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Biomedical subjects

N Takata

Publications and source records attributed to N Takata.

At least 37 records · Page 2Linked to original sources
PubMed1996

Suppression of hepatic allograft rejection in the rat by mitomycin C-treated donor splenocytes: in situ splenic distribution of donor class I major histocompatibility complex antigen-positive cells in the recipient.

A single intravenous injection of 3 x 10(6) donor splenocytes treated with mitomycin C (MMC) 7 days before hepatic transplantation prolongs survival of hepatic allografts in the ACI(RT1a) to LEW(RT1(1)) rat combination. This effect is donor specific. The in situ distribution in the recipient of the donor cells administered preoperatively was investigated using intracellularly fluorescence-labeled donor splenocytes. The donor cells were accumulated mainly in the splenic white pulp and lymph nodes at 12 and 24 hr after injection. Contrarily, very few cells were seen in the thymus, liver, kidney, and lung. The number of cells with dull and weak fluorescence began to increase in the splenic white pulp and lymph nodes at 24 hr after injection. This may indicate the breakdown of donor cells by recipient cells. In contrast, a number of donor cells could be detected even after 48 hr and a few cells at 7 days after splenocyte injection in the LEW-to-LEW isogeneic combination. As we previously revealed the role of class I major histocompatibility complex (MHC) antigens in prolonging hepatic allograft survival in the rat, the splenic distribution of donor class I MHC-positive cells in the recipient after intravenous administration of MMC-treated donor splenocytes was studied using immunostaining with a MN4-91-6 mouse anti-rat RT1.Aa class I MHC monoclonal antibody. The donor class I-positive cells accumulated mainly in the splenic white pulp at 12 and 24 hr after injection. This is similar to that observed in the fluorescence study. Within 48 hr after injection, most cells had disappeared from the recipient tissue. These findings suggest that the splenic white pulp, a T-dependent area, may play an important role in inducing immunological unresponsiveness.

Animals↗
PubMed1996

Identification and characterization of a mitochondrial endonuclease from yeast, Schizosaccharomyces pombe.

Schizosaccharomyces pombe mitochondria were isolated from the cells treated with Novozyme 234, and purified in a Percoll gradient. A zymographic assay in a SDS-polyacrylamide gel containing single-stranded DNA revealed that an endonuclease of 32 kDa is associated with the mitochondria. The endonuclease was extracted from the mitochondria with 0.5 M KCl and was partially purified. The 32-kDa enzyme degraded both DNA and RNA at a weak alkaline pH, but preferred single-stranded DNA. The enzyme required Mg2+ or Mn2+, but not Ca2+ or Zn2+ for activity, and was inhibited by 50% with a 150 mM salt solution. Nicks generated by the enzyme could be resealed with T4 DNA ligase, indicating that the enzyme produces 5'-P and 3'-OH ends.

DNA, Single-Stranded↗
PubMed1995

Characterization of hepatic allograft infiltrates in rats pretreated with donor-specific blood transfusion (DST).

A single intravenous injection of 1 ml freshly heparinized donor blood given 7 days prior to transplantation prolonged significantly the survival of subsequent hepatic allografts in fully allogeneic ACI(RT1a)-to-LEW(RT1(1)) rats. The cellular identity of allograft infiltrates was investigated at various times after transplantation using OX8 (CD8) and W3/25 (CD4) monoclonal antibodies. The number of CD8+ cells increased rapidly and reached a peak on Day 3 after transplantation of the untreated allografts. Similarly, the number of CD8+ cells in the allografts from DST-treated rats was maximum on Day 3 and decreased gradually thereafter. The maximum number of CD4+ cells was found on Day 3 in untreated allografts. In contrast, no significant infiltration of CD4+ cells occurred during the first 7 days after transplantation in DST-treated allografts. Thereafter, the number of CD4+ cells increased rapidly and reached a peak on Day 14. CD4+ cells remained persistently elevated in hepatic allografts of rats pretreated with DST, but did not become functionally competent or initiate rejection. These findings suggest that persistent infiltration by CD4+ cells is a characteristic feature of long-surviving hepatic allografts in rats pretreated with DST.

Animals↗
PubMed1994

Follow-up study of combination treatment (TAE and PEIT) for unresectable hepatocellular carcinoma.

The subjects were 35 patients with unresectable hepatocellular carcinoma. The patients were divided into a transcatheter arterial embolization group (TAE group, 18 cases) and a combination therapy group receiving both TAE and percutaneous ethanol injection therapy (TAE+PEIT group, 17 cases). The 50% survival period was 21.1 months for the TAE group and 37.8 months for the TAE+PEIT group (P < 0.05). The longest survival period in the TAE group was 89 months. In the TAE+PEIT group, one patient has survived for 59 months. The actuarial 1-, 2-, and 3-year survival rates for the TAE group were 82%, 45%, and 22%, respectively. For the TAE+PEIT group the rates were 83%, 64%, and 64%, respectively. The TAE+PEIT group showed a significantly higher survival rate in the 895- to 1,074-day period as compared with the TAE group (P < 0.05). Overall, the survival rate tended to be higher in the TAE-PEIT group (P < 0.1). The therapeutic responses of tumors were measured by the maximal reduction rate within 6 months of TAE and PEIT. In the TAE group, a PR was seen in only four cases. In the TAE+PEIT group, CRs and PRs were achieved significantly more frequently than in the TAE group. When the patients were divided into a responder group (CR, PR, and MR) and a nonresponder group (NC and PD), survival was significantly longer in the responder group. The findings of the present study suggest that the combination therapy was useful for improving the survival of patients with unresectable hepatocellular carcinoma.

Adult↗
PubMed1994

Ion loss due to initial recombination in a parallel-plate cavity ionization chamber.

Collection efficiencies for ion loss due to initial recombination and back-diffusion were measured for several humidities using a parallel-plate cavity ionization chamber irradiated with 60Co gamma-rays. It was shown, from measurements in a range of inverse electric field strengths from 0.05 to 14 mm V(-1), that initial recombination took place both in clusters and columns of ions produced along the path of the secondary electrons ejected by the y-rays. The ion loss due to recombination in clusters was found to increase with humidity, but that in columns did not. Effects of ion clustering reactions on recombination may be reduced after longer periods of ion drift, when recombination in columns takes place. Ion loss due to back-diffusion was also found to have no dependence on humidity.

Artifacts↗
PubMed1994

The effects of humidity on volume recombination in ionization chambers.

Saturation curves were measured with a parallel-plate ionization chamber for air with humidities of 0%-81%. From the curves, values of m--which is equal to (alpha/eK+ K-)1/2 where alpha is the recombination coefficient, e the charge of an ion, and K+ and K- are mobilities of positive and negative ions, respectively-were obtained. It was confirmed that humidity was the decisive cause of the increase in the value of m with the lifetime of ions in the ionization chamber. It was found that the value of m increases sharply in a range of small values of the product of the ion lifetime and the partial pressure of water vapour and increases more slowly at high values of this parameter.

Artifacts↗
PubMed1994

Abnormal factor VIII Hiroshima: defect in crucial proteolytic cleavage by thrombin at Arg1689 detected by a novel ELISA.

We have established an ELISA for detecting thrombin cleavage of the FVIII light chain at Arg1689. The method used a coating alloantibody which recognized amino acid residues 2248-2312 in the C2 domain, together with a second monoclonal antibody, NMC-VIII/10, which recognized residues 1675-1684 in the amino-terminal region of the light chain. FVIII antigen (FVIII:Ag) was measured after treatment of plasma with various concentrations of thrombin. The FVIII:Ag of normal plasma was reduced in a dose-dependent manner by the thrombin, falling to 28% in the presence of 100 U/ml enzyme. The concentration of thrombin that achieved 50% reduction (IC50) was approximately 1.0 U/ml. The plasma of four haemophilia A positive (A+) and two haemophilia A reduced (AR) patients were analysed. The IC50 of all patients was more than 1.0 U/ml, indicating that thrombin cleavage of the FVIII light chain was defective. One haemophilia A+ plasma did not respond to thrombin in this ELISA system. The patient (TI) was a haemophiliac with FVIII coagulant activity of 0.04 U/ml and FVIII:Ag of 1.78 U/ml. In addition, immunoblotting of the purified FVIII from TI showed that thrombin cleavage of the 80 kilodalton (kD) light chain was impaired. The patient's DNA was amplified using the polymerase chain reaction with a set of synthetic oligonucleotide primers spanning amino acid residues 1646-1714. Sequence analysis of the amplified DNA fragments revealed a cytosine to thymine transition, converting an arginine 1689 to cysteine. This abnormal FVIII was designated as FVIII Hiroshima. Our ELISA system is a simple and useful method of evaluating the proteolytic cleavage by thrombin at Arg1689.

Arginine↗
PubMed1994

Extraserosal invasion in advanced gastric cancer: evaluation with MR imaging.

PURPOSE: To evaluate the usefulness of magnetic resonance (MR) imaging in the diagnosis of extraserosal invasion in advanced gastric cancer. MATERIALS AND METHODS: MR imaging was performed in 48 patients with advanced gastric cancer, and the results were correlated with the histopathologic findings. Images perpendicular to the gastric wall with cancer were obtained with spoiled gradient-recalled acquisition in the steady state (GRASS). The degree of serosal invasion was classified on the basis of the appearance of a low-signal-intensity band around the lesion. RESULTS: Advanced gastric cancer appeared as a thickened wall of high signal intensity after the administration of contrast material. A low-signal-intensity band disappeared or showed irregularity in the area of extraserosal invasion by the gastric cancer. The MR imaging-determined grade correlated with the histopathologic findings for 11 of 14 (79%) pT2 tumors, 23 of 24 (96%) pT3 tumors, and eight of 10 (80%) pT4 tumors. The overall accuracy was 88%. CONCLUSION: Presence of a low-signal-intensity band at MR imaging is useful for the preoperative evaluation of serosal invasion.

Adult↗
PubMed1994

Liver regeneration after orthotopic reduced-size hepatic transplantation in the rat.

These experiments were undertaken to study the effects of cyclosporine on liver regeneration after an isogeneic orthotopic reduced-size hepatic transplantation in rats. The incorporation of bromodeoxyuridine into the DNA of the remnant hepatocytes was evaluated at various time points by immunohistochemical staining. Cyclosporine (10 mg/kg/day) significantly augmented BrdU incorporation into hepatocytes after hepatectomy. The maximum labeling index was observed at 24 hr after hepatectomy. In contrast, the maximum labeling index in the recipient rats not receiving cyclosporine was seen at 36 hr after reduced-size hepatic transplantation, and 10 mg/kg/day of cyclosporine decreased the labeling index at 36 hr after grafting. A lower dose of cyclosporine (3 mg/kg/day), however, significantly increased the labeling index in the recipient rats, which reached a peak at 24 hr after grafting as compared with the transplant recipients not receiving cyclosporine. This dosage shortened the time it took for the reduced-size hepatic transplant labeling index to peak. These findings suggest that after reduced-size hepatic transplantation, the liver graft is more sensitive to both hepatotrophic and hepatotoxic effects of cyclosporine.

Animals↗
PubMed1993

In situ macrophage distribution in the hepatic allograft associated with rejection in the rat.

The association of macrophage infiltration with orthotopic rat liver transplant rejection was studied in the ACI(RT1a) to the LEW(RT1(1)) rat combination, using immunohistochemical staining with several monoclonal antibodies at different time points. LEW recipients of ACI liver transplants experienced severe acute rejection, with a mean survival of 10.2 +/- 0.7 days. An indirect immunoperoxidase technique on cryostat sections of the liver grafts was used to determine the localization of macrophages infiltrating the grafts as defined by specific rat anti-macrophage monoclonal antibodies designated TRPM-3 and KI-M2R. In addition, the monoclonal antibodies MRC OX3 and MRC OX6 were used to detect the macrophages that expressed Ia antigens. MRC OX3 binds only with the host LEW Ia antigens, but MRC OX6 binds with both host LEW and donor ACI Ia antigens. OX3+ and OX6+ macrophages were seen in the periportal area of the hepatic allograft on Day 5; thereafter, the number of these cells increased in the periportal and pericentral areas as well as in the sinusoidal lumens. A large number of TRPM-3+ cells were also seen at the periportal area in the hepatic allograft on Day 5, whereas there was no increase in the number of KI-M2R+ cells. In addition, most of the infiltrating mononuclear cells were OX3+. These findings suggest that a large number of TRPM-3+ macrophages of recipient origin migrate into the hepatic allograft soon after transplantation. A progressive relative increase in host TRPM-3+ macrophages is a characteristic feature of ongoing first-set rejection in the rat hepatic allograft.

Animals↗
PubMed1993

Effect of cyclosporine on liver regeneration after orthotopic reduced-size hepatic transplantation in the rat.

These experiments were undertaken to study the effects of cyclosporine A (CsA) on liver regeneration after an isogeneic orthotopic reduced-size hepatic transplantation (RSHT) in rats. Male Wistar rats were treated with or without a daily injection of CsA beginning 24 hr before surgery and were subjected to a 68% partial hepatectomy. A isogeneic orthotopic reduced-size hepatic transplantation was performed in recipient rats pretreated with or without CsA. A daily injection of CsA was continued until the recipient rats were sacrificed. Animals were sacrificed at various time points (12, 24, 36, 48, and 72 hr) postoperatively. The incorporation of bromodeoxyuridine (BrdU) into the DNA of the remnant hepatocytes was evaluated by immunohistochemical staining with a monoclonal antibody against BrdU. CsA (10 mg/kg/day) significantly augmented BrdU incorporation into hepatocytes after hepatectomy. The maximum labeling index (LI) was observed at 24 hr after hepatectomy. In contrast, the maximum LI in the recipient rats not receiving CsA was seen at 36 hr after RSHT, and 10 mg/kg/day of CsA decreased the LI at 36 hr after RSHT. A lower dose of CsA (3 mg/kg/day), however, significantly increased the LI in the recipient rats (P < 0.01), and it reached a peak at 24 hr after RSHT when compared to the transplant recipients not receiving CsA. The time course of the increase in the LI in the transplant recipient rats receiving 3 mg/kg/day of CsA was similar to that observed in the rats after hepatectomy. This dosage improved the delay in the reduced-size hepatic transplant LI reaching its peak.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effect of cyclosporine on distribution of macrophage subpopulations in rat hepatic allograft.

Macrophage subpopulations infiltrating the grafts of ACI(RT1a) to LEW(RT1(1)) orthotopic rat liver transplants treated with or without immunosuppressive therapy were studied using immunohistochemical staining. LEW recipients of ACI liver transplants experienced severe acute graft rejection, with a mean survival of only 10.2 +/- 0.7 days. An indirect immunoperoxidase technique on cryostat sections of the liver grafts was used to determine the localization of macrophage subpopulations infiltrating the grafts, as defined by specific anti-rat macrophage monoclonal antibodies, designated TRPM-1 (pan-macrophage), TRPM-3 (activated macrophage) and Ki-M2R (tissue macrophage). TRPM-1+ or TRPM-3+ cells gradually increased on days 5 and 7 in the untreated hepatic allografts, whereas no significant changes in the number of these cells were observed in the isografts. Treatment with cyclosporine (CsA) greatly decreased the number of these two different types of cells infiltrating the hepatic allografts, compared to the untreated hepatic allografts or the isografts. The time course of the accumulation of these cells in the allografts treated with CsA showed a similar pattern; the cells increased gradually by day 5 and thereafter decreased. This pattern is different from that observed in the untreated allografts or in the isografts. There was no significant difference in the number of Ki-M2R+ cells between the untreated hepatic allografts and the isografts. However, the number of the Ki-M2R+ cells in the hepatic allografts treated with CsA was much less than that of either the untreated allografts or the isografts. These findings suggest that a progressive relative increase in host TRPM-3+ macrophage is a characteristic feature of ongoing first-set rejection in the rat hepatic allograft.2+ allograft, even when compared with the isografts.

Animals↗
PubMed1993

Phase I/II trial of didanosine (2',3'-dideoxyinosine) in hemophiliac patients with AIDS or AIDS-related complex.

Forty-three hemophiliacs with AIDS or ARC received a daily dose of 334 or 500 mg didanosine (2',3'-dideoxyinosine or ddI) orally in 2 divided doses in phase I/II, open-label clinical trial conducted in Japan. Twenty-eight patients completed 6 months of therapy. There was an increase in circulating CD4(+) cells in 19 valuable patients from 91 +/- 25 (mean +/- SE) at entry to 131 +/- 38 at 24 weeks of therapy P = 0.01; Wilcoxon signed rank). Fourteen of 37 patients met the criteria for CD4 rise >/= 50/mm3 rise or >/= 50% increase from entry values) for more than 4 consecutive weeks. Twenty patients were p24 positive at entry. Nine out of the 10 evaluable patients (90%) showed a decline in p24 antigen at weeks 20-24 (P = 0.02). Thirty-five patients had symptoms related to HIV-1 infection at entry. Twenty-seven patients reported improvements in constitutional symptoms during therapy. Nine patients presented with possible drug-related adverse effects, and didanosine was discontinued in 6 patients (one each with edema; abdominal pain with anorexia; hematuria with edema and rash; sense of abdominal distension with anorexia; diarrhea and abdominal pain; and irritability). One patient had a transient increase in serum amylase level to twice the upper limit of normal, but he continued to receive the drug. These data suggest that didanosine was generally well tolerated in hemophiliacs with AIDS or ARC, and its administration correlated with improvement in constitutional symptoms and laboratory findings. The adverse effects of didanosine seen in this population were moderate to mild, and no complications related to hemorrhagic diathesis were observed, although the relative risk of acute pancreatitis in this population (while not seen in the present study to date) requires more study.

Journal Article↗
PubMed1993

[Mutations of HIV-1 RT gene isolated from patients treated with AZT].

HIV-1 strains were isolated from three patients treated with AZT and from three patients not treated with AZT. Progenomes of HIV-1 RT gene were amplified by PCR and cloned to M13mp18 vecter. Four amino acid mutations in RT gene (Asp67, Lys70, Thr215, Lys219) associated with resistance to AZT were analysed. All of the 14 clones obtained from the three patients with AZT therapy had mutations at codon 215 (Thr-->Tyr or Phe). Some of the 14 clones also had other mutations at codon 67 (Asp-->Asn or Ser), codon 70 (Lys-->Arg) and codon 219 (Lys-->Glu). All of 18 clones obtained from the patients not treated with AZT have no mutation at any codon mentioned above.

Amino Acid Sequence↗