Effect of a novel immunosuppressive agent, deoxyspergualin, on rejection in kidney transplant recipients.
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Azathioprine↗
Biomedical subjects
K Ota
Publications and source records attributed to K Ota.
[Contents of calcium, phosphorus and aluminum in central nervous system, liver and kidney of rabbits with experimental atherosclerosis--scavenger effects of vinpocetine on the deposition of elements].
The aims in this study were designed to clarify the contents of calcium (Ca), phosphorus (P) and aluminum (Al) in central nervous system (CNS), liver and kidney of rabbits with atherosclerosis experimentally induced by cholesterol-rich diet, and investigate scavenger effect of 14-ethoxycarbonyl-(3 alpha, 16 alpha-ethyl)-14,15-eburnamenine (vinpocetine) on the deposition of these elements in CNS and soft tissues of experimental atherosclerosis. Sixteen male rabbits were divided into 4 groups. Each group was fed with standard diet (Group A), standard diet containing 1.5% cholesterol (Group B), standard diet containing 1.5% cholesterol plus oral administration of 3 mg/kg/day vinpocetine (Group C), and standard diet containing 1.5% cholesterol plus administration of 10 mg/kg/day vinpocetine (Group D). After 3 months' feeding, experimental atherosclerosis was produced with a modified method of Kritchevsky et al in rabbits of Groups B, C and D. Blood was collected by cardiocentesis under the anesthesia of ether and then rabbits sacrificed to remove CNS and other tissues. The blood was stood for 1 hour at room temperature and separated by centrifugation at 3000 rpm for 10 min to determine serum total cholesterol, phospholipids, HDL-cholesterol, peroxide lipid, NEFA and calcium levels. Ca, P and Al contents in the frontal lobe, pons, cerebellum, spinal cord, liver and kidney were determined by neutron activation analysis. Ca contents of CNS, liver and kidney in Group B significantly increased than those of Group A (p less than 0.01), and significantly decreased in Groups C and D compared with those of Group B (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Aluminum↗
A novel rescue drug, 15-deoxyspergualin. First clinical trials for recurrent graft rejection in renal recipients.
The present multicentral clinical study performed in 6 institutes demonstrated that the novel immunosuppressive agent, 15-deoxyspergualin (DSG), is very effective on rejection. In 34 cases of rejection, 30 were treated with DSG at 40 mg/m2 (1 case), 80 mg/m2 (7 cases), 120 mg/m2 (9 cases), 180 mg/m2 (9 cases), and 220 mg/m2 (8 cases). The overall remission rate was 79% in 34 cases of rejection including accelerated, acute, and chronic rejection in different periods after transplantation. Analyzing the remission rates of early phase acute rejection occurring within 3 months after transplantation according to treatment pattern, the remission rate was 100% in 3 cases treated with DSG alone (using DSG 1 week or longer after other agents), 88% in 8 cases treated by rescue use of DSG (using DSG within 1 week after other agents), and 86% in 7 cases treated by combined use of DSG with other agents. Adverse reactions included reductions in WBC and platelets, anemia, perioral numbness, gastrointestinal troubles, and others. However all these symptoms were so mild that DSG treatment was not discontinued. Further studies are necessary on the effect of DSG, especially in acute rejection under conditions that reduce the many influences of other agents as much as possible.
Adult↗
Organ transplantation in Japan--present status and problems.
Kidney transplantation was first performed in Japan in 1956. Liver, heart, and pancreas transplantation began in 1964, 1968, and 1984, respectively. From 1964 until the end of 1987, 5328 kidney transplantations were performed in 122 facilities. A total of 75.7% of the grafts came from living related donors and 24.3% from cadavers. Although there were 80,553 patients on dialysis at the end of 1987, only 572 renal transplants were performed that year. No liver or heart transplantations have been performed since 1968. In this review, data from the Japanese National Registry on Dialysis and Transplantation are presented. In addition, the social problems and public attitude towards brain death legislation and organ transplantation are discussed.
Attitude↗
Effect of hyperbaric oxygen therapy on essential haematuria.
Forty-three patients with essential haematuria were studied for 35 days to determine the efficacy of hyperbaric oxygen (OHP) exposure on haemostatic ability. Out of 15 untreated patients, haematuria persisted for the study period in all but one patient (6.7%). Out of 11 patients who received 90 mg/day of carbazochrome sodium sulfate and 750 mg/day of tranexanic acid excellent haemostatic results had been obtained in 2 (18.2%). Results of exposure of 17 patients to 2 atm. pressure of OHP for 90 min daily were excellent in 10 (58.8%) and good in one (5.9%). No serious adverse effects had been noted following OHP treatment. These results indicate that OHP can be applied for the treatment of essential haematuria if routine haemostatic drugs fail to improve the condition.
Adrenochrome↗
Leukocytosis in mice following therapy with a novel antitumor agent, RA-700.
Nine daily intravenous (iv) injections of RA-700 (an antitumor cyclic hexapeptide) at doses of 2 to 6 mg/kg/day caused increases of WBC counts at 4-6 days after treatment in normal C57BL/6 X DBA/2 (BDF1) mice. The percentages of neutrophils and lymphocytes were modified. There was a decrease of colony-forming units in culture (CFUc) in bone marrow to 40% of the control value on day 1 but CFUc rapidly returned to normal values on day 3. The colony-forming units in spleen (CFUs) in bone marrow decreased during treatment. On the other hand, CFUc and CFUs in spleen were increased from the initiation of treatment to the time prior to the increase of WBC count. Spleen weight increased after treatment, and histologically, increases of immature and also mature granulocytes and megakaryocytes were observed. However, RA-700 did not stimulate the progress of hematoprogenitors in vitro. The results indicated that RA-700 stimulates the progress of hematoprogenitors in the spleen, but this effect is probably indirect.
Animals↗
Pathological observations in HTLV-I associated myelopathy.
The following are the clinical and autopsy findings in a 63-year-old woman with myelopathy associated with the human T-cell lymphotropic virus Type I (HTLV-I). HTLV-I antibody was positive in both the serum and cerebrospinal fluid (CSF). In the lower thoracic region, demyelination and the loss of axons were accompanied by a proliferation of astrocytes, and gliosis was found in the lateral columns. Perivascular and parenchymal infiltrations of macrophages, lymphocytes, and plasma cells were also observed, but neither viral inclusion bodies nor atypical lymphocytes were found.
Axons↗
Clinical application of a self-sealing poly(ether-urethane) graft applicable to blood access for hemodialysis.
A poly(ether-urethane) graft (PEU) has been developed by our group and examined clinically. From July 1986, four straight and 11 loop grafts were implanted in 15 patients on maintenance hemodialysis. One straight and three loop grafts thrombosed between 1-6 months after the operation. One loop graft was ligated to remedy edema caused by a preexisting subclavian vein thrombosis. Angiographic findings of the grafts revealed a smooth positioning of the graft in most of the cases with minimal to moderate stenosis at anastomotic sites. Punctured sites were identified as tiny filling defects on the wall. However, neither stenosis nor aneurysmal dilatation were observed. Specimens of the graft were obtained from three patients to examine histological findings. Neointimal coverage was observed near the anastomotic site in a specimen obtained 6 months after the operation. The bare luminal surface still remained at the center of the graft. No clinical sign of peripheral thrombi was found. In addition to the clinical experience, this study is supplemented with the preliminary result of an animal experiment using a newly modified PEU graft with an open structure on the luminal surface.
Animals↗
Preventive effect of vinpocetine on calcifications: atherosclerosis in experimental rabbits.
The action of vinpocetine (14-ethoxycarbonyl-(3 alpha, 16 alpha-ethyl)-14, 15 eburnamine) on calcifications in liver, kidney, and CNS tissues from cholesterol-induced atherosclerosis in 16 experimental rabbits was studied. Three of 4 groups (4 rabbits each group) feeding on a cholesterol-rich diet developed atherosclerosis after 3 months. Two of the 4 groups were also fed vinpocetine supplements and analysis by neutron activation method showed a decrease in calcium content in CNS tissues and in liver and kidney. Results suggest that vinpocetine acts to decalcify cholesterol-induced atherosclerotic lesions in these tissues.
Animals↗
[Efficacy of ganciclovir against cytomegalovirus nephropathy after kidney transplantation].
A 32-year-old man who had received a kidney transplant from a living related donor, contracted cytomegalovirus (CMV) pneumonitis in the 8th month. He was treated with human interferon-beta and cured of the pneumonitis. After that, his serum creatinine value increased gradually. Renal biopsy revealed the cells with intranuclear inclusion bodies in the renal tubulus and the cells were positive for CMV antigens by direct immunofluorescence test using FITC-labeled mouse monoclonal antibody against an early antigen. He was hospitalized with persistent CMV viruria and treated with ganciclovir. Ganciclovir was administered daily in doses of 3 mg per kg per day for 32 days by intravenous drip infusion and thereafter the same dose was given 3 times weekly for 8 weeks. His urine was positive for CMV before the ganciclovir treatment and became negative on the 31st day after the treatment. The anti-CMV effect of ganciclovir was evidenced by gradual decrease in titer (PFU) of infectious CMV in the urine samples. His serum creatinine value decreased from 3.2 mg/dl to 2.8 mg/dl, and no adverse effect was noticed. Thus, ganciclovir is considered to be efficacious against CMV infections in kidney transplant recipients.
Adult↗
Attenuation of the osmotic release of vasopressin by enkephalins in dogs.
To assess the possible role of circulating enkephalins in the osmotic release of vasopressin, Met5 (M-Enk)- or Leu5-enkephalin (L-Enk) dissolved in 0.9 or 10% NaCl was infused to either anesthetized or conscious dogs at a dose of 3.5 nM.kg-1.min-1 for 15 min. Intravenous infusion of M-Enk or L-Enk produced 150- to 200-fold increases in their plasma levels, and the elevated levels were maintained during the infusion. Although blood pressure (BP) in anesthetized dogs decreased significantly during L-Enk infusion, BP in conscious dogs was unaffected by both enkephalins. Neither M-Enk nor L-Enk infusion affected plasma vasopressin concentration (PAVP) in these anesthetized and conscious dogs that were not osmotically stimulated. PAVP in conscious time control dogs increased significantly after start of 10% NaCl infusion in spite of an increase in BP. M-Enk or L-Enk significantly blunted the increase in PAVP induced by 10% NaCl infusion. This attenuation was not accompanied by any significant changes in plasma sodium concentration and BP compared with those of time control dogs. Thus increase in plasma enkephalins attenuates the osmotic release of vasopressin.
Animals↗
Responses of vasopressin, atrial natriuretic peptide, and blood pressure to central osmotic stimulation.
To assess whether intracerebroventricular osmoreceptors are involved in vasopressin (AVP) and atrial natriuretic peptide (ANP) release and in the pressor response to centrally administered hypertonic NaCl, artificial cerebrospinal fluid (ACSF) or ACSF made hypertonic by adding 0.2 M NaCl, 0.4 M mannitol, and 0.4 M glucose in isotonic ACSF or 0.4 M urea was infused into the 3rd ventricle of conscious rats. In addition, intravenous infusion of [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-(O-methyl)tyrosine]AVP (TMeAVP), a V1-AVP antagonist, was given in rats receiving intracerebroventricular infusion of 0.2 M NaCl in isotonic ACSF. Intracerebroventricular 0.2 M NaCl, 0.4 M mannitol, and 0.4 M glucose in isotonic ACSF increased plasma AVP and mean arterial pressure (MAP) without changing heart rate (HR) or plasma ANP. Urea at 0.4 M decreased plasma AVP and ANP with a slight rise in MAP but no change in HR. ACSF alone did not affect plasma AVP, ANP, MAP, or HR. Intravenous TMeAVP attenuated the pressor response to infusion of 0.2 M NaCl in isotonic ACSF, decreased plasma ANP, but did not affect HR. These results indicate that central osmoreceptors are involved in the release of AVP and in the pressor response to centrally administered hypertonic NaCl.
Animals↗
Acute hydrothorax in continuous ambulatory peritoneal dialysis--a collaborative study of 161 centers.
Follow-up studies on 3,195 patients from 161 centers in Japan undergoing continuous ambulatory peritoneal dialysis (CAPD) were performed for 1-104 months to clarify the incidence as well as the clinical features of acute hydrothorax. In these studies, 50 patients (1.6%) developed this complication. Twenty-seven (54%) were men, and 23 (46%) were women, ranging in age from 6 to 79 (average 49) years. The interval between onset of CAPD and hydrothorax ranged from 1 day to 8 years. Four had left-sided, and 2 had bilateral hydrothorax, but the majority (88%) were right-sided. Dyspnea was experienced by 37 of these 50 patients, but the remaining 13 (26%) patients were asymptomatic. Hydrothorax was fully resolved in 27 of them following a brief interruption of CAPD or the combined use of small exchange volumes in a semi-sitting position and pleurodesis with tetracycline or other agents. The remaining 23 patients (46%) were switched to hemodialysis permanently. Despite recurrence, 1 patient continued successfully on CAPD. It was concluded that acute hydrothorax is one important possible complication, although the risk may be low. Constant surveillance is necessary to detect pleural effusions in patients during CAPD.
Acute Disease↗
A case of acute tubulointerstitial nephritis and uveitis syndrome with a dramatic response to corticosteroid therapy.
A 23-year-old female with acute renal failure associated with acute tubulointerstitial nephritis and uveitis is reported. Renal tubular acidosis and inflammatory reactions consisting of markedly increased erythrocyte sedimentation rate and high serum immunoglobulin levels were seen on admission. Light microscopy revealed infiltration of mononuclear cells in the interstitium. Immunofluorescence of renal tissues was negative in staining for immunoglobulins, fibrinogen, and complement components. Bone marrow specimens did not show any granulomatous lesions. The etiology of this tubulointerstitial nephritis and uveitis syndrome was not clear. Immunological evaluation showed a slight decrease of the OKT4/OKT8 ratio in the peripheral blood. OKT8- and OKM1-positive cells had infiltrated diffusely into the renal interstitium. Acute tubulointerstitial nephritis and uveitis responded dramatically to steroid therapy. It was suggested that immunological factors might correlate with the onset and/or development of this syndrome. It is indicated that high-dose steroid therapy might be useful for patients with acute interstitial nephritis and uveitis.
Adult↗
Modification of serum beta-2-microglobulin in chronic hemodialysis patients.
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Humans↗
Protein components of amyloid-like kidney stones of chronic hemodialysis patients.
We have examined amyloid-like kidney stones, commonly found in patients on maintenance hemodialysis. Extraction of protein from the stones and Western blot analysis were performed. beta 2-Microglobulin (beta 2MG), serum amyloid P component (SAP), lysozyme and PAS-positive substance were identified in the stones. It is suggested that calcium-mediated association of beta 2MG, lysozyme, SAP and PAS-positive substance may have an important role in the process of the formation of kidney stones in chronic hemodialysis patients.
Adult↗
Towards an ideal polyurethane graft for hemodialysis.
Numerous studies have been reported in the field of vascular graft in recent years. The main interest in these studies has focused on producing either a small diameter arterial graft or prosthesis for veins. Polyurethane polymers are emerging because of their superior mechanical, chemically stable and biocompatible nature. Above all, the prominent blood compatibility and elasticity has attracted many investigators to investigate the material for vascular grafts with small diameter. Although several difficulties still remain to be solved, important factors such as anti-thrombogenicity of materials, compliance in long term, porosity, surface microstructure, and permeability are discussed on the basis of many experimental results. In addition, our basic as well as clinical examination of polyurethane graft as a blood access for hemodialysis are presented along with future prospects and difficulties to overcome.
Arteries↗
Comparison of the efficacy of endoscopic ultrasonography and submucosography in diagnosing the depth of gastric cancer invasion.
Diagnosis of the depth of the cancer invasion is necessary to select the indication of endoscopic treatment. We used endoscopic ultrasonography (EUS) and Submucosography (SMG) to diagnose the depth of cancer invasion and compared their efficacy against 63 lesions in 60 cases of gastric and esophageal cancers. SMG could diagnose the invasion correctly in 97% of m (mucosa) cancers, 88% of sm (submucosa) cancers and 100% of advanced cancers. On the other hand, linear-type EUS could diagnose the cancer invasion correctly in 60% of the m cancers, 83% of the sm cancers and 100% of advanced cancers. The results of the comparison of radial-type EUS and SMG showed similar results. Both EUS and SMG are appropriate for the judgement of endoscopic treatments. However, for the selection of the indication of endoscopic treatment which is applied to relatively small sized lesions in general, SMG appears to be superior to EUS in both resolution power and accuracy in shooting.
Aged↗