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Biomedical subjects

M Yano

Publications and source records attributed to M Yano.

At least 199 records · Page 11Linked to original sources
PubMed1999

The hypervariable region 1 protein of hepatitis C virus broadly reactive with sera of patients with chronic hepatitis C has a similar amino acid sequence with the consensus sequence.

Hypervariable region 1 (HVR1) proteins of hepatitis C virus (HCV) have been reported to react broadly with sera of patients with HCV infection. However, the variability of the broad reactivity of individual HVR1 proteins has not been elucidated. We assessed the reactivity of 25 different HVR1 proteins (genotype 1b) with sera of 81 patients with HCV infection (genotype 1b) by Western blot. HVR1 proteins reacted with 2-60 sera. The number of sera reactive with each HVR1 protein significantly correlated with the number of amino acid residues identical to the consensus sequence defined by Puntoriero et al. (G. Puntoriero, A. Lahm, S. Zucchelli, B. B. Ercole, R. Tafi, M. Penzzanera, M. U. Mondelli, R. Cortese, A. Tramontano, G. Galfre', and A. Nicosia. 1998. EMBO J. 17, 3521-3533. ) (r = 0.561, P < 0.005). The most widely reactive HVR1 protein, 12-22, had a sequence similar to the consensus sequence. The peptide with C-terminal 13-amino-acids sequence of HVR1 protein 12-22 (NH2-CSFTSLFTPGPSQK) was injected into rabbits as an immunogen. The rabbit immune sera reacted with 9 of 25 HVR1 proteins of genotype 1b including HVR1 protein 12-22 and with 3 of 12 proteins of genotype 2a. These results indicate that the HVR1 protein broadly reactive with patients' sera has a sequence similar to the consensus sequence, can induce broadly reactive sera, and could be one of the candidate immunogens in a prophylactic vaccine against HCV.

Amino Acid Sequence↗
PubMed1999

Rice gibberellin-insensitive dwarf mutant gene Dwarf 1 encodes the alpha-subunit of GTP-binding protein.

A rice Dwarf 1 gene was identified by using a map-based cloning strategy. Its recessive mutant allele confers a dwarf phenotype. Linkage analysis revealed that a cDNA encoding the alpha-subunit of GTP-binding protein cosegregated with d1 in 3,185 d1 segregants. Southern hybridization analysis with this cDNA as a probe showed different band patterns in several d1 mutant lines. In at least four independent d1 mutants, no gene transcript was observed by Northern hybridization analysis. Sequencing analysis revealed that an 833-bp deletion had occurred in one of the mutant alleles, which resulted in an inability to express GTP-binding protein. A transgenic d1 mutant with GTP-binding protein gene restored the normal phenotype. We conclude that the rice Dwarf 1 gene encodes GTP-binding protein and that the protein plays an important role in plant growth and development. Because the d1 mutant is classified as gibberellin-insensitive, we suggest that the GTP-binding protein might be associated with gibberellin signal transduction.

Journal Article↗
PubMed1999

Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group. Inhibition of Hepatocarcinogenesis by Interferon Therapy.

BACKGROUND: Previous studies on the effect of interferon therapy on the incidence of hepatocellular carcinoma have not sufficiently assessed degree of liver fibrosis, a major risk factor for hepatocellular carcinoma. OBJECTIVE: To evaluate the effect of interferon therapy on incidence of hepatocellular carcinoma, adjusting for risk factors, including the degree of liver fibrosis. DESIGN: Retrospective cohort study. SETTING: Seven university hospitals and one regional core hospital in Japan. PATIENTS: 2890 patients with chronic hepatitis C who had undergone liver biopsy since 1986. Of these patients, 2400 received interferon and 490 were untreated. MEASUREMENTS: The degree of liver fibrosis was assessed from stage F0 (no fibrosis) to stage F4 (cirrhosis). Response to interferon was determined virologically and biochemically. Screening for development of hepatocellular carcinoma was performed periodically during an average follow-up of 4.3 years. Effect of interferon therapy on the risk for hepatocellular carcinoma was analyzed by using Cox proportional hazards regression. RESULTS: Hepatocellular carcinoma developed in 89 interferon-treated patients and in 59 untreated patients. Among untreated patients, the annual incidence of hepatocellular carcinoma increased with the degree of liver fibrosis, from 0.5% among patients with stage F0 or F1 fibrosis to 7.9% among patients with stage F4 fibrosis. The cumulative incidence in treated and untreated patients differed significantly for patients with stage F2 fibrosis (P = 0.0128) and for those with stage F3 fibrosis (P = 0.0011). In multivariate analysis, interferon therapy was associated with a reduced risk for hepatocellular carcinoma (adjusted risk ratio, 0.516 [95% CI, 0.358 to 0.742]; P < 0.001), especially among patients with sustained virologic response (risk ratio, 0.197 [CI, 0.099 to 0.392]), among those with persistently normal serum alanine aminotransferase levels (risk ratio, 0.197 [CI, 0.104 to 0.375]), and among those with alanine aminotransferase levels less than two times the upper limit of normal (risk ratio, 0.358 [CI, 0.206 to 0.622]). CONCLUSIONS: Interferon therapy significantly reducesthe risk for hepatocellular carcinoma, especially among virologic or biochemical responders.

Alanine Transaminase↗
PubMed1999

Inhibitory effect of Epstein-Barr virus activation by Citrus fruits, a cancer chemopreventor.

To search useful compounds in Citrus fruit for cancer chemoprevention, we carried out a primary screening of extracts of fruit peels and seeds from 78 species of the genus Citrus and those from two Fortunella and one Poncirus species, which were closely related to the genus Citrus. These Citrus extracts inhibited the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) as a useful screening method for anti-tumor promoters. Our results indicated that Citrus containing substances may be inhibit susceptibility factors involved in the events leading to the development of cancer.

Animals↗
PubMed1999

Isolation and characterization of rice MADS box gene homologues and their RFLP mapping.

Thirty-five MADS box gene homologues were identified through a large-scale cDNA analysis in rice. Based on the nucleotide sequences of the 3'-untranslated region, these clones were classified into 11 independent species. Seven species were found to be new among the rice MADS box gene family, and the other 4 corresponded to the previously reported OsMADS1, OsMADS2, OsMADS4, and OsMADS5. The full nucleotide sequences of the 7 new species were determined. Each clone encoded a deduced protein of 164-267 amino acids. The K-domain of the MADS protein was conserved in all clones though with lower degree in clone S10304. Reverse transcription PCR analysis showed that clones E31254 and E31864 were expressed mainly in panicles. Dendrogram analysis suggested that E31254 and E31864 are close to Arabidopsis AGL9 and AP1, respectively. Restriction fragment length polymorphism (RFLP) linkage mapping revealed that the rice MADS box gene homologues reported here are not clustered but are located throughout the genome. The locus of E31864 on the RFLP map was closely linked to the long sterile lemma gene, g-1.

Amino Acid Sequence↗
PubMed1999

Prognostic significance of heat shock proteins 27 and 70 in patients with squamous cell carcinoma of the esophagus.

BACKGROUND: Heat shock proteins (HSPs) first were defined as proteins induced by heat shock and other environmental and pathophysiologic stresses and are implicated in protein-protein interactions such as folding, translocation, and prevention of inappropriate protein aggregation. Many of their functions suggest that they play important roles in cancer. METHODS: Immunohistochemical study for HSP 27 and HSP 70 was performed on buffered formalin fixed, paraffin embedded sections of 102 esophageal squamous cell carcinoma specimens using monoclonal anti-HSP 27 antibody and anti-HSP 70 antibody. RESULTS: Normal squamous cells expressed both HSP 27 and HSP 70 with the exception of the basal layer. In cancerous tissue, expression of HSP 27 was evaluated as positive (+) (39 cases; 38%), reduced (+/-) (53 cases; 52%), or negative (-) (10 cases; 10%) and expression of HSP 70 was evaluated as (+) (14 cases; 14%), (+/-) (57 cases; 56%), or (-) (31 cases; 30%). There was a strong correlation between the expression of HSP 27 and HSP 70 (P < 0.0001). When compared with clinicopathologic features, expression of both HSP 27 and HSP 70 correlated negatively with lymph node metastases (P < 0.05), but not with depth of invasion or histologic grade. The reduction of the HSPs was associated significantly with poor postoperative survival (P < 0.0001). In addition, multivariate analysis revealed that HSP 27 (-) was the strongest prognostic factor among the clinicopathologic features. CONCLUSIONS: This study suggests that the expression of HSP 27 and HSP 70 frequently is reduced in patients with esophageal squamous cell carcinoma and therefore should be considered an independent prognostic factor of this disease.

Adult↗
PubMed1999

Expression of hsp90 and cyclin D1 in human breast cancer.

The integral roles of heat shock proteins (hsps) in the cell cycle and in multistep processes leading to tumorigenesis have been implied. We examined the expression of hsp90alpha, hsp90beta and cyclin D1 in human breast cancer. Levels of mRNAs coding for hsp90alpha and cyclin D1 were significantly higher in cancer tissues than in non-cancer tissues. Moreover, there was a close relationship between the extent of the two mRNA levels, suggesting that increased expression of hsp90alpha, an isoform of the hsp90 family, is associated with the proliferation of human breast cancer. Hsp90beta was expressed in cancer cells, but not associated with cell proliferation.

Breast Neoplasms↗
PubMed1999

Specific sandwich-type enzyme immunoassays for smooth muscle constricting novel 31-amino acid endothelins.

We established highly sensitive and specific sandwich-enzyme immunoassays (EIAs) for three newly discovered bioactive 31-amino acid endothelins [ETs(1-31)], which can detect as little as 0.16 pg/well of ET-1(1-31), 0.39 pg/well of ET-2(1-31), and 0.16 pg/well of ET-3(1-31). The EIAs showed no crossreactivity with 21-amino acid endothelins [ETs(1-21)] or big ETs at the usual assay concentrations below 1-5 ng/ml. In reversed-phase HPLC, immunoreactive ETs(1-31) in the granulocytes of normal human subjects eluted at the exact positions of authentic ETs(1-31), except for the presence of one additional unknown immunoreactive ET-1(1-31). The results also indicate that ETs(1-31) exist in the granulocytes at levels higher than or similar to those of ETs(1-21). This study is the first to establish EIAs for novel bioactive ETs(1-31). These assays can be utilized to assess the pathophysiological roles of ETs(1-31).

Chromatography, High Pressure Liquid↗
PubMed1999

Genetic polymorphisms of drug-metabolizing enzymes and susceptibility to head-and-neck squamous-cell carcinoma.

We have investigated the association between the polymorphisms of drug-metabolizing enzymes and susceptibility to head-and-neck squamous-cell carcinoma (HNSCC). PCR-based analysis was performed on 145 Japanese patients and 164 healthy Japanese controls to determine genotypes of polymorphisms in CYP1A1, CYP2E1, GSTM1, GSTP1, and NAT2. Patients and controls were compared by multivariate analysis. The CYP1A1 Val/Val genotype was seen more frequently in patients than in controls [odds ratio (OR) 4.1, p = 0.038). The frequency of the slow plus intermediate NAT2 genotypes was also higher in patients (OR 2.0, p = 0.039). When we analyzed the distributions of the genotypes in 69 laryngeal and 45 pharyngeal cancer patients, laryngeal cancer patients had a higher frequency of NAT2 slow or intermediate genotype (OR 2.7, p = 0.011) and GSTP1 AA genotype (OR 2.4, p = 0.047) than controls. Pharyngeal cancer patients had a higher frequency of the CYP1A1 Val/Val genotype than controls (OR 5.7, p = 0.034), suggesting that different organs may be responsive to different chemicals from the environment. Furthermore, 23 patients who developed multiple cancers (HNSCC plus other) were compared with 115 patients with HNSCC alone. There was no significant difference in the polymorphisms between the 2 groups, though excessive alcohol consumption (more than 50 g/day of ethanol) appeared to be a risk factor for multiple cancers (p = 0.053).

Aged↗
PubMed1999

The extracellular processing of HIV-1 envelope glycoprotein gp160 by human plasmin.

Cleavage of the envelope glycoprotein precursor gp160 of HIV-1 is a prerequisite for the infectivity of HIV-1, and occurs at least in part before gp160 reaches the cell surface. Kexin/subtilisin-related endopeptidases are proposed enzyme candidates for this intracellular processing. In this study, we reveal the possibility that plasminogen binds to the cell surface and part of gp160 escaping intracellular processing is cleaved by plasmin extracellularly. Plasmin cleaves gp160 precisely at the C-terminal arginine residue of gp120, and the processing is effectively inhibited by an analogue peptide of the cleavage motif (RXK/RR) and by plasmin inhibitors.

Amino Acid Sequence↗
PubMed1999

Concurrent chemotherapy (5-fluorouracil and cisplatin) and radiation therapy followed by surgery for T4 squamous cell carcinoma of the esophagus.

BACKGROUND AND OBJECTIVES: Since the prognosis of patients with T4 squamous cell carcinoma (SCC) of the esophagus is extremely poor, an effective multimodal treatment needs to be established. METHODS: Forty-five patients with SCC of the esophagus at the T4 classification of the disease but no hematogenous metastasis were treated with concurrent chemoradiation therapy followed by surgical resection. Twenty-eight patients were treated with a regimen (protocol A) of 5-fluorouracil 750 mg/m2 on days 1-5 and 22-26, and cisplatin 70 mg/m2 on days 1 and 22. The remaining 17 patients were treated with a modified regimen (protocol B) of 5-fluorouracil 400 mg/m2 and cisplatin 10 mg/m2 on days 1-5, 8-12, 15-19, and 22-26. Radiation was delivered daily for 5 days/week for 4 weeks at the rate of 2 Gy/day to a total dose of 40 Gy in both protocols. RESULTS: A major clinical response was observed in 29 [3 complete response (CR) and 26 partial response (PR)] patients (64.4%). Twenty-eight patients (62.2%) underwent esophagectomy with no postoperative death. The median survival time of the resected patients (959 days) was significantly longer than that of the non-resected patients (178 days). Protocol B showed significantly higher pathologic effectiveness than protocol A. The pathologic CR rate for the main tumors was 1 (6.3%) of 16 patients for protocol A and 7 (58.3%) of 12 patients for protocol B. The pathologic CR rate for metastasized lymph nodes was 4/11 (36.4%) for protocol A and 5/5 (100%) for protocol B. Good histological response of the main tumors correlated well with long survival. The treatments were well tolerated except for one treatment-related death. CONCLUSIONS: Concurrent chemoradiation therapy followed by surgery is an effective and safe multimodal therapy for patients with primary inoperable T4 SCC of the esophagus.

Aged↗
PubMed1999

Benefit of intravascular ultrasound in Wiktor stent implantation.

The goal of this study was to evaluate retrospectively the efficacy and safety of intravascular ultrasound (IVUS) during Wiktor stent implantation. Until 1996, the success of stent implantation was assessed by angiographic criteria only, but in 1997, the procedure was expanded to include pre- and postprocedural IVUS imaging. Sixty-six patients were included, 28 treated in 1996 (group A) and 38 treated in 1997 (group B). Stent size was larger in group B than in group A (3.6+/-0.4 vs. 3.1+/-0.2, P < 0.001). Acute gain was greater in group B than in group A (2.58+/-0.61 vs. 2.11+/-0.56, P < 0.001). Restenosis rate was 31% in group A and 14% in group B. No major acute complications due to IVUS examination occurred. IVUS is helpful in choosing optimal stent size.

Aged↗
PubMed1999

Perioperative blood transfusion as a prognostic indicator in patients with hepatocellular carcinoma.

We studied the relation of perioperative blood transfusion and the outcomes in 175 patients with hepatocellular carcinoma (HCC) who underwent hepatic resection from 1986 to 1994 in our hospital. Hepatectomy was performed in 23 (13.1%) patients with and 152 (86. 9%) without blood transfusions. The cumulative cancer-free survival rates for patients who had received blood transfusion was significantly lower than that for patients who had not received blood transfusions (p = 0.003). Further examinations revealed a significant difference in cancer-free survival rates for stage I-II patients (n = 75) of HCC (p = 0.02) but not for stage III-IV patients (n = 56) (p = 0.06). Cox regression analysis for recurrence revealed that blood transfusion was the most significant prognostic indicator (p = 0.001) for recurrence in stage I-II patients but not in stage III-IV patients (p = 0.99). These results suggest that a perioperative blood transfusion may be a significant prognostic indicator for patients with HCC who had underwent hepatectomy, especially in stage I-II patients of HCC.

Adult↗
PubMed1999

Apoptosis and remodelling of beta cells by paracrine interferon-gamma without insulitis in transgenic mice.

AIMS/HYPOTHESIS: To examine whether interferon-gamma destroys islet beta cells directly or indirectly through lymphocyte activation, or whether direct action of interferon-gamma on beta cells by itself induces diabetes without insulitis. METHODS: To avoid possible nonspecific breakdown of beta cells by transgenic overexpression of interferon-gamma by the insulin promoter, we generated transgenic mice expressing interferon-gamma under the control of rat glucagon promoter (RGP-IFN-gamma-Tg mice). RESULTS: The absence of insulitis in RGP-IFN-gamma-Tg mice enabled us to investigate the direct effects of paracrine interferon-gamma. In RGP-IFN-gamma-Tg mice, serum concentrations of interferon-gamma and tumour necrosis factor-alpha (TNF-alpha) were 50 and 6 times higher than those in their littermates, respectively, and glucose-responsive insulin secretion decreased to one-half the level of that in the littermates. Transgenic interferon-gamma induced remodelling of beta cells where apoptosis of many beta cells was compensated by their vigorous regeneration and diabetes did not occur in most of the RGP-IFN-gamma-Tg mice. CONCLUSION/INTERPRETATION: Interferon-gamma alone is insufficient for the complete destruction of beta cells in vivo, and factors other than interferon-gamma including activated lymphocytes or other cytokines, are necessary in addition to interferon-gamma for the development of Type I (insulin-dependent) diabetes mellitus.

Animals↗
PubMed1999

A new technique for laparoscopic resection of a submucosal tumor on the posterior wall of the gastric fundus.

Several reports have been published which describe the technique of using an Endo GIA to resect submucosal tumors on the anterior wall of the stomach. Lesions on the posterior wall, however, especially near the esophagocardiac junction (ECJ), are difficult to resect using these reported techniques. This is because the surgeon must divide the omentum and enter the omental bursa in order to use a similar extraluminal technique. Furthermore, special care must be taken to ensure that resections do not involve the ECJ and narrow the esophagus. In order to overcome these difficulties, we have proposed a new technique for the laparoscopic excision of a submucosal tumor located on the posterior wall of the gastric fundus. The principle of this procedure involves the intraluminal resection of the submucosal tumor, including the surrounding stomach wall, using the Endo GIA. This technique is safe, simple, and effective. We believe that we are the first to address the excision of a submucosal lesion by resecting the full thickness of the posterior gastric wall lesion intraluminally.

Esophagogastric Junction↗
PubMed1999

Clinical features of 89 patients with autoimmune hepatitis in Nagasaki Prefecture, Japan.

We examined the clinical characteristics of 89 patients with autoimmune hepatitis (AIH) in Nagasaki Prefecture, Japan, and assessed the usefulness of a provisional scoring system for the diagnosis of AIH proposed by the International Autoimmune Hepatitis Group in 1993. The majority of patients were middle-aged women in their fifties. All patients showed a hepatitic picture. Forty-three patients (48%) had an insidious or chronic onset, while 34 (38%) had an acute onset, and 12 (14%) had liver cirrhosis at presentation. Seventy-nine patients (89%) were positive for antinuclear antibody (ANA), and 5 (6%) were positive for antibody to the hepatitis C virus (anti-HCV). The prognosis was good, with 90% 3-year survival, and most patients responded well to treatment with corticosteroids. The international scoring system was useful for the diagnosis of AIH in most of our patients; the percentages of patients with definite and probable AIH were 48% and 47%, respectively. However, certain factors, such as negative ANA, positive antimitochondrial antibody, concurrent infection with hepatitis B or C virus, and insufficient response to treatment precluded the diagnosis of AIH in some patients. Whether these patients were indeed "true" AIH patients is not clear at present, and further investigation of such patients may be useful for a better understanding of AIH.

Adolescent↗
PubMed1999

Role of preoperative chemoradiation in the management of upper third thoracic esophageal squamous cell carcinoma.

BACKGROUND: The treatment of upper thoracic esophageal cancer remains challenging, and combined treatment is necessary to improve the outcome. We conducted preoperative chemoradiation therapy (CRT) for potential T4 tumors located in the upper third esophagus and carried out a retrospective study to elucidate the role of preoperative CRT. METHODS: Surgical resection was performed on 64 patients with upper thoracic esophageal cancer. Thirty-seven of these patients underwent primary resection, while 27 underwent preoperative CRT and surgery. The regimen of chemotherapy consisted of daily tegaful or 5-fluorouracil plus cisplatin. Concurrent radiation therapy of 4,000 cGy was conducted over 4 weeks. RESULTS: There were no differences in either tumor depth and nodal involvement or the surgical morbidity and mortality between the two groups. Seven of 27 patients downstaged to a complete pathologic response, and 13 patients showed a partial response. The 5-year survival rates were 42% in the preoperative CRT group and 27% in the surgery group, and these were not significantly different. In all patients, the depth of tumor influenced the prognosis significantly, while operative curability, nodal involvement, or the number of metastatic nodes showed a tendency to influence the prognosis. CONCLUSIONS: Preoperative CRT contributed to downstaging of the tumors and did not increase the operative mortality. Preoperative CRT was useful in the management of upper thoracic esophageal cancer, especially in advanced cases.

Antineoplastic Combined Chemotherapy Protocols↗