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Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 505 records · Page 28Linked to original sources
PubMed1996

Serum concentrations of basic fibroblast growth factor in collagen diseases.

BACKGROUND: Basic fibroblast growth factor (bFGF), a cytoplasmic polypeptide growth regulator that induces endothelial cell and fibroblast proliferation, is produced by endothelial cells and skeletal muscle. OBJECTIVE: We hypothesized that this factor is involved in fibrotic changes in muscle and skin in collagen diseases. METHODS: The serum level of bFGF was measured in 74 patients with systemic sclerosis, 12 with systemic lupus erythematosus, 33 with dermatomyositis, 13 with Raynaud's disease, and 20 control subjects. RESULTS: bFGF was undetectable in the serum of normal persons, but detectable levels were found in 31 of 74 patients with systemic sclerosis and 7 of 33 patients with dermatomyositis. Elevated serum bFGF level was correlated with an elevated plasma endothelin level and anticentromere antibody in patients with systemic sclerosis. An elevated serum bFGF level correlated with lung fibrosis and an elevated creatine kinase level in the patients with dermatomyositis. CONCLUSION: Measurement of the serum bFGF level may be useful to detect vascular damage in patients with systemic sclerosis and muscule fibrosis in patients with dermatomyositis.

Adolescent↗
PubMed1996

Expression of PDGF, IGF-II, bFGF and TGF-beta 1 in pulmonary adenocarcinoma.

Effects of the expression of the platelet-derived growth factor (PDGF), insulin-like growth factor-II (IGF-II), basic fibroblast growth factor (bFGF) and transforming growth factor (TGF)-beta 1 were studied individually and in combinations with the clinicopathologic features and prognosis of pulmonary adenocarcinoma using paraffin embedded tissue specimens. Tumor sections from 90 patients with pulmonary adenocarcinoma were stained immunohistochemically for PDGF, IGF-II, bFGF and TGF-beta 1 by the ABC method. The survival rate was worse in patients in whom each of the four growth factors was expressed than in those where growth factors were not expressed. The reduced expression of the four growth factors correlated with less tumor aggressiveness and better prognosis of pulmonary adenocarcinoma.

Adenocarcinoma↗
PubMed1996

A case of ovarian carcinoma with production of granulocyte colony-stimulating factor.

A 60-year-old female with ovarian carcinoma showed marked leucocytosis. After exploratory laparotomy she had received carboplatin-based chemotherapy, but she died of respiratory failure. In this case the immunohistochemical examination of the tumour cells showed partial-positive staining for anti-G-CSF monoclonal antibody in addition to the elevation of the serum G-CSF concentration. This case is the first report of an ovarian carcinoma producing G-CSF.

Adenocarcinoma↗
PubMed1996

Autoantibodies to mitochondrial 2-oxo-acid dehydrogenase complexes in localized scleroderma.

Sera from patients with localized scleroderma frequently produce cytoplasmic staining by indirect immunofluorescence, although the antigen remains to be determined. We studied the prevalence, antigen specificity and associated clinical characteristics of anti-cytoplasmic antibodies in localized scleroderma. Serum samples from 60 patients with localized scleroderma were examined by indirect immunofluorescence analysis and immunoblotting. By immunofluorescence analysis on HEp-2 cell substrate, seven of 60 (12%) patients were shown to be positive for anti-cytoplasmic antibodies. Among these, six patients with generalized morphea had anti-mitochondrial antibodies as shown by immunoblotting: they showed reactivity with the E2 component of pyruvate dehydrogenase complex (PDC), with protein X, and with the E2 component of alpha-oxo-glutarate dehydrogenase complex, while two of them showed reactivity with PDC-E1 alpha. One of these patients who was positive for anti-PDC-E1 alpha antibody showed laboratory abnormalities, suggesting the presence of primary biliary cirrhosis. The age of disease onset was significantly higher in these six patients than in those without anti-mitochondrial antibodies. Furthermore, five of them were classified into generalized morphea with multiple plaque lesions but without linear lesions (multiple plaque type). These observations suggest that major antigens for anti-cytoplasmic antibodies in patients with localized scleroderma are mitochondrial enzymes, 2-oxo-acid dehydrogenase complexes. Patients with anti-mitochondrial antibodies may comprise a unique subset of localized scleroderma designated multiple plaque type of generalized morphea of older onset.

Adolescent↗
PubMed1996

Measurement of anticardiolipin antibodies by ELISA using beta 2-glycoprotein I (beta 2-GPI) in systemic sclerosis.

In order to determine the prevalence and clinical significance of beta 2-GPI-dependent anticardiolipin antibodies (beta 2-GPI/aCL) in patients with systemic sclerosis (SSc), serum samples from 80 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), and 120 healthy control subjects were examined by ELISA using purified beta 2-GPI. IgG isotype beta 2-GPI/aCL was present in eight of 80 patients with SSc (10%), and the presence of beta 2-GPI/aCL IgG was significantly correlated with the presence of isolated pulmonary hypertension (PH). Furthermore, levels of beta 2-GPI/aCL IgG were significantly correlated with levels of mean pulmonary arterial pressure. These data suggest that IgG isotype beta 2-GPI/aCL might be a serological indicator of the severity of PH in patients with SSc.

Antibodies, Anticardiolipin↗
PubMed1996

Changes in M-CSF-like activity during chicken embryonic development.

We have established a method for separation of chicken bone-marrow cells using Percoll density gradient centrifugation, and have developed a new method for determining chicken M-CSF-like activity employing a liquid culture. Using this method, we determined M-CSF-like activities in egg yolk, chorioallantoic fluid (CAF) and amniotic fluid (AmF), and studied the effects of M-CSF on development of chicken embryos. M-CSF-like activity in egg yolk was at a high level before the incubation of the egg; it began to decrease on the third day of incubation and rapidly decreased on the fourth day, and no significant activity was detected after the tenth day of incubation. M-CSF-like activity in CAF was very low, and it exhibited almost no change during development. No M-CSF-like activity was detected in AmF throughout the experimental period.

Allantois↗
PubMed1996

Clonal dominance of human autologous cytotoxic T lymphocytes against gastric carcinoma: molecular stability of the CDR3 structure of the TCR alphabeta gene.

In our previous study, RT-PCR suggested that cytotoxic T lymphocyte (CTL) clones may specifically recognize human autologous gastric signet ring cell tumor (HST2) by using TCR products of Valpha7 and Vbeta20 subfamilies. In this report, we first determined the TCR nucleotide sequences of one such CTL from patient's peripheral blood lymphocytes (PBL), the PBL were newly stimulated with a mixed lymphocyte-autologus tumor cell (HST2) culture (MLTC) and cytotoxic T cell lines, such as HPBL3x, were obtained. RT-PCR and the nucleotide sequence data indicated that HPBL3x also showed TCR Valpha7 and Vbeta transcripts, and that HPBL3x TCR was composed of the exact same CDR3 gene structures as those of the TcHLT2 clone. T cells with same TCR structures were also detected in patient's non-treated peripheral blood, although they were infrequent. These data indicated that functional cytotoxic T cells with these distinct CDR3 equivalent structures were the dominant effector cells against HST2 autologous tumor cells. Moreover, the highly dominant and reproducible clonal expansion of T cells bearing heterodimeric TCR with identical variable, N diversity and constant region structures suggest that the molecular nature of governing antigenic peptide to TcHDT2 may be stable and perhaps immunologically dominant in the interaction between CTL and HST2 autologous tumor cells.

Amino Acid Sequence↗
PubMed1996

Alterations in activity of protein tyrosine phosphatase SH-PTP1 in autoimmune MRL/mpj-lpr/lpr mice.

Activities of protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) in autoimmune MRL/MpJ-lpr/lpr mice (lpr mice) were measured and compared with the activities in the tissues from MRL/MpJ-+/+ mice (+/+ mice) as the control. In the spleen and liver, PTK activities in cytosol and membrane fractions were about 1.7- and 1.3-fold, respectively, higher in lpr mice than +/+ mice. PTP activities in cytosol and membrane fractions from lpr mice were 1.7- and 1.3-fold, respectively, higher in spleen, and 2.5- and 1.3-fold, respectively, higher in liver compared with those of the controls. These results demonstrate that the mutation of lpr gene resulted in elevation of PTK and PTP activities. Then, we measured the amounts and activities of SH-PTP1, a cytosolic PTP playing a crucial role in intracellular signaling from Fas antigen. The amounts of SH-PTP1 were about 4-fold larger in thymus, spleen, and lymphnodes than in liver, but there was no marked difference in the amounts between lpr and +/+ mice. On the other hand, activity of SH-PTP1 was definitely lower in lpr spleen and lymphnodes than +/+ spleen, but several times higher in lpr liver than +/+ liver. Tyrosine phosphorylation levels of SH-PTP1 in spleen of lpr and +/+ mice were similar. However, in liver, it was less phosphorylated in lpr than in +/+ mice. This hypophosphorylation might cause the activation of SH-PTP1 activity in lpr liver.

Animals↗
PubMed1996

Immunohistochemical detection of basic fibroblast growth factor as a prognostic indicator in pulmonary adenocarcinoma.

The expression of basic fibroblast growth factor (bFGF) was studied immunohistochemically in tissue specimens from 157 patients with pulmonary adenocarcinoma. Tumor cells that expressed bFGF were found in 89 patients (74%). The expression of bFGF was correlated with T and M in the TNM classification, disease stage and curability. The 5-year survival rate was 24% in bFGF-positive patients but 66% in bFGF-negative patients, the difference being significant (P<0.01). The 5-year survival rate of patients with stage I disease was 73% in those who were bFGF-positive but 88% in those who were bFGF-negative, the difference being significant (P<0.05). Multivariate analysis showed that the expression of bFGF was significantly related to prognosis. These findings suggest that bFGF plays an important role in tumor progression and that its expression may be a useful prognostic indicator for pulmonary adenocarcinoma.

Adenocarcinoma↗
PubMed1996

Connective tissue growth factor gene expression in tissue sections from localized scleroderma, keloid, and other fibrotic skin disorders.

Connective tissue growth factor (CTGF) is a novel peptide that exhibits platelet-derived growth factor-like activities and is produced by skin fibroblasts after activation with transforming growth factor-beta. Coordinate expression of transforming growth factor-beta followed by CTGF during wound repair suggests a cascade process for control of tissue regeneration. We recently reported a significant correlation between CTGF mRNA expression and histologic sclerosis in systemic sclerosis. To confirm the relation between CTGF and skin fibrosis, we investigated CTGF gene expression in tissue expression in tissue sections from patients with localized scleroderma, keloid, other sclerotic skin disorders using nonradioactive in situ hybridization. In localized scleroderma, the fibroblasts with positive signals for CTGF mRNA were scattered throughout the sclerotic lesions with no preferential distribution around the inflammatory cells or perivascular regions, whereas the adjacent nonaffected dermis was negative for CTGF mRNA. In keloid tissue, the fibroblasts positive for CTGF mRNA were diffusely distributed, especially in the peripheral expanding lesions. In scar tissue, however, the fibroblasts in the fibrotic lesions showed partially positive signals for CTGF mRNA. In eosinophilic fasciitis, nodular fasciitis, and Dupuytren's contracture, CTGF mRNA was also expressed partially in the fibroblasts of the fibrotic lesions. Our findings reinforce a correlation between CTGF gene expression and skin sclerosis and support the hypothesis that transforming growth factor-beta plays an important role in the pathogenesis of fibrosis, as it is the only inducer for CTGF identified to date.

Adolescent↗
PubMed1996

Inhibition of natural killer cell cytotoxicity by cell growth-related molecules.

Certain MHC class I molecules on target cells are known to inhibit the cytotoxic action of NK cells. By using monoclonal antibody (mAb) Cho-1, we have found inhibitory non-MHC class I cell surface molecules that are noncovalently-associated with 200 kDa and 40 kDa antigens. Poly I-C-induced rat NK cells were not cytotoxic to rat fetus-derived fibroblast WFB cell line. In contrast, NK cells were cytotoxic to H-ras oncogene-induced transformants of WFB, W14 and W31. FACS analysis indicated that mAb Cho-1 reacts with WFB, but not with W14 and W31 cells. Thus, this antigen may disappear concomitantly with cell growth and transformation. Cho-1 antigens were also expressed on other NK-resistant lines, such as mouse BALB3T3 fibroblast, EL-4 lymphoma and human fibroblast HEPM. However, they were not expressed on NK-sensitive mouse YAC-1 and H-ras transformant (Brash) of BALB3T3 cells. Furthermore, treatment of target cells with IFN-gamma clearly induced the cell surface expression of Cho-1 antigens, and conferred a resistance to NK cytolysis on target cells. These data strongly suggest that Cho-1 antigen expression may correlate with target cell susceptibility to NK cells. Indeed, treatment of NK-resistant WFB as well as HEPM cells with F(ab')2 fragments of mAb Cho-1 resulted in the acquisition of susceptibility to NK cytolysis. Cho-1 antigens may be novel molecules that regulate the NK resistance of cells.

Animals↗
PubMed1996

Establishment and characterization of human gastric carcinoma lines with high metastatic potential in the liver: changes in integrin expression associated with the ability to metastasize in the liver of nude mice.

There is a need to establish animal models which are suitable for investigation of human gastric cancer metastasis to the liver. To this end, a human gastric carcinoma line, AZ521 was injected into the spleens of nude mice. Cells from the few liver metastatic foci of injected AZ521 were expanded "in vitro" and subsequently injected into the spleens of nude mice. By repeating these procedures three times, we were able to obtain a cell line, designated as AZ-H3c, with high metastatic potential in nude mice. Liver metastasis developed in 15 of 21 (71%) animals injected with AZ-H3c, but only in 14% of those injected with parental AZ521. Further, AZ-H3c caused faster tumor development than did AZ521. However, the primary AZ-H3c tumors and liver metastatic AZ-H3c tumors showed essentially the same histological appearance. We also analyzed the cell surface expression of adhesion molecules. The data showed that the expression of VLA-1, VLA-2, VLA-3, VLA-4, VLA-5 was enhanced in AZ-H3c. In contrast, the expression of VLA-6, (alpha(v)beta3), E-cadherin, ICAM-1 and LFA-1 was reduced in this high-metastatic line. These results suggest that (beta1) integrins play an important role in the liver metastasis of human gastric carcinoma cells. Our high-metastatic line should be useful for studies aimed at the prevention of liver metastasis.

Animals↗
PubMed1996

Veno-occlusive disease of the liver following bone marrow transplantation: a clinical-pathological study of autopsy cases.

A total of 28 patients with leukemia underwent intensive therapy with megadose chemotherapy and stem cell transplantation. Of 16 patients who had busulfan therapy, 2 developed the clinical syndrome of veno-occlusive disease of the liver (VOD) characterized by progressive abnormalities in liver function, abdominal pain, and ascites. Postmortem findings showed VOD of the central and sublobular hepatic vein. Immunohistochemical analysis using anti-actin and CD34 mAb was employed in an attempt to clarify the process of fibrosis. Actin positive cells had accumulated around the central vein. Ito cell activation might be responsible for secondary fibrosis following endothelial injury. We report autopsy findings and immunohistochemical results.

Adolescent↗
PubMed1996

Interaction between cell-surface-expressed 70-kilodalton heat shock protein-like antigen and CD3(+)4(-)8(-) killer T cells.

The 70-kilodalton heat shock proteins may be expressed on the cell surface by an unknown mechanism and may interact with CD3+4-8- T cell receptor-alpha beta-killer (DNT) cells. In this interaction, certain cellular nascent or mutant peptides may be important (the complexes of 70-kilodalton heat shock protein and cellular peptides directly interact with DNT cells). The results imply that the interaction between 70 kilodalton heat shock proteins and DNT cells may also work in graft rejection. By using antibodies that react with the cell surface-expressed 70-kilodalton heat shock proteins, one may overcome graft rejection.

Animals↗
PubMed1996

Non-major histocompatibility complex antigen class I-regulatory molecule for cytotoxicity by natural killer cells.

The mechanism of the cytotoxicity by natural killer (NK) cells is not known. It is speculated that there exist several positively regulated and negatively regulated target molecules expressed on the target cell surface. Although one of the latter is considered to be major histocompatibility complex antigen (MHC) class I, in this study we described a novel non-MHC class I molecule that may negatively regulate the NK cytotoxicity. This antigen is defined by monoclonal antibody Cho-1 and is composed of noncovalently associated antigens that are 40 and 200 kilodaltons in molecular size. The expression of this antigen is reduced along with the cell growth induced by growth factors and/or oncogenes. Thus, Cho-1-defined antigen appears to be involved as one of the resistant molecules in the cytotoxic mechanism of NK cells.

Animals↗