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Biomedical subjects

A Maezawa

Publications and source records attributed to A Maezawa.

34 records · Page 2Linked to original sources

Evaluation of blood coagulation-fibrinolysis system in patients receiving chronic hemodialysis.

We determined plasma levels of thrombomodulin, thrombin-antithrombin III complex (TAT), protein C, protein S, and plasmin-alpha 2 plasmin inhibitor complex (PIC) before and after hemodialysis in 54 patients receiving chronic hemodialysis, to evaluate the blood-coagulation system and to evaluate the antithrombogenicity of various dialyzer membranes. Predialysis levels of thrombomodulin and TAT were both significantly increased compared with normal control values, but levels of protein C, protein S, and PIC were not changed. In patients dialyzed with ethylene vinyl alcohol (EVAL) and polysulfone membranes, postdialysis levels of thrombomodulin, TAT, protein C, protein S, and PIC were not significantly different from the predialysis levels. However, in patients dialyzed with regenerated cellulose and polymethyl-methacrylate (PMMA) membranes, postdialysis levels of thrombomodulin, TAT, and PIC were significantly higher than predialysis levels. We conclude that patients on maintenance hemodialysis were considered to be in a state of hypercoagulability before hemodialysis, and a single hemodialysis session using regenerated cellulose and PMMA membrane may have caused injury to vascular endothelial cells, hypercoagulability, and enhancement of fibrinolytic activity.

Adult↗

Serotonin metabolism in patients undergoing hemodialysis.

To determine the pathogenic role of serotonin (5-HT), we investigated 5-HT metabolism in undergoing hemodialysis (HD). Mean value of platelet 5-HT in patients undergoing HD was significantly lower than that of normal controls (0.22 + or - 0.16 pmol/10(5) platelets versus 0.35 + or - 0.13 pmol/10(5) platelets, p <0.02). While platelet uptake of 5-HT in normal controls reached a plateau in each experiment after incubation with authentic 5-HT for 60 min, platelet uptake of 5-HT in patients undergoing HD reached various levels. We found significantly lower platelet 5-HT levels in patients with diabetes mellitus (DM) after HD compared with those in patients with chronic glomerulonephritis (p <0.05). The pathogenic role of serotonergic amplifying mechanism especially in patients with DM should be investigated. Second, we investigated plasma 11-dehydro-thromboxane B2 (11-DTXB2) levels in patients undergoing HD. Mean level of plasma 11-DTXB2 concentration in patients after HD was significantly higher than in patients before HD (32.8 + or - 17.0 pg/ml versus 23.7 + or - 7.2 pg/ml, p <0.02). Increased plasma levels of 11-DTXB2 after HD were regarded as an indication of hypercoagulation. Our results provide evidence that several factors such as hypercoagulation, heparin, 5-HT uptake of platelet, or causal diseases of renal failure could be responsible for the lower platelet 5-HT levels in patients undergoing HD.

Adult↗

The kinetics of the pathogenic pronase-digested renal proximal tubular antigen and antibody in rat active Heymann nephritis.

We investigated the pathogenesis of active Heymann nephritis in the rat by conducting immunofluorescent and immunoblotting studies of the pathogenic antigen and the autoantibody, and by detecting this antigen-bound IgGs. Rat IgG was detected along the glomerular basement membrane (GBM) and significant proteinuria was observed 6 weeks after the injection of rat pronase-digested tubular brush border antigen. Circulating antibody which bound only to the brush border of proximal tubules of normal rat, appeared 2 weeks after antigen injection. Eluted antibody from nephritic kidney 6 weeks after immunization bound exclusively to the brush border of the proximal tubules of normal rat kidney. Monoclonal antibody against the nephritogenic 0.3 M antigen, which bound exclusively to the brush border in the normal rat, bound to the GBM in a fine granular fashion, as well as to the brush border from nephritic rats, indicating the deposition of nephritogenic 0.3 M antigen in the GBM of nephritic rats. On immunoblotting, both the circulating antibody and eluted antibody obtained from the nephritic kidney 6 weeks after immunization recognized the 0.3 M antigen. This antigen-bound IgG appeared in circulation at 2 weeks, becoming smaller in size at 4 weeks and disappearing 12 weeks after immunization. Thus, it is suggested that active Heymann nephritis in rats was induced by deposition of the circulating 0.3 M antigen-bound IgG complexes in the subepithelial space of GBM.

Animals↗

[Clinical analysis of 14 patients with anti-myeloperoxidase antibody positive rapid progressive glomerulonephritic syndrome].

We investigated the clinical features and outcome of 14 patients with anti-myeloperoxidase antibody (MPO-ANCA) positive rapidly progressive glomerulonephritic syndrome. Underlying diseases included microscopic polyarteritis in 6 patients, idiopathic crescentic glomerulonephritis with lung hemorrhage in 2 patients, idiopathic glomerulonephritis in 3 patients, rapidly progressive glomerulonephritic syndrome without renal biopsy in 1 patient, crescentic glomerulonephritis associated with Sjögren syndrome and progressive systemic sclerosis in 1 patient and crescentic glomerulonephritis associated with sarcoidosis in 1 patient. Five patients were male (mean age, 59.2 years) and 9 were female (mean age, 54.0 years). On admission, most patients had anemia, leukocytophilia, and marked elevation of C-reactive protein (CRP). Average hemoglobin, white blood cell count and CRP levels on admission were 8.1 mg/dl, 11,500/mm3 and 14.7 mg/dl, respectively. Average serum creatinine was 4.0 mg/dl. All patients were treated with steroids either with or without cyclophosphamide. As the patients recovered clinically, the MPO-ANCA titers declined. Although most patients responded well to immunosuppressive therapy, some died of serious complications (such as acute respiratory distress syndrome, fungal infection, and pneumocystis pneumonia). The prognosis of patients with severe renal failure was especially poor. We conclude that early diagnosis, treatment and intensive care during immunosuppressive therapy are very important in the management of MPO-ANCA-positive rapidly progressive glomerulonephritis.

Adolescent↗

A major pathogenic antigen of Heymann nephritis is present exclusively in the renal proximal tubule brush border--studies with a monoclonal antibody against pronase-digested tubular antigen.

We have isolated a nephritogenic 120-kD antigen from rat renal tubule brush border that induces rat Heymann nephritis. A MoAb that recognized this antigen reacted exclusively with the brush border on indirect immunofluorescence and immunoelectron microscopy. Rabbit antiserum against this antigen also reacted exclusively with the brush border. With the injection of this antiserum, rabbit IgG became detectable along the glomerular basement membrane (GBM) after 3 days. Our 120-kD antigen was shown to have a close relationship with gp330 based on the following: (i) this antigen can induce active Heymann nephritis as gp330; (ii) our MoAb reacted with the immune deposits of nephritic kidneys induced not only by the 120-kD antigen but also by gp330, and conversely, rabbit antiserum against gp330 reacted with those induced by the 120-kD antigen as well as gp330; and (iii) by immunoblotting, polyclonal antibodies against the 120-kD antigen reacted with gp330 and polyclonal antibodies against gp330 reacted with the 120-kD antigen. These observations indicate that antigen present exclusively in the brush border can induce active Heymann nephritis, and the common antigenic determinants shared by brush border and the coated pits of glomerular epithelium may not be a prerequisite to induce nephritis. A more precise relationship between the 120-kD antigen and reported C14 fusion protein or 40-kD alpha 2MRAP remains to be established.

Animals↗

Combined treatment with cyclophosphamide and prednisolone can induce remission of nephrotic syndrome in a patient with renal amyloidosis, associated with rheumatoid arthritis.

A 67-year-old woman, who had been diagnosed with classical rheumatoid arthritis (RA), was admitted to our hospital because of massive proteinuria. Biopsy of the kidney revealed deposition of amyloid fibrils in the subepithelial and subendothelial spaces of the glomerular capillary walls. Though the treatment with prednisolone and dipyridamole against nephrotic syndrome and amyloidosis due to RA was not effective, cyclophosphamide, which was added after tapering of prednisolone, was able to induce remission of nephrotic syndrome after two years. The levels of CRP and serum amyloid A protein (SAA) returned to within the normal limits. As the impairment of renal function is thought to be due to deposition of amyloid supplied from the precursors of amyloid fibrils filtered from the general circulation in RA patients, remission of nephrotic syndrome might result from the suppression of production of SAA or removal of amyloid fibrils. Cyclophosphamide, which has the potential both to suppress disease activity in RA and to produce degradation of amyloid fibrils in glomeruli, may be useful against renal or systemic amyloidosis complicated by RA.

Aged↗

Evaluation of intraplatelet and urinary 5-hydroxytryptamine (5-HT), and urinary 5-hydroxyindoleacetic acid (5-HIAA) levels in patients with toxemia of pregnancy.

Toxemia of pregnancy is considered to represent a disorder of activated blood coagulation. To identify possible indicators for evaluating the clinical course of toxemia, we measured the intraplatelet and urinary levels of 5-HT and its urinary metabolite, 5-HIAA in 25 patients with toxemia vs. 29 non-toxemic pregnant women. 5-HT and 5-HIAA were assayed by high performance liquid chromatography (HPLC). During the 24-34 weeks of gestation, the toxemic patients and the non-toxemic women each had low intraplatelet levels of 5-HT which didn't differ significantly. A significant (p < 0.05) decrease in intraplatelet 5-HT was observed in the toxemic patients vs. the non-toxemic women after the 35th week of gestation until delivery. The untake of exogenous 5-HT by platelets was increased in the toxemic patients, and their urinary (5-HT+5-HIAA) value increased significantly (p < 0.05) as compared with the non-toxemic women after the 35th week of gestation until delivery. A decrease in the intraplatelet level of 5-HT and an increase in the urinary level of (5-HT+5-HIAA) were observed in the toxemic patients, findings that paralleled the progression of this disorder. Serial measurements of intraplatelet and urinary levels of 5-HT and urinary levels of 5-HIAA in the toxemic patients revealed a significant correlation between disease activity and those levels. These observations support the concept that the measurement of intraplatelet and urinary levels of 5-HT and of urinary levels of 5-HIAA may be useful in following the clinical course of the toxemic patients.

Adult↗

FK506, a novel immunosuppressive agent, induces antigen-specific immunotolerance in active Heymann's nephritis and in the autologous phase of Masugi nephritis.

FK506 is a new drug which has potent immunosuppressive activity. We studied its immunosuppressive effects on active Heymann's nephritis and the autologous phase of Masugi nephritis. The induction of active Heymann's nephritis was completely suppressed by FK506 injected simultaneously with the antigen (day 1) and then daily for 14 days at a dose of 0.64 mg/kg per day or more. With a lower dosage of this agent, antibody production and immune deposits in the glomerular basement membrane occurred despite the suppression of proteinuria. Similar results were obtained in rats on other treatment schedules (1-7 days or day 8-14 days duration). Rats that were prevented from developing Heymann's nephritis or the autologous phase of nephrotoxic antiserum nephritis by FK506 treatment exhibited a suppressed immune response to a second immunization of the same antigen even 4 weeks after cessation of drug administration: however, they developed antibodies when inoculated with other antigens. Rat peripheral leucocyte counts and serum creatinin were not remarkably influenced by the administration of FK506. These results indicate that FK506 has potent immunosuppressive activity, and it is suggested that it is able to induce an antigen-specific immunotolerance.

Animals↗

Long-term observation of passive Heymann nephritis.

Chronic renal lesion with membranous changes and massive proteinuria similar to human membranous nephropathy was induced in rats through repeated intravenous injections of gamma-globulin fraction of rabbit anti-rat F X 1A antisera (GRAFA) 0.37-1.5 mg/100 g body weight. The injections were administered every 2 or 3 days over a 68-day period for a total of 26 times. It is suggested that a sufficient amount of GRAFA was given to the rats to induce renal lesion, judging from the result that no remarkable differences were observed between the severity of the histopathological and clinical changes in each rat given the various doses of GRAFA. Furthermore, this renal lesion is considered to correspond to human membranous nephropathy morphologically and clinically, judging from the fact that the protein excretion was kept at a plateau, and the capillary lumen was kept almost intact with advanced membranous changes.

Animals↗

Rhabdomyosarcoma in a patient with mosaic Klinefelter syndrome and transformation of immature teratoma.

A 27-year-old man was found to have a mediastinal tumour and the histological diagnosis was immature teratoma. Remission was achieved by chemotherapy and total resection. However, he developed anaemia and leukoerythroblastosis after 2 years of remission, and was referred to our hospital. Rhabdomyosarcoma cells were detected in the bone marrow and pleural effusion. Moreover, karyotype analysis of peripheral blood and bone marrow cells revealed mosaic-type Klinefelter syndrome. We diagnosed the case as transformation of teratoma into rhabdomyosarcoma in Klinefelter syndrome. Although intensive chemotherapy was performed, the patient died with meningeal infiltration.

Adult↗

Successful treatment of patients with rheumatic disorders and acquired factor VIII inhibitors with cyclophosphamide and prednisolone combination therapy: two case reports.

Acquired haemophilia associated with autoimmune disorders can be fatal and has been reported to be refractory to steroid therapy alone. We report two cases of female patients, aged 24 years and 54 years, with acquired haemophilia caused by factor VIII inhibitors. Underlying diseases were systemic lupus erythematosus in the 24-year-old patient and rheumatoid arthritis in the 54-year-old patient. Both conditions were nearly quiescent when the patients manifested haemorrhagic diathesis. In response to combination therapy with prednisolone and cyclophosphamide, coagulation abnormalities were resolved together with complete elimination of factor VIII inhibitors in both patients. Thus, combination therapy with alkylating agents may be recommended as initial therapy for the management of autoimmune patients with factor VIII inhibitors.

Adult↗