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Biomedical subjects

K Tamura

Publications and source records attributed to K Tamura.

At least 271 records · Page 15Linked to original sources
PubMed1999

A phase II study employing combination regimens containing KRN8602 in drug-resistant acute myeloid leukemia and acute lymphoblastic leukemia. KRN8602 Leukemia Study Group.

We conducted a phase II multicenter study in order to evaluate the efficacy and toxicity of two combination regimens containing KRN8602 (MX2) for drug-resistant acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). AML was treated with KRN8602, 15 mg/m2 i.v. push for 5 days, and cytarabine (AraC), 100 mg/m2 by 24 h coutinuous infusion for 7 days. ALL was treated with KRN8602, 15 mg/m2 i.v. push for 5 days, vincristine (VCR), 1.4 mg/m2 i.v. push, once weekly, and prednisolone (PSL), 40 mg/m2, 3 h infusion for 5 days. In AML and ALL, the complete remission (CR) rate was 36.4% (16 of 44) and 24.1% (seven of 29), and the overall response rate (CR+PR) was 52.3% (23 of 44) and 51.7% (15 of 29), respectively. Among the 29 relapsed cases of AML, a higher CR rate, 51.7% (15 of 29), was obtained. A high incidence of nausea/vomiting and anorexia was observed, and some patients experienced central nervous system disorders and peripheral neuropathy. There was a low incidence of severe neurotoxicities; all other toxicities were manageable. KRN8602 was found to overcome drug resistance clinically, confirming results based on the preclinical studies. We conclude that KRN8602 is an effective novel anthracycline for drug-resistant acute leukemias.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

I-123 MIBG cardiac imaging in diabetic neuropathy before and after epalrestat therapy.

I-123 metaiodobenzylguanidine (MIBG) scintigraphy is a new method to evaluate cardiac sympathetic nerve disturbance in patients with diabetes mellitus. Epalrestat specifically inhibits aldose reductase and improves diabetic neuropathy. The authors report a case of improvement in cardiac sympathetic dysfunction using MIBG scintigraphy with epalrestat therapy. In this case, epalrestat effectively reversed diabetic neuropathy, and MIBG scintigraphy was useful to evaluate the effect of epalrestat.

3-Iodobenzylguanidine↗
PubMed1999

Renin-angiotensin system and fibronectin gene expression in Dahl Iwai salt-sensitive and salt-resistant rats.

OBJECTIVE: The tissue renin-angiotensin system and extracellular matrix are involved in the cardiovascular hypertrophy and remodeling induced by hypertension. In this study, we examined the gene expression of the tissue renin-angiotensin system and fibronectin in inbred Dahl Iwai salt-sensitive and salt-resistant rats. MATERIALS AND METHODS: Eight pairs of 6-week-old male Dahl Iwai salt-sensitive and salt-resistant rats were fed either a low- or high-salt diet (0.3% or 8% NaCl, respectively) for 4 weeks. Activities of the circulating renin-angiotensin system were measured by radioimmunoassay and the gene expression of tissue angiotensinogen, the angiotensin II type 1 receptor (AT1) and fibronectin were analyzed by Northern blot analysis. RESULTS: Salt loading significantly increased blood pressure and produced cardiovascular hypertrophy and nephrosclerosis in the salt-sensitive rats. Activities of the circulating renin-angiotensin system were lower in salt-sensitive rats than in salt-resistant rats fed the low-salt diet, and salt loading lowered these activities in salt-resistant rats but not in salt-sensitive rats. In salt-resistant rats, salt loading increased renal, cardiac and aortic angiotensinogen, AT1 and fibronectin messenger (m)RNA expression except for aortic fibronectin mRNA expression. In contrast, in the salt-sensitive rats, salt loading stimulated the expression of cardiac fibronectin and aortic angiotensinogen, AT1 and fibronectin mRNAs. Furthermore, the cardiac and aortic fibronectin mRNA levels in salt-sensitive rats were higher than those in salt-resistant rats when both strains were fed the high-salt diet. CONCLUSIONS: These results demonstrate that the expression of tissue angiotensinogen, AT1 and fibronectin mRNAs is regulated differently in Dahl Iwai salt-sensitive and salt-resistant rats, and indicate that salt-mediated hypertension activates the cardiac fibronectin gene independently of the tissue renin-angiotensin system and stimulates the aortic fibronectin gene with activation of the tissue renin-angiotensin system.

Angiotensin I↗
PubMed1999

Comparative significance of p53 and WAF/1-p21 expression on the efficacy of adjuvant chemotherapy for resectable invasive ductal carcinoma of the pancreas.

p53 tumor-suppressor gene has a dual role as a trigger of apoptosis and as an initiator of DNA repair. The cyclin-dependent kinase inhibitor WAF/1-p21 is induced by wild-type p53 and has been implicated as a downstream mediator of the growth-suppressing and apoptosis-promoting function of wild-type p53, suggesting an impact on the effectiveness of chemotherapy. This study was designed to assess the significance of p53 and WAF/1-p21 expression in the prognosis of patients and the efficacy of adjuvant chemotherapy for resectable invasive ductal carcinoma (IDC) of the pancreas. A total of 58 patients with primary IDC of the pancreas underwent pancreatectomy between 1982 and 1996: 28 patients underwent surgery alone, and 30 patients received postsurgical adjuvant chemotherapy. p53 and WAF/1-p21 were stained immunohistochemically with anti-p53 monoclonal antibody (mAb) and anti-WAF/1-p21 mAb. p53 was positively expressed in 29 (50%) of 58 primary lesions, and p21 was expressed in 24 (41%) lesions; however, p21 expression did not necessarily correlate with p53 expression. The survival curve of the patients with p53(+) IDC was significantly lower than that of those with p53(-) IDC, and p21(+) patients showed a higher survival curve than did p21(-) patients, but this difference was not statistically significant. When p53 and p21 expression were analyzed in combination, the patients with p53(+)p21(-) IDC were found to have a significantly poorer prognosis than others. On the other hand, the survival curve of the adjuvant chemotherapy group was also higher than that of the surgery-alone group, but this difference was not significant. In a multivariate analysis, p21 expression was a significantly low risk factor for death due to IDC overall, and adjuvant chemotherapy was found to decrease the risk of death from IDC in p53(+) patients. Evaluation of expression of p53 and WAF/1-p21 may be beneficial in the prediction of the patient's prognosis as well as prediction of the effects of adjuvant chemotherapy in pancreatic cancer patients.

Adult↗
PubMed1999

Dynamic light-scattering and preliminary crystallographic studies of the sensor domain of the haem-based oxygen sensor FixL from Rhizobium meliloti.

FixL is a transmitter protein in a two-component system which acts as an oxygen sensor when the symbiotic Rhizobia resides in root nodules of host plants. The oxygen-sensor domain of Rhizobium meliloti FixL (RmFixLH) was purified by His-tag affinity and isoelectronic focusing chromatographies, without the use of gel-filtration chromatography. Dynamic light-scattering measurements of RmFixLH thus obtained revealed it to be monodispersive and present as a homodimer in solution. A single crystal of RmFixLH in the met (Fe3+) form was grown in 100 mM acetic acid/NaOH buffer at pH 4.6 in the presence of 200 mM ammonium acetate, using 40%(w/v) PEG 4000 as a precipitant. A crystal of the ferrous CO form of RmFixLH was also prepared by reduction of the met crystal with Na2S2O4 in an atmosphere of CO. The crystals (0.2 x 0.05 x 0.01 mm) belong to the monoclinic system (C2) with unit-cell parameters a = 60.94, b = 37.44, c = 54.14 A, beta = 115.29 degrees and diffract X-rays to 1.7 A resolution at station BL44B2 of SPring-8, Japan. Bijvoet difference Patterson maps show a clear peak corresponding to the haem iron in RmFixLH.

Bacterial Proteins↗
PubMed1999

[Isolation of Shiga toxin-producing Escherichia coli O157:H7 from processed salmon roe associated with the outbreaks in Japan, 1998, and a molecular typing of the isolates by pulsed-field gel electrophoresis].

Shiga toxin-producing Escherichia coil (STEC) O157 were isolated from processed salmon roe which had been a suspected food item in sporadic infections which occurred in Japan in 1998. A total of 45 samples of the processed salmon roe were pre-enriched in trypticase soy broth (TSB) at 36 degrees C for 6 h and novobiocin-supplemented modified EC broth (mEC-NB) at 42 degrees C for 18 h. After the pre-enrichments, the cultures were examined for possible occurrence of STEC O157, using an immunomagnetic separation (IMS) method. From the examination, a total of 84 strains of STEC O157:H7 that were positive for both stx 1 and stx 2 genes were isolated. By applying the most-probable-number technique, it was estimated that the number of STEC O157 was in the range of 0.73-1.5 per 10 g of the processed salmon roe. Subsequent analysis of the isolates by a pulsed-field gel electrophoresis (PFGE) revealed a pattern commonly seen in 82 isolates and another pattern in two isolates. Clinical isolates from 7 patients also showed an identical pattern to those of the 82 isolates and one isolate from a patient showed the other pattern identical to those of the two isolates. The isolates were found to belong to the phage type 14.

DNA, Bacterial↗
PubMed1999

Alterations of autonomic nervous activity in recurrence of variant angina.

OBJECTIVE: To investigate whether autonomic nervous activity is involved in the recurrence of spontaneous coronary spasm in variant angina. DESIGN: Retrospective analysis. SETTING: Cardiology department of a university hospital. PATIENTS: 18 patients with variant angina were divided into single attack group (SA; nine patients) and multiple attack group (MA; nine patients) according to the frequency of ischaemic episodes with ST segment elevation during 24 hour Holter monitoring. METHODS: Heart rate variability indices were calculated using MemCalc method, which is a combination of the maximum entropy method for spectral analysis and the non-linear least squares method for fitting analysis, at 30 second intervals for 30 second periods, from 40 minutes before the attack to 30 minutes after the attack. High frequency (HF; 0.04-0.15 Hz) was defined as a marker of parasympathetic activity, and the ratio of low frequency (LF; 0.15-0.40 Hz) to high frequency (LF/HF) as an indicator of sympathetic activity. The averaged value during the 40 to 30 minute period before an attack was defined as the baseline. RESULTS: Compared with baseline, the HF component decreased in both groups at two minutes before the attack (p < 0.01), and the LF/HF ratio decreased at three minutes before the attack (p < 0.01). The baseline LF/HF was lower in the MA group than in the SA group (p < 0. 01). CONCLUSIONS: A reduction of sympathetic activity may play a key role in determining the recurrence of transient ischaemic events caused by spontaneous coronary spasm in patients with variant angina.

Aged↗
PubMed1999

Lung abscess caused by Paecilomyces lilacinus.

We report the case of a 57-year-old man who was referred to our department for further investigation of an abnormal chest shadow. Radiography on admission demonstrated a coin lesion in the right hilum. To make a final diagnosis, right middle lobectomy was performed and the mass was revealed to be a fungal abscess. Further examination confirmed that the fungus was Paecilomyces lilacinus. This is the first reported case of lung abscess caused by P. lilacinus in an otherwise healthy person.

Humans↗
PubMed1999

Simultaneous improvement of minimal-change nephrotic syndrome and anemia with steroid therapy.

A 56-year-old man presented with transient anemia in minimal-change nephrotic syndrome. Following nephrotic syndrome, anemia suddenly appeared without renal dysfunction. The anemia might be attributable to hemodilution because of significant correlations between the values of hemoglobin concentration and serum total protein or blood urea nitrogen during the clinical course. A low serum level and a low urinary excretion of erythropoietin were found, and when nephrotic syndrome ameliorated with steroid therapy, urinary erythropoietin excretion and anemia disappeared. This case indicated disappearance of the exponential increase of endogenous erythropoietin in acute anemia in nephrotic syndrome probably due to urinary losses and altered biosynthesis of erythropoietin. We report a case of the simultaneous improvement of both nephrotic syndrome and anemia with steroid therapy.

Anemia↗
PubMed1999

Interferon regulatory factors regulate interleukin-1beta-converting enzyme expression and apoptosis in vascular smooth muscle cells.

-Apoptosis has been reported to play a pivotal role in vascular remodeling. However, cellular mechanisms of apoptosis in vascular smooth muscle cells (VSMCs) have not been well defined. In this study, we focused on interleukin-1beta-converting enzyme (ICE), a key protease in the induction of apoptosis in lymphocytes and fibroblasts. We observed an increase in ICE mRNA expression in rat aortic VSMCs after serum depletion, with a peak at 12 hours and then a gradual decline. This was associated with DNA fragmentation, a hallmark of apoptosis and morphological changes of apoptosis. Treatment of these VSMCs with the ICE inhibitor N-(N-acetyl-tyrosinyl-valinyl-alaninyl)-3-amino-4-oxob utanoic acid (YVAD-CHO) attenuated DNA fragmentation. The increased ICE mRNA expression was preceded by an increase in the mRNA expression of interferon regulatory factor (IRF)-1, peaking at 6 hours after serum removal, and a rapid but transient decrease in IRF-2 mRNA expression, reaching a nadir at 3 hours after serum depletion. To demonstrate that these reciprocal changes in IRF-1 and IRF-2 regulated ICE expression and induced apoptosis, we transfected antisense oligonucleotides for IRF-1 and IRF-2 into VSMCs and examined ICE mRNA expression and apoptotic changes. IRF-1 antisense pretreatment attenuated the increase in ICE expression and reduced apoptotic changes, whereas IRF-2 antisense treatment increased ICE mRNA expression and enhanced apoptotic changes. Taken together, our results suggest that serum growth factor depletion in VSMCs upregulates IRF-1 and downregulates IRF-2, thereby increasing ICE expression and inducing apoptosis.

Animals↗
PubMed1999

AT2 receptor and vascular smooth muscle cell differentiation in vascular development.

The angiotensin II type 2 (AT2) receptor is transiently expressed at late gestation in the fetal vasculature, but its expression rapidly declines after birth. We have previously demonstrated that the expression of this receptor mediates decline in vascular DNA synthesis that occurs at this stage of vascular development. To examine further the role of the AT2 receptor in vasculogenesis, we have focused on the effect of the AT2 receptor on vascular smooth muscle cell (VSMC) differentiation. In this study, we examined the time-dependent expression of differentiation markers for VSMCs in the aorta of wild-type and AT2 receptor-null mice. alpha-Smooth muscle actin was expressed at the early stage of differentiation and exhibited unchanged expression before and after the peak of AT2 receptor expression, which was observed at embryonic day 20, neonatal day 1, and thereafter. No difference in alpha-smooth muscle actin expression was observed between the wild-type and AT2 receptor-null mice. In contrast, the mRNA levels for calponin, expressed in the late stage of VSMC differentiation, were significantly higher in the wild-type mouse aorta as compared with the AT2 receptor-null mice, which correlates with expression of the AT2 receptor. Moreover, the protein levels of calponin and high-molecular-weight caldesmon (h-caldesmon) showed lower expression in the aorta of AT2 receptor knockout mice at 2 and 4 weeks after birth. Taken together, our results suggest that the AT2 receptor promotes vascular differentiation and contributes to vasculogenesis.

Aging↗
PubMed1999

Angiotensinogen gene polymorphism near transcription start site and blood pressure: role of a T-to-C transition at intron I.

Molecular variants of the angiotensinogen gene, a key component of the renin-angiotensin system, are considered genetic risk factors for primary hypertension. A relation between the angiotensinogen gene locus and hypertension has been found in whites, Japanese, and African Caribbeans but not in Chinese. The lack of a consistent association between M235T polymorphism at exon 2 and hypertension has suggested that another site in linkage disequilibrium with M235T is the causal mutation. We studied the relations among plasma angiotensinogen concentrations, blood pressure, related clinical variables, and mutations of the 5' upstream core promoter region of the human angiotensinogen gene in 274 subjects recruited from our outpatient clinic. We confirmed that plasma angiotensinogen concentration was significantly correlated with A-20C mutation and percent body fat and found that systolic and diastolic blood pressures were significantly correlated with G-6A and T+68C mutations. These results suggest that mutations near the transcription start site may be associated with increased blood pressure.

Angiotensinogen↗
PubMed1999

Elevated circulating levels of basic fibroblast growth factor and vascular endothelial growth factor in patients with acute myocardial infarction.

Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have both shown strong angiogenetic effects in ischemic animal models and it has been reported that these growth factors were increased after acute myocardial ischemia. However, there have been few reports on the serum levels of bFGF and VEGF after acute myocardial infarction (AMI), in particular there has not been a comparative study of bFGF and VEGF in human subjects. The time course of circulating levels of bFGF and VEGF was examined in 36 patients with AMI who were within 24h of the onset of the AMI. The serum bFGF and VEGF levels of 50 age- and sex-matched healthy volunteers served as the baseline value. All the patients had undergone coronary angiography on the day of admission (Day 0), but prior to that the serum bFGF and VEGF levels were examined by enzyme-linked immunoassay. The serum bFGF and VEGF levels were also evaluated on Days 7, 14 and 28. Creatine kinase, myosin light chain I and troponin-T were measured subsequently and radionuclide examinations were performed during the early phase of AMI to determine the infarct size. The serum bFGF levels were significantly increased at Day 0 and were maintained until Days 7 and 14. Although serum VEGF levels at Day 0 were similar to the baseline values, they showed a remarkable increase by Days 7 and 14. A high serum level of bFGF was detected in the acute phase of AMI, and a later increase in VEGF was determined in the sub-acute phase, which suggest that these 2 growth factors play an important role at different time points of the reconstructing process of infarcted myocardial tissue.

Acute Disease↗
PubMed1999

Exercise-induced uncommon atrioventricular nodal reentrant tachycardia with sick sinus syndrome: a case report.

Exercise seldom provokes tachycardia in patients with paroxysmal supraventricular tachycardia (PSVT). This report presents a case of exercise-induced uncommon atrioventricular nodal reentrant tachycardia (AVNRT) with sick sinus syndrome. Treadmill exercise testing provoked AVNRT of long RP' with good reproducibility. Uncommon AVNRT was confirmed by the lack of atrial pre-excitation during PSVT and para-Hisian pacing. The patient has been successfully treated with verapamil and DDD pacing for 5 years.

Aged↗
PubMed1999

The expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and its regulation by ovarian steroids in rat uterine stromal cells.

The effects of ovarian steroids on the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) in rat uterus were examined. Intense expression of GM-CSF mRNA was dispersedly located in the endometrial-myometrial junction and stroma of the uterus. GM-CSF was immunohistochemically localized in stromal cells and luminal epithelium. Ovariectomy significantly reduced the appearance of GM-CSF-mRNA-positive cells and the levels of expression for GM-CSF mRNA in the whole uterus, whereas treatment with 17beta-estradiol (E2) or a combination of E2 and progesterone (P4) for 5 days on ovariectomized animals recruited GM-CSF-mRNA-positive cells and stimulated its expression. The combined treatment with E2 and P4 also stimulates the expression for GM-CSF mRNA and the production of immunoreactive GM-CSF in the stromal tissues. These data suggest that the expression of GM-CSF in uterine stromal cells is partially regulated by ovarian steroids.

Animals↗