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Biomedical subjects

M Yamauchi

Publications and source records attributed to M Yamauchi.

At least 253 records · Page 14Linked to original sources
PubMed1994

Association between restriction fragment length polymorphism of the human cytochrome P450IIE1 gene and susceptibility to alcoholic liver cirrhosis.

OBJECTIVES: Cytochrome P450IIE1 (P450IIE1) is involved in ethanol metabolism and in the metabolic activation of carcinogenic nitrosoamines. The purpose of our investigation was to determine whether P450IIE1 restriction fragment length polymorphisms (RFLP) were associated with the development of alcoholic cirrhosis in Japanese alcoholics. METHODS: We determined the human P450IIE1 RFLP with the restriction endonucleases, RsaI and PstI, using the polymerase chain reaction (PCR) on lymphocytes from 82 male Japanese alcoholics. Twenty patients had alcoholic fatty liver or nonspecific reaction (nonfibrotic group), and 62 had severe hepatic fibrosis or liver cirrhosis (fibrotic group). RESULTS: PCR-RFLP revealed three P450IIE1 genotypes, namely, heterozygotes [type B (c1/c2)] and two homozygotes [types A (c1/c1) and C (c2/c2)]. Homozygotes (c1/c1) were significantly more prevalent in the fibrotic group than in the nonfibrotic group (p < 0.05). CONCLUSIONS: This result suggests that susceptibility to alcoholic liver cirrhosis may be associated with the RsaI and PstI polymorphism of the P450IIE1 gene.

Cytochrome P-450 CYP2E1↗
PubMed1994

[Tissue concentration of tegafur suppository in patients with head and neck cancer--concentration of 5-FU in cancer tissue].

Fifty patients with head and neck cancer were treated with tegafur suppository for 7 days preoperatively. The tissues were obtained during surgical operation and the concentrations of 5-FU in cancer tissue, normal tissue and blood were measured. It was revealed that a high concentration of 5-FU was seen in cancer tissue and then metastatic lymph nodes. The 5-FU concentration in cancer tissue was parallel with T stage of the patients. Subsites which showed a high concentration of 5-FU were nasal-paranasal cavity, tongue and mesopharynx. The tegafur suppository was useful because of the high concentration in cancer tissue and metastatic lymph nodes without any obvious side effects in the head and neck region.

Adult↗
PubMed1994

[An analysis of autopsy cases with cancer of unknown primary site].

A retrospective review of autopsy cases with cancer of clinically unknown primary site seen at Shikoku Cancer Center Hospital from 1959 to 1992 was performed. Fifty three cases (3.1%) were registered as having cancer of unknown primary site among 1690 consecutive autopsy cases with malignancies except for leukemias and brain tumors. Major discrepancies on the primary site between the clinical diagnoses and the autopsy reports were present in 30 cases (1.8%). Twelve cases (0.7%) with malignancy of peritoneum or retroperitoneum primary were found that were clinically regarded as peritonitis carcinomatosa. Latent cancer, in which a new primary cancer was subsequently identified at autopsy, was recognized in 190 cases (11.2%). The mean age in latent cancer group was significantly higher than in control group, but patients with cancer of unknown primary site tended to be somewhat younger. A high male: female ratio was found in latent cancer group, whereas it was reverse in cases with clinically undetermined primary cancer. Survival overall was poor, with a median survival of 5 months. As diagnostic techniques (such as sonography, computerized tomography scanning and nuclear scans) have been improved, cases with cancer of unknown primary site have tended to decrease, but the percentage of cases presenting latent cancer has remained relatively stable over the years. Precise autopsy examination revealed that the primary sites of clinically undetermined cancers were ovary, pancreas, stomach, gallbladder and peritoneum in order of decreasing frequency. The metastatic pattern and histologic types were not different from that in the control group.

Aged↗
PubMed1993

Growth inhibition of human gastrointestinal cancer xenograft lines by treatment with CPT-11 and VP-16.

A water-soluble and stable camptothecin derivative, CPT-11, was found to possess a strong antitumor activity against various murine tumors. In the present study, CPT-11 was tested against ten human gastrointestinal cancer xenograft lines carried by nude mice. CPT-11 was very effective against nine xenograft lines, with the exception of one xenograft. On the other hand, VP-16 was ineffective against all these xenograft lines. Therefore, CPT-11 is expected to be clinically more effective against gastrointestinal cancer than the topo II targeting agent.

Adult↗
PubMed1993

Microdissection and microcloning of genomic DNA markers from human chromosomal region 11q23.

A human genomic DNA library was constructed by using a microdissection-microcloning procedure with polymerase chain reaction (PCR) techniques on DNA from the chromosome 11q23 region. A total of 450 recombinant pUC clones were isolated from the library. Their insert sizes ranged from 150 to 850 bp with a mean of 320 bp. Fifty pUC clones were randomly selected and analyzed in detail. Southern blot analyses showed that 21 (42%) clones were unique DNA sequences, 20 (40%) clones were repetitive sequences, and 9 (18%) clones had no detectable hybridization. The unique sequences were used further in a secondary screening of a partially digested human genomic DNA library constructed in phage vector, and 4 clones were isolated. The chromosomal locations of these phage clones were confirmed to be in the q23 region of chromosome 11 by fluorescence in situ suppression hybridization. These pUC microclones isolated from the chromosomal region-specific genomic DNA library will be useful in the construction of physical contig maps with yeast artificial chromosome and/or cosmid clones and in the positional cloning of disease-associated genes localized to the q23 region of chromosome 11.

Chromosome Mapping↗
PubMed1993

The UDP-galactose translocator gene is mapped to band Xp11.23-p11.22 containing the Wiskott-Aldrich syndrome locus.

We have cloned a segment of the human gene encoding UDP-galactose translocator by genetic complementation of its defective mutant in mouse FM3A cells. Chromosome mapping using fluorescent in situ hybridization revealed that the cloned gene hybridized to the Xp11.23-11.23 region of the X chromosome. This region is shared by the locus of Wiskott-Aldrich syndrome, an X-linked recessive immunodeficiency disorder, characterized by defective sugar chains on cell surface components. Genetic and phenotypic similarities suggest a possible link between UDP-galactose translocator and the Wiskott-Aldrich syndrome (WAS).

Animals↗
PubMed1993

Site comparisons of dentine collagen cross-links from extracted human teeth.

Covalent intermolecular cross-links in collagen provide the dentine matrix with stability and tensile strength. The density of collagen cross-links varies depending on the site within the same tissue. This variation is probably due to factors such as the different amounts of stress and different turnover rates at the respective sites. The aim was to quantify the collagen cross-links in different tooth groups as an adaptation to functional requirements. For this purpose, the types and content of major cross-links in dentine collagen of human teeth from three different sites were measured and compared: incisors, premolar-canines and molars. After removal of cementum and pulp, 23 extracted teeth at different ages (27-69 yr) were individually pulverized and demineralized with EDTA. Collagen was reduced with standardized NaB3H4, hydrolysed, and subjected to amino acid and cross-link analyses. Each cross-link was quantified on the basis of mole per mole of collagen. The results indicated: (1) all teeth contained labile, reducible (dehydro-dihydroxylysinonorleucine and dehydro-hydroxylysinonorleucine) and stable, non-reducible (pyridinoline and its lysyl analogue) cross-links, and (2) the content of both reducible and non-reducible cross-links was least in incisors and greatest in molars. This suggests that dentine collagen matrix maybe functionally adaptive.

Adult↗
PubMed1993

Influence of an intermittent compressive force on matrix protein expression by ROS 17/2.8 cells, with selective stimulation of osteopontin.

The purpose of this study was to determine the response of bone cells to physical stress. Intermittent compressive force (ICF) was applied to 13 kPa to subconfluent ROS 17/2.8 cells at 18 cycles/min. After 48 h of this application, the cells were labelled with [35S]-methionine or [32PO4]. Application of ICF over this time did not alter the synthesis of type I collagen, fibronectin or bone SPARC (osteonectin) compared to that of control cells. However, the activity of alkaline phosphatase was increased 1.5-fold, and the synthesis of a 32PO4-labelled, 75-kDa phosphoprotein, recognized as osteopontin by immunoprecipitation with specific antibodies, was increased 1.4-fold. Also, an increase in osteopontin mRNA starting within 12h of ICF application was observed. The selective increase in osteopontin expression associated with ICF may be important in the remodelling of bone tissues during growth and development and in response to functional forces.

Alkaline Phosphatase↗
PubMed1993

Collagen fibril diameter and its relation to cross-linking of collagen in the skin of patients with amyotrophic lateral sclerosis.

The diameter of collagen fibrils and the age-related, stable cross-link, histidinohydroxylysinonorleucine (HHL), of skin tissue (left biceps) were measured and compared in 11 patients with amyotrophic lateral sclerosis (ALS) and 7 controls. In ALS patients, it was found that (1) the diameter of collagen fibrils and the content of HHL were negatively and significantly associated with the duration of illness (r = -0.74, P < 0.01 and r = -0.72, P < 0.02, respectively), and (2) there was an appreciable positive correlation between the diameter of collagen fibrils and the content of HHL (r = 0.73, P < 0.02). These findings were not observed in controls. These suggest there is a close relationship between the decreased amount of HHL and the small diameter of collagen fibrils in ALS.

Aged↗
PubMed1993

Expression of carcinoembryonic antigen (CEA) and nonspecific crossreacting antigen (NCA) in gastrointestinal cancer; the correlation with degree of differentiation.

In spite of its reputation as a tumour marker, little is known about the function of carcinoembryonic antigen (CEA). We examined the mRNA expression of CEA and NCA in 26 gastric and 14 colorectal cancers together with adjacent morphologically normal mucosae. There was no significant difference between the CEA mRNA levels of colorectal cancer and adjacent mucosa, whereas the CEA mRNA levels were significantly elevated in gastric cancer compared with normal gastric mucosa. The expression of NCA, on the other hand, was more cancer-specific and was significantly up-regulated in both gastric and colorectal cancers compared with the corresponding normal mucosae. No correlation was found between the mRNA level and plasma CEA value. No significant up-regulation was recognised in the node positive cancer, cancer with distant metastasis, or the metastatic tissues themselves. Marked diversity in the degree of differentiation in gastric cancer tissues, however, resulted in varied expression of the CEA gene family, compared with the constantly high expression found in colorectal cancer. Further analysis revealed significant up-regulation of NCA in well and moderately differentiated gastric cancers over poorly differentiated cancers, suggesting that NCA might have roles in differentiation.

Antigens, Neoplasm↗
PubMed1993

Clustered base substitutions in CTP synthetase conferring drug resistance in Chinese hamster ovary cells.

Dominantly acting mutations that eliminate the allosteric regulation of CTP synthetase confer a form of multidrug resistance and a mutator phenotype to cultured Chinese hamster ovary cells. Mutations responsible for this phenotype have been identified in 23 independent strains selected for resistance to arabinosyl cytosine and 5-fluorouracil. All these mutations were due to base substitutions at seven sites within a highly conserved region of the ctps gene. This clustering should make it feasible to assess the role of such mutations in the development of drug resistance encountered in the treatment of malignant disease.

Animals↗
PubMed1993

Serum vitronectin receptor in alcoholic liver disease: correlation with fibronectin receptor and morphological features.

In order to clarify the significance of serum level of vitronectin receptor (VNR) in alcoholic liver disease (ALD), we have investigated the relationship with fibronectin receptor (FNR) and histological liver features in 21 ALD patients. Serum level of VNR and FNR was measured by enzyme immunoassay. Liver disease activity was scored based on levels of fibrosis and focal intralobular necrosis and degeneration. The serum level of VNR (micrograms/ml) was significantly higher in the patients with hepatic fibrosis (9.87 +/- 2.51) and liver cirrhosis (10.80 +/- 1.52) than in normal subjects (5.51 +/- 0.52, P < 0.01) and fatty liver subjects (6.58 +/- 0.58, P < 0.05). A positive correlation was found between serum levels of VNR and fibronectin receptor (FNR) (P < 0.05). A positive correlation was observed between the serum level of FNR and the degree of hepatic fibrosis or focal intralobular necrosis and degeneration, while no correlation was found between the serum level of VNR and the degree of histological features. A positive correlation was also noted between the serum level of FNR and N-terminal type III procollagen aminopeptide (PIIIP) (P < 0.001), while no correlation was observed between the serum level of VNR and PIIIP. We conclude that the serum level of VNR is increased in patients with advanced alcoholic liver disease. However, the mechanism by which serum levels of beta subunit of VNR and FNR are increased may be different.

Adult↗
PubMed1993

Serum level of carbohydrate-deficient transferrin as a marker of alcoholic liver disease.

Serum levels of carbohydrate-deficient transferrin (CDT) were assayed in 87 patients with alcoholic liver disease, 25 alcoholics without liver disease, 25 cases with viral liver disease and 37 healthy subjects, by two different methods (Pharmacia CDT RIA kit and Axis % CDT kit). The serum level of Pharmacia-CDT was significantly higher in the patients with alcoholic liver disease (38.9 +/- 2.8 U/l) compared to the normal subjects (18.9 +/- 0.2 U/l), alcoholics without liver disease (21.7 +/- 1.5 U/l) and non-alcoholic liver disease (viral liver disease) (23.4 +/- 1.6 U/l) (P < 0.001). The serum level of Axis-CDT was also significantly higher in the patients with alcoholic liver disease (4.22 +/- 0.48%) compared to the normal subjects (0.84 +/- 0.14%), alcoholics without liver disease (1.14 +/- 0.23%) and non-alcoholic liver disease (1.84 +/- 0.29%) (P < 0.001). A significant correlation was found between serum levels of CDT determined by the two kits (r = 0.718, P < 0.001). The serum level of Axis-CDT was significantly higher in patients with alcoholic hepatitis compared to the normal subjects (P < 0.005), while the serum level of Pharmacia-CDT was not increased in the patients with alcoholic hepatitis. These results indicate that determination of serum CDT levels is a useful marker of alcoholic liver disease, not a marker for alcohol consumption. Axis-CDT is more useful than Pharmacia-CDT for assaying the serum level of CDT in patients with alcoholic liver disease.

Adult↗
PubMed1993

Serum levels of intercellular adhesion molecule-1 in patients with alcoholic liver disease.

Serum levels of intercellular adhesion molecule-1 (ICAM-1) were measured in 37 patients with alcoholic liver disease, six alcoholics without liver disease and ten healthy subjects. The serum level of ICAM-1 was significantly higher in the patients with alcoholic cirrhosis than in the noncirrhotic alcoholic liver disease patients (P < 0.005) and the healthy subjects (P < 0.001). Furthermore, the serum level of ICAM-1 was significantly higher in the patients with alcoholic hepatitis than in those with alcoholic cirrhosis (P < 0.001). No significant difference in serum ICAM-1 levels was found between normal subjects and alcoholics without liver diseases. In the patients with alcoholic hepatitis, serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) derived from macrophages were increased in the presence of endotoxemia. The increase in serum ICAM-1 may therefore be related to the strong expression of ICAM-1 of hepatocytes and endothelial cells accompanied by the increase in serum TNF-alpha.

Adult↗
PubMed1993

Prenatal diagnosis of fragile X syndrome by direct detection of the dynamic mutation due to an unstable DNA sequence.

The fragile X syndrome is the most common familial form of mental retardation. The mutation causing the syndrome is dynamic mutation due to an unstable DNA (CCG)n repeat localized at Xq27.3. We have previously reported a PCR procedure to prepare a diagnostic probe, pPCRfx1, which can be used to determine the genotype of fragile X mutation individuals by Southern blot analysis. In the present study, pPCRfx1 was applied to the prenatal diagnosis, using chorionic villus cells, of a fetus which was at risk of having fragile X syndrome. In the PstI assay, the Southern blot showed the typical pattern of a female carrier with the full mutation. Analysis of the DNA methylation patterns by EcoRI + EagI assay showed that the EagI restriction site was not methylated on the mutated X chromosome of chorionic villi, but the sites were totally methylated in the brain and other tissues of the fetus. Thus the fetus was diagnosed to be a heterozygous female carrier of the dynamic mutation involved in the fragile X syndrome.

Blotting, Southern↗
PubMed1993

Heritable unstable DNA sequences and hypermethylation associated with fragile X syndrome in Japanese families.

Fragile X syndrome, associated with the fragile site at Xq27.3 (FRAXA), is the most common form of familial mental retardation. The fragile X mutation has recently been characterized as a heritable unstable DNA sequence, p(CCG)n/p(CGG)n, in the FRAXA locus. In the present study, a correlation between fragile X-genotypes in the FRAXA locus and hypermethylation of an adjacent CpG island was examined in four Japanese families with fragile X syndrome. We show here that the heritable unstable DNA sequences in the fragile X chromosome usually increase in size when transmitted by female carriers, and that the degree of methylation in the CpG island correlated with the increased sizes of the unstable DNA sequences. When a hypermethylated full mutation was transmitted by a male to his daughters, both the size of the unstable DNA sequence and the degree of the methylation reduced to the premutation range. Our observations suggest that female meiosis has a greater potential for amplifying unstable DNA sequences and that amplified DNA sequences can be transmitted through germ cells, while male germ cells seem not to be able to tolerate highly amplified unstable DNA sequences.

Base Sequence↗