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Biomedical subjects

Y Niho

Publications and source records attributed to Y Niho.

At least 199 records · Page 11Linked to original sources
PubMed1996

Production of the third and fourth component of complement (C3, C4) by smooth muscle cells.

Production of the third and fourth components of complement (C3, C4) by smooth muscle cells was investigated by using normal human aortic smooth muscle cells (AoSMC), human smooth muscle cell line (G402) and vascular smooth muscle cells obtained from human umbilical cord vein (UVSMC). AoSMC spontaneously produced both C3 and C4 at 15 ng/10(6) cells/72 hr and 22 ng/10(6) cells/72 hr, respectively, and both were enhanced by interferon-gamma (IFN-gamma). Although phorbol 12-myristate 13-acetate (PMA) and tumour necrosis factor-alpha (TNF-alpha) enhanced C3 production, C4 production was reduced by these agents. On the other hand, G402 produced C4 but not C3 in a dose-dependent manner when cultured with IFN-gamma. UVSMC produced only a small amount of C3 and C4 compared with AoSMC or G402. C3 and C4 produced by AoSMC were confirmed to be identical with their human serum counterparts as determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and measurement of haemolytic activity. Northern blotting analysis showed that the expression of mRNA of C3 and C4 was enhanced by TNF-alpha and IFN-gamma, respectively, in AoSMC. Our findings suggest the importance of smooth muscle cells as a source of components of complement in vascular diseases including vasculitis.

Aorta↗
PubMed1996

High frequency of the MAGE-1 gene expression in hepatocellular carcinoma.

The MAGE-1 gene, originally isolated from a human melanoma cell line, directs the expression of a potential tumor-rejection antigen, MZ2-E. This antigen is recognized by autologous cytotoxic T lymphocytes in association with a major histocompatibility complex class I molecule (HLA-A1), and has provided a basis for specific immunotherapy for melanoma patients. Here we show a high frequency of expression of the MAGE-1 gene in hepatocellular carcinoma (HCC). We examined the expression of the MAGE-1 gene in cell lines originated from hepatoma cells and in tumor and nontumor tissues of livers with HCC by reverse-transcription polymerase chain reaction (RT-PCR) and subsequent Southern blotting. MAGE-1 messenger RNA (mRNA) was expressed in three of four HCC cell lines (75%) and in 16 of 20 (80%) resected HCCs though none was detected in nontumor tissues. The high frequency expression of MAGE-1 gene in HCCs suggests the possibility as a target for tumor-specific immunotherapy for HCC patients.

Adolescent↗
PubMed1996

G-CSF-induced mobilization of peripheral blood stem cells from healthy adults for allogeneic transplantation.

We investigated a dose-escalation effect of G-CSF (5, 10, and 15 micrograms/kg) on mobilization of committed and primitive hemopoietic progenitor cells, including CFU-GM, BFU-E, and long-term culture-initiating cells (LTC-IC) in addition to CD34+ cells and yields of progenitor cells in PBSC harvests obtained by leukapheresis of healthy adult donors. Results indicate that the mobilization of these progenitor cells is both dose and time dependent. Despite the very small number of healthy donors studied, it is estimated from our data that a sufficient number of CD34+ cells for allogeneic PBSC transplant (PBSCT) could be collected using a 5 day administration of 10 micrograms/kg of G-CSF to normal adult donors. Adverse effects include general fatigue and bone pain in most of the donors and fever and headache in some. These symptoms were well tolerated in most instances. Laboratory test abnormalities, including transient thrombocytopenia, increased platelet aggregation, and increased serum levels of some liver enzymes, were induced by G-CSF administration, but all were reversible within a short time. These observations suggest that hemopoietic stem cells for allogeneic PBSCT can be mobilized by short-term administration of a relatively high-dose G-CSF.

Adult↗
PubMed1996

[Anti-platelet antibody and severe thrombocytopenia during interferon-alpha therapy for chronic active hepatitis C].

We herein report a case of chronic hepatitis C where the patient developed severe thrombocytopenia during interferon therapy. The patient was a 61-year-old woman, who received interferon therapy on April 27, 1993 under the diagnosis of C type chronic active hepatitis. After 4 weeks, her platelet count had decreased to 18,000/microliters and intraoral hemorrhage had begun. Although she received 250 mg of methylprednisolone and 20 U of platelet transfusion three times, her platelet count continued to decrease to 4,000/microliters on both May 28, and on June 3, 1993, and so she was transferred to our hospital on June 4. On her second admission to our hospital, although the platelet-associated IgG (PA-IgG) had increased markedly and the megakaryocytes in her bone marrow had decreased, her platelet count had already increased to 37,000/ microliters, and this gradually returned to a normal level accompanied with a decrease of PA-IgG within one month In this case, although we found immunological abnormalities (high level of IgG, positive ANA and positive anti-smooth muscle antibody) prior to interferon treatment, we could not diagnose the patient as having suffered from autoimmune disease, including autoimmune hepatitis, because she did not satisfy the necessary criteria and because she did not have any symptoms suggesting autoimmune disease. We consider that there may be the possibility that interferon induced only an anti-platelet antibodies that caused the high level of PA-IgG and decreased the production level of platelets within the bone marrow.

Adolescent↗
PubMed1996

Fas antigen (CD95) and hematopoietic progenitor cells.

We investigated the expression of an apoptosis associated antigen (Fas) (CD95) on hematopoietic progenitor cells. Freshly isolated CD34+ cells from bone marrow did not express Fas. However, interferon-gamma (IFN-gamma) and/or tumor necrosis factor-alpha (TNF-alpha) induced dose-dependent expression of both Fas mRNA and Fas protein on the surface of CD34+ cells after 48 hours of serum-free culture. TNF-alpha-induced Fas expression was mediated by p55-TNF-alpha receptor. Induced Fas was functional as it could transduce apoptotic signals in response to anti-Fas monoclonal antibody (MoAb). The Fas-defective 1pr mice are reported to have abnormally radio-resistant hematopoietic stem cells. Consequently, we also investigated the relation between Fas and ionizing radiation. Human CD34+ cells expressed Fas following low-dose ionizing radiation in a dose-dependent fashion. Fas induced on CD34+ cells mediated apoptosis in response to anti-Fas MoAb. We evaluated the expression of Fas and Bel-2 on CD34+ hematopoietic progenitor cells expanded in vitro. CD34+ cells isolated from bone marrow were cultured with hematopoietic growth factors for 7 days. Approximately half of the freshly isolated CD34+ cells expressed Bel-2. CD34+ cells cultured with hematopoietic growth factors gradually became positive for Fas and rapidly lost Bel-2 expression. Furthermore apoptosis was induced in the cultured CD34+ population in response to anti-Fas MoAb. Thus, functional Fas can be induced on hematopoietic progenitor cells in vitro by negative hematopoietic regulators, ionizing radiation, as well as positive hematopoietic regulators. The Fas system is thought to play an important role at the level of hematopoietic progenitor cells in both physiologic and pathologic conditions.

Animals↗
PubMed1996

Rotenone, a mitochondrial NADH dehydrogenase inhibitor, induces cell surface expression of CD13 and CD38 and apoptosis in HL-60 cells.

We previously demonstrated that the mitochondrial NADH dehydrogenase subunit 2 (ND2) gene was overexpressed in human acute myelogenous leukemia (AML) cells. Since this finding suggested that ND2 gene expression was related to myeloid differentiation, we here investigated the effects of rotenone, a specific NADH dehydrogenase inhibitor, on HL-60 cell growth, differentiation and death. Fifty nM rotenone inhibited the growth of HL-60 cells and caused an increase in the cell population in the G(2) +M phase. In the quantitative comparison of myeloid antigen, the expression of CD13 and CD38 were relatively increased in the rotenone-treated cells. These findings suggest that the inhibition of NADH dehydrogenase changes the cell cycle and induces some specific surface antigens of HL-60 cells. On the other hand, the expression of ND2 gene remained unchanged after the rotenone treatment, suggesting the rotenone-mediated mitochondrial inhibition did not affect the mitochondrial gene expression. Five mu M rotenone strongly inhibited the cellular proliferation. Electron microscopy and an electrophoretic analysis of DNA showed that the majority of the HL-60 cells were induced into typical apoptosis within 24-48 hours. On the basis of this and other studies, we believe that mitochondrial function is directly involved in both cellular differentiation and apoptotic cell death.

ADP-ribosyl Cyclase↗
PubMed1996

Tumor necrosis factor production by rat Kupffer cells-regulation by lipopolysaccharide, macrophage activating factor and prostaglandin E2.

Tumor necrosis factor (TNF) is considered to be deeply involved in the hepatocyte damages in severe hepatitis. To delineate which mediators are involved in the production of TNF in vivo, we examined regulatory mechanisms of the production of TNF by rat Kupffer cells using a variety of mediators. Lipopolysaccharide (LPS) markedly induced TNF production by Kupffer cells. Kinetic studies revealed a rapid release of TNF within 3-4 hrs after the addition of LPS to the culture medium. Spleen cell derived-macrophage activating factor prepared from rat spleen cells did not by itself induce the production of TNF. However, the presence of a small amount of the factor during or before exposure to LPS induced higher levels of TNF, suggesting that macrophage activating factor had a priming effect. Recombinant human interferon-gamma and recombinant human granulocyte-macrophage colony stimulating factor, the natural types of which are components of the macrophage activating factor, displayed similar effects. Prostaglandin E2 (PGE2) and dexamethasone both inhibited LPS-induced TNF production in a dose dependent manner. Indomethacin, a cyclooxygenase inhibitor, increased LPS-induced TNF production. Interestingly, a combination of PGE2 and indomethacin inhibited TNF production more strongly than PGE2 alone, suggesting that the simultaneous treatment with PGE2 and indomethacin decreases liver damage in severe hepatitis rather than PGE2 alone. In addition, PGE2 pretreatment reduced the response to the newly added PGE2, suggesting the presence of a desensitization mechanism in the PGE2 receptor system. These findings suggest that spleen cell-derived macrophage activating factor and bowel-derived LPS take important parts in TNF production through the portal blood in the liver in vivo.

Animals↗
PubMed1996

High prevalence of T cell receptor D delta 2(D delta)J delta rearrangement in CD7-positive early T cell acute lymphoblastic leukemia.

We have studied the molecular characteristics of the T cell receptor (TcR) genes in 16 patients with CD7+ early T cell acute lymphoblastic leukemia (T-ALL), defined as being positive for CD7 but negative for CD3/4/8, myeloperoxidase (MPO), and CD19/20. Using gene analysis, rearrangement was demonstrated in one patient for immunoglobulin heavy chain (IgH) gene, five for TcR-beta gene, and four for TcR-gamma gene. Fifteen patients (94%) had rearranged band(s) involving the joining region of the TcR-delta chain gene. In nine cases these were the only rearrangements, whereas in six cases TcR-beta and/or TcR-gamma gene rearrangements were found as well. The D delta 2(D delta)J delta 1 rearrangement was demonstrated in 87.5% (14/16) of cases. D delta 2(D delta)J delta 3 was recognized in one patient, D delta 2D delta 3 was found in three, and V(D)DJ using only V delta 2 and V delta 3 was recognized in two patients. We found no V2D delta 3, V3D delta 3, or V1(D)DJ delta rearrangement patterns. Five of nine cases with DDJ delta were positive for cytoplasmic CD3 epsilon(CyCD3 epsilon). Our data suggest that DDJ delta joining occurs at an early stage during T cell differentiation, followed by rearrangements of V delta to the DDJ delta complex. Furthermore, our findings suggest that DDJ delta recombination occurs earlier than expression of CyCD3 epsilon protein products. DDJ delta rearrangements have never been observed in non-T cell malignancies, such as precursor-B-ALL or acute myeloid leukemia. Therefore, detection of DDJ delta rearrangement in the TcR-delta locus is a useful tool to establish lineage and clonality of leukemic cells in the most immature stages of T cell development.

Antigens, CD↗
PubMed1996

Serum concentration of the soluble interleukin-2 receptor for monitoring acute graft-versus-host disease.

Soluble interleukin-2 receptors (sIL-2R) are elevated in various disorders involving the activation of T cells. We measured serial serum concentrations of sIL-2R in 30 patients receiving allogeneic BMT to evaluate the usefulness of sIL-2R as a parameter for acute GVHD. In the 17 patients who developed acute GVHD, the sIL-2R concentration rose significantly on day 3 following transplantation, preceding the occurrence of acute GVHD. This change was not seen in the 13 patients without acute GVHD. The serum concentration of sIL-2R decreased as the acute GVHD subsided. The peak concentration of serum sIL-2R correlated with the severity of the acute GVHD. Simultaneous measurement of tumor necrosis factor alpha (TNF alpha) showed a significant rise in patients with acute GVHD, that became evident earlier than the sIL-2R elevation. TNF alpha concentrations also decreased following treatment of the acute GVHD. However, significant rise in TNF alpha were also seen in the early phase of allogeneic BMT in patients who did not develop acute GVHD. Our data suggest that the serum concentrations of sIL-2R as well as TNF alpha might reflect the severity of acute GVHD, and that the serum sIL-2R concentration might be a sensitive and practical indicator for acute GVHD.

Acute Disease↗
PubMed1996

Suppression of superoxide anion production by interleukin-10 is accompanied by a downregulation of the genes for subunit proteins of NADPH oxidase.

Interleukin-10 (IL-10) inhibited the production of superoxide anion (02-) by both unactivated and interferon-gamma (IFN-gamma)-activated human monocytes. Simultaneous addition of IL-10 with IFN-gamma at the start of incubation was necessary for an optimal inhibitory effect. The degree of inhibition was substantially comparable to that of IL-4, and the combination of suboptimal concentrations of IL-10 and IL-4 produced an additive effect. A similar effect was also obtained when viral IL-10 (vIL-10) was used instead of IL-10. The inhibitory effect of IL-10 was accompanied by the reduced accumulation of transcripts for heavy chain subunit of cytochrome b558 (gp9l-phox) and 47-kD cytosolic factor (p47-phox), components of the O2--generating NADPH oxidase system. Reduction of the mRNAs was distinct within 24 hours. On the other hand, the induced O2- production by human monocytic leukemia cell lines (THP-1 and HL60) was not inhibited by IL-10. The amount of gp9l-phox and p47-phox mRNAs remained unchanged even in the presence of excess amount of IL-1O. Taken together, these results suggest that IL-10 inhibits 02- production by downregulation of the gp9l-phox and p47-phox genes in human monocytes.

Depression, Chemical↗
PubMed1996

[Fas antigen expression on human hematopoietic progenitor cells].

We investigated the expression of Fas(CD95) on hematopoietic progenitor cells. CD34+ cells freshly isolated from bone marrow did not express Fas. However, interferon-gamma(IFN-gamma) and/or tumor necrosis factor-alpha (TNF-alpha) induced the expression of Fas after 48 hours of serum-free culture. The TNF-alpha-induced Fas expression is mediated by p55-TNF-alpha receptor. Human CD34+ cells expressed Fas following low dose ionizing radiation in a dose-dependent fashion. CD34+ cells isolated from bone marrow were cultured with hematopoietic growth factors for 7 days. CD34+ cells cultured with hematopoietic growth factors gradually became positive for Fas and rapidly lost Bcl-2 expression. Fas system is considered to play important roles at the level of hematopoietic progenitor cells in both physiologic and pathologic conditions.

Animals↗
PubMed1996

[Comparative trial of granisetron alone and granisetron plus methylprednisolone for prevention of nausea and vomiting during cancer chemotherapy].

A crossover clinical trial between granisetron alone and granisetron combined with methylprednisolone (MPL) was undertaken for the prevention of nausea and vomiting during chemotherapy, including cisplatin, in 12 patients with advanced primary and metastatic lung cancer. The antiemetic effect was obtained in 91.7% (11/12 cases) of patients receiving granisetron alone compared to 100% (12/12 cases) of patients receiving the combination of granisetron plus MPL. Complete control of anorexia was achieved in 91.6% (11/12 cases) of patients receiving the combination compared to 58.3% (7/12 cases) of patients receiving granisetron alone. Moreover there was a significant improvement of delayed clinical symptoms including nausea, vomiting, and anorexia in the patients receiving the combination of granisetron plus MPL. Our data suggest that the antiemetic effect of the combination of granisetron plus MPL is superior to granisetron alone in patients receiving cancer chemotherapy.

Adult↗
PubMed1996

[Cytomegalovirus disease accompanied by severe hypoproteinemia in a patient with adult T-cell leukemia-lymphoma].

A 62-year-old Japanese man complained of fever, general fatigue, anorexia and watery diarrhea during remission of adult T-cell leukemia-lymphoma. Laboratory examinations showed severe hypoproteinemia (2.9 g/dl). However, neither intestinal lesions associated with ATL nor findings suggesting protein losing gastroenteropathy were observed. Cytomegalovirus (CMV) antigen detection assay using peripheral blood leukocytes revealed that he had an active CMV infection with hemophagocytic syndrome. Treatment with ganciclovir and methylprednisolone led to an improvement of hypoproteinemia. CMV disease and associated hemophagocytic syndrome should be considered as a cause of hypoproteinemia in an immunocompromised host.

Cytomegalovirus Infections↗
PubMed1996

Serial chromosomal change during the progression of hepatocellular carcinoma.

We investigated the chromosomal loss pattern of a primary large nodule and one of the disseminated intrahepatic small nodules of hepatocellular carcinoma in one patient using RFLP analysis. Using D17S30 probe mapping to 17p, loss of heterozygosity was observed both the main nodule and the disseminated nodule, however, using IGLV probe mapping to 22q, loss of heterozygosity was observed only in the disseminated nodule. This is the case in which serial loss of chromosome in the progression on hepatocellular carcinoma was highly suggested.

Carcinoma, Hepatocellular↗
PubMed1996

[Factors predictive of early mortality after acute myocardial infarction].

OBJECTIVES: (1) To define the clinical and laboratory findings predictive of early mortality after myocardial infarction (AMI), 100 consecutive patients were studied. (2) To elucidate the serum potassium (K) concentration and its clinical significance after AMI, 38 patients were studied. RESULTS: (1) The 30-day mortality was greater for women than for men, for patients with diabetes mellitus than for those without, and for patients with previous MI than for those without. Clinical and laboratory findings predictive of early mortality were cardiogenic shock, congestive heart failure, perforation or rupture of the ventricle, and presence of bundle branch block and extensive anterior AMI on electrocardiogram. The presence of bradyarrhythmia, ventricular tachyarrhythmias, and high blood levels of peak creatinine phosphokinase (CPK) or myosin or atrial natriuretic peptide (ANP) were not independent predictors of early mortality. Patients complicated with congestive heart failure showed higher levels of peak CPK and ANP and patients with cardiogenic shock showed higher levels of ANP. (2) Serum K concentration was lower on admission than the following days, and it showed a negative correlation with plasma epinephrine. The lower serum K was accompanied with more severe ventricular arrhythmias on 24-hour electrocardiogram. CONCLUSION: (1) Early mortality after AMI is related to left ventricular function rather than to arrhythmias. (2) Serum K is lower in the early phase of AMI and is related with plasma catecholamines and severe ventricular arrhythmias.

Aged↗
PubMed1996

Successful foscarnet therapy for mucocutaneous infection with herpes simplex virus in a recipient after unrelated bone marrow transplantation.

A 36-year-old Japanese man who received an unrelated bone marrow transplant (BMT) developed severe mucocutaneous infection with herpes simplex virus (HSV) type 1 during oral acyclovir prophylaxis. The lesions progressed despite treatment with intravenous acyclovir and vidarabine. The HSV isolates were sensitive acyclovir, vidarabine and foscarnet in vitro, but peripheral CD3- or CD19-positive cells were barely detectable even 4 months after transplant. A 12-day course of treatment with foscarnet led to a rapid improvement. Foscarnet therapy should be considered for all severe HSV infections following BMT, regardless of whether or not the HSV isolates are sensitive to acyclovir.

Acyclovir↗
PubMed1996

[Comparison between monotherapy with imipenem/cilastatin sodium (IPM/CS) and combinations of IPM/CS and other drugs for treating bacterial infections in patients with hematopoietic disorders].

One hundred and nine patients with infections concurrent with hematopoietic disorders were treated with imipenem/cilastatin sodium (IPM/CS) either alone (IPM/CS monotherapy) or in combination with other antimicrobial drugs (IPM/CS combination therapy). The following results were obtained. 1. One hundred and nine patients were allocated at random to two groups: 53 patients to IPM/CS monotherapy and 56 patients to IPM/CS combination therapy. Fourteen patients (6 and 8 in the 2 groups, respectively) were excluded from the clinical evaluation. There were not significant differences between the two groups with respect to the background. 2. The efficacy rates of the 2 treatments against bacterial infections were as follows: in the IPM/CS monotherapy group, 62.5% in 8 patients with sepsis, 75.0% in 23 patients with fever of undetermined origin (FUO), 50.0% in 10 patients with pneumonia, and 68.3% in the 47 patients, and in the IPM/CS combination group, 85.7% in 7 patients with sepsis, 63.6% in 24 patients with FUO, 50.5% in 8 patients with pneumonia, and 67.4% in the 48 patients. The differences between the two groups were not significant. 3. Among the drugs used in combination with IPM/CS, antibiotics other than penicillins, cephalosporins, and aminoglycosides were used in 12 patients and a high efficacy rate of 91.7% was obtained. 4. Bacteriologically, 19 and 17 strains were isolated from the IPM/CS monotherapy and combination therapy groups respectively, and the eradication rates were 100% and 88.9% respectively. 5. Side effects were noted in 2 patients in the IPM/CS monotherapy group and 7 in the combination therapy group, but all of these resolved after discontinuation or completion of the treatment. The efficacies against severe bacterial infections in the presence of hematopoietic disorders were not different between IPM/CS alone and IPM/CS in combination with other antibiotics. Adverse reactions were uncommon with the monotherapy.

Adolescent↗