Biomedical subjects

H Sugimura

Publications and source records attributed to H Sugimura.

At least 37 records · Page 2Linked to original sources

PubMed1993

Identification of protein-tyrosine kinase genes preferentially expressed in embryo stomach and gastric cancer.

For identification of the protein-tyrosine kinases that are expressed in embryo stomach and gastric cancer, a 16-day rat embryo stomach and two human gastric cancer cDNA expression libraries were screened with an anti-phosphotyrosine antibody. Eight cDNAs encoding protein-tyrosine kinase were isolated, and Northern blot analysis revealed that five out of eight clones were highly expressed in rat embryo stomach, but not in adult rat stomach. From nucleotide sequence analysis, these five cDNAs were identified as elk, erk, esk, TTK and fyn, respectively. We report here that the expression levels of two families of receptor type tyrosine kinase genes, elk/erk and esk/TTK are developmentally regulated in rat stomach and highly expressed in human gastric cancer tissues. These findings suggest that elk/erk and esk/TTK genes play important roles in embryonic development and carcinogenesis of the stomach.

Adenocarcinoma↗

PubMed1993

Over-expression of HOX-8, the human homologue of the mouse Hox-8 homeobox gene, in human tumors.

A human ovarian yolk sac tumor cDNA library was screened for homeobox genes with an oligonucleotide probe under low stringent condition. Three homeobox genes were isolated, two of which were identified as HHO.c1 and HB24. The third was highly homologous with the mouse Hox-8 gene and was designated as HOX-8. Studies on RNAs from 25 human tumor tissues and cell lines showed that the profile of HOX-8 expression was different from those of HHO.c1 and HB24. The expression of HOX-8 was not detected in hematopoietic tumor cells, in which HHO.c1 and HB24 were highly expressed. HOX-8 was expressed at higher levels in a variety of tumors of epithelial origin than in their corresponding normal tissues more frequently than HHO.c1 and HB24. All three homeobox genes were highly expressed in a yolk sac tumor, an immature tumor of gonadal origin. These results suggest that HOX-8 plays a more important role in human tumors of epithelial origin than those of hematopoietic origin.

Animals↗

PubMed1993

Overexpression of p53 as a possible prognostic factor in human thyroid carcinoma.

A total of 110 cases of thyroid carcinomas were examined immunohistochemically to evaluate the overexpression of mutant forms of p53 protein in the light of their relationship with their histological subtypes. A polyclonal antibody, CM-1, was applied to the routine formalin-fixed, paraffin-embedded tissues for this survey. Overall, immunohistochemically detected p53 expression confined to the nucleus was identified in 22.7% of the thyroid carcinomas. A significant difference in the positivity of p53 among histological subtypes was noted; the positivity was 11.1% of the cases in well-differentiated papillary carcinoma, 14.3% in well-differentiated follicular carcinoma, 40.9% in poorly differentiated carcinoma, and 63.6% in undifferentiated carcinoma. No immunohistochemical positivity was found in adjacent non-neoplastic tissues or in benign lesions, including follicular adenoma, adenomatous goiter, and chronic thyroiditis. These results suggest that overexpression of p53 is not a responsible factor for the oncogenesis itself, but rather that it plays a crucial role in aggressive subtypes of thyroid carcinomas. Additionally, the distinct entity of poorly differentiated carcinoma, previously categorized in the well-differentiated carcinoma under the name of papillary or follicular carcinoma, was statistically confirmed.

Carcinoma↗

PubMed1992

Cytochrome P450IIE1 genetic polymorphisms, racial variation, and lung cancer risk.

Cytochrome P450IIE1 is responsible for the activation of carcinogenic N-nitrosamines, benzene, urethane, and other low-molecular-weight compounds. Restriction fragment length polymorphisms (PstI and RsaI restriction enzymes) have been identified in the cytochrome P450IIE1 transcription regulatory region that may affect expression. This study describes the PstI and RsaI polymorphisms in different racial populations and in a case-control study of lung cancer. The allelic frequencies were markedly different in Japanese, African-Americans, and Caucasians: the PstI rare allele was present at a frequency of 2% in Caucasians, 5% in African-Americans, and 24% in Japanese (P < 0.05). For the RsaI rare allele, frequencies were 2% in Caucasians, 2% in African-Americans, and 27% in Japanese (P < 0.05). The assay was also applied to 128 individuals enrolled in a case-control study of lung cancer. Although limited in statistical power, the data indicate no evidence for an association in the aggregate of cytochrome P450IIE1 PstI [for which the odds ratio was 0.7 (95% confidence interval (C.I.) = 0.2-2.8)] or RsaI [for which the odds ratio was 0.9 (95% C.I. = 0.2-5.4)] restriction fragment length polymorphisms with lung cancer in this U.S. population. When analyzed by race, the lung cancer odds ratio for the PstI mutant allele in African-Americans was 0.19 (95% C.I. = 0.03-1.38), and in Caucasians it was 4.13 (95% C.I. = 0.34-48.8). For the RsaI mutant allele, the odds ratios were 0.20 (95% C.I. = 0.02-2.43) and 4.28 (95% C.I. = 0.35-50.6), respectively. The ethnic differences of these restriction fragment length polymorphisms might be related to genetic susceptibilities for lung cancer among Caucasians and for gastric or esophageal cancer among Japanese.

Alleles↗

PubMed1992

Evaluation of an oleic acid water-in-oil-in-water-type multiple emulsion as potential drug carrier via the enteral route.

A water-in-oil-in-water (W/O/W) emulsion composed of oleic acid was used as a carrier of carboxyfluorescein (CF) via the enteral route, as a model for future drug transport. The absorption of CF in the small intestine of rats given the emulsion (W/O/W group) was compared with the absorption in a group administered CF alone (CF group), and a group administered a mixed micelle of oleic acid and a surface-active agent in CF solution (MM group). Higher amounts of CF were absorbed in the W/O/W and MM groups than in the CF group. At 120 min, the amount of CF remaining in the intestinal tract was smaller in the MM group than in the W/O/W group. In the early period, CF excretion into bile was higher in the MM group than in the W/O/W group, but from 120 to 360 min, CF excretion in the W/O/W group was higher than in the MM group (non-specific). The blood CF level was significantly higher at 240 and 360 min in the W/O/W group than in the other two groups. The highest concentration in lymph was found in the W/O/W group. The W/O/W emulsion was considered superior to the micelles because it maintained a higher blood level of CF over long periods and transferred it to the lymph. This suggests that the W/O/W emulsion is applicable as a drug carrier via the enteral route.

Administration, Oral↗

PubMed1992

An ultrastructural study of the developing urogenital tract in early human fetuses.

OBJECTIVES: This study examines the gonoducts during the ambisexual stage of human fetal development to define their ultrastructural characteristics, including the origin and antomic relationship of the mesonephric and paramesonephric ducts during gonoductal development. STUDY DESIGN: The reproductive tracts from five fetuses ranging in gestational age from 35 to 45 days were processed for ultrastructural examination. The developing mesonephric ducts, paramesonephric ducts, and their surrounding mesenchyme were studied with a Phillips 300 transmission electron microscope. RESULTS: The mesonephric ducts and paramesonephric ducts have distinctive cytoplasmic and cell surface ultrastructural characteristics, as well as different morphologic patterns of epithelial-mesenchymal interaction. Cephalad portions of mesonephric ducts and paramesonephric ducts are separated by mesenchyme, but more caudal aspects move progressively closer until they are juxtaposed but separate. CONCLUSIONS: Early mesonephric ducts and paramesonephric ducts may be distinguished because of their distinctive ultrastructural features; epithelial-mesenchymal interaction may be important in their differentiation and maintenance; both gonoducts retain their morphologic identity throughout, supporting their separate origins.

Cell Nucleolus↗

PubMed1992

The debrisoquine metabolic phenotype and DNA-based assays: implications of misclassification for the association of lung cancer and the debrisoquine metabolic phenotype.

Debrisoquine is an antihypertensive drug that is metabolized by cytochrome P4502D6. Deficient metabolism is inherited as an autosomal recessive condition. We previously reported in a case-control study that extensive metabolizers of debrisoquine were at greater risk of lung cancer compared to poor and intermediate metabolizers. Cloning of the gene that encodes P4502D6 (CYP2D6) led to the identification of both wild-type and mutant forms of the gene. Subsequently, a DNA-restriction fragment length polymorphism (RFLP) was identified, and a Southern hybridization-based test was developed in an attempt to define the genotype. When the DNA-RFLP test was applied to stored DNA from our study subjects there was neither a significant association with the metabolic phenotype nor an association with lung cancer. Further work has demonstrated that the wild-type gene, which was characterized by a 29-kb allele, can also contain mutations that result in nonfunctional or absent proteins. When these mutations are present, individuals exhibit the poor or intermediate metabolizer phenotype in spite of the presence of the 29-kb putative wild-type allele. Sequence determination of the mutants led to the development of techniques to exploit the polymerase chain reaction, which, together with Southern analysis, have been reported to detect as many as 95% of poor metabolizers. This technique is being used to examine the association of the extensive metabolizer genotype with lung cancer in the subjects from the case-control study. Preliminary results indicate a weak association between the homozygous wild-type genotype and lung cancer; in contrast, the extensive metabolizer phenotype is strongly associated with lung cancer in this subset.(ABSTRACT TRUNCATED AT 250 WORDS)

Case-Control Studies↗

PubMed1992

Polycyclic aromatic hydrocarbon-DNA adducts and the CYP1A1 restriction fragment length polymorphism.

Human cancer risk assessment at a genetic level involves the investigation of carcinogen metabolism and DNA adduct formation. Wide interindividual differences in metabolism result in different DNA adduct levels. For this and other reasons, many laboratories have considered DNA adducts to be a measure of the biologically effective dose of a carcinogen. Techniques for studying DNA adducts using chemically specific assays are becoming available. A modification of the 32P-postlabeling assay for polycyclic aromatic hydrocarbon DNA adducts described here provides potential improvements in quantification. DNA adducts, however, reflect only recent exposure to carcinogens; in contrast, genetic testing for metabolic capacity indicates the extent to which carcinogens can be activated and exert genotoxic effects. Such studies may reflect both separate and integrated risk factors together with DNA adduct levels. A recently described restriction fragment length polymorphism for the CYP1A1, which codes for the cytochrome P450 enzyme primarily responsible for the metabolic activation of carcinogenic polycyclic aromatic hydrocarbons, has been found to be associated with lung cancer risk in a Japanese population. In a subset of individuals enrolled in a U.S. lung cancer case-control study, no association with lung cancer was found.

Blotting, Southern↗

PubMed1992

Relationship of H-ras-1, L-myc, and p53 polymorphisms with lung cancer risk and prognosis.

Proto-oncogenes (H-ras-1 and L-myc) and tumor-suppressor gene (p53) loci have been implicated in lung carcinogenesis. DNA restriction fragment length polymorphisms at these gene loci are being evaluated in a case-control study as markers predictive of risk for cancer or of prognosis when cancer is present. The cases and controls had a cigarette-smoking history of 40 or more pack years or other abnormalities in pulmonary function tests, their ages were closely matched (64 years for cases and 61 years for controls) and the ratio of Caucasians to African Americans was close to unity (cases, 0.95:1.00, controls, 1.00:0.88). The H-ras-1 gene contains an insertion deletion polymorphism. Inheritance of rare H-ras-1 alleles, defined by MspI digestion, confers a relative risk for lung cancer of 2.0 (95% confidence interval, 0.5-7.3) for Caucasians and 3.2 (0.9-11.6) for African Americans (74 cases, 67 controls). The L-myc gene sequence has a restriction site (EcoR1) polymorphism between the second and third exons. Inheritance of restriction site-present alleles was reported to confer poor prognosis (presence of lymph node metastases) in Japanese lung cancer patients. This hypothesis was tested in both case-control study subjects (56 cases, 55 controls) and additional surgical cases (40), but no evidence was found to support the hypothesis in the U.S. population. The p53 gene is a tumor-suppressor gene that can encode either a proline or an arginine in the 72nd residue. No associations was found between the minor allele (proline) and diagnosis of lung cancer (76 cases, 68 controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

PubMed1992

Synthesis of 2'-deoxy and 2',3'-dideoxynucleoside derivatives from thioglycosides.

The synthesis of both 2'-deoxy and 2',3'-dideoxynucleoside derivatives by the reaction of thioglycosides with nucleoside bases was examined. The stereochemical outcome at the anomeric position was found to depend on the protecting groups and the C-3 configuration in the sugar moiety, the kind of activator, and the reaction temperature. Based on these findings, 2'-deoxy-D-xylo nucleoside and 2',3'-dideoxynucleoside derivatives have been synthesized in beta-selective manner.

Deoxyribonucleosides↗

PubMed1992

[Surgery versus detachable balloon embolization of pulmonary arteriovenous fistula: clinical experience].

We experienced 4 pulmonary arteriovenous fistula cases 2 of which were treated surgically and 2 were subjected to detachable balloon embolization therapy. Favorable results were obtained in the detachable balloon embolization therapy. In treating pulmonary arteriovenous fistula, if the lesion is in the position where the catheter can be reached easily and is composed of a single afferent-efferent vessel unit, it would be advisable to perform the embolization therapy first, and then to apply an operative procedure preserving lung tissue as much as possible.

Adult↗

PubMed1991

Racial variation in the distribution of Ha-ras-1 alleles.

Restriction fragment length polymorphism analyses of the Ha-ras-1 proto-oncogene were undertaken in white and black populations residing in the Baltimore-Washington metropolitan area to address whether specific rare alleles of the Ha-ras-1 proto-oncogene locus vary in their distribution among different racial groups. High-molecular-weight genomic DNA samples from the lungs of 80 lung cancer patients and 92 accident victims were digested with appropriate restriction enzymes and subjected to Southern analysis using the 6.6-kb BamHI human Ha-ras-1 recombinant fragment from the plasmid pEC. Thirty allelomorphs of different sizes were detected among the 172 study subjects. An association was observed between race and specific alleles. Rare alleles were more frequent in black cancer patients and trauma victims than in whites. Within each racial category, lung cancer patients had an excess of rare alleles. These data indicate the importance of controlling for racial variation when designing studies to determine human cancer risk factors.

Adult↗

PubMed1991

The histopathology of the liver in older patients with hepatitis B virus surface antigenaemia.

The histopathology of the liver and the detectability of intrahepatic hepatitis B virus (HBV) markers were studied in 34 autopsy cases in elderly patients (mean age 73.9 years, range 60-91 years) who had had a history of positive HBV surface antigenaemia prior to death. Seven of 14 persistent HBV carrier cases (group A) in which long-lasting HBV surface antigen (HBsAg) carriage in the sera had been confirmed by sequential assays, and 5 out of 15 HBV-infected people (group C, single assay) showed significant primary liver damages including chronic hepatitis, toxic hepatitis, liver cirrhosis and hepatocellular carcinoma. In 5 cases (group B), one of which was type B liver cirrhosis, HBsAg became negative and HBsAb appeared during the follow-up period (up to 33 months). Among confirmed HBV carriers, HBsAg and HBV core antigen were most frequently found in the liver of cirrhotic cases with and without hepatocellular carcinoma (5 of 6), whereas these were rarely detected in those with non-specific changes or slight hepatitic activity (1 of 7). All 5 cases in group B were negative for histological HBV-related antigens and the findings in group C were variously interpreted. Post-mortem cases of the aged HBV carriers who survived their mean life expectancy represent an important population in which to study the natural history of HBV carriers.

Aged↗

PubMed1991

Effect of hemodialysis on the concentration of the seven tumor markers carcinoembryonic antigen, alpha-fetoprotein, squamous cell carcinoma-related antigen, neuron-specific enolase, CA 125, CA 19-9 and CA 15-3 in uremic patients.

The incidence of the 7 tumor markers carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), squamous cell carcinoma-related antigen (SCC), neuron-specific enolase (NSE), CA 125, CA 19-9 and CA 15-3 was studied before and after hemodialysis (HD) in 144 uremic patients who had no malignancies. Before HD, of all tumor markers, the mean concentration of SCC only exceeded the normal value. The positive rate was highest in SCC (95.1%), and that of CEA and NSE was 25.7 and 10.6%, respectively. However, AFP was within the normal range in all cases. Among CA antigens, the positive rate of CA 125 was 7.6%, of CA 19-9 was 6.3% and of CA 15-3 was 3.5%. After HD, the incidence as well as the mean concentration of all tumor markers increased. A parallel increment of total protein was observed after HD. The membrane filter used in HD appears to be insufficient to remove tumor marker proteins during HD. It is necessary to consider the clinical interpretation of elevated tumor markers in patients with uremia.

Antigens, Neoplasm↗

PubMed1991

[Effect of short-term administration of medroxyprogesterone acetate on side reactions of combination chemotherapy with ADR, VDS and CDDP in primary lung cancer].

The effect of short-term (10 days) Medroxyprogesterone acetate (MPA) administration on side reactions of combination chemotherapy with ADR, VDS and CDDP for primary lung cancer was studied by comparisons of MPA administration group (20 cases) with non administration group (30 cases). 1) Frequency of vomiting, duration of nausea and body weight loss were significantly improved in MPA administration Group (p less than 0.01). 2) Leukocyte and neutrophil counts in MPA administration group especially 7-10 days after of chemotherapy were maintained higher than these of non administration group (p less than 0.05). 3) Major side effects including thromboembolism in MPA administration group had not been observed. These results indicated that short-term MPA administration was relatively safe and effective in combination chemotherapy including CDDP.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Biochemical and molecular epidemiology of cancer.

Examples of practical approaches to molecular epidemiology of human cancer are described. Biomarkers of carcinogen exposure or inherited host factors for cancer susceptibility are discussed. Major advances have been made in the detection of carcinogenmacromolecular adducts through the use of high performance liquid chromatography, immunoaffinity chromatography, the 32P-postlabeling assay, enzyme immunoassays, gas chromatography/mass spectroscopy and synchronous spectrophotofluorimetry. The polycyclic aromatic hydrocarbon-DNA adducts are the most extensively studied in this field and together with antibodies to these adducts found in human serum, they have become useful indicators of exposure to carcinogens. Assays for various kinds of alkyl-DNA adducts have also been developed and the presence of these adducts have been documented in human tissues. Carcinogen-protein adducts have proven to be useful molecular dosimeters of carcinogen exposure. For example, 4-aminobiphenyl hemoglobin adducts are highly correlated with exposure to tobacco smoke. The study of the molecular aspects of interindividual differences in the metabolism and activation of xenobiotics and other genetic markers [DNA-restriction fragment length polymorphisms (RFLPs), mutations, and functional loss of specific genes in carcinogenesis] is an emerging new field that is discussed in the context of genetic susceptibility to cancer. The cytochrome P450 phenotypes and acetylation phenotype are examples of genetic markers that indicate an individual's potential for metabolism of exogenous substances. Further, inherited genetic polymorphic markers, e.g., DNA-RFLPs at protooncogene loci (HRAS-1 and L-myc) have been examined in a case-control study of lung cancer. Data concerning mutations of protooncogenes (H-, K-, and N-RAS) and tumor suppressor genes (retinoblastoma and p53 genes) in various common cancers are providing evidence of multiple genetic lesions that occur during the multistage process of carcinogenesis.

Biomarkers↗

PubMed1990

Restriction fragment length polymorphism analysis of the L-myc gene locus in a case-control study of lung cancer.

The L-myc DNA-restriction fragment length polymorphism, revealed by EcoRI, has been studied in both a lung cancer case-control framework and a cohort of 40 non-diseased unrelated individuals. No association was found between the L-myc allelic frequencies and disease status, tumor stage or lung cancer histology. A strong association was, however, observed between the L-myc allelic frequencies and ethnic origin (black or white) of the subjects. Among American whites the allelic distribution at the L-myc proto-oncogene locus was almost identical to that previously reported for Japanese subjects. Among the American black population there was a significantly higher frequency of the presence of the polymorphic EcoRI restriction site in the second intron of the L-myc proto-oncogene. These data emphasize the importance of conducting epidemiologic studies that control for ethnic factors and indicate that L-myc EcoRI allelotypes do not appear to be predictive of lung cancer risk or disease status in American blacks and whites.

Alleles↗

PubMed1990

Association of rare alleles of the Harvey ras protooncogene locus with lung cancer.

The hypothesis that rare variable nucleotide tandem repeat alleles of the Ha-ras-1 polymorphism are an inherited predisposing factor in human lung carcinogenesis has been evaluated in an age, race, and smoking matched case-control study. Twenty-three different alleles were identified by their restriction fragment length in DNA isolated from peripheral blood lymphocytes and were categorized into three groups: common; intermediate; and rare. The frequencies of rare alleles in blacks with either squamous cell carcinoma, large cell carcinoma, or small cell carcinoma were found to be significantly higher than those among groups of control subjects that were comprised of chronic obstructive pulmonary disease patients and patients with cancer at sites other than the lung. A similar trend which did not reach statistical significance was observed in whites. These data are consistent with the hypothesis that inheritance of Ha-ras-1 rare restriction fragment length alleles represents a genetic risk factor for some human lung cancers. The biological basis of this observation remains to be clarified, and it is possible that ethnic variations in rare allele frequencies are responsible for the differences noted. However, the data suggest that further evaluation of the Ha-ras-1 polymorphism as a marker of individual lung cancer susceptibility is warranted.

Adenocarcinoma↗