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H Kanda

Publications and source records attributed to H Kanda.

At least 145 records · Page 8Linked to original sources

[Experimental studies on the mode of action of cyclosporine and FK506 assessed by proliferation response of human cloned T lymphocytes].

We applied cloned human T lymphocytes established in our laboratory to evaluate the mode of action of Cyclosporine (CsA) and FK506. Phenotypic and functional analysis led us to conclude that HTL403 was a helper T cell clone and HTL805 a cytotoxic one. Susceptibility of HTL-403 to the immunosuppressants demonstrated that alloantigen-driven proliferative response can recover to the rIL2-driven level by the addition of rIL2 at higher concentration of the agents. Although full recovery was not observed in FK506, this finding indicated that FK506 as well as CsA inhibit IL2 secretion from HTL403. FK506 showed remarkable suppressive effect on the proliferative response of HTL-805 even at a considerably low concentration, while CsA suppressed such a response dose-dependently. We concluded that FK506 can be used to reverse ongoing acute rejection as well as to prevent acute rejection.

Cell Division↗

Mouse-human chimeric monoclonal antibody to carcinoembryonic antigen (CEA): in vitro and in vivo activities.

Mouse-human chimeric antibody specific for human carcinoembryonic antigen (CEA) was produced by recombinant DNA techniques. The genes of the mouse variable regions of heavy and light chains were cloned from the mouse hybridoma, 2.7.1G.10., which secreted anti human CEA antibody (IgG1, kappa), and were joined with human gamma 1 and kappa constant genes. The affinity of the resultant chimeric antibody to its relevant antigen was the same as that of the parental mouse monoclonal antibody when analysed by Scatchard plot analysis. The chimeric antibody showed a potent antibody dependent cell-mediated cytotoxicity (ADCC) activity with human peripheral blood mononuclear cells against CEA-positive human adenocarcinoma cells. In vivo imaging analysis revealed that the present chimeric antibody was specifically localized on the tumor site. These results indicate that our mouse-human chimeric antibody is a promising reagent for the diagnosis and therapy of CEA-positive human cancers.

Amino Acid Sequence↗

Clinicopathological study on end-stage reflux nephropathy in renal-transplanted children.

Five children with end-stage reflux nephropathy underwent kidney transplantation at our clinic. Reflux nephropathy was studied clinically and histologically. All children had proteinuria before starting hemodialysis, and hypertension was present in 2 cases. Three children underwent antireflux operations prior to transplantation. The original kidneys exhibiting reflux were removed during renal transplantation. All original kidneys exhibited atrophy and scarring. Focal and segmental glomerulosclerosis was found in 4 cases. PAS deposition in the interstitium, suggestive of Tamm-Horsfall glycoprotein, was found in all cases. No recurrent signs of focal and segmental glomerulosclerosis have been found in the children who have been followed up from 1 to 6 years after transplantation.

Adolescent↗

[Urinary FDP D-dimer and E fragments in renal transplantation].

Both D-dimer and E fragments in urinary FDP were determined in renal transplantation patients. Urinary D-dimer fragments increased in 14 out of 20 acute rejections (70.0%) and in 6 out of 18 chronic rejections (33.3%). Urinary E fragments increased in 8 out of 9 acute rejections (88.9%) and in 4 out of 5 chronic rejections (80.0%). It is suggested that urinary FDP-E fragment is a better indicator to detect or predict rejection than the whole Urinary FDP. The appearance of D-dimer in the urine indicates intravascular coagulation in glomeruli followed by a secondary fibrinolysis in the course of the rejection reaction. The urinary D-dimer/FDP ratio which was used as the indicator of fibrinolytic activity in glomeruli was obtained in various conditions of renal transplants. The ratios were relatively high in the urines from well functioning grafts. This ratio deteriorated at the onset of rejection crisis and tended to go upward during the course of the recovery when the rejection was reversible. In the cases of irreversible acute rejection and chronic rejection, these ratios remained at a low level. D-dimer/FDP ratio might be useful indicator to predict the reversibility of rejection and the prognosis of renal allograft. Furthermore, these findings suggest that fibrinolytic and thrombolytic therapy by the tissue-type plasminogen activator (t-PA) along with immunosuppressive drugs might be more effective for the treatment of these rejections.

Fibrin Fibrinogen Degradation Products↗

[Management of hypertension after renal transplantation].

We report the clinical result of our management for post-transplant hypertension in 47 renal allograft recipients who were followed up for more than one year after transplantation. Hypertension developed in 4 (26.7%) out of 15 cases who were treated with conventional immunosuppressive therapy (Group I) and 18 (56.3%) out of 32 cases treated with CsA (Group II). In group I, all the 6 patients who had been nephrectomized their original kidney at the time of transplantation did not develop hypertension. And the blood pressure before transplantation had a marked effect on post-transplant blood pressure. In group II, there were many recipients who had become hypertensive after transplantation though most of them became normotensive with dose reduction of immunosuppressants. Ten normotensive patients before transplantation who had not developed hypertension retained their normal blood pressure throughout the course without any antihypertensive medication. We could find no correlation between graft function and blood pressure, although recipients with poor graft function had a tendency to be hypertensive. A satisfactory fall in blood pressure in the patients treated with CsA was observed when the immunosuppressive regimen was changed to triple therapy to reduce the dose of CsA. The recorded blood pressure were 174.0 +/- 19.0/105.2 +/- 16.5 mmHg after transplantation and 145.2 +/- 15.7/78.4 +/- 17.1 mmHg at the latest follow-up. We performed original nephrectomy in 6 patients whose blood pressure could not have been controlled by the antihypertensive medication. All the venous sampling studies showed that increased renin secretion was confined to original kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[The effects of thromboxane A2 synthetase inhibitor on chronic rejection of kidney transplantation].

There has been no useful treatments for chronic vascular rejection (CVR) after kidney transplantation until now. Recently, however, some reports have suggested that the thromboxane A2 synthetase inhibitor, OKY-046, is useful in reducing proteinuria in nephrotic syndrome and preventing progression of CVR. Five patients with CVR (serum creatinine range: 1.7-2.6 mg/dl) were treated with OKY-046 for over one year and the effect of OKY-046 was evaluated. One patient developed acute rejection and another renal hypertension during this study. Except for the cases of acute rejection and renal hypertension, serum creatinine slightly decreased in 1 case and remained unchanged in 2 cases. Urinary excretion of protein and thromboxane B2 decreased significantly but prostaglandin E2 did not change in the treatment of the deterioration with OKY-046. We concluded that OKY-046 was effective in preventing graft function and decreasing urinary protein excretion in kidney transplant recipients with CVR.

Acrylates↗

[Clinical studies on hyperuricemia and gout after transplantation].

We performed renal transplantation on 67 patients (living 37, cadaver 30) between November 1975 and December 1987. Twenty-seven of the 67 patients had hyperuricemia (serum uric acid: male greater than or equal to 8.0 mg/dl, female greater than or equal to 7.0 mg/dl) and 2 of them had episodes of gout. However, there was no correlation between serum creatinine and uric acid in 27 hyperuricemic patients. Twelve of 27 hyperuricemic patients were treated with either allopurinol or benzbromarone. These therapies were effective for 9 of them and serum uric acid level controlled well. One of 2 gouty patients developed gout 4 years after cadaveric renal transplantation. She was treated with anodyne and benzbromarone for gout. These treatments were effective and she has been in good condition. We consider it necessary to treat hyperuricemia after renal transplantation and to control serum uric acid well.

Adult↗

Lymphocyte spontaneous blastogenesis as a monitor of renal allograft rejection.

Spontaneous blastogenesis (SB) of peripheral blood lymphocytes was studied by determining protein synthesis using 3H-leucine to establish an immunological monitoring method after renal transplantation. In acute rejection, the SB level was twice as high as those in ATN and in the quiescent state. A rise in SB level comparable to that in rejection was observed in patients with infection. The SB level was continuously determined postoperatively in eight patients undergoing renal transplantation. Of the eight patients, three showed acute rejection four times in total. Elevation of SB level was simultaneously observed at each rejection episode. Rejection was not noted in any of the other five patients. False positive elevation of SB level was observed five times. The cause of the false positive changes was unknown in three cases and due to infection in two cases. Elevation of SB level is considered to be nonspecific and represents total lymphocyte activity. Due to its simple procedure and quick results, this method should provide a useful clinical parameter of rejection.

Graft Rejection↗

[Interaction between phenobarbital and ciclosporin following renal transplantation: a case report].

We report a case of decreased ciclosporin (CsA) trough level due to the interaction with phenobarbital after living renal transplantation in a 15-year-old male. Two other cases prescribed valproate sodium as an anticonvulsant, showed no change in the plasma CsA levels. Therefore, it is necessary to recognize the drug interaction with CsA, and appropriate drug should be chosen in clinical renal transplantation.

Adolescent↗

General pharmacology of beraprost sodium. 2nd communication: effect on the autonomic, cardiovascular and gastrointestinal systems, and other effects.

Beraprost sodium (sodium (+/-)-(1R*,2R*,3as*,8bS*)-2,3,3a,8b-tetrahydro-2- hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H- cyclopenta[b]benzofuran-5-butyrate, TRK-100) is an orally active epoprostenol (prostaglandin I2, PGI2) analogue. Its general pharmacological effects on peripheral organs were studied. 1. In isolated organs, beraprost sodium relaxed the trachea and increased atrial beating rate (2.4 x 10(-5) mol/l). It also dose-dependently contracted the stomach, aorta, ileum and uterus (2.4 x 10(-7)-2.4 x 10(-4) mol/l). These effects of beraprost sodium were similar, but inferior to those of PGI2 and PGE1. 2. Intravenous administration of beraprost sodium produced a dose-related decrease in blood pressure (BP), its potency being about 1/3 times that of PGI2 in anesthetized rats and dogs. Beraprost sodium and PGI2 had no effects on heart rate (HR), and enhanced respiration in conjugation with a decrease in BP. Oral administration of beraprost sodium in high doses (1-3 mg/kg in rats and 0.3 mg/kg in dogs) caused a decrease in BP. A compensatory tachycardia and an elevated plasma renin activity (PRA) occurred after low doses (0.1-0.3 mg/kg) in rats. In contrast, a change of HR and PRA in rabbits and dogs was mild. 3. Beraprost sodium produced suppression of digestive organs: markedly, gastric motility and secretion and intestinal transport; slightly, but significantly, biliary secretion. On the other hand, it enhanced ileal motility at a high dose (300 micrograms/kg i.v.). 4. Oral administration of beraprost sodium caused a decrease in urinary volume and electrolyte excretion in rats. 5. Oral administration of beraprost sodium prolonged bleeding time in mice, while it had no effect on the blood coagulation system in vitro. In addition, beraprost sodium had no hemolytic action. 6. The other effects of beraprost sodium were weak. Beraprost sodium had no local anesthetic activity and no effect on salivation, pupil size and neuromuscular transmission in the skeletal muscle. Beraprost sodium slightly contracted the uterus of non-pregnant rats in situ and dose-independently inhibited carrageenin-induced paw edema. In conclusion, beraprost sodium produced various effects on the autonomic, cardiovascular, and gastrointestinal systems. Probably, these effects may be based on its own action like PGI2.

Anesthetics, Local↗

[Dobutamine infusion test for predicting the postoperative recovery of left ventricular function in patients with chronic aortic regurgitation].

In order to predict the postoperative recovery of left ventricular (LV) function after valve replacement, dobutamine (DOB) infusion tests were performed on 21 patients with chronic aortic regurgitation (AR). As a predictor of the LV functional reserve. delta mVcf, calculated from the difference between the mVcf in echocardiographs before and after DOB infusion, was used. According to the values of delta mVcf, patients were classified into two groups. The good-response group consisted of 15 patients with delta mVcf greater than or equal to 0.45 cir/sec, and the poor-response group consisted of 6 patients with delta mVcf less than 0.45 cir/sec. Comparison of the early postoperative values in these two groups disclosed that the LV end-systolic dimensions (LVDs) and the %fractional shortening (%FS) improved in the good-response group, whereas in the poor-response group, the LVDs remained above 40 mm and the %FS, below 28% in the early postoperative period. A significant correlation was found between the preoperative delta mVcf and early postoperative %FS in both groups. The value of delta mVcf improved postoperatively, both in the good-response group and in the poor-response group; the %FS increased in the poor-response group late postoperatively. In patients whose delta mVcf did not improve in the postoperative DOB infusion test, the %FS remained depressed throughout the follow-up periods. Thus, the postoperative delta mVcf showed a significant correlation with the late postoperative %FS. In conclusion, DOB infusion tests were found to be an excellent indicator for estimating the amount and time course of improvement of LV function after surgery.

Aortic Valve↗

[The influence of left ventricular function on surgical risk in mitral stenosis].

The influence of left ventricular (LV) function on surgical risk was assessed in 98 patients with mitral stenosis (MS) using echocardiographic studies including a dobutamine test in 42 cases. Intraoperative LV myocardial biopsy was also performed in 24 cases. Preoperatively, depressed LV function [% fractional shortening (%FS) less than or equal to 27%] was observed in 21 patients (21%). Seven patients had postoperative LV failure, five of whom had preoperative depression of LV function. Among these five patients, three had low cardiac output; and in the other two preoperative %FS was severely depressed. In cases of poor responses to preoperative dobutamine, postoperative improvement in %FS and the cardiac index were not as marked in the good-response group, and some of these patients had LV failure postoperatively. Percent fibrosis of the LV myocardium, which was demonstrated by intraoperative biopsy, correlated negatively with preoperative %FS, and %fibrosis was greater in the group responding poorly to dobutamine administration, especially in patients with postoperative LV failure. These results suggest that some patients with MS were developing LV failure postoperatively due to impaired myocardium. Myocardial fibrosis seemed to be an important causative factor in these patients. Preoperative evaluation utilizing dobutamine administration is useful in screening for high-risk patients.

Adult↗