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Biomedical subjects

H Kishimoto

Publications and source records attributed to H Kishimoto.

At least 109 records · Page 6Linked to original sources

Induction of CD38/NADase and its monoclonal antibody-induced tyrosine phosphorylation in human leukemia cell lines.

We previously reported that CD38 characterized as an ecto-enzyme of NAD+ glycohydrolase (NADase) was specifically induced by retinoic acid (RA) in human promyelocytic leukemia HL-60 cells and that anti-CD38 monoclonal antibody (mAb) induced tyrosine phosphorylation of cellular proteins in the RA-differentiated cells. In the present study, we found that CD38/NADase was induced in human monocytic leukemia THP-1 cells not only by RA but also by dibutyryl cAMP, which had no effect on the induction of CD38 in HL-60 cells. Similarly in the RA-differentiated HL-60 cells, tyrosine phosphorylation by anti-CD38 mAb was also observed in the CD38-expressing THP-1 cells, regardless of whether CD38 was induced by RA or dibutyryl cAMP. Such tyrosine phosphorylation was, however, not observed in human lymphoblastic leukemia Jurkat cells which had been treated by RA to produce CD38. Thus, the induction of CD38/NADase appeared to be not limited for RA-dependent differentiation and not always linked to protein-tyrosine phosphorylation in human leukemic cell lines.

ADP-ribosyl Cyclase↗

Surgical atrial septostomy without cardiopulmonary bypass.

Surgical atrial septostomy using a special atriotomy knife without cardiopulmonary bypass in patients with obstruction of the left-sided atrioventricular valve and complex cardiac anomalies is described. This procedure is effective, safe, and economical for patients in the acute stage after intracardiac repair, and available for patients with a closed fossa ovalis.

Cardiac Surgical Procedures↗

Repair of aortopulmonary window in an infant with extremely low birth weight.

Although transaortic patch repair under cardiopulmonary bypass is a suitable procedure for aortopulmonary window, another method without cardiopulmonary bypass may be the only one for an infant with extremely low birth weight. We describe a successful repair of an infant with extremely low birth weight (758 g) by closing the window with a clip through a left thoracotomy. Cardiac catheterization 7 months after the operation showed no residual shunt and no stenosis of ascending aorta, pulmonary artery, or coronary arteries in the patient, whom we believe to be one of the smallest with successful repair.

Aortopulmonary Septal Defect↗

An in vitro investigation of the tooth strains associated with four different restorations in Class II cavity.

The purpose of this study was to examine tooth strains in Class II preparations. A Class II cavity was prepared in 16 permanent premolars, and a strain gauge was attached to the buccal surface of each tooth. Each cavity was then restored with bonded amalgam, bonded gallium, composite, or composite with a resin liner. The tooth strains created by these four restorations were determined and evaluated with a strain indicator. The results of this study indicated that composite restorations with and without resin liner created much greater strains to tooth structure than did bonded amalgam and bonded gallium restorations. The application of resin liner before placement of the composite was effective for decreased tooth strain.

Alloys↗

Pharmacokinetics of mycophenolate mofetil, a new immunosuppressant, in rats.

Mycophenolate mofetil (MPM), a new immunosuppressant, is the morpholinoethyl ester of mycophenolic acid (MPA). The distribution in blood and pharmacokinetics of MPA after administration of MPM were examined. The plasma to erythrocyte concentration ratio was low (0.10-0.15). MPA existed in rat plasma as the highly bound form (bound fraction was 9.79 +/- 0.57%). MPA disappeared from the systemic circulation with biexponential decay. After i.v. administration of MPM at the doses of 8.3, 16.7, and 33.3 mg/kg, the total clearance of MPA was 0.241 +/- 0.056, 0.321 +/- 0.126, and 0.317 +/- 0.092 L/h/kg, respectively. The terminal elimination half-live were 5.17 +/- 1.44, 8.89 +/- 2.76, and 7.94 +/- 2.94 h, respectively. After i.d. administration of MPM at the doses of 8.3, 16.7, 33.3, and 50.0 mg/kg, the terminal elimination half-live were 6.41 +/- 4.16, 4.49 +/- 2.20, 7.58 +/- 3.72, and 8.18 +/- 1.32 h, respectively. The mean peak times were within 30 min. The systemic availability of MPA after i.d. administration of MPM (at 8.3, 16.7, and 33.3 mg/kg) was calculated using the corresponding mean AUCiv, and the values were 84.3 +/- 35.0%, 69.9 +/- 25.7%, and 63.6 +/- 8.8%, respectively.

Animals↗

Determination of L-buthionin (SR)-sulfoximine, gamma-glutamylcysteine synthetase inhibitor in rat plasma with HPLC after prelabeling with dansyl chloride.

L-(SR)-Buthionin sulfoximine (L-(SR)-BSO) is a potent and specific inhibitor of gamma-glutamylcysteine synthetase, which catalyzes the first reaction of glutathione biosynthesis. A selective, sensitive, and simple high-performance liquid chromatographic method was developed for the determination of L-(SR)-BSO in rat plasma. After the compound was labeled with dansyl chloride (Dns-Cl) under optimal conditions, it was separated in a Zolbax-ODS column with a mobile phase that consisted of 0.01M phosphate buffer, methanol, and acetonitrile (8:1:3, v/v). The compound was detected with a fluorescence detector at an excitation wavelength of 335 nm and an emission wavelength of 525 nm using a xenon lamp. The coefficients of variation (DV) from the interassay in the low and high concentrations (10 and 500 micrograms/mL of L-(SR)-BSO in rat plasma) were 2.5 and 4.8%, respectively. The CVs from the intra-assay in the low and high concentrations were 3.2 and 5.6%, respectively. The minimum concentration of L-(SR)-BSO that could be determined was 10 micrograms/mL when 100-microL serum samples were used. The detection limit was 50 ng per injection volume. This method enables pharmacokinetic and pharmacodynamic studies in rats.

Animals↗

Age-dependent alteration of the serum-unbound fraction of nicardipine, a calcium-channel blocker, in man.

To determine whether the age-dependent increase in the pharmacological effect of calcium-channel blockers is a result of age-dependent alteration of the unbound fraction the drug in serum, the unbound fraction of the nicardipine was investigated in the serum of 38 adults. The unbound concentration of nicardipine in serum to which nicardipine (205.4 ng mL-1) had been added was determined by ultracentrifugation to range from 0.49 to 4.01% (mean +/- s.d., 1.55 +/- 0.78%). Non-glycosylated albumin was most strongly correlated with age (r = 0.901). Total bilirubin was weakly correlated with age whereas levels of alpha-1-acid glycoprotein, triglycerides and glycosylated albumin were not correlated with age. A significant (P < 0.01) linear correlation was obtained between the unbound fraction of nicardipine and parameters such as age, albumin, albumin/globulin ratio, albumin/glycosylated albumin ratio, non-glycosylated albumin and total bilirubin. To assess the relative effect of each variable on the unbound fraction of nicardipine, stepwise multiple linear regression was performed using age and biochemical parameters. The three variables (non-glycosylated albumin, total bilirubin and age) were entered into the regression equation. The results of this study showed that the major ligand of nicardipine in serum was non-glycosylated albumin, which decreased with age. It was, moreover, shown that the serum-unbound concentration of nicardipine increased with age. This finding would be one factor accounting for the increase in the pharmacological effect of nicardipine with age. In addition, our predicted model for the unbound fraction of nicardipine might be useful in determining the appropriate nicardipine dose for the elderly.

Adult↗

Leukaemia cutis in chronic CD8+ T lymphocytic leukaemia.

A 66-year-old woman with CD8+ chronic lymphocytic leukaemia developed multiple indurated erythema or plaques. A skin biopsy specimen showed dense infiltration of leukaemia cells in the dermis and subcutaneous tissue. Most of the infiltrating cells were CD8 + cells. To our best knowledge, leukaemia cutis such as this case showing plaques with diffuse infiltration of CD8 + cells has not been reported previously.

Aged↗

Dynamic MR imaging and early-phase helical CT for detecting small intrahepatic metastases of hepatocellular carcinoma.

OBJECTIVE: We performed a study to evaluate the sensitivities of multislice dynamic MR imaging and early-phase helical CT as noninvasive methods for detecting small intrahepatic metastases of hepatocellular carcinomas. MATERIALS AND METHODS: Dynamic and spin-echo MR imaging and early- and delayed-phase helical CT of the liver were performed for patients with multiple hepatocellular carcinomas before transcatheter arterial chemoembolization. Forty-nine patients had 242 intrahepatic metastases less than 3 cm in diameter. Using iodized-oil CT after transcatheter arterial chemoembolization as a gold standard, the sensitivity of MR imaging for detecting intrahepatic metastases was compared with that of CT. RESULTS: Of the 242 nodules, 225 were diagnosed as hepatocellular carcinomas by iodized-oil CT. Of these, dynamic MR imaging and early-phase CT were significantly superior to those of spin-echo MR imaging (p < .0001) and delayed phase CT (p < .0001) for tumors less than 1 cm in diameter. CONCLUSION: Dynamic MR imaging and early-phase CT of the liver are the most sensitive noninvasive means of detecting small intrahepatic metastases of hepatocellular carcinoma before and after treatment.

Carcinoma, Hepatocellular↗

Physical dissociation of the TCR-CD3 complex accompanies receptor ligation.

Recent studies indicate that there may be functional uncoupling of the TCR-CD3 complex and suggest that the TCR-CD3 complex is composed of two parallel signal-transducing units, one made of gamma delta epsilon chains and the other of zeta chains. To elucidate the molecular mechanisms that may explain the functional uncoupling of TCR and CD3, we have analyzed their expression by using flow cytometry as well as immunochemical means both before and after stimulation with anti-TCR-beta, anti-CD3 epsilon, anti-CD2, staphylococcal enterotoxin B, and ionomycin. We present evidence that TCR physically dissociates from CD3 after stimulation of the TCR-CD3 complex. Stimulation with anti-CD3 resulted in down-modulation of TCR within 45 min whereas CD3 epsilon was still expressed on the cell surface as detected by flow cytometry. However, the cell surface expression of TCR and CD3 was not affected when cells were stimulated with anti-TCR-beta under the same conditions. In the case of anti-CD3 treatment of T cells, the TCR down-modulation appeared to be due to the internalization of TCR, as determined by immunoelectron microscopy. Immunochemical analysis of cells after stimulation with either anti-TCR or anti-CD3 mAbs revealed that the overall protein levels of TCR and CD3 were similar. More interestingly, the dissociation of the TCR-CD3 complex was observed with both treatments and occurred in a manner that the TCR and the associated TCR-zeta chain dissociated as a unit from CD3. These results provide the first report of physical dissociation of TCR and CD3 after stimulation through the TCR-CD3 complex. The results also suggest that the signal transduction pathway triggered by TCR may differ from that induced by CD3.

Animals↗

Optimal degree of pulmonary artery banding--adequate circumference ratio to calculated size from normal pulmonary valve dimensions.

These findings suggest that PA banding may be suitable in children with congenital heart disease and excessive pulmonary flow, and that best results are obtained when the band circumference is < 90% of the standard pulmonary valve-ring circumference, as calculated from an equation derived from normal pulmonary valve dimensions. This guideline applies equally well to small infants weighing < 3 kg and to larger patients.

Body Weight↗

A novel type of cell death of lymphocytes induced by a monoclonal antibody without participation of complement.

A monoclonal antibody, RE2, raised by immunizing a rat with cell lysate of a mouse T cell clone, was found to directly kill interleukin 2-dependent T cell clones without participation of serum complement. Fab fragments of RE2 had no cytolytic activity, while the cross-linking of Fab fragments with anti-rat immunoglobulin reconstituted the cytotoxicity. The cytotoxicity was temperature dependent: the antibody could kill target cells at 37 degrees C but not at 0 degrees C. Sodium azide, ethylenediaminetetraacetic acid, and forskolin did not affect the cytolytic activity of RE2, while the treatment of target cells with cytochalasin B and D completely blocked the activity. This suggested that the cell death involves a cytoskeleton-dependent active process. Giant holes on the cell membrane were formed within 5 minutes after the treatment with RE2, as observed by scanning electron microscopy. There was no indication of DNA fragmentation nor swelling of mitochondria during the cytolysis, suggesting that the cell death is neither apoptosis nor typical necrosis. The antibody also killed T cell lymphomas and T and B cell hybridomas only when these cells were preactivated with concanavalin A, lipopolysaccharide, or phorbol myristate acetate. Preactivated peripheral T and B cells were sensitive to the cytotoxicity of RE2, while resting T and B cells were insensitive. These results provide evidence for a novel pathway of cell death of activated lymphocytes by membrane excitation.

Animals↗

Interruption of aortic arch associated with pulmonary valve stenosis.

A newborn male is described who presented with interruption of aortic arch associated with ventricular septal defect and pulmonary valve stenosis. He underwent total corrective surgery and was discharged with good clinical results. The combination of significant right ventricular outflow obstruction and interruption of aortic arch is incompatible with fetal survival unless there are large collateral arteries which arise early in pregnancy. This is the first report of this combination of lesions.

Aorta, Thoracic↗

Upregulation of surface markers on dying thymocytes.

Using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) to detect cells undergoing early apoptosis, we have defined the surface markers expressed on CD4+CD8+ thymocytes undergoing spontaneous or steroid-induced apoptosis in tissue culture. Some surface markers, e.g., CD4, CD8, and heat stable antigen, are downregulated on apoptotic thymocytes. Surprisingly, however, other markers are upregulated; this applies to T cell receptor beta/CD3, CD69, and CD25 expression. Upregulation of these markers is restricted to a discrete subset of apoptotic cells.

Animals↗

Stability and pharmacokinetic studies of a new immunosuppressant, mycophenolate mofetil (RS-61443), in rats.

Mycophenolate mofetil (MPM), a new immunosuppressant, is a morpholinoethyl ester of mycophenolic acid (MPA). The enzymatic and non-enzymatic hydrolysis was studied in an artificial digestive fluid, rat plasma, and tissue homogenates. MPM was chemically stable in the artificial digestive fluid. In rat tissue homogenates and plasma, MPM was rapidly hydrolysed to MPA. The conversion rate of MPM to MPA in various rat tissue homogenates was in the order of liver > kidney > plasma > small-intestine epithelial cells. After the intravenous injection of MPM at 16.7 mg kg-1, the terminal elimination half-life, t1/2 beta, was 4.74 +/- 0.33 (mean +/- SD)h, and the area under the plasma concentration versus time curve, AUC, was 48.78 +/- 6.01 micrograms h mL-1. After intraduodenal (ID) administration of MPM at 16.7 mg kg-1, t1/2 beta was 3.92 +/- 1.05 h, and the AUC was 38.08 +/- 8.30 micrograms h mL-1. The systemic availability of MPA after ID MPM dosing was 1.52 times higher than that after ID administration of MPA. This result supports the usefulness of MPM as an oral prodrug of MPA as a new oral immunosuppressant.

Animals↗