Biomedical subjects

T Sakata

Publications and source records attributed to T Sakata.

At least 91 records · Page 5Linked to original sources

PubMed2000

Loss of diurnal variation in ornithine decarboxylase and apoptosis in small intestine of Mongolian gerbils.

The aim of this study was to examine the diurnal variations in ornithine decarboxylase (ODC) activity and apoptosis in the small intestinal mucosa of Mongolian gerbils. First, the feeding, drinking, and ambulatory patterns of the gerbils were recorded. The results indicated that Mongolian gerbils lost diurnal cyclicity in feeding, drinking, and ambulatory patterns. Second, ODC activity and apoptosis in the intestinal mucosa of gerbils were characterized by measurements at four time points (11:00, 17:00, 23:00, and 05:00 h; light period, 08:00-20:00 h). Apoptosis was evaluated in terms of percent fragmented DNA (fragmented DNA/total DNA). Neither ODC activity nor apoptosis showed diurnal variation in the jejunal mucosa of the Mongolian gerbils. In 48-h fasted gerbils, ODC activity in the intestinal mucosa decreased, but this activity increased significantly 2 h after refeeding; percent fragmented DNA increased in the intestinal mucosa, and returned to the control level 2 h after refeeding. These results indicate that postprandial local nutrients are an important factor in regulating diurnal variation in ODC activity and apoptosis in the small intestine of gerbils.

Animals↗

PubMed2000

Novel mutations of the ATP7B gene in Japanese patients with Wilson disease.

Wilson disease (WD) is an autosomal recessive disorder characterized by copper accumulation in the liver, brain, kidneys, and corneas, and culminating in copper toxication in these organs. In this study, we analyzed mutations of the responsible gene, ATP7B, in four Japanese patients with WD. By direct sequencing, we identified five mutations, of which two were novel, and 16 polymorphisms, of which 6 were novel. The mutations 2871delC and 2513delA shift the reading frame so that truncated abnormal protein is expected. In contrast to these mutations found in patients with hepatic-type of early onset, the mutations A874V, R778L, and 3892delGTC were either missense mutations or in frame 1-amino acid deletion, and occurred in the patients with hepato-neurologic type of late onset. The mutations 2871delC and R778L have been previously reported in a relatively large number of Japanese patients. In particular, R778L is known to be more prevalent in Asian countries than in other countries of the world. Our data are compatible with the hypothesis that the mutations tend to occur in a population-specific manner. Therefore, the accumulation of the types of mutations in Japanese patients with WD will facilitate the fast and effective genetic diagnosis of WD in Japanese patients.

5' Untranslated Regions↗

PubMed2000

Short chain fatty acids but not lactate or succinate stimulate mucus release in the rat colon.

BACKGROUND: Short chain fatty acids (SCFAs) affect various intestinal functions. Mucus is an important physiological component of the intestinal mucosal barrier. However, the effect of SCFAs or other organic acids on the intestinal mucus release is poorly understood. The aim of this study was to investigate whether lumen SCFA stimulates mucus release into the rat colon. METHODS: A solution of SCFA, lactate or succinate was infused into the colon of anesthetized rats, and we then measured the hexose content of the effluent. We also examined the influence of cholinergic antagonists on the effects of SCFA. RESULTS: A SCFA mixture (75 mM acetate, 35 mM propionate and 20 mM butyrate) or individual SCFAs (130 mM) increased the mucus release into the colon in a similar manner. The individual SCFAs, but not lactate or succinate, stimulated colonic mucus secretion in similar concentration-dependent manners. Butyrate stimulated colonic mucus secretion at 20 mM, but acetate, propionate, lactate and succinate at this concentration did not. Pretreatment with an anti-cholinergic agent diminished the stimulatory effects of SCFAs on mucus secretion. CONCLUSIONS: Lumen SCFAs, but not lactate or succinate, stimulate mucus release from the rat colon via a cholinergic nerve mechanism.

Animals↗

PubMed2000

Decreased colonic mucus in rats with loperamide-induced constipation.

Constipation is a risk factor of colorectal cancer. Mucin is a major component of lumenal mucus, which protects the colorectal mucosa against mechanical and chemical damage. The aim of this study was to evaluate mucus production and to quantitate lumen mucus in a rat model of spastic constipation. We induced constipation with loperamide (1.5 mg/kg), and histochemically evaluated mucus production and the thickness of the mucus layer at the fecal surface. We quantitated the mucus attached to the mucosal surface using colonic perfusion with N-acetylcysteine. While more feces remained in the colon, there was less fecal excretion and lower fecal water content in loperamide-administered rats than in control rats. Crypt epithelial cells contained less mucus in constipated rats than in control rats. The mucus layer at the fecal surface was thinner and less mucus was recovered from the mucosal surface in constipated rats than in control rats. Mucus production of crypt epithelial cells and mucus at the fecal and mucosal surface were reduced by loperamide-induced constipation.

Animals↗

PubMed2000

Analysis of tumor necrosis factor-alpha promoter polymorphism in type 1 diabetes: HLA-B and -DRB1 alleles are primarily associated with the disease in Japanese.

Polymorphisms in the 5'-flanking region of the tumor necrosis factor (TNF)-alpha gene were examined to study the genetic background of type 1 diabetes in Japanese. Five different biallelic polymorphisms were examined in 136 type 1 diabetic patients and 300 control subjects. The frequencies of individuals carrying TNF-alpha-857T allele (designated as TNFP-D allele) or -863A/-1,031C allele (designated as TNFP-B allele) were significantly increased in the patients as compared with the controls. Since these TNF-alpha alleles are in linkage disequilibria with certain DRB1 and HLA-B alleles, two-locus analyses were carried out. The TNFP-D allele did not increase the risk in either the presence or absence of the DRB1*0405 or HLA-B54 allele, while the DRB1*0405 and HLA-B54 alleles per se could confer susceptibility in both the TNFP-D allele-positive and -negative populations. Moreover, an odds ratio was remarkably elevated in the population carrying both DRB1*0405 and HLA-B54. Similarly, the TNFP-B allele did not show significant association with the disease in either the HLA-B61-positive or -negative population, while the HLA-B61 allele could significantly increase the risk in the TNFP-B allele-positive population. These data suggest that the associations of TNFP-D and -B alleles may be secondary to their linkage disequilibria with the susceptible HLA class I and class II alleles. Because HLA-B and DRB1 genes were independently associated, both of these genes may be contributed primarily to the pathogenesis of type 1 diabetes in Japanese.

Adolescent↗

PubMed2000

Expression of rat uncoupling protein family mRNA levels by chronic treatment with thyroid hormone.

The present study was conducted to assess the effects of chronic treatment with triiodothyronine (T3) on mRNA expression of uncoupling protein (UCP) family in male Wistar King A rats. Subcutaneous injection of T3 (37 nmol/body weight 100 g) over 7 d increased mRNA expression of UCP1 in brown adipose tissue (BAT), UCP2 in white adipose tissue (WAT), and UCP3 in skeletal muscle (MSL) mRNA by 1.3, 1.7, and 2.0-fold, respectively. In contrast, the expression of ob gene mRNA in WAT and serum leptin level in the T3-treated rats decreased by 0.5-fold of the controls. These results suggest that T3 may increase UCP family expression independent of leptin action.

Adipose Tissue↗

PubMed2000

Mucosa-associated lymphoid tissue lymphoma of the rectum that regressed spontaneously.

We report a case of mucosa-associated lymphoid tissue (MALT) lymphoma of the rectum that regressed spontaneously. A 76-year-old man visited our hospital because of positive faecal occult blood testing. Colonoscopic examination revealed a slightly yellowish protruded lesion with a grooved depression in the lower rectum and two flat elevations in the upper rectum. Microscopic and immunohistological studies led to a diagnosis of MALT lymphoma. As the patient exhibited severe renal dysfunction and angina pectoris, the lesions were left untreated. Three months later, the protruded lesion became flat and the other lesions became unclear. He was followed up closely with endoscopy, but no relapse of these lesions was detected 19 months after the diagnosis.

Aged↗

PubMed2000

Age-related changes of cornu ammonis 1 pyramidal neurons in gerbil transient ischemia.

This study reports that postischemic apoptotic cell death of the hippocampal cornu ammonis (CA) 1 neurons is delayed in aged gerbils. Age-related changes in the process of CA1 neuronal death following transient ischemia was studied. Two groups of Mongolian gerbils were used in this study, which compared adult (4-month-old) and aged (24-month-old) animals by hematoxylin-eosin stain, in situ nick-end labeling (TUNEL method) and electron microscopy. In the process of neuronal death, neuronal loss of the aged group was histologically less severe than that of the adult group. TUNEL-positive cells were found on days 3-5 after ischemia in the adult group, while they were still found on day 7 in the aged group. The apoptotic process of the aged group was delayed compared to the adult group. Furthermore, lipofuscin was ultrastructurally observed inside the apoptotic body 5 days after ischemia in CA1 pyramidal neurons of the aged group. It is likely that colocalization of lysosomal enzyme cathepsin D with lipofuscin might be associated with the age-related alteration of lysosomal system in the neurons. Altogether these data suggest that age-related lysosomal changes might affect the apoptotic cascade process in postischemic CA1 neurons.

Aging↗

PubMed2000

Immunohistochemical demonstration of cyclin D1 in bladder cancers as an inverse indicator of invasiveness but not an independent prognostic factor.

BACKGROUND: Cyclin D1 is essential for G1 progression through the cell cycle phase. It is a possible proto-oncogene whose aberrant expression may be responsible for the occurrence of some types of human neoplasms. The objective of the present study was to demonstrate immunohistochemically cyclin D1 expression in bladder cancer tissues and establish any relationship with the histologic findings and the clinical course. METHODS: Tissue from 102 patients with bladder cancers and bladder tissue from five normal subjects were used for an immunohistochemical study of cyclin D1 using the avidin-biotin complex method. RESULTS: Nuclear staining of cyclin D1 was found in 79 (77%) out of the 102 cases of bladder cancer. The five cases of normal epithelium had no immunostaining for cyclin D1. All grade 1 tumors were positive for cyclin D1. With the advance of tumor grade the incidence of cyclin D1 decreased. All pTa tumors stained positively for cyclin D1, whereas the positive staining rates of invasive tumors were 47% in pT1, 73% in pT2, 31% in pT3 and 0% in pT4 tumors. Although a univariate analysis revealed patients with lesions positive to cyclin D1 had more favorable survival rates than those with negative findings, a multivariate analysis showed that positivity for cyclin D1 is not an independent prognostic factor. No relationship was discovered between positivity for cyclin D1 and tumor recurrence in patients with superficial bladder cancers. CONCLUSIONS: These findings suggest that cyclin D1 demonstrated immunohistochemically could be used as an inverse indicator for the level of invasiveness of bladder cancer, but not as an independent prognostic factor.

Adult↗

PubMed2000

Regional fat deposition in the legs is useful as a presumptive marker of antiatherogenesity in Japanese.

To examine the pathological role of regional fat deposition in development of metabolic and cardiovascular disorders, regional fat distribution was evaluated using metabolites and hormones as measures of obesity-related disorders. The subjects enrolled were 100 sex-matched inpatients, who were admitted, regardless of their body mass index values, for further examination of unusual results from periodic medical screening tests, and for examination of obesity-induced complications and treatment of obesity. Body fat distribution was analyzed using dual energy X-ray absorptiometry (DEXA). Analysis of parameters regarding fat distribution showed that gender was one of the determinants affecting correlation between fat distribution and metabolites of fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), total cholesterol (TC), or triglyceride (TG). However, regardless of gender, both leg trunk fat (L/Tr) and arm trunk fat (A/Tr) ratios negatively correlated with a total body fat (% total fat) ratio, whereas the intercept value of female regression line in L/Tr was greater than that in males, but not in A/Tr. Percentage total fat, L/Tr, and A/Tr in males correlated significantly with FPG, TC, TG, low-density lipoprotein (LDL), very low density lipoprotein (VLDL), atherogenic index (A.I.), and apoB/A1 only low density lipoprotein (LDL) was significantly correlated solely to L/Tr and A/Tr. These results indicate that regional fat distribution in males may not be a major determinant for development of metabolic disorders in obese patients. Unlike male regional fat distribution, female L/Tr correlated significantly not only with TC, TG, and LDL, but also with FPG and HbA1c, although both of the latter 2 glucose-related parameters in males showed no correlation with any parameters of fat deposition. The remaining female parameters of fasting plasma insulin, VLDL, A.I., and ApoB/A1 correlated with each of the three parameters of fat deposition, as similarly shown in males. The powerful and negative correlation was thus evident, particularly in females, between leg fat deposition and parameters of glucose and lipid metabolites. The resulting information provides a novel insight that regional fat deposition at the legs is useful as a marker for metabolic and cardiovascular disorders associated with obesity.

Adipose Tissue↗

PubMed2000

Tissue-specific expression of the uncoupling protein family in streptozotocin-induced diabetic rats.

The vulnerability of streptozotocin (STZ)-induced diabetic rats to cold stress has been established. One of the elements controlling body temperature is thermogenesis, in which uncoupling protein (UCP) is known to play an important role. We have examined UCP2 and UCP3 expressions in brown adipose tissue (BAT), white adipose tissue (WAT), and skeletal muscle (MSL) during the acute and chronic phases of STZ-induced diabetes in rats. The long-term effect and the effect of insulin treatment thereafter were also unexplored previously and are examined in this study. In the acute phase of diabetes (2.5 days after STZ injection), UCP2 gene expression in BAT, WAT, and MSL, and UCP3 expression in the muscle were significantly increased. In the chronic phase of diabetes (21 days after STZ injection), UCP2 and UCP3 expression in the MSL were restored to the control levels without insulin supplementation. UCP2 in BAT and WAT remained high in the chronic phase, whereas UCP3 expression in BAT and WAT, which did not change in the acute phase, was significantly decreased. Insulin supplementation restored UCP2 expression in BAT and WAT, but over-corrected UCP3 in WAT above the control and did not affect UCP3 expression in BAT. Insulin supplementation depressed UCP3 expression in the MSL below control. These results indicate that the effects of STZ-induced diabetes on UCPs gene expression are tissue-specific as well as dependent on the duration of diabetes.

Adipose Tissue↗

PubMed2000

Suppression of cesium-induced ventricular tachyarrhythmias by atrial natriuretic peptide in rabbits.

BACKGROUND: Intravenous injection of cesium chloride (Cs) causes ventricular tachyarrhythmias in rabbits. We investigated whether these tachyarrhythmias were caused by increased pressure load and whether they could be suppressed by atrial natriuretic peptide (ANP). METHODS AND RESULTS: Cs was injected in a bolus dose (1.5 mmol/kg), which was repeated 20 minutes later. Rabbits were then divided into 3 groups: control, ANP-treated, and hydralazine-treated groups. ANP or hydralazine was administered between the first and second Cs injections. The experiments were performed during intrinsic sinus rhythm (protocol A) or during ventricular pacing (protocol B). In protocol A, the second injection of Cs in the control group induced early afterdepolarizations and ventricular tachycardia, which were preceded by a marked increase in left ventricular end-diastolic pressure (LVEDP). Both ANP and hydralazine significantly suppressed Cs-induced increase in LVEDP. The arrhythmia score after the second injection of Cs was significantly lower in the ANP-treated and hydralazine-treated group compared with the control group (P < .005 and P < .05, respectively). In protocol B, the duration of left ventricular monophasic action potential and early afterdepolarization amplitude before and/or after the injections of Cs did not differ significantly between control and ANP-treated groups. CONCLUSIONS: Our results suggest that increased pressure load may play a role in the arrhythmogenic effect of Cs. The protective effect of ANP against Cs-induced ventricular tachycardia may be explained in part by a reduction in pressure overload. However, this effect might also be explained by the diverse action of ANP on the cardiovascular system.

Action Potentials↗

PubMed2000

Lack of an association between T-wave alternans and ST-segment depression during exercise-induced ambulatory ischemia.

It is known that T-wave alternans (TWA), which identify patients at risk for arrhythmic events, often occur during acute coronary occlusion in association with ST-segment elevation. To test the hypothesis that TWA is associated with a certain state/severity of myocardial infarction/ischemia, we assessed the association between TWA and ST-segment depression during exercise-induced ambulatory ischemia. Of 351 consecutive patients with coronary artery disease who underwent assessment of microvolt TWA by exercise, 23 patients with effort angina without a history of infarction with ST depression (> or =0.11 mV) during TWA test were selected. These patients were compared with 222 postinfarction patients consisting of 38 patients with, and 184 patients, without the ST depression, and 18 normal individuals. The incidence (9%) of determinate TWA in the patients with angina was significantly (P < .0001) lower than that (52%) in the postinfarction patients. There was no significant difference between the angina patients and the controls (6%). There was also no difference between the patients with (58%) and without the ST depression (51%) in the postinfarction patients. Moreover, no correlation existed between the TWA voltage and the ST-depression magnitude in both angina and postinfarction patients. We concluded that there is no association between TWA and ambulatory ischemia with ST depression.

Coronary Disease↗

PubMed2000

Studies on congenital protein C deficiency in Japanese: prevalence, genetic analysis, and relevance to the onset of arterial occlusive diseases.

Hereditary protein C deficiency is associated with a predisposition to venous thrombosis. We identified 43 patients with protein C deficiency by screening approximately 26,800 patients admitted to the National Cardiovascular Center Hospital. The observed prevalence of protein C deficiency was 1 per 620. We performed genetic analyses of 57 Japanese families with protein C deficiency. Combined with the results of the other studies in 10 families, the 67 Japanese families with protein C deficiency have been examined and 39 different gene defects have been identified. Some changes were solely identified in Japanese subjects, whereas others showed no such ethnic bias. The recurrent defects of Phe139Val, Arg169Trp, Val297Met, and Met364Ile substitutions and a G8857 deletion were found in 33 Japanese families, accounting for 49% of Japanese families with protein C deficiency, Finally, we examined the relevance of protein C deficiency to the onset of arterial occlusive diseases. In the examination of whether protein C deficiency hastens arterial occlusion, we found a significant difference (p = 0.02) in the age at onset of acute myocardial infarction between the patients with protein C deficiency (n = 10: 49.4 +/- 14.8 years) and a group of patients with normal protein C levels (n = 42: 60.5 +/- 10.6 years). At the onset of atherothrombotic cerebral infarction, the patients with protein C deficiency were significantly (p = 0.022) younger (n = 11:57.4 +/- 12.8 years) than those with normal protein C levels (n = 48: 64.6 +/- 10.1 years). Thus, we conclude that congenital protein C deficiency hastens the onset of arterial occlusive diseases, especially acute myocardial infarction, in Japanese subjects.

Age of Onset↗

PubMed2000

Impact of a new quinolone, DU-6859a, and two oral carbapenems, CS-834 and L-084, on the rat and mouse caecal microflora.

We determined the influence of a new quinolone, DU-6859a, and two oral carbapenems, CS-834 and L-084, on the rat and mouse caecal microflora. The caecum-skin fistula-implanted rats and conventional mice were given oral antimicrobials at doses of 30 mg/kg bid for 5 days. DU-6859a generated a marked decrease in the numbers of caecal flora except for enterococci. CS-834 and L-084 had little impact on the rat caecal flora. CS-834 caused a great decrease in the numbers of mouse caecal flora but L-084 did not. In vitro studies suggest that the difference is due to the extension of inactivation of antimicrobials by caecum contents.

Animals↗

PubMed2000

Does hypertension confer a hypercoagulable state in stroke-prone spontaneously hypertensive rats?

OBJECTIVE: To verify whether hypertension confers a hypercoagulable state in a hypertensive animal model. DESIGN: The parameters of blood coagulation were compared between stroke-prone spontaneously hypertensive rats (SHR-SP) and Wistar-Kyoto (WKY) rats. Each rat group consisted of a younger subgroup at 8-12 weeks old (n = 12) and an older subgroup at 16-20 weeks old (n = 12). METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT), fluorogenic PT, fibrinogen, fibrin/fibrinogen degradation products (FDP), thrombin-anti-thrombin III complex (TAT), factor Xa activity, anti-thrombin III (AT-III), tissue factor pathway inhibitor (TFPI), protein C and C1 inhibitor were measured in both rat groups. RESULTS: There was no significant difference in FDP and TAT levels between SHR-SP and WKY rats even at 16-20 weeks when SHR-SP developed severe hypertensive vascular lesions. Contrary to expectations, fluorogenic PT and factor Xa activity were significantly lower in SHR-SP than in WKY rats. While there was no significant difference in AT-III, TFPI and protein C activities between SHR-SP and WKY rats, C1 inhibitor activity was significantly higher in SHR-SP than in WKY rats. The elevated C1 inhibitor activity was inversely correlated with the reduced factor Xa activity. Gel-filtered fractionated plasma with C1 inhibitor activity had an inhibitory effect on the purified rat factor Xa, and immunodepletion of C1 inhibitor from the fractionated plasma attenuated the inhibitory effect CONCLUSION: These results suggest that SHR-SP get into a hypocoagulable state rather than a hypercoagulable state, and that the reduction of factor Xa activity in SHR-SP may be related to the elevation of C1 inhibitor activity.

Animals↗

PubMed2000

Radiofrequency catheter ablation from the left sinus of Valsalva in a patient with idiopathic ventricular tachycardia.

We report the case of a 54-year-old woman with idiopathic VT originating in the left ventricular outflow tract. She initially presented with palpitations and light-headedness. The morphology of the PVCs exhibited an inferior axis and tall R waves were noted in all the precordial leads. Spontaneous PVCs were transiently terminated by an intravenous injection of adenosine triphosphate. Radiofrequency catheter ablation from the left sinus of Valsalva successfully abolished the PVCs and the VT.

Catheter Ablation↗

PubMed2000

Impaired response of UCP family to cold exposure in diabetic (db/db) mice.

Impaired activity of the uncoupling protein (UCP) family has been proposed to promote obesity development. The present study examined differences in UCP responses to cold exposure between leptin-resistance obese (db/db) mice and their lean (C57Ksj) littermates. Basal UCP1 and UCP3 mRNA expression in brown adipose tissue was lower in obese mice compared with lean mice, but UCP2 expression in white adipose tissue (WAT) was higher. Basal skeletal muscle UCP3 did not change remarkably. The UCP family mRNAs, which were upregulated 12 and 24 h after cold exposure (4 degrees C), were returned to prior levels 12 h after rewarming exposure (21 degrees C) in lean mice. The accelerating effects of cold exposure on the UCP family were impaired in db/db obese mice. Together with these changes, WAT lipoprotein lipase mRNA was downregulated, and the concentration of serum free fatty acid was increased in response to cold exposure in the lean mice but not in db/db obese littermates. The impaired function of the UCP family and diminished lipolysis in response to cold exposure indicate that the reduced lipolytic activity may contribute to the inactivation of the UCP family in db/db obese mice.

Adipose Tissue↗