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Biomedical subjects

T Yajima

Publications and source records attributed to T Yajima.

At least 127 records · Page 7Linked to original sources

Nasal absorption of 2',3'-didehydro-3'-deoxythymidine (D4T) and its esters in rats.

Nasal absorption of 2',3'-didehydro-3'-deoxythymidine (D4T) and its esters (5'-acetyl D4T: C2-D4T and 5'-hemisuccinyl D4T: Suc-D4T) was investigated in rats. Bioavailability of D4T following intranasal (i.n.) administration was 98.0%, and the elimination from plasma was as rapid as that following intravenous administration of D4T. There seemed to be complete and rapid absorption of D4T from the nasal cavity. The plasma concentration-time profile of D4T following i.n. administration of C2-D4T was almost the same as that after administration of D4T itself. This suggests that C2-D4T was rapidly absorbed from the nasal cavity, and that some amount of dosing C2-D4T was hydrolyzed to D4T before entering the systemic circulation. In contrast, Suc-D4T showed slower absorption in the i.n. administration, and the plasma D4T level was maintained for a long period.

Absorption↗

Plasma and urinary metabolites of efonidipine hydrochloride in man.

1. The plasma and urinary metabolite profiles of efonidipine hydrochloride, a new dihydropyridine calcium antagonist, have been examined in six healthy male volunteers after oral dosing. 2. Unchanged drug in plasma was determined by hplc-ms. Five metabolites in plasma and five metabolites and unchanged drug in urine were identified by hplc. 3. The main plasma metabolites were N-dephenylated-efonidipine and deaminated-efonidipine. 4. No significant amount of unchanged drug was excreted in urine. In the urine collected for 24 h after a oral dosing, 1.1% of the dose was excreted as deaminated-efonidipine, and 0.5% as a pyridine analogue of deaminated-efonidipine.

Adult↗

Successful treatment with cyclosporin A of pure red cell aplasia associated with rheumatoid arthritis.

We describe the first report of a patient with rheumatoid arthritis (RA) who developed refractory pure red cell aplasia that was successfully treated with cyclosporin A (CyA). Since no inhibitory activity against bone marrow was observed in the whole serum, it is possible that the clinical efficacy of CyA on both RA and aplasia was explained by its effects on T cells that might be involved in the development of these diseases.

Arthritis, Rheumatoid↗

Effects of nicorandil on kinetics of oxygen uptake at the onset of exercise in patients with coronary artery disease.

The beneficial effects of coronary vasodilators on exercise capacity in patients with angina pectoris are well known. However, their effects on oxygen uptake (VO2) kinetics at the onset of exercise have not been elucidated. The present study was undertaken to determine the acute effects of nicorandil, a newer coronary vasodilator, on the kinetics of VO2 at the onset of exercise in patients with ischemic heart disease. Ten patients with significant coronary stenosis performed constant mild-intensity cycle exercise (32 +/- 3 W) for 6 minutes after oral administration of 10 mg of nicorandil or an identical placebo in a double-blind, crossover manner. Nicorandil had no effect on resting heart rate, blood pressure, or VO2. However, the time constant for the increase in VO2 during constant work rate exercise was significantly shorter (the kinetics of VO2 were faster) after administration of nicorandil than after placebo (46.5 +/- 13.3 vs 51.1 +/- 11.9 seconds; p = 0.039). The increase in VO2 at 6 minutes compared with 3 minutes of constant work, which reflects the VO2 kinetics, also was reduced with nicorandil (3.8 +/- 37.9 vs 27.5 +/- 27.1 ml/min; p = 0.022). Nicorandil was found to increase the rate of VO2, increase during the onset of constant work rate exercise, probably as a result of an improved response in cardiac output. Analysis of VO2 kinetics provides new and useful parameters for the evaluation of circulatory adjustments at the onset of exercise in patients with ischemic heart disease.

Adult↗

Evaluation of exercise capacity using submaximal exercise at a constant work rate in patients with cardiovascular disease.

BACKGROUND: Symptom-limited incremental exercise tests are used to estimate the severity of cardiovascular disease and the patient's daily activity. However, there is a need for objective parameters for submaximal exercise. To test the hypothesis that a decrease in maximal exercise capacity can be estimated by oxygen uptake (VO2) kinetics, we measured the time constant of VO2 both during the onset of constant work rate exercise at 50 W and during recovery from this exercise and compared it with data obtained during maximal exercise in patients with cardiovascular disease and in normal subjects. METHODS AND RESULTS: A total of 34 patients with cardiovascular disease and 14 normal subjects performed 6 minutes of 50-W constant work rate exercise and an incremental exercise test to the symptom-limited maximum on a cycle ergometer. VO2 was calculated from respiratory gas analysis on a breath-by-breath basis. The time constant of VO2 during the onset of 50-W exercise was 61.4 +/- 15.2 seconds in patients with cardiovascular disease, significantly longer (the kinetics of VO2 were slower) than that in normal subjects (48.8 +/- 10.4 seconds, P = .008). The time constant of VO2 during the onset of exercise was significantly negatively correlated with peak VO2 (r = -.67) and maximal work rate (r = -.66). The time constant during recovery, which did not differ significantly from that of exercise, was also prolonged in patients with cardiovascular disease; it showed a negative correlation with peak VO2 (r = -.63) and maximum work rate (r = -.54). CONCLUSIONS: The time constant of VO2 during and after recovery from 50 W of constant work rate exercise, which does not require the subject's maximal effort, is a useful and objective measure of exercise capacity in patients with mild to moderate cardiovascular disease.

Adult↗

Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes.

The interaction of mucosal lymphocytes and intestinal epithelial cells is thought to be important in regulating immune response in the intestinal mucosa, but conclusive evidence is limited. Here we demonstrate the expression of IL-7 mRNA in human intestinal mucosa by combined reverse transcription PCR and Southern blot hybridization. Immunohistochemistry and in situ hybridization confirm the presence of IL-7 in intestinal epithelial cells, especially in epithelial goblet cells. Moreover, IL-7 receptor expression in mucosal lymphocytes is demonstrated by immunohistochemistry and in situ hybridization, as well as by Southern blot and flow cytometric analysis of freshly isolated lamina propria lymphocytes. In contrast, IL-7 receptor could not be detected in the cell surface of freshly isolated PBLs. The functional activity of IL-7 receptor is demonstrated by the utility of recombinant IL-7 to stimulate the growth of lamina propria lymphocytes, and conversely inhibit CD3-dependent proliferation of these cells. In contrast, IL-7 caused no significant increase in DNA synthesis and cell numbers when added to PBLs. These findings suggest that human intestinal epithelial cells and epithelial goblet cells produce IL-7, and locally produced IL-7 may serve as a potent regulatory factor for intestinal mucosal lymphocytes.

Adult↗

[A case report of annuloaortic ectasia with coarctation of the aorta and "high take off" of the right coronary artery].

A 21-year-old male who had annuloaortic ectasia with coarctation of the aorta and "high take off" of the right coronary artery underwent two stage operations. A bypass operation using an artificial graft was performed for coarctation of the aorta at the first procedure. The second procedure, Cabrol's operation, was performed on 83rd day after the first operation. At the second operation we found "high take off" of the right coronary artery. The right coronary artery originated about five centimeters above the rim of the left sinus of Valsalva. Post-operative cause was uneventful. Annuloaortic ectasia combined with coarctation of the aorta and "high take off" of the right coronary artery is very rare in the literature.

Adult↗

[Sequential coronary artery bypass grafting utilizing the internal thoracic and gastroepiploic artery as in situ grafts].

36 consecutive patients (male:female = 33:3, mean age 57.3) underwent sequential coronary artery bypass grafting (CABG) utilizing the left internal thoracic artery (LITA, n = 30), right gastroepiploic artery (RGEA, n = 8) as in situ grafts. Two patients received sequential bypass grafting with both grafts simultaneously. No right internal thoracic arteries were used except for one as a free nonsequential graft. Taking into account the adjunctive venous anastomoses and the arterial nonsequential anastomoses, there were 3.5 anastomoses per patients. Proxymal side-to-side anastomosis of LITAs were all constructed on the diagonal branches except for one on the proxymal Left Anterior Descending Coronary Artery (LAD), whereas that of the RGEAs were on the proxymal Right Coronary Artery (RCA) (2), distal RCA (6) or distal circumflex (1). Distal end-to-side anastomoses of LITAs were all on the LAD, and those of the RGEAs were on the distal RCA (3) or distal circumflex artery (5). Proxymal side-to-side anastomoses were always performed first, allowing us to assess the distal flow through the graft before we anastomose it to the distal branch. We routinely obtain a preoperative angiogram of the arterial grafts, which enable us to fully assess the suitability of the arteries as in situ grafts. There were no perioperative deaths, nor perioperative myocardial infarctions, however, two patients died of extracardiac causes at 42 and 68 days after operation respectively. For the thirty four survivors, followup was complete (4-49 months, average 12.3 months). One still had angina of Canadian Cardiovascular Society Classification (CCSC) class 2, and 33 were free of angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Immunosuppressive agents in the treatment of Crohn's disease and ulcerative colitis.

Low doses of 6-mercaptopurine (6MP) were used for the treatment of inflammatory bowel disease, and 20-30 mg/day was found to be effective for patients with ulcerative colitis who were corticosteroid-dependent or corticosteroid-resistant. Corticosteroid was tapered in 20 of 21 patients with ulcerative colitis. Of 15 patients who were refractory to conventional therapy, 11 responded to 6MP treatment. The same doses of 6MP were given to patients with Crohn's disease who were corticosteroid-dependent or who had associated fistula. Treatment with 6MP did not influence the changes in colonic or ileac lesions in Crohn's disease. However, the fistulas were closed or improved in 70% of 10 patients by 6MP treatment. The adverse effects of small doses of 6MP were minimal. These results confirm that immunosuppressive agents are effective for patients with inflammatory bowel disease. In a rat colitis model induced by immunization with trinitrobenzene (TNB), we used anti-CD4 monoclonal antibodies to prevent colonic inflammation; these antibodies were effective for this colitis model, suggesting that a novel therapy targeting CD4 intestinal lymphocytes may be feasible in the treatment of Crohn's disease.

Animals↗

CD4+ intestinal mucosal lymphocytes in the pathogenesis of Crohn's disease.

To analyze the nature of intestinal mucosal lymphocytes in Crohn's disease, we established T cell lines of patients' intraepithelial lymphocytes. T cell lines from the affected terminal ileum of the patients showed an increased proportion of CD4+V beta 5.2/5.3+ T cells. These cells were increased in number after stimulation with staphylococcal enterotoxins C1 and D, showed an increase in cytolytic activity, and produced a large amount of interferon-gamma. To clarify the role of CD4+ mucosal lymphocytes in the intestinal inflammation, we then developed a novel colitis model by immunizing a rat with trinitrobenzenesulfonic acid (TNB) emulsion with adjuvant. Deep ulceration and granuloma formation in this colitis model resembled the histopathological findings of human Crohn's disease. Immunohistochemical and flow cytometric analysis demonstrated that the number of CD45RC(high)CD4+ mucosal lymphocytes was increased. Interestingly, the administration of anti-CD4 Abs prevented severe inflammation in the model. After treatment with anti-CD4 Abs, the anti-TNB Ab titer, the number of CD45RC(high)CD4+ cells, and interferon-gamma mRNA expression were significantly decreased in the mucosa of the model. These results suggest that some subsets of CD4+ mucosal lymphocytes play an important role in the triggering and progression of inflammation in Crohn's disease.

Animals↗

Clinical evaluation of a new type of centrifugal pump.

The major problems with existing centrifugal pumps are leakage, mechanical trauma, and thrombus formation. In consideration of these problems, a new compact centrifugal pump system was developed. The purpose of this study was to evaluate the new centrifugal pump system clinically. Ten patients underwent open heart surgery with a centrifugal pump or a roller pump. During surgery, hemodynamic and hematological data were obtained. A pulsatile assist device in the pump circuit was used in patients with severe heart disease. There was neither operative death nor hospital mortality, and there was no difference with regard to hemodynamic data between the two groups. The centrifugal pump groups, however, had significantly lower hemolysis, especially during prolonged cardiopulmonary bypass. This centrifugal pump could also create sufficient pulsatile flow with a pulsatile assist device. Postoperative macroscopic and microscopic findings demonstrated the smooth surface of the pump without thrombus formation. This centrifugal pump system might be useful for prolonged cardiopulmonary bypass.

Adolescent↗

Oxygen uptake kinetics are determined by cardiac function at onset of exercise rather than peak exercise in patients with prior myocardial infarction.

BACKGROUND: Resting cardiac function does not necessarily affect exercise capacity. However, to determine whether it affects early dynamics of oxygen uptake (VO2) during exercise, we measured VO2 during a constant work rate and during incremental exercise testing in patients with a history of myocardial infarction. VO2 kinetics and exercise capacity were compared between patients with relatively high left ventricular ejection fractions (LVEF > or = 35%, group 1) and those with lower ejection fractions (LVEF < 35%, group 2). METHODS AND RESULTS: Forty patients with a history of prior myocardial infarction (age, 57 +/- 10 years) were monitored during 6 minutes of moderate constant work rate testing (40 +/- 8 W) and during symptom-limited incremental exercise testing with a cycle ergometer. VO2 was calculated from respired gas analysis on a breath-by-breath basis. Cardiac output determinations were made with a computerized cadmium telluride detector every 10 seconds during exercise. The VO2 time constant during constant work rate exercise was slower in group 2 (58.0 +/- 7.6 seconds) compared with group 1 (45.8 +/- 10.5 seconds, P = .0002), indicating slower kinetics in group 2. The time constant for the rise in cardiac output during exercise was also slower in patients with lower EFs (63.0 +/- 12.8 versus 50.0 +/- 12.2 seconds). However, there were no differences in exercise capacity parameters, such as the VO2 or cardiac output at peak exercise, obtained during incremental exercise testing among the two groups. CONCLUSIONS: The prolonged time constant of VO2, which is primarily determined during early parts of exercise, reflects delayed cardiac output response in patients with severely impaired LV function. The time constant of VO2 during submaximal constant work rate exercise can be used as a sensitive and discriminant measure of impaired cardiac reserve in these patients.

Adult↗

Mechanism of periodic breathing in patients with cardiovascular disease.

Although periodic breathing consisting of alternating hyperpnea and hypopnea has been recognized in heart failure patients, its mechanism has not been clarified. We hypothesized that heart failure patients who have oscillations in ventilation will also be found to have oscillations in pulmonary blood flow, as reflected in left ventricular ejection fraction. To test this hypothesis, we analyzed continuously gas exchange and left ventricular ejection fraction during exercise in cardiac patients who exhibited periodic breathing. Out of 48 consecutive patients with reduced left ventricular function who performed a symptom-limited incremental exercise test using an upright cycle ergometer, we selected 5 patients who exhibited clear ventilatory oscillations during exercise. These patients repeated the same exercise test on another day for measuring gas exchange and left ventricular ejection fraction continuously. Oscillatory changes were noted both in left ventricular ejection fraction and in ventilation in these patients. These observations offer support for the hypothesis that fluctuations in pulmonary blood flow are primarily responsible for the periodic breathing seen in heart failure patients.

Aged↗

Stimulation of bicarbonate secretion by luminal short-chain fatty acid in the rat and human colon in vitro.

Acetic, propionic and butyric acids constitute the predominant luminal anions in the colon. Several in vivo studies have suggested that these short-chain fatty acids (SCFAs) induce HCO3- accumulation in the colonic lumen. The purpose of this study was to delineate the mechanism underlying the SCFA-induced HCO3- accumulation in chamber-mounted mucosae from the rat and human colon under short-circuit conditions. HCO3- transport from the serosa bathed with a HCO3(-)-containing solution to the lumen bathed with a HCO3- (and Cl-)-free solution was evaluated from the luminal alkalization rate (JOHSL) by using a pH-stat system. In the rat distal colon, luminal propionate (25 mM) enhanced JOHSL from 0.32 +/- 0.19 to 3.18 +/- 0.22 mumol/cm2/h (n = 5, means +/- SE). Luminal acetate and butyrate (25 mM) similarly enhanced JOHSL. The magnitude of the increase in JOHSL induced by SCFA did not significantly vary among these three SCFAs. On the other hand, luminal lactate (25 mM) failed to affect JOHSL. The SCFA-induced increase in JOHSL was greatly reduced to approximately 30% of the original level when HCO3- was removed from the serosal solution. The short-circuit current and the transepithelial conductance were barely altered by luminal SCFAs or lactate. In the human colon, luminal propionate (25 mM) also caused an increase in JOHSL from 0.54 +/- 0.36 to 1.57 +/- 0.62 mumol/cm2/h (n = 4), which was significantly attenuated by removing serosal HCO3-. These results demonstrate that luminal SCFAs stimulate HCO3- secretion in the colon.

Acetates↗

X-arrestin: a new retinal arrestin mapping to the X chromosome.

We have been using a differential cDNA cloning approach to isolate human retina-specific and retina-enriched genes [1]. A 1,314 bp cDNA was isolated by this approach, representing a highly retina-specific message encoding a 388 amino acid protein showing 58%, 50%, and 49% homology to bovine beta-arrestin, and bovine and human retinal arrestin (S-antigen), respectively. Chromosomal mapping localized this new arrestin gene to the proximal long arm of the X chromosome, hence it was named X-arrestin. In situ hybridization demonstrated its expression in the inner and outer segments and the inner plexiform regions of the retina.

Amino Acid Sequence↗

Osteoporosis and reduction of residual ridge in edentulous patients.

The relationship between the height of the mandibular residual ridge and the severity of osteoporosis in elderly edentulous patients was investigated. The height of the mandibular residual ridge was measured by use of the mental foramen on panoramic radiographs. The severity of osteoporosis was determined by examining frontal and lateral radiographs of the vertebrae. All of the patients received a blood analysis. The correlation coefficient between age and the height of residual ridge was -0.38, which was statistically significant (p < 0.01). The residual ridge in women was lower than that of men, showing a statistical significance (p < 0.01). The correlation coefficient was -0.42 between degree of severity of osteoporosis and the height of the residual ridge, which was significant (p < 0.01). The parathyroid hormone level was high in the patients with a low residual ridge, and the calcitonin (CT) level was low. This study indicates that osteoporosis strongly affects reduction of the residual ridge in edentulous patients.

Age Factors↗