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Biomedical subjects

M Kyo

Publications and source records attributed to M Kyo.

At least 73 records · Page 4Linked to original sources

The significant effect of HLA-DRB1 matching on long-term kidney graft outcome.

Serotyping and genotyping (polymerase chain reaction with sequence-specific oligonucleotide probes method) were conducted on 520 unrelated individuals to determine the linkage disequilibrium of HLA-B and HLA-DRB1. Analyses of 511 kidney transplants (300 related and 211 cadaver recipients) were carried out at 4 transplant centers using the linkage disequilibrium of HLA-B and HLA-DRB1 established previously. All transplant recipients received CsA immunosuppression and were transplanted from June 1983 to December 1991. There were 51 significant linkages formed between HLA-B and HLA-DRB1 alleles (P < 0.05). DRB1-compatible transplants experienced a comparable 5-year graft success rate of 94% as did the HLA-identical recipients with a 100% 5-year success rate. However DRB1-incompatible recipients displayed a significantly reduced 5-year graft survival rate of 73% (73% vs. 94% P < 0.01). The 5-year graft survival rate of HLA-DR-incompatible recipients of 71% was compatible to the 73% for HLA-DRB1-incompatible recipients. No variation of rejection rate for DRB1-compatible grafts was seen in any of the 4 transplant centers. The results also indicated that HLA-DRB1 compatibility was essential for optimal success rate, regardless of HLA class I mismatches. The overall conclusion was that matching for HLA-DR was important to achieve optimal kidney graft survival on the molecular level but not on the serotyping level.

Alleles↗

Cellular mechanisms: induction of heart allograft survival in rats by 15-deoxyspergualin.

Survival of ACI rat heart grafts in Lewis rat (LEW) recipients treated with a short course of 15-deoxyspergualin (DSG), in a dose of 5 mg/kg daily beginning from day 4 of grafting, was markedly prolonged, with a mean survival time of 29.8 +/- 3.0 days. On day 20 after grafting, the cellular mechanism of inducing allograft survival after DSG treatment was analyzed by testing the activation of spleen cells in several assay systems. The results indicate that spleen cells from DSG-treated rats with surviving heart allografts show almost no proliferative response against donor strain stimulator cells in the mixed lymphocyte reaction (MLR) as compared with controls. Their cytotoxic activity was lower than that of spleen cells from rats with heart allograft rejection towards donor strain target cells. Adding various concentrations of spleen cells from DSG-treated LEW rats with surviving ACI heart allografts to the MLR when the responder cells from normal LEW rats were exposed to irradiated ACI or Wistar (third party) stimulator cells revealed a strong suppression, in a cell-dose-dependent manner. Moreover, the transfer of 2.0 x 10(8) spleen cells from DSG-treated LEW rats with surviving ACI heart allografts to an irradiated grafted host did not prolong the survival either of the ACI heart grafts or of the third party Wistar heart grafts. These results suggest that the proliferative response and cytotoxic activity are lowered and suppressor cells are induced by treatment with DSG, in rats with surviving allografts.

Animals↗

Control of humoral and cellular immunity-mediated accelerated heart allograft rejection in sensitized rats by low dose FK 506 and splenectomy.

UNLABELLED: ACI heart grafts are rejected, at an accelerated pace, in Lewis (LEW) rats sensitized by donor-type blood admixed with immunoadjuvant (adjuvant complete Freund, ACF) 7 days earlier. In an in vitro study, the anti-ACI cytotoxic antibody titers in the serum increased from 1:4 in nonsensitized rats to 1:128 in sensitized rats; the spontaneous blastogenesis in spleen cells was higher in sensitized rats than in nonsensitized rats; spleen cells from sensitized rats showed a strong proliferative response against donor strain stimulator cells compared with the control; the cytotoxic T cell activity of spleen cells from sensitized rats was higher than that of spleen cells from nonsensitized rats. Treatment with low dose FK 506 in combination with splenectomy (Spx) synergistically prolonged the heart allograft survival in this sensitized rat model. IN CONCLUSION: (1) Both humoral and cellular responses against the donor antigen appear in the serum and in the spleen of rats sensitized by donor-type blood admixed with immunoadjuvant ACF. (2) A low dose of FK 506 together with Spx appears to control this sensitization through different mechanisms, resulting in a prolongation of heart allograft survival.

Animals↗

Early diagnosis of kidney transplant rejection and cyclosporin nephrotoxicity by urine cytology.

A total of 2000 urine samples from 53 kidney transplant recipients were studied to develop a routine method for the early diagnosis of rejection and cyclosporin (CSA) nephrotoxicity in urine. New-Sternheimer staining and an immunocytochemical technique were used together with classical Papanicolaou staining to differentiate cells in the urine. After cell count and differentiation of second morning urine samples with New-Sternheimer and Papanicolaou stains, immunocytochemistry was performed using antibodies against the following antigens: CD2, CD4, CD8, CD25, CD71 (transferrin receptor), HLA-DR and cytokeratin (Lu-5). Cell counts were obtained for the positively-reacting cells per millilitre of urine. By New-Sternheimer and Papanicolaou staining, CSA nephrotoxicity was characterized by the predominance of proximal tubular cells. During rejection episodes, increased numbers of mononuclear cells and renal epithelial cells were found. Immunocytochemical analysis showed a significant increase in CD2-, CD4-, CD8-, CD25-, CD71-, and HLA-DR-positive epithelial cells and in the ratio HLA-DR/cytokeratin-positive epithelial cells in rejection. CD25-positive cells had the highest sensitivity and specificity for the diagnosis of rejection. Our urine cytology technique proved to be a useful and non-invasive method for the early diagnosis of rejection and CSA nephrotoxicity.

Adolescent↗

In vivo and in vitro mechanisms of cardiac allograft acceptance in the rat after short treatment with 15-deoxyspergualin.

15-Deoxyspergualin (DSG) has been reported to be a useful immunosuppressive agent already used to inhibit acute rejection in clinical transplantation. In the present study, the survival of heart allograft in rats after a short course of DSG treatment and the mechanisms underlying DSG-induced heart allograft acceptance were studied. Male LEW rats were used as recipients. Male ACI and Wistar rats were used as donors and third-party donors, respectively. Survival of ACI heart grafts in LEW recipients treated with a short course of DSG starting on day 4 after grafting was markedly prolonged, with a mean survival time of 16.6 +/- 5.8 days and 29.8 +/- 3.0 days at doses of 2.5 mg/kg per day and 5 mg/kg per day, respectively. On day 20 after grafting, the mechanism of inducing allograft survival after DSG treatment at a dose of 5 mg/kg per day was analyzed by testing the activation of spleen cells or serum in several assay systems. Spleen cells from DSG-treated rats with surviving heart allografts showed almost no proliferative response against donor strain stimulator cells compared with controls. The cytotoxic activity towards donor strain target cells of spleen cells from DSG-treated rats with surviving heart allografts was lower than that of spleen cells from rats with rejected heart allografts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Renal graft rejection or cyclosporin toxicity? Early diagnosis by a combination of Papanicolaou and immunocytochemical staining of urinary cytology specimens.

A method is described for distinguishing between graft rejection and cyclosporin nephrotoxicity in renal allograft recipients by analyzing fresh morning urine samples. The technique combines classic Papanicolaou with immunocytochemical staining and was performed in urine specimens from a series of 42 patients. Early-stage cyclosporin toxicity was usually associated with increased numbers of proximal tubular cells only, whereas in rejection and late-stage toxicity there were increases in both tubular cells and in lymphocytes and monocytes (greater than 2000 cells/ml urine). Differentiation between these two clinical conditions was achieved by immunostaining, which revealed that increased numbers of CD25+ and CD8+ cells, as well as an increase in the HLA-DR/Lu5 ratio, were typical of rejection. CD25 positivity proved to be the best indicator of rejection, with a sensitivity and specificity of more than 90%. A cytodiagnostic algorithm is presented that is based on cell numbers and types, including immunophenotypes. The proposed method has the advantage of being noninvasive and appears to represent a reliable and rapid adjunct for the monitoring of graft function, especially in high-risk patients on cyclosporin immunosuppression.

Adolescent↗

[Clinical statistics on inpatients admitted to the Department of Urology, Hyogo Prefectural Hospital Nishinomiya during 20 years from 1972 to 1991].

A statistic analysis was carried out on the 4,956 inpatients admitted to our Department of Urology from April 1972 to December 1991. The patients included 3,399 males and 1,557 females. A total of 4,105 operations including 255 renal allotransplantations were performed on 3,590 patients. Open surgery for upper urinary tract stones has been replaced by extracorporeal shock-wave lithotripsy (ESWL) in the last three years.

Adult↗

Hepatitis C virus infection in patients with chronic liver diseases.

Antibodies against hepatitis C (HCV) in 512 patients were measured by an enzyme immunoassay (Ortho-HCV ELISA). The frequency of anti-HCV was 80%, 86%, 85% in nonB (NB) chronic hepatitis (CH), cirrhosis (LC), hepatocellular carcinoma (HCC), respectively; 70%, 90% in alcoholic (AL) LC, HCC; 15%, 33%, 58% in hepatitis B (HB) CH, LC, HCC, respectively. Anti-HCV positive cirrhotics had a shorter survival time and earlier development of HCC than anti-HCV negative cirrhotics. The findings suggest that HCV is a major cause of NB chronic liver diseases and may play a pathogenetic role in AL and HB liver diseases.

Adult↗

Effect of FK-506 on heart allograft survival in the highly sensitized recipient rats as compared with ciclosporin and 15-deoxyspergualin.

The effect of FK-506 on allograft survival in unsensitized recipients has been established in several animal experimental models. In this present study, we investigated the immunosuppressive capacity of FK-506, in comparison with ciclosporin (Cs) and 15-deoxyspergualin (DSG), on heart allograft in presensitized rats. Heart grafts from male ACI rats were heterotopically transplanted to male LEW rats. All recipient rats were sensitized with donor-type whole blood admixed with immunoadjuvant (adjuvant complete Freund) 7 days prior to transplantation. FK-506, Cs and DSG were administered from day 0 to day 14 posttransplantation. The results showed that both FK-506 and Cs significantly prolonged heart allograft survival of presensitized recipients in a dose-dependent manner. The minimum effective dose in the treatment was less for FK-506 than for Cs. However, DSG showed almost no effect of prolongation in this experiment.

Animals↗

Multidisciplinary treatment for bladder carcinoma--biological response modifiers and kampo medicines.

Authors studied the effects of several biological response modifiers (BRMs) on bladder carcinoma. On carcinogenesis in BBN-induced bladder carcinoma rats, Schizophyllan (SPG) showed inhibition of body weight loss and thymus weight loss. Bladder weight increase was also inhibited. SPG prolonged cancer-bearing survival time, and postponed malignant changes of bladder mucosa. On thymocytes of SPG-treated cancer-bearing rats, rosette-forming thymocytes increased. In clinical study, SPG, OK-432, ubenimex and kampo medicine were used as BRMs. As a result, the number of suppressor-inducer T cells increased, and in cytotoxic T cells a slow fall was observed. On helper-inducer T cells, a slow rise and decrease were noticed in the SPG group, and the reverse tendency was seen in the ubenimex and OK-432 group.

Adjuvants, Immunologic↗

Hepatitogenicity of three plaque purified mutants of hepatotropic mouse hepatitis virus, MHV-2.

Hepatitogenicity of three plaque purified mutant strains of mouse hepatitis virus, designated as MHV-2S, -2M and -2L, isolated from MHV-2 infected SR-CDF1-DBT cells was studied. After intraperitoneal inoculation with 2 x 10(5) PFU of parental MHV-2 and its mutants to 4-week-old female ICR mice, 40% of mice inoculated with MHV-2S and 20% of mice with -2M died in one week, whereas with -2L all mice survived. All mice inoculated with MHV-2 died in 3 days postinoculation (p.i.). Virus titer of the liver of mice inoculated with MHV-2, -2S and -2M reached peaks (MHV-2:10(7) PFU/0.2 g, -2S: 10(5) PFU/0.2 g and -2M: 10(6) PFU/0.2 g) at 96 hr p.i., while with -2L a peak titer (10(3) PFU/0.2 g) was shown at 48 hr p.i. Immunofluorescence revealed MHV specific antigen in the liver of MHV-2S infected mice in and around necrotic areas though less extensive than that of parental MHV-2 infected mice. With MHV-2M specific fluorescence was restricted in degenerated hepatocytes in the small necrotic foci. In mice inoculated with MHV-2L only faint fluorescence was detected. Histopathologically, in the liver of MHV-2S infected mice zonal necrosis and cell infiltration were observed. There were spotty necrosis and focal cell infiltration in the liver of MHV-2M infected mice and only small inflammatory foci were seen in MHV-2L infected mice. Large number of extracellular virions were detectable in MHV-2S but not in -2M and -2L infected mice by electron microscopy.

Animals↗

[Clinical effect on tumor regression and tissue concentration of peplomycin treated with peplomycin emulsion in hydroxypropylcellulosum].

Peplomycin emulsified in hydroxypropyl cellulosum (HPC-PEP) was prepared for intravesical chemotherapy. Clinical efficacy of HPC-PEP and tissue concentration of peplomycin (PEP) were studied in 12 patients with bladder tumor. Histopathology showed transitional cell carcinoma; 2 in grade 1,8 in grade 2, and 2 in grade 3. The total volume of 30 ml HPC-PEP was prepared from a mixture of 2% HPC and 90 mg PEP in 15 ml saline, and was intravesically administered through a urethral catheter and retained for two hours. Clinical evaluation 7 days after the initial instillation demonstrated good tumor regression in 2, good response in 5, and no change in 5. The mean PEP level in tumor tissue was 0.36 microgram/gr after 7 days and 0.19 microgram/gr even after 14 days. These clinical observations and tissue levels of PEP suggest that HPC-PEP might be useful as an intravesical instillation agent for bladder tumor.

Administration, Intravesical↗