[Serum levels of interleukin 6 in patients with inflammatory bowel disease].
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Biomedical subjects
Publications and source records attributed to M Sada.
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HLA DQ beta chain, in particular amino acid at position 57, has been reported to contribute to susceptibility and resistance to Type 1 (insulin-dependent) diabetes mellitus in Caucasians. Resistance has been proposed to be conferred by aspartic acid at this position. To ascertain the association of HLA DQ beta and DR beta genes with Type 1 diabetes in Japanese subjects, ten Japanese Type 1 diabetic patients were investigated at DNA level. Genomic DNA was amplified by polymerase chain reaction, and dot blot analysis was carried out using the amplified DNA with allele specific oligonucleotide probes. All patients had aspartic acid at position 57 of at least one of their two DQ beta chains, and there was no significant difference of amino acids at the same position of DR beta chain in patients compared to control subjects. These data indicate that the protective role of aspartic acid at position 57 of DQ beta chain is less significant in Japanese compared with Caucasian subjects.
Nuclear magnetic resonance (NMR) imaging was used to measure tissue sodium-23 in the myocardium undergoing cardiac rejection. In six dogs, the donor heart was heterotopically transplanted into the recipient's chest cavity. The dogs were then killed and sodium-23 images of the excised hearts were obtained using a high field (1.5 Tesla) NMR imaging system. Proton NMR imaging of each excised heart was also performed and T1, T2 relaxation times were calculated. Subsequently, these data were correlated with pathological findings of mild, moderate and severe rejection. The correlation coefficients between the rejection score and the T1, T2 relaxation times and sodium NMR signal intensity were 0.79, 0.70 and 0.84, respectively. Severely rejected areas of the myocardium were visualised by increased sodium NMR signals. These findings suggest that an increase of sodium NMR intensity is mainly caused by an increase of intracellular sodium content due to irreversible myocardial necrosis. Sodium NMR allows evaluation of the location and extent of rejection of myocardium after heart transplantation.
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Seven canine donor hearts in which atrial septal defect and tricuspid regurgitation had previously been produced were heterotopically transplanted into the recipients' chest cavities. Indium-111 antimyosin myocardial imaging of the excised heart was performed using a scinticamera. Magnetic resonance imaging was also performed and the T2 relaxation time calculated. Subsequently, these data were correlated with pathological findings, which indicated the degree of rejection. Indium-111 antimyosin uptake was high in moderate and severe rejection, but the T2 relaxation time was prolonged even in mild rejection. Thus indium-111 antimyosin uptake was specific, and the T2 relaxation time was sensitive, for detecting the severity and extent of cardiac rejection. Although ex vivo experimental results have been reported, these new methods allow characterisation and accurate evaluation of myocardial tissue undergoing cardiac rejection.
It is important in heart transplantation to evaluate precisely the extent and location of cardiac rejection. At present, right ventricular endomyocardial biopsy has been used as the gold standard, however, establishment of noninvasive, simple, and easy diagnostic procedure is desired. The canine donor heart, in which atrial septal defect and tricuspid regurgitation had been produced beforehand, was heterotopically transplanted into the recipient's chest cavity. In seven dogs, two to three mCi of 111In-antimyosin was injected intravenously upon cardiac rejection before the heart was excised. 111In-antimyosin myocardial imaging was then performed using a gamma camera. In the same slice, a histopathological rejection score was calculated and divided into mild, moderate or severe injection. The uptake of 111In-antimyosin was significantly higher in moderate and severe rejected myocardium, since this agent produced a specific and selective localization and concentration in areas of myocardial damage. Therefore, this new technique allows the evaluation of therapeutic intervention upon cardiac rejection and may replace right ventricular endomyocardial biopsy.
It is important to evaluate the severity and extent of cardiac rejection in heart transplantations. Eight heterotopic heart transplantations using mongrel dogs were performed, and grated magnetic resonance imaging (MRI) of the donor hearts was carried out. High signal intensity was obtained in the rejected myocardium at the time of cardiac rejection, especially from the right ventricular wall to the intraventricular septal wall compared with the left ventricular posterolateral wall. In addition, MRI was performed in the excised heart. High signal intensity was also observed in the same region of the excised donor hearts. The histopathological rejection scores were well in agreement with prolonged T1 and T2 relaxation times; severe and mild rejection of the myocardium were distinguished by the T1 and T2 relaxation times. Our results suggest that MRI is able to visualize the transplanted myocardium undergoing rejection and that the right ventricular wall is more sensitive to cardiac rejection than the left. MRI may allow noninvasive evaluation of the severity and extent of cardiac rejection.
It is important to evaluate the severity and extent of cardiac rejection in heart transplantation. Six heterotopic heart transplantation models in the peritoneal cavity were prepared with 12 adult mongrel dogs and in vivo imaging of the donor heart was performed using gated magnetic resonance imaging, (MRI) and Gd-DTPA contrast enhancement. In cardiac rejection, high signal intensity was obtained in the rejected myocardium, especially from the right ventricular wall to the intraventricular septal wall. The rejected myocardium was clearly visualized after administration of Gd-DTPA (0.5 mmol/kg body weight) via the femoral vein in all donor hearts. The mean ratios of signal intensity calculated from the rejected and normal myocardium were also increased from 25% to 42% after administration of Gd-DTPA. On the other hand, in the cases with no rejection, whole myocardium was visualized homogeneously before and after Gd-DTPA and there was no high signal intensity. Thus, our method has the potential of assessing the extent and severity of cardiac rejection using gated MRI and Gd-DTPA contrast enhancement.
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An experimental model was designed to study hemodynamic and left ventricular functional changes in the course of and after brain death in 13 mongrel dogs. Brain death was induced by creating intracranial hypertension by inflating a balloon inserted into the subdural space. Hemodynamic parameters and left ventricular systolic function as assessed by echocardiography were measured before and during intracranial hypertension and 30 min and 1, 2, 3, 5 and 8 hrs after brain death. During intracranial hypertension, heart rate, systemic and pulmonary blood pressures, cardiac output and systemic vascular resistance raised significantly. After brain death, all parameters decreased rapidly and significantly, and then stabilized. On comparison with values obtained before intracranial hypertension, systemic blood pressure decreased markedly following brain death, while no marked change was noted in cardiac output. This result is attributable to a marked reduction in peripheral vascular resistance following the induction of intracranial hypertension. The left ventricular end-diastolic and end-systolic diameters did not change; consequently, fractional shortening did not change, either. The Weissler's index improved after brain death, reflecting a marked reduction in systemic vascular resistance. This indicates limited usefulness of afterload-dependent cardiac indices. At the agonal period of brain death, three of 13 dogs died because of ventricular fibrillation or a marked decline in systemic blood pressure. Within five to eight hours after brain death, seven dogs died because of intractable acidosis. These results represent the specific hemodynamic features occurring after brain death. It is thought that recognition of these features is useful in managing cases of brain death and in selecting donors for heart transplants.
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This is a report of a patient who underwent cadaveric renal transplantation in spite of the presence of three HLA-A, B and two DR antigen mismatches between the recipient and donor. The recipient received more than 20 units of blood before transplantation. The crossmatch between the recipient's serum and the T and B cells of the donor was negative. The patient exhibited hepatic dysfunction from the early posttransplant period, which eventually led to discontinuation of azathioprine or Bredinin at one year posttransplantation. Thereafter, only betamethasone was administered once every 3 days. The patients has maintained good renal function for more than one year following withdrawal of the immunosuppressants. It appeared that transplantation tolerance was established in this patient. Therefore, we examined the mechanisms sustaining the tolerance. Both nylon-wool-adherent, alloantigen-specific suppressor T cells and nonadherent, nonspecific suppressor T cells were observed in the lymphocytes of the patient after transplantation. It was also shown that suppressive antibody was present in the serum directed toward the clone of autologous lymphocytes that reacted with the mixed lymphocyte reaction (MLR) antigen of the donor. In the inhibition test against various types of MLR antigens using this suppressive antibody, it was found that the reaction against the donor cells was suppressed when the responding cells shared the same class I antigen with the recipient. When the stimulating cells had the class II antigen of the donor, the reaction of the specific responding cells was also inhibited. These inhibiting effects were only seen when the responding cells were pretreated with the antibody, but not when stimulating cells were pretreated.
In this study, the method of preserving isolated canine hearts for transplantation was established. The newly-developed method is named retrograde coronary sinus microperfusion technique. Canine hearts were arrested and cooled to 4 degrees C by means of normograde coronary perfusion with Collins' solution containing 10% fluorocarbon (FC) in order to avoid myocardial damage during warm ischemic time. Then, the hearts, immersed in Collins' solution, were retrogradely perfused through a coronary sinus at a rate of 60 ml/hr or 30 ml/hr with above-mentioned solution. After preservation for 36 hours, heterotopic heart transplantation was performed in an abdominal cavity of a recipient dog. The 36 hour-preserved hearts restored their cardiac beat after reperfusion with recipient blood. Histological observation did not show any abnormal findings in these preserved hearts. In order to evaluate the cardiac functions of preserved hearts for 24 to 36 hours, left ventricular end-systolic pressure-volume ratio (Emax) and end-diastolic pressure-volume relation were measured. Both were well restored in 24 hour-preserved hearts. The 36 hour-preserved hearts resulted in Emax within a satisfactory range, while end-diastolic pressure was elevated in all cases. This was markedly impaired with infusion of isoproterenol. These results strongly suggested that transplantation using 24 hour-preserved hearts could be performed well. On the other hand, the 36 hour-preserved hearts were considered to function satisfactorily under careful management after grafting. The retrograde coronary sinus microperfusion method developed here was found to be useful for a distant heart procurement.
The immunosuppressive factors in uraemic sera were studied. Sera were obtained from 46 uraemic patients with a mean serum creatinine of 1.24 mM/1 +/- 0.36 (s.d.) prior to being introduced to dialysis therapy. Normal peripheral blood mononuclear cells, which were incubated in vitro with pokeweed mitogen (PWM) in the presence of 10% uraemic sera plus 10% pooled normal human serum sustaining the culture, showed decreased 3H-thymidine uptake compared to the control culture with normal sera. The immunosuppressive activity of uraemic sera was partially lost by in vitro dialysis, although a moderate degree of suppressive potency to the normal cells cultured with PWM remained in the dialysed uraemic sera. The remaining inhibitory activity in the dialysed sera was found to be unrelated to anti-lymphocyte antibodies.
Clinicopathological studies were carried out in fifty nine surgical cases of carcinoma of Vater's ampulla. In the point of view of the developmental process of the carcinoma, they were divided into the following two types; tumor-forming type and ulcerative type. No significant difference in survival time was noticed between two types. In the ulcerative type, prognosis was much better in the cases of carcinoma with small ulcer than those of carcinoma with large ulcer. The "early cancer" in which carcinoma did not extend beyond the sphincter of Oddi showed better prognosis than the "advanced cancer" in which carcinoma infiltrated into the pancreas. There were 10% of vascular permeation and 20% of metastasis into lymph nodes in the "early cancer", while there were 92% of vascular permeation and 71% of metastasis into lymph nodes in the "advanced cancer". Although high incidence of positive tissue-CEA (28 out of 34 cases, 82.4%) was observed, 9 out of 19 cases (47.4%) showed slight increase of serum-CEA level. The diagnostic value of serum-CEA seemed to be relatively low in carcinoma of Vater's ampulla.
103 adult patients with biopsy-proved IgA nephropathy were typed for HLA-A and HLA-B antigens and 80 of these cases were typed for HLA-DR antigens. A significant association with HLA-DR4 was clearly noted (pc less than 0.04). The high phenotype frequency (PF) of BW35 was observed in the patients, but not statistically significant (pc less than 0.2). Two groups, the stable group and progressive group, were selected from all patients according to their clinical courses. The PF of HLA-DR4 was significantly higher in the stable group than the progressive group (pc = 0.005). The PF of BW35 was also higher in the stable group, but this difference was not statistically significant (pc = 0.6). The frequency of the combination of HLA-BW35 and DR4 increased significantly as compared to that in the control group. Further, the patients who had both of these antigens showed favorable courses. These results suggest that the HLA-DR4 antigen, especially a combination of HLA-BW35 and DR4 antigens are related to the occurrence of benign IgA nephropathy.
A total of 60 leprosy patients, 28 of lepromatous and 32 of tuberculoid form, and 70 active tuberculosis patients was compared with a control of 184 for 34 HLA specificities. The most interesting finding was an increased frequency (10.0%) for HLA-B8 (corrected P = 0.062, relative risk = 20.3) in the leprosy patients as compared with the control group, despite the fact that the frequency of HLA-B8 was extremely low in Japanese. Furthermore, all leprosy patients with B8 had leprous member(s) in their family.