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Biomedical subjects

S Kawabata

Publications and source records attributed to S Kawabata.

At least 163 records · Page 9Linked to original sources

Total gastrectomy for gastric cancer: 12-year data and review of the effect of performing lymphadenectomy.

A total of 1,272 patients with gastric cancer were admitted to our institute for surgery during 12 years (1975-1986). Of these, 1,059 (83.4%) underwent gastrectomy. Among these, 252 (23.8%) were total gastrectomy (TG), involving 160 (63.5%) cases of cancer mainly located in the upper third of the stomach, 81 (32.1%) in the middle third and 11 (4.4%) in the lower third. Radical TG was performed in 65.9% and palliative TG in 34.1%. Roux-en-Y reconstruction was selected in 80%, jejunal interposition in 17.6% and double tract in 2.4%. The survival rate was improved by introducing extended lymph node dissection, especially in the cases of stage III & IV cancer in which a combined pancreatico-splenectomy could lead to cure when associated with lymphadenectomy. In cases of a positive serosal exposure, the 5-year survival rate was increased by extended lymphadenectomy from 21% to 46% (p < 0.02). Anastomotic leakage occurred in 4.2%. The postoperative mortality rate was 1.6%, occurring in only 4 patients.

Adenocarcinoma↗

Phenthoate metabolites in human poisoning.

Five metabolites were detected in the plasma and urine of a patient following ingestion of the organophosphate insecticide, phenthoate. Intact phenthoate was detected only in gastric lavage fluid. After methylation of acidic extracts of plasma and urine, phenthoate acid, demethyl phenthoate, demethyl phenthoate oxon acid, demethyl phenthoate S-isomer, and demethyl phenthoate acid S-isomer were identified with synthesized phenthoate analogues by gas chromatography and gas chromatograph-mass spectrometry. The main metabolites were phenthoate acid and demethyl phenthoate oxon acid. Although demethyl phenthoate oxon acid was a significant metabolite, no phenthoate oxon, phenthoate oxon acid or demethyl phenthoate oxon were detected. If the oxon was formed in the patient, it may have been rapidly degraded by carboxylesterase or glutathione transferase to demethyl phenthoate oxon acid.

Chromatography, Gas↗

[Detection of HTLV-I proviral DNA by PCR method from bronchoalveolar lavage cells of HTLV-I carriers].

To elucidate whether or not human T-lymphotropic virus type I (HTLV-I) infected cells exist in the lungs of HTLV-I carriers, we examined bronchoalveolar lavage (BAL) cells for the presence of HTLV-I proviral DNA by the polymerase chain reaction (PCR) method. The cells were harvested from HTLV-I seropositive individuals with or without various respiratory diseases. The HTLV-I pX region was detected from separated BAL cells by dot blot hybridization after PCR in all 14 HTLV-I seropositive individuals tested. Four out of these 14 individuals were asymptomatic HTLV-I carriers, while the other ten had symptoms, including those of bacterial pneumonia, chronic respiratory tract infection, interstitial pneumonia, atypical mycobacterial infection, bronchitis, mediastinal lymphadenitis and bronchial asthma. HTLV-I proviral DAN was detected in BAL cells from patients with a normal proportion of lavage lymphocytes and a normal CD4/CD8 ratio. These findings suggest that HTLV-I infected cells may commonly exist in the lower respiratory tract and alveolar space without producing characteristic symptoms/signs, and that any causal relation to the pulmonary lesion must therefore be carefully elucidated, in HTLV-I carriers.

Aged↗

[Complete response in a case of unresectable gastric cancer treated by combined chemoimmunotherapy of MMC, 5-FU and OK-432].

A 68-year-old female patient with unresectable advanced gastric cancer was treated by combined administration of MMC (10 mg/month), 5-FU (200 mg/day) and OK-432 (5KE/2 weeks). Two months after starting the treatment, there was a diminution in the serum CEA level. Six months later, the CEA had decreased to the normal level, primary and metastatic sites completely disappeared and no cancer cell was confirmed by endoscopic biopsy. The patient has survived for 33 months of a state of complete response.

Adenocarcinoma↗

Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis.

8-Oxoguanine (8-oxo-7, 8-dihydroguanine) is produced in DNA, as well as in nucleotide pools of cells, by active oxygen species normally formed during cellular metabolic processes. 8-Oxoguanine nucleotide can pair with cytosine and adenine nucleotides at almost equal efficiencies, and transversion mutation ensues. Human cells contain enzyme activity, which hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, and this enzyme is responsible for preventing misincorporation of 8-oxoguanine into DNA. We purified this particular human enzyme to physical homogeneity and determined a partial amino acid sequence. We then cloned the cDNA for human 8-oxo-dGTPase and examined its nucleotide sequence. The human protein comprises 156 amino acid residues and has some sequence homology with the Escherichia coli MutT protein, which has a distinct 8-oxo-dGTPase activity. When the human cDNA was expressed in E. coli mutT- mutant cells, there was a significant amount of 8-oxo-dGTPase activity. In such cells, the frequency of spontaneous mutation was greatly reduced. We propose that the human 8-oxo-dGTPase protects genetic information from the untoward effects of endogenous oxygen radicals.

Amino Acid Sequence↗

Somatostatin inhibits gastrin-induced histamine secretion and synthesis in the rat.

Somatostatin is a potent inhibitor of gastric acid secretion. However, the effect of somatostatin on gastric histamine secretion and synthesis has not been well understood, despite the fact that histamine plays a key role in the regulation of gastric acid secretion. This study was designed to determine the effect of somatostatin on gastric histamine mobilization and acid secretion in conscious rats. In conscious rats with a gastric fistula, a 4 h intravenous infusion of gastrin-17 I (1 nmol/kg/h) evoked a marked increase in fundic histidine decarboxylase activity (the sole histamine-forming enzyme) and reduced fundic histamine content with a concomitant increase in gastric acid secretion. Somatostatin-14 (10 nmol/kg/h) significantly inhibited gastrin-induced gastric acid secretion and fundic histidine decarboxylase activity and prevented a gastrin-induced decrease in fundic histamine content. In conscious rats with a vesical fistula, somatostatin-14 (10 nmol/kg/h) significantly inhibited the urinary histamine excretion induced by a gastrin-17 I (1 nmol/kg/h) infusion. These findings suggest that the inhibitory action of somatostatin on gastrin-induced acid secretion is mediated by the inhibition of histamine mobilization.

Animals↗

Rabbit liver microsomal endopeptidase with substrate specificity for processing proproteins is structurally related to rat testes metalloendopeptidase 24.15.

The detergent extract of rabbit liver microsomes contains an endopeptidase (MEP) with substrate specificity for peptides containing Arg residues at the P1 and P4 positions in the cleavage site (Kawabata, S., and Davie, E. W. (1992) J. Biol. Chem. 267, 10331-10336). These sequences occur in many proproteins such as the vitamin K-dependent proproteins and prohormones. A cDNA coding for MEP has been obtained from three overlapping clones isolated from two rabbit liver lambda gt10 cDNA libraries. The longest open reading frame of the 3507-base pair cDNA codes for a protein of 704 amino acids, of which 406 residues were confirmed by amino acid sequence analysis. MEP contains a putative active site of -His-Glu-X-X-His-, which is typical of mammalian zinc metallopeptidases. Based on a hydropathy plot, MEP is a hydrophilic protein with no transmembrane domain and no NH2-terminal signal sequence. Amino acid sequence analysis identified Asn at the three potential N-glycosylation sites in the enzyme, indicating that MEP contains no N-linked sugar. MEP is homologous with rat testes metalloendopeptidase 24.15 (60% identity), rat mitochondrial intermediate peptidase (24% identity), Escherichia coli dipeptidyl carboxypeptidase (25% identity), and the open reading frame YCL57w present in yeast chromosome III (35% identity).

Amino Acid Sequence↗

Secondary structural features of modules M2 and M3 of barnase in solution by NMR experiment and distance geometry calculation.

Proteins consist of structural units such as globular domains, secondary structures, and modules. Modules were originally defined by partitioning a globular domain into compact regions, each of which is a contiguous polypeptide segment having a compact conformation. Since modules show close correlations with the intron positions of genes, they are regarded as primordial polypeptide pieces encoded by exons and shuffled, leading to yield new combination of them in early biological evolution. Do modules maintain their native conformations in solution when they are excised at their boundaries? In order to find answers to this question, we have synthesized modules of barnase, one of the bacterial RNases, and studied the solution structures of modules M2 (amino acid residues 24-52) and M3 (52-73) by 2D NMR studies. Some local secondary structures, alpha-helix, and beta-turns in M2 and beta-turns in M3, were observed in the modules at the similar positions to those in the intact barnase but the overall state seems to be in a mixture of random and native conformations. The present result shows that the excised modules have propensity to form similar secondary structures to those of the intact barnase.

Amino Acid Sequence↗

Effects of selected surfactants on purified glucosyltransferases from mutans streptococci and cellular adherence to smooth surfaces.

The inhibitory effect of non-ionic, anionic, cationic and ampholytic surfactants on cellular growth of Streptococcus mutans MT8148 and S. sobrinus 6715, on glucan synthesis by the purified glucosyltransferase (GTase) from these organisms, and on bacterial adherence to glass surfaces was examined in vitro. Cationic surfactants exhibited marked bactericidal activities. Anionic and ampholytic compounds were less strongly bactericidal and non-ionic surfactants produced only slight inhibition of cell growth under the conditions tested. Some non-ionic compounds had no effect on this. Glucan synthesis by GTase from mutans streptococci was inhibited by anionic and cationic surfactants. Among various GTase proteins, insoluble glucan synthesising GTases, i.e., S. mutans CA-GTase and S. sobrinus GTase-I were those most effectively inhibited by these agents. However, it was noted that whereas lower concentrations of cationic surfactants enhanced these GTase activities, higher concentrations of the surfactants were inhibitory. Non-ionic detergents stimulated soluble glucan synthesis from S. mutans CF-GTase and cationic and ampholytic surfactants enhanced or inhibited glucan synthesis depending on the concentrations of the surfactants. Sucrose-dependent cellular adherence of resting cells of mutans streptococci to glass surfaces was inhibited by the addition of surfactants that annulled the GTase activities.

Bacterial Adhesion↗

Inhibitory effect of oolong tea polyphenols on glycosyltransferases of mutans Streptococci.

Oolong tea extract (OTE) was found to inhibit the water-insoluble glucan-synthesizing enzyme, glucosyltransferase I (GTase-I), of Streptococcus sobrinus 6715. The GTase-inhibitory substance in the OTE was purified successive adsorption chromatography on Diaion HP-21 and HP-20 columns; this was followed by further purification by Sephadex LH-20 column chromatography. A major fraction that inhibited GTase activity (fraction OTF10) was obtained, and the chemical analysis of OTF10 indicated that it was a novel polymeric polyphenol compound that had a molecular weight of approximately 2,000 and differed from other tea polyphenols. Catechins and all other low-molecular-weight polyphenols except theaflavin derived from balck tea did not show significant GTase-inhibitory activities. It was found that OTE amd PTF10 markedly inhibit GTase-I and yeast alpha-glucosidase, but not salivary alpha-amylase. Various GTases purified from S. sobrinus and Streptococcus mutans were examined for inhibition by OTE and OTF10. It was determined that S. sobrinus GTase-I and S. mutans cell-free GTase synthesizing water-soluble glucan were most susceptible to the inhibitory action of OTF10, while S. sobrinus GTase-Sa and S. mutans cell-associated GTase were moderately inhibited; no inhibition of S. sobrinus GTase-Sb was observed. Inhibition of a specific GTase or specific GTases of mutants streptococci resulted in decreased adherence of the growing cells of these organisms. The inhibitory effect of OTF10 on cellular adherence was significantly stronger than that of OTE.

Bacterial Adhesion↗

Increased vasopressin secretion and release in mice transgenic for the rat arginine vasopressin gene.

The rat arginine vasopressin (AVP) genomic sequence has been utilized to develop a line of transgenic mice homozygous and heterozygous for the transgene. Expression of the rat AVP gene was demonstrated by Southern blotting and resulted in increased amounts of AVP in hypothalamus and frontotemporal brain cortex. Secretion of AVP from the neurohypophysial system results in an increased concentration of the hormone in the plasma and in an increased excretion in the urine in amounts three to five times those of normal mice. Extraneural ectopic hormone production was found only in the pancreas. Despite chronic hypersecretion of AVP, 24-hour urine volume and osmolality did not show evidence of increased antidiuretic hormone action on the kidney, so that, under basal conditions, the water balance in the animals is unaffected.

Animals↗

Oolong tea polyphenols inhibit experimental dental caries in SPF rats infected with mutans streptococci.

An extract of oolong tea (semifermented tea leaves of Camellia sinensis) and its chromatographically isolated polyphenolic compound was examined for in vitro inhibitory effects on glucosyltransferases (GTases) of mutans streptococci and on caries development in Sprague-Dawley rats infected with mutans streptococci. The samples showed no detectable effect on the growth of mutans streptococci. However, insoluble glucan synthesis from sucrose by the GTases of Streptococcus mutans MT8148R and Streptococcus sobrinus 6715 was markedly inhibited, as was sucrose-dependent cell adherence of these mutans streptococci. The administration of the oolong tea extract and the isolated polyphenol compound into diet 2000 and drinking water resulted in significant reductions in caries development and plaque accumulation in the rats infected with mutans streptococci. The active components in the oolong tea extract were presumptively identified as polymeric polyphenols which were specific for oolong tea leaves. These results indicate that the oolong tea polyphenolic compounds could be useful for controlling dental caries.

Animals↗

Transgenic mouse models of vasopressin expression.

Arginine vasopressin is a nine-amino acid neuropeptide hormone important in the regulation of water metabolism. It also may have a role in other physiological functions, such as blood pressure regulation and the response to stress. Whole animal studies have provided a good understanding of vasopressin physiology and regulation of the normal vasopressin gene, and in vitro cell culture studies have demonstrated important features of the intracellular regulation of vasopressin gene expression. Transgenic mice provide useful models for the study of the in vivo regulation of gene expression. Previously reported mouse lines transgenic with vasopressin gene constructs have not expressed the transgene in a tissue distribution similar to that detected for the endogenous mouse vasopressin gene. An 8.2-kb genomic construct of the rat vasopressin gene, including 3 kb each of 5' and 3' flanking sequences, has been used to develop a line of transgenic mice. These animals express the transgene in a tissue-specific manner, demonstrate appropriate osmotic regulation of transgenic vasopressin mRNA, and have normal water metabolism. Animals homozygous for the 8.2-kb transgene have increased basal plasma levels of vasopressin peptide but have no apparent change in basal water metabolism. The findings with this and other previously reported mouse lines transgenic for vasopressin constructs provide a basis for developing future transgenic lines to study the in vivo regulation of the vasopressin gene.

Animals↗

Expression of the rat arginine vasopressin gene in transgenic mice.

A line of mice has been developed which are transgenic for an 8.2-kilobase (kb) genomic clone of the rat vasopressin (VP) gene. Using a polymerase chain reaction technique, the rat VP (rVP) transgene was shown to have tissue-specific mRNA expression in the hypothalamus, temporal lobe, parietal cerebral cortex, cerebellum, and posterior pituitary, similar to the tissue distribution of endogenous mouse and rat VP expression. Expression of transgenic rVP mRNA was also found in the lung and pancreas of the transgenic mice, sites of known ectopic expression of VP. Using two methods, Northern blot analysis with species-specific cRNA probes and a quantitative polymerase chain reaction technique, the quantity of rVP transgene mRNA was shown to regulate appropriately in response to an osmotic stimulus. After 72 h of water deprivation, the quantity of transgenic rVP mRNA increased 6.8 +/- 3.0-fold. This was not significantly different than the fold increase in mouse VP mRNA quantity seen in nontransgenic mice (4.8 +/- 1.5) but was significantly different (P < 0.05) than the 1.2 +/- 0.03-fold increase in rat VP mRNA seen in normal rats after water deprivation. In the rat hypothalamus, VP mRNA poly(A) tail length increases with osmotic stimulation, while in the mouse it does not. The poly(A) tail of transgenic rVP mRNA expressed in mouse hypothalamus did not increase in length after osmotic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Para-aortic lymph node dissection for the treatment of advanced gastric cancer.

Para-aortic lymph node (No. 16) metastasis has been accepted as a factor responsible for non-curability in gastric cancer surgery. Recently in Japan, after detailed experimental and clinical studies of the lymph flows from the stomach and/or perigastric nodes to these No. 16 nodes, it is now considered to be curable. From 5 autopsy cases, the mean number of No. 16 nodes has been determined to be 43. The frequency of positive No. 16 metastasis (No. 16(+)) was found to be 24%, occurring in 35 of 144 cases with advanced gastric cancer following R3 gastrectomy plus No. 16 dissection. The 5 year-survival rate of R3+ No. 16 dissection was 70.1% in n1(+), 49.8% in n2(+) and 24.3% in n3(+) and had better prognoses (by Kaplan-Meier statistics) than those without dissection of the No. 16 nodes. Only 37 patients in the Japanese literature have had No. 16 dissections, and were confirmed histologically to have had No. 16(+) and subsequently survived more than 5 years. The number of those surviving No. 16(+) can be expected to increase in the near future with the adoption of R3 gastrectomy plus No. 16 dissection.

Aorta, Abdominal↗

Early gastric cancer with juxta lymph node (n3) metastasis.

From 1976 to 1992, a total of 714 cases of early gastric cancer (EGC) were treated by resection in the First Department of Surgery, Kurume University Hospital. For EGC, the overall lymph node metastasis rate is generally 10%, with the lymph node metastasis observed mainly in the Group 1 perigastric nodes in both mucosal cancer and submucosal cancer. Three rare cases of an early gastric cancer with Group 3 juxta regional lymph node metastasis are described because Group 3 lymph nodes are rarely discovered. To our knowledge, only 14 other cases of EGC with juxta regional lymph node metastasis have been reported in the Japanese literature.

Aged↗

Retrospective studies of synchronous double early gastric cancer.

From 1984 to 1990, 922 cases of gastric cancer underwent resection in the First Department of Surgery, at Kurume University Hospital. Of these, 381 (41.3%) cases were early gastric cancer (EGC). Among these EGC, synchronous double early gastric cancer (double EGC), according to the diagnostic criteria of Moertel, was found in 49 (12.9%) cases involving 98 foci. In cases of a double EGC, the primary and secondary foci can be distinguished. Double EGC occurred more frequently in males than females (7.1:1). In the elderly, the incidence of a double EGC was higher than the incidence of a single EGC. Double EGC occurred more frequently in the lower third of the stomach than a single EGC. And a macroscopically elevated and histologically differentiated type primary focus was more frequently found in double EGC than in single EGC. Of the 49 secondary foci in the double EGC, 12 (24.5%) foci were a microcarcinoma of less than 5 mm in greatest diameter, and 48 (98%) were limited to the mucosa (m-cancer). Therefore, a preoperative detailed examination of the whole stomach by endoscopy and an intraoperative careful search under gastrotomy must be made in the remnant of the stomach in cases of distal or proximal partial gastrectomy to ensure adequate excision.

Aged↗