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Biomedical subjects

K Sugihara

Publications and source records attributed to K Sugihara.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effect of interferon therapy on Japanese chronic hepatitis C virus patients with anti-liver/kidney microsome autoantibody type 1.

AIM: The aim of this study was to determine the prevalence of anti-liver/kidney microsome autoantibody type 1 (anti-LKM-1) among hepatitis C virus (HCV)-infected Japanese patients at various stages (chronic hepatitis, liver cirrhosis and hepatocellular carcinoma), and to assess the influence of anti-LKM-1 on interferon therapy. METHODS: A total of 390 serum samples from 215 HCV-infected patients with chronic hepatitis (HCV-CH), 81 HCV-infected patients with liver cirrhosis (HCV-LC), and 94 HCV-HCC infected patients were subjected to examination. Ninety-one HBsAg-positive patients and 137 healthy subjects served as controls. Anti-liver/kidney microsome autoantibody type 1 was determined by using a newly developed ELISA using recombinant cytochrome P450 IID6 as the antigen. RESULTS: Anti-liver/kidney microsome autoantibody type 1 was detected in six of the 390 (1.5%) chronic HCV-infected patients (four were HCV-CH and two were HCV-LC); in contrast, it was not detected in control groups. Among the 110 HCV-CH patients treated with interferon (IFN), four were positive for anti-LKM-1. No change in anti-LKM-1 immunoreactivity from negative to positive during interferon therapy was observed. Moreover, no increase in the serum alanine aminotransferase level was observed in these four patients with anti-LKM-1. CONCLUSION: Our study indicates that: (i) anti-LKM-1 does not aggravate the liver disease associated with HCV infection; and (ii) no change in anti-LKM-1 immunoreactivity from negative to positive or no aggravations of liver dysfunction were observed among HCV-CH patients during the IFN therapy for Japanese patients with liver disease.

Autoantibodies↗
PubMed2001

Solitary fibrous tumor in the mental region.

Solitary fibrous tumor (SFT) is a rare, benign, soft tissue tumor that most commonly occurs in the pleura; however, it has recently been described in other sites of the body. To date, eight examples of oral SFT have been reported. This paper is a description of the first case of an SFT occurring as a soft tissue tumor in the mental region. Histologically, the tumor was composed predominantly of rather uniform spindle-shaped fibroblastic cells arranged in vague fascicles or in a haphazard fashion, intermingled with abundant collagen fibers. Immunohistochemically, the tumor cells were positive for CD34 and vimentin, and weakly positive for muscle actin and alpha-smooth muscle actin. The diagnosis of SFT may be difficult as this tumor shares a number of histological features with other soft tissue tumors. Awareness of its occurrence in the oral cavity is important so that confusion with other spindle cell neoplasms can be avoided.

Actins↗
PubMed2001

Radiographic evaluation of malignant fibrous histiocytoma affecting maxillary alveolar bone: a report of 2 cases.

OBJECTIVE: The purpose of this study was to evaluate the radiographic findings of malignant fibrous histiocytoma (MFH) and to discuss the contribution of these findings to a differentiation of MFH from other malignant tumors of the head and neck. STUDY DESIGN: Two cases of MFH of the maxillary sinus affecting the alveolar bone were evaluated radiographically and scintigraphically. RESULTS: We reported the following findings, which have only seldom been described: the presence of fairly well-demarcated bone destruction in the intraoral radiograph; the relatively smooth surface, uniform density, or no necrotic area of the tumor; in computed tomograph images showing the clear separation of the tumor from surrounding soft tissues; bone scintigraphs reflecting the periosteal reaction to tumor invasion; and lymphoscintigraphy of the metastatic lymph nodes. CONCLUSION: We evaluated the radiographic findings from 2 cases of MFH and describe findings that may aid in the differentiation of MFH. These radiographic features may help dentists differentiate MFH from other malignant tumors in the head and neck, although MFH is a rare disease and there are no radiographic findings that would indicate a specific diagnosis of MFH.

Alveolar Process↗
PubMed2001

Dynamic scintigraphy with thallium-201 chloride (Tl-201) for the diagnosis of tumors of the head and neck.

OBJECTIVE: The purpose of this study was to differentiate between malignant tumors and benign tumors of the head and neck by means of thallium-201 chloride scintigraphy. STUDY DESIGN: Thallium-201 chloride (Tl-201) scintigraphy and Ga-67 citrate (Ga-67) scintigraphy were performed in 10 patients with a benign tumor and in 90 patients with a malignant tumor. The blood flow index and the tumor retention index were obtained by means of Tl-201 scintigraphy. The blood flow index = the count of tumor/the count of control in the early dynamic scan from 30 to 120 seconds after injection, and the tumor retention index = (the count of tumor/the count of control in the delayed dynamic scan 2.5 hours after injection)/(the count of tumor/the count of control in the early dynamic scan from 4 to 5 minutes after injection). RESULTS: The early and delayed scans with Tl-201 demonstrated a very high correlation with the blood flow index. The tumor retention index had a tendency to increase in malignant tumors, especially in the poorly differentiated tumors and the severely invasive tumors. Likewise, the tumor retention index decreased in benign tumors. These results proved to be statistically significant, and in turn Tl-201 scintigraphy was deemed superior to Ga-67 scintigraphy. Tl-201 scintigraphy was also useful in detecting small-size tumors. CONCLUSION: The tumor retention index of Tl-201 was useful for the differentiation of malignant tumors of the head and neck from benign tumors of the same areas.

Adenocarcinoma↗
PubMed2001

Non-enzymatic reduction of aliphatic tertiary amine N-oxides mediated by the haem moiety of cytochrome P450.

1. The mechanism of reduction of aliphatic tertiary amine N-oxides to tertiary amines in liver microsomes was examined and a novel type of reduction by cytochrome P450 was found. 2. Rat liver microsomes exhibited a significant N-oxide reductase activity toward brucine N-oxide and imipramine N-oxide in the presence of both NAD(P)H and FAD under anaerobic conditions. These N-oxide reductase activities were inhibited by carbon monoxide or air. However, the activities were not abolished by boiling the microsomes; indeed, in the case of brucine N-oxide, the activity was enhanced. 3. The activity toward brucine N-oxide was also observed after the conversion of cytochrome P450 to cytochrome P420. Cytochrome P4502B1 alone exhibited the reductase activity in the presence of both NAD(P)H and FAD. After the removal of haem from cytochrome P4502B1, the activity was observed in the haem moiety, but not in the cytochrome P450 apoprotein. 4. Photochemically reduced FAD was effective in the reduction in place of NAD(P)H and FAD. 5. The N-oxide reduction appears to proceed non-enzymatically, catalysed by the haem group of cytochrome P450 in the presence of a reduced flavin.

Amines↗
PubMed2001

Enzymatic and non-enzymatic reduction of brucine N-oxide by aldehyde oxidase and catalase.

1. Brucine N-oxide was reduced by aldehyde oxidase in rabbit liver cytosol in the presence of an electron donor, 2-hydroxypyrimidine, under anaerobic conditions. The flavoprotein purified from rabbit liver exhibited significant reductase activity in the presence of electron donors. 2. Brucine N-oxide was also reduced by rabbit liver cytosol and blood in the presence of both a reduced pyridine nucleotide and FAD under anaerobic conditions. The N-oxide reductase activities were inhibited by carbon monoxide and air. However, these activities were not abolished whe n liver cytosol and blood were boiled. Rabbit erythrocytes exhibited the reductase activity, but not plasma. 3. When liver cytosol or blood was separated by DEAE-cellulose column chromatography, the fractions with the reducing activity in the presence of both NADH and FAD also showed catalase activity. 4. Catalase catalysed the brucine N-oxide reduction in the presence of both NAD(P)H and FAD. Hematin also exhibited the reductase activity in the presence of both NAD(P)H and FAD. Photochemically reduced FAD was effective in the reduction instead of NAD(P)H and FAD. 5. Bricine N-oxide reduction proceeds via two routes in liver cytosol and blood. One is enzymatic reduction by aldehyde oxidase; the other is non-enzymatic reduction catalysed by the haem group of catalase in the presence of reduced flavin.

Aldehyde Oxidase↗
PubMed2001

Is lymphadenectomy needed for all submucosal gastric cancers?

OBJECTIVE: To find out if it is feasible to extend the indication for local resection of submucosal gastric cancer without increasing the risk of lymph node metastases. DESIGN: Retrospective study. SETTING: University hospital, Japan. SUBJECTS: 104 patients with gastric cancer confined to the submucosal layer who underwent conventional gastrectomy with lymphadenectomy. INTERVENTIONS: The risk of nodal metastases was analysed retrospectively depending on the depth of submucosal invasion, size of the tumour, and other clinicopathological findings. MAIN OUTCOME MEASURES: The degree of submucosal invasion, size of the tumour, and incidence of lymph node metastasis. RESULTS: 15/104 patients (14%) had lymph node metastases. No patient in whom submucosal invasion was less than 500 microm or tumour was less than 15 mm in diameter developed lymph node metastases. Fewer patients had lymphatic permeation (37/89) and venous involvement (21/89) in the group without lymph node metastases. CONCLUSION: These data seem to support the hypothesis that early, minimally invasive, gastric cancer measuring < 15 mm in diameter could be treated by endoscopic mucosal or local resection, and gastrectomy with lymphadenectomy might be unnecessary.

Adult↗
PubMed2001

Expression of pyrimidine nucleoside phosphorylase (PyNPase) in colorectal cancer.

BACKGROUND: We investigated the expression of PyNPase both in cancer cells and in stroma cells to clarify the correlation between PyNPase expression and the prognosis of patients with colorectal cancer. METHODS: Using immunohistochemical staining with an anti-PyNPase antibody, the PyNPase expression in tissues from 114 patients with stage II or III colorectal cancer was examined. From the correlation between PyNPase expression and the clinicopathological findings, the prognosis for survival was analyzed. RESULTS: The expression of PyNPase was classified as negative or positive on the basis of staining. No relationship between PyNPase expression and any of the clinicopathological findings was identified. However, a relationship was observed regarding positive staining between cancer cells and stroma cells. The prognosis of patients with positive staining in both cancer cells and stroma was worse than that of other patients. In multivariate analyses, expression in cancer cells was the strongest predictor of prognosis. CONCLUSIONS: PyNPase expression appears to be a relevant factor for predicting the prognosis of colorectal cancer.

Adult↗
PubMed2001

Extremely high drug-reductase activity based on aldehyde oxidase in monkey liver.

Drug-reducing ability of monkey liver cytosol was examined in this study. Monkey liver cytosol exhibited significant reductase activities toward zonisamide, sulindac and imipramine N-oxide in the presence of 2-hydroxypyrimidine or benzaldehyde, an electron donor to aldehyde oxidase. These activities were abolished by inhibitors of aldehyde oxidase, such as menadione. These reductase activities in monkeys were extremely high compared to those in other animals. The zonisamide reductase activity of monkey liver cytosol was about 40-fold higher than that of the liver microsomes. It appears that the high levels of aldehyde oxidase exists in monkey liver, and zonisamide, sulindac and imipramine N-oxide are mainly reduced by this enzyme, not by cytochrome P450.

Aldehyde Oxidase↗
PubMed2001

Thymidylate synthase gene expression in primary colorectal cancer and metastatic sites.

Thymidylate synthase (TS) expression has been identified as an important predictor of response to 5-fluorouracil (5-FU). However, there is relatively little information on the heterogeneity of TS mRNA expression between primary and metastatic tumors, as well as differential expression of TS mRNA in metastatic sites. In this study, TS mRNA expression was measured in primary colorectal cancer tumors and various metastatic tumors. The median TS/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ratio was 0.98 in primary tumors, 0.70 in liver metastases, 1.92 in lymph node metastases, and 3.42 in pulmonary metastases. A significantly higher expression of TS mRNA was observed in pulmonary and lymph node metastases compared with their respective primary tumors. In contrast, TS mRNA expression in hepatic metastases was significantly lower than in primary tumors. Similar results were observed in tumors obtained from the same patient. These results may explain the difference in the clinical response to 5-FU-based chemotherapy between various metastatic sites. The discordant TS expression between primary and metastatic tumors is a critical factor that must be taken into account when TS is being used as a predictive biomarker for the antitumor effect of 5-FU-based chemotherapy.

Adenocarcinoma↗
PubMed2001

Usefulness of long axis M-mode echocardiographic measurements for optimum dialysis in patients on maintenance hemodialysis: comparison with changes in plasma levels of atrial natriuretic peptide and brain natriuretic peptide.

UNLABELLED: It has been suggested that analyzing the left ventricular long axis motion can result in the sensitive detection of cardiac functional disorders. AIM: To evaluate the usefulness of left ventricular long axis indices in managing patients on maintenance hemodialysis. METHODS: Eighteen hemodialysis patients (mean age 51 +/- 10 years) as well as 16 healthy persons (mean age 49 +/- 9 years) were examined. Echocardiograms were recorded, and the plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured before and after a session of hemodialysis. The following parameters were measured: the left atrial diameter (LAD) and end-diastolic left ventricular diameter (LVDd) from M-mode echocardiograms, the end-diastolic LV volume (LVEDV) and ejection fraction (EF) from 2-D echocardiography, the E/A ratio from transmitral Doppler, the atrial systolic excursion of long axis motion of the mitral ring (ALAM) and maximal lengthening rate of the mitral ring toward the left atrium during the early diastolic phase (MLRe) from LV long axis M-mode echocardiograms. RESULTS: LAD, LVDd, LVEDV, and ALAM showed a positive correlation with plasma levels of ANP and BNP. EF, the E/A ratio, and MLRe showed a negative correlation with plasma levels of ANP and BNP. Changes in ALAM and plasma levels of ANP during hemodialysis were larger in the subgroup of ALAM < or = 0.55 cm before hemodialysis than in the subgroup of ALAM < 0.55 cm before hemodialysis. CONCLUSION: These results indicate that the left ventricular long axis index can detect a disorder of left ventricular diastolic function, and that a hemodialysis patient whose ALAM before hemodialysis is < 0.55 cm is dialyzed with good volume control conditions.

Adult↗
PubMed2000

Alterations and hypermethylation of the p14(ARF) gene in gastric cancer.

p14(ARF), generated through an alternative splicing process that replaces the first exon, 1alpha, of p16(INK4a) with exon 1beta, located >15 kb upstream of exon 1alpha, has been shown to function as a growth suppressor. We examined 11 gastric cancer cell lines for mRNA expression, homozygous deletion, mutation, and promoter methylation of the p14(ARF) gene. No mRNA expression was detected in 5 of the 7 diffuse-type cell lines. All intestinal cell lines displayed normal levels of expression except for one with a low level of expression. Of the 5 cell lines without expression, 3 (MKN45, NUGC-2, and NUGC-4) and 1 (KATO III) displayed homozygous deletion and methylation of the p14(ARF) gene, respectively. No mutation was found in the whole coding region of the p14(ARF) gene in 8 cell lines without homozygous deletion. Our results indicate that the p14(ARF) gene is more frequently inactivated by homozygous deletion or methylation in diffuse-type gastric cancer cell lines (5/7, 71.4%) than in intestinal ones (0/4, P = 0.022). When we also analyzed 62 primary gastric cancers for the methylation status of the p14(ARF) promoter region, the methylation frequency tended to be higher in diffuse-type gastric cancers (15/33, 45.5%) than in intestinal ones (7/28, 25%). Thus, p14(ARF) alterations might be involved in diffuse-type gastric carcinogenesis.

Carrier Proteins↗
PubMed2000

Metabolic activation of the proestrogens trans-stilbene and trans-stilbene oxide by rat liver microsomes.

A liver microsome-mediated activation of the proestrogens trans-stilbene and trans-stilbene oxide was found in this study. trans-Stilbene and trans-stilbene oxide were negative in estrogen reporter assay using estrogen-responsive human breast cancer cell line MCF-7 and growth assay in rat pituitary tumor cell line MtT/E-2. However, these compounds exhibited estrogenic activity after incubation with liver microsomes of 3-methylcholanthrene-treated rats in the presence of NADPH. In contrast, cis-stilbene and cis-stilbene oxide did not show estrogenic activity after such incubation. When trans-stilbene was incubated with the liver microsomes of 3-methylcholanthrene-treated rats in the presence of NADPH, two metabolites were detected by HPLC. They were identified unequivocally as trans-4-hydroxystilbene and trans-4, 4'-dihydroxystilbene by mass and UV spectral comparison with authentic samples. The oxidase activity of the liver microsomes toward trans-stilbene was inhibited by SKF 525-A and alpha -naphthoflavone. Minor activity was observed when liver microsomes of untreated or phenobarbital-treated rats were used instead of those from 3-methylcholanthrene-treated rats. trans-4-Hydroxystilbene and trans-4,4'-dihydroxystilbene exhibited significant estrogenic activities. These results suggest that the estrogenic activities of trans-stilbene and trans-stilbene oxide were due to formation of hydroxylated metabolites.

Animals↗
PubMed2000

Distinction of differentiated type early gastric carcinoma with gastric type mucin expression.

BACKGROUND: Intestinal and diffuse gastric carcinomas differ in morphology and growth behavior. Differentiated type gastric carcinoma (DGC), which corresponds roughly with the intestinal type of Lauren, can demonstrate phenotypic properties associated with mucin expression and brush border. However, their clinical significance is controversial. A classification based on mucin phenotype and brush border was performed to determine the clinicopathologic diversity of DGCs in their early stage. METHODS: A total of 120 specimens from 116 DGC patients with definite submucosal invasion were evaluated both macroscopically and histologically. All sections were examined immunohistochemically with human gastric mucin, Muc-2, and CD10 and with mucin histochemically with paradoxical concanavalin A staining and high iron Diamine-Alcian Blue. They were classified into gastric type (G-type), intestinal type (I-type), mixed gastric and intestinal type (M-type), or null type (N-type) phenotypes. The immunoreactivity of E-cadherin and beta-catenin also was investigated to determine the correlation between mucin phenotype and clinicopathologic factors. RESULTS: The G-type phenotype was found to be in contrast to I-type: G-type was an independent factor associated with lymph node metastasis. Significant correlations were observed between the G-type phenotype and the complex type carcinoma found that was histologically: lymphatic invasion, lymph node metastasis, and the abnormal expression of E-cadherin. A significant difference in the proportion of mucin phenotypes between papillary type and tubular type carcinoma was observed. G-type was found to be the predominant phenotype in papillary carcinoma in contrast to tubular carcinoma. CONCLUSIONS: The G-type mucin phenotype and papillary adenocarcinoma should be distinguished from other types of DGCs because of their increased malignant potential in the incipient phase of invasion and metastasis. The significance of G-type and papillary adenocarcinoma should be reflected in the treatment of patients with early stage DGCs, including endoscopic mucosal resection.

Adenocarcinoma↗
PubMed2000

Quantification of telomerase activity in sporadic colorectal carcinoma: association with tumor growth and venous invasion.

BACKGROUND: Activation of telomerase, a ribonucleoprotein enzyme complex that synthesizes telomere repeats, is associated with acquisition of unlimited cellular proliferation and is commonly detected in human cancer. Measurement of telomerase activity (TA) may provide important information as a diagnostic marker or a prognostic indicator. The authors studied the quantification of TA and assessed its utility as a prognostic marker in sporadic colorectal carcinoma. METHODS: Sixty surgical specimens, including 30 specimens of cancer tissue and 30 specimens of corresponding normal colorectal mucosa, were examined. TA was measured by a fluorescence-based telomeric repeat amplification protocol assay. The authors determined the telomerase index (TI = log (A-B), where A represented TA of cancer tissues and B represented TA of normal mucosa) and examined the relation between TI and clinicopathologic factors using the Student t test, analysis of variance, the Chi-square test, and the Fisher PLSD as a post hoc test. RESULTS: TA of cancer and corresponding normal mucosa was 51.87+/-27.38 and 7.14+/-9.85, respectively (P<0.0001). The cutoff value was determined to be 26 in a receiver operating characteristic study, with 90% sensitivity, 96.7% specificity, and 96.4% positive predictive value. TI was closely correlated with depth of invasion (P = 0.0129) but not with age, gender, histologic type, location, lymph node metastasis, lymphatic infiltration, or Dukes stage. There was a significant difference in TI between tumors with and without venous invasion (P = 0.0003). Four of five tumors with synchronous liver metastasis showed high TI (1.555 <TI). CONCLUSIONS: High TI may be a risk factor for metastasis of colorectal carcinoma to the liver.

Adenocarcinoma↗
PubMed2000

Immunohistochemical study of MUC1 mucin in premalignant oral lesions and oral squamous cell carcinoma: association with disease progression, mode of invasion, and lymph node metastasis.

BACKGROUND: MUC1 mucin is a transmembrane, mucin-like glycoprotein encoded by the MUC1 gene. Although MUC1 expression has been identified in a variety of neoplastic tissues, to the authors' knowledge, few studies have examined MUC1 expression in premalignant and malignant oral lesions. METHODS: A total of 36 specimens of oral epithelial dysplasia, 12 carcinoma in situ (CIS) specimens and 77 specimens of oral squamous cell carcinoma (OSCC), were examined by both light and electron microscopy using immunohistochemical staining of MUC1 mucin. Relations between staining patterns and clinicopathologic findings also were examined. RESULTS: Distinct membrane MUC1 mucin staining patterns were identified in epithelial dysplasia (33.0%), CIS (50.0%), and OSCC (59.7%) cases. A predominantly cytoplasmic staining pattern was detected in epithelial dysplasia (5.6%), CIS (41.7%), and OSCC (32.5%) cases. Significant positive correlations were found between MUC1 mucin membranous immunoreactivity and disease progression from epithelial dysplasia to OSCC (P < 0.01), mode of tumor invasion (P < 0.02), and lymph node metastasis (P < 0.01). Furthermore, the malignant transformation of oral epithelium, tumor invasion, and tumor metastasis were associated with higher MUC1 mucin expression in the cytoplasm (P < 0.01). In addition to the usual cell surface expression, cytoplasmic expression of MUC1 mucin was confirmed by colloidal gold labeling with transmission electron microscopy. CONCLUSIONS: The results of the current study suggest that determination of MUC1 mucin expression may be a parameter in the diagnosis of premalignant and malignant lesions arising in the oral cavity and that this expression may affect the malignant behavior of OSCC. MUC1 mucin expression may be a useful diagnostic marker for prediction of the invasive/metastatic potential of OSCC.

Carcinoma, Squamous Cell↗
PubMed2000

Methylation of the hMLH1 promoter in familial gastric cancer with microsatellite instability.

Microsatellite instability (MSI), which is recognized as an important mechanism in tumorigenesis, has been reported in familial gastric cancers (FGC). However, genetic defects responsible for this phenotype, that is, mutations in mismatch-repair genes such as hMLH1 and hMSH2, have not been detected in most FGC cases. Earlier studies have shown that the promoter region of the hMLH1 gene was methylated in some sporadic colorectal and endometrial cancers. To determine how FGC acquire MSI, we examined the MSI status, hMLH1-protein expression and methylation status of the hMLH1-promoter region in FGC cases. Out of 9 cancers, 6 from 8 FGC kindreds showed MSI at one or more loci; no germline mutations in the hMLH1 or hMSH2 genes were detected; 4 cancers exhibiting MSI displayed aberrant hMLH1 expression: complete loss in one, decreased level in another, and partially staining pattern in the remaining 2. Methylation in the hMLH1-promoter region was found in these 4 cases. In contrast, the cancers displaying hMLH1-protein expression were not methylated in the hMLH1-promoter region. Our data show a significant association between the absence of hMLH1 expression and methylation of its promoter in FGC cases with MSI. This suggests that the mechanism of inactivation of hMLH1 is epigenetic and that there are other genes responsible for FGC.

Adaptor Proteins, Signal Transducing↗