K Kato

Juntendo University, Edo, Tōkyō, Japan

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Publications (125)223.22 Total impact

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    Diabetes Care 03/2000; 23(2):253-4. DOI:10.2337/diacare.23.2.253 · 8.57 Impact Factor
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    ABSTRACT: Hepatocyte transplantation is a potential therapeutic modality for overcoming the shortage of liver donors, and the clinical application of allogeneic hepatocyte transplantation has been considered. However, there are two major problems with allogeneic hepatocyte transplantation: protection of transplanted hepatocytes from rejection and stimulation of the rapid proliferation of surviving cells. Without immunosuppression, allogeneic hepatocytes are rapidly rejected within a few days after transplantation, even though it is relatively easy to induce immunotolerance after allogeneic whole liver transplantation. Accordingly, different rejection mechanisms seem to operate after allogeneic hepatocyte transplantation and whole liver transplantation. To overcome the rejection of transplanted hepatocytes, induction of donor-specific unresponsiveness to graft without compromising the host immune system would be ideal. We previously reported that the Fas-Fas ligand system plays a critical role in the CD28-independent pathway of hepatocyte rejection. Therefore, blockade of rejection using CTLA4 immunoglobulin (CTLA4Ig) or anti-CD80/86 monoclonal antibodies and anti-FasL monoclonal antibody may prolong the survival of transplanted allogeneic hepatocytes. Furthermore, administration of hepatocyte growth factor (HGF) can promote the proliferation of allogeneic hepatocytes and this may lead to the development of a functioning liver substitute.
    Journal of Gastroenterology and Hepatology 10/1998; 13 Suppl:S119-23. · 3.63 Impact Factor
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    ABSTRACT: The expression and enzymatic activity of the cytochrome P450 LAomega within intrasplenically transplanted hepatocytes was investigated. Fetal hepatocytes were harvested from spontaneously hypertensive rats and transplanted into recipient adult spontaneously hypertensive rat spleens. Microscopic examination revealed masses of hepatocytes in the red pulp. Immunochemical studies detected cytochrome P450 LAomega in transplanted hepatocytes by 6 and 10 weeks after transplantation. Cytochrome P450 LAomega mRNA accumulates at 6 weeks after transplantation. Cytochrome P450-arachidonic acid omega/omega-1 hydroxylase activity (formation of 20/19-hydroxyeicosatetraenoic acid) was detected at 10 weeks after transplantation. These results demonstrated that fetal hepatocytes grow in the spleen and function similarly to adult hepatocytes.
    Transplantation 09/1998; 66(4):441-5. · 3.78 Impact Factor
  • Transplantation Proceedings 03/1998; 30(1):13-5. DOI:10.1016/S0041-1345(97)01164-0 · 0.95 Impact Factor
  • Transplantation Proceedings 03/1998; 30(1):16-8. DOI:10.1016/S0041-1345(97)01165-2 · 0.95 Impact Factor
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    ABSTRACT: Mitral valve aneurysm is defined as a localized protrusion of the valve with a different radius from that of the remaining portion of the valve. The medical records and pathological findings of seven patients with mitral valve aneurysm [aged 48-69 years (mean 64), 4 males] and the pathological findings of other 29 Japanese cases were reviewed. All seven patients were diagnosed pathologically as infective endocarditis, but two patients had no documentation of clinical symptoms suggestive of infective endocarditis (latent infective endocarditis). The underlying lesion of the heart was aortic valve disease and/or fibrosal degeneration of the mitral valve. Only 29 of 36 Japanese case reports stated a precise description of the valve pathology. Of these 29 cases, 23 were associated with infective endocarditis, two with rheumatic valvular disease with fusion and/or shrinkage of the chordae tendineae, three with mitral valve prolapse or myxomatous degeneration of the mitral valve, and one with aortitis syndrome. Neovascularization was described in eight cases. Neovascularization with thick wall should be considered as post-inflammatory vascularization. This review indicates that patients with latent infective endocarditis and mitral valve aneurysm should be considered as potential candidates for valve surgery.
    Journal of Cardiology 02/1998; 31 Suppl 1:19-33; discussion 34-6. · 2.57 Impact Factor
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    ABSTRACT: Cytolytic induction of T cells requires both the T-cell receptor (TCR)-mediated antigenic stimulation and the CD28-mediated co-stimulatory signal. Blockade of the interactions between CD28 and its ligands, CD80 and CD86, prolongs the survival of allografts in some transplantation models. However, we found that allogeneic hepatocytes were completely rejected within 7 days after intrasplenic transplantation, even when treated with monoclonal antibodies (mAbs) against CD80 and CD86 (anti-CD80/86). Recent studies have shown that there are two main mechanisms of T-cell-mediated cytotoxicity, perforin-based and Fas-based ones. It has been shown that the liver is highly sensitive to induction of apoptosis by an agonistic anti-Fas mAb. We then investigated the role of the Fas/Fas ligand (FasL) system in the CD28-independent allogeneic hepatocyte rejection. With the anti-CD80/86 mAb treatment, hepatocytes from C57BL/6 lpr/lpr (B6 lpr) mice, which express little Fas antigen, could survive for 7 days after intrasplenic transplantation, and hepatocytes from C57BL/6 (B6) mice could also survive for 7 days in the spleen of C3H/ He gld/gld (C3H gld) mice, which express no functional FasL. CD28-independent induction of cytotoxicity against allogeneic hepatocytes was not observed when the effector cells were derived from C3H gld mice. These results indicated that the Fas/FasL system plays a critical role in the CD28-independent pathway of allogeneic hepatocyte rejection.
    Hepatology 11/1997; 26(4):944-8. DOI:10.1053/jhep.1997.v26.pm0009328317 · 11.19 Impact Factor
  • Transplantation Proceedings 07/1997; 29(4):2029-31. DOI:10.1016/S0041-1345(97)00217-0 · 0.95 Impact Factor
  • Transplantation Proceedings 07/1997; 29(4):2187-8. DOI:10.1016/S0041-1345(97)00286-8 · 0.95 Impact Factor
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    ABSTRACT: We report the advantage of employing transanal endoscopic microsurgery (TEM) using the contact Nd:YAG laser for the treatment of a rectal anastomotic stenosis. A 72-year-old woman was admitted to our hospital with a postoperative rectal anastomotic stenosis. Twenty months prior to admission, the patient underwent a low anterior resection for the treatment of the rectal cancer using an EEA stapling device. A barium enema and colonoscopy revealed a rectal stenosis, 0.8-cm diameter. This stenosis was at the anastomotic site, approximately 4.0 from the dental line. An endoscopic treatment was performed transanally using the contact Nd:YAG laser. The stenotic rectal wall was fulgurated or vaporized completely. There were no intraoperative or postoperative complications. We concluded that TEM appears to be a safe and minimally invasive procedure. Furthermore, the contact Nd:YAG laser is very effective in treating the gastrointestinal stenotic area. To our knowledge, this is the first successful report of this novel procedure.
    Surgical Endoscopy 06/1997; 11(5):485-7. DOI:10.1007/s004649900398 · 3.31 Impact Factor
  • K Kato, K Okumura, H Yagita
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    ABSTRACT: Our recent studies using various costimulatory molecules have demonstrated that antitumor effect could be induced by B7- or B70-transduced mouse tumors. To augment antitumor effect in vivo, the combination therapy with a costimulatory gene and a cytokine, interkeukin 12 (IL-12), gene to treat metastatic mouse lung tumor was investigated. We transfected with mouse B7 and/or IL-12 into mouse lung carcinoma 3LL, and three transfectants (IL-12/3LL, B7/3LL and IL-12/B7/3LL) were generated. CTL activity induced by the inoculation of IL-12/B7/3LL was increased about 10-fold compared with parental 3LL inoculation. We then examined the therapeutic efficacy of combination with B7 and IL-12-transduced tumors. Four weeks after 3LL inoculation, lung metastasis was significantly reduced by IL-12/B7/3LL post-inoculation, indicating that potent therapeutic antitumor immunity can be induced by combination with costimulators B7 and IL-12. Recently, it was reported that p40 subunit of IL-12 appeared to be a specific inhibitor for IL-12 heterodimer in vitro. To clarify the biological functions of p40 in vivo, we generated the myoblast transfectants which produced IL-12 p40 alone. Local production of IL-12 p40 from transfectant could suppress allogenic CTL induction and Th1-type antibodies (IgG2a/2b/3) production in vivo. Furthermore, IL-12 p40 producing myoblast are less susceptible to rejection compared with parental myoblast, indicating that IL-12 p40 gene transfer may be useful therapeutically in Th1-mediated transplantation and autoimmune disorders.
    Leukemia 05/1997; 11 Suppl 3:572-6. · 9.38 Impact Factor
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    ABSTRACT: Laparoscopic cholecystectomy (LC) has become the standard treatment for removing a diseased gallbladder. Endoscopic surgical techniques are used to perform appendectomies, bowel resections, and gastrectomies. This minimally invasive surgery is favored because it decreases the patients' postoperative pain and length of hospitalization. However the incidence of complications with this technique is not negligible. As a new technique is evolving, the potential for complications is high. This increase in complication rate is undoubtedly due to inexperience during the initial phase of the surgeon's learning curve. Demand for the procedure has required rapid training and credentialing of many surgeons with limited experience in endoscopy and the use of instruments that allow only limited viewing of abdominal structures.
    Surgical technology international 02/1997; 6:127-31.
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    ABSTRACT: We examined the expression and enzymatic activity of cytochrome P450 LA omega within transplanted hepatocytes. Fetal hepatocytes were harvested at day 20 of gestation from spontaneously hypertensive rats (SHRs) and transplanted into recipient adult SHR spleens. Microscopic examination of the recipient spleens at 4 and 10 wk after transplantation revealed masses of hepatocytes with cord-like structures in the red pulp. Immunochemical studies detected cytochrome (cyto) P450 LA omega in the fetal hepatocytes before transplantation without prior induction. Although the cyto P450 LA omega was not detected by the second week after transplantation, by the 6th and 10th wk after transplantation, it was. Cyto P450-arachidonic acid omega/omega-1 hydroxylase activity (formation of 20- and 19-hydroxyeicosatetraenoic acid) was detected at 10 wk after transplantation, but not 2 or 6 wk after transplantation. These results demonstrated that fetal hepatocytes can be transplanted successfully into recipient spleens and then grow in the spleens, as in the case of the adult hepatocyte response.
    Cell Transplantation 01/1997; 6(5):531-4. DOI:10.1016/S0963-6897(97)00072-9 · 3.57 Impact Factor
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    ABSTRACT: The pathogenesis of nonrheumatic calcification of the mitral valve was investigated by analyzing the clinical and echocardiographic characteristics of patients with mitral valvular calcification without any findings suggestive of rheumatic heart disease or infective endocarditis. Calcification of the mitral valve was observed in nine patients, who all had calcified stenotic (aortic valve area < 1 cm2) bicuspid aortic valve. Calcification of the mitral valve was localized to the basal portion of ventricular aspect of the anterior mitral leaflet and contiguous to that of the aortic valve. Mobility and thickness of the mitral leaflet was normal except for the calcified portion. Calcification of the mitral valve was not contiguous to posterior mitral annular calcification nor was related to direction of aortic regurgitant flow. In patients with calcified stenotic bicuspid aortic valve, calcification of the mitral valve was not associated with location of the two aortic cusps, aortic valve area, aortic valvular peak pressure gradient, direction of the left ventricular outflow, end-diastolic left ventricular outflow tract dimension, end-diastolic dimension of the aortic annulus, incidence of aortic regurgitation, calcification of the aortic arch, or risk factors of atherosclerosis. Six patients with mitral valvular calcification had aortic valve replacement. Preoperative coronary angiogram of these patients was normal. Calcification of the aortic valve was on the ventricular and aortic aspects. The calcification of the aortic valve, anterior mitral ring, or anterior mitral leaflet was not rheumatic in these six patients. Rheumatic disease, risk factors of atherosclerosis, mechanical stress by left ventricular outflow or aortic regurgitant flow, or mitral annular calcification did not appear to be related to mitral valvular calcification. The distribution of aortic and mitral valvular calcification suggested that the calcification of the mitral valve was due to progression of calcification of the bicuspid aortic valve.
    Journal of Cardiology 10/1996; 28(4):221-6. · 2.57 Impact Factor
  • Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 09/1996; 93(8):565-8.
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    ABSTRACT: The p40 subunit of interleukin 12 (IL-12p40) has been known to act as an IL-12 antagonist in vitro. We here describe the immunosuppressive effect of IL-12p40 in vivo. A murine myoblast cell line, C2C12, was transduced with retro-virus vectors carrying the lacZ gene as a marker and the IL-12p40 gene. IL-12p40 secreted from the transfectant inhibited the IL-12-induced interferon gamma (IFN-gamma) production by splenocytes in vitro. Survival of C2C12 transplanted into allogeneic recipients was substantially prolonged when transduced with IL-12p40. Cytokine (IL-2 and IFN-gamma) production and cytotoxic T lymphocyte induction against allogeneic C2C12 were impaired in the recipients transplanted with the IL-12p40 transfectant. Delayed-type hypersensitivity response against C2C12 was also diminished in the IL-12p40 recipients. Furthermore, serum antibodies against beta-galactosidase of the T-helper 1-dependent isotypes (IgG2 and IgG3) were decreased in the IL-12p40 recipients. These results indicate that locally produced IL-12p40 exerts a potent immunosuppressive effect on T-helper 1-mediated immune responses that lead to allograft rejection. Therefore, IL-12p40 gene transduction would be useful for preventing the rejection of allografts and genetically modified own cells that are transduced with potentially antigenic molecules in gene therapy.
    Proceedings of the National Academy of Sciences 09/1996; 93(17):9085-9. DOI:10.1073/pnas.93.17.9085 · 9.81 Impact Factor
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    ABSTRACT: Fetal hepatocytes were harvested at day 20 of gestation from spontaneously hypertensive rats (SHR) and then transplanted into recipient adult SHR spleens. Morphological examination of the recipient spleens revealed that, after 4 and 10 wk, large masses of hepatocytes were present in the red pulp with apparent cord-like structures. Larger batches of hepatocytes were observed in the spleens at 10 wk after than at 4 wk after transplantation. Of major significance was the fact that hepatocyte transplanted spleens were able to express several families of cytochrome P450 (cyto P450) proteins 2-10 wk after transplantation. Immunochemical determinations revealed that cytos P450 IA1, P450 IIB1, P450 p, P450 HLp, and P450 LA omega could be detected without any prior induction. All were intensely expressed 6 wk after transplantation; however, P450 IA1 and P450 IIB1 did not appear to be expressed by 2 wk after transplantation. Although cytos P450 p and P450 HLp did not appear to be expressed by 10 wk after transplantation, they were induced with dexamethasone at that time. Cyto P450 LA omega and peroxisomal acyl CoA oxidase were expressed 6 wk after transplantation in a 70% hepatectomized host. These results demonstrate that fetal hepatocytes can be successfully transplanted into the spleens of recipients and that the fetal hepatocytes appear to grow and develop cyto P450 metabolizing systems.
    Cell Transplantation 09/1996; 5(5 Suppl 1):S27-30. DOI:10.1016/0963-6897(96)00035-8 · 3.57 Impact Factor
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    ABSTRACT: We attempted multilocational hepatocyte transplantation (HCTx) including hepatocyte-bearing polyurethane foam (PUF) to treat congenitally ascorbic acid (AsA) biosynthetic enzyme-deficient (ODS-od/od) rats. Hepatocytes isolated from the liver of congeneic rats were transplanted into the portal vein (Pv), spleen (Sp), omentum (Om), and mesentery (Ms). Hepatocyte-bearing PUF was transplanted into the Om and Ms. Experimental groups were divided into four groups (group I; Pv + Sp, group II; Pv + Sp + Om + Ms, group III; Pv + Sp + hepatocyte-bearing PUF, group IV; control). The average serum AsA level of the surviving rats in group II and III was significantly higher than that in group I 3 mo after HCTx. Histological examination showed small foci of surviving hepatocytes in the Om and Ms tissues and in the connective tissue in the PUF. ODS-od/od rats survived for a long time by multilocational HCTx.
    Cell Transplantation 09/1996; 5(5 Suppl 1):S23-5. DOI:10.1016/0963-6897(96)00034-6 · 3.57 Impact Factor
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    ABSTRACT: We have investigated the availability of multiporous microcarriers (MCs) for immobilizing isolated rat hepatocytes, but the pore size of MCs was too small (35 microns) for hepatocyte immobilization. In this study, we immobilized isolated rat hepatocytes on MCs with larger pores, and evaluated their metabolic activity. Isolated hepatocytes were immobilized on MCs precoated with collagen by the intermittent stirring method and by aspiration, and the cell-protein content per 100 mg MCs was determined for comparison of these methods. Metabolic activity was evaluated by analyzing NH3 metabolism, urea nitrogen synthesis and glucose synthesis. The aspiration method immobilized significantly more of hepatocytes on MCs than the intermittent stirring method (p < 0.05). A stationary culture of hepatocytes immobilized on MCs showed a similar NH3 metabolism to monolayer cultured hepatocytes, and hepatocytes immobilized on MCs in a floating culture showed significantly higher NH3 metabolism than those in a stationary culture (p < 0.01). However, monolayer cultured hepatocytes showed higher glucose synthesis than hepatocytes immobilized on MCs in a stationary culture (p < 0.01). In conclusion, hepatocytes immobilized on MCs proved to be useful as a bioreactor in a hybrid artificial liver.
    Cell Transplantation 09/1996; 5(5 Suppl 1):S35-7. DOI:10.1016/0963-6897(96)00089-9 · 3.57 Impact Factor
  • Acta Crystallographica Section A Foundations of Crystallography 08/1996; 52(a1):C373-C373. DOI:10.1107/S0108767396084644 · 2.07 Impact Factor

Publication Stats

894 Citations
223.22 Total Impact Points


  • 1991–1998
    • Juntendo University
      • • Second Department of Surgery
      • • Department of Immunology
      Edo, Tōkyō, Japan
  • 1994–1997
    • New York Medical College
      • • Department of Surgery
      • • Department of Medicine
      New York, New York, United States
  • 1991–1996
    • The Cardiovascular Institute
      Tōkyō, Japan
  • 1993
    • Dana-Farber Cancer Institute
      • Department of Medical Oncology
      Boston, Massachusetts, United States
    • Tsukuba Research Institute
      Edo, Tōkyō, Japan
  • 1970–1971
    • Nagoya University
      • Division of of Internal Medicine
      Nagoya, Aichi, Japan