared in Hokkaido, Fukushima, Kanagawa and Okinawa prefectures between June 1996 and March 1997, and attempted to isolate VTEC. The results are described below. 1) VTEC was isolated from 68 (27.1%) of 251 fecal samples tested. VTEC was isolated from 14 (28.0%) of 50 in Hokkaido, 13 (26.0%) of 50 in Fukushima, 20 (39.2%) of 51 in Kanagawa and 21 (21.0%) of 100 in Okinawa. There were no difference in the prevalence among the prefectures. 2) Toxin type and serotype of 85 isolates were determined. Thirty-three isolaties (38.8%) were classified into VT1 toxin and VT2 toxin, respectively, and 19 isolates (22.4%) were classified as the strain that produces both VT1 and VT2 toxins. The toxin types of these isolates were divided by serotypes. The VT1-producing isolates were the most frequent among O111:H-. The VT2-producing isolates included O2:H12, O2:H29, O2:H-, O82:H8, O82:HUT, O153:H19, O153:H42 and O153:H-. Among the isolates producing both VT1 and VT2 toxins, O153:H19 was relatively frequent. Based on findings that many bacterial strains coinciding with toxin types and serotypes of human-derived VTEC isolated from dairy cattle, it was suggested that dairy cattle are closely related to VTEC infection in human as a source of infection.

Animals↗

[Evaluation of CO2 condition for antibiotic susceptibility test of Helicobacter pylori on microdilution broth].

We determined the MICs of clarithromycin for 32 Helicobacter pylori strains isolated from gastric mucosa of patients, by using microdilution broth method under different microaerobic conditions (CO2: 5% and 15%). The pH of broth was more acidic at 15% CO2 than that of at 5% CO2. The MICs of clarithromycin for all H. pylori strains at 15% CO2 condition were higher than that of clarithromycin at 5% CO2 condition. Comparing the MICs with the results of eradication therapy, we concluded that the measurement of MIC under 5%CO2 condition is more useful for expecting the clinical outcome.

Carbon Dioxide↗

Analyses of spatial distributions of sulfate-reducing bacteria and their activity in aerobic wastewater biofilms.

The vertical distribution of sulfate-reducing bacteria (SRB) in aerobic wastewater biofilms grown on rotating disk reactors was investigated by fluorescent in situ hybridization (FISH) with 16S rRNA-targeted oligonucleotide probes. To correlate the vertical distribution of SRB populations with their activity, the microprofiles of O(2), H(2)S, NO(2)(-), NO(3)(-), NH(4)(+), and pH were measured with microelectrodes. In addition, a cross-evaluation of the FISH and microelectrode analyses was performed by comparing them with culture-based approaches and biogeochemical measurements. In situ hybridization revealed that a relatively high abundance of the probe SRB385-stained cells (approximately 10(9) to 10(10) cells per cm(3) of biofilm) were evenly distributed throughout the biofilm, even in the oxic surface. The probe SRB660-stained Desulfobulbus spp. were found to be numerically important members of SRB populations (approximately 10(8) to 10(9) cells per cm(3)). The result of microelectrode measurements showed that a high sulfate-reducing activity was found in a narrow anaerobic zone located about 150 to 300 microm below the biofilm surface and above which an intensive sulfide oxidation zone was found. The biogeochemical measurements showed that elemental sulfur (S(0)) was an important intermediate of the sulfide reoxidation in such thin wastewater biofilms (approximately 1,500 microm), which accounted for about 75% of the total S pool in the biofilm. The contribution of an internal Fe-sulfur cycle to the overall sulfur cycle in aerobic wastewater biofilms was insignificant (less than 1%) due to the relatively high sulfate reduction rate.

Aerobiosis↗

Cloning and characterization of a novel membrane-associated antigenic protein of Helicobacter pylori.

Infection by Helicobacter pylori, a noninvasive bacterium, induces chronic leukocyte infiltration in the stomach by still largely unknown molecular mechanisms. We investigated the possibility that a membrane protein of H. pylori induces an inflammatory reaction in the subepithelial tissue of the stomach. By generating an expression library of H. pylori chromosomal DNA and screening with rabbit antiserum raised to a membrane fraction of H. pylori and sera of infected patients, we cloned a 16.0-kDa protein (HP-MP1) which appeared to attach to the inner membrane of the H. pylori in a homodimeric form. Anti-HP-MP1 antibodies were detected in the sera of infected patients but not in those of uninfected controls. Coincubation of monocytes with recombinant HP-MP1 led to cell activation and production of interleukin-1alpha (IL-1alpha), tumor necrosis factor alpha, IL-8, and macrophage inflammatory protein 1alpha. The results indicate that HP-MP1 is an antigenic membrane-associated protein of H. pylori which potentially activates monocytes. This suggests that HP-MP1 may play roles in the pathogenesis of perpetual tissue inflammation associated with H. pylori infection.

Antibodies, Bacterial↗

Microglia express CCR5, CXCR4, and CCR3, but of these, CCR5 is the principal coreceptor for human immunodeficiency virus type 1 dementia isolates.

Microglia are the main human immunodeficiency virus (HIV) reservoir in the central nervous system and most likely play a major role in the development of HIV dementia (HIVD). To characterize human adult microglial chemokine receptors, we analyzed the expression and calcium signaling of CCR5, CCR3, and CXCR4 and their roles in HIV entry. Microglia expressed higher levels of CCR5 than of either CCR3 or CXCR4. Of these three chemokine receptors, only CCR5 and CXCR4 were able to transduce a signal in microglia in response to their respective ligands, MIP-1beta and SDF-1alpha, as recorded by single-cell calcium flux experiments. We also found that CCR5 is the predominant coreceptor used for infection of human adult microglia by the HIV type 1 dementia isolates HIV-1DS-br, HIV-1RC-br, and HIV-1YU-2, since the anti-CCR5 antibody 2D7 was able to dramatically inhibit microglial infection by both wild-type and single-round luciferase pseudotype reporter viruses. Anti-CCR3 (7B11) and anti-CXCR4 (12G5) antibodies had little or no effect on infection. Last, we found that virus pseudotyped with the DS-br and RC-br envelopes can infect cells transfected with CD4 in conjunction with the G-protein-coupled receptors APJ, CCR8, and GPR15, which have been previously implicated in HIV entry.

AIDS Dementia Complex↗

Effect of an exercise-heat acclimation program on body fluid regulatory responses to dehydration in older men.

We examined if an exercise-heat acclimation program improves body fluid regulatory function in older subjects, as has been reported in younger subjects. Nine older (Old; 70 +/- 3 yr) and six younger (Young; 25 +/- 3 yr) male subjects participated in the study. Body fluid regulatory responses to an acute thermal dehydration challenge were examined before and after the 6-day acclimation session. Acute dehydration was produced by intermittent light exercise [4 bouts of 20-min exercise at 40% peak rate of oxygen consumption (VO(2 peak)) separated by 10 min rest] in the heat (36 degrees C; 40% relative humidity) followed by 30 min of recovery without fluid intake at 25 degrees C. During the 2-h rehydration period the subjects drank a carbohydrate-electrolyte solution ad libitum. In the preacclimation test, the Old lost approximately 0.8 kg during dehydration and recovered 31 +/- 4% of that loss during rehydration, whereas the Young lost approximately 1.2 kg and recovered 56 +/- 8% (P < 0.05, Young vs. Old). During the 6-day heat acclimation period all subjects performed the same exercise-heat exposure as in the dehydration period. Exercise-heat acclimation increased plasma volume by approximately 5% (P < 0.05) in Young subjects but not in Old. The body fluid loss during dehydration in the postacclimation test was similar to that in the preacclimation in Young and Old. The fractional recovery of lost fluid volume during rehydration increased in Young (by 80 +/- 9%; P < 0.05) but not in Old (by only 34 +/- 5%; NS). The improved recovery from dehydration in Young was mainly due to increased fluid intake with a small increase in the fluid retention fraction. The greater involuntary dehydration (greater fluid deficit) in Old was accompanied by reduced plasma vasopressin and aldosterone concentrations, renin activity, and subjective thirst rating (P < 0.05, Young vs. Old). Thus older people have reduced ability to facilitate body fluid regulatory function by exercise-heat acclimation, which might be involved in attenuation of the acclimation-induced increase in body fluid volume.

Acclimatization↗

Evaluation of the protective effects of alkaloids isolated from the hooks and stems of Uncaria sinensis on glutamate-induced neuronal death in cultured cerebellar granule cells from rats.

We have previously shown that an aqueous extract of the hooks and stems of Uncaria sinensis (Oliv.) Havil., Uncariae Uncus Cum Ramulusis, protects against glutamate-induced neuronal death in cultured cerebellar granule cells by inhibition of Ca2+ influx. Because it is not known which components of Uncaria sinensis are active, in this study we have evaluated, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) staining, the neuroprotective effects of the oxyindole alkaloids corynoxeine, rhynchophylline, isorhynchophylline and isocorynoxeine, and the indole alkaloids geissoschizine methyl ether, hirsuteine and hirsutine, isolated from the hooks and stems of Uncaria sinensis, on glutamate-induced cell death. We also investigated the inhibitory effects of the compounds on 45Ca2+ influx in cultured rat cerebellar granule cells. Cell viability evaluated by the MTT assay was significantly increased by application of rhynchophylline (10(-3) M), isorhynchophylline (10(-4)-10(-3) M), isocorynoxeine (10(-4)-10(-3) M), hirsuteine (10(-4)-3 x 10(-4) M) or hirsutine (10(-4)-3 x 10(-4) M) compared with exposure to glutamate only, with the effect of isorhynchophylline being the strongest. The increased 45Ca2+ influx into cells induced by glutamate was significantly inhibited by administration of rhynchophylline (10(-3) M), isorhynchophylline (3 x 10(-4)-10(-3) M), isocorynoxeine (3 x 10(-4)-10(-3) M), geissoschizine methyl ether (10(-3) M), hirsuteine (3 x 10(-4)-10(-3) M) or hirsutine (3 x 10(-4)-10(-3) M). These results suggest that oxyindole alkaloids such as isorhynchophylline, isocorynoxeine and rhynchophylline and indole alkaloids such as hirsuteine and hirsutine are the active components of the hooks and stems of Uncaria sinensis which protect against glutamate-induced neuronal death in cultured cerebellar granule cells by inhibition of Ca2+ influx.

Alkaloids↗

Does coronary artery morphology predict favorable results of intracoronary thrombolysis in patients with unstable angina pectoris?

The efficacy of intracoronary thrombolysis (ICT) for unstable angina pectoris (UAP) has been limited, despite the similar pathogenesis between UAP and acute myocardial infarction. To ascertain the subset of UAP suitable for ICT, the clinical responses to ICT were assessed in patients with UAP. Eighty-2 patients with medically refractory angina were divided into 2 groups according to the coronary artery morphology of the culprit lesion before ICT: (1) lesions with acute cut off and/or filling defects (AC) and (2) lesions with a tapered shape (TA). The TIMI flow grade was determined from coronary angiograms before and immediately after ICT. The diameter stenosis (%DS) and minimal lumen diameter (MLD) of the culprit lesion were determined using quantitative coronary angiographic analysis before and immediately after ICT. In addition, inhospital cardiac event rates including urgent/emergency coronary angioplasty or bypass surgery, nonfatal myocardial infarction or cardiac death were compared between the 2 groups. Multivariate logistic regression analysis was performed using 13 clinical factors contributing to successful ICT. The results showed that all 3 coronary angiographic parameters (TIMI flow, %DS, and MLD) significantly improved in the AC group (p<0.01, p<0.01 and p<0.05, respectively), whereas none of these parameters improved in the TA group. The inhospital cardiac event rate after ICT was significantly higher in the TA group (76%) than in the AC group (48%; p=0.016). Odds ratio predicting successful ICT was 7.09 (p<0.01) for the AC lesion, and 2.54 (p<0.01) for new angina. In conclusion the AC lesions are more commonly associated with coronary thrombosis that responds to ICT than are the TA lesions. Thus, the coronary angiographic morphology may be an important predictor for a successful ICT in patients with medically refractory UAP.

Aged↗

Dose estimations of fast neutrons from a nuclear reactor by micronuclear yields in onion seedlings.

Irradiations of onion seedlings with fission neutrons from bare, Pb-moderated, and Fe-moderated 252Cf sources induced micronuclei in the root-tip cells at similar rates. The rate per cGy averaged for the three sources, , was 19 times higher than rate induced by 60Co gamma-rays. When neutron doses, Dn, were estimated from frequencies of micronuclei induced in onion seedlings after exposure to neutron-gamma mixed radiation from a 1 W nuclear reactor, using the reciprocal of as conversion factor, resulting Dn values agreed within 10% with doses measured with paired ionizing chambers. This excellent agreement was achieved by the high sensitivity of the onion system to fast neutrons relative to gamma-rays and the high contribution of fast neutrons to the total dose of mixed radiation in the reactor's field.

Fast Neutrons↗

Naturally occurring Tyzzer's disease in a calf.

Naturally occurring Clostridium piliforme infection (Tyzzer's disease) was found in a calf. Light microscopic examination revealed multifocal coagulative necrosis in the liver, catarrhal gastroenteritis, tracheitis and pneumonia, and thymic atrophy. Warthin-Starry staining clearly showed large filamentous bacilli in bundles or criss-cross patterns within the hepatocytes and epithelium and smooth muscle cells of the ileum and cecum. Immunohistochemistry using anti-C. piliforme RT and MSK strain antisera showed positive reaction against the bacilli. Electron microscopic examination revealed bacilli within the hepatocytes that demonstrated a characteristic vegetative form, with peritrichous flagella, and spores. The polymerase chain reaction (PCR) study using the paraffin-embedded liver sections, the 196-bp DNA fragment specific to 16S ribosomal RNA of C. piliforme was amplified. The characteristics of these bacilli are consistent with those of of C. piliforme. The PCR technique using paraffin-embedded sections should be useful for confirming C. piliforme infection in spontaneous cases.

Animals↗

Enterocolitis associated with dual infection by Clostridium piliforme and feline panleukopenia virus in three kittens.

Dual infection by Clostridium piliforme and feline panleukopenia virus (FPLV) was found in three kittens. In all cases, we found focal necrosis and desquamation of epithelial cells with occasional neutrophil infiltration in the large intestine. Large filamentous bacilli and spores were observed in the epithelium by using the Warthin-Starry method. Electron microscopy revealed the vegetative forms with characteristic peritrichous flagella and spore forms. Immunohistochemically, these bacilli showed a positive reaction with mouse antisera against the RT and MSK C. piliforme strains. Polymerase chain reaction (PCR) using cecum specimens demonstrated the 196-bp band specific to C. piliforme 16S rRNA. All three kittens were also diagnosed as FPLV-infected on the basis of the characteristic mucosal lesions, including intranuclear inclusions and PCR study for the FPLV genomic DNA. The PCR techniques are useful for confirming the C. piliforme and FPLV infection in spontaneous cases.

Animals↗

Evaluation of PCR as a means of identification of Pasteurella pneumotropica.

A polymerase chain reaction with new primers (new PCR) designed from Pasteurella pneumotropica 16S rDNA as an identification system for this organism was compared with the PCR reported by Wang et al. (Wang's PCR) by using 15 bacterial reference species and 70 clinical isolates with the conventional identification system. For the 15 reference strains, both PCRs were identical. For the 70 clinical isolates, the new PCR and Wang's PCR showed consistency with the conventional system in 62.9% (44/70) and 51.4% (36/70), respectively. Twenty-six isolates were inconsistent with the conventional system and the new PCR with respect to morphology and serology. These findings suggested that the new PCR was more sensitive than Wang's PCR, and the new PCR in combination with morphology and serology is useful for P. pneumotropica identification.

Animals↗