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Biomedical subjects

Haruhiko Yoshida

Publications and source records attributed to Haruhiko Yoshida.

At least 55 records · Page 3Linked to original sources
PubMed2005

Amebic colitis in asymptomatic subjects with positive fecal occult blood test results: clinical features different from symptomatic cases.

Amebiasis is a common parasitic infectious disease in developing countries. In developed countries, it is occasionally encountered in travelers to the tropics and in homosexual males. During the past eight years, we detected four cases of amebic colitis among 5,193 subjects who underwent colonoscopy because of positive fecal occult blood test results in a mass screening. All four cases did not have any abdominal symptoms. Ulcerative lesions were observed only in the cecum and ascending colon; another portion of the colon and rectum appeared normal. We may encounter amebic colitis during colonoscopic examination even in subjects who are asymptomatic.

Animals↗
PubMed2004

Functional variability of cagA gene in Japanese isolates of Helicobacter pylori.

CagA protein of Helicobacter pylori is injected into the epithelium, where CagA undergoes tyrosine phosphorylation and activates proliferation signals. However, the importance of these CagA activities for pathogenesis has yet to be resolved. The aim of this study is to analyze the genetic and functional variability of cagA gene of clinical strains in relation to gastric diseases. Thirty-six H. pylori strains were isolated from Japanese patients with various gastric diseases and examined. All 36 strains were found to contain cagA and cagE gene and to induce CagA phosphorylation upon infection. The intensity of CagA phosphorylation expressed in HeLa cells by transfection was highly correlated to the number of R1 region. The phosphorylation intensity was slightly higher in strains from chronic atrophic gastritis (CG); however, the differences were not statistically significant. These CagA proteins also activated the serum response element (SRE) reporter by 5- to 14-fold, above the level of the control. CagA proteins which lack R2 or R3 region exhibited smaller ability for SRE activation. The average of SRE activation was slightly higher in strains from cases of gastric cancer (GC; 11.4+/-1.6), MALT lymphoma (ML; 10.7+/-1.0), and chronic atrophic gastritis (CG; 11.2+/-1.6) than in those of duodenal ulcer (DU; 8.3+/-1.9) or gastric ulcer (GU; 9.0+/-1.1). In summary, most Japanese H. pylori strains contained CagA transport system and induced CagA phosphorylation, and the levels of the intensity of phosphorylation and the ability to induce SRE varied among strains. Although the association between CagA activities and disease outcome shown in this study is not very strong, variety of CagA structure, which induces variable activities, may be one of the reasons why H. pylori induces distinct diseases on host.

Amino Acid Sequence↗
PubMed2004

Prevention and treatment of hepatocellular carcinoma.

Viral hepatitis, by either hepatitis C virus (HCV) or hepatitis B virus (HBV), is the dominant cause of hepatocellular carcinoma (HCC). This is to say that HCC may be prevented by controlling viral infection. Horizontal transmission of HCV has become obsolete owing to the discovery of the virus. Vertical transmission of HBV during delivery has been effectively prevented by vaccination and immunization of neonates. The efficacy of interferon therapy against HCV was recently much improved. We now possess several powerful antiviral drugs against HBV. There has been progress also in the treatment of HCC, and together with advances in diagnostics facilitating HCC detection at an early stage, tumor nodules can often be completely removed either by medical ablation or surgical resection. Nevertheless, recurrence of HCC after apparently curative treatment is extraordinarily frequent, since the remaining liver is still at a particularly high risk of HCC. An effective treatment of HCC should include measures to control de novo carcinogenesis.

Carcinoma, Hepatocellular↗
PubMed2004

Treatment of hepatocellular carcinoma by percutaneous tumor ablation methods: Ethanol injection therapy and radiofrequency ablation.

In Japan, approximately 30,000 patients died of hepatocellular carcinoma (HCC) in 2003. Ten percent had hepatitis B virus infection and 80% had hepatitis C virus (HCV) infection, indicating that viral hepatitis accounted for >90% of cases of HCC. In comparison, only 3% (1.5%, hepatitis B virus; 1.5%, HCV) of the general population is infected with these viruses. We treated 1238 patients between 1992 and the end of 2003 by means of percutaneous tumor ablation (PTA): 524 patients, by percutaneous ethanol injection therapy (PEIT); 85 patients, by percutaneous microwave coagulation therapy; and 629 patients, by radiofrequency ablation (RFA). Three-, 5-, 7-, and 10-year survival rates of the 1238 patients were 69%, 50%, 34%, and 19%, respectively. When limited to tumors </=3 cm in diameter and </=3 in number of cancer nodules (3-3 rule), 5-year survival rates reached 64.7% for PEIT. However, to achieve a 40% survival rate in year 5 after PEIT, the indication for treatment can be expanded to a 4 (size)-3 (number) rule or 5 (size)-1 (number) rule. The recent introduction of RFA may further change the rules. HCV-related HCC generally develops on the background of advanced fibrosis/cirrhosis. An issue of much concern is that it may subsequently recur in a location other than that of the primary lesion. We initiated a prospective controlled study to evaluate treatment with PTA and interferon. Results suggest that if the virus is eradicated, a 5-year survival rate as high as 80% can be expected.

Aged↗
PubMed2004

Neither hepatitis C virus genotype nor virus load affects survival of patients with hepatocellular carcinoma.

OBJECTIVE: Hepatitis C virus (HCV) genotype and virus load, the strongest determinants of the efficacy of interferon therapy, have been presumed to be associated with risk for hepatocellular carcinoma (HCC). This study was conducted to elucidate whether these two factors are capable of predicting the prognosis of patients with HCC. METHODS: A total of 371 patients with HCV infection (258 men and 113 women; median age, 66 years; range, 37-88 years) who developed HCC between January 1993 and December 1999 were enrolled. Overall survival and recurrence-free survival were analysed with the Cox proportional hazard regression according to HCV genotype (type 1 versus type 2) and virus load (above versus below 100 kIU/ml). RESULTS: Of the 371 patients, 346 received locoregional treatments (ethanol injection, microwave, radiofrequency, or surgery), and 307 achieved complete response as determined by subsequent imaging studies. The remaining 25 patients underwent arterial embolization or chemotherapy. Cox proportional hazard regression showed that neither genotype (P = 0.814) nor virus load (P = 0.958) were significant predictors for survival (P = 0.814 and 0.958, respectively) and recurrence (P = 0.505 and 0.736, respectively). CONCLUSIONS: Neither genotype nor virus load of HCV affected prognosis of HCC patients.

Adult↗
PubMed2004

A novel display of reconstruction computed tomography for the detection of small hepatocellular carcinoma.

PURPOSE: To evaluate the usefulness of the alternate display of arterial and equilibrium phase images (ADAEI) of 2 mm-pitch reconstruction computed tomography (CT) in the detection of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: One hundred and eleven nodules in 72 patients were confirmed as HCC by radiology, histology, or clinical course. Blinded to the outcome, we retrospectively reviewed the CT images obtained with dual-phase spiral CT (Radix Prima, Hitachi Medical, Tokyo, Japan) by ADAEI and by conventional display on cut films. Scanning for the arterial and equilibrium phases was initiated at 33 and 120 s, respectively, after starting the injection of contrast medium (iopamidol 3 ml/s) with a section thickness of 5 mm and a table feed speed of 5-7 mm/s. In ADAEI, all images were reconstructed with a 2-mm interval, and displayed on the monitor in an alternating fashion so that an image in the arterial phase was followed by the corresponding image in the equilibrium phase, and then by the next pair of images in the craniocaudal direction. RESULTS: All 20 HCC nodules larger than 20 mm in diameter were detected by both ADAEI and the conventional display (NS). On the other hand, detectability of smaller HCC nodules was 91/91 (100%) and 72/91 (79%), respectively (P<0.0001 by McNemar' test). False-positively identified HCC nodules, including those diagnosed as possible HCC, were 11 by ADAEI and eight by conventional display. CONCLUSION: The novel, alternate display, ADAEI of 2 mm-pitch reconstruction CT images was useful in detecting small HCC nodules while not requiring additional equipment or expense.

Aged↗
PubMed2004

Evaluation of transcatheter arterial embolization prior to percutaneous tumor ablation in patients with hepatocellular carcinoma: a randomized controlled trial.

BACKGROUND: Transcatheter arterial embolization (TAE) may reduce the risk of hepatocellular carcinoma (HCC) recurrence when performed before percutaneous tumor ablation (PTA), either percutaneous ethanol injection therapy (PEIT) or radiofrequency ablation (RFA). We conducted a randomized, controlled trial comparing the use of TAE combined with percutaneous ethanol injection therapy (TAE/PEIT) to the use of PEIT only to assess the effects on HCC recurrence and survival. We continued the study after the introduction of RFA and compared TAE combined with RFA (TAE/RFA) with RFA only. METHODS: Between March 1997 and April 2001, 42 HCC patients were enrolled who satisfied the following inclusion criteria: (1) uninodular HCC as determined by angiography under computed tomography, (2) arterial hypervascularity, and (3) no prior history of HCC treatment. Twenty-two patients were treated with TAE/PTA (PEIT, 12; RFA, 10) and 20 patients with PTA only (PEIT, 14; RFA, 6). RESULTS: There were four cases of local recurrence in the PTA-only group and none in the TAE/PTA group (P=0.043). The four patients with local recurrence were treated with PEIT. None of the patients treated with RFA showed local recurrence. The effect of TAE on overall recurrence was not significant (P=0.4179). In the multivariate analysis, prior TAE was not significant for survival (P=0.514). CONCLUSIONS: TAE has a limited use in suppressing local recurrence when performed before PEIT but not before RFA.

Aged↗
PubMed2004

Cyclooxygenase-2 in human malignant fibrous histiocytoma: correlations with intratumoral microvessel density, expression of vascular endothelial growth factor and thymidine phosphorylase.

Cyclooxygenase-2 (COX-2) has been found to be up-regulated in several types of human malignant tumors and proposed to have a role in the angiogenic process. This study examined the expression of COX-2 in two human malignant fibrous histiocytoma (MFH) cell lines by Western blotting, which showed a specific single band at 72 kDa. Immunohistochemistry was conducted in 35 MFHs and 30 benign fibrohistiocytic tumors (BFHTs), comparing the expression of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP), as well as intratumoral microvessel density (IMVD). COX-2 expression was noted in 22 (62.9%) MFHs, but in no BFHT. IMVD values were significantly higher in the MFHs (90.6+/-8.0) than BFHTs (27.9+/-3.1), and also in the COX-2 positive (104.5+/-11.3) than negative (67.2+/-5.8) MFHs. VEGF and TP expression was also associated with a significantly higher level of COX-2, as well as greater IMVD. The highest IMVD values were noted in the 17 MFHs (120.8+/-11.5) expressing all three factors. Clinical analysis demonstrated poorer survival in the 18 COX-2 positive MFHs than in the 10 negative ones, although the small number of cases did not reveal a significant difference. The results overall indicated that COX-2 expression is associated with intratumoral angiogenesis, which might provide favorable conditions for tumor progression in human MFHs.

Aged↗
PubMed2004

Genes associated with human hepatocellular carcinoma cell chemosensitivity to 5-fluorouracil plus interferon-alpha combination chemotherapy.

Recently, combined chemotherapy with 5-fluorouracil (5-FU) and interferon (IFN)-alpha has been reported to show marked effects in patients with advanced hepatocellular carcinoma. We investigated the genes associated with susceptibility to this combination therapy. The gene expression profiles of eight human hepatocellular carcinoma cells (HepG2, Hep3B, Huh7, Huh6, PLC/PRF/5, HLE, HLF, and SK-Hep1) were evaluated using an oligonucleotide microarray that consisted of 3,800 genes. The 50% growth inhibitory concentration (GI50) values for 5-FU, IFN-alpha, and the combination of 5-FU plus IFN-alpha were determined by the MTT assay. We selected genes that were expressed differentially between the cells with increased susceptibility to the combination therapy and the remaining cells. Relevance networks of the gene expression patterns and GI50 values of the susceptible cells were constructed to find genes associated with susceptibility to the combination therapy. Of the eight cells tested, five showed increased susceptibility to 5-FU plus IFN-alpha compared with 5-FU treatment alone. Among the 3,800 genes, 25 were expressed differentially between susceptible cells and resistant cells. The relevance networks revealed that sensitivity to 5-FU plus IFN-alpha involved the expression of 27 independent genes, which included 10 genes that are commonly associated with sensitivity to 5-FU alone. We selected a set of genes to predict susceptibility to 5-FU plus IFN-alpha combination therapy. We also selected genes that play key roles in the synergistic effect of this combination therapy. These gene sets should prove useful in evaluations of the efficacy and underlying molecular mechanisms of this combination therapy.

Antineoplastic Agents↗
PubMed2003

Helicobacter pylori induces antiapoptosis through buclear factor-kappaB activation.

Although Helicobacter pylori is classified as a definite carcinogen, the mechanism underlying gastric carcinogenesis is not yet clear. We previously have shown that H. pylori activates an antiapoptotic gene, the cellular inhibitor of apoptosis protein 2 (c-IAP2), the underlying mechanism of which was investigated in the present study. cDNA array and real-time PCR analyses indicated that H. pylori showed a stimulatory effect on the expression of c-IAP2. Isogenic mutant strains with impaired cag pathogenicity island (cagPAI) expression showed weaker induction. Analyses that used the in situ terminal deoxynucleotide transferase-mediated dUTP nick end-labeling method indicated suppression of antiapoptosis by the antisense c-IAP2 oligonucleotide. Reporter assays with deletion and mutation constructs for the c-IAP2 promoter showed that nuclear factor-kappaB (NF-kappaB) binding sites are indispensable for transactivation. Super-repressor IkappaBalpha or NF-kappaB inhibitor reduced c-IAP2 transactivation by H. pylori, and exogenous expression of c-IAP2 inhibited apoptosis seen with H. pylori. In conclusion, H. pylori induces antiapoptosis through c-IAP2 transactivation following cagPAI-dependent NF-kappaB activation. The interaction of these stimuli may play a role in gastric carcinogenesis.

Apoptosis↗
PubMed2003

Interferon therapy after tumor ablation improves prognosis in patients with hepatocellular carcinoma associated with hepatitis C virus.

BACKGROUND: Even after the surgical or medical treatment of hepatocellular carcinoma, tumors frequently develop at new foci, leading to a poor prognosis. OBJECTIVE: To assess whether combined tumor ablation and interferon therapy can reduce the occurrence of new foci of hepatocellular carcinoma, thereby improving survival rate. DESIGN: Randomized, controlled study. SETTING: University hospital. PATIENTS: 74 patients with compensated cirrhosis, three or fewer nodules of hepatocellular carcinoma, and low hepatitis C virus RNA loads (< or =2 x 10(6) copies/mL). INTERVENTION: After all patients had complete ablation of lesions by percutaneous ethanol injection therapy, 49 patients were assigned to receive 6 million U of interferon three times weekly for 48 weeks and 25 did not receive treatment. MEASUREMENTS: Abdominal ultrasonography, computed tomography, and determination of blood biochemical measures. RESULTS: Of the 49 patients treated with interferon, 21 showed a sustained biochemical response and 14 showed a sustained virologic response. The rate of first recurrence of new foci of hepatocellular carcinoma was similar in patients treated with interferon and untreated patients; however, the rates of second or third recurrence seemed to be lower in the interferon group than in the untreated group. Patients treated with interferon had a survival rate of 68% at 5 years and 53% at 7 years; untreated patients had a survival rate of 48% at 5 years and 23% at 7 years. CONCLUSION: After tumor ablation by ethanol injection, interferon therapy may enhance patient survival in selected patients with chronic hepatitis C.

Adult↗
PubMed2002

Hepatocellular carcinoma in elderly patients: beneficial therapeutic efficacy using percutaneous ethanol injection therapy.

BACKGROUND: The age of patients with hepatocellular carcinoma (HCC) has been increasing worldwide. The objective of this study was to assess the efficacy and safety of percutaneous ethanol injection therapy (PEIT) in elderly patients with HCC. METHODS: The authors retrospectively analyzed 653 patients who were treated with PEIT between 1985 and 1997. One hundred thirty-seven patients were age > or = 70 years, 90 of 137 patients (66%) were male, and 106 of 137 patients (77%) were positive for hepatitis C virus antibodies. Both survival rates and standardized mortality ratios (SMRs) related to the causes of death were compared between patients age > or = 70 years and patients age < 70 years. RESULTS: With the exception of greater maximum tumor size in elderly patients age > or = 70 years, the clinical features of tumors and underlying liver disease were similar to those of patients age < 70 years The survival rates after PEIT in patients age > or = 70 years were 83%, 52%, and 27% at 1 year, 3 years, and 5 years, respectively. These results were comparable to the rates for patients age < 70 years (1 year, 90%; 3 years, 65%; and 5 years, 40%). In addition, there was no difference in mortality from extrahepatic disease between the two groups (9.8% for patients age > or = 70 years vs. 9.4% for patients age < 70 years; P > 0.999). The SMR of patients age > or = 70 years who died of causes related to extrahepatic disease (SMR, 0.56; 95% confidence interval [95%CI], 0.18-1.30) was lower compared with the SMR of patients age < 70 years (SMR, 1.75; 95%CI, 1.07-2.71). The SMR of patients age > or = 70 years who died of causes related to liver disease (SMR, 115; 95%CI, 84.1-153.0) was similar to that of patients age < 70 years (SMR, 120; 95%CI, 103.0-138.0). CONCLUSIONS: These results provide support for the treatment of patients with HCC age > or = 70 years by tumor ablation using PEIT.

Administration, Cutaneous↗
PubMed2002

Helicobacter pylori activates the proto-oncogene c-fos through SRE transactivation.

Epidemiological studies have demonstrated a strong association between Helicobacter pylori infection and gastric cancer. However, there have been few detailed studies on the mechanism of cellular proliferation by H. pylori. Thus, we examined activation of the proto-oncogene c-fos to elucidate the underlying mechanism of cell proliferation caused by H. pylori. Activation of c-fos was evaluated in human gastric cancer cells (TMK1) by Northern blot and reporter assays with deletion analysis of the c-fos transcriptional control region. c-fos promoter activation and transcription were enhanced when cocultured with cag-positive strains. H. pylori-mediated c-fos promoter activation was inhibited by MEK1/2 inhibitor (U0126). The deletion analysis indicated that serum response element (SRE) was required for the activation of c-fos by H. pylori. In conclusion, c-fos promoter activation and transcription were enhanced through the activation of extracellular signal-regulated kinases (ERK)/mitogen-activated protein kinase (MAPK) cascade in gastric cancer cells when cocultured with H. pylori possessing intact cag PAI. SRE is required for the activation of c-fos by H. pylori. These results suggest a direct involvement of H. pylori infection in cellular proliferation, which may play a role in neoplastic transformation.

Adult↗