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Biomedical subjects

K Tanabe

Publications and source records attributed to K Tanabe.

At least 289 records · Page 16Linked to original sources

[Factors affecting exercise capacity after coronary bypass grafting].

In order to determine the contribution of cardiac reserve and the peripheral muscle to exercise capacity in patients after Coronary Artery Bypass Grafting (CABG), 19 patients (18 males, 1 female, mean age 63.3 +/- 7.1 years, mean numbers of grafting 2.5 +/- 0.8) performed exercise tests at 1 week, 3 weeks, and 3 months after CABG. Ventilatory gas was analyzed throughout the testing and anaerobic threshold (AT) and peak oxygen uptake (peak VO2) was determined. During exercise testing, the cardiac index (CI) was measured, and the change in CI during exercise, delta CI = (CI at peak exercise) (CI at rest), was calculated. O2 delivery was derived from the product of CO and the oxygen content of arterial blood at peak exercise. The sectional area of the thigh muscles at the level of 10 cm above the patella was measured using a computed tomography before each test. Average peak VO2 at 1 week after CABG was 867 +/- 171 ml/min and it increased to 1,214 +/- 246 ml/min at 6 months. Average AT did not change from 1 week to 3 weeks, however, it increased significantly from 665 +/- 122 ml/min at 3 weeks to 873 +/- 181 ml/min at 6 months. The muscle area of the thigh increased significantly from 170 +/- 24 cm2 at 3 weeks after CABG to 186 +/- 27 cm2 at 3 months. delta CI showed a tendency to increase from 6.6 +/- 1.2 l/min/m2 at 1 week after CABG to 7.3 +/- 1.3 l/min/m2 at 3 weeks, and also showed a tendency to increase from 3 weeks to 6 months. Peak VO2 and AT correlated to delta CI at 1 weeks and also it correlated significantly to both the muscle area of the thigh and delta CI at 3 weeks, 3 months, and 6 months after CABG. The delta value of peak VO2 from 1 week to 3 weeks showed a significant correlation to those of delta CI and O2 delivery. Moreover, the delta values of peak VO2 and AT from 3 weeks to 3 months showed a correlation to those of delta CI and O2 delivery. These results suggest that both cardiac reserve and peripheral factors contribute to the exercise capacity up to 3 months after CABG, and, in particular, O2 delivery are important to increase exercise capacity.

Cardiac Output↗

[A case of a premenopausal woman with advanced breast cancer treated with aromatization inhibition in combination with luteinizing hormone-releasing hormone agonist].

A 44-year-old premenopausal woman having local recurrence and pleural and bone metastases of breast cancer was treated with aromatization inhibition in combination with Luteinizing Hormone-releasing Hormone (LH-RH) agonist. The dominant site of metastasis was a painful local lesion invading the chest wall. A partial response by reducing the size of the local lesion was attained 3 months after initiation of treatment. This result suggested that treatment using aromatization inhibition in combination with LH-RH agonist would be effective in premenopausal breast cancer. To confirm the effectiveness of this treatment, comparative study between aromatization inhibition in combination with LH-RH agonist aromatization inhibition alone and anti-estrogen in combination with LH-RH agonist are needed.

Adult↗

[Mechanism of increase in exercise tolerance in patients with acute myocardial infarction].

The contribution of cardiac output reserve and the skeletal muscle to exercise capacity was investigated in 24 patients with acute myocardial infarction. Symptom-limited exercise tests with a cycle ergometer were performed at 1 week, 3 weeks, and 3 months after the onset of the first infarction. Ventilatory gas was analyzed throughout the testing, and peak oxygen uptake (peak VO2) and anaerobic threshold (AT) were determined. During the test, the cardiac index (CI) was measured by the dye dilution method and the change in CI during exercise (delta CI) was calculated as an index of cardiac output reserve. The cross-sectional area of the thigh muscles (CSA) at the level of 10 cm above the patella was measured using computed tomography. Peak VO2 and AT increased significantly from 1 week to 3 months after the onset of infarction. delta CI increased significantly from 1 week to 3 weeks, and CSA increased significantly from 3 weeks to 3 months. Peak VO2 correlated significantly with both delta CI and CSA at each measurement point, as was AT with delta CI and CSA. Change in peak VO2 correlated with change of delta CI from 1 week to 3 weeks, and also with both delta CI and CSA from 3 weeks to 3 months. These results suggest that both cardiac output reserve and peripheral factors contribute to the exercise capacity up to 3 months after the onset of myocardial infarction. In particular, peripheral factors such as muscle volume are important to improve exercise capacity from 3 weeks to 3 months.

Aged↗

Antithrombotic and hemorrhagic effects of DX-9065a, a direct and selective factor Xa inhibitor: comparison with a direct thrombin inhibitor and antithrombin III-dependent anticoagulants.

(+)-2S-2-[4-[[(3S)-1-Acetimidoyl-3- pyrrolidinyl]oxy]phenyl]-3-[7-amidino-2-naphthyl]propanoic acid hydrochloride pentahydrate (DX-9065a) is an antithrombin III (AT III)-independent and selective inhibitor of activated blood coagulation factor X (FXa). The aim of the present study was to compare the antithrombotic and hemorrhagic effects of DX-9065a with a direct thrombin inhibitor and AT III-dependent anticoagulants in rat models of thrombosis and bleeding. Rats were administered intravenously DX-9065a (0.1-1 mg/kg/h), argatroban (0.1-1 mg/k/h), low molecular weight heparin (25-100 anti-XaU/kg/h), unfractionated heparin (25-100 anti-XaU/kg/h) or Orgaran (30-300 anti-XaU/kg/h) for 1 h. DX-9065a dose-dependently inhibited both thrombus formation and elevation in plasma thrombin-AT III complex (TAT) level in a copper wire-inserted arteriovenous (AV) shunt model in rats. The dose required for 50% inhibition of thrombus formation was 0.27 mg/kg/h. DX-9065a did not prolong transection bleeding time up to 7.78 mg/kg/h. Argatroban and AT III-dependent anticoagulants also inhibited both thrombus formation and TAT elevation, but prolonged bleeding time at a slightly higher dose than the effective dose. These results suggest that direct and selective inhibition of factor Xa by DX-9065a is preferable for the treatment of thrombosis in the aspect of lack of compromising primary hemostasis.

Animals↗

Doppler estimation of pulmonary artery end-diastolic pressure using contrast enhancement of pulmonary regurgitant signals.

Pulmonary artery (PA) end-diastolic pressure is used as an estimate of PA wedge pressure. We evaluated contrast enhanced pulmonary regurgitant signals in the assessment of PA end-diastolic pressure in 24 patients in a critical care unit. Right atrial pressure was estimated by the percent decrease of the inferior vena caval diameter with inspiration. Weak or absent pulmonary regurgitant signals were enhanced by sonicated albumin (Albunex) in 23 patients (96%). The Doppler-determined PA end-diastolic pressure (the sum of the pulmonary regurgitant pressure gradient at end-diastole and the right atrial pressure) was significantly correlated with the catheter-determined PA end-diastolic pressure (y = 0.85x + 1.72, r = 0.93). Compared with invasive hemodynamic monitoring, the contrast-enhanced Doppler technique using Albunex is effective for measuring PA end-diastolic pressure, even in critically ill patients.

Aged↗

Status of microchimerism in recipients 15 years after living related kidney transplantation.

To study the relevance of microchimerism to the long-term outcome of renal allografting, we analyzed the frequency of microchimerism in kidney transplant recipients who had stable graft function for 15 years or longer. Among the 104 recipients who underwent kidney transplantation between 1971 and 1980, 27 renal allografts (26%) are still functioning. Among these 27 patients, 13 recipients whose donor was still alive and cooperative were investigated for the presence of microchimerism in the peripheral blood and for their immunological status. Microchimerism was tested using the polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) method. To test the sensitivity of PCP-SSCP, the peripheral blood obtained within 5 weeks after transplantation (four kidney transplants, three liver transplants) was also examined. Microchimerism was detectable in five patients within 5 weeks of transplantation (kidney transplantation, 3/4; liver transplantation 2/3. However, in the patients studied 15 years after transplantation, microchimerism was detected in only one recipient (1/13). In this chimeric patient, mixed lymphocyte response revealed high responsiveness against donor antigen. In contrast, some patients who did not have chimerism showed donor-specific hyporesponsiveness in mixed lymphocyte response assay and did not develop antidonor antibody, according to flow cytometric analysis. Microchimerism is an infrequent state in the long-term survivors of kidney allografting, and this state is irrelevant to donor-specific unresponsiveness.

Adult↗

Ethanol sclerosis can be a safe and useful treatment for pericardial cyst.

We report the case of a 41-year-old man with a pericardial cyst treated by percutaneous aspiration and ethanol injection. He was referred to our hospital because of electrocardiographic abnormality. On admission, chest x-ray revealed a large pericardial cyst in the right cardiophrenic angle. The cyst was examined by echocardiography, computed tomography, and cytological analysis of aspiration fluid from the cyst. Ethanol sclerosis was applied for treatment of the cyst, which had continued to increase in size. There was no recurrence of the cyst 6 months after the treatment. Percutaneous ethanol sclerosis can be the first choice of treatment for pericardial cyst.

Adult↗

Causes of long-term graft failure in renal transplantation.

A single-center experience of 980 consecutive renal transplant recipients treated with cyclosporine (CyA) was reviewed to analyze the causes of renal allograft loss and the factors affecting long-term renal survival in CyA-treated kidney transplants. In all, 217 grafts were lost during the observation period, with the most common causes of graft loss being chronic rejection (96 cases, 44%), death with a functioning graft (52 cases, 24%), glomerulonephritis (28 cases, 13%), and acute rejection (20 cases, 8%). The actuarial 10-year survival of patients with living and cadaveric grafts was 93% and 91%, respectively. The actuarial 10-year survival of living and cadaveric grafts was 70% and 63%, respectively. Patients were divided into two groups, namely a graft-survival group (n = 763) and a graft-loss group (n = 217). There was no significant difference between the two groups in terms of sex, donor source, donor age, recipient age, duration of hemodialysis, retransplants, transfusions, presensitization, of HLA match. There was no difference between the graft-survival group and the graft-loss group in the mean CyA dose given or the mean CyA trough level measured at any time following transplantation. Acute rejection episodes occurred in patients from the graft-survival group (55%) as compared with those from the graft-loss group (83%; P < 0.00001). These data suggest that long-term graft survival in CyA-treated kidney transplant patients is primarily influenced by the occurrence of rejection episodes rather than by the drug dose or the duration of CyA administration. CyA nephrotoxicity was not the major risk factor for long-term graft survival in CyA-treated renal transplants.

Adult↗

Synergistic effect of donor-specific blood transfusion and a short course of deoxyspergualin in rat kidney transplantation.

Deoxyspergualin (DSG), an analogue of spergualin produced by B. laterosporus, has a strong immunosuppressive effect in various transplantation models. We have investigated the mechanism of donor-specific prolongation of survival time in rat kidney grafting by donor-specific blood transfusion (DST) and a short course of DSG. Lewis (LEW) kidney allografts were transplanted into fully allogeneic BN rats. Fresh, whole LEW blood 1.0 ml, was injected i.v. into BN rats 2 days prior to transplantation. Then, DSG, 6 mg/kg per day, was administered by i.m. injection on days 0, 1, and 2 after transplantation. The recipients were divided into five groups: group 1 (n = 6) no treatment: group 2 (n = 6) DST only; group 3 (n = 7) DSG only; group 4 (n = 7) DST and DSG; and group 5 (n = 6), third party (ACI rats) blood transfusion and DSG. Lymphocytes (cervical lymph nodes) and serum were harvested from BN recipients on day 7 postgrafting. For suppressor cell assays, lymphocytes from BN recipients in each group were added as a third cell to the mixed lymphocyte reaction (MLC) between nontransplanted BN lymphocytes (responder) and LEW or other third party (PVGC, ACI, WKA rats) lymphocytes (stimulator). Antidonor lymphocytotoxic antibody (ADLA) was checked by microcytotoxicity assays. Median survival times (MST) for each group were: group 1, 10 days; group 2, 10 days; group 3, 13 days; group 4, 75 days; and group 5, 13 days. Remarkable prolongation of MST was only noted in group 4. In the suppressor cell assay, group 4 showed significant suppression (40%; P > or = 0.05); the other groups did not show any suppression. This suppressive activity in group 4 was effective only during the MLC between BN and LEW, not during the MLC of third party-BN combinations. Thus, suppressor cells from DST/DSG-treated BN recipients appear to be donor-specific. In the microcytotoxicity assay, the only group that showed any ADLA was group 2, which was not treated with DSG. These results clearly show that both induction of donor-specific suppressor cells and inhibition of ADLA production are associated with the remarkable donor-specific prolongation of kidney allograft survival in DST/DSG-treated recipients.

Animals↗

Removal of anti-A/B antibodies for successful kidney transplantation between ABO blood type incompatible couples.

A growing shortage of cadaveric donors has prompted expansion of the criteria for acceptable living donors. Because of this, ABO-incompatible kidney transplantation has been carried out. To remove anti-A and/or anti-B antibodies, the recipients received one or two sessions of double filtration plasmapheresis (DFPP) and three or four sessions of immunoadsorption prior to transplantation until the anti-A IgG/IgM titers and/or anti-B IgG/IgM titers decreased to 1:16 or less. Our immunosuppressive protocol involved treatment with the drugs methylprednisolone, cyclosporine, azathioprine, anti lymphocyte globulin and deoxyspergualin. The patient survival was 98% at 1 month, 98% at 3 months, 94% at 6 months, and 92% at 1-5 years. Graft survival was 92% at 1 month, 88% at 3 months, 85% at 6 months, 81% at 1 year, and 76% at 5 years. Both DFPP and/or immunoadsorption eliminated anti-ABO antibodies from ABO-incompatible kidney transplant recipients effectively and safely. The results of the ABO-incompatible kidney transplantation were acceptable and not different from those of ABO-compatible cases.

ABO Blood-Group System↗

Synthesis, miscoding specificity, and thermodynamic stability of oligodeoxynucleotide containing 8-methyl-2'-deoxyguanosine.

8-Methyl-2'-deoxyguanosine (8-MedG) was synthesized by reacting dG under the methyl radical generating system and incorporated into oligodeoxynucleotides using phosphoramidite techniques. The site-specifically modified oligodeoxynucleotide containing a single 8-MedG was then used as a template for primer extension reactions catalyzed by the 3' --> 5' exonuclease-free (exo-) Klenow fragment of Escherichia Coli DNA polymerase I and mammalian DNA polymerase alpha. Primer extension catalyzed by the exo- Klenow fragment readily passed the 8-MedG lesion in the template while that catalyzed by pol alpha was retarded opposite the lesion. The fully extended products formed during DNA synthesis were analyzed to quantify the miscoding specificities of 8-MedG. Both DNA polymerases incorporated primarily dCMP, the correct base opposite the lesion, along with small amounts of incorporation of dGMP and dAMP. In addition, two-base deletion was observed only when the exo- Klenow fragment was used. The thermodynamic stability of 8-MedG in the duplex was also studied. The duplex containing 8-MedG:dG was more thermally and thermodynamically stable than that of dG:dG. The duplex containing 8-MedG:dA was more thermodynamically stable than that of dG:dA. We conclude that 8-MedG is a miscoding lesion and capable of generating G --> C and G --> T transversions and deletion in cells.

Chemical Phenomena↗

Effects of cilazapril on exercise tolerance in the chronic phase of acute myocardial infarction.

The present study was conducted to investigate the effects of cilazapril on exercise tolerance and the hormone kinetics of catecholamines, the reninangiotensin-aldosterone system and alpha-atrial natriuretic peptide (ANP) in patients in the chronic phase of acute myocardial infarction (AMI). The subjects consisted of 19 cases of AMI. Cardiopulmonary exercise testing was performed 1 month after the onset of AMI, and patients were randomly assigned to either a group treated with 1 mg/day of cilazapril (9 cases) and or an untreated group (10 cases). After the completion of 2 months of exercise training at the anaerobic threshold (AT), blood samples were taken during a cardiopulmonary exercise test and various hormones were measured. In comparing the parameters of exercise tolerance before and after the completion of exercise training there were no significant differences between the 2 groups with respect to oxygen uptake, oxygen pulse, or exercise time at AT or at peak exercise. With regard to temporal changes in exercise tolerance, oxygen uptake, oxygen pulse and exercise time all tended to increase in both groups. With regard to hormone kinetics, the alpha-ANP concentration at peak exercise was significantly lower, and the noradrenaline secretions also tended to be lower, in the cilazapril-treated group, even though the peak exercise time was similar in both groups. These results may be support the hypothesis that cilazapril mitigates the left ventricular load during exercise therapy in patients in the chronic phase of AMI.

Aldosterone↗

Monitoring exposure to atomic bomb radiation by somatic mutation.

Atomic bomb survivors are a population suitable for studying the relationship between somatic mutation and cancer risk because their exposure doses are relatively well known and their dose responses in terms of cancer risk have also been thoroughly studied. An analysis has been made of erythrocyte glycophorin A (GPA) gene mutations in 1,226 atomic bomb survivors in Hiroshima and Nagasaki. The GPA mutation frequency (Mf) increased slightly but significantly with age at the time of measurement and with the number of cigarettes smoked. After adjustment for the effect of smoking, the Mf was significantly higher in males than in females and higher in Hiroshima than in Nagasaki. All of these characteristics of the background GPA Mf were in accord with those of solid tumor incidence obtained from an earlier epidemiological study of A-bomb survivors. Analysis of the dose effect on Mf revealed the doubling dose to be about 1.20 Sv and the minimum dose for detection of a significant increase to be about 0.24 Sv. No significant dose effect for difference in sex, city, or age at the time of bombing was observed. Interestingly, the doubling dose for the GPA Mf approximated that for solid cancer incidence (1.59 Sv). And the minimum dose for detection was not inconsistent with the data for solid cancer incidence. The dose effect was significantly higher in those diagnosed with cancer before or after measurement than in those without a history of cancer. These findings are consistent with the hypothesis that somatic mutations are the main cause of excess cancer risk from radiation exposure.

Adult↗

The influence of cytokines on the adhesion of renal cancer cells to endothelium.

PURPOSE: The development of tumor metastasis requires direct adhesive interactions between tumor cells and vascular endothelium. We examined the adherence of renal cell carcinoma (RCC) lines to endothelium after stimulation with different cytokines that induce expression of the vascular adhesion molecules endothelial leukocyte adhesion molecule (ELAM)-1, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1, MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVEC) were used to determine the adhesion of the RCC lines CCF-RC1, 2 and 7 to endothelium. Expression of cell adhesion molecules (CAM) on HUVEC and RCC lines was measured with immunoflowcytometry. RESULTS: Stimulation of HUVEC with rIl-1 beta, rTNF-alpha, or PMA resulted in a time-dependent 1.4- to 2.9-fold increase of RCC adhesion to HUVEC. Significant increased tumor cell binding was observed after 4 hours and paralleled the time-dependent induction of ELAM-1 and VCAM-1. Immunocytometry demonstrated the presence of the ligands sialyl Lewis X and VLA-4 on RCC, and blocking studies with monoclonal antibodies directed against tumor cell-endothelial interactions mediated by VCAM-1/VLA-4 and ELAM-1/sialyl Lewis X demonstrated marked inhibition of tumor cell adherence to cytokine-stimulated HUVEC. CONCLUSIONS: This study demonstrates that cytokine-induced increases in RCC adherence to HUVEC are mediated in part by VCAM-1/VLA-4 and ELAM-1/sialyl Lewis X interactions and suggest that these molecules may play an important role in the ability of RCC to metastasize.

Carcinoma, Renal Cell↗