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Biomedical subjects

T Nishihara

Publications and source records attributed to T Nishihara.

At least 91 records · Page 5Linked to original sources
PubMed1998

A novel retinoic acid receptor (RAR)-selective antagonist inhibits differentiation and apoptosis of HL-60 cells: implications of RARalpha-mediated signals in myeloid leukemic cells.

Retinoic acid (RA) induces HL-60 cells to differentiate terminally into mature granulocytes, which subsequently die by apoptosis. The biological effects of RA are mediated by two distinct families of transcription factors: retinoic acid receptors (RARs) and retinoid X receptors (RXRs). RARs and RXRs form heterodimers and regulate retinoid-mediated gene expression. We have recently developed a novel RAR-selective antagonist (ER27191) which prevents RAR activation by retinoids. Using this RAR-selective antagonist, and RXR and RAR agonist, we demonstrate the RAR-mediated signaling pathway is important for differentiation and apoptosis of myeloid leukemic cells. Simple activation of RXRs is not sufficient to induce apoptosis of the cells. Interestingly, the combination of the RAR-selective antagonist and 9-cis RA resulted in partial differentiation and apoptosis of HL-60 and NB4 cells, whereas the RAR antagonist completely blocked all-trans RA-induced differentiation and apoptosis of the cells. Additional experiments showed that levels of BCL-2 protein decreased during differentiation of myeloid leukemic cells. Furthermore, HL-60 cells transduced with a bcl-2 expression vector showed the same differentiation response to retinoids as did parental HL-60 cells even though apoptosis was inhibited in these bcl-2-transduced cells, suggesting that differentiation and apoptosis are regulated independently in myeloid leukemic cells.

Alitretinoin↗
PubMed1998

Correlation between Bcl-X expression and B-cell hybridoma apoptosis induced by activin A.

In this study, we examined the role of bcl-XL and bcl-XS in apoptotic cell death of HS-72 cells induced by activin A. Immunoblot analysis revealed that a band of Bcl-XL was detected in HS-72 cells cultured with or without activin A. Although untreated HS-72 cells did not express Bcl-XS, the expression of Bcl-XS was significantly increased when cultured with activin A. We also investigated the expression of Bcl-XS and Bcl-XL in HS-72 cells cultured with activin A in the presence of protein kinase C inhibitor 1-(5-isoquinotinesulfonyl)-2-methylpiperazine dihydrochloride (H7), which suppressed apoptosis in HS-72 cells induced by activin A. Exposure to H7 apparently increased the level of Bcl-XL in HS-72 cells cultured with or without activin A. In contrast, no detectable band of Bcl-XS was found in HS-72 cells cultured with activin A and H7. These findings indicate that Bcl-XL upregulation and Bcl-XS downregulation induced by H7 might correlate with the suppression of activin A-induced apoptosis in B-lineage cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

The role of activin type I receptors in activin A-induced growth arrest and apoptosis in mouse B-cell hybridoma cells.

Activins transduce their signals by binding to activin type I receptors and activin type II receptors, both of which contain a serine/threonine kinase domain. In this study, we established stable transfectants expressing two types of activin receptors, ActRI and ActRIB, to clarify the role of these receptors in activin signalling for growth inhibition in HS-72 mouse B-cell hybridoma cells. Over-expression of ActRI suppressed activin A-induced cell-cycle arrest in the G1 phase caused by inhibition of retinoblastoma protein phosphorylation through induction of p21CIP1/WAF1, a cyclin-dependent kinase inhibitor, and subsequent apoptosis. In contrast, HS-72 clones that over-expressed ActRIB significantly facilitated activin A-induced apoptosis. These results indicate that ActRI and ActRIB are distinct from each other and that the ActRI/ActRIB expression ratio could regulate cell-cycle arrest in the G1 phase and subsequent apoptosis in HS-72 cells induced by activin A.

Activin Receptors, Type I↗
PubMed1998

Caspases (interleukin-1beta-converting enzyme family proteases) are involved in the regulation of the survival of osteoclasts.

Osteoclast-like multinucleated cells (OCLs) were prepared on collagen gels in a coculture system of mouse bone marrow cells and osteoblasts, and purified by collagenase and a subsequent pronase treatment. More than 80% of the purified OCLs were found to undergo apoptotic cell death by 48 h during the culture in a culture medium containing 10% fetal bovine serum (FBS). Withdrawal of FBS from the culture medium accelerated the cell death, which induced more than 80% of OCLs to undergo apoptotic cell death by as early as 18 h. Two peptide inhibitors of caspases (interleukin-1beta-converting enzyme family proteases), benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethyl ketone (Z-VAD-FMK) and benzyloxycarbonyl-Asp-Glu-Val-Asp (OMe)-fluoromethyl ketone (Z-DEVD-FMK), extended the survival time of OCLs in the presence and absence of 10% FBS, but the effect was rather limited in the absence of FBS. Because interleukin-1alpha (IL-1alpha) and the macrophage colony stimulating factor (M-CSF) are known to promote the survival of osteoclasts, we examined the effect of the peptide inhibitors and these cytokines. Combinations of the peptide inhibitors and IL-1alpha, or the peptide inhibitors and M-CSF, were more effective than the inhibitors alone. When endogenous caspase activities of OCLs were analyzed using fluorescence peptide substrates, the activities, in particular, caspase-3 (CPP32)-like activity, were markedly increased in OCLs by the withdrawal of FBS from the culture medium. IL-1alpha and M-CSF suppressed the activation of the caspases. In addition, western blot analysis revealed that the expression of Bcl-2, which inhibits the activation of caspases, was very weak or even negligible in OCLs. Taken together, these results suggest that the caspases are involved in the regulation of survival and apoptotic cell death of osteoclasts.

Amino Acid Chloromethyl Ketones↗
PubMed1998

D-erythrulose reductase can also reduce diacetyl: further purification and characterization of D-erythrulose reductase from chicken liver.

We have discovered new characteristics of D-erythrulose reductase, namely, that it can catalyze reduction of not only D-erythrulose but also such diketones as diacetyl. These substrates have a common structure with two neighboring carbonyls possibly in s-cis plane structure, showing that the enzyme may rigorously distinguish between substrates and other compounds. D-Erythrulose reductase was predominantly located in the kidney and the liver of the chicken. The obtained results suggest that D-erythrulose reductase plays an important role in metabolizing alpha-dicarbonyls in animal organs, because these diketones widely occur in natural foods.

Animals↗
PubMed1998

Two different types of humoral immune response to Actinobacillus actinomycetemcomitans in high-responder periodontitis patients.

Actinobacillus actinomycetemcomitans is considered to be an aetiological agent in various forms of periodontitis, with serotype b-specific carbohydrate being the immunodominant antigen of A. actinomycetemcomitans Y4 in high-responder patients. Lipopolysaccharide (LPS) of the organism may also be an important antigen. The purpose of the present study was to clarify the importance of LPS as an antigen of A. actinomycetemcomitans. Twenty patients who had high antibody titres to strain Y4 were selected, and the reactivity of their sera with LPS was determined by ELISA and Western blotting. Two groups of patients were observed: group 1 had high IgG titres only to serotype b strain, whereas group 2 had high IgG titres to serotypes a, b and c strains. The results of adsorption tests showed that anti-A. actinomycetemcomitans Y4 antibody in group 1 patients mostly consisted of antibody reactive with the serotype b-specific carbohydrate, whereas the antibody in group 2 patients mostly consisted of antibody reactive with the LPS of all serotypes. These data show that anti-LPS antibody is present and predominant in anti-A. actinomycetemcomitans Y4 antibody from some high-responder patients, and indicate an important role for LPS as an antigen in the humoral immune response to the organism.

Actinobacillus Infections↗
PubMed1998

Differentiation of clinical isolates of Actinobacillus actinomycetemcomitans using an insertion sequence, ISAa1.

We previously identified an IS200-like sequence (ISAa1) in the genome of Actinobacillus actinomycetemcomitans FDC Y4. One or more hybridizing bands to the ISAa1 probe were detected in each of several reference strains, representing three of the serotypes (a through c) of A. actinomycetemcomitans. In this study, we examined whether a restriction fragment-length polymorphism (RFLP) with ISAa1 as a probe could differentiate clinical isolates. One or more hybridizing bands were detected in each of the 27 strains examined, which could be divided into seven groups according to restriction fragment-length polymorphism pattern. Several strains were observed with identical restriction fragment-length polymorphism types but with different serotypes. Conversely, strains were also observed with differing restriction fragment-length polymorphism types and identical serotypes.

Adolescent↗
PubMed1998

Recombinant human bone morphogenetic protein-2 stimulates osteoblast differentiation and suppresses matrix metalloproteinase-1 production in human bone cells isolated from mandibulae.

Bone morphogenetic protein (BMP), a member of the transforming growth factor superfamily, is one of the most potent growth factors that stimulate osteoblast differentiation and bone formation. We investigated the effects of recombinant human BMP-2 (rhBMP-2) on osteoblast differentiation and matrix metalloproteinase-1 (MMP-1) production in human bone cells (HBC) isolated from mandibulae of 3 adult patients. rhBMP-2 at concentrations over 50 ng/ml significantly stimulated alkaline phosphatase activity and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosphate accumulation, which are early markers of osteoblast differentiation, in HBCs. rhBMP-2 (500 ng/ml) also enhanced the level of PTH/PTH related-peptide receptor mRNA expression in HBCs. Although neither HBCs untreated nor treated with rhBMP-2 produced measurable amounts of osteocalcin, which is a marker of more mature osteoblasts, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] induced ostocalcin mRNA expression and its protein synthesis in these cells. rhBMP-2 inhibited 1,25(OH)2D3-induced osteocalcin synthesis in HBCs at both the mRNA and protein level. rhBMP-2 also significantly suppressed MMP-1 production and MMP-1 mRNA expression at concentrations over 500 ng/ml. These results suggest that rhBMP-2 exerts anabolic effects on human osteoblastic cells derived from mandibulae by stimulation of osteoblast differentiation and down-regulation of MMP-1 synthesis.

Adult↗
PubMed1998

Involvement of prostaglandin E2 and interleukin-1 alpha in the differentiation and survival of osteoclasts induced by lipopolysaccharide from Actinobacillus actinomycetemcomitans Y4.

Lipopolysaccharide (LPS) is a bacterial cell component that plays multifunctional roles in inflammatory reactions. LPS from various periodontal pathogens is supposed to be a major virulence factor of periodontal diseases. In the present study, we demonstrated that LPS from periodontopathic bacterium Actinobacillus actinomycetemcomitans Y4 (Y4 LPS) stimulated osteoclast formation in mouse bone marrow culture systems. Addition of anti-interleukin-1 alpha (IL-1 alpha) antibody or indomethacin in the marrow cultures resulted in the suppression of osteoclast differentiation. Quantitative analyses revealed that Y4 LPS stimulated the production of IL-1 alpha and prostaglandin E2 (PGE2) by bone marrow cells. Furthermore, an immunoblot analysis showed that Y4 LPS stimulated bone marrow cells to upregulate the expression of cyclooxygenase-2, a rate-limiting enzyme for the conversion of arachidonic acid to prostanoids. These findings suggest that both IL-1 alpha and PGE2 are involved in the LPS-mediated osteoclast differentiation. In addition, we found that Y4 LPS supported the survival of osteoclasts. Addition of anti-IL-1 alpha antibody in the osteoclast culture resulted in a reduction of osteoclast survival. Indomethacin, however, showed no effect on osteoclast survival. These findings suggest that the increased PGE2 and IL-1 alpha synthesis by bone marrow cells may play an important role in the differentiation and survival of osteoclasts induced by A. actinomycetemcomitans LPS.

Aggregatibacter actinomycetemcomitans↗
PubMed1998

Actinobacillus actinomycetemcomitans toxin induces both cell cycle arrest in the G2/M phase and apoptosis.

We found that the culture supernatant of the periodontopathic bacterium Actinobacillus actinomycetemcomitans had a cytotoxic effect on several cell lines. In this study, we purified the toxin from the culture supernatant of A. actinomycetemcomitans Y4 by a four-step procedure: ammonium sulfate precipitation, POROS HQ/M column chromatography, polymyxin B matrix column chromatography, and Mono-Q column chromatography. The purified toxin gave two major bands of protein with molecular masses of 80 and 85 kDa upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The mechanism of cell death of the B-cell hybridoma cell line HS-72 was examined by observing changes in nuclear morphology, an increase in the proportion of fragmented DNA, and the typical ladder pattern of degraded chromosomal DNA, indicating the induction of apoptosis. Overexpression of human Bcl-2 suppressed apoptosis in HS-72 cells, indicating that the toxin from A. actinomycetemcomitans induces apoptosis by a Bcl-2-inhibitable mechanism. Flow cytometric analysis revealed that the toxin caused cell cycle arrest in the G2/M phase and apoptosis in HS-72 cells. In addition, aurintricarboxylic acid, a DNA endonuclease inhibitor, markedly decreased the percentage of apoptotic cells but had no effect on cell cycle arrest in the G2/M phase. Taken together, these findings suggest that the toxin from A. actinomycetemcomitans could mediate the development of periodontal diseases through cell cycle arrest in the G2/M phase and apoptosis in B lymphocytes of periodontal tissue.

Aggregatibacter actinomycetemcomitans↗
PubMed1998

A survey of potential risk factors for HIV transmission through dental practice in Japan.

A survey was conducted to find potential risk factors for HIV transmission through dental practice. Self-administered questionnaires were distributed to the members of the dental associations of various prefectures and small cities in Japan. A total of 747 questionnaires was returned by dentists. The findings revealed several problems. Gloves, masks, and other protective garments were generally worn, but most dentists did not always use them during the full course of treatment limiting usage to surgical treatment, and when treating patients in "high-risk groups" and in dental practice the exact percentage of the dentists who reused a used anesthetic liquid cartridge is 12.7%. The effectiveness of the education for dentists regarding AIDS was statistically clarified. It is obviously necessary to provide important information regarding AIDS and HIV transmission to the dentists. Potential risk for HIV transmission through dental practice will be prevented by AIDS education for the dentists.

Adult↗
PubMed1998

A case of intraductal papilloma of breast in advanced age.

Breast tumors have their various biological characteristics as to advanced age of patients. Intraductal papilloma is a benign tumor of the breast which is known to occur in the premenopausal young females. Tumors of the breast in the senile females are found mainly to be breast cancers. No any cases of intraductal papilloma over 80-years were reported in Japan to date. We have recognized mammary tumors in old aged patients to be cancers, but it is necessary to put it into mind there are a few intraductal papillomas even if advanced in age. In this report, we present the most senile case with intraductal papilloma in our institute.

Aged↗
PubMed1998

[Fatal pulmonary thromboembolism in a patient with paroxysmal nocturnal hemoglobinuria].

A 38 year old woman with paroxysmal nocturnal hemoglobinuria was admitted to our hospital because of hemoptysis. Pulmonary infarction was diagnosed by the perfusion lung scan. In spite of the administration of prednisolone, dextran, low molecular weight heparin, and warfarin, she died of pulmonary infarction and secondary pulmonary hypertension. Autopsy revealed thromboembolism of both pulmonary arteries and hepatic central vein thrombosis. Recent understanding of the pathogenesis and incidence of thromboembolism in paroxysmal nocturnal hemoglobinuria was discussed.

Adult↗
PubMed1997

Identification of the transcriptional repression domain of nuclear factor 1-A.

We previously showed that nuclear factor 1-A (NF1-A) binds to the silencer elements in the glutathione transferase P (GST-P) gene, and the carboxy terminal region of NF1-A represses the transcription activity of human metallothionein IIA (hMTIIA) promoter. In this study, we identified a repression region which is divided into two 100 amino acid domains (RD1 and RD2). RD1 increased the repression activity of RD2 to the hMTIIA promoter activity. The NF1-A repression domain inhibited the promoter activities of not only the hMTIIA gene but also those of the GST-P and CCAAT/enhancer binding protein delta genes. RD1 and RD2 had abundant serine and glycine residues, and proline and serine residues, respectively. Whereas some repression domains identified previously are enriched with alanine, proline, or serine, and are associated with the general transcription factors, the NF1-A repression domains did not interact with transcription factor IIB, TATA-binding protein (TBP), or TBP-associated factors in vitro.

CCAAT-Enhancer-Binding Proteins↗
PubMed1997

18F-fluorodeoxyglucose positron emission tomography and the prognosis of patients with pancreatic adenocarcinoma.

BACKGROUND: Fluorodeoxyglucose (FDG) detected by positron emission tomography (PET) can be used to measure the glycolytic activity of tumor cells. Though the prognosis of patients with pancreatic adenocarcinoma is usually poor, a subset of patients with good prognoses may be discovered by determining the degree of FDG integration into tumors. METHODS: Fourteen patients with histologically proven pancreatic adenocarcinoma underwent 18F-FDG PET. The standardized uptake value (SUV) of 18F-FDG was calculated, and the patients were divided into high (> or = 3.0) and low (< 3.0) SUV groups. RESULTS: The two groups were not significantly different in terms of age, tumor location and size, staging, and treatment. However, analysis by the Kaplan-Meier method revealed that the groups had different prognoses (log rank test, P < 0.05). The mean survival of patients with high SUV was 5 months, whereas that of patients with low SUV was 14 months. There were not strong correlations between the SUVs and tumor size (0.56), serum carbohydrate antigen 19-9 (0.39), or carcinoembryonic antigen (0.52). CONCLUSIONS: SUV calculated with 18F-FDG can be utilized as a prognostic factor for patients with pancreatic adenocarcinoma.

Adenocarcinoma↗