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Hiroshi Kitamura

Publications and source records attributed to Hiroshi Kitamura.

At least 73 records · Page 4Linked to original sources
PubMed2003

Xenogeneic thymokidney and thymic tissue transplantation in a pig-to-baboon model: I. Evidence for pig-specific T-cell unresponsiveness.

BACKGROUND: The potential of xenotransplantation for clinical application will require overcoming barriers of humoral and cellular rejection, through strategies using immune suppression or tolerance induction. This laboratory has previously reported the induction of tolerance in the discordant xenogeneic model of pig-to-rodent thymic transplantation. We also have described a miniature swine model of fully mismatched allogeneic composite vascularized thymokidney transplantation that induced transplantation tolerance. We tested a combination of these approaches in a clinically relevant pig-to-primate model of xenotransplantation. METHODS: Composite thymokidney grafts were prepared 40 to 80 days before transplantation by the autologous implantation of thymic tissue under the renal capsule of human decay-accelerating factor transgenic swine. Baboons received xenotransplants of both human decay-accelerating factor composite thymokidneys and omental implants of thymic tissue. Recipients were treated with an immunosuppressive-conditioning regimen including thymectomy or thymic irradiation, extracorporeal immunoadsorption of anti-alphaGal antibodies and T-cell depletion. Recipients were followed for indicators of xenograft rejection, T-cell depletion and reconstitution, anti-alphaGal antibody levels, and mixed lymphocyte responses. Immunologic responses were studied in those animals that survived for more than 3 weeks. RESULTS: Thymokidney xenografts survived for up to 30 days, with evidence of viable thymic epithelium and Hassall's corpuscles under the renal capsule and in the omental implants, and with evidence of few host lymphocytes. Three animals demonstrated donor-specific unresponsiveness, while maintaining normal alloresponses, in mixed-lymphocyte-response assays performed after immunosuppression had been stopped. Rejected grafts demonstrated humoral damage without evidence of cellular infiltrates. After graftectomy, one animal maintained donor-specific cellular unresponsiveness and stable anti-alphaGal antibody levels for more than 2 months. CONCLUSIONS: We concluded that composite thymokidney and thymic-tissue xenotransplantation from swine to baboons can induce donor-specific cellular unresponsiveness and stable anti-alphaGal antibody levels, suggesting avoidance of sensitization after xenotransplantation. The presence of viable donor-swine thymic epithelium could have a role in the development of donor-specific T-cell tolerance. Further strategies to address humoral rejection could prolong graft survival and result in long-term tolerance to xenografts.

Animals↗
PubMed2003

Xenogeneic thymus transplantation in a pig-to-baboon model.

BACKGROUND: We have tested whether fetal porcine thymic tissue transplantation can lead to tolerance across a discordant (pig-to-baboon) xenogeneic barrier. METHODS: Six baboons underwent a conditioning regimen with thymectomy, splenectomy, and anti-monkey CD3 antibody conjugated to a diphtheria toxin binding site mutant (FN18-CRM9). Porcine fetal or neonatal thymic tissue was transplanted into three baboons. Three control baboons received either no transplanted pig tissue (n=1) or adult pig lymph node (n=2). Cellular responses and skin xenografts were used to test for tolerance. RESULTS: After T-cell depletion and thymic transplantation, recovery of thymus-dependent naïve-type CD4 cells (CD4/CD45RA ) and in vitro xenogeneic hyporesponsiveness were observed. No sensitization of alpha-galactosyl antibody responses was observed. The thymic grafts survived up to 48 days. Porcine skin xenografts were performed in two of these animals with survival of 22 and 24 days. Only two of these animals were completely T-cell depleted, and both failed to recover thymus-dependent T cells (CD4/CD45RA ). In one animal, general in vitro hyporesponsiveness was observed, with subsequent death from infection. The second animal demonstrated delayed recovery of T cells and prolonged general hyporesponsiveness in vitro. Neither animal demonstrated prolongation of porcine skin grafts compared with allografts (both rejected by day 13). CONCLUSIONS: Porcine thymic tissue is able to induce xenogeneic hyporesponsiveness. More efficient thymic engraftment may allow this approach to induce xenograft tolerance.

Animals↗
PubMed2003

A small, incidentally detected pancreatic somatostatinoma: report of a case.

We report an asymptomatic 72-year-old woman with a small, incidentally detected, pancreatic somatostatinoma. The tumor, measuring 1 cm in diameter, showed a hypervascular pattern of contrast enhancement on computed tomography, and was found angiographically to receive a blood supply from the posterior superior pancreaticoduodenal artery. The results of preoperative hormonal assays all were normal. No assay for somatostatin was performed. No abnormality in either the pituitary or parathyroid was found. We thus considered the tumor to be a sporadic, nonfunctioning endocrine cell tumor, and enucleation was carried out. As some tumor cells in the resected specimen showed immunoreactivity for somatostatin, a diagnosis of somatostatinoma was made. Therefore, the possibility of somatostatinoma should be kept in mind when making a differential diagnosis of pancreatic endocrine tumors in cases where even a small hypervascular tumor is detected on enhanced computed tomography.

Aged↗
PubMed2003

Identification of an electron densification of the glomerular basement membrane in renal biopsy specimens.

Ultrastructural examination of renal biopsy specimens is often necessary to establish a diagnosis. We have noted, in some renal biopsies, that normal-appearing glomerular basement membrane (GBM) shows an electron densification. The aim of this study was to describe this phenomenon and assess the degree of its occurrence. We reviewed ultrastructural pathology records of 153 renal biopsy patients with special reference to the careful examination of the electron micrographs. Of these, 28 cases (18%) showed a definite and homogeneous electron densification of normal-appearing GBM in the glomeruli. The pathological diagnosis in these cases was IgA nephropathy in 15, minimal change nephrotic syndrome in 6, interstitial nephritis in 3, membranoproliferative glomerulonephritis in 2, and nephritis of Henoch-Schonlein purpura and membranous nephropathy in 1 case each. In addition, frequent deposition of IgG without C3 in the GBM (86%) and glomerular endothelial cell edema (96%) were observed. No apparent correlation could be ascertained between the presence of the electron densification and pathological diagnosis. It is suggested that electron densification of the GBM may be caused by the penetration of some electron-dense materials into the GBM as a result of an abnormality in the glomerular filtration barrier and that this could be considered as a sign of altered properties of the lamina densa.

Adolescent↗
PubMed2003

Tranexamic acid-induced visual impairment in a hemodialysis patient.

We report a case of overdosage of tranexamic acid (TNA), which was suggested as the cause of visual impairment in a 56-year-old man. He had been undergoing chronic hemodialysis for 1 year, following 10 years of peritoneal dialysis. He had been hospitalized for an emergency operation for a bleeding ulcer of the stomach and duodenum. After the operation, he experienced a gradual loss of sight over about 1 week, although his general condition was good. He received intravenous injections of TNA as a hemostat during hospitalization for the operation. Two weeks after the operation he became blind. Retinography was flat and his visual field had become narrowed. On fluorescein angiography, microgranular hyperfluorescence, which indicated malfunction of the pigmented layer of the retina, was observed. No abnormality of the brain or the optic nerve was shown by magnetic resonance imaging. Concentrations of vitamins and trace minerals in the blood were within the normal ranges. Administration of vitamins A and B(12) did not improve his sight. However, discontinuation of TNA rapidly restored his sight, within a few days. He had received TNA once before because of bleeding ulcer, and his sight had been impaired at that time. Based on the repeated episodes, it was strongly suggested that an overdose of TNA in this dialysis patient caused the sight disturbance. Because TNA is metabolized by the kidney, caution is necessary when prescribing TNA for patients with renal failure.

Angiography↗
PubMed2003

Alpha-fetoprotein-producing carcinoma of the colon: report of a case and review of the literature.

PURPOSE: We describe a rare case of an alpha-fetoprotein-producing carcinoma originating in the transverse colon of a 59-year-old Japanese male. METHODS: The patient reported an abdominal mass and weight loss. On examination, a tumor of the transverse colon and multiple masses in the liver were found. The serum alpha-fetoprotein level was extremely high (12,873 ng/ml). The patient underwent right hemicolectomy and intraoperative biopsy of a liver mass. RESULTS: Histologically, the colon cancer was composed of three different components: a well-differentiated tubular adenocarcinoma, a tubulopapillary carcinoma consisting of cells with clear cytoplasms, and a "hepatoid carcinoma." The hepatoid carcinoma was composed of large polygonal cells with abundant eosinophilic or clear cytoplasms, arranged in a trabecular or solid pattern, and showing marked vascular invasion. Immunohistochemically, alpha-fetoprotein was strongly expressed, largely in the hepatoid carcinoma and partially in the tubulopapillary carcinoma. The liver biopsy specimen showed morphologic and immunohistochemical features similar to those of the hepatoid carcinoma of the colon and was therefore diagnosed as a metastasis. The patient died of the cancer two months after surgery. CONCLUSION: Based on our experience of this patient and a review of the literature, alpha-fetoprotein-producing colorectal carcinomas are generally associated with a poor prognosis because of the frequent occurrence of blood-borne metastases.

Adenocarcinoma↗
PubMed2003

Retroperitoneoscopic nephrectomy of a horseshoe kidney with renal-cell carcinoma.

A 55-year-old man had a solid tumor in the right part of a horseshoe kidney. He had previously undergone open cholecystectomy and appendectomy with panperitonitis. Retroperitoneoscopic nephrectomy was performed, with rapid recovery and good short-term results. This appears to be the first case of endoscopic surgery on a horseshoe kidney using ultrasonic shears for cancer.

Carcinoma, Renal Cell↗
PubMed2003

Bacterial lipopolysaccharide-induced expression of the IkappaB protein MAIL in B-lymphocytes and macrophages.

Molecule possessing ankyrin-repeats induced by lipopolysaccharide (MAIL), a recently cloned nuclear IkappaB protein induced by lipopolysaccharide (LPS) stimulation in lymphoid organs, is involved in the regulation of inflammatory responses. The present in situ hybridization and immunohistochemical analyses revealed the distinct expression of the MAIL mRNA and protein in B-lymphocytes of the white pulp of the spleen and cortical lymphoid follicles of lymph nodes in LPS-injected mice. MAIL signals were also localized in F4/80-positive macrophages in these organs. LPS clearly induced MAIL expression in cultured B-lymphocytes and monocytes/macrophages, but only faintly so in T-lymphocytes, fibroblasts, and endothelial cells. MAIL was also induced by inflammatory cytokines such as interleukin-1 and -6, and tumor necrosis factor in cultured cells. Northern blot, Western blot, and in situ hybridization analyses showed that the major expression product of the Mail gene was a long splicing variant (MAIL-L) rather than a short one, both in lymphoid organs and cultured cells. These results collectively indicate that LPS induces MAIL-L predominantly in B-lymphocytes and macrophages.

Adaptor Proteins, Signal Transducing↗
PubMed2003

[A case of advanced breast cancer with multiple lung, bone and lymph node metastases successfully treated with 5'-DFUR alone].

A 78-year-old female patient with locally advanced breast cancer, bleeding from a deep ulcer, and with multiple bone, lung and distant lymph node metastases was successfully treated with 5'-DFUR alone. She was at first treated with docetaxel + 5'-deoxy-5-fluorouridine (5'-DFUR) + tamoxifen, but they were discontinued because of deep venous thrombosis. She underwent simple mastectomy due to periodically recurring bleeding and infection. After administration of 5'-DFUR alone, a decrease of abnormal accumulation on a bone scintigram was obtained in 10 months, the lung metastases were diagnosed as being in complete remission (CR) at 11 months and the lymph node metastases were diagnosed as being in CR at 14 months. These states have continued to the present. The administration of 5'-DFUR alone is suitable for tumor dormancy in some cases.

Aged↗
PubMed2002

Vascularized islet-cell transplantation in miniature swine. I. Preparation of vascularized islet kidneys.

BACKGROUND: Whereas clinical pancreatic transplantation has been highly successful in correcting the hyperglycemia of insulin-dependent diabetes mellitus (type 1), the results of islet transplantation have been disappointing. This discrepancy may be because of, at least in part, nonspecific loss of islets during the time required for revascularization. To test this hypothesis, we have designed composite kidney grafts containing vascularized autologous islets that can be used to compare the engraftment potential of vascularized versus nonvascularized islet tissue. METHODS: (1) Islet-cell isolation: miniature swine underwent either partial pancreatectomy to isolate autologous islets or total pancreatectomy to isolate minor antigen-mismatched islets. Islets were purified from excised pancreatic tissue by enzymatic digestion and discontinuous density gradient purification. Isolated islets were cultured for 3 days before transplant. (2) Creation of vascularized islet kidneys (IK): autologous islets alone (n=6), minor-mismatched islets alone (n=3), and minor-mismatched islets plus simultaneous autologous thymic tissue (n=3) were transplanted beneath the renal capsule of juvenile miniature swine. Minor antigen-mismatched islets were also transplanted into both the vascularized thymic graft of a thymokidney (to produce a thymo-islet kidney [TIK]) and the contralateral native kidney (n=3) and both the host thymus and beneath the renal capsule (n=2). All recipients receiving minor-mismatched islets were treated with a 12-day intravenous (IV) course of either cyclosporine A (CsA) at 10 mg/kg per day or FK506 at 0.15 mg/kg per day. (3) Assessment of Function: to evaluate the function of the transplanted islets, three animals bearing TIK and IK underwent total pancreatectomy 3 months following islet transplantation. RESULTS: (1) Islet-cell yields: an average of 254,960+/-51,879 (4,452+/-932 islet equivalents [IEQ]/gram of pancreas) and 374,410+/-9,548 (4,183+/-721 IEQ/gram of pancreas) viable islets were obtained by partial pancreatectomy and complete pancreatectomy, respectively. (2) Creation of IK: autologous islets engrafted indefinitely, whereas recipients of minor-mismatched islets alone rejected the islets within 2 months. However, when minor-mismatched islets were implanted into both the thymokidney and the contralateral kidney of animals bearing a thymokidney, the islets engrafted indefinitely in both sites (>3 months). Simultaneous implantation of islets into the host thymus and under the renal capsule also led to permanent engraftment of minor-mismatched islets. (3) Function of vascularized islets: three animals with both a TIK and an IK in place for 3 months underwent total pancreatectomy. All three animals maintained normoglycemia thereafter. In two of these animals, the IKs were removed 2 months after the pancreatectomy, and in both cases normoglycemia was maintained thereafter by the TIK. CONCLUSIONS: The implantation of islets beneath the autologous renal capsule permitted the establishment of a vascular supply and thereby supported normal islet-cell growth and function. The presence of thymic tissue beneath the autologous renal capsule facilitated the engraftment of minor-mismatched islets, and such grafts achieved results similar to autologous islet transplants. Therefore, the ability to create vascularized islet grafts may provide a strategy for successful islet transplantation across allogeneic and potentially across xenogeneic barriers.

Animals↗
PubMed2002

Autologous graft-versus-host disease in a porcine bone marrow transplant model.

BACKGROUND: Autologous graft-versus-host disease (autoGvHD) has been reported in patients and can be induced in rodents by syngeneic bone marrow transplantation (BMT) and a brief administration of cyclosporine A (CsA). To our knowledge, there is no previous large-animal model for this phenomenon, nor is there a model in which autoGvHD occurs spontaneously after autologous bone marrow transplant (autoBMT) in the absence of CsA induction. During our studies of autoBMT in miniature swine, performed without CsA treatment, we noted the frequent occurrence of a rash consistent with autoGvHD. We hypothesized that the extent of peripheral blood contamination of the bone marrow (BM) inoculum before transplant may have correlated with the incidence of such autoGvHD. METHODS: Retrospective analysis of the prevalence of autoGvHD in swine was carried out in all animals that had become engrafted after autoBMT in our laboratory. Subsequent prospective experiments attempted to induce autoGvHD by transplanting autologous BM enriched with autologous peripheral blood into lethally irradiated animals. RESULTS: Our data showed that autoGvHD frequently occurs in swine after autoBMT, with the most severe cases of the disease occurring in animals with the highest levels of peripheral blood contamination of the BM inoculum. Furthermore, mixed lymphocyte reactions (MLR) against self antigens were positive only in animals affected by autoGvHD. CONCLUSION: These findings provide the first evidence for autoGvHD without the use of CsA in a preclinical BMT model. The role of autologous T cells needs further delineation but may help to explain the occasional occurrences of autoGvHD that have been reported in humans after autoBMT.

Animals↗
PubMed2002

Vascularized thymic lobe transplantation in miniature swine: I. Vascularized thymic lobe allografts support thymopoiesis.

BACKGROUND: Vascularized thymokidney transplants have previously been shown to induce tolerance across major histocompatibility complex barriers. The ability to perform vascularized thymic lobe transplantation could permit such tolerance to be induced with any cotransplanted solid organ or tissue. For this reason, we have developed a technique for vascularized thymic lobe transplantation in miniature swine. METHODS: Thymic vessels (n=2) were anastomosed to the carotid artery and the external jugular vein of naïve minor-mismatched recipients treated with a 12-day course of cyclosporine A (10 mg/kg/day). Graft survival and thymopoiesis were assessed by histology, immunohistochemistry, and fluorescence-activated cell sorting. Allele-specific antibodies 74-12-4 and pig allelic antigen (PAA) were used to distinguish donor and recipient cells. RESULTS: Allografts showed intact cortical and medullary structure posttransplantation, without evidence of rejection or ischemia. Recipient thymocytes repopulated the donor cortical thymus by POD30 and increased in the cortex and medulla by POD60. CONCLUSIONS: Our study demonstrates the technical feasibility of vascularized thymic lobe transplantation and the support of thymopoiesis by such transplants in a large animal model. This technique may offer a novel strategy to induce transplant tolerance across allogeneic and xenogeneic barriers, and to support long-term thymopoiesis in immunodeficient hosts.

Animals↗
PubMed2002

Correlation between microbubble contrast-enhanced color doppler sonography and immunostaining for Kupffer cells in assessing the histopathologic grade of hepatocellular carcinoma: preliminary results.

PURPOSE: The aim of this study was to determine the histopathologic grades of hepatocellular carcinomas (HCCs) on the basis of the presence of Kupffer cells, using color Doppler sonography with the liver-specific microbubble contrast agent Levovist. METHODS: Color Doppler sonograms generated by stimulated acoustic emission were obtained 7 minutes after intravenous injection of 5 ml of Levovist (300 mg/dl) in patients with histopathologically confirmed HCCs. CT scans were also obtained and evaluated, and hematoxylin and eosin staining for morphologic examination and immunostaining (anti-CD68) for detecting Kupffer cells were performed for confirmation of the sonographic findings. RESULTS: Eighteen tumors had a defect in the color Doppler signal (color void) that corresponded with the baseline gray-scale image of the tumor. On histopathologic examination, these 18 tumors were all found to be either poorly or moderately differentiated HCCs with either a marked reduction in the number of or the absence of Kupffer cells. The remaining 2 tumors showed color signals. Histopathologic examination of these 2 tumors disclosed well-differentiated components within the tumors, with Kupffer cells in the tumor tissue. CONCLUSIONS: Color Doppler sonography using a liver-specific microbubble ultrasound contrast agent appears to reflect the histopathologic features of HCCs and may thus be useful for differentiating liver tumors and determining a treatment strategy.

Adult↗
PubMed2002

Canine mitochondrial uncoupling proteins: structure and mRNA expression of three isoforms in adult beagles.

Uncoupling proteins (UCPs) are members of the mitochondrial transporter family that dissipate the proton gradient as heat more than via ATP synthesis. In the present study, nucleotide and amino acid sequences of UCPs 1, 2 and 3 of a dog were determined, and their mRNA expression in various peripheral tissues was examined. The sequences were highly (76-97%) homologous to those of other species. Although lower homologies (60-74%) were found when compared among the three canine UCPs, their deduced amino acid sequences had some common domains, such as three mitochondrial carrier protein motifs, six transmembrane alpha-helix domains, and putative purine nucleotide binding domains. By Northern blot analyses, UCP1 mRNA was not detected in any tissues examined. UCP2 mRNA was expressed in most tissues, particularly abundantly in adipose tissue, spleen and lung. Two sizes of UCP3 mRNA were found exclusively in heart and skeletal muscle. These results suggest that canine UCPs have uncoupling activity, and are involved in the regulation of metabolic heat production and/or energy expenditure, as do those of other species.

Adipose Tissue↗
PubMed2002

Modulation of the in vivo primate anti-Gal response through administration of anti-idiotypic antibodies.

Polyclonal anti-idiotypic antibodies (AIA) were generated against human Gal alpha 1,3Gal antibodies (anti-Gal) isolated from a single donor. Specificity of the AIA was demonstrated by selective binding to anti-Gal antibodies (Ab) and absence of reactivity to non-Gal Ab. The idiotopes identified by AIA were present on anti-Gal Ab from all of the human samples evaluated (n=59) as well as on pooled samples, demonstrating that a restricted number of dominant idiotopes characterized the human anti-Gal Ab response. Furthermore, the AIA had cross-species reactivity with baboon serum samples (n=19), suggesting that the overall shape of the anti-Gal Ab combining site is conserved throughout the Old World primates and providing additional evidence of the limited heterogeneity of the anti-Gal Ab repertoire. In order to evaluate the potential effect of AIA in the modulation of the anti-Gal response in vivo, a baboon was injected with repeated doses of the purified AIA. Following AIA treatment, new Ab were generated that reduced Ab-mediated cytotoxicity to porcine cells. Furthermore, administration of the AIA to a baboon prolonged the survival of intravenously infused pig hematopoietic cells when compared with their survival in a control baboon that did not receive prior AIA treatment but underwent a similar conditioning regimen.

Animals↗
PubMed2002

Recurrence of renal cell carcinoma more than 5 years after nephrectomy.

OBJECTIVES: We evaluated clinical features and predictive factors for the recurrence of renal cell carcinoma (RCC) developing more than 5 years after nephrectomy. METHODS: We retrospectively reviewed 239 patients with RCC who underwent surgery for the primary lesion. To identify factors that affected recurrence more than 5 years after nephrectomy (delayed recurrence) and its clinical outcomes, we performed a multivariate analysis using Cox's proportional hazards model and a survival study. RESULTS: Recurrence developing within 5 years after nephrectomy (early recurrence) was found in 57 patients and delayed recurrence in 11 patients. The multivariate analysis revealed no clinical and pathologic features influencing delayed recurrence in 114 patients who survived more than 5 years after nephrectomy without having early recurrence. The patients with delayed recurrence showed better clinical outcomes than those with early recurrence when the rate was determined from the time of recurrence. CONCLUSIONS: Although delayed recurrence is not a rare event for patients with RCC, no clinical and pathologic factors at the time of the initial treatment can predict the recurrence. Patients who are free of recurrence for more than 5 years after surgery for a primary lesion should be carefully followed up for delayed recurrence.

Adult↗
PubMed2002

Does transurethral resection of the prostate facilitate detection of clinically significant prostate cancer that is missed with systematic sextant and transition zone biopsies?

BACKGROUND: A prospective study was conducted to determine whether transurethral resection of the prostate (TURP) facilitates detection of prostate cancer that is missed with systematic sextant biopsies associated with transition zone (TZ) biopsies. METHODS: A total of 139 consecutive patients underwent transperineal TZ biopsies of each lobe in addition to a transrectal systematic sextant peripheral zone (PZ) biopsy. Patients whose biopsies were negative for cancer received TURP for relief of lower urinary tract obstruction when indicated. RESULTS: Cancer was detected in biopsy specimens of 40 patients. Of these cancers, 18 originated in the PZ alone and 22 were located both in the TZ and the PZ. No cancers were detected in the TZ alone. Of 99 patients who were proven not to have cancer by the biopsies, 18 were indicated for TURP. Five of these patients (28%) had cancer in the resected tissues. All cancers were clinically organ confined and their Gleason sum scores were 2-5. Cancer-positive chips accounted for less than 10% of all resected specimens. Of the 66 patients with negative biopsies and without indication for TURP, four (6%) were revealed to have an elevation of the serum PSA level during follow up. They were later proven to have cancer by a second biopsy. CONCLUSION: Routine use of TZ biopsy is not warranted for detection of cancer. Transurethral resection of the prostate can detect cancers in patients with negative PZ and TZ biopsies. However, cancers detected by TURP may not always be clinically significant and only four of 66 patients who were not indicated for TURP and received a close follow up were later found to have cancer, although their follow-up period was short. Thus, it still remains to be elucidated whether TURP is necessary for all patients with negative biopsies of the prostate.

Aged↗