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Biomedical subjects

T Yoshiki

Publications and source records attributed to T Yoshiki.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Retroviruses and autoimmune diseases].

Various genetic factors and environmental factors are intricately intertwined in the pathomechanism of autoimmune diseases. Retroviruses, represented by HTLV-I and HIV, are known to relate to autoimmune disorders. However, the pathogenetic role of retrovirus and the relationship between retrovirus and autoimmune diseases are not clear. We found autoimmune diseases, such as arthritis, myositis, arteritis, dermatitis and T cell abnormality in HTLV-I transgenic rats, and studied the pathomechanism of the diseases by cell transfer experiments. Here we describe the relationship between retrovirus and autoimmune diseases and suggest that retrovirus plays a important role in the autoimmune diseases.

Animals↗
PubMed1998

Promotion of early osteoclastogenesis and B lymphopoiesis in the bone marrow of transgenic rats with the env-pX gene of human T-cell lymphotropic virus type I.

Human T-cell lymphotropic virus type I (HTLV-I) is associated with various clinical disorders including adult T cell leukemia, myelopathy, arthropathy. Hypercalcemia resulting from osteoclast activation and a variety of hematopoietic abnormalities have been also observed in HTLV-I infected patients, however, precise mechanism about initial trigger(s) prior to presenting symptoms is still unknown. In this study, to assess effects of HTLV-I on hematopoiesis, we analysed characteristics of early hematopoietic precursors in HTLV-I env-pX transgenic rats. Progenitor cells for osteoclasts were significantly increased even in the marrow of asymptomatic env-pX rats. Progenitors for B cells were also highly enriched, while colony forming cells (CFC) elicited by GM-CSF(CFU-GM) and M-CSF(CFU-M) were comparable to normal littermates. Following arthritis in env-pX transgenic rats, osteoclastogenesis was further augmented and the CFCs were increased. Bone marrow cells carrying adjuvant-induced arthritis retained a constant number of progenitors for osteoclast and B lymphocytes, whereas the number of CFU-GM and CFU-M increased. These results indicate that the env-pX transgene affect early stages of osteoclast and B-cell lineages prior to developing diseases, in contrast, an increase of the CFCs was caused indirectly by arthritis. This study provides a novel standpoint for the mechanisms of pathogenesis by HTLV-I.

Animals↗
PubMed1998

Persistent and secondary adenovirus-mediated hepatic gene expression using adenovirus vector containing CTLA4IgG.

Adenovirus vectors can transfer recombinant genes efficiently into a wide variety of cells in vivo, but have serious limitations: gene expression is transient and secondary gene transfer is inefficient or impossible because of cellular and humoral immune responses against adenovirus-transduced cells. To solve these limitations, we have constructed an adenovirus vector, Adex1CACTLA4IgG, that expresses CTLA4IgG molecules. After in vivo administration of Adex1CACTLA4IgG (9.0 x 10(9) PFU), the peak level of serum CTLA4IgG was 29.8 mg/ml on day 4. The serum CTLA4IgG concentration gradually fell but was still 5.7 mg/ml on day 90. However, the serum concentration of CTLA4IgG was elevated after a second administration of Adex1CACTLA4IgG. The production of antibody against adenovirus was completely prevented after treatment with Adex1CACTLA4IgG. In addition, coadministration of Adex1CALacZ with Adex1CACTLA4IgG induced persistent hepatic expression of beta-Gal molecules, while administration of Adex1CALacZ alone induced transient expression of beta-Gal molecules. More importantly, on day 160 a secondary challenge with Adex1CALacZ was possible in mice treated with Adex1CALacZ plus Adex1CACTLA4IgG. Thus, we have demonstrated that (1) gene expression of a recombinant adenovirus, Adex1CACTLA4IgG, is persistent in liver and secondary administration of this adenovirus is possible, (2) coadministration of Adex1CACTLA4IgG virus with another adenovirus, AdexCALacZ, prolongs AdexCALacZ-mediated gene expression, and (3) Adex1CACTLA4IgG is useful for secondary challenge with Adex1CALacZ.

Abatacept↗
PubMed1998

Interleukin-6 produced by pancreatic carcinoma cells enhances humoral immune responses against tumor cells: a possible event in tumor regression.

Production of interleukin-6 (IL-6) by human pancreatic carcinoma cells inversely correlates with potentials for blood-borne metastasis to the liver in nude mice. IL-6 cDNA was transfected to PCI-43, one of our cultured pancreatic carcinoma cell lines that does not produce IL-6 and generates numerous metastases to the liver. An IL-6 high-producer clone (PCI-43h) generated few metastases; IL-6 production thus has a direct effect on metastasis, whereas other transfectants (PCI-43l and PCI-43n), which are IL-6 low-, and IL-6 non-producers, respectively, did generate metastases. Tumor-reactive IgG, which mediated antibody-dependent cellular cytotoxicity (ADCC) in vitro, was detected in sera from recipient nude mice inoculated with PCI-43h but not in sera from mice given PCI-43l, PCI-43n or parent PCI-43. Tumor-reactive IgM was detected in sera from all mice, irrespective of inoculated PCI-43 species, with a slight augmentation being noted in PCI-43h-inoculated nude mice. Severe combined immunodeficiency (SCID) beige mice were then used as recipients for PCI-43 species, and tumorigeneity was examined by s.c. inoculation of a suboptimal number of PCI-43 transfectants (1 x 10(6)/0.1 ml). Only PCI-43h formed palpable masses in SCID beige mice, whereas it first grew to be palpable but subsequently became not palpable in nude mice, thereby revealing a dual action of tumor-derived IL-6. Thus, tumor-derived IL-6 confers growth promotion in SCID beige mice, while the same cytokine exhibits anti-tumorigenic functions, presumably through humoral immune responses, in nude mice.

Animals↗
PubMed1998

Expression of uroplakin Ib and uroplakin III genes in tissues and peripheral blood of patients with transitional cell carcinoma.

Uroplakins (UPs), urothelium-specific transmembrane proteins, are present only in urothelial cells. We have determined the nucleotide sequences of human UP-Ib and UP-III and synthesized specific primer pairs. The two UP genes were expressed in both cancerous and noncancerous urothelial taken from all patients examined by reverse transcription-polymerase chain reaction (RT-PCR). These genes were also detected in the peripheral blood of 3 patients with metastatic transitional cell carcinoma (TCC), but not in that from 9 patients with non-metastatic TCC or 3 healthy volunteers. The sensitivity of our assay was sufficient to detect one cancer cell in 5 ml of peripheral blood. Detection of UP gene-expression in blood by RT-PCR may provide helpful information for the diagnosis and management of TCC.

Adult↗
PubMed1998

Azathioprine-induced megaloblastic anemia with pancytopenia 22 years after living-related renal transplantation.

Macrocytosis and megaloblastic changes in the bone marrow are frequently seen in renal transplant recipients treated with azathioprine (Az). However, severe anemia is a rare side effect of Az. We recently observed a case of severe megaloblastic anemia with pancytopenia in a renal transplant recipient who had been receiving Az therapy for 22 years. The patient was a 46-year-old woman who had been administered Az and prednisolone at a dose of approximately 1.7 mg/kg and 0.17 mg/kg daily, respectively. A bone marrow aspiration revealed megaloblastic anemia with the depletion of myeloid cells and megakaryocytes. She did not have vitamin B12 or folate deficiency. Therefore, FK506 (tacrolimus), a macrolide produced by Streptomyces tsukubaensis, which acts directly on T cells and is known to have less myelosuppression than Az, was substituted for Az. Although the leukopenia improved, the anemia and thrombocytopenia did not improve in the short term. She developed dyspnea and severe subcutaneous bleeding of the right lower extremity due to knee contusions. Hemodialysis was started to treat her uremic state. Although it was impossible to evaluate the long-term effects of FK506 therapy for the pancytopenia in our case, the conversion from Az to a less myelosuppressive drug, such as FK506, should be considered in renal transplant recipients with severe myelosuppression caused by long-term Az treatment.

Anemia, Megaloblastic↗
PubMed1998

Tissue-specific high-level expression of human endogenous retrovirus-R in the human adrenal cortex.

In an attempt to clarify the biological nature of a human endogenous retrovirus (HERV), HERV-R, which is a single-copy type of HERVs and is conserved as a full-length viral sequence, the expression of HERV-R mRNA in normal autopsied systemic organs was examined by Northern blot analysis. The expression showed different levels among individuals, with the adrenal glands expressing the highest level of HERV-R among all organs tested, except for the placenta. In various adrenal tumors, HERV-R was expressed at high levels in all cortical adenomas but less so in pheochromocytomas. In situ hybridization revealed the expression of HERV-R to be localized in all layers of the adrenal cortex, but not in the medulla. This high-level expression of HERV-R in the adrenal cortex may possibly relate to differentiation and/or steroid production by adrenocortical cells.

Adrenal Cortex↗
PubMed1998

[Adenocarcinoma of the bladder 19 years after the augmentation ileocystoplasty: report of a case].

We report a case of adenocarcinoma of the augmented bladder 19 years after ileocystolasty. The patient was a 53-year-old man who underwent right nephrectomy and ileocystoplasty (Pyrah's method) for contracted bladder due to tuberculosis in 1965. In another hospital, transurethral resection (TUR) was performed against a tumor in the anastomotic site between the bladder and the ileal segment in 1996. Histopathological examination of the specimen obtained by TUR revealed poorly-differentiated mucinous adenocarcinoma. In our hospital, partial cystectomy with total resection of ileal segment and ileocystoplasty were performed. The tumors located in the anastomotic site between the bladder and ileal segment as well as in the ileal segment. Histopathological examination revealed poorly-differentiated mucinous adenocarcinoma. The patient has survived 12 months without any evidence of tumor recurrence. To our knowledge, this is the eighth case report in Japan.

Adenocarcinoma, Mucinous↗
PubMed1997

Molecular nature of a sperm acrosomal antigen recognized by HS-13 monoclonal antibody.

Among the numerous monoclonal antibodies generated against human sperm antigens, HS-13 monoclonal antibody was shown to react with an intra-acrosomal antigen from human, mouse and rat. In this study, HS-13 was used as the affinity ligand for the purification of the cognate antigen from human sperm by immunoaffinity chromatography. The purified cognate antigen from human sperm, designated as HSAg-13, was found to be a protein with a molecular weight of approximately 80 kDa on SDS-PAGE in the presence of reducing reagents. This monoclonal antibody was used as the probe to study the tissue distributions and developmental expression of the cognate antigen from human, mouse and rat by immunohistochemical assays. It was concluded that the antigen recognized by HS-13 antibody is highly sperm specific and found only in sperm and mature testis, but not in any other somatic tissues examined in human and mouse. The antigen was shown to be expressed at the postmeiotic stages of spermatogenesis in mouse and rat. By using indirect immunofluorescent staining assay, HS-13 was shown to react only with the methanol-fixed acrosome-intact sperm but not with the live sperm. Following calcium ionophore A23187 treatment, acrosome-reacted sperm showed either negative staining or residual staining in the equatorial region, suggesting the intra-acrosomal location of HSAg-13. The spontaneous acrosome reaction following overnight incubation in BWW medium resulted in a statistically significant decrease of antibody-stained human sperm. In view of excellent correlations for the scoring of acrosome-intact sperm with that of fluorescence-labeled Pisum sativum agglutinin (PSA) probe, HS-13 monoclonal antibody can be routinely used for monitoring sperm capacitation and acrosome reaction.

Acrosome↗
PubMed1997

c-erbB-2 oncoprotein: a potential biomarker of advanced prostate cancer.

BACKGROUND: Overexpression of the c-erbB-2 oncogene has been implicated in the development and/or prognosis of several human carcinomas, including that of the prostate. Recently, c-erbB-2 protein was found to be released in the circulation. The present study was undertaken to study the significance of serum c-erbB-2 protein determination in men with prostate cancer. METHODS: Serum c-erbB-2 protein determination was performed via immunoradiometric assay using two monoclonal antibodies that react with the extracellular domain of the protein. The study population consisted of 71 untreated prostate cancer patients. Of those, 33 with stage D2 disease entered a follow-up study. As control, serum c-erbB-2 protein levels were determined in 92 patients with benign prostatic hypertrophy. In addition, elevations of c-erbB-2 protein were examined in patients with various disease statuses: clinically well controlled (28 patients), disease progression (24 patients), and end-stage disease (17 patients). RESULTS: Elevation of serum c-erbB-2 protein level was observed in patients in advanced stages, such as stage D2 disease (30%), disease progression (42%), and end-stage disease (82.4%). In the follow-up study, patients with an elevated c-erbB-2 level had a significantly shorter interval to disease progression than did those with a normal level. CONCLUSIONS: The results suggest that c-erbB-2 can be used as a biomarker to identify a malignant subgroup in prostate cancer.

Biomarkers, Tumor↗
PubMed1997

Interleukin-1alpha regulates Thy-1 expression on rat vascular endothelial cells.

We recently reported that Thy-1, a surface molecule induced on the rat endothelium, regulates vascular permeability at sites of inflammation. Although the rat inferior vena cava (IVC) did not express Thy-1 in vivo, cultured endothelial cells from the IVC did express Thy-1, thereby suggesting that the expression was acquired during cultivation of the cells in vitro, possibly by autoactivation by cytokine-like substances. Interleukin (IL)-1alpha but not tumor necrosis factor (TNF)-alpha or interferon (IFN)-gamma was detected in culture supernatants of rat endothelial cells (REC) by ELISA. The production of IL-1alpha by REC was augmented by exogenously added IL-1alpha, thereby implying the presence of autocrine regulation by IL-1alpha. The unaltered expression of Thy-1 by exogenously added IL-1alpha suggests that Thy-1 expression on REC had already been maximally induced by autologous cytokines; the expression of Thy-1 on REC was lowered by inhibiting protein kinase C and by depleting IL-1alpha activity from culture supernatants. Although cytokine-like regulators, other than IL-1alpha, TNF-alpha, or IFN-gamma, produced by REC may also modulate the expression of Thy-1, it is at least in part mediated by IL-1alpha in vitro. Moreover, Thy-1 expression was induced on rat vascular endothelium at the subcutis where recombinant IL-1alpha was injected. The evidence indicates that IL-1alpha functions as one regulator responsible for the induction of Thy-1 on REC, in vitro as well as in vivo.

Animals↗
PubMed1997

Induced expression of Thy-1 molecules on dermal endothelial cells in skin allografts.

We obtained evidence in a foregoing study that inducible Thy-1 on vascular endothelial cells functions as a possible vascular permeability modulator in the rat. We now report on the regulation and function of endothelial Thy-1 in skin allograft rejection in the rat. While no obvious expression of Thy-1 antigen on the vasculature can be seen in normal organs, dermal endothelial cells do express Thy-1 during allogeneic skin graft rejection and Freund's complete adjuvant (FCA)-induced inflammation. The antigen was weakly induced on tubular epithelial, but not on endothelial cells during kidney allograft rejection, and not in FCA-induced inflammation of the kidney. In contrast, Thy-1 antigen was not induced in the rejected lung or in FCA-induced inflammation of the lung. This pattern of Thy-1 regulation was transcriptionally regulated. Administration of anti-Thy-1 antibodies generated increased vascular permeability in skin allografts, although this procedure did not modulate survival of the grafts.

Animals↗
PubMed1997

Gastrointestinal hepatoid adenocarcinoma: venous permeation and mimicry of hepatocellular carcinoma, a report of four cases.

AIMS: Four cases of hepatoid adenocarcinoma, three in the stomach, and one in the sigmoid colon, are presented to emphasize venous permeation and mimicry of hepatocellular carcinoma by metastatic liver nodules. METHODS AND RESULTS: Tumour cells in all cases extensively invaded vems, and intravenous tumour thrombi in two cases were grossly observed as anastomosing, worm-like cords up to 10 mm in diameter in the lesser omentum and mesentery in continuity with the primary mucosal lesions. The cytological features and trabecular architecture of the metastatic liver nodules in these subjects mimicked primary hepatocellular carcinoma. In a third case the tumour contained grossly visible bile in a metastatic lung nodule, but there was no evidence of bile production in the primary gastric or metastatic liver lesions. In the fourth case, detailed histopathological study revealed a gastric origin of the hepatoid adenocarcinoma, rather than primary hepatocellular carcinoma metastatic to the stomach, the initial diagnosis. CONCLUSIONS: These cases are reported here to draw attention to this rare variant of gastrointestinal adenocarcinoma, its mimicry of hepatocellular carcinoma when metastatic to the liver and other sites, and its propensity for venous permeation.

Adenocarcinoma↗
PubMed1997

A wide spectrum of collagen vascular and autoimmune diseases in transgenic rats carrying the env-pX gene of human T lymphocyte virus type I.

To investigate the pathogenesis of human T lymphocyte virus type I (HTLV-I)- related diseases, the env-pX gene of HTLV-I was introduced into the germline of inbred Wistar-King-Aptekman-Hokudai rats. A wide spectrum of collagen vascular diseases was evident in the transgenic rats, including chronic destructive arthritis similar to rheumatoid arthritis, necrotizing arteritis mimicking polyarteritis nodosa, polymyositis, myocarditis, dermatitis, and chronic sialoadenitis and dacryoadenitis resembling Sjögren's syndrome in humans. Thymic atrophy with the depletion of CD4 and CD8 double-positive thymocytes was also observed. In these animals, a number of autoantibodies, including high titers of rheumatoid factor, were present in the serum. We propose that the HTLV-I env-pX gene region may play a pathogenetic role in the development of collagen vascular and autoimmune diseases associated with autoimmune phenomenon.

Animals↗