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E Nakamura

Publications and source records attributed to E Nakamura.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Expression of major histocompatibility complex antigens and adhesion molecules on renal cell carcinoma cells, and effect of interferon-alpha and/or cimetidine on the expression].

Recently the combined therapy with interferon-alpha (IFN-alpha) and cimetidine has been reported to be effective against advanced renal cell carcinoma (RCC). IFN-alpha and cimetidine have an antitumor effect partly due to enhancement of cytotoxic activity of lymphocytes against cancer cells. We examined the expression of major histocompatibility complex (MHC) antigens and adhesion molecules on 4 fresh RCC cells and 5 RCC cultured cell lines, which have an important role in recognition and killing of cytotoxic lymphocytes against cancer cells. The effect of treatment with IFN-alpha and/or cimetidine on the expression of MHC antigens and adhesion molecules on RCC cells was also investigated. MHC class I and leukocyte function-associated antigen-3 (LFA-3) were expressed on all RCC cells, but not MHC class II. Intercellular adhesion molecule-1 (ICAM-1) and B7 were expressed on 6 and 5 of 8 RCC cells, respectively. IFN-alpha significantly augmented the expression of MHC class I in 6 of 9 RCC cells, ICAM-1 in 1 and LFA-3 in 2 of 8 RCC cells. However, IFN-alpha did not affect the expression of MHC class II and B7. On the other hand, cimetidine enhanced the expression of LFA-3 in 2 of 8 RCC cells, but not MHC antigens, ICAM-1 or B7. The combination of IFN-alpha and cimetidine did not show a synergistic enhancing effect on the expression of MHC antigens, ICAM-1, LFA-3 or B7. These results suggest that IFN-alpha augments the sensitivity of RCC cells to lysis by cytotoxic lymphocytes partly due to the enhancement of expression of MHC class I, ICAM-1 and LFA-3 on RCC cells, and that cimetidine also augments the susceptibility of RCC cells to lymphocytes by the enhanced expression of LFA-3 on RCC cells.

Adjuvants, Immunologic↗
PubMed1997

Involvement of NK1+ CD4- CD8- alphabeta T cells and endogenous IL-4 in non-MHC-restricted rejection of embryonal carcinoma in genetically resistant mice.

Non-MHC-restricted rejection mechanisms against the murine MHC-negative F9 embryonal carcinoma cells were analyzed. Strains of C57BL/6 (B6) background were resistant to the tumors irrespective of H-2 haplotypes, while others, including BALB/c background, were susceptible. This resistance was suggested to be mediated primarily by the host thymus-dependent alphabeta T cells, since both athymic B6 nude and normal B6 mice depleted with alphabeta T cells showed susceptible phenotype. The difference of the nature of alphabeta T cells infiltrating in H-2-identical B6- and BALB.B-derived tumors was then comparatively analyzed. It was revealed that unique T cells with NK1+ CD4- CD8- (double negative (DN)) alphabeta TCR+ phenotype were accumulated significantly in B6, but few in BALB.B mice. The population freshly isolated from the F9 tumor tissues preferentially expressed potent IL-4 mRNA, and was suggested to be mostly responsible for the endogenous IL-4 production. Indeed, the injection of either anti-NK1.1 or anti-IL-4-neutralizing Ab into the normal B6 rendered them significantly susceptible to the tumor cells. These results strongly suggested that NK1+ DN alphabeta T cells were responsible primarily for the rejection mechanisms against F9 tumors. Histologically, F9 tumors in B6 mice were characterized by abundant macrophage infiltration and massive tumor necrosis, neither of which was observed in those in BALB.B nor B6 mice preinjected with anti-IL-4 Ab, indicating that both histologic features in the resistant strain were dependent on the endogenous IL-4. Present results provide one of the first instances in which a recently emerging minor T cell subpopulation, thymus-dependent NK1+ DN alphabeta T cells, plays an essential role in anti-tumor responses in vivo.

Animals↗
PubMed1997

HLA-DRB1*0101 and *0405 as protective alleles in Japanese patients with renal cell carcinoma.

A variety of malignancies have been linked to major histocompatibility complex genes, including the DRB1 alleles. The association of certain DRB1 antigens with renal cell carcinoma (RCC) has been both claimed and disclaimed. To determine whether HLA-DRB1 genotypes are associated with RCC, we used the modified PCR-RFLP method for the high-resolution HLA-DRB1 genotyping of 96 Japanese RCC patients. There were no significantly frequent HLA-DRB1 alleles, whereas the DRB1*0101 and *0405 alleles had significantly lower frequencies [P = 0.004, relative risk (RR) = 0.2 and P = 0.002, RR = 0.4) in the RCC patients than in the healthy Japanese controls (n = 1216). Moreover, patients with the HLA-DRB1 *0101 or *0405 allele tended to be in earlier stages and to have less aggressive tumors than patients with neither of these alleles. The corresponding serotyping subclassification, however, showed a significantly lower frequency only for DRB1-DR1 (P = 0.01, RR = 0.3). High-resolution genotyping is essential because the polymorphism of the peptide-binding domain of major histocompatibility complex class II molecules is more precisely determined by genotypes than serotypes. In addition, inherent technical difficulties and potential typing errors render serotyping inefficient. Our data suggest that HLA-DRB1*0101 and *0405 are protective alleles for both RCC development and tumor progression.

Adult↗
PubMed1997

Identification of domains on the extrinsic 33-kDa protein possibly involved in electrostatic interaction with photosystem II complex by means of chemical modification.

The extrinsic 33-kDa protein of photosystem II (PSII) was modified with various reagents, and the resulting proteins were checked for the ability to rebind to PSII and to reactivate oxygen evolution. While modification of more than eight carboxyl groups of aspartyl and glutamyl residues with glycine methyl ester did not affect the rebinding and reactivating capabilities, modification of amino groups of lysyl residues with either N-succinimidyl propionate or 2, 4,6-trinitrobenzene sulfonic acid or modification of guanidino groups of arginyl residues with 2,3-butanedione resulted in a loss of rebinding and reactivating capabilities of the 33-kDa protein. Moreover, the number of lysyl and arginyl residues susceptible to modification was significantly decreased when the protein was bound to PSII as compared with when it was free in solution, whereas the number of carboxyl groups modified was little affected. These results suggested that positive charges are important for the electrostatic interaction between the extrinsic 33-kDa protein and PSII intrinsic proteins, whereas negative charges on the protein do not contribute to such interaction. By a combination of protease digestion and mass spectroscopic analysis, the domains of lysyl residues accessible to N-succinimidyl propionate or 2,4, 6-trinitrobenzene sulfonic acid modification only when the 33-kDa protein is free in solution were determined to be Lys4, Lys20, Lys66-Lys76, Lys101, Lys105, Lys130, Lys159, Lys186, and Lys230-Lys236. These domains include those previously reported accessible to N-hydroxysuccinimidobiotin only in solution (Frankel and Bricker (1995) Biochemistry 34, 7492-7497), and may be important for the interaction of the 33-kDa protein with PSII intrinsic proteins.

Amino Acid Sequence↗
PubMed1997

Purification and characterization of a glutamic-acid-specific endopeptidase from Bacillus subtilis ATCC 6051; application to the recovery of bioactive peptides from fusion proteins by sequence-specific digestion.

Screening cultures of nonpathogenic microorganisms led us to a glutamic-acid-specific endopeptidase from Bacillus subtilis ATCC 6051, which we purified and named BSase. The nucleotide sequence encoding BSase, with a molecular mass of 23,894 Da, completely agreed with that of the mpr gene, which had been reported by Rufo Jr. and Sloma et al. to encode a metalloprotease [J Bacteriol (1990) 172: 1019-1023 and 1024-1029 respectively]. However, enzymatic characterization revealed it to have the catalytic triad of a serine protease and not the consensus sequence of a metalloprotease, and it was inhibited by diisopropylfluorophosphate. We therefore consider BSase (mpr) to be a serine protease. In the alignment of the acidic-amino-acid-specific proteases, the proteases from bacilli have a highly conserved histidine residue, which is most important in the histidine triad in the proteases from streptomycetes. Furthermore, Ca2+ was necessary for its activity and stability. BSase cleaved the C-terminal glutamic acid with high specificity and was very stable over a wide pH range. On the basis of these properties, we tried to retrieve a bioactive peptide from a fusion protein by sequence-specific digestion, and succeeded in obtaining the bioactive peptide. BSase was found to be very useful as a tool for selective cleavage.

Amino Acid Sequence↗
PubMed1997

Drug disposition of incadronate, a new bisphosphonate, in rats with bone metastases.

1. Drug disposition of incadronate in the nude rat with bone metastases induced by A375 human melanoma cells was studied after intravenous administration. 2. The pharmacokinetics of incadronate (plasma concentration, urinary excretion and bone uptake) in rat with bone metastases was not markedly different from that in the control rat. This compound, however, was selectively taken up in the bone region around metastatic tumour nests. 3. Drug concentrations in the bone region around tumour nests were 3-10 micrograms/g, these levels being higher than the IC50 (0.35 microgram/ml) for the inhibitory effect of this drug on osteoclasts in vitro. 4. In contrast, concentrations in the tumour nest itself was < 0.7 microgram/g, being markedly lower than the IC50 (35 micrograms/ml) for the inhibitory effect on the proliferation of tumour cells in vitro. 5. These results strongly suggest that pharmacological action of incadronate in mouse with bone metastases (inhibitory effect on the growth of metastatic tumour in bone) is caused not by the direct action on the tumour cells but by the distribution of the drug in the perifocal bone region followed by inhibition of the activity of osteoclasts, resulting in inhibition of the osteolytic process, which is necessary for the progress of metastatic tumour.

Animals↗
PubMed1997

Characterization of a novel cell damage model induced by acid and pepsin using rat gastric epithelial cells: protective effect of sucralfate.

We have established a new model for rat gastric epithelial cell (RGM1) damage caused by both acid and pepsin. Exposure of RGM1 to an acidified medium (pH 3.5-5.0) for 10-50 min decreased cell viability in a time- and pH-dependent manner. Pepsin (0.5-1.0 mg/mL) at pH 4.5 potentiated cell damage in a concentration-dependent manner. Based on these results, two types of cell damage models caused by incubation of cells at pH 4.0 and with pepsin (0.75 mg/mL) at pH 4.5 for 30 min, respectively, were established. The intracellular pH (pHi) gradually decreased with a decrease in medium pH and an increase in exposure time. At pH < or = 4.0, pHi reached approximately pH 6.3. Pepsin at pH 4.5 caused a further reduction in pHi compared with the acidified medium alone. Pepsin pre-incubated with pepstatin did not induce any cell damage. Pretreatment with sucralfate (0.1-3 mg/ mL) for 2 h significantly prevented cell damage caused at both pH 4.0 and with pepsin at pH 4.5 in a concentration-dependent manner. Sucralfate (3 mg/mL) significantly prevented the reduction in pHi at pH 4.0 or with pepsin at pH 4.5. 16,16-Dimethyl prostaglandin E2 (30 micrograms/mL) had no effect on either cell damage or pHi. These cell damage models involving RGM1 are useful for studying the mechanism underlying cell damage and for the screening of cytoprotective drugs.

Animals↗
PubMed1996

NK 1+ CD4- CD8- alphabeta T cells in the peritoneal cavity: specific T cell receptor-mediated cytotoxicity and selective IFN-gamma production against B cell leukemia and myeloma cells.

NK1+ double negative (DN) alphabeta T cells were present in the peritoneal exudate cells (PEC) of both normal and athymic B6 mice, accounting for as much as 25% of the total T cells, while their numbers were far less in the PEC of BALB/c and (BALB/c x B6)F1 mice. IL-2-dependent clones established from the DN alphabeta T cell population in the PEC of IL-2 receptor alpha-chain transgenic B6 mice exhibited potent cytotoxicity against a series of B cell lineage leukemias and myelomas, such as CD5+BCL1 and MOPC, without affecting NK-susceptible targets. The cytotoxicity of the clones against BCL1 and MOPC was specifically inhibited by anti-CD3, anti-alphabetaTCR, or anti-relevant Vbeta (Vbeta8) Ab, but not by control Abs, indicating that it was mediated by the specific alphabetaTCR/CD3. Other BALB/c-derived target cells expressing both MHC class I and class II were not affected, and neither Ab against them affected the cytotoxicity, strongly suggesting that the cytotoxicity of NK1+ DN alphabeta T cell clones was independent of the particular MHC Ags. The clones produced IFN-gamma, but little IL-2 or IL-4, in response to anti-CD3 stimulation, to the susceptible, but not resistant, targets, and to IL-12. The clones exhibited TCRalpha (Valpha8) distinct from an invariant TCRalpha (Valpha14) reported to dominate in thymic NK1+ alphabeta T cells. The presence of DN alphabeta T cells with similar functional features in the normal PEC was confirmed by the short term stimulation in vitro. The present results along with other recent reports strongly suggested that, like the mainstream alphabeta T cells, the NK1+ DN alphabeta T cell population consisted of functionally heterogeneous subsets.

Amino Acid Sequence↗
PubMed1996

Effects of habitual physical exercise on physiological age in men aged 20-85 years as estimated using principal component analysis.

A population of 221 healthy adult men (aged 20-85 years) was studied to determine whether those who exercised regularly were in good biological condition, and also whether those who were in a state of high physical fitness were in a good state biologically, in terms of physiological age (PA) and physical fitness age (FA) as estimated by principal component analysis. A group of 17 physiological function tests and 5 physical fitness tests were employed to estimate PA and FA, respectively. The results of this study indicated that those who maintained high physical fitness at all age decade groups from 20 to 79 years had a trend towards maintaining a relatively lower PA (physiologically younger). Mean PA and FA of the trained group were younger by 4.7 and 7.3 years, respectively than those of the untrained group. In addition, the slope of regression line of PA on chronological age was more gentle in the trained group than that in the untrained group. These results would suggest that those who are in a state of high physical fitness maintain a relatively good physiological condition, and that regular physical exercise may delay physiological changes normally seen with aging, and consequently may increase the life span.

Adult↗
PubMed1996

Gastric duplication cyst: evaluation by endoscopic ultrasonography and magnetic resonance imaging.

Endoscopic ultrasonography (EUS) and magnetic resonance imaging (MRI) are becoming popular methods for examining tumorous lesions along the upper gastrointestinal tract. Though duplication cysts are uncommon, EUS findings from gastric duplication cysts have accumulated and proven very useful for preoperative diagnosis. There have been few reports, however, concerning MRI findings from these cysts. We report herein the case of a 25-year-old man with a gastric duplication cyst. EUS demonstrated a cystic mass adjacent to the fourth layer of the stomach wall. MRI revealed a cyst containing low signal-intensity fluid and high signal-intensity fluid separated by levels. In addition to the characteristic findings from preoperative examinations, the unique histological findings from the cyst are also described.

Adult↗
PubMed1996

Tenosynovial giant-cell tumor arising from the anterior cruciate ligament of the knee.

The localized form of tenosynovial giant-cell tumor is rarely located intraarticularly, especially in the large weight-bearing joints. We report the first case of localized, intraarticular tenosynovial giant-cell tumor arising from the anterior cruciate ligament of a knee in which locking and effusion had occurred. After arthroscopic removal of this tumor, the patient became asymptomatic.

Adult↗
PubMed1996

An endoscopic follow-up study of the development of diffuse antral vascular ectasia.

No endoscopic follow-up studies are available on the development of diffuse antral vascular ectasia (DAVE). We present here a ten-year follow-up study from discrete initial lesions to the full picture of DAVE. In a 72-year-old female patient with liver cirrhosis, the earliest findings of DAVE were several red spots, with or without a white halo, in the distal antrum. During follow-up, the spots increased in number, coalesced, and extended to the proximal antrum. Three years after the initial findings, latent hemorrhage occurred at a time when confluent lesions were formed. One year later, diffuse distribution of the antral lesions was observed, which led to the diagnosis of DAVE and developed to the full picture within three more years. Two years later, the patient presented with hematemesis, which confirmed the diagnosis of DAVE clinically. Treatment consisted of monopolar electrocoagulation, leading to a stable hemoglobin value for one year. This case study provides some substantial clues to the early detection and treatment of DAVE.

Aged↗
PubMed1996

Cyst sclerotherapy with minocycline hydrochloride in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: The enlarged cysts in autosomal dominant polycystic kidney disease (ADPKD) frequently cause abdominal discomfort. Cyst sclerotherapy with minocycline hydrochloride was performed to relieve this symptom. METHODS: Ten symptomatic ADPKD cases were recruited. As a sclerosant, minocycline hydrochloride solution (10 mg/dl) was used. This solution was instilled into the cysts under ultrasonographic control. Renal volume was calculated before therapy and at 6-month intervals thereafter. Renal function and blood pressure were regularly monitored. The effect of sclerotherapy on symptoms was also assessed at 6-month intervals. RESULTS: At 6 months, renal volume was statistically lower than the presclerotherapy, and was associated with improvement in chronic symptoms. However, such ameliorating effects were blunted at 12 months. Renal volume reduction at 6 and 12 months showed a significant positive correlation with the dose of minocycline injected. No significant influence in renal function and blood pressure was observed. CONCLUSIONS: These results suggest that cyst sclerotherapy with minocycline hydrochloride is a valid treatment regime for the relief of chronic symptoms in ADPKD cases, although repeated application of this approach may be required to obtain a more long-term effect.

Adult↗