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Biomedical subjects

H Ishiguro

Publications and source records attributed to H Ishiguro.

At least 91 records · Page 5Linked to original sources
PubMed1999

Effects of guanylin and uroguanylin on rat jejunal fluid and electrolyte transport: comparison with heat-stable enterotoxin.

The effects of rat guanylin, human guanylin, human uroguanylin and STa on net fluid and electrolyte transport in the closed jejunal loop were compared in anesthetized rats. STa administered into the lumen caused a concentration-dependent (10(-8) to 10(-6) M) inhibition of net fluid and NaCl absorption in the jejunal loop. Uroguanylin had a similar but weaker effect than STa. Both rat and human guanylin inhibited fluid and NaCl absorption only at 10(-6) M. Their order of potency was STa > human uroguanylin > rat guanylin = human guanylin. Changing the luminal pH from 5 to 8 failed to affect the action of guanylin on fluid absorption. Both STa and uroguanylin, but not guanylin, increased the luminal pH by stimulating bicarbonate secretion. Pretreatment of the jejunal loop with guanylin (10(-6) M) 5 min before the instillation of STa (10(-7) M) significantly reduced the inhibitory effect of STa on fluid absorption. It is concluded that guanylin and uroguanylin administered into the rat jejunal lumen have an STa-like action on fluid and electrolyte transport. Guanylin may act as an endogenous antagonist of STa in the rat jejunum and prevent excessive fluid loss by STa.

Animals↗
PubMed1999

The 5' region of the tryptophan hydroxylase gene: mutation search and association study with alcoholism.

A deficiency in the serotonergic system has been suggested as a negative reinforcer in alcoholism. Tryptophan hydroxylase (TPH) is critical in the fine-tuning of serotonergic neurotransmission. We observed a significantly high frequency of the A allele of the IVS7+218A>C polymorphism in intron 7 of the TPH gene in Japanese alcoholics with histories of drinking-related antisocial behaviors compared with that of Japanese controls (p = 0.006). However, this polymorphism is intronic, and a study of TPH mRNA did not detect aberrant splice products or polymorphic nucleotides linked to this polymorphism. Therefore, we screened for variations in the promoter and 5'-untranslated region of the gene. Three novel variants/polymorphisms, -1066G>A in the 5' flanking region, IVS1B+23(GTTTT)4-5 in intron 1B, and IVS1C+50T>C in intron 1C, were identified. The -1066G>A and IVS1C+50T>C polymorphisms were in modest linkage disequilibrium with the IVS7+218A>C polymorphism. However, no significant association was found between the three novel polymorphisms and alcoholism. Although our findings reiterate that TPH may play some role in the genetic predisposition to alcoholism, the mechanism remains unknown.

Adult↗
PubMed1999

Isolation and characterization of a human cDNA homologous to the Xenopus laevis XCAP-C gene belonging to the structural maintenance of chromosomes (SMC) family.

We have isolated a human cDNA encoding a protein of 1288 amino acids that shows 77% identity in amino acid sequence to XCAP-C, Xenopus chromosome-associated polypeptide-C, belonging to the family of structural maintenance of chromosomes (SMC), which is known to play a crucial role in the proper condensation and segregation of mitotic chromosomes. In particular, an almost 200-amino-acid domain in the N-terminal, including an NTP-binding motif and that in the C-terminal domain, including a DA-box, were well conserved and showed 95% identity between human and frog, indicating that these two domains are functionally very important. The transcript of this gene was expressed ubiquitously in various human tissues, but thymus, testis, and colon seemed to express this gene more abundantly. We also determined its chromosomal location at 3q26.1 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMed1999

Nicotine withdrawal up-regulates c-Fos transcription in pheochromocytoma cells.

The influence of nicotine on the expression of Fos family proteins, which specifically formed complexes with the AP-1 sequence, was assessed. mRNA for c-Fos, c-jun and jun-B were up-regulated at 0.5 h after nicotine treatment, elevated c-Fos also being apparent after withdrawal. Although nicotine failed to up-regulate the mRNA level of the fra-1 gene, the Fra- protein was highly expressed after both treatment and withdrawal. These results indicate that nicotine treatment may affect the transcriptional activity of many genes through c-Fos and c-Jun protein expression in neural cells, and that Fra-1 protein may make a contribution. These changes in immediately early genes (IEGs) may be associated with nicotine withdrawal symptoms.

Adrenal Gland Neoplasms↗
PubMed1999

Molecular understanding of chronic pancreatitis: a perspective on the future.

Despite the recent development of medical imaging technology, chronic pancreatitis can only be diagnosed when the disease is fully established. This is due to the lack of specific and sensitive markers for this disease. The discovery of mutations in the cationic trypsinogen gene in patients with hereditary pancreatitis and a high incidence of mutations in the cystic fibrosis transmembrane conductance regulator gene in patients with chronic pancreatitis might be important clues to understanding the molecular mechanisms of this disease. The interaction between ethanol and ion channels might be the missing link between alcohol ingestion and chronic pancreatitis.

Adult↗
PubMed1999

Identification of a novel polymorphism of the human dopamine transporter (DAT1) gene and the significant association with alcoholism.

Human dopamine transporter gene (DAT1) has a variable number of tandem repeats (VNTR) in its 3'-untranslated region (UTR). The association between the VNTR polymorphism and neuropsychiatric disorders has been studied, but their relationship is still unclear. Here we identified a novel polymorphism in the 3'-UTR of the DAT1 gene, G2319A, and a significant association between the polymorphism and alcoholism was observed in both genotypic and allelic frequencies (P = 0.040 and 0.019, extended Fisher's exact test, respectively). There was a significant gene dose effect on the risk for alcoholism associated with the 2319-A allele (chi2 = 6.16, df = 2, P = 0.046, linearity tendency test: Cochranq-Armitage analysis). Moreover, in the haplotype analysis with G2319A- and VNTR-polymorphisms, a positive gene dose efffect on the risk with the A10 allele (P = 0.044, linearity tendency test) and a negative gene dose effect with the G10 allele (P = 0.010, linearity tendency test) for alcoholism were significantly detected. Odds ratio for alcoholism with the A10 and G10 alleles were 1.76 (1.12-2.76) and 0.53 (0.32-0.79), respectively. These results indicate that the DAT1 gene may confer vulnerability to alcoholism.

3' Untranslated Regions↗
PubMed1999

Supportive evidence for contribution of the dopamine D2 receptor gene to heritability of stature: linkage and association studies.

Increases in height were reported in children chronically exposed prenatally and postnatally to D2 receptor-blocking drugs. A possible haplotypic association between stature and the DRD2 gene was also reported. In this study, we examined linkage between stature and DRD2 by genotyping a dinucleotide repeat polymorphism in 79 sib-pairs aged 8-17 years. An association between stature and a putative functional polymorphism in the promoter region of the DRD2 gene was examined in the sib-pairs and in 125 unrelated male adults. All the subjects were Japanese. Linkage (p = 0.004, SIBPAL) and an association (p = 0.009, paired t-test, in the sib-pairs; p = 0.006, ANOVA, in the adults) with stature were suggested. These findings indicate that DRD2 is one of the genes that contribute to heritability of stature.

Adolescent↗
PubMed1999

Association study between high and low activity polymorphism of catechol-O-methyltransferase gene and alcoholism.

Catechol-O-methyltransferase (COMT) is a key modulator of dopaminergic and noradrenergic neurotransmission. There is a functional polymorphism of the COMT gene, Val108Met in the soluble form of the enzyme (Val158Met in the membrane-bound form). Involvement of the dopaminergic systems in alcoholism has been suggested in mice and humans. We examined associations between this polymorphism and alcoholism in 175 Japanese alcoholics and 354 age- and gender-matched Japanese controls. No significant difference in the allelic distributions in alcoholics and controls and no significant associations between antisocial behaviors in alcoholics and this polymorphism were observed. Therefore, the COMT gene is not likely to play a significant role in alcoholism.

Adult↗
PubMed1999

Ovarian function after bone marrow transplantation performed before menarche.

AIM: To examine the long term effect of bone marrow transplantation (BMT) on ovarian function in girls. METHODS: Eighteen girls who underwent BMT before menarche, had been disease free for more than six years, and were over 14 years of age at the time of study were investigated. The preparative regimen consisted of irradiation and chemotherapy. The occurrence of menarche and changes in basal serum follicle stimulating hormone (FSH) concentrations were studied. RESULTS: Twelve patients achieved menarche at a median age of 12.8 years. Age at transplant was significantly younger in patients who achieved menarche than in those who did not (mean (SD), 7.2 (0.5) v 11.1 (1.7) years). Basal FSH began to rise to menopausal concentrations after 10 years of age, and the girls who did not experience menarche had a sustained rise in FSH concentrations. Among those with raised FSH concentrations, five girls experienced menarche while serum FSH values were decreasing and four achieved menarche while FSH remained raised. CONCLUSIONS: The high incidence of menarche suggests a favourable outcome of ovarian function in girls who undergo BMT at a young age.

Adolescent↗
PubMed1999

Arginine vasopressin inhibits fluid secretion in guinea pig pancreatic duct cells.

The effects of arginine vasopressin (AVP) on pancreatic ductal secretion were studied in guinea pigs. In the isolated vascularly perfused pancreas, AVP reduced secretin-stimulated fluid secretion and increased the vascular resistance when the perfusion rate was held constant. In the isolated interlobular duct segments, AVP inhibited secretin-stimulated fluid secretion, indicating the direct inhibitory action of AVP on the duct cells. AVP affected neither the basal nor the secretin-induced cAMP productions, suggesting that AVP inhibits the fluid secretion at a point distal to the production of cAMP. AVP increased intracellular Ca(2+) concentration ([Ca(2+)](i)) in the absence of extracellular Ca(2+). When [Ca(2+)](i) was elevated by the application of thapsigargin, AVP caused a rapid decrease in [Ca(2+)](i). AVP seems to activate both Ca(2+) release from intracellular stores and Ca(2+) efflux across the plasma membrane, but its relation to the inhibition of fluid secretion remains to be clarified. It is concluded that AVP directly inhibits secretin-stimulated ductal fluid secretion in the guinea pig pancreas.

Animals↗
PubMed1999

Molecular forms of serum pancreatic stone protein in acute pancreatitis.

CONCLUSION: Elevation of serum pancreatic stone protein-(PSP) S1 suggests activation of trypsinogen in the pancreas. This information would prompt the start of intensive treatment and may improve prognosis of acute pancreatitis (AP). BACKGROUND: PSP exists in two molecular forms, PSP-S2-5 and PSP-S1. PSP-S1 is produced by enzyme cleavage of PSP-S2-5 by trypsin. Total serum PSP rose in AP, but little is known about its molecular forms. In this study, we characterized the molecular forms of serum PSP in AP. METHODS: Sera were taken from 8 patients with severe acute pancreatitis (sAP) and from 11 patients with mild acute pancreatitis (mAP). Serum PSP was characterized by high-performance liquid chromatography (HPLC) followed by the specific enzyme immunoassay (EIA). RESULTS: The total serum PSP in sAP was higher than in mAP, but the difference was not significant. The PSP-S1 was detected in serum in all (7/7) patients in sAP and in 72% (8/11) of patients in mAP. Serum level of PSP-S1 was significantly higher in sAP than that in mAP (p < 0.05), and the cutoff value to distinguish the two groups was 30 ng/mL. Serum PSP-S1 did not show significant correlation with total PSP, immunoreactive trypsin, or C-reactive protein.

Acute Disease↗
PubMed1999

A prospective multicenter trial evaluating diagnostic validity of multivariate analysis and individual serum marker in differential diagnosis of pancreatic cancer from benign pancreatic diseases.

CONCLUSION: A multivariate analysis of CAMPAS-PX2 can increase its diagnostic accuracy in differential diagnosis of pancreatic cancer from benign pancreatic or extrapancreatic disease, when compared with CA19-9 alone. However, the improvement in diagnostic accuracy is still not satisfactory in spite of an elaborate combination of serum markers in diagnosis for pancreatic cancer. Optimal combination of a sensitive serum marker and another diagnostic modality, such as ultrasonography, can be a practical way to improve important diagnostic and cost-effectiveness in diagnosis for pancreatic cancer. BACKGROUND: No specific biological test has yet been developed for diagnosis of pancreatic cancer, although increasing numbers of tumor markers become available. For improvement in the diagnostic and cost effectiveness, it is important to select optimal combination of several serum markers relatively independent of each other. METHODS: A new model of discriminant function, computer-aided multivariate and pattern analysis system for pancreatic cancer examination 2 (CAMPAS-PX2), was developed based on the data of the 23 serum tumor markers from the first prospective trial (1) to differentiate between pancreatic cancer and benign pancreatobiliary disease by logistic regression analysis using a stepwise selection method. In 243 patients suspected of having pancreatic pancreatic cancer by a multicenter prospective study, the diagnostic value of the multivariate analysis, CAMPAS-PX2, was compared with the 23 markers. RESULTS: Pancreatic cancer was subsequently identified in 27 patients. Positive in disease, negative in health, and area under receiver operating characteristic curve were significantly higher by CAMPAS-PX2 (89, 87, 91%) than by CA 19-9 (78, 82, 84%), the most sensitive marker among the 23 markers.

Biomarkers, Tumor↗
PubMed1999

A synergistic effect of serotonin transporter gene polymorphism and smoking in association with CHD.

Serotonin induces vasoconstriction in the presence of atherosclerotic lesions. Platelets acquire serotonin from the extracellular space by serotonin transporter and release it following aggregation. There is a functional polymorphism in the serotonin transporter (5-HTT) gene promoter associated with transcriptional efficacy and plasma serotonin levels. To examine whether the polymorphism is associated with coronary heart disease (CHD) in the Japanese, we analyzed 144 male CHD patients with an onset age before 65 and 222 apparently healthy men. The L allele was observed significantly more frequently in the CHD patients (26%) than in the control subjects (19%); the odds ratio was 1.48 (p <0.03). A significant interaction between the polymorphism and smoking was observed for CHD (p = 0.03), suggesting that the two have a synergistic effect on CHD. Odds ratio of the combination of the L allele and smoking was 1.95 (p <0.003). The 5-HTT gene promoter polymorphism may play a role in susceptibility to CHD, particularly when it is combined with smoking.

Adult↗
PubMed1999

Effect of a new inhibitor of type II phospholipase A2 on experimental acute pancreatitis in rats.

The catalytic activity of type II phospholipase A2 (PLA2) in blood has been reported to increase in acute pancreatitis and to reflect the severity of pancreatitis. In this study, we evaluated the effects of a new inhibitor of type II PLA2, S5920/LY315920Na, on trypsin-taurocholate-induced pancreatitis in rats. Hemorrhagic pancreatitis was induced by an infusion of a mixture of trypsin and taurocholate into the pancreatic duct. S5920/LY315920Na was administered subcutaneously at 0 h and 3 h after the induction of pancreatitis. Survival rates for 24 h in rats treated with 0.1 and 1 mg/kg of S5920/LY315920Na were significantly higher than that in untreated rats (71 and 86% vs. 14%). Serum levels of amylase and lipase in rats treated with 1 mg/kg of S5920/LY315920Na were significantly lower than those in untreated rats (amylase, 6,903 vs. 32,516 U/L; and lipase, 514 vs. 6,710 U/L) at the time of death or 24 h after the induction of pancreatitis. Plasma levels of S5920/LY315920Na were enough to inhibit catalytic activity of PLA2 in plasma for 9 h. A new inhibitor of type II PLA2, S5920/LY315920Na, inhibited catalytic activity of PLA2 and improved the survival rate in experimental hemorrhagic pancreatitis in rats.

Acetates↗
PubMed1999

Association between drinking-related antisocial behavior and a polymorphism in the serotonin transporter gene in a Japanese population.

BACKGROUND: Involvement of the serotoninergic system (S/S) in alcoholism has been suggested in both mice and humans. Previous studies have suggested the S/S genotype of the serotonin transporter gene promoter polymorphism to be associated with severe alcohol dependence marked by severe withdrawal symptoms. It has also been associated with alcoholics who exhibit a dissocial personality disorder. METHODS: We examined the polymorphism in 166 Japanese alcoholics who experienced withdrawal seizure or delirium and 290 Japanese controls. RESULTS: The S/S genotype was not increased in the patients. Exploratory analyses showed significantly less frequent S allele and S/S genotype frequencies in the alcoholics with a history of drinking-related arrests than in the controls (p = 0.009 and p = 0.03, respectively), perhaps reflecting previously reported harm avoidance personality traits associated with S/S. Alcoholics with the L allele had a significantly earlier onset of alcohol dependence than those with the S/S genotype (p = 0.01). CONCLUSIONS: The present study failed to provide supportive evidence for an association of the S/S genotype with severe alcoholism marked by physical withdrawal symptoms or with antisocial behaviors among the Japanese. Although our data support involvement of the central serotoninergic system in some types of alcoholism, the potential association findings of this study emerged as only exploratory and, therefore, should be understood as tentative until replicated in other studies.

Adult↗
PubMed1999

Association between serotonin transporter gene polymorphism and smoking among Japanese males.

The serotoninergic system may be involved in smoking behavior because nicotine increases brain serotonin secretion, nicotine withdrawal decreases serotonin levels, and a selective serotonin reuptake inhibitor antagonizes the response to nicotine. Compared with the L allele, the S allele of the polymorphism in the upstream regulatory region of the serotonin transporter gene is associated with decreased transcription efficiency of the 5-HTT gene promoter. We examined this polymorphism in a Japanese population consisting of 387 males from two different areas in Japan. The L allele was observed significantly more often in smokers (21%) than in nonsmokers (lifetime nonsmokers + ex-smokers, 14%; P = 0.005). The presence of the L allele (the L/L + L/S genotypes) was also significantly increased in smokers (37%) compared with that in nonsmokers (24%; P = 0.003). The present study suggests that individuals with the S/S genotype are less inclined to smoke and/or can more easily stop smoking than others, supporting a role of the serotoninergic system in smoking behavior.

Adult↗
PubMed1999

[Hereditary ataxias in Akita prefecture].

To provide a genetic survey of hereditary ataxia, we performed PCR screening of SCA1, SCA2, MJD1 (SCA 3), SCA6, DRPLA, with 71 patients in 61 families living in Akita prefecture (1,205,571 population in 1997) in Japan. Of 71 patients in 61 families, 18 MJD1, 14 SCA6, 5 DRPLA, 1 SCA1 and 1 SCA2 patients were detected. Eighty percent of autosomal dominant inherited spinocerebellar degeneration (AD-SCD) including 7 spoladic patients genetically diagnosed as AD-SCD was MJD1 (45.7%) and SCA6 (34.3%). These suggest the prevalence rate of hereditary ataxias in Akita prefecture; 1.5 and 1.2/100,000 of MJD1 and SCA6, respectively. Only one patient of SCA1 was detected, which was frequently reported in Hokkaido and Tohoku area in Japan.

Genetic Testing↗