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Biomedical subjects

K Takeda

Publications and source records attributed to K Takeda.

At least 487 records · Page 27Linked to original sources
PubMed1998

Assessment of myocardial fibrosis in cardiomyopathic hamsters with gadolinium-DTPA enhanced magnetic resonance imaging.

RATIONALE AND OBJECTIVES: The authors investigated whether magnetic resonance (MR) imaging enhanced with gadolinium (Gd)-DTPA would be useful for assessment of myocardial fibrosis in cardiomyopathy. METHODS: The authors compared MR images of the excised heart after Gd-DTPA injection with histopathologic findings in 33 hamsters with cardiomyopathy of the Bio 14.6 strain and 26 healthy hamsters of various age groups and assessed localization of Gd-14C-DTPA by autoradiography in the myocardium of three hamsters with cardiomyopathy. RESULTS: The mean signal intensity ratios for the entire myocardium in hamsters with cardiomyopathy relative to that in healthy hamsters was significantly higher in a younger age group than in an older age group (1.30+/-0.09 versus 1.03+/-0.08, P < 0.001, respectively). This myocardial enhancement was more obvious in areas containing massive fibrosis in the early and mid stages than in the late stage. Autoradiograms of hamsters with cardiomyopathy showed patchy or linear increases in uptake, corresponding to the areas of myocardial fibrosis. Gadolinium-14C-DTPA radioactivity ratios of myocardial fibrosis to healthy myocardium were significantly higher in the early and mid stages than in the late stage (P < 0.01). CONCLUSIONS: Myocardial fibrosis with high cellularity and proliferation of vessels was delineated as an area enhanced with Gd-DTPA on MR images, and its signal intensity decreased with the late stage of myocardial fibrosis.

Analysis of Variance↗
PubMed1998

Evaluation of altered myocardial high energy phosphate metabolism in patients on maintenance dialysis using phosphorus-31 magnetic resonance spectroscopy.

RATIONALE AND OBJECTIVES: Assessment of left ventricular metabolism and function is important in patients on maintenance dialysis because congestive heart failure occurs quite frequently and has a poor prognosis. The purpose of this study was to evaluate the changes of myocardial high energy metabolism in dialysis patients by using phosphorus-31 (31P) magnetic resonance (MR) spectroscopy. METHODS: Phosphorus-31 spectra were obtained from anteroseptal wall of the heart in six normal subjects (mean age, 24 +/- 1 years) and 14 dialysis patients (mean age, 52 +/- 11 years), using a 1.5-tesla clinical MR system. Four patients had previous history of heart failure. Echocardiography was performed in all patients to evaluate left ventricular (LV) hypertrophy and LV function. RESULTS: The averaged ratio of phosphocreatine (PCr)/beta-adenosine triphosphate (beta-ATP) in dialysis patients (1.15 +/- 0.25 mean +/- standard deviation), was significantly lower than that in healthy subjects (1.63 +/- 0.21; P < 0.01). There was no significant difference in PCr/beta-ATP ratios between the non-LV hypertrophy group (1.21 +/- 0.24; n = 7) and the LV hypertrophy group (1.09 +/- 0.24; n = 7). The averaged PCr/beta-ATP ratio in four patients with history of heart failure (0.96 +/- 0.18) was significantly lower than that of the 10 patients without history of heart failure (1.22 +/- 0.23; P < 0.05). CONCLUSIONS: These results indicate that patients on maintenance dialysis have decreased PCr/beta-ATP ratio and 31P MR spectroscopy can provide noninvasive assessment of altered high energy phosphate metabolism.

Adenosine Triphosphate↗
PubMed1998

Augmented response of endothelin-A and endothelin-B receptor stimulation in coronary arteries of hypertensive hearts.

To determine whether the vasoconstrictor response to endothelin-1 (ET-1) is altered in coronary vessels of hypertensive hearts and the role of ETA and ETB receptors in these responses to ET-1, the vasoconstrictor response to ET-1 in coronary vessels was measured with or without ETA and ETB receptor antagonists. In isolated hearts of spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat, the coronary perfusion pressure was measured on a Langendorff apparatus with constant pressure (75 mm Hg). Coronary perfusion resistance (CPR) (mm Hg/ml/min/g) was calculated. ET-1 elicited dose-dependent increases of CPR in both normotensive and SHR rat hearts. However, the responses were significantly greater in SHR than those of WKY. Pretreatment with the ETA antagonist FR139317 and the ETB antagonist BQ788 inhibited CPR increases with ET-1 infusion. However, vasoconstrictor responses to ET-1 were still greater in SHR than in WKY after FR139317 or BQ788 infusion. These findings suggest that the augmented vasoconstrictor response of coronary artery to ET-1 is mediated by both ETA and ETB receptors. These changes may contribute to the impaired coronary circulation in hypertension.

Animals↗
PubMed1998

Blockade of angiotensin II receptors inhibits the increase in blood pressure induced by insulin.

To elucidate whether hyperinsulinemia increases blood pressure by increasing sympathetic outflow via the activation of the central angiotensin system, insulin was infused into urethane-anesthetized rats intravenously (i.v.) or intracerebroventricularly (i.c.v.) under euglycemic conditions. Infusion (i.v.) of insulin elicited pressor effects in a dose-dependent manner (13, 20, and 40 mU/min). Although depressor responses to i.v. injections of hexamethonium were significantly greater in insulin-infused than in saline-infused rats, i.v. captopril and d(CH2)5Tyr(Me)-arginine vasopressin did not show any differences between the groups. Infusions (i.c.v.) of insulin (8 mU/10 microl) also induced cardiovascular acceleration and augmented the depressor response to i.v. hexamethonium in insulin-infused rats. The i.c.v. pretreatment with the angiotensin II antagonist losartan inhibited the pressor responses to both the i.c.v. and i.v. infusion of insulin. These results suggest that the increase in blood pressure induced by euglycemic hyperinsulinemia is elicited by sympathetic activation and that hyperinsulinemia stimulates the angiotensin system in the brain to increase sympathetic nerve activity.

Angiotensin II↗
PubMed1998

Criteria for diagnosis of acute pancreatitis in Japan and clinical implications.

The Japanese grading system for severity of acute pancreatitis has evolved from results of a national survey on 2,553 patients managed in 523 major medical centers in Japan between 1982 and 1986. It was devised to embrace the predictive factors that would offer high sensitivity and specificity in rendering an accurate diagnosis. In this system, computed tomographic (CT) examination is used for estimating the severity of acute pancreatitis. Combining criteria from laboratory data, clinical signs, and CT findings, the system appears cumbersome. However, it is actually more flexible in that only few criteria, from the wide range of findings actually covered, are needed to predict severity. Its rationale stems from a national effort to improve the outcome of this life-threatening disease. Further prospective studies are needed to determine its accuracy and superiority.

Acute Disease↗
PubMed1998

Surgical aspects and management of acute necrotizing pancreatitis: recent results of a cooperative national survey in Japan.

A cooperative national survey between 1991 and 1994 recently clarified the status of acute necrotizing pancreatitis in Japan. The overall mortality rate was 20.8%; however, the mortality rate in patients with infection was 33.3%, and the mortality rate in patients who underwent surgery was 27.4%. With regard to surgical procedures, drainage procedures (mobilization of the pancreatic bed and retroperitoneal drainage) were performed most frequently, and one third of the patients who underwent drainage procedures needed reoperation. Although debridement of the necrotic tissue (necrosectomy or resection of the pancreas) was performed in 33.3%, the mortality rate was 35.3%. There was no difference in the mortality rate between early and delayed operation. Recently two new modalities have been advocated for the management of severe acute pancreatitis in Japan. One is continuous regional arterial infusion of protease inhibitor and antibiotics, and the other is continuous hemodiafiltration. Further work is needed to establish the most effective procedures for the management of acute necrotizing pancreatitis and debridement of pancreatic infection.

Adolescent↗
PubMed1998

Treatment for advanced testicular cancer with high-dose chemotherapy and autologous blood stem cell transplantation.

BACKGROUND: This study was carried out to investigate the efficacy and safety of high-dose chemotherapy (HDC) for the treatment of patients with advanced testicular cancer. METHODS: Seven patients were treated with high-dose carboplatin, etoposide, and ifosfamide followed by autologous blood stem cell transplantation. One patient received 1 cycle, 4 patients received 2 cycles, and 2 patients received 3 cycles of HDC. We performed a total of 15 autologous blood stem cell transplantations: 8 with autologous bone marrow; 6 with peripheral blood stem cells; and 1 with peripheral blood stem cells in addition to autologous bone marrow. RESULTS: Four of the 7 patients achieved a pathologic complete response via early use of HDC and additional salvage surgery. All 4 patients are still alive without evidence of disease at 12, 30, 33, and 54 months, respectively. One patient is alive with active disease at 35 months. Two patients refractory to conventional chemotherapy died of progressive disease at 5 and 27 months, respectively. The hematologic recovery after HDC was rapid, and peripheral blood stem cells tended to have shorter hematologic recovery compared with those from autologous bone marrow, although the difference was not significant. Nonhematologic toxicity was usually mild and manageable. CONCLUSION: High-dose chemotherapy, followed by autologous blood stem cell transplantation, may be safe and effective for patients with advanced testicular cancer, particularly when early use of HDC is conducted for chemotherapy-sensitive patients. A further large, long-term, follow-up study will be needed to define the role of HDC.

Adolescent↗
PubMed1998

A big gene linked to small eyes encodes multiple Mitf isoforms: many promoters make light work.

Among more than 80 different loci related to mouse coat color, microphthalmia-associated transcription factor (Mitf) encoded at the mouse microphthalmia locus is one of the most exciting molecules that regulates the development and survival of many cell types, including melanocyte, retinal pigment epithelium (RPE), and mast cells. Mitf and its human homolog MITF consist of at least three isoforms, referred to as Mitf-A/MITF-A, the heart-type Mitf-H/MITF-H, and the melanocyte lineage-specific Mitf-M/MITF-M, respectively. These isoforms differ in the amino-terminal domains but share a transactivation domain and a basic helix-loop-helix and leucine-zipper structure that is required for DNA binding and dimerization. MITF-M is exclusively expressed in melanocytes and melanoma cells, but not in other cell types, including RPE cells. In contrast, MITF-A mRNA is widely expressed in many cell types. These three isoform mRNAs are possibly generated by differential usage of the gene promoters and by alternative splicing. We predict that the entire MITF gene spans about 200 kb of DNA. Like MITF-M, MITF-A is able to activate the two melanogenesis gene promoters, tyrosinase and tyrosinase-related protein 1. These results suggest that melanogenesis may be regulated by different MITF isoforms in melanocyte and RPE. Possible implications of the multiplicity in Mitf/MITF isoforms are discussed.

Amino Acid Sequence↗
PubMed1998

ZIP kinase, a novel serine/threonine kinase which mediates apoptosis.

We have identified a novel serine/threonine kinase, designated ZIP kinase, which mediates apoptosis. ZIP kinase contains a leucine zipper structure at its C terminus, in addition to a kinase domain at its N terminus. ZIP kinase physically binds to ATF4, a member of the activating transcription factor/cyclic AMP-responsive element-binding protein (ATF/CREB) family, through interaction between their leucine zippers. The leucine zipper domain is necessary for the homodimerization of ZIP kinase as well as for the activation of kinase. Immunostaining study showed that ZIP kinase localizes in the nuclei. Overexpression of intact ZIP kinase but not catalytically inactive kinase mutants led to the morphological changes of apoptosis in NIH 3T3 cells, suggesting that the cell death-inducing activity of ZIP kinase depends on its intrinsic kinase activity. Interestingly, the catalytic domain of ZIP kinase is closely related to that of death-associated protein kinase (DAP kinase), which is a mediator of apoptosis induced by gamma interferon. Therefore, both ZIP and DAP kinases represent a novel kinase family, which mediates apoptosis through their catalytic activities.

3T3 Cells↗
PubMed1998

Nitric oxide regulates energy metabolism and Bcl-2 expression in intestinal epithelial cells.

Nitric oxide (NO) inhibits the respiration of mitochondria and enteric bacteria, particularly under low O2 concentration, and induces apoptosis of various types of cells. To gain insight into the molecular role of NO in the intestine, we examined its effects on the respiration, Ca2+ status, and expression of Bcl-2 in cultured intestinal epithelial cells (IEC-6). NO reversibly inhibited the respiration of IEC-6 cells, especially under physiologically low O2 concentration. Although NO elevated cytosolic Ca2+ as determined by the fura 2 method, the cells were fairly resistant to NO. Kinetic analysis revealed that prolonged exposure to NO elevated the levels of Bcl-2 and suppressed the NO-induced changes in Ca2+ status of the cells. Because Bcl-2 possesses antiapoptotic function, toxic NO effects might appear minimally in enterocytes enriched with Bcl-2. Thus NO might effectively exhibit its antibacterial action in anaerobic intestinal lumen without inducing apoptosis of Bcl-2-enriched mucosal cells.

Animals↗
PubMed1998

Combination of irinotecan and etoposide for treatment of refractory or relapsed small-cell lung cancer.

PURPOSE: To determine the response rate, survival, and toxicity of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with etoposide, a topoisomerase II inhibitor, in refractory or relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: Twenty-five patients with refractory or relapsed SCLC were entered onto the trial. All 25 patients had been pretreated with some form of cisplatin-based combination chemotherapy and had also received previous etoposide- or anthracyclinecontaining chemotherapy. The median time off chemotherapy was 6.7 months (range, 0.9 to 23.5). Patients were treated at 4-week intervals using CPT-11 (a starting dose of 70 mg/m2 intravenously on days 1, 8, and 15) plus etoposide (80 mg/m2 intravenously on days 1 to 3), with a subsequent dose based on toxicity. In addition, recombinant human granulocyte colony-stimulating factor (rhG-CSF; 2 microg/kg/d) was given from day 4 to day 21, except on the days of CPT-11 administration. RESULTS: All patients were assessable for toxicity and survival. Twenty-four patients were assessable for response. There were 14 partial responses (PRs) and three complete responses (CRs), for an overall response rate of 71% (95% confidence interval, 53% to 89%). The median response duration was 4.6 months. Median survival was 271 days. Major toxicities were myelosuppression (predominantly leukopenia) and diarrhea. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 56% and 20% of patients, respectively. Grade 3 to 4 diarrhea was observed in 4%. There was one treatment-related death due to severe myelosuppression. CONCLUSION: A combination of CPT-11 and etoposide with rhG-CSF support is an active therapy against refractory or relapsed SCLC and deserves to be studied more extensively in a phase III trial.

Adult↗
PubMed1998

Effect of dibromochloropropane (DBCP) on the hormone receptors of the male rat reproductive system.

The effects of dibromochloropropane (DBCP), a pesticide, on the male rat reproductive system were examined at morphological and hormonal expression levels. Changes of Leydig cells and seminiferous tubules were examined in rats treated with one subcutaneous (s.c.) injection of DBCP at doses of 10, 50, 75 and 100 mg/kg of body weight. The Leydig cells degenerated and decreased in number in those rats with an s.c. injection of DBCP at a dose of 50 mg/kg of body weight. However, these morphological changes were not significant in those rats that were treated with four separate s.c. injections of DBCP at 10 mg/kg of body weight. The expression of luteinizing hormone receptor mRNA, which is specifically expressed in Leydig cells, was decreased significantly in the DBCP-treated rats as compared with the normal-control rats. The expression of follicle-stimulating hormone receptor mRNA was decreased to a mild degree in DBCP-treated rats. At a dose of 75 mg/kg of body weight, seminiferous tubules as well as Leydig cells were severely damaged morphologically and at hormonal receptor expression levels. Multinucleated giant cells appeared at a dose of 75 mg/kg of body weight. All the rats died at a dose of 100 mg/kg of body weight. Our data indicate that DBCP had a cytotoxic effect on the male rat reproductive system in a dose-dependent manner.

Animals↗
PubMed1998

Lack of pharmacokinetic interaction between mexiletine and omeprazole.

OBJECTIVE: To investigate the effect of omeprazole on the pharmacokinetics of mexiletine. METHODS: Nine healthy male Japanese volunteers participated in a crossover study. On day 1, the subjects received mexiletine 200 mg. On days 2-7, they received omeprazole 40 mg, and on day 8 they received mexiletine 200 mg and omeprazole 40 mg concomitantly. Serum concentrations of mexiletine were determined just before drug administration and at 1, 2, 3, 4, 6, 8, 12, and 24 hours on day 1 and day 8. RESULTS: No differences in mexiletine concentrations were observed between the two phases of the study. The mean AUCs after administration of mexiletine alone and in combination with omeprazole 40 mg/d were 6.26 and 6.20 ng.h/L, respectively. CONCLUSIONS: These findings suggest that omeprazole does not affect mexiletine metabolism.

Administration, Oral↗
PubMed1998

Low incidence of minor myocardial damage associated with coronary stenting detected by serum troponin T comparable to that with balloon coronary angioplasty.

The use of the serum troponin T (TnT) level as a means of assessing minor myocardial injury, which affects the long-term prognosis, has not been fully clarified in patients with coronary artery disease in whom a coronary stent has been implanted. We measured the TnT level to determine the incidence of myocardial damage associated with stent implantation. A total of 29 patients who underwent successful stent implantation (stenting group) were studied and compared with 45 patients who underwent successful coronary balloon angioplasty during the same period (balloon angioplasty group). The serum TnT level was measured by enzyme immunoassay 36 hours after the stenting or balloon angioplasty. The activities of serum creatine kinase (CK) and its isoenzyme MB (CK-MB) were measured by a modified Rosalski method and an immunoinhibition method, respectively, before, immediately after, and 6, 12, and 24 hours after the procedure. Elevation of the TnT level was found in 3.4% (1/29; 0.35 ng/ml) of the patients in the stenting group and in 8.9% (4/45; 0.75 +/- 0.21 ng/ml) of those in the balloon angioplasty group. Elevation of the CK and CK-MB activities was found in 3.4% (1/29; 163 IU/l) and 0%, respectively in the stenting group, and 15.5% (7/45; 375 +/- 143 IU/l) and 4.4% (2/45; 24 and 49 IU/l), respectively, in the balloon angioplasty group. TnT elevation was not invariably accompanied by CK or CK-MB elevation, or by angiographically visible side branch occlusion. For TnT, CK-MB activity and CK activity, there was no significant difference between in the incidence of elevation in the balloon angioplasty group and that in the stenting group. In summary, the incidence of myocardial damage associated with stent implantation seems to be low and comparable to that associated with balloon angioplasty. Despite the low incidence, measurement of the serum TnT level in addition to CK-MB measurement is essential in assessing minor myocardial damage.

Aged↗
PubMed1998

Two cases of myelodysplastic syndrome with extramedullary polyclonal plasma cell proliferation and autoantibody production: possible role of soluble Fas antigen for production of excessive self-reactive B cells.

Two cases of myelodysplastic syndrome (MDS) with extramedullary polyclonal plasma cell proliferation and autoantibody production are reported. These cases, which showed leukemic change of refractory anemia with excess of blast (RAEB), developed lymph node swelling and muscle abscess; both were infiltrated mainly with plasma cells, without preceding infection. The proliferation of plasma cells was polyclonal and was proven by negative rearrangement of immunoglobulin heavy chain gene or polyclonal staining of immunoglobulin light chains. These patients showed polyclonal gammopathy and autoantibody production such as positive antinuclear factor and direct antiglobulin test. As was observed in one of the present cases, and as we reported previously, the elevated level of soluble Fas antigen in MDS patients, and its inhibition of apoptotic signaling may be responsible for the excessive accumulation of self-reactive B cells, resulting in these clinical manifestations.

Aged↗