Present status of kidney donation in Japan.
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Biomedical subjects
Publications and source records attributed to K Ota.
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More than 100,000 uremic patients have been maintained by various blood purification modalities in Japan. However, their quality of life is far from satisfaction not only in terms of physical problems related to the complications specific to long-term dialysis treatment, but also the restriction in social activities by spending much time for hospital dialysis. A graft functioning rate in kidney transplantation has been remarkably improving after introduction of Cyclosporine A as an immunosuppressant and is presently approximately 90% one year after transplantation. As long as the transplanted kidneys function, further extensive social activities and highly-graded quality of life is warranted compared to artificial kidney treatment. On the other hand, patients in end-stage renal diseases and with rejected transplants are expected to undergo safe kidney transplantations as being maintained by dialysis therapy. Furthermore, recent development in blood purification technology has made the specific kidney transplantations successful in recipients with the preformed antibody (-ies) and the incompatible ABO blood type antibody (-ies). Nowadays, relation between blood purification and kidney transplantation is not competitive, but mutually supplementary as a matter of realism.
Rheumatoid arthritis (RA) occurred frequently in women. Exogenous estrogen has been reported to alleviate the symptoms of patients with RA. But the implications of sex hormones and immunological abnormalities in RA remain to be elucidated. Therefore, we measured sex hormones (LH, FSH, estradiol, testosterone and prolactin), bone metabolic markers (midregion and carboxy terminal mainly recognized PTH1-84, intact PTH1-84, bone GLA protein and alkaline phosphatase), bone mineral, in lumbal bone with quantitative tomography (QCT) and with of cortex with microdensitometry in 52 females with RA and 46 females with osteoarthritis (OA) as a control group. Sex hormones and bone metabolic markers were analyzed as independent variables of serum LH, FSH and estradiol levels, using one way analysis, in patients with RA and OA. The more increased serum FSH and LH levels were, the more decreased serum estradiol levels were in both RA and OA groups, when they were considered as independent variables. These results indicate that the secretory function of pituitary and ovary axis hormones are normally enacted in RA. On the other hand, when the sex hormones of the patients under 53 years of age were studied in both groups, serum FSH adn LH showed significantly higher levels, while serum estradiol levels revealed decreased tendency in RA, compared with these in RA. Thus the pituitary ovary secretory function in patients with RA was suggested to be disturbed in early stage of age, indicating that the sex hormones would be partly implicated in calcium and bone metabolism in patients with RA.
We report two cases of amyotrophic lateral sclerosis (ALS), in which metal analysis revealed markedly higher aluminum concentration in the central nervous system (CNS) as well as higher calcium and lower magnesium concentration and higher Ca/Mg ratios compared with controls. Case 1 was a 55-year-old housewife and total duration of illness was 2 years and 2 mon from onset of clinical symptom. Case 2 was a 80-year-old woman and total duration of illness was 10 mon. Results showed that neither were exposed to toxic environments nor any neurologic disease in the past history. Postmortem examination disclosed motor neuron death and degeneration of pyramidal tracts. The significance of metal metabolism in pathogenesis of amyotrophic lateral sclerosis is discussed.
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The difficulty in obtaining suitable organs for the transplantation is a major problem in Japan. In this study, we assessed the suitable procedure for multiple organ preservation and evaluated organ viabilities after preservation with an unique technique. The heart and lung were preserved with UCLA Formula alone and the liver was preserved with Euro-Collins' solution. The mean ischemic times of the heart, lung and liver were 4.3 hours, 7.5 hours, and 6 hours, respectively. The viability of the heart graft following orthotopic transplantation was evaluated with cardiac output and Left Ventricular End-Diastolic Pressure (LVEDP) under the constant pre-load (CVP 7 mmHg). Cardiac outputs (ml/min.) were 4.01 +/- 1.36 before operation, 3.26 +/- 0.26 at 1 hour after transplantation, 3.24 +/- 0.26 at 4 hours after transplantation (NS). LVEDP (mmHg) was 7.1 +/- 0.8 before operation, 6.5 +/- 0.86 at 1 hour, and 7.4 +/- 1.2 at 4 hours after transplantation (NS). The viability of transplanted lung was evaluated with pressure-tidal volume curve and arterial oxygen tension (PO2) when right pulmonary artery and bronchus were occluded. There was no statistical difference in pressure-volume curve and PO2 tension between the phases of pre- and post-transplantation. After liver transplantation, ICG test (15 min.) showed a sufficient value of 35-40%. In conclusion, the procedures of multiorgan preservation using UCLA Formula and Euro-Collins' solution were successfully performed and its viability of grafts after transplantation remained sufficient.
A double-blind, placebo-controlled, cross-over clinical trial of recombinant human granulocyte colony-stimulating factor (rG-CSF), produced by Chinese hamster ovary cells, was conducted in 46 patients receiving intensive chemotherapy for non-Hodgkin's lymphoma. Each patient received 2 cycles of CHOP therapy. rG-CSF (2 micrograms/kg/day) or its placebo was given subcutaneously to each patient for 14 days from 2 days after initiation of the chemotherapy, in a cross-over fashion. rG-CSF significantly increased the absolute neutrophil counts (ANC) at nadir, and reduced the number of days with ANC less than 1,000/mm3 and also the number of days for recovery to ANC greater than or equal to 2,000/mm3. Bone marrow examination showed a significant increase in the number of myeloid cells after rG-CSF treatment. 12 infective episodes were observed during placebo cycles, while 6 infective episodes were observed during rG-CSF cycles. No serious side effects were observed. We concluded that rG-CSF was effective in neutropenia induced by intensive chemotherapy for non-Hodgkin's lymphoma.
A clinical trial of recombinant human granulocyte colony-stimulating factor (rG-CSF), produced by Chinese hamster ovary cells, was conducted in 66 patients receiving intensive chemotherapy for non-Hodgkin's lymphoma. Each patient received 2 cycles of CHOP therapy, and one cycle of them was performed with rG-CSF treatment and another one without rG-CSF treatment, in a cross-over fashion. rG-CSF (0.4, 2, 5, 10 micrograms/kg/day) was given intravenously or subcutaneously to each patient for 14 days from 2 days after initiation of the chemotherapy. rG-CSF increased the absolute neutrophil counts (ANC) at nadir, and reduced the period of neutropenia with ANC less than 1,000/mm3 and also the period for restoration to ANC greater than or equal to 2,000/mm3 after initiation of chemotherapy. These effects were remarkable at doses of more than 5 micrograms/kg/day intravenously and 2 micrograms/kg/day subcutaneously. Fourteen infective episodes were observed during the cycles of chemotherapy without rG-CSF treatment, while 7 infective episodes were observed during the cycles with rG-CSF treatment. rG-CSF was well tolerated. These results demonstrated that rG-CSF was effective in neutropenia induced by cancer chemotherapy at a intravenous dose of 5 micrograms/kg/day and a subcutaneous does of 2 micrograms/kg/day.
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Multiple sclerosis is thought to be an autoimmune disease of the central nervous system mediated by T cells specific for a myelin antigen. Myelin basic protein has been studied as a potential autoantigen in the disease because of its role as an encephalitogen in experimental autoimmune encephalomyelitis and post-viral encephalomyelitis and because of the presence in the blood of multiple sclerosis patients of in vivo-activated T cells reactive to myelin basic protein. Immune involvement in multiple sclerosis has been further suggested by the association with the major histocompatibility complex class II phenotype DR2, DQw1. To define the T-cell specificity toward myelin basic protein, 15,824 short-term T-cell lines were established from multiple sclerosis subjects, subjects with other neurological diseases, and normal controls. Here we report a higher frequency of T-cell lines reactive with a DR2-associated region of myelin basic protein between residues 84-102 in patients with multiple sclerosis compared with controls. A second region, identified between residues 143-168, was recognized equally in multiple sclerosis patients and controls and was associated with the DRw11 phenotype. These DR2 and DRw11 associations were also observed among T-cell lines generated from family members of a multiple sclerosis patient. The immunodominant 84-102 peptide from myelin basic protein was both DR2- and DQw1-restricted among different T-cell lines. These results raise the possibility that this immunodominant region may be encephalitogenic in some DR2+ individuals.
Multiple sclerosis (MS) may be an autoimmune disease mediated by T cells specific for a myelin protein. Investigations have demonstrated myelin basic protein (MBP)-reactive T cells that were activated in vivo in MS patients, suggesting that MBP may be a target antigen in MS. The variable (V) region of the T cell receptor (TCR) beta chain was examined among 83 T cell lines from both MS patients and healthy subjects that were reactive with the immunodominant region of human MBP (residues 84 to 102) or with a second immunodominant region of MBP (143 to 168). V beta 17 and to a lesser extent V beta 12 were frequently used in recognition of MBP(84-102) among different individuals. In contrast, V beta 17 was very infrequent among lines reactive with MBP (143-168). These data demonstrate shared TCR V beta gene usage for the recognition of immunodominant regions of the human autoantigen MBP. Such TCR structures may be used as targets for specific immunotherapy in MS.
A case of lymphoepithelial cyst in the pancreas was reported. A 64-year-old man without any specific complaints was found to have a cystic lesion in the anterior portion of the pancreas, as revealed by ultrasonography of the abdomen at an annual medical examination in 1988. This was dissected easily from the pancreas. Histologically, it was diagnosed to be a benign lymphoepithelial cyst in the pancreas. Cysts of this type are rare, and their histogenesis is also not well understood.
Recent epidemiological changes in patterns of foci of amyotrophic lateral sclerosis (ALS) in the Western Pacific suggest that environmental factors play a contributory role in the pathogenic process of this disorder. In this experimental study on rats, a similar situation of dietary mineral imbalance was created as is found in the soil and drinking water of these ALS foci with a low content of calcium (Ca) and magnesium (Mg) and a high content of aluminum (Al). In groups of rats fed a low Ca diet, low Ca-Mg diet, and low Ca-Mg plus high Al diet, serum Ca levels were found to be lower than those in a group fed a standard diet. Also, serum Mg levels were lower in the groups fed a low Ca-Mg diet and a low Ca-Mg plus high Al diet than in the groups fed a standard diet and only a low Ca diet. There was no significant difference in Mg content of central nervous system (CNS) tissues of groups fed unbalanced and standard diets, except for a significant decrease in Mg content of the spinal cord of rats fed a low Ca-Mg plus high Al diet. Mg content of the lumbar spine and cortical bone decreased in the unbalanced diet groups compared with that of a group fed a standard diet. These findings suggest that under the disturbed bone mineralization induced by unbalanced mineral diets, Mg may be mobilized from bone to maintain the level necessary for vital activity in soft tissues including CNS tissue.
The effect of cyclosporin A (CyA) on experimental allergic neuritis (EAN) was examined. CyA suppressed the development of actively induced EAN. The earlier treatment with CyA was begun, the more effective was its effect. CyA was effective even after the development of clinical signs. In actively induced EAN, cessation of CyA treatment lead to the development of EAN. However, in passively induced EAN, it did not. We could not find any differences in the distribution of infiltrating T cell subsets between the control group and the CyA-treated group.
A new immunomodulating agent, bestatin (INN: Ubenimex has low toxicity even after long-term oral administration and has significant modifications in immunological response. A cooperative randomized controlled study of bestatin immunotherapy in combination with remission maintenance chemotherapy for adult acute nonlymphocytic leukemia (ANLL) was performed. After induction of complete remission, patients were randomized to the bestatin group (30 mg/bw per os (po) daily) and the control group. The 101 eligible cases (bestatin: 48, control: 53) were analyzed; the bestatin group achieved longer remission than the control group and a statistically significant longer survival. Though this prolongation of remission was not significant in the bestatin group compared to the control group in the 15-49 yr age group, in the 50-65 yr age group it was significantly longer. Bestatin is shown to be a clinically useful drug for immunotherapy of adult ANLL, since it has prolonged survival and remission especially in elderly patients, with few side-effects.
The effect of food deprivation on the pulsatile release of LH was examined in the normal cycling and the ovariectomized (OVX) adult female rat. In the cycling animals, there were significant decreases in the mean plasma LH levels as well as the frequency and amplitude of the LH pulse 48 h after the onset of food deprivation. On the other hand, food deprivation for up to 72 h did not cause any changes in pulsatile LH release in the OVX animals. No difference in the changes in body weight and blood glucose concentration were found between the cycling and OVX rats throughout the period of food deprivation for up to 96 h. These findings suggest that ovarian factors play an important role in the early manifestation of the effect of food deprivation on pulsatile LH release and that metabolic changes as expressed by decreases in body weight and blood glucose level per se were not the direct causes in the decrease of LH release during the period of food deprivation.
To assess the effect of cardiopulmonary denervation on the release of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP), either hemorrhage (1.0 ml.kg-1.min-1, for 40 min) or an infusion of 3% dextran in lactated Ringer solution (RL) (3% dextran in RL, 1.0 ml.kg-1.min-1, for 40 min) was carried out in chronic cardiopulmonary denervated (CPD, n = 7) and sham-operated (SO, n = 7) dogs under anesthesia. Plasma AVP increased significantly in both groups during hemorrhage, but its rise was significantly attenuated in CPD dogs. Plasma ANP decreased similarly during hemorrhage in both groups. An infusion of 3% dextran in RL decreased significantly plasma AVP during its whole period in SO dogs, but AVP release was only suppressed in the late period in SO dogs. Plasma ANP increased significantly during its infusion in both groups. These results indicate that cardiopulmonary denervation may attenuate the release of AVP in response to either hemorrhage or blood volume expansion but may not affect the release of ANP in response to the blood volume change. Moreover, a large increase in plasma ANP may attenuate the release of AVP.
Long-term mass transfer and nutritional and metabolic stability of end-stage renal disease patients maintained on continuous ambulatory peritoneal dialysis (CAPD) continue to be of concern. This study longitudinally monitored 43 Japanese CAPD patients (29 males, 14 females) from three centres within the Tokyo Metropolitan Area for an average period of 15 +/- (SD) 8 months. The mean time for patients on CAPD at study initiation was 18 +/- 15 months. Monitored parameters included urea and creatinine mass transfer coefficients, clearances and blood levels, ultrafiltration, lipid levels, dietary protein intake, and weight. Lipid data were also gathered retrospectively from patient records from the time of CAPD initiation. The results were analyzed using regression growth curve analysis and analysis of variance. Statistically significant linear rises with time were apparent only for the creatinine mass transfer coefficients, although this was not considered clinically significant in terms of changes either in peritoneal creatinine clearances or ultrafiltration. Serum cholesterol levels were found to rise significantly above pre-dialysis levels 11 months after CAPD onset, thereafter returning to levels not significantly above baseline levels. In summary, CAPD provided stable, acceptable treatment over the study period.