Biomedical subjects

T Ashida

Publications and source records attributed to T Ashida.

At least 19 recordsLinked to original sources

PubMed2006

K-ras mutations and cell kinetics in Helicobacter pylori associated gastric intestinal metaplasia: a comparison before and after eradication in patients with chronic gastritis and gastric cancer.

BACKGROUND: Helicobacter pylori related gastric intestinal metaplasia (IM) is considered to be a precancerous lesion. AIMS: To identify the effects of H pylori eradication on K-ras mutations, cell kinetics in IM and histological changes in patients with and without gastric cancers in a one-year prospective study. METHODS: Patients included group A (n = 39), chronic gastritis, and group B (n = 53), intestinal-type early gastric cancer patients who had all undergone endoscopic mucosal resection (n = 25) or surgical resection (n = 28). K-ras codon 12 mutations in IM were examined, followed by DNA sequencing analysis. Proliferating and apoptotic cells were detected with anti-Ki-67 antibody and using the TUNEL method, respectively. RESULTS: The incidence of K-ras mutations in the cancer was only 3.8%. The mutant K-ras in IM was observed more frequently in group A (46.2%) than in group B patients (1.9%) (p<0.005). After eradication, the K-ras mutations significantly declined to 12.8% in group A (p<0.005). The mutation pattern of K-ras codon 12 before eradication was that GGT was mainly changed to AGT (50%) in group A. AGT transformation was not affected by treatment. Apoptosis in IM showed an increase after H pylori eradication in both groups (p<0.05 in group A) although no histological improvement in IM was observed. The monocyte score was significantly higher in group A than in group B (p<0.05); the score improved significantly after eradication. CONCLUSIONS: K-ras mutations in IM do not always play a role in gastric carcinogenesis but cell kinetics, especially apoptosis, in IM may contribute to it. There are early events in K-ras mutations which are influenced by H pylori infection; some mutations may also be selected by eradication. These unstable K-ras mutations in IM may be related to lymphocyte infiltration caused by H pylori infection.

Apoptosis↗

PubMed2005

Phase II study of irinotecan, leucovorin, 5-fluorouracil and tegafur/uracil for metastatic colorectal cancer.

Irinotecan combined with continuous-infusion 5-fluorouracil (5FU) has been shown to be an effective and tolerable regimen in the treatment of metastatic colorectal cancer (MCRC). Tegafur/uracil (UFT) during 5FU infusion enhances plasma 5FU concentration, mimics continuous 5FU infusion and delivers the drug to target tumor cells. We conducted a phase II trial of four-agent combined therapy for MCRC, giving patients (pts) intravenous irinotecan (30 mg/m2 on day 1), leucovorin (LV, 200 mg/m2 on day 1 and 2), 5FU (300 mg/m2 on day 1 and 2), and UFT (400 mg/day for 14 days). The main endpoint was the objective tumor response rate. Sixteen pts with a good performance status were enrolled from February 2001 to May 2002. The response rate was 19% (3 partial responses), and 13 pts had stable disease. The median time to progression was 5.2 months, and the median survival time was 20.2 months. Considering the low toxicity and reasonable cost, this regimen deserves further investigation.

Adolescent↗

PubMed2002

Office blood pressure variability as a predictor of acute myocardial infarction in elderly patients receiving antihypertensive therapy.

Larger variability of office blood pressure (BP) was reportedly associated with a higher risk of stroke or mortality from all causes. In the present study, we focused on the relationship of variability of office BP and occurrence of acute myocardial infarction (MI). We registered 139 patients receiving antihypertensive therapy for more than 1 year who experienced first-ever episode of MI at the age of 60 years or over. At least two sex- and age-matched (+/- 5 years) control patients were registered for every MI patient. Average systolic and diastolic BP during the 12-month period prior to the occurrence of MI, or the time of registration in the case of control patients, was similar in both patient groups. The office BP variability was evaluated by calculating the variation coefficient (VC) of BP. VC of diastolic BP was significantly higher in the MI patients (10.0 +/- 4.0%) compared with the control patients (8.8 +/- 3.4%). VC of systolic BP was not different between the MI and the control patients. Multiple logistic analysis revealed the relationship of the VC for office diastolic BP to the occurrence of MI was significant after adjustment for BP level, age, gender, body mass index, serum total cholesterol concentrations, diabetes mellitus, and current smoking. In conclusion, larger long-term variability of office diastolic BP during antihypertensive therapy is a predictor of MI.

Age Distribution↗

PubMed2001

Measurement of plasma brain natriuretic peptide level as a guide for cardiac overload.

OBJECTIVES: We examined whether measurement of the plasma BNP concentrations might be useful for the early diagnosis of the existence and severity of disease in patients with heart disease in daily clinical practice. METHODS AND RESULTS: The plasma BNP and ANP concentrations in 415 patients with heart disease and hypertension and 65 control subjects were measured. Patients with heart disease had higher plasma BNP and ANP concentrations than did those with hypertension or control subjects. Among the etiology of cardiac diseases, specifically dilated cardiomyopathy and hypertrophic cardiomyopathy, was associated with the highest plasma BNP concentrations, whereas dilated cardiomyopathy was associated with the highest plasma ANP concentrations. Plasma BNP concentrations showed an increase as the severity of the heart disease, as graded according to the NYHA classification of cardiac function, increased. In both patients with heart disease and hypertension, the plasma BNP values were higher in those who had abnormalities in their echocardiogram and electrocardiogram as compared to those without any abnormalities. The plasma BNP levels also showed a significant correlation with left ventricular wall thickness and left ventricular mass. On the other hand, the plasma ANP levels showed significant correlations with left ventricular dimension. Receiver operative characteristic analysis revealed that plasma BNP levels showed substantially high sensitivity and specificity to detect the existence of heart diseases. CONCLUSION: Measurements of the plasma BNP concentrations is useful to detect the existence of the diseases, and abnormalities of left ventricular function and hypertrophy in patients with heart disease in daily clinical practice.

Atrial Natriuretic Factor↗

PubMed2001

Serum KL-6 levels in patients with pulmonary complications after allogeneic bone marrow transplantation.

KL-6, a mucinous high-molecular weight glycoprotein expressed on type 2 pneumocytes, has been shown to be elevated in the serum and bronchoalveolar lavage fluid of patients with interstitial pneumonitis (IP). We measured the serum levels of KL-6 in patients after they had undergone allogeneic bone marrow transplantation (BMT) to determine whether KL-6 could be a clinically useful indicator for the development of IP. The serum concentrations of KL-6 were determined by a sandwich-type enzyme-linked immunosorbent assay using an anti-KL-6 monoclonal antibody. A total of 1028 samples were tested from 76 patients (78 transplantations) who received BMTs. The KL-6 values were markedly elevated in patients with pulmonary complications, but not in those with acute and chronic graft-versus-host disease, hemorrhagic cystitis, herpes encephalitis, sepsis, and veno-occlusive disease. The serum levels of KL-6 from patients with pulmonary complications were significantly higher than from those without pulmonary complications (P < .001) and those with other complications (P < .001). Of the 12 patients with pulmonary complications, 6 had idiopathic IP (IIP). The levels were not high at the onset of IIP. Four of 6 IIP patients showed marked elevations of KL-6 levels in parallel with the severity of IP and died of respiratory failure without response to treatment. Assessment of serum KL-6 levels might not be useful for the early diagnosis of IP, but may be a useful indicator for monitoring the severity of IP after BMT.

Adolescent↗

PubMed2001

Concentration of progenitor cells collected from bone marrow fluid using a continuous flow cell separator.

In ABO major incompatibility on bone marrow transplantation (BMT), red cells must be removed from collected marrow fluid to prevent hemolysis. We report the concentration of progenitor cells collected using a continuous flow cell separator (Cobe Spectra). The average volume of concentrated bone marrow was 132 +/- 47 ml and that of red cells included was 5.1 +/- 2.4 ml. The red cell removal rate was 97.6%. The recovery rate was 40.6% for total nuclear cells, 77.9% for mononuclear cells, 100% for CD34+ cells, and 93.9% for colony forming unit granulocyte-macrophage. Eighteen patients undergoing allogeneic BMT showed no signs of fever or hemolysis during concentrated marrow fluid transfusion. The recovery rate of progenitor cells was high, indicating sufficient recovery of hemopoiesis. This technique is applicable in ABO-incompatible BMT and in frozen-storage stem cells.

ABO Blood-Group System↗

PubMed2001

Reduced expression of syndecan-1 affects metastatic potential and clinical outcome in patients with colorectal cancer.

Syndecan-1 is a transmembrane heparansulfate proteoglycan which regulates cell-to-cell or cell-to-extracellular matrix interactions and may influence malignant cell behavior. We investigated the alterations of syndecan-1 expressions in colorectal cancers and analyzed the relationship between histological and clinical characteristics. Syndecan-1 protein expression in colorectal cancer tissues was investigated with immunohistochemical staining of resected specimens. In situ hybridization was performed using syndecan-1 riboprobe to confirm the transcriptional signals. Syndecan-1 mRNA expression in cancer cell lines cultured with or without methylation inhibitor was also analyzed by quantitative PCR. Out of 105 specimens tested, less than 25% of tumor cells were stained with anti-syndecan-1 monoclonal antibody in 36 (34.3%). In situ hybridization showed a similar staining profile to that of immunohistochemistry. Syndecan-1 mRNA expression was increased by the methylation inhibitor 5-aza-2'-deoxycytidine, suggesting that the hypermethylation is involved in the suppression of syndecan-1 expression. Clinically, the incidence of metastasis to lymphnode or liver in patients with syndecan-1-negative tumors was significantly high. Among T1 colorectal cancers displaying a primary invasive phase, lymphnode metastasis, undifferentiated characters and 'budding' of cancer cells were more common in syndecan-1-negative tumors. The survival rate in patients with syndecan-1-negative tumors was decreased significantly in a stage-independent manner. These results suggest that the reduction of syndecan-1 expression in colorectal cancer cells, which is supposed to be regulated at the transcription level, is closely related to invasive character. The evaluation of syndecan-1 expression in colorectal cancer may allow prediction of patients' survival after surgery.

Adenocarcinoma↗

PubMed2001

Medication management skill and regimen compliance are deteriorated in the elderly even without obvious dementia.

We investigated whether regimen comprehension deteriorated in the elderly patients who did not suffer from obvious dementia. Eligible patients were ambulatory elderly patients who did not show any signs of dementia and could visit our outpatient clinic by themselves. 138 patients (age: 43-89, 75 males and 63 females, underlying diseases: hypertension, hyperlipidemia, arrhythmia etc.) were tested with a regimen comprehension scale (RCS: Jpn J Geriat 1997; 34: 209-214). The differences in scores among individuals increased with age. Scores of 5 or less in the RCS were recorded in 10 out of 69 patients aged 65 or more, but no such scores were recorded in younger patients (p < 0.01). The 60 patients who scored less than full marks were classified into two groups, the T-group (tutored by pharmacists), and a Non Tutored group. RCS was tested again in both groups. Only in the T-group (n = 28), did the second scores increase significantly (from 7.2 +/- 0.9 to 8.6 +/- 2.0 (m +/- SD); p < 0.01) after tutorial by pharmacists. Comparing the 7 patients who obtained an RCS score of 5 or less and age- and gender-matched controls who got full marks, there was no difference in the HDS-R test. These results suggest that even in elderly patients who did not show any signs of dementia, the regimen comprehension deteriorated with age, and tutorials in medication protocols were considered to be effective.

Adult↗

PubMed2001

Profiles of patients who control the doses of their antihypertensive drugs by self-monitoring of home blood pressure.

The present study profiled patients who control doses of antihypertensive drugs by themselves based on self-monitoring of their blood pressure (self-controllers). A total of 1,028 consecutive outpatients who were taking antihypertensive drugs and who were attending the cardiovascular outpatient clinic of our institute responded to a questionnaire in 1998. They were asked how often they measured their blood pressure, how often they missed taking their medication, and whether or not they had a chance to adjust the doses of antihypertensive drugs by themselves based on self-monitored blood pressure. The frequency of self-controlling of antihypertensive drugs was also examined in 918 patients on antihypertensive drugs in 1997. In 1997, 23 of 918 patients (2.5%) were self-controllers, and 26 of 1,028 patients (2.5%) were self-controllers in 1998. The frequency of home blood-pressure measurement was significantly greater in self-controllers than in the remaining patients (non self-controllers) (p<0.01). The prevalence of proteinuria was significantly less in the former than in the latter. Prior to the start of antihypertensive drugs, blood pressure was significantly lower for the self-controllers (154.4+/-3.8/96.4+/-1.4 mmHg) than for the non self-controllers (169.3+/-0.7/101.7+/-0.4 mmHg) (p<0.001). Clinically measured blood pressures did not differ significantly between the self-controllers and non self-controllers. Thus, about 2.5% of patients on antihypertensive drugs controlled their drug doses by themselves based on self-monitoring of their blood pressure. These patients were characterized by having a milder form of hypertension and by more frequent home blood-pressure measurement than non self-controllers.

Aged↗

PubMed2001

[An autopsied case of marked cardiac hypertrophy due to multifactorial heart disease in an 85 year-old man who had been socially active].

An autopsied 85-year-old man had suffered from a mild form of diabetes mellitus since the age of 67 and had experienced the first episode of heart failure with arapid ventricular rate of atrial fibrillation at the age of 72. He had remained socially active until he died suddenly of ventricular fibrillation, although he had complications of aortic regurgitation at the age of 76 and later mitral regurgitation at the age of 80. Chest roentgenograms showed gradual increase in the cardiothoratic ratio which reached 68.1% at the final stage. Autopsy revealedmarked left ventricular hypertrophy with a heart weight of 580 g, degeneration ofaortic valves, thickening of mitralvalve cusps and moderate coronary atherosclerosis without ischemic myocardial lesions. There were no specific lesions suggestive of primary cardiomyopathies on microscopic observations and the lesions of both aortic and mitral valves were not significant enough to explain the clinical findings of aortic and mitral regurgitation. Because the pathological examination failed to identify a single disease which was responsible for the marked cardiachypertrophy, we eventually reached the conclusion that the cardiac hypertrophy developed based on a multifactorial heart disease.

Activities of Daily Living↗

PubMed2001

[Treatment of hypertension with dyslipidemia].

Lifestyle modifications are the first approach to the treatment of dyslipidemia and hypertension, that is, control of overweight; reduced intake of saturated fat, cholesterol, sodium chloride, and alcohol; and increased physical activity. In high doses, thiazide diuretics and loop diuretics can induce at least short-term increases in levels of total plasma cholesterol, triglycerides, and low-density lipoprotein cholesterol. Low-dose thiazide diuretics do not produce these effects. beta-blockers may increase levels of plasma triglycerides transiently and reduce levels of high-density lipoprotein cholesterol. alpha-blockers may decrease serum cholesterol concentration to a modest degree and increase high-density lipoprotein cholesterol. Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium antagonists, and central adrenergic agonists have clinically neutral effects on levels of serum lipids and lipoproteins.

Adrenergic alpha-Antagonists↗

PubMed2001

[Differential diagnosis of chronic myeloid leukemia and the related disorders].

Chronic myeloid leukemia(CML) is a generic term that includes five subtypes; i.e. chronic granulocytic leukemia(CGL) (95% of all CML, 90% are Ph+, 5% are Ph-, BCR/ABL+), atypical CML(survival is worse than that of CGL), chronic myelomonocytic leukemia(a subtype of myelodysplastic syndrome), chronic neutrophilic leukemia (Ph-, BCR/ABL-) and juvenile CML(Ph-, BCR/ABL-). It is not so easy to make a diagnosis of Ph-negative CML. Also, about 25% of adult acute lymphoid leukemia(ALL) patients and some essential thrombocythemia patients have Ph chromosome. In addition, about a half of cases with Ph-positive ALL have the same size of BCR/ABL fusion protein as that in Ph-positive CML. It is necessary to distinguish them by the distinctive morphological, cytogenetical and immunological characteristics of these diseases.

Diagnosis, Differential↗

PubMed2000

Expression of glucocorticoid receptor beta in lymphocytes of patients with glucocorticoid-resistant ulcerative colitis.

BACKGROUND & AIMS: Recently, the glucocorticoid receptor beta (hGRbeta) was suggested to play a role as a dominant negative regulator for determining glucocorticoid response. The aim of this study was to clarify whether reverse-transcription polymerase chain reaction (RT-PCR) analysis of hGRbeta messenger RNA (mRNA) can predict the response to glucocorticoids in patients with ulcerative colitis. METHODS: Total RNA obtained from peripheral blood mononuclear cells (PBMCs) of 23 patients with ulcerative colitis and 20 healthy volunteers was reverse transcribed; the resulting complementary DNA was amplified using specific primers for hGRalpha and hGRbeta. Protein expression of hGR in PBMCs was confirmed by immunoprecipitation-Western blot analysis. RESULTS: The expression of hGRalpha mRNA (477 base pairs) was detected in all patients and all healthy volunteers. In contrast, a hGRbeta mRNA (366 base pairs) was detected in 1 (9.1%) of 11 glucocorticoid-sensitive patients, 10 (83.3%) of 12 glucocorticoid-resistant patients, and 2 (10%) of 20 healthy volunteers. The positive rate of hGRbeta mRNA in the resistant group was significantly higher than that in the sensitive group (P = 0.0019). The hGRbeta band could be detected by immunoprecipitation-Western blotting in hGRbeta mRNA-positive patients. CONCLUSIONS: The results show that the expression of hGRbeta mRNA in PBMCs examined by RT-PCR may serve as a novel predictor of glucocorticoid response in ulcerative colitis.

Adolescent↗

PubMed2000

Increases in intracellular calcium of arterial smooth muscle cells in transgenic mice overexpressing Na+/H+ exchanger.

We produced transgenic mice overexpressing Na+/ H+ exchanger as a model of salt-sensitive hypertension and reported that dietary salt loading elevates blood pressure in these transgenic mice. We speculate that this blood pressure elevation may be attributed to the elevation of intraarterial smooth muscle Ca2+ concentration through Na+/Ca2+ exchange. To test this hypothesis, we measured the isometric tension of aortic rings and intracellular free calcium ([Ca2+]i) of cultured smooth muscle cells. In the transgenic mice, the aortic ring contraction induced by 5 mM caffeine (percentage of 60 mM K-induced contraction) was significantly greater than control mice (60.1 +/- 5.5% vs. 44.8 +/- 3.1%). The mean [Ca2+]i in vascular smooth muscle cells (VSMCs) of transgenic mice (123.1 +/- 19.7 nM) was higher than those in VSMCs of control mice (66.6 +/- 7.2 nM). These observations suggest that dietary salt loading increases the concentration of calcium in arterial smooth muscle cells in this transgenic mice. These findings are helpful in tracing the causes of salt-sensitive hypertension.

Animals↗

PubMed2000

A comparative study of changes in fecal flora in patients preconditioned with either amphotericin B or fluconazole for allogeneic bone marrow transplantation.

The present study investigated fecal flora changes in 20 patients who received either the nonabsorbable antifungal agent amphotericin B, or the absorbable antifungal agent fluconazole, with tobramycin and vancomycin as preparation for undergoing allogeneic bone marrow transplantation (BMT). The oral antibiotic regimen consisted of tobramycin (540 mg/day, three times a day), vancomycin (1,500 mg/day, three times a day) and either amphotericin B (2,400 mg/day, twice a day) (AMPH group) or fluconazole (400 mg/day, twice a day) (FLCZ group) and was designed to prevent infections from microorganisms in the gut. Aerobic bacterial colonies were not detected on the day of BMT or 1 week after BMT, except in 1 case unable to take the full antibiotic regimen due to nausea and vomiting. Anaerobic bacterial colonies were not detected on the day of BMT except in this single case. Furthermore, there were no episodes of bacterial infection. In both groups, Candida colonies were detected in some case. Candida colonies were also detected in the pharynx and urine. However, there were no fungal infections. The present report suggests that amphotericin B and fluconazole administrations, with tobramycin and vancomycin, are equally effective for protection against bacterial and fungal infections in BMT recipients.

Adolescent↗

PubMed2000

Balloon-occluded endoscopic retrograde ileography.

For diagnostic ileography, the authors developed balloon-occluded endoscopic retrograde ileography and performed 77 studies in 36 consecutive patients with Crohn disease. Balloon-occluded endoscopic retrograde ileography proved to be useful in visualization of minute mucosal lesions such as aphthous ulcers and lymphoid hyperplasia in the distal ileum, and satisfactory ileographic images of Crohn disease were obtained in 54 (70%) studies.

Adolescent↗

PubMed2000

Relationship between home blood pressure measurement and medication compliance and name recognition of antihypertensive drugs.

This study examined the relationship of home blood pressure measurement to medication compliance and name recognition of antihypertensive drugs in outpatients with hypertension. A total of 1,452 consecutive outpatients (842 males, 610 females; mean age 65+/-11 yr) seeking care at our institute answered questions at our cardiovascular outpatient clinic such as whether they had a sphygmomanometer at home, how often they measured their blood pressure at home, and how often they missed taking their medication. Among a total of 777 patients on antihypertensive drugs who had a sphygmomanometer at home, 16 of the 242 patients (6.5%) who measured their home blood pressure every day occasionally missed taking their medication, whereas this number was 22 for the 216 patients (10.1%) who measured their home blood pressure several times a week, 16 for the 146 patients (11.0%) who measured their home blood pressure several times a month, and 25 for the 173 patients (14.5%) who never measured their home blood pressure (p< 0.01 between patients who measured their home blood pressure every day and those who did not measure their home blood pressure). Among a total of 271 patients taking one or two antihypertensive drugs, the number of patients who could name their antihypertensive drugs was 47 of the 86 patients (55%) who measured their home blood pressure every day, 43 of the 78 patients (55%) who measured their home blood pressure several times a week, 24 of the 41 patients (58%) who measured their home blood pressure several times a month, and 22 of the 66 patients (33%) who never measured their home blood pressure (p< 0.02). In conclusion, medication compliance and antihypertensive drug name recognition were better in patients who measured their home blood pressure than in patients who did not measure their home blood pressure. From these results, we conclude that physicians should recommend home blood pressure measurement to patients being treated with antihypertensive drugs, because there is a possibility that home blood pressure measurement might improve medication compliance.

Aged↗

PubMed2000

Office blood pressure variability as a predictor of brain infarction in elderly hypertensive patients.

Large 24-h blood pressure (BP) variability and an excessive drop in BP during nighttime are associated with a higher risk of cardiovascular events. Data are lacking regarding the prognostic significance of variability in BP measured during office visits. We analyzed the relationship between office BP variability and the risk of brain infarction in elderly patients receiving antihypertensive therapy. Patients who experienced their first-ever stroke at the age of 60 years or over were registered in the study. At least 2 sex- and age-matched control patients were registered for each case patient. Office BP at each clinic visit and known cardiovascular risk factors were recorded. The BP variability was defined as the variation coefficient (VC) of office BP. In this report, we analyze the data of brain infarction patients. The VC of both systolic and diastolic BPs was significantly higher in the brain infarction patients than in the control patients. Higher office BP variability was associated with a higher risk of brain infarction after adjustment for BP level and other confounding factors. Regarding diastolic BP, the association of brain infarction with the maximal value for the difference of office BPs taken at any consecutive two visits (Max-deltaBP) or the difference between the highest and lowest values of office BP (BP-range) recorded during a 1-year period prior to the event was also significant. In conclusion, a retrospective case-control study suggested that office BP variability was an independent predictor of brain infarction. Either the Max-deltaBP or the BP-range may be surrogate indices of diastolic BP variability.

Aged↗