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Biomedical subjects

K Kawakubo

Publications and source records attributed to K Kawakubo.

At least 19 recordsLinked to original sources
PubMed2001

Effect of diet on changes in small intestinal blood flow following intracolonic administration of indomethacin to rats.

Liquid diet (LD) is known to be protective against indomethacin-induced enteropathy, which is thought to be associated with ischemic change. We tested the hypothesis that the solid component of diet modulates small intestinal blood flow (SIBF) following indomethacin administration. In the first experiment, male Wistar rats were divided into 18-hr-fasted and normal diet groups. Indomethacin (20 mg/kg) or vehicle was administered intracolonically. SIBF was measured on both the mesenteric and antimesenteric sides of the intestine, using the hydrogen gas clearance method. In the second experiment, rats were given LD alone or LD with increasing concentration of soluble/insoluble fiber for seven days. The baseline SIBF was significantly higher in the groups with normal diet and LD with fiber than in the fasting and LD groups. Following indomethacin administration, SIBF gradually decreased in the groups with normal diet and LD with insoluble fiber, while neither liquid diet nor fasting reduced SIBF. There was no difference in SIBF between the mesenteric and antimesenteric sides of the intestine in any group. Our findings suggest that solid components of diet increase basal SIBF and decrease SIBF following indomethacin administration.

Animals↗
PubMed2001

Relationship between total and regional bone mineral density and menopausal state, body composition and life style factors in overweight Japanese women.

OBJECTIVE: To investigate whether menopausal state, body composition and lifestyle factors influence total and regional bone mineral density in overweight Japanese women. DESIGN: Cross-sectional study of women who were recruited to the weight reduction program held at community-based health promotion center in Tokyo area. SUBJECTS: A total of 178 women with a mean age of 48 y old (20-69 y) with a clear menstrual history and BMI over 24. MEASUREMENTS: Total, regional and lumbar spine bone mineral density (BMD) and body composition were measured using DXA (Lunar). Menstrual history was taken by a questionnaire and walking steps per day and energy intake were measured. Physical fitness was assessed by cardio-respiratory fitness and leg extension power. Subjects were divided into pre-menopausal and post-menopausal groups. RESULTS: Pre-menopausal group had significantly higher total body BMD as well as regional BMD than post-menopausal group. However, no differences in BMI, percentage fat and fat mass (FM) were seen between the two groups. The multiple regression analysis stepwise method revealed that total and regional BMD correlated with menopausal state and total FM independently. Total and regional BMD did not correlate with total non-fat soft tissue mass (NFSM), energy intake, walking steps or physical fitness levels. Trunk and lower extremities BMD correlated with corresponding regional FM and NFSM, and upper extremities BMD correlated with only corresponding body part NFSM after adjusting menopausal state. CONCLUSION: Total and regional BMD had strong negative correlation with menopausal state rather than total FM in overweight Japanese women. Weight-bearing site BMD correlated with corresponding body part FM and NFSM and non-weight bearing site BMD only correlated with corresponding body part NFSM after adjusting for menopausal state.

Absorptiometry, Photon↗
PubMed2001

Effects of ten year body weight variability on cardiovascular risk factors in Japanese middle-aged men and women.

OBJECTIVE: The purpose of the present study was to determine the effects of weight variability on cardiovascular risk factors (CRF) based on a large sample of community-resident Japanese males and females. METHOD: A total of 3564 men and 1955 women, all Japanese, aged 30-69 y in the baseline year (1987), were followed-up for up to 10 y (end-point in 1996). Height, body weight, systolic and diastolic blood pressure, fasting serum total cholesterol, triglyceride and fasting plasma glucose were measured as an annual health check-up. At least six times in 10 y, body mass index (BMI) mean was calculated as an index of the BMI level of each subject (BMI mean). Direction and magnitude of the change in a subject's BMI was determined by a regression slope of BMI values over time (BMI slope). BMI fluctuation was defined as the root mean square error (BMI RMSE) of a regression line. The slopes of the five CRF were calculated using each regression equation over time. RESULTS: The BMI slope strongly correlated to each CRF slope independent of baseline age, baseline CRF value, smoking habit, BMI mean and BMI RMSE. BMI RMSE did not correlate to any CRF slopes. CONCLUSION: This study indicates that weight gain and weight loss have a much greater effect on CRF change than does weight fluctuation in Japanese middle-aged men and women.

Adult↗
PubMed2001

Gastroprotective and vasodilatory effects of epidermal growth factor: the role of sensory afferent neurons.

Epidermal growth factor (EGF) has been shown to exert gastric hyperemic and gastroprotective effects via capsaicin-sensitive afferent neurons, including the release of calcitonin gene-related peptide (CGRP). We examined the protective and vasodilatory effects of EGF on the gastric mucosa and its interaction with sensory nerves, CGRP, and nitric oxide (NO) in anesthetized rats. Intragastric EGF (10 or 30 microg) significantly reduced gastric mucosal lesions induced by intragastric 60% ethanol (50.6% by 10 microg EGF and 70.0% by 30 microg EGF). The protective effect of EGF was significantly inhibited by pretreatment with capsaicin desensitization, human CGRP1 antagonist hCGRP-(8-37), or N(omega)-nitro-L-arginine methyl ester (L-NAME). Intravital microscopy showed that topically applied EGF (10-1,000 microg/ml) dilated the gastric mucosal arterioles dose dependently and that this vasodilatory effect was significantly inhibited by equivalent pretreatments. These findings suggest that EGF plays a protective role against ethanol-induced gastric mucosal injury, possibly by dilating the gastric mucosal arterioles via capsaicin-sensitive afferent neurons involving CGRP and NO mechanisms.

Afferent Pathways↗
PubMed2001

Telomere dynamics in myelodysplastic syndromes and acute leukemic transformation.

Myelodysplastic syndromes (MDS) are characterized by cytopenias in the blood and dysplastic features in the hematopoietic cells. Although the impact of cytogenetic abnormalities is considerable for prognosis, the exact genetic mechanism of MDS remains undetermined. In this study we assessed cytogenetic changes, microsatellite alterations, and telomere dynamics in order to obtain further insight into the pathogenesis of MDS. Thirty-three percentage of MDS patients and 60% of post-MDS acute leukemia (post-MDS AML) had de novo microsatellite changes. In the MDS phase, however, > 60% of patients showed reduction of telomere lengths without microsatellite changes, indicating that telomere reduction in most MDS patients does not seem to be directly linked to genome instability, or that reduction of telomere length does not induce microsatellite changes in the MDS phase. Some MDS patients had microsatellite changes without telomerase elevation, indicating that genome instability might accumulate during the disease progression in some MDS patients, and this condition (cellular senescence) may be related to ineffective hemopoiesis in MDS patients. In contrast, 40% of post-MDS AML patients had elevated telomerase activity with microsatellite changes, indicating that approximately 40% of patients with post-MDS AML patients had accumulation of genome instability resulting in elevated telomerase activity in an attempt to obtain genetic stability. However, the remaining MDS patients had microsatellite changes without telomerase up-regulation, suggesting that some MDS had genome instability even after leukemic transformation. Most MDS patients with elevated telomerase activity in the AML phase had elevated telomerase activity even in the MDS phase without apparent change in telomere length before and after leukemic transformation. These findings indicate that telomerase activity in the MDS phase may be independent of telomere length, although telomere shortening seems to be related to genomic instability, and this process may be linked to apoptosis of MDS cells.

Cell Transformation, Neoplastic↗
PubMed2001

[Cost and effectiveness of exercise therapy for patients with essential hypertension].

PURPOSE: While exercise therapy is established as an appropriate treatment for essential hypertension, its economic profile has not been fully evaluated. The purpose of this study is to evaluate cost and effectiveness in comparison with drug therapy. SUBJECTS AND METHODS: The study subjects were hypertensive patients under treatment at an outpatient clinic. Fifty-seven were selected on a non-randomized manner for exercise therapy and the same number of patients was chosen for drug therapy after matching age, sex, medication and complications. The following data were collected during three months of intervention. 1) Effectiveness: Change of systolic blood pressure before and after the intervention. 2) Cost: equipment, personnel expenses for exercise therapy and fees for health check-ups (exercise therapy); fees for consultation, laboratory examination and medications (drug therapy), 3) Cost-effectiveness: cost per 1 mmHg systolic blood pressure reduction. We evaluated the variance of cost-effectiveness by controlling the number of program participants, personnel expenses, and equipment expenses of exercise therapy. We also simulated how the cost-effectiveness of exercise therapy would improve by modifying the number of exercise participants, personnel and equipment expenses. RESULTS: The cost-effectiveness per 1 mmHg systolic blood pressure reduction was yen 11,268 for exercise therapy and yen 2,441 for drug therapy. Extending program facilities and increasing the number of participants would improve the cost-effectiveness of exercise therapy, but there were limitations to how far this could be achieved in the hospital setting. CONCLUSION: Differences in cost-effectiveness between exercise and drug therapies are attributed to differences in personnel expenses. Although they could be reduced by managerial effort of the hospital to some extent, outsourcing of exercise therapy to community-based facilities should be considered.

Cost-Benefit Analysis↗
PubMed2000

Human RNA-specific adenosine deaminase (ADAR1) gene specifies transcripts that initiate from a constitutively active alternative promoter.

The human ADAR1 gene specifies two size forms of RNA-specific adenosine deaminase, an interferon (IFN) inducible approximately 150 kDa protein and a constitutively expressed N-terminally truncated approximately 110 kDa protein, encoded by transcripts with alternative exon 1 structures that initiate from different promoters. We have now identified a new class of ADAR1 transcripts, with alternative 5'-structures and a deduced coding capacity for the approximately 110 kDa protein. Nuclease protection and 5'-rapid amplification of cDNA ends (5'-RACE) revealed five major ADAR1 transcriptional start sites that mapped within the previously identified and unusually large (approximately 1.6 kb) exon 2. These transcripts were observed with RNA from human amnion U cells and placenta tissue. Their abundance was not affected by IFN-alpha treatment of U cells in culture. Transfection analysis identified a functional promoter within human genomic DNA that mapped to the proximal exon 2 region of the ADAR1 gene. Promoter activity was not affected by IFN. These results suggest that transcripts encoding the constitutively expressed approximately 110 kDa form of the ADAR1 editing enzyme are initiated from multiple promoters, including one within exon 2, that collectively contribute to the high basal level of deaminase activity observed in nuclei of mammalian cells.

5' Untranslated Regions↗
PubMed2000

Intracisternal PYY inhibits gastric lesions induced by ethanol in rats: role of PYY-preferring receptors?

We previously reported that intracisternal (i.c.) injection of peptide YY (PYY) and low doses of thyrotropin-releasing hormone (TRH) or TRH analog, RX 77368, increased the resistance of the gastric mucosa to ethanol injury through vagal pathways in rats. The gastroprotective effect of i.c. injection of PYY/neuropeptide NPY (NPY) agonists with differential in vitro affinity to the Y receptor subtypes was examined in urethane-anesthetized rats. Intragastric administration of ethanol (45%, 5 ml/kg) results in mucosal lesions covering 23+/-2% of the gastric corpus in 1 h. PYY (500 ng, i.c.) significantly reduced ethanol-induced gastric lesions by 52%. [Pro34]PYY (PYY-preferring/Y1/Y5/Y4 subtypes) injected i.c. at 50, 100, 200 or 500 ng, reduced dose dependently gastric lesions to 15.4+/-2.2%, 11.4+/-3.1%, 8.6+/-2.9% and 5.4+/-2.2%, respectively. PYY3-36, (Y2/Y4 subtypes), [Leu31, Pro34]NPY (Y1/Y5), NPY (Y3/Y1/Y5/Y2) and pancreatic polypeptide (PP, Y4) injected i.c. at 500 ng did not influence significantly ethanol-induced gastric lesions. Combined i.c. injection of RX 77368 (1 ng) and Pro34PYY (25 ng), at sub-threshold doses given singly, reduced ethanol-induced gastric injury to 12.9+/-2.3% while RX 77368 (1 ng) plus PYY3-36 (500 ng) or [Leu31, Pro34]NPY (25 ng) had no effect. These findings indicate that i.c. PYY-induced gastric protection against 45% ethanol is mediated by a Y receptor subtype which bears similarity with the putative PYY-preferring receptor and distinct from the currently defined Y1/Y5; in addition, there is a synergistic interaction between activation of this PYY-preferring receptor and i.c. TRH to increase the resistance of the gastric mucosa to injury caused by 45% ethanol.

Animals↗
PubMed2000

Assessment of the primary effect of aging on heart rate variability in humans.

Beat-to-beat heart rate variability (HRV), reflecting cardiac autonomic control mechanisms, is known to change with age. However, the degree to which this change is mediated by aging per se or by physiologic changes characteristic of normative aging is still unclear. This study was designed to examine the association of aerobic fitness, body habitus or obesity, and blood pressure with age-related changes in HRV. Resting HRV data was recorded from 373 healthy subjects (124 men, 249 women; age range, 16-69 y) and analyzed by coarse-graining spectral analysis to decompose the total spectral power into its harmonic and fractal components. The low- and high-frequency (LF, 0.0-0.15 Hz; HF, >0.15 Hz) harmonic components were calculated from the former, whereas the latter was used to calculate the integrated power (FR) and the spectral exponent , beta, which were, in turn, used to evaluate the overall complexity of HRV. Factor analysis was performed to test whether potentially age-related changes in the components of HRV might be observed secondarily through other variables affecting HRV. Significant (p <0.05) age-related changes in the harmonic (HF and LF) and fractal (FR and beta) components of HRV were generally consistent with those described in the literature. In addition, factor analysis showed that there was a unique common factor that primarily explained correlations among age, HF, and beta (p <0.05) without the contributions from LF, FR, aerobic fitness, body habitus or obesity, and blood pressure. It was concluded that, in this population-based sample, age-related changes in HF and beta, both of which reflect vagal modulation of heart rate, were primarily mediated by aging per se and not by physiologic changes characteristic of normative aging.

Adolescent↗
PubMed2000

Endoscopic ultrasound features of protein-losing gastropathy with hypertrophic gastric folds.

BACKGROUND AND STUDY AIMS: We aim to clarify the endoscopic ultrasound (EUS) features of protein-losing gastropathy with hypertrophic gastric folds (PLGH), including Ménétrier's disease. PATIENTS AND METHODS: We analyzed the EUS and histologic findings in five patients who underwent both endoscopic ultrasonography and endoscopic resection. RESULTS: Histologically, we diagnosed one patient as having acute gastritis, three patients as having Ménétrier's disease, and the remaining patient as having hypertrophic lymphocytic gastritis (HLG). Helicobacter pylori was recognized in all but one patient. At EUS every patient was found to have giant gastric folds (13 to 20 mm in diameter), resulting from echogenic thickening of the mucosal layer with or without cystic components. Two patients who underwent eradication therapy of H. pylori showed both clinical and morphologic resolution. CONCLUSIONS: Echogenic thickening of the mucosal layer may be a characteristic EUS feature of protein-losing gastropathy with hypertrophic gastric folds, and H. pylori may be one of the causative agents.

Adolescent↗
PubMed2000

Peripheral PYY inhibits intracisternal TRH-induced gastric acid secretion by acting in the brain.

The site of action of peripheral peptide YY (PYY)-induced inhibition of vagally stimulated gastric acid secretion was studied using immunoneutralization with PYY antibody in urethan-anesthetized rats. Gastric acid secretion (59+/-7 micromol/90 min) stimulated by intracisternal injection of the stable thyrotropin-releasing hormone (TRH) analog RX-77368 (14 pmol/rat) was dose-dependently inhibited by 52%, 69%, and 83% by intravenous infusion of 0.25, 0.5, and 1.0 nmol. kg(-1) x h(-1) PYY, respectively. PYY or PYY(3-36) (2.4 pmol/rat) injected intracisternally also inhibited the acid response to intracisternal RX-77368 by 73% and 80%, respectively. Intravenous pretreatment with PYY antibody (4.5 mg/rat), which shows a 35% cross-reaction with PYY(3-36) by RIA, completely prevented the inhibitory effect of intravenously infused PYY (1 nmol x kg(-1) x h(-1)). When injected intracisternally, the PYY antibody (280 microg/rat) reversed intracisternal PYY (2.4 pmol)- and intravenous PYY (1 nmol x kg(-1) x h(-1))-induced inhibition of acid response to intracisternal RX-77368 by 64% and 93.5%, respectively. These results provide supporting evidence that peripheral PYY inhibits central vagal stimulation of gastric acid secretion through an action in the brain.

Animals↗
PubMed2000

Telomere dynamics and genetic instability in disease progression of chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is characterized by a Philadelphia (Ph) translocation creating a novel BCR-ABL oncoprotein, and CML patients have a chronic phase for several years followed by an intractable blast cell proliferation, called blast transformation. In the blast phase, more than 60% of patients show additional cytogenetic changes, e. g., double Ph, +8, i(17q). In this review, we would like to address genetic changes, including genome instability, cytogenetic changes, and telomere dynamics that relate to karyotypic instability. In the chronic phase, approximately 60% of CML patients show reduced telomere length without highly elevated telomerase activity or microsatellite alterations, indicating that telomere reduction may be linked to cell replication. Therefore, the Ph translocation might be a first event to immortalize cell proliferation. In the blast phase, 50% of CML patients have high levels of elevated telomerase activity and the same number of patients had microsatellite changes. Of note is that most patients with telomerase up-regulation in the blast phase had additional cytogenetic changes and >60% of them showed microsatellite changes at least at one locus. In contrast, most patients without telomerase activity did not show microsatellite changes. These findings may indicate that telomerase up-regulation in the blast phase of CML patients is closely associated with microsatellite changes (representative of genome instability), while blast cells in the remaining patients (30%) maintain their proliferative capability without microsatellite changes and telomerase up-regulation. This further suggests that there is also an unknown mechanism for genome stability without the process of telomerase up-regulation in some patients with CML in blast crisis.

Cell Transformation, Neoplastic↗
PubMed2000

Risk factors for ischemic heart disease in an urban area of Japan: a case-control study in AMHTS.

OBJECTIVES: In Japan controversy exists as to whether or not the risk factors for ischemic heart disease (IHD) are the same as in western countries. We conducted a case-control study on IHD to clarify the risk factors in males in an urban area of Japan using our automated multiphasic health testing and services (AMHTS) system. METHOD: Cases were the clients who took the health check-up between January 1987 and July 1994 and had onset of IHD after the check-up. For each case five clients were selected as controls by conditional matching. The check-up data were compared between cases and controls 11 years, 6 years and just before the onset of the heart diseases. RESULTS: The statistically significant items were as follows: (1) Eleven years before the onset: Total cholesterol (T-Chol) for myocardial infarction (MI), and fasting blood sugar (FBS) for angina pectoris (AP). (2) Six years before the onset: T-Chol, electrocardiographic (ECG) findings and the complaint of palpitation or breathlessness for MI, and FBS and palpitation or breathlessness for AP. (3) Just before the onset: T-Chol, the complaint of chest pain, FBS, smoking index and hypertensive status for MI and palpitation or breathlessness, ECG findings, chest pain, systolic blood pressure and erythrocyte sedimentation rate at 60 minutes for AP. In conclusion, the risk factors for MI in males in an urban area of Japan are the same as in western countries. The most significant risk factor for AP in males in an urban area of Japan is fasting blood sugar.

Adult↗