The role of podocytes in the development of glomerular sclerosis.
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Animals↗
Biomedical subjects
M Nagata
Publications and source records attributed to M Nagata.
Relaxation oscillations and toroidal-current regeneration in a helicity-driven spheromak.
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Journal Article↗
Combination of immunosuppressive drugs for organ transplantation.
Several novel immunosuppressive agents have been developed in recent years. They exhibited not only remarkable immunosuppressive potency but also side effects. They are still short of the final goal in terms of immunosuppression for organ transplantation. Combination treatment is more effective and safer to use, and it will prevail in the future.
Amylases↗
High-dose chemotherapy with autologous bone marrow transplantation in the treatment of advanced gastric cancer.
BACKGROUND: Clinical usefulness of high-dose chemotherapy with autologous bone marrow transplantation (ABMT) in the treatment of gastric cancer was investigated. METHODS: Ten patients with late-stage gastric cancer (four recurrent and six primary cases) with measurable lesions were treated with high-dose combination therapy consisting of etoposide (VP-16) (1200 mg/m2), adriamycin (80 mg/m2), and cisplatin (120 mg/m2) or carboplatin (900 mg/m2) (high-dose etoposide, adriamycin, and cisplatin [EAP] therapy). Afterward, 1 x 10(7)/kg of mononuclear cells, which were prepared from autologous bone marrow before treatment and cryopreserved, were transfused intravenously. RESULTS: All patients recovered from the aplastic period without severe complications. Of nine assessable cases, partial response was observed in eight (89% response rate). CONCLUSION: High-dose EAP therapy with ABMT is recommended as adjuvant therapy accompanied with radical operation for late-stage gastric cancer.
Adult↗
Prevention of autoimmune type I diabetes by CD4+ suppressor T cells in superantigen-treated non-obese diabetic mice.
The development of autoimmune type I diabetes in the NOD mouse appears to be controlled by both genetic and environmental factors. This investigation was initiated to determine whether exogenous superantigens, as environmental factors, can influence the development of diabetes. Several staphylococcal enterotoxins (SE) (SEA, SEC1, SEC2, or SEC3), which are known superantigens, were injected i.v. into female NOD mice at 4 and 10 wk of age. At 32 wk of age, the incidence of diabetes in the SE-treated mice ranged from 6 to 12.5%; this was significantly lower than that of mice treated with PBS--64%. There was no significant difference in effectiveness among the various SE used. SE induced a modest decrease in T lymphocytes bearing specific V beta TCR 2 wk after injection, but this effect did not persist past 4 wk. To elucidate the mechanism of the SE effect, suppressor activity in SE-treated mice was evaluated. Splenocytes from SE-treated mice inhibited the transfer of diabetes by splenocytes from acutely diabetic NOD mice when injected into irradiated young NOD mice; only 10% became diabetic. In contrast, 83% of the mice receiving splenocytes from PBS-treated control mice became diabetic. Suppressor activity of splenocytes from SE-treated mice was diminished by the depletion of CD4+ T cells, but not by the depletion of CD8+ T cells, indicating that the suppressor cells belonged to the CD4+ T class of lymphocytes. On the basis of these observations, we conclude that exogenous superantigens activate CD4+ suppressor T cells, leading to the prevention of autoimmune type I diabetes in NOD mice.
Animals↗
[A case of Epstein-Barr virus infection with splenic hemorrhage and pleural effusion].
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Adult↗
Surgical effects of trabeculotomy ab externo on adult eyes with primary open angle glaucoma and pseudoexfoliation syndrome.
OBJECTIVES: Retrospective and prospective studies examined the surgical effects in lowering intraocular pressure levels of trabeculotomy ab externo in adult eyes with either primary open angle glaucoma or pseudoexfoliation syndrome. We report the results of primary trabeculotomy as an intervention for glaucoma. PATIENTS: Included in the retrospective study were 357 eyes of 227 patients with primary open angle glaucoma and 82 eyes of 65 patients with pseudoexfoliation syndrome, each of which underwent trabeculotomy ab externo alone and none of which had a history of laser or surgical treatment for ocular disease. Included in the prospective study were 33 eyes of 22 patients with primary open angle glaucoma and 17 eyes of 15 patients (older than 40 years) with pseudoexfoliation syndrome. RESULTS: A life-table analysis for the retrospective study showed that the final success probability (mean +/- SE) at 5 years after surgery was 73.5% +/- 6.3% in eyes with pseudoexfoliation syndrome, which is significantly better than 58.0% +/- 3.1% in eyes with primary open angle glaucoma (P < .05). Also, the higher the preoperative intraocular pressure levels are, the less likely that the postoperative intraocular pressure levels will be brought under control (P < .01). Surgical outcome in the prospective study demonstrated success in 27 (79%) of 34 eyes after 3 years and in 16 (64%) of 25 eyes after 5 years, with medication. Complications included Descemet's membrane detachment (one eye), cyclodialysis (one eye), and decreased visual acuity due to progression of cataract (four eyes). CONCLUSION: The surgical results of trabeculotomy ab externo remain effective in controlling intraocular pressure levels for a long time in selected patients. It thus appears that trabeculotomy ab externo can be considered as an alternative choice of surgical treatment in some cases of glaucoma.
Adult↗
Colorimetric chemosensitivity testing using sulforhodamine B.
A colorimetric chemosensitivity test was investigated using sulforhodamine B (SRB), which stains protein synthesized by cells, as an end-point marker. Four cultured cell lines, 9 human tumor xenografts serially transplanted into nude mice, and 14 fresh surgical specimens were subjected to this assay. The optimal conditions for the assay were 3-5 x 10(4) cells per well in a 96-microplate, an SRB concentration of 4%, and an incubation time of more than 10 minutes. When mitomycin C, doxorubicin, cisplatin, and 5-fluorouracil were assessed by the SRB assay, the concentration-effect curves revealed a sharp slope between plateaux at low and high concentrations, suggesting that this assay has an excellent sensitivity which can assess the effect of drugs as "all or none." Although this high sensitivity resulted in good reproducibility of the assay for cultured cell lines, the predictive rate of the SRB assay for the chemosensitivity of human tumor xenografts in vivo was limited to 63.9%. As a result, this SRB assay is thought to be useful for evaluating the chemosensitivity of cultured cells as all or none, since it can assess directly cellular protein synthesis, which is one of the most important parameters of cell renewal, with excellent sensitivity.
Animals↗
Loss of mitotic activity and the expression of vimentin in glomerular epithelial cells of developing human kidneys.
Glomerular epithelial cells (GECs) have been considered as post-mitotic cells. In order to establish the stage when GECs stop dividing, the expression of proliferating cell nuclear antigen (PCNA/cyclin) in GECs during glomerulogenesis in human kidneys was studied by the streptavidin-biotin staining technique with monoclonal antibodies. Antibody specific for PCNA/cyclin reacted with almost all the cell nuclei of nephrogenic vesicles, as well as those of S-shaped bodies, the cells of which in the lower limb are progenitors of GECs. However, this reaction was markedly reduced in GECs at the capillary loop stage and entirely disappeared at the maturational stage. In contrast to the expression of PCNA/cyclin, vimentin-specific antibody did not react with nephrogenic vesicles and the lower limb of S-shaped bodies, whereas vimentin was ubiquitously expressed in the GECs at the capillary loop stage, as well as at the maturational stage. Furthermore, these two antigens were not co-expressed in the same glomerulus during glomerulogenesis, as revealed by analysis of serial sections. These results lead to the conclusion that expression of PCNA/cyclin and vimentin during glomerulogenesis is fairly stage-dependent, and GECs rapidly lose their mitotic activity at the capillary loop stage.
Cyclins↗
Lymphocyte subsets in hemodialysis patients treated with recombinant human erythropoietin.
We investigated whether recombinant human erythropoietin (rhEPO) therapy affected the lymphocyte subsets in patients on long-term maintenance hemodialysis (HD) with severe anemia. Before treatment, the numbers of peripheral blood lymphocyte, CD3+, CD4+, CD8+, and CD20+ cells were decreased in HD patients compared to those in healthy subjects, while the number of CD3+HLA-DR+ cells was increased in HD patients compared to that in healthy subjects. Furthermore, the number of CD4+CD45RA+ (naive T) cells was markedly decreased in HD patients (112 +/- 77 vs 241 +/- 146/microliters; P < 0.01). The number of CD8+S6F1+ (cytotoxic T) cells in HD patients was also less than that in healthy subjects (247 +/- 104 vs 122 +/- 83/microliters; NS). During a 6-month period of rhEPO therapy, we found that the low level of CD4+CD45RA+ cells gradually increased (from 112 +/- 18 to 163 +/- 24/microliters; P < 0.01) with the elevation of hematocrit values (from 21.5 +/- 1.7 to 28.2 +/- 3.5%; P < 0.05). The number of CD3+HLA-DR+ cells decreased after 1 month of rhEPO therapy (from 93 +/- 14 to 46 +/- 13/microliters) and gradually declined throughout the 6-month study period. In our in vitro study, we demonstrated that no effects were observed on [3H]thymidine uptake in the T cell subsets at various concentrations of rhEPO. These results suggest that rhEPO-induced immunoregulation is mediated by an indirect stimulatory effect on the immune system, this stimulation being accompanied by an improvement in physical condition.
Adult↗
The evidence of platelet activation in bronchial asthma.
The possible involvement of platelets in bronchial asthma was investigated under three different conditions: (1) chronic asthma, (2) bronchial provocation inhaling house dust mite (HDM), and (3) status asthmaticus. Plasma levels of beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), and in part, platelet-activating factor (PAF) were measured. Approximately one third of the subjects with symptomatic or asymptomatic chronic asthma showed an increased level of beta-TG or PF4. Statistically significant differences occurred in beta-TG and PF4 levels only between healthy controls and symptomatic subjects. Five out of six subjects showed no elevation of beta-TG and PF4 during immediate asthmatic response. In two out of nine subjects with status asthmaticus, beta-TG or PF4 was elevated, and statistically significant correlations occurred between the initial level of PAF and that of beta-TG or PF4. Those results suggest that the platelet activation in the circulation is sometimes provoked in asthma, but plasma level of alpha-granule-derived proteins does not reflect the intensity or severity of asthma, and that PAF is likely to be a mediator responsible for the platelet activation.
Adolescent↗
Effect of ascorbic acid 2-0-alpha-glucoside on hydrocortisone-induced cataract formation in developing chick embryos: I. Comparison of the preventive effect of ascorbic acid derivatives.
The effect of ascorbic acid 2-O-alpha-glucoside (AA-2G) on hydrocortisone (HC)-induced lens opacity in developing chick embryo was examined and compared with those of ascorbic acid (AsA) and ascorbic acid 2-phosphate (AA-2P). The opacity was dose-dependently inhibited by a single administration of 10 or 20 mumol/egg of AA-2G and by three repeated administrations of 1, 3 or 10 mumol/egg of AA-2G. AA-2G was the most effective among the three compounds. Glucose did not enhance the preventive effect of AsA against HC-induced opacity, and neither dehydro ascorbic acid nor glucose also prevented HC-induced cataract. In the histological study, we observed many small vacuoles in the nuclear region of the opaque lens treated with HC. AA-2G inhibited the formation of such vacuoles, an effect closely correlated with the prevention of cataract formation.
Animals↗
Effects of rapamycin in experimental organ allografting.
The immunosuppressive effect of rapamycin (RAPA), a macrolide antibiotic produced by Streptomyces hygroscopicus, was tested using allografts in the rat and dog. It was immunosuppressive at a dose of 3.0 mg/kg/day for 8 days in skin allografts and 0.1 mg/kg/day for 11 days using cardiac allografts in the rat. It prevented rejection of renal allografts in beagle dogs at a dose of 0.3 mg/kg; however, emaciation and gastrointestinal toxicity resulted in some deaths in dogs. Mucosal necrosis and vasculitis in the submucosal layer were the predominant findings at autopsy in dogs receiving RAPA. Serum amylase values rose soon after commencement of RAPA treatment. Combined drug treatment with CsA at a nonimmunosuppressive dose of 3.2 mg/kg in the rat or 2.5 mg/kg in the dog was synergistic, with a low dose of 0.1 mg/kg/week RAPA. Combined therapy of CsA and RAPA also inhibited the frequency of vasculitis and emaciation in dogs. The present data suggest that RAPA is immunosuppressive in organ allografting and that the combination of CsA and RAPA would be effective clinically.
Animals↗
Pre-column derivatization and its optimum conditions for quantitative determination of urinary hydroxylysine glycosides by high-performance liquid chromatography.
A method has been developed for rapid analysis of the urinary hydroxylysine glycosides [glucosyl-galactosyl-hydroxylysine (GGH) and galactosyl-hydroxylysine (GH)] as collagen metabolites. The glycosides were fluorometrically derivatized with 5-dimethylaminonaphthalene-1-sulfonyl chloride, and then subjected to reversed-phase high-performance liquid chromatography using a gradient system. Suitable standard hydroxylysine glycosides which were not diastereoisomers were prepared from human urine. Urinary GGH and GH were analyzed within 1 h, including column washing. This method was applied to the urine samples of 68 healthy persons of different ages.
Adult↗
Central alpha 2-adrenoceptor-mediated inhibition of gastric motility in rats.
We investigated the subtype of alpha-adrenoceptors participating in central noradrenergic inhibition of gastric motility in urethane-anesthetized rats. Noradrenaline at 10 nmole administered intracisternally (i.c.) significantly decreased gastric motility. Yohimbine at 10 nmole, i.c., but not the same dose of prazosin, abolished this noradrenaline-induced decrease in gastric motility. Clonidine at 10 nmole, i.c., but not phenylephrine at 20 nmole, significantly decreased gastric motility. These results suggest that alpha 2-adrenoceptor-mediated mechanisms in the brain stem are involved in noradrenergic inhibitory regulation of gastric motility.
Adrenergic alpha-Agonists↗
Diagnostic study of a synthetic human corticotropin-releasing hormone (hCRH) in healthy adult males: its plasma pharmacokinetics and the effects on the urinary excretion of steroid hormones.
The pharmacokinetics, responses of plasma ACTH and cortisol, urinary excretion of steroid hormones, and safety of MCI-028, a synthetic human corticotropin-releasing hormone (hCRH), were examined in eight healthy adult male volunteers after intravenous administration of 33, 100 and 200 micrograms of the drug. The disappearance of MCI-028 from plasma could be fitted to a biexponential decay curve, the plasma half-lives (T1/2) were 0.12 to 0.15 h for alpha phase, and 0.57 to 0.67 h for beta phase. Plasma ACTH and cortisol concentrations and the urinary excretion of steroid hormones (particularly free cortisol) increased significantly in relation to the MCI-028 dose administrated. Although hot flushing and an increase in the heart rate were observed at higher doses, they were mild and transient. It is also considered that the urinary excretion of free cortisol after the administration of MCI-028 can be an index reflecting the functioning of this system.
17-Hydroxycorticosteroids↗
Effect of rush immunotherapy in house-dust-mite (HDM)-sensitive adult bronchial asthma: changes in in vivo and in vitro responses to HDM.
An open study was conducted to evaluate the changes in in vivo and in vitro responses to house-dust-mite (HDM) after rush immunotherapy (RI). A 7-day RI protocol using an extract containing HDM allergen was administered to 12 subjects with HDM-sensitive asthma, and the effects on bronchial responsiveness and serum antibody levels were evaluated up to 16 or 20 weeks after RI. The levels of HDM-specific IgG, IgG1 and IgG4 antibodies were significantly elevated from 4 or 8 weeks after RI. Provocative doses causing a 20% fall in FEV1 (PD20) by allergen inhalation were elevated in all subjects at 16 to 20 weeks after RI. There was a high correlation between the increase in log-PD20 and the increase in the ratio of HDM-specific IgG4 to IgG1 (r = 0.68, p < 0.05). The results suggest that RI elicits the improvement of allergen-specific bronchial responsiveness and the increase in serum antibody levels within a relatively short period.
Adolescent↗
[Expression on major histocompatibility complex antigen and effect of IFN-alpha on renal cell carcinoma].
Eighteen patients with renal cell carcinoma subjected to nephrectomy were examined for expression of major histocompatibility complex (MHC) class-I and -II antigens by staining with monoclonal antibodies. The neoplastic tissue and normal tissue were examined by the indirect immuno-peroxidase method. Only four of the eighteen patients expressed class-I antigen and no patient expressed class-II antigen in the neoplastic tissue. The normal tissue of all patients expressed class-I antigen. Subsequently, carcinoma tissue was incubated in the tissue culture medium RPMI1640 containing various concentrations of interferon (IFN)-alpha (0, 10, 30, 100 IU/ml) for 24 hours. The incubation of the renal cell carcinoma tissue with the medium without IFN-alpha did not affect the expression of class-I. Furthermore, the relationship between IFN-alpha concentration and the expression of MHC antigens was investigated. Groups incubated with 10, 30, and 100 IU/ml interferon showed enhanced expression of class-I compared with the control group (p < 0.05, p < 0.001, p < 0.05, respectively). The expression in the 100 IU/ml group tended to decrease. Staging and grading in patients did not correlate with class-I expression statistically. The expression of MHC class-II antigen remained unexpressed by IFN-alpha treatment. There results suggest some relationship between the expressed MHC class-I antigen and IFN-alpha therapy in renal cell carcinoma. Further, the interferon concentration giving the greatest degree of class-I expression was suggested to be the best therapeutic dose of IFN-alpha, and the expression level of MHC class-I antigen was considered to be of prognostic value.
Aged↗