Biomedical subjects

H Sugimura

Publications and source records attributed to H Sugimura.

At least 73 records · Page 4Linked to original sources

PubMed1994

Overexpression of ERK, an EPH family receptor protein tyrosine kinase, in various human tumors.

The ERK gene has been isolated as a genomic DNA encoding a part of the receptor protein-tyrosine kinase which belongs to the EPH subfamily. We previously identified a partial complementary DNA (cDNA) encompassing the catalytic domain of ERK from the expression library of human gastric cancer with an antiphosphotyrosine antibody. Using this cDNA as a probe, the cDNAs encoding mature ERK protein were isolated. The putative mature ERK protein, a total of 967 deduced amino acid residues, showed high homology with chicken Cek5 (92.5%) and mouse Nuk (99.1%). Chromosomal in situ hybridization revealed that human ERK cDNA is localized to chromosome 1p34-35. In Northern blot analysis of normal human tissues, the ERK gene was ubiquitously expressed mainly in cells of epithelial origin but not in the brain. Studies on RNAs from 76 human tumor tissues and cell lines showed that ERK is expressed at higher levels in various tumors of epithelial origin than in corresponding normal tissues, most frequently in gastric cancers (12 of 16, 75.0%). Overexpression of ERK was also detected in one osteosarcoma cell line. These findings suggest that ERK plays some significant role in carcinogenesis in the stomach and other tissues.

Amino Acid Sequence↗

PubMed1994

Isolation of complementary DNA encoding K-cadherin, a novel rat cadherin preferentially expressed in fetal kidney and kidney carcinoma.

Complementary DNA for a novel member of the cadherin family, designated K-cadherin, was isolated from a rat renal cell carcinoma complementary DNA library by screening it with a short complementary DNA probe which was initially obtained from the RNA of day 16 fetal Wistar rat stomach mucosa by the polymerase chain reaction. The deduced primary structure of K-cadherin is 789 amino acid residues, which contain five internal repeats in its extracellular domain, a single putative transmembrane domain, and a cytoplasmic tail characteristic of those of classic type cadherins. K-cadherin exhibits low homology with mature proteins of mouse N- (38%), E- (35%), and P-cadherin (32%), and high homology with a partially identified human cadherin-6 protein (95%) at the amino acid level. Northern blot analysis revealed a high level of expression of K-cadherin mRNA in fetal rat kidney and brain, and rat kidney carcinoma with two major transcripts, 4.1 and 8.0 kilobases in size, whereas there was very weak or no expression in any organ of adult rats. The level of K-cadherin expression was also elevated in some human kidney cancer tissues. In the developing kidney, in situ hybridization showed localization of K-cadherin mRNA in the nephroblastic epithelial cells of comma bodies coinciding with those in the process of polarization during glomeruloneogenesis. These results demonstrate that K-cadherin must have important functions in both the process of kidney development and tumorigenesis of some types of kidney cancer.

Amino Acid Sequence↗

PubMed1994

Mapping of the human C3G gene coding a guanine nucleotide releasing protein for Ras family to 9q34.3 by fluorescence in situ hybridization.

C3G, a human guanine nucleotide releasing protein for Ras protein, was mapped to human chromosome 9q34.3 by fluorescence in situ hybridization with R-banded chromosomes. C3G was originally identified as one of the CRK-binding proteins, similar to c-abl (9q34.1). Our result suggests that the downstream factors of Crk are localized in close proximity on chromosome 9.

Chromosome Banding↗

PubMed1994

Magnetic resonance imaging of bone marrow changes after irradiation.

RATIONALE AND OBJECTIVES: Signal changes of irradiated bone marrow are thought to represent fatty change. However, more recent studies have indicated that other factors may contribute to these signal changes. We performed animal studies to investigate magnetic resonance (MR) signal change factors in correlation with histologic findings. MATERIALS AND METHODS: Forty-two male Wistar rats were given single doses (3, 8, and 20 Gy) of irradiation. Magnetic resonance imaging (1.5 T) was performed using spin-echo technique. RESULTS: In the acute phase (days 1-3), the T1 time was prolonged, probably secondary to decreased cellularity and edema. After this phase, the irradiated marrow showed marked T1 and T2 shortening that correlated with hemorrhage. In the chronic phase (after day 10), fatty replacement, fibrosis, and regeneration were observed. T2 times were stable in spite of regeneration because of the susceptibility effect of hemosiderin. CONCLUSION: The MR signal changes of irradiated marrow reflect not only fatty replacement, but hemorrhage as well.

Animals↗

PubMed1994

Stepwise participation of p53 gene mutation during dedifferentiation of human thyroid carcinomas.

The spectrum of p53 gene mutations was investigated in thyroid carcinomas with respect to histopathological classification. In all histological subtypes of thyroid carcinoma that had previously revealed positivity in immunohistochemical staining for p53 protein, single-stranded conformation polymorphism analysis and direct sequencing were performed to detect point mutations between exons 5 and 8. In well differentiated papillary and follicular carcinomas, in which we had already known that 11.1 and 14.3% of the cases, respectively, revealed p53 overexpression as determined by immunohistochemistry, genetic aberrations were undetectable. In poorly differentiated carcinoma, in which 40.9% had revealed overexpression, two of six cases revealed point mutations at codon 244 in exon 7 and at codon 278 in exon 8. In undifferentiated carcinoma, in which 63.6% had revealed overexpression, four of six cases examined showed point mutations at codon 157 in exon 5, at codon 248 in exon 7, and at codon 273 and a two-base insertion between codons 266 and 267 in exon 8. These results strongly suggest the crucial role of p53 gene aberration and protein overexpression in a biologically aggressive subtype, possibly as a stepwise participation in the process of tumor dedifferentiation in human thyroid carcinomas.

Amino Acid Sequence↗

PubMed1994

Benign schwannoma of the esophagus: report of two cases with immunohistochemical and ultrastructural studies.

Two cases of benign schwannoma of the esophagus are presented. The tumors were found in the thoracic esophagus of women of 56 and 64 years of age, respectively, who had complained of dysphagia and back pain. Tumorectomies were performed and the tumors were found to be located within the esophageal wall arising from the muscularis propria. The tumors were examined immunohistochemically and ultrastructurally. These tumors were identical in gross, histological and electron microscopic features. Grossly, the tumors showed yellowish-white cut surfaces without hemorrhage or necrosis. Microscopically, they were composed of spindle-shaped cells showing moderate variation in size and shape, and nuclear palisading. Lymphoid aggregates with germinal centers surrounded the tumors. Immunohistochemically, strong reactions for S-100 protein and neuron-specific enolase were observed in the cytoplasm of spindle cells, whereas reactions for muscle actin and desmin were negative. These findings, together with electron microscopic observations, supported the Schwann cell origin of these tumors.

Esophageal Neoplasms↗

PubMed1994

Alteration of immunoreactivity by hydrated autoclaving, microwave treatment, and simple heating of paraffin-embedded tissue sections.

The effects of treatment in a hydrated autoclave (121 degrees C, 2 atm for 20 min), microwave oven (in water), and simple heating (60 degrees C overnight in distilled water or 90 degrees C for 10 min in ZnSO4) on the stainability of 56 antigens by commercially available antibodies in formalin-fixed paraffin-embedded tissue sections were evaluated. The detectability of nuclear antigens, glycoprotein, lymphocytic surface markers, and chromogranin A was significantly and reproducibly improved by these treatments, whereas the detectability of viral antigens and peptide hormones was attenuated or unchanged. This enhancement includes not only the distinctiveness of the positive staining, but also the number of positive cells, as revealed by comparing serial sections. Among these four heating procedures, microwave heating and autoclaving were more effective than the others on p53, c-erbB-2, and CA125, whereas simple heating was best for smooth-muscle actin (HHF35 and CGA7). Generally the effects of the heating procedures for these antigens were consistent among the cases, but the effects on GFAP varied with the case. The alterations we observed could significantly influence the interpretation of immunohistochemical staining of currently popular tumor markers such as p53 in terms of their prevalence (28% vs 64% in gastric cancer; 36% vs 82% in metastatic liver cancer) and other diagnostically important markers.

Antigen-Antibody Reactions↗

PubMed1994

Cytochrome P-450 lA1 genotype in lung cancer patients and controls in Rio de Janeiro, Brazil.

Mspl restriction fragment length polymorphism in cytochrome P-450 IA1 (CypIA1) gene, which has been associated with lung cancer susceptibility in Japanese, was studied in persons from Rio de Janeiro, in the framework of a hospital-based, age, race (black or nonblack), and gender-matched case-control study (n = 222; 110 cases and 112 controls). Contrary to the hypothesis, there was no difference in the frequency of the C genotype (Mspl site-present homozygous), even after racial breakdown. There were no significant differences between cases and controls when categorized according to tobacco consumption. The lifetime quantity of tobacco smoked was not different among lung cancer patients with three different genotypes (A, Mspl site-absent, homozygous; B, heterozygote; and C). The background frequency of the Mspl polymorphism C genotype is a little less than 10%, similar to that of the Japanese healthy population. The CyplA1 Mspl polymorphism itself does not seem to be related to susceptibility to bronchial carcinogenesis in this area.

Adult↗

PubMed1994

Analysis of cytochrome P450 2E1 genetic polymorphisms in relation to human lung cancer.

Human cancer risk assessment using molecular genetic techniques is a rapidly emerging field. Many studies suggest that both inherited and acquired genetic predispositions play an important role in carcinogenesis. Cytochrome P450 (CYP) 2E1 is involved in the metabolic activation of N-nitrosamines and other low molecular weight compounds. A recently described genetic polymorphism of CYP2E1 [DraI restriction fragment length polymorphism (RFLP)] has been associated with an increased risk of lung cancer in Japanese. We have assessed the allelic frequency of three RFLPs (PstI, RsaI, and DraI) in African-Americans (n = 109), Caucasian Americans (n = 153), and octogenarian Japanese (n = 42), and also in a United States case-control study of lung cancer (histologically confirmed lung cancer, n = 58; controls, n = 56; total, n = 114). The relationship of the CYP2E1 DraI polymorphism to other CYP2E1 polymorphisms (PstI and RsaI RFLP) was examined. The allelic frequency of the DraI C minor allele for all subjects was 0.09 in Caucasians, 0.09 in African-Americans, and 0.31 in Japanese. In the case-control study of lung cancer, no association of the CYP2E1 DraI genotype with lung cancer was found (odds ratio, 1.57; 95% confidence interval, 0.59-4.18). Comparison after discordant CYP2E1 genotypes suggests the presence of different haplotypes in Americans and Japanese. These results indicate that the CYP2E1 DraI RFLP is probably not a cancer risk factor in United States Caucasian or African-Americans, although statistical power is limited given the low frequency of the CYP2E1 DraI C minor alleles.

Aged↗

PubMed1993

Germ-line p53 mutation is uncommon in patients with triple primary cancers.

We examined five patients with multiple primary cancers who had a history of three different types of primary cancers for germ-line p53 mutations. The germ-line p53 mutation was detected in a patient who conformed to the Li-Fraumeni syndrome, but not in the other four patients. The diagnosis of these four patients did not fall in the category of Li-Fraumeni syndrome. This result indicates that germ-line p53 mutations are uncommon even in patients with triple primary cancers.

Female↗

PubMed1993

Effects of pituitary adenylate cyclase activating polypeptide (PACAP) on the cardiovascular system.

The effects of pituitary adenylate cyclase activating polypeptide (PACAP) on the cardiovascular system were examined. When PACAP-38 (270 or 420 pmol/kg body weight) was administered intravenously to the anesthetized dogs, both mean arterial pressure and left ventricular systolic pressure increased within 2 min after a temporal depression. Pulmonary arterial systolic pressure increased promptly. These hemodynamic values and heart rates (HR) 5 min after injection were significantly higher than the corresponding values in physiological saline injected dogs, and some effects were still sustained over 15 min. Cardiac output and stroke volume also increased and the values at 5 min were significantly higher than those in controls. The high dose of PACAP-38 (420 pmol/kg) evoked greater responses than those induced by the low dose (270 pmol/kg). Plasma adrenaline, but neither noradrenaline nor dopamine concentration significantly increased 15 min after injection of 420 pmol/kg PACAP-38. Moreover, PACAP-38 clearly stimulated cyclic AMP production in rat cardiac myocytes with EC50 of 1.5 x 10(-9) M and plasma cAMP levels significantly and dose-dependently increased in dogs 5 min after administration. These results first demonstrated that PACAP has inotropic and chronotropic actions on the heart possibly by a direct stimulation of adenylate cyclase in cardiac myocytes and also that the cardiovascular functions may be possibly modified by an evoked adrenaline secretion in vivo.

Animals↗

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

Acute renal failure after exercise in a child with renal hypouricaemia.

We describe a 12-year-old boy with renal hypouricaemia who presented with acute renal failure after a 6-h sports training session. Back and loin pain were noted at presentation. Although serum creatinine and blood urea nitrogen were elevated, the serum uric acid concentration was normal (2.6 mg/dl). This decreased to 0.3 mg/dl after recovery. The pyrazinamide and probenecid tests revealed that the cause of renal hypouricaemia in this patient was totally defective uric acid reabsorption. Acute renal failure after exercise is a rare but serious complication in paediatric patients with renal hypouricaemia.

Acute Kidney Injury↗

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↗

PubMed1993

Possible association of p53 overexpression and mutation with high-grade chondrosarcoma.

Overexpression and point mutation of the p53 protein/gene was investigated in a series of chondrosarcoma by an immunohistochemical approach, and direct sequencing of the genomic DNA, respectively. In 2 of the 16 cases studied, both of which were high grade chondrosarcomas (grade III), immunodetectable p53 was identified. Histologically, one was ordinary type and the other a clear cell variant. However, no positivity was observed in the other cases including nine of low grade, ordinary type, three of low grade, clear cell type, and two of extraskeletal myxoid chondrosarcoma. Direct sequencing, following polymerase chain reaction amplification of exons 5-9 of the p53 gene in 14 cases, in which fresh materials were available, successfully demonstrated base substitution mutations in only two cases with detectable p53 overexpression on immunohistochemistry. Their details were GTC (valine) to TTC (phenylalanine) at codon 157 in exon 5, and CGT (arginine) to CAT (histidine) at codon 273 in exon 8. No mutation was detected in the other 12 cases which were negative for p53 immunostaining. These findings strongly suggest that p53 mutation plays a crucial role in the biologically aggressive subtype, and possibly in the process of tumor progression in human chondrosarcoma.

Adult↗

PubMed1993

Stereocontrolled synthesis of beta-2'-deoxy and 2',3'-dideoxynucleosides by intramolecular glycosylation.

Intramolecular glycosylation of phenyl 3-O-benzyl-2-deoxy-5-O-(4-methoxy-2-pyrimidyl)-1-thio-D-ribofuranoside and 2,3-dideoxy-5-O-(4-methoxy-2-pyrimidyl)-1-thio-D-glycero-pentofuranos ide by activation with dimethyl(methylthio)-sulfonium tetrafluoroborate followed by hydrolysis gave the corresponding beta-2'-deoxy and beta-2',3'-dideoxypyrimidine nucleoside derivatives respectively in good yields.

Deoxyribonucleosides↗

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↗