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Biomedical subjects

Hiroyuki Okada

Publications and source records attributed to Hiroyuki Okada.

At least 55 records · Page 3Linked to original sources
PubMed2004

Serum antibodies to Helicobacter pylori and its heat-shock protein 60 correlate with the response of gastric mucosa-associated lymphoid tissue lymphoma to eradication of H. pylori.

BACKGROUND AND AIMS: Eradication of Helicobacter pylori leads to regression of mucosa-associated lymphoid tissue (MALT) lymphomas. In this study, we measured serum antibodies to H. pylori and H. pylori-recombinant heat-shock protein 60 (rHSP60) in patients with gastric MALT lymphoma to determine whether humoral immune responses to the bacterial antigens correlate with the efficacy of eradication therapy. METHODS: Serum samples were obtained from 33 patients with H. pylori-positive gastric MALT lymphoma before undergoing therapy to eradicate the bacteria. Anti-H. pylori antibodies were measured in a commercial assay and in immunoassays to lysates and rHSP60 which were prepared from ATCC 43504 strain. RESULTS: Helicobacter pylori were eradicated in all 33 patients, and the lymphoma completely regressed histologically in 26 patients (79%). Pre-treatment titers of serum antibody to H. pylori and to rHSP60 in the patients whose tumor regressed were significantly higher than titers in patients whose tumors did not regress (p =.0011 and.035, respectively). By logistic regression analysis, age (odds ratio = 0.88, 95% confidence interval = 0.80-0.99), endoscopic appearance (0.053, 0.004-0.65), titers of anti-H. pylori antibodies (67.6, 2.5-1800), and titers of anti-rHSP60 antibody (6.4, 1.2-36) were identified as significantly associated factors with the outcome of MALT lymphoma. CONCLUSIONS: Measurement of serum antibodies to H. pylori and HSP60 might be useful for predicting the response of gastric MALT lymphoma to eradication of H. pylori.

Adult↗
PubMed2004

Complement regulatory proteins in normal human esophagus and esophageal squamous cell carcinoma.

BACKGROUND: Altered expression of three complement regulatory proteins, decay-accelerating factor (CD55), membrane cofactor protein (CD46) and homologous restriction factor 20 (CD59) has been identified in human gastrointestinal malignancies, but their expression in esophageal cancer has not been described. Therefore the purpose of the present paper was to study the distribution of these proteins in human normal and malignant esophageal mucosa. METHODS AND RESULTS: In the normal esophageal mucosa, CD55 predominantly stained on the cell membrane of squamous epithelium in the superficial and prickle cell layers, whereas CD46 most intensely stained on the cell membrane in the basal and parabasal cell layers. In contrast to this reciprocal expression of CD55 and CD46, CD59 was broadly distributed on the cell membrane in all layers. In the esophageal squamous cell carcinoma, CD55 staining was intense in the stroma but was negligible in the cancer cells. In contrast, CD46 and CD59 stained almost uniformly on the tumor cell membrane. There was a significant difference in the intensity of the staining of CD55 and CD46 among cells in various layers of normal esophageal mucosa and esophageal carcinoma cells, but not in the staining of CD59. Similar expression patterns of the three complement regulatory proteins in carcinoma cells and in normal epithelium in the basal and parabasal cell layers were observed. CONCLUSIONS: These observations on the expression of the three complement regulatory proteins would help understanding of the host immune responses involving the complement system against esophageal squamous cell carcinoma.

Antigens, CD↗
PubMed2004

Focal fatty liver in a heifer: utility of ultrasonography in diagnosis.

A 30-month-old Holstein heifer presented with a history of decreased appetite and respiratory signs. Sonographic examination of the liver incidentally revealed an area of increased echogenicity between the portal vein and the gallbladder. The lesion was nonspherical and had no mass effect or displacement of the adjacent vessels. Its boundaries, to the liver, were geographic. The liver specimen was histologically compatible with a diagnosis of focal fatty liver change (FFLC). The sonographic features of focal fatty infiltration of the liver are characteristic. Recognition of the ultrasonographic data is important to differentiate FFLC from other lesions.

Animals↗
PubMed2004

[Interluekin-1 beta genetic polymorphism influences the impact of cytochrome P 2C19 genotype on the cure rate of H. pylori eradication therapy].

Genetic polymorphism of interleukin(IL)-1 beta is associated with differences in gastric acid suppression in response to H. pylori infection. Thus, the polymorphism might affect H. pylori eradication therapy since antibiotics used in treatment regimens may be acid-sensitive. We examined the impact of IL-1 beta genetic polymorphism on the cure rate of triple therapy for H. pylori in relation to cytochrome P(CYP)2C19 genotype. In the normal acid-secretion IL-1 beta genotype group, the cure rate among CYP2C19 poor metabolizers was significantly higher than among those in the CYP2C19 extensive metabolizer groups. IL-1 beta genetic polymorphism, although not an independent factor in treatment outcome, influences the impact of the CYP2C19 genotype on the cure rate of H. pylori eradication therapy.

Amoxicillin↗
PubMed2003

Early therapy monitoring with FDG-PET in aggressive non-Hodgkin's lymphoma and Hodgkin's lymphoma.

This study was designed to determine the value of 2-[fluorine-18]-fluoro-2-deoxy- d-glucose positron emission tomography (FDG-PET) in the early assessment of therapy response in lymphoma patients. We studied 20 patients with pathologically proven lymphoma, including 17 patients with aggressive non-Hodgkin's lymphoma and three patients with Hodgkin's lymphoma. All patients underwent whole-body FDG-PET imaging at baseline and after 1-2 cycles of chemotherapy. PET images were analysed visually and quantitatively by calculating the standardised uptake value (SUV). In each patient, we measured the SUV of the tumour demonstrating the highest FDG uptake at baseline study and the SUV of the same tumour after 1-2 cycles of therapy. The achievement of complete response was assessed on the basis of a combination of clinical findings and the results of conventional imaging modalities. Follow-up of progression-free survival (PFS) was obtained for the validation of PET data. Of the 20 patients, ten achieved complete remission at the completion of chemotherapy and the other ten did not respond to chemotherapy. Of the ten responders, four are still in remission (PFS 24-34 months) while the other six have relapsed (PFS 8-16 months). For the prediction of 24-month clinical outcome, visual analysis of PET after 1-2 cycles showed high sensitivity (87.5%) and accuracy (80%) but low specificity (50%). Comparison with the baseline SUVs revealed that the responders showed a significantly greater percent reduction in SUV after 1-2 cycles of therapy as compared with the non-responders (81.2%+/-9.5% vs 35.0%+/-20.2%, P<0.001). In addition, using 60% reduction as a cut-off value, the responders were clearly separated from the non-responders, with the exception of one non-responder. In conclusion, when performed early during chemotherapy, FDG-PET may be predictive of clinical outcome and allows differentiation of responders from non-responders in cases of aggressive lymphoma.

Adult↗
PubMed2003

Release of decay-accelerating factor into stools of patients with colorectal cancer by means of cleavage at the site of glycosylphosphatidylinositol anchor.

The expression of decay-accelerating factor (DAF), a cell-membrane-complement regulator, is enhanced in colorectal cancer, and DAF is detected in the stools of patients with colorectal cancer. In this study, to elucidate mechanisms whereby DAF is released into the colonic lumen, we analyzed and compared the properties of DAF in stools and colorectal-cancer tissues. Stool specimens taken before surgery and tissue samples from surgically resected colorectal cancers were obtained from 21 patients. We analyzed DAF in stool and tissue specimens using immunoblotting, ultracentrifugation, and phase separation with Triton X-114. We analyzed the expression profile of DAF mRNA in cancer tissues using reverse transcription-polymerase chain reaction to determine whether DAF transcripts for a secretory form of DAF were present. With the use of immunoblotting, stool DAF was detected as a broad band with a molecular weight of around 70,000 kDa that migrated slightly more slowly than cancer-tissue DAF. About 90% of stool DAF was present as a soluble form that remained in the 100,000 g supernatant after ultracentrifugation. On phase separation with Triton X-114, the soluble stool DAF was partitioned mainly into the aqueous phase, indicating its hydrophilic nature and lack of the fatty-acid glycosylphosphatidylinositol anchor component. In colorectal cancer tissues, reverse transcription-polymerase chain reaction experiments revealed a nonspliced DAF messenger RNA that encodes a secretory form of DAF in just 2 of the 21 specimens examined. These data suggest that DAF is released from colorectal cancer cells by way of cleavage of membrane-bound DAF at the site of the glycosylphosphatidylinositol anchor.

Adult↗
PubMed2003

A monoclonal antibody to rat asialoglycoprotein receptor that recognizes an epitope specific to its major subunit.

We previously developed three mouse monoclonal antibodies (MoAbs) identifying the domain-specific plasma membrane proteins of rat hepatocytes. Based on the results of immunohistochemical and immunoblot analysis, one of them, clone 8D7, likely recognizes the rat asialoglycoprotein receptor (ASGPR), which consists of three polypeptide subunits: rat hepatic lectin (RHL)-1, RHL-2 and RHL-3. In this study, we examined the reactivity of MoAb 8D7 with these subunits in order to identify specifically the protein it recognizes. RHL-1 and RHL-2/3 were expressed in COS-1 mammalian kidney cells transfected with cloned cDNAs. Reactivity of MoAb 8D7 with these proteins was examined by flow cytometry, immunoblotting, and an immunofluorescence staining. By flow cytometry, MoAb 8D7 reacted with cell surface proteins on the COS-1 cells transfected with RHL-1 cDNA but not with RHL-2/3 cDNA. By immunoblotting, the antibody recognized proteins (molecular weights 45 and 96 kDa) in RHL-1-expressing cells but not in the RHL-2/3 cDNA-transfected cells. Immunoreactive staining with MoAb 8D7 was observed on the cell surface and in the cytoplasm of RHL-1-transfected COS-1 cells but not in cells expressing RHL-2/3. These findings indicate that MoAb 8D7 recognizes a subunit-specific epitope on RHL-1 of rat ASGPR.

Journal Article↗
PubMed2003

Interleukin-1beta genetic polymorphism influences the effect of cytochrome P 2C19 genotype on the cure rate of 1-week triple therapy for Helicobacter pylori infection.

OBJECTIVES: Genetic polymorphism of interleukin (IL)-1beta is associated with differences in gastric acid suppression in response to Helicobacter pylori (H. pylori) infection. Thus, the polymorphism might affect H. pylori eradication therapy, as antibiotics used in treatment regimens may be acid sensitive. In this study, we examined the impact of IL-1beta genetic polymorphism on the cure rate of triple therapy for H. pylori in relation to cytochrome P (CYP) 2C19 genotype and antibiotic resistance. METHODS: A total 249 patients with peptic ulcer disease were randomized to receive one of the following regimens: amoxicillin and clarithromycin together with omeprazole, lansoprazole, or rabeprazole. CYP2C19 and IL-1beta-511 genetic polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The intention-to-treat-based overall cure rate was 74.3% (95% CI=68-79%). In the normal acid secretion IL-1beta genotype group, the cure rate among CYP2C19 poor metabolizers (93.3%, 95% CI=56-99%) was significantly higher than among subjects in the CYP2C19 homozygous (60.0%, 95% CI=38-78%) and heterozygous (63.6%, 95% CI=46-78%), i.e., extensive metabolizer, groups (p<0.05). In the low acid secretion IL-1beta genotype group, there was no difference in the cure rate among the CYP2C19 genotype groups. Multiple logistic regression analysis identified susceptibility to clarithromycin (p<0.0001) and CYP2C19 genotype status (p=0.03) as significant independent factors for treatment failure. CONCLUSION: IL-1beta genetic polymorphism, although not an independent factor in treatment outcome, influences the impact of the CYP2C19 genotype on the cure rate of 1-wk triple therapy for H. pylori infection.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

Testing of multiple samples increases the sensitivity of stool decay-accelerating factor test for the detection of colorectal cancer.

OBJECTIVES: We previously reported that the measurements of stool decay-accelerating factor (DAF), a membrane-bound, complement regulatory protein, may be valuable for the detection of colorectal cancer. Recently we have refined the immunoassay for stool DAF. In the present study, using the refined assay, we measured stool DAF concentrations in multiple samples from patients with colorectal cancer and in healthy controls to determine whether testing of multiple samples would increase the sensitivity of the stool DAF test. METHODS: DAF was measured in three spontaneously passed stool samples from each of 100 patients with colorectal cancer and 100 control subjects without apparent colorectal disease. RESULTS: The stool DAF concentrations in the patients with colorectal cancer (median 11.1 ng/g stool; interquartile range 2.9-32.7 ng/g) were significantly higher than concentrations in the subjects without colorectal diseases (median 1.6 ng/g stool; interquartile range 0.4-3.4 ng/g) (p<0.0001). Testing of two samples from each patient significantly increased the sensitivity (72%) of the stool DAF test without significantly decreasing its specificity (92%). The stool DAF test was positive in more than one half of patients with colorectal cancer at a relatively early TNM stage or with negative fecal occult blood test. CONCLUSIONS: These findings suggest that stool DAF is a marker of colorectal cancer independent of fecal occult blood and testing of two samples increases the sensitivity of the stool DAF test. Measurement of stool DAF now seems worthy of further consideration as a noninvasive method for the detection of colorectal cancer.

Adult↗
PubMed2003

Association of dopamine transporter loss in the orbitofrontal and dorsolateral prefrontal cortices with methamphetamine-related psychiatric symptoms.

OBJECTIVE: The authors examined dopamine transporter density in the orbitofrontal cortex, dorsolateral prefrontal cortex, and amygdala in methamphetamine users and assessed the relationship of these measures to the subjects' clinical characteristics. METHOD: Positron emission tomography with [(11)C]WIN 35,428 was used to examine the regions of interest in 11 methamphetamine users and nine healthy comparison subjects. Psychiatric symptoms were evaluated with the Brief Psychiatric Rating Scale. RESULTS: Dopamine transporter density in the three regions studied was significantly lower in the methamphetamine users than in the comparison subjects. The lower dopamine transporter density in the orbitofrontal and dorsolateral prefrontal cortex was significantly correlated with the duration of methamphetamine use and the severity of psychiatric symptoms. CONCLUSIONS: Chronic methamphetamine use may cause dopamine transporter reduction in the orbitofrontal cortex, dorsolateral prefrontal cortex, and amygdala in the brain. Psychiatric symptoms in methamphetamine users may be attributable to the decrease in dopamine transporter density in the orbitofrontal cortex and the dorsolateral prefrontal cortex.

Adult↗
PubMed2003

Flow cytometric analysis of peripheral blood mononuclear cells induced by experimental endotoxemia in horse.

Cellular activation and functional cell surface markers were evaluated during experimentally-induced endotoxemia in healthy horses. Eight healthy adult horses were infused a low dose of endotoxin (lipopolysaccharide from Escherichia coli O26: B6, 30 ng/kg of body weight, IV) and five control horses were given an equivalent volume of sterile saline solution. Venous blood samples were collected for flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and to measure plasma endotoxin concentrations. Clinical signs of endotoxemia were recorded at 10, 20, 30, 40, 50 min, 1, 2, 3, 4, 8, 16, 24 and 48 hr after endotoxin or saline solution administration. Clinical findings characteristic of endotoxemia (tachycardia, tachypnea, increased rectal temperature, and leukopenia) occurred transiently in all horses administered endotoxin; however, plasma endotoxin concentrations were detectable in only 50% (4/8) of the endotoxin-infused horses. The percentage of CD4(+), CD5(+), and CD8(+) cells decreased while the percentage of CD14(+), IgM(+), and MHC class II(+) cells increased significantly after endotoxin infusion. Alterations in the immunophenotype of PBMCs from horses with experimentally-induced endotoxemia were associated with changes in vital signs, indicating that endotoxin altered the immuno balance.

Animals↗
PubMed2003

Imaging of gynecologic tumors: comparison of (11)C-choline PET with (18)F-FDG PET.

UNLABELLED: This study was designed to compare the value of PET using (11)C-choline with that of PET using (18)F-FDG for the diagnosis of gynecologic tumors. METHODS: We examined 21 patients, including 18 patients with untreated primary tumors and 3 patients with suspected recurrence of ovarian cancer. (11)C-choline PET and (18)F-FDG PET were performed within 2 wk of each other on each patient. The patients fasted for at least 5 h before the PET examinations, and PET was performed 5 min ((11)C-choline) and 60 min ((18)F-FDG) after injection of each tracer. PET images were corrected for the transmission data, and the reconstructed images were visually analyzed. Then, the standardized uptake value (SUV) was calculated for quantitative assessment of tumor uptake. PET results were compared with surgical histology or >6 mo of clinical observations. RESULTS: Of 18 untreated patients, (11)C-choline PET correctly detected primary tumors in 16 patients, whereas (18)F-FDG PET detected them in 14 patients. In 1 patient with small uterine cervical cancer and 1 diabetic patient with uterine corpus cancer, only (11)C-choline PET was true-positive. Both tracers were false-negative for atypical hyperplasia of the endometrium in 1 patient and were false-positive for pelvic inflammatory disease in 1 patient. For the diagnosis of recurrent ovarian cancer (n = 3), (11)C-choline PET and (18)F-FDG PET were true-positive in 1 patient, whereas neither tracer could detect cystic recurrent tumor and microscopic peritoneal disease in the other 2 patients. In the 15 patients with true-positive results for both tracers, tumor SUVs were significantly higher for (18)F-FDG than for (11)C-choline (9.14 +/- 3.78 vs. 4.61 +/- 1.61, P < 0.0001). In 2 patients with uterine cervical cancer, parailiac lymph node metastases were clearly visible on (18)F-FDG PET but were obscured by physiologic bowel uptake on (11)C-choline PET. CONCLUSION: The use of (11)C-choline PET is feasible for imaging of gynecologic tumors. Unlike (18)F-FDG PET, interpretation of the primary tumor on (11)C-choline PET is not hampered by urinary radioactivity; however, variable background activity in the intestine may interfere with the interpretation.

Adenocarcinoma↗
PubMed2002

Ovarian cancer recurrence: role of whole-body positron emission tomography using 2-[fluorine-18]-fluoro-2-deoxy- D-glucose.

This study was designed to assess the value of whole-body positron emission tomography (PET) using 2-[fluorine-18]-fluoro-2-deoxy- D-glucose (FDG) for the diagnosis of recurrent ovarian cancer. Twenty-five patients who had previously undergone surgery for ovarian cancer were imaged using whole-body FDG-PET. During the 4 weeks preceding the PET study, conventional imaging, comprising computed tomography (CT) and magnetic resonance (MR) imaging of the abdomen and/or pelvis, was performed and serum CA125 levels were measured. PET imaging was commenced at 60 min after the intravenous administration of FDG in all patients. PET results were compared with the results of conventional imaging and CA125 levels, and related to pathological findings and clinical follow-up for more than 6 months. FDG-PET showed a sensitivity of 80% (16/20), a specificity of 100% (5/5) and an accuracy of 84% accuracy (21/25) for the diagnosis of recurrent ovarian cancer. The sensitivity, specificity and accuracy of conventional imaging were 55% (11/20), 100% (5/5) and 64% (16/25), respectively. PET could detect recurrent lesions in seven of nine patients in whom conventional imaging was falsely normal, while conventional imaging was true positive in two of four patients with false-negative PET results. The CA125 results showed a sensitivity of 75% (15/20), a specificity of 100% (5/5) and an accuracy of 80% accuracy (20/25). Among the 15 patients with true-positive CA125 results, PET correctly detected abnormal foci of recurrence in 13 patients (86.7%) whereas conventional imaging showed recurrent lesions in only eight patients (53.3%). In conclusion, our preliminary study demonstrates that FDG-PET may be accurate and useful for the detection of tumour recurrence when conventional imaging is inconclusive or negative, especially in patients with abnormal CA125 levels.

Adenocarcinoma↗
PubMed2002

Randomized open trial for comparison of proton pump inhibitors in triple therapy for Helicobacter pylori infection in relation to CYP2C19 genotype.

BACKGROUND AND AIMS: Genetic polymorphism of cytochrome P450 (CYP) 2C19 influences the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin. However, in triple therapy (PPI plus amoxicillin and clarithromycin), little is known about the impact of CYP2C19 polymorphism, or the use of rabeprazole, which is not well metabolized by CYP2C19. The efficacy of three PPI (omeprazole, lansoprazole, and rabeprazole) in a 1-week triple regimen were compared in relation to CYP2C19 polymorphism. METHOD: One hundred and eighty-three patients were randomized to receive one of the following regimens: amoxicillin 500 mg t.i.d., clarithromycin 200 mg t.i.d., and PPI (omeprazole 20 mg, lansoprazole 30 mg, or rabeprazole 10 mg) b.i.d. CYP2C19 polymorphism was analyzed by PCR restriction fragment length polymorphism. RESULTS: Intention-to-treat-based overall cure rates for omeprazole, lansoprazole or rabeprazole regimens were 83.1% (95% confidence interval (CI): 69-89%), 86.7% (CI: 75-93%), and 76.6% (CI: 64-85%), respectively, without significant difference. The cure rate of the rabeprazole regimen (but not the lansoprazole or omeprazole regimens) tended to be correlated with CYP2C19 genotypes (P = 0.076). In patients with a homozygous extensive metabolizer genotype, the per protocol-based cure rate with rabeprazole (62.5%) was significantly lower than that with lansoprazole (90.0%; P = 0.038). CONCLUSION: The overall cure rate of 1-week triple therapy for H. pylori eradication was not significantly different between regimens with omeprazole, lansoprazole or rabeprazole, but the impact of CYP2C19 genetic polymorphism on the cure rate appeared to differ between these PPI.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2002

Advances in the development of a reliable assay for the measurement of stool decay-accelerating factor in the detection of colorectal cancer.

We have previously shown that stool concentrations of decay-accelerating factor (DAF; CD55), a membrane-bound complement-regulatory protein, are significantly elevated in patients with colorectal cancer and that the measurement of stool DAF may be a valuable test for the detection of colorectal cancer. Accordingly, we are working to develop a clinically useful immunoassay for fecal DAF. A requirement for such assay is a plentiful and reliable supply of anti-DAF antibodies. We developed a sandwich enzyme-linked immunosorbent assay (ELISA) for DAF in stool specimens, using two monoclonal anti-DAF antibodies recognizing different epitopes on the DAF molecule. When we first used a biotin-labeled antibody and enzyme-linked streptavidin method, we often observed stool interference, probably due to the presence of a substance(s) with biotin activity which non-specifically bound to the Fc portion of IgG of the first anti-DAF antibody on the ELISA wells. By the use of inorganic salts in the sample-dilution buffer and HRP-labeled anti-DAF as second antibody, we circumvented the stool interference and established that the new ELISA system could reliably measure DAF at low concentrations in stool specimens. Because the new assay system uses only monoclonal antibodies, we can now consistently supply ample amounts of antibodies for routine measurement of stool DAF.

Adolescent↗
PubMed2002

Effect of simple motor performance on regional dopamine release in the striatum in Parkinson disease patients and healthy subjects: a positron emission tomography study.

To investigate changes in dopamine release in the striatum during motor exercise in human subjects with and without striatal dopamine denervation, eight healthy subjects and eight patients with Parkinson disease (PD) were measured during unilateral foot extension/flexion movement using positron emission tomography with [11C]raclopride. Five subjects in each group were later scanned in the resting condition. Estimation of binding potential (k3/k4) of [11C]raclopride was based on Logan plot method. Significant reductions in [11C]raclopride k3/k4 were found in the dorsal putamen contralateral to the exercise side in the healthy group and ipsilaterally in the PD group. Spearman rank correlation analysis showed that [11C]raclopride k3/k4 correlated inversely with the decrease in performance (velocity and motion range) in the dorsal putamen contralaterally in the healthy group and ipsilaterally in the PD group. These results suggest that simple but laborious motor exercise (motor stimulation) generates significant dopamine release in the dorsal striatum contralateral to the motor execution in humans. Lack of the crossed pattern and ipsilateral increase in dopamine release in the dorsal striatum during the unilateral limb movement may reflect the pathophysiology for hypokinetic and insufficient coordinating movement in PD.

Aged↗