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Biomedical subjects

H Goto

Publications and source records attributed to H Goto.

At least 271 records · Page 15Linked to original sources
PubMed1997

Positive correlation between levels of IL-1 or IL-2 and 1,25(OH)2D/25-OH-D ratio in synovial fluid of patients with rheumatoid arthritis.

The present study determined the levels in synovial fluid (SF) of vitamin D metabolites (1,25-dihydroxyvitamin D (1,25(OH)2D), 24,25-dihydroxyvitamin D (24,25(OH)2D) and 25-hydroxyvitamin D (25-OH-D)), and of the cytokines. We evaluated SF from 21 patients with rheumatoid arthritis (RA) and 6 patients with osteoarthritis (OA). The levels of vitamin D metabolites in SF, as determined by two different extraction methods, were significantly correlated (p < 0.05, n=7). The levels of 3 vitamin D metabolites were significantly higher in the RA SF than in OA SF (p < 0.05). The ratio of 1,25(OH)2D/25-OH-D in RA SF, which is presumed to reflect the activity of 25-OH-D-1-hydroxylase (1-OH-ase), was positively correlated with the levels of interleukin-1alpha (IL-1alpha), IL-1beta, and IL-2 in such SF, and was significantly higher than that in sera from RA patients. This suggests an important role for these cytokines in the activation of 1-OH-ase in RA synovium. The ratio of 24,25(OH)2D/25-OH-D, which is presumed to reflect 25-OH-D-24-hydroxylase (24-OH-ase) activity, was significantly correlated with 1,25(OH)2D levels only in RA SF, but not in sera from RA patients, suggesting a local regulation of vitamin D metabolism that 1,25-(OH)2D induces 24-OH-ase as in other target cells. Our observations suggested that 1,25(OH)2D and 24,25(OH)2D are produced locally from 25-OH-D in RA synovium, and that the syntheses of 1,25(OH)2D and 24,25(OH)2D may be affected by IL-1/IL-2 and 1,25(OH)2D in RA SF, respectively.

Arthritis, Rheumatoid↗
PubMed1997

A translocation between 3q21 and 12q24 in a patient with minimally differentiated acute myeloid leukemia (AML-M0).

Only a small number of reports have described the cytogenetic analysis of minimally differentiated acute myeloid leukemia (AML, M0). We performed a cytogenetic analysis on a patient with AML (M0) with a normal platelet count. It revealed a chromosomal translocation between chromosome bands 3q21 and 12q24. 3q. Abnormalities in AML are known to be associated with normal or elevated platelet counts. 3q21 and 12q24 are common translocation sites in AML patients, but this is the first report of translocation t(3;12)(q21;q24) in an AML patient.

Cell Differentiation↗
PubMed1997

Pentoxifylline down-regulates adhesion molecule expression and inflammatory cytokine production in cultured peripheral blood mononuclear cells from patients with HTLV-I-associated myelopathy.

To clarify if pentoxifylline (PTX) may have therapeutic potential for human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM), we investigated the in vitro effect of PTX on spontaneous proliferation of peripheral blood lymphocytes (SPP), as well as on the expression of adhesion molecules, such as lymphocyte function antigen-1 (LFA-1) and very late activation antigen-4 (VLA-4), and the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and granulocyte-monocyte colony stimulating factor (GM-CSF), in cultured PBMC from 10 HAM patients, compared with control subjects. SPP in HAM patients was significantly suppressed in a dose-dependent manner with PTX. Using flow cytometry, PTX was found to down-regulate the expression of LFA-1 and VLA-4 on CD4+ and CD8+ T cells in HAM patients as well as control subjects. However, the fall in the expression of LFA-1 and VLA-4 on CD4+ T cell population in HAM patients was higher than that of control subjects. PTX caused a significant suppression of spontaneous production of TNF-alpha by cultured PBMC of HAM patients. It also caused a small but significant suppression GM-CSF and IFN-gamma production. Collectively, our results suggest that PTX might be therapeutically effective at critical points in the immunopathogenesis of HAM.

Adult↗
PubMed1997

A virus-neutralizing epitope on the glycoprotein of rabies virus that contains Trp251 is a linear epitope.

We have established a hybridoma producing monoclonal antibody (MAb) against a linear epitope of glycoprotein (G protein) of the RC-HL strain of rabies virus. This MAb15-13 showed almost the same neutralizing activity to all of five rabies fixed strains, including RC-HL, and reacted to the denatured G protein in western blot analysis. To characterize and map this linear epitope, an antigenic variant NR15-13 was selected from RC-HL strain in the presence of neutralizing MAb15-13. The variant reacted with MAb15-13 in an immunofluorescent antibody test but was not neutralized by the antibody and the antibody did not bind to the variant G protein in a Western blot analysis. The variant NR15-13 had an amino acid substitution at position 251 of the G protein, where tryptophan of the parental RC-HL strain was replaced by arginine. Site-directed mutagenesis analysis using the expression system in simian COS7 cells revealed that a single amino acid substitution at 251-tryptophan by arginine on the G protein of the parental RC-HL strain abolished the antigenicity of the epitope for MAb15-13 in western blot analysis, and the replacement of 251-arginine by tryptophan recovered the activity. These results strongly suggest that tryptophan at position 251 on the G protein is essential for construction of the linear epitope against MAb15-13.

Animals↗
PubMed1997

Up-regulation of iNOS mRNA expression and increased production of NO in human monoblast cell line, U937 transfected by HTLV-I tax gene.

We investigated the mRNA expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) in human T cell lymphotropic virus type I (HTLV-I) p40tax-transfected U937 cells, a human monoblast cell line. Transfection of HTLV-I p40tax U937 cells induced up-regulation of iNOS mRNA expression and subsequent NO production. Furthermore, interferon gamma (IFN-gamma) stimulation of HTLV-I p40tax-transfected U937 cells enhanced iNOS mRNA expression and NO production. The kinetics of iNOS mRNA expression and NO production indicated maximal effect at 24 and 48 hours, respectively, after culture with or without IFN-gamma. These findings suggest that HTLV-I p40tax can act as a transactivator of NO production in cells of Mo/M phi lineage. To what extent this mechanism may be involved in the pathogenesis of HTLV-I-associated diseases warrants further investigation.

Enzyme Induction↗
PubMed1997

Overexpression of PRAD1/cyclin D1 in plasma cell leukemia with t(11;14)(q13;q32).

Two patients with plasma cell leukemia (PCL) with a t(11;14)(q13;q32) translocation are reported. Case 1 is a 64-year-old woman diagnosed as having primary PCL (IgA/lambda, Stage III) with high serum LDH and beta 2-microglobulin (beta 2MG) levels. She was treated with combination chemotherapy but died of gastrointestinal bleeding on the 45th hospital day. Case 2 is a 52-year-old man, initially diagnosed with multiple myeloma (IgG/kappa, Stage III) in August 1993. Relapse several months after primary chemotherapy was characterized by a rapid increase in plasma cells in peripheral blood, high serum LDH and beta 2MG levels, and resistance to further chemotherapy. Both cases showed complex karyotypic abnormalities including t(11;14), and Northern analysis revealed overexpression of the PRAD1/ cyclin D1 gene. The PRAD1 gene is found on chromosome band 11q13 and encodes cyclin D1. Cyclin D1 plays an important role in control of the cell cycle, and overexpression of PRAD1/cyclin D1 may be involved in disease progression in these cases.

Chromosomes, Human, Pair 11↗
PubMed1997

Flow cytometric analysis of Thy-1 expression in CD34-positive acute leukemia.

We analyzed the expression of the Thy-1 antigen (CD90) in CD34+ acute leukemia using two-color flow cytometry. Leukemic cells were obtained from the bone marrow (BM) and/or the peripheral blood (PB) of 57 patients: 37 with acute myelogenous leukemia (AML) including nine with secondary AML following myelodysplastic syndrome (MDS/AML), and 20 with acute lymphoblastic leukemia (ALL) including three with chronic myelogenous leukemia in blast crisis (CML-BC) of the lymphoid type. Among these patients, one (3.6%) with de novo AML, two (22.2%) with MDS/AML, three (17.6%) with de novo ALL, and two (66.7%) with CML-BC coexpressed CD34 and Thy-1 (CD34+ Thy-1+) on more than 20% of the mononuclear cells within 'lymph' plus 'blast' window. Thy-1 was rarely expressed in de novo acute leukemia especially in AML. Interestingly, in 1 patient with CML-BC, the leukemic cells in BM were divided into two subpopulations (CD34+ Thy-1low and CD34+ Thy-1high), whereas most of the CD34+ leukemic cells in PB were Thy-1high. However, the mechanism for the mobilization of CD34+ Thy-1high leukemic cells into the PB is unknown.

Acute Disease↗
PubMed1997

Serum thrombopoietin levels in patients undergoing autologous peripheral blood stem cell transplantation.

Recently, the ligand for c-mpl has been cloned and initial studies have shown it to be the platelet regulatory factor, thrombopoietin (TPO). To elucidate the role of TPO in the reconstitution of megakaryopoiesis and platelet production after stem cell transplantation, we measured serum TPO levels in nine patients undergoing autologous peripheral blood stem cell transplantation (PBSCT) and in healthy volunteers. Serum TPO levels significantly correlated with the degree of peripheral thrombocytopenia and a strong inverse correlation between serum TPO level and platelet count was observed (r = -0.700, P < 0.001). Serum TPO levels began to rise as the platelet count decreased after chemotherapy, TPO levels peaked at over 25.00 fmoles/ml between days 0 and 10; TPO levels then decreased gradually as the platelet count began to rise. One patient with multiple myeloma received purified CD34+ peripheral blood stem cells. No difference was observed in the kinetics of serum TPO levels between unfractionated and purified PBSCT. These observations suggest that TPO plays a critical role in the reconstitution of megakaryopoiesis and platelet production after PBSCT.

Adolescent↗
PubMed1997

Comparison of cytomegalovirus (CMV) antigenemia and CMV in bronchoalveolar lavage fluid for diagnosis of CMV pulmonary infection after bone marrow transplantation.

A comparative cytomegalovirus (CMV) diagnostic study was carried out on 30 bone marrow transplant patients. Forty-three bronchoalveolar lavage fluid (BALF) samples from these patients were examined for CMV by viral culture, polymerase chain reaction (PCR), shell vial and cytology. In parallel, peripheral blood samples were subjected to CMV antigenemia assay. CMV was detected in 12 (27.9%) of the 43 BALF samples (10 samples in viral culture, 10 samples in PCR, eight samples in shell vial and three samples in cytology). The CMV antigenemia assay yielded a positive result for six samples. The rates of agreement between results of the CMV antigenemia assay and results of each of the BALF tests were as follows: 81.4% with viral culture, 76.7% with PCR, 86.0% with shell vial, and 88.4% with cytology. Although the sensitivity of the CMV antigenemia assay was inferior to the sensitive tests of BALF samples, statistically significant correlations were demonstrated between the CMV antigenemia assay, viral culture, shell vial and cytology. Although the CMV antigenemia assay was shown to be useful for detection of CMV, it may be necessary to confirm not only the sensitivity but also the specificity of this method for prevention of CMV disease after BMT.

Adolescent↗
PubMed1997

Intraductal ultrasonography of the pancreas: development and clinical potential.

Intraductal ultrasound (IDUS) probes mounted with 30 MHz or 20 MHz transducers were evaluated in the diagnosis of 239 patients with pancreatic disease (including 48 cancers, 90 mucin-producing tumors, seven islet-cell tumors, two metastatic pancreatic tumors, seven serous cystadenomas, one pancreatic teratoma, three solid cystic tumors, 49 cases of chronic pancreatitis, 25 cases of focal pancreatitis, and seven cases of pancreatolithiasis). The probe was inserted via the papilla into the main pancreatic duct. In terms of resolution, IDUS at 20 MHz was able to image cystic lesions of less than 30 mm in diameter and solid lesions of less than 20 mm in diameter. With regard to vessels, IDUS was able to image the entire cross-section of the portal vein and other large veins. IDUS was useful in detecting carcinoma in situ and small tumors, in assessing the intraductal spread of the tumor and its pancreatic parenchymal invasion in mucin-producing tumors of the main duct, and in assessing the indications for surgery by revealing mural nodules in mucin-producing tumors of the ductal branches. IDUS was also useful in evaluating the feasibility of partial resection of the tumor in mucin-producing tumors of the ductal branches and pancreatic islet-cell tumors, in accurately locating multiple lesions in pancreatic islet-cell cancer, and in differentiating benign from malignant cases of localized stenosis of the main pancreatic duct related to pancreatic stenting. With IDUS, the site of pancreatic stones could be identified in order to assess the need for endoscopic treatments such as stenting of the pancreatic duct and the bile duct, and the use of pulsed-dye laser treatment under pancreatoscopy for pancreatic stones. Acute pancreatitis as a complication occurred in one of the 239 patients who underwent IDUS (0.4%). An awareness of the limitations and usefulness of IDUS in evaluating pancreatic diseases can contribute to the treatment of these conditions.

Aged↗
PubMed1997

Monoclonal antibody #5-2-26 recognizes the phosphatase-sensitive epitope of rabies virus nucleoprotein.

We prepared monoclonal antibodies (MAbs) against the rabies virus N protein, among which one antibody (MAb 5-2-26) was shown to lack reactivity with the phosphatase-treated N protein. The MAb was able to recognize the sodium dodecyl sulfate (SDS)-denatured N protein. The MAb did not recognize the N-protein analogues produced in Escherichia coli (E. coli), indicating that the N-gene products were not normally processed in E. coli after translation. On the other hand, the MAb reacted normally with N-gene products produced in COS-7 cells, but not with those produced in the presence of K-252a (a protein kinase inhibitor of a broad spectrum). The MAb displayed weak cross-reactivity with the Triton-insoluble network structures composed of several components, while another phosphoprotein (M1) of the virus was not recognized at all. These results suggest that MAb 5-2-26 preferentially recognizes a phosphatase-sensitive linear epitope of N protein, which may enable further investigations to be conducted on the mechanism of N-protein phosphorylation and its role(s) in virus replication.

Animals↗
PubMed1997

Identification of a phosphatase-sensitive epitope of rabies virus nucleoprotein which is recognized by a monoclonal antibody 5-2-26.

We have investigated a phosphatase-sensitive sequential epitope of the nucleoprotein (N), one of the phosphoproteins of rabies virus, which is recognized by the monoclonal antibody (MAb) #5-2-26. The epitope was shared in common by all of the rabies virus strains we tested, including the HEP, ERA, CVS and Japanese strains (Nishigahara and Komatsukawa). Thin layer chromatography of the acid hydrolyzates of 32P-labeled N protein showed that the protein contained phosphoserine and phosphothreonine at a molar ratio of about 4 to 1, while no phosphotyrosine was detected. Immunoprecipitation studies with several deletion mutants of the N protein showed that the epitope is located in a region spanning from amino acid 344 to 415. If the phosphatase-sensitive epitope is located at or near the phosphoamino acid, the location of the latter could be narrowed further to a region from amino acid 354 to 389 by comparing the amino-acid sequences among the viral strains. To examine this assumption, point mutation was introduced by amino-acid substitution with alanine at either of five potential phosphorylation sites (i.e., positions 354, 375, 377, 386 and 389) in the 354-389 region. Among those, only one substitution, at position 389, greatly affected the antigenicity. Substitution of serine-389 by threonine also reduced the antigenicity. These results strongly suggest that serine-389 is a phosphorylation site and essential for constructing or stabilizing the antigenic structure for MAb 5-2-26.

Amino Acid Sequence↗
PubMed1997

Relationship between local immune response to Helicobacter pylori and the diversity of disease: investigation of H. pylori-specific IgA in gastric juice.

In order to evaluate the relationship between local immune response to Helicobacter pylori and the diversity of disease, 77 asymptomatic subjects who underwent a health examination were studied. Helicobacter pylori-specific IgG in serum and H. pylori-specific IgA in gastric juice were measured by ELISA, and the measured IgA titre was classified into two grades, low or high. Histological classification of gastritis was performed according to the Sydney system. Cytokines in gastric juice were also measured, and the cytotoxin-associated gene A (cagA) status of H. pylori was tested by PCR. Of the 65 subjects who were positive for H. pylori-specific IgG in serum, 38 (58.5%) were classified as H. pylori-specific IgA low titre in gastric juice and 27 (41.5%) had high titres. In the IgG-positive, IgA-low group, the rate of peptic ulcers (especially duodenal ulcers) in endoscopic findings was higher (P < 0.05); the score of activity and the density of H. pylori were higher (P < 0.001 and P < 0.05, respectively); the score of metaplasia was lower (P < 0.05); and the level of interleukin-1 beta was lower (P < 0.05) than in the IgG-positive, IgA-high group. The positive rate of the cagA gene was 84.4% and there was no significant difference between the two groups. There were differences in endoscopic and histological findings between the IgG-positive, IgA-low and the IgG-positive, IgA-high groups. It is suggested that persons infected with H. pylori can be divided into two different states of disease according to local immune response.

Antibodies, Bacterial↗
PubMed1997

Effects of thrombopoietin (c-mpl ligand) on growth of blast cells from patients with transient abnormal myelopoiesis and acute myeloblastic leukemia.

Thrombopoietin (TPO) is a ligand for c-mpl that promotes both proliferation and differentiation of megakaryocytes in vivo and in vitro. We investigated the expression of c-mpl transcripts and the effects of recombinant human TPO (rhTPO) on the proliferation and differentiation of human leukemic cell lines or fresh samples obtained from 32 patients with transient abnormal myelopoiesis (TAM) or acute myeloblastic leukemia (AML). Cells were cultured with TPO alone or combined with rh interleukin-3 (IL-3) or stem cell factor (SCF). Expression of c-mpl was verified in 6 of 13 cases tested. All but one of the cases that showed c-mpl expression responded to TPO. Blasts from all cases of TAM or French-American-British (FAB) subtype M7 showed growth responses to TPO with higher sensitivity than cells of other FAB subtypes and these responses were increased by addition of rhIL-3 or rhSCF in some cases. Responses of cells of other FAB subtypes varied. In addition, increased expression of platelet-specific surface antigens on MO7E cells after incubation with rhTPO was observed. These data suggest that TPO may be involved in the abnormal proliferation and differentiation of human leukemic cells, especially of M7 and TAM cells, considered to be of megakaryocytic lineage.

Adult↗
PubMed1997

VP16 targets an amino-terminal domain of HCF involved in cell cycle progression.

The herpes simplex virus (HSV) regulatory protein VP16 activates HSV immediate-early gene transcription through formation of a multiprotein-DNA complex on viral promoters that includes the preexisting nuclear proteins HCF and Oct-1. The HCF protein is a complex of amino- and carboxy-terminal polypeptides derived from a large (approximately 2,000-amino-acid) precursor by proteolytic processing. Here we show that a 361-residue amino-terminal region of HCF is sufficient to bind VP16, stabilize VP16-induced complex assembly with Oct-1 and DNA, and activate transcription in vivo. This VP16 interaction region contains six kelch-like repeats, a degenerate repeat motif that is likely to fold as a distinctive beta-propeller structure. The third HCF kelch repeat includes a proline residue (P134) that is mutated to serine in hamster tsBN67 cells, resulting in a temperature-sensitive defect in cell proliferation. This missense mutation also prevents direct association between HCF and VP16, suggesting that VP16 mimics a cellular factor required for cell proliferation. Rescue of the tsBN67 cell proliferation defect by HCF, however, requires both the VP16 interaction domain and an adjacent basic region, indicating that HCF utilizes multiple regions to promote cell cycle progression.

Amino Acid Sequence↗
PubMed1997

Kinetics of fibroblasts in ulcer healing in rats: interference with indomethacin.

OBJECTIVE: The authors reported that the repair of submucosal tissue is important in ulcer healing. The kinetics of fibroblasts have not been well known in gastric ulcer healing. The effect of subcutaneous administration of indomethacin (1 mg/kg) to submucosal tissue was also examined. METHOD: Immunohistological staining was done using the antibodies for the proliferating cell nuclear antigen prolyl 4-hydroxylase and alpha-smooth muscle actin in acetic acid induced gastric ulcers in rats. The terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate-biotin nick end labeling method was also employed. RESULTS: The granulation tissue consisted predominantly of lymphocytes in indomethacin-treated rats. In the control group, proliferative cell nuclear antigen positive cells were at their peak 5 days after ulcer formation (day 5). Prolyl 4-hydroxylase positive fibroblasts were maximal on day 10. Alpha-smooth muscle actin positive myofibroblasts were few on day 5 and increased on day 15. In terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate-biotin nick end labeling, positive cells were sporadically seen on days 20 and 30. In indomethacin-administered rats, the fibroblasts proliferated weakly. The numbers of prolyl 4-hydroxylase and alpha-smooth muscle actin positive spindle-shaped cells were fewer and their appearance delayed. Nick end labeling positive cells were few before day 30 and sporadically observed on days 50 and 80. CONCLUSION: The results indicate that fibroblasts differentiated into several phenotypes and finally underwent apoptosis.

Acetic Acid↗