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Y Hashimoto

Publications and source records attributed to Y Hashimoto.

At least 127 records · Page 7Linked to original sources
PubMed2001

[Usefulness of power Doppler ultrasound in a patient with renal cell carcinoma in the wall of a simple renal cyst].

We present a case of renal cell carcinoma in the wall of a simple renal cyst. A 54-year-old man visited our hospital with a complaint of right back pain. Ultrasound study revealed right hydronephrosis, a ureteral stone, and a 9 x 8 cm renal cyst, with a tumor, 2 cm in diameter, in the cyst wall. Power Doppler Ultrasound and enhanced computed tomography demonstrated hypervascularity of the tumor. Clinically, he was diagnosed as renal cell carcinoma and nephrectomy was performed. Pathological findings of the tumor showed clear cell carcinoma in the wall of a simple renal cyst. Twelve months after the nephrectomy, he was free from recurrence.

Carcinoma, Renal Cell↗
PubMed2001

Selective activation of apoptosis program by S-p-bromobenzylglutathione cyclopentyl diester in glyoxalase I-overexpressing human lung cancer cells.

PURPOSE: Glyoxalase I (GLO1) is an enzyme that plays a role in the detoxification of methylglyoxal, a side-product of glycolysis. We previously reported that GLO1 was a resistant factor to antitumor agent-induced apoptosis, and that S-p-bromobenzylglutathione cyclopentyl diester (BBGC), an effective inhibitor of GLO1, selectively sensitized to etoposide the drug-resistant human leukemia cells that overexpressed GLO1. In this study, we quantitatively measured GLO1 enzyme activity in various human solid tumor cells, and the antiproliferative effect of the GLO1 inhibitor was examined. EXPERIMENTAL DESIGN: BBGC-induced apoptosis was assessed by flow cytometry. To evaluate antitumor activity of BBGC in vivo, we developed human cancer xenografts in nude mice. RESULTS: We found that GLO1 enzyme activity was higher in all of the 38 human cancer cell lines that we examined than in the normal tissue samples. Moreover, GLO1 activity was frequently elevated in human lung carcinoma cells. Positive correlation between cellular GLO1 activity and BBGC sensitivity was observed in the lung cancer cell lines. Human lung cancer NCI-H522 and DMS114 cells, expressing higher GLO1 activity, underwent apoptosis when treated with BBGC, whereas A549 cells, expressing lower activity, did not. BBGC induced the activation of the stress-activated protein kinases c-Jun NH(2)-terminal kinase 1 (JNK1) and p38 mitogen-activated protein kinase (MAPK), which led to caspase activation in GLO1-overexpressing tumor cells. BBGC significantly inhibited the growth of xenografted DMS114 and human prostate cancer DU-145. CONCLUSIONS: Our present results indicate that GLO1 is a tumor-specific target enzyme especially in human lung carcinoma cells and that the GLO1 inhibitor is a potent chemotherapeutic agent to repress GLO1-overexpressing human tumors.

Animals↗
PubMed2001

[Reference intervals of urinary biochemical analysis in Japanese men].

To determine the reference intervals of urinary albumin, immunoglobulin G, transferrin, alpha 1 microglobulin, and N-acetyl-beta-D-glucosaminidase, we measured those components and creatinine in urine from men with normal blood pressure(systolic < or = 139 mmHg and diastolic < or = 89 mmHg), HbA1c < or = 5.8% and negative qualitative tests of urinary protein and hematuria. The subjects were 150 men in their thirties, 136 in their forties, and 135 in their fifties. Urines was collected in the morning after at least 12 hours fast and stored at -80 degrees C until assayed. The levels of creatinine decreased with age, whereas no change was observed in the levels of other urinary components. Consequently, the levels of those components expressed as g. creatinine increased with age. The reference intervals per g. creatinine were determined for each age-bracket using the iterative truncation method after logarithmical transformation of the values.

Acetylglucosaminidase↗
PubMed2001

Immunohistochemical demonstration of chromogranin A in endocrine organs of the rat and horse by use of region-specific antibodies.

Chromogranin A (CgA) is an acidic glycoprotein that is co-stored with hormones or neurotransmitters in granular components of endocrine cells and neurons, and released together with them in response to adequate stimulation. In addition to acting as a packaging protein, CgA functions as a precursor molecule that yields several bioactive peptides by proteolytic cleavage. The purpose of this study is to elucidate how different the processing of CgA is among endocrine tissues by immunostaining using multiple region-specific antisera, and to evaluate the availability of region-specific antisera. When various endocrine organs of rats were immunostained with four region-specific antisera against rat CgA (CgA 1-28, 94-130, 296-314, and 359-389), all amine/peptide-secreting endocrine tissues except the pineal body were stained positively. The adrenal medulla and gastric endocrine cells were equally intensely immunoreactive to all four antisera, while the other endocrine tissues, represented by pancreatic islets, showed different staining patterns depending on the antiserum. These results suggest that the processing of CgA differs from tissue to tissue. An antiserum against horse CgA 335-365, corresponding to rat CgA 359-389 which shows the highest concentration in the plasma and urine of the rat, again stained all endocrine tissues of the horse except the pineal body. Therefore, the anti-horse CgA 335-365 serum is useful for immunohistochemical survey of horse CgA, and may make possible the establishment of a CgA assay system for the measurement of CgA in the plasma, urine and saliva.

Animals↗
PubMed2001

Immunoglobulin heavy chain gene analysis of ocular adnexal extranodal marginal zone B-cell lymphoma.

PURPOSE: To clarify the cellular origin of extranodal marginal-zone B-cell lymphoma (EZML) of the mucosa-associated lymphoid tissue (MALT) type in ocular adnexa, the somatic mutation was analyzed in the immunoglobulin heavy-chain variable region (VH) gene. METHODS: Eight cases of EZML in the orbit and four in the conjunctiva were studied. The VH genes were amplified by a seminested PCR and sequenced directly. These were compared with the closest published VH germline segments to determine the somatic mutation frequency. Intraclonal microheterogeneity, which was termed the ongoing mutation frequency in the current study, was estimated by counting the number of single nucleotide substitutions in individual clones and dividing by the total number of nucleotides analyzed. Nine cases of gastrointestinal EMZL were also examined for comparison. RESULTS: The somatic mutation frequency varied between 2.0% and 12.7%, with a mean value of 7.9%. Ten cases with intraclonal microheterogeneity showed between one and six further substitutions. The average of ongoing mutation frequency was 0.11%, with a range of 0% to 0.25%. In the gastrointestinal EMZLs, the average of somatic mutation frequency was 8.5% (1.5%-14.2%) and of ongoing mutation frequency was 0.51% (0.25%-0.75%). CONCLUSIONS: The average of ongoing mutation frequency in ocular adnexal EMZL was lower than that in gastrointestinal EMZL. Both ocular adnexal and gastrointestinal EMZLs are derived from postgerminal center memory B cells, but the low ongoing mutation frequencies of ocular adnexal EMZL may result from less antigen stimulation and follicular colonization in the orbit relative to gastrointestinal EMZL.

Adult↗
PubMed2001

Increased concentrations of protein gene product 9.5 in the synovial fluid from horses with osteoarthritis.

Our previous study established protein gene product 9.5 (PGP 9.5), a ubiquitin C-terminal hydrolase, as a specific cytochemical marker of synovial lining cells (type B synoviocytes) in the horse joint. The present study aimed to detect PGP 9.5 in the synovial fluid and shows that PGP 9.5 is a valuable marker of osteoarthritis in the horse. Immunohistochemical staining confirmed rich and consistent localization of PGP 9.5 immunoreactivity in the cytoplasm of synovial lining cells in the normal horse joint. Western blot analysis of synovial fluid from normal joints could detect a significant band corresponding to that contained in the brain and synovial membrane extracts. When 60 synovial fluid samples from normal and abnormal joints were assayed with an enzyme-linked immunosorbent assay (ELISA) system, the concentration of PGP 9.5 tended to be elevated in osteochondrosis dissecance, inflammatory arthropathy and intra-articular fracture, among which a statistically significant elevation was recognizable between the intra-articular fracture and the control. Thus, this study demonstrated the possibility that PGP 9.5, derived from synovial lining cells, may be a new biochemical marker for arthritic disorders of the horse.

Animals↗
PubMed2001

Potential for error when assessing blood cyanide concentrations in fire victims.

The present study explores toxicologic significance of blood cyanide concentrations in fire victims. Headspace gas chromatography was used for cyanide detection. Analysis of blood samples from ten fire victims (postmortem interval = 8 h to 3 to 5 d) detected zero to 11.9 mg/L of cyanide and a large difference in cyanide concentrations among victims. Carboxyhemoglobin (COHb) saturation was in the range of 24.9 to 84.2%. To examine the effects of methemoglobinemia and postmortem interval on blood cyanide concentrations in fire victims, an experiment was carried out using rabbits as the animal model. The rabbits were sacrificed by intramuscular injection of 1 mL/kg 2% potassium cyanide 5 min after intravenous injection of 0.33 mL/kg of 3% sodium nitrite (Group A, n = 3) or physiological saline (Group B, n = 6). Average methemoglobin contents immediately before potassium cyanide administration were 6.9 and 0.8% in Groups A and B, respectively. Average cyanide concentrations in cardiac blood at the time of death were 47.4 and 3.56 mg/L, respectively. When blood-containing hearts of the rabbits (n = 3 for Group B) were left at 46 degrees C for the first 1 h, at 20 to 25 degrees C for the next 23 h and then at 4 degrees C for 48 h, approximately 85 and 46% of the original amounts of blood cyanide disappeared within 24 h in Groups A and B, respectively. After the 72-h storage period, 37 and 10%, respectively, of the original amounts of cyanide remained in the blood. When the other three hearts in Group B were left at 20 to 25 degrees C for the last 48 h without refrigeration, cyanide had disappeared almost completely by the end of the experiment. The present results and those published in the literature demonstrate that the toxic effects of cyanide on fire victims should not be evaluated based solely on the concentration in blood.

Animals↗
PubMed2001

[Critical role for cell cycle regulators in androgen receptor function].

Androgen plays an important role in the growth of prostate cancer, but the molecular mechanism that underlies development of resistance to antiandrogen therapy remains unknown. Cyclin E has now been shown to increase the transactivation activity of the human androgen receptor (AR) in the presence of its ligand dihydrotestosterone. The enhancement of AR activity by cyclin E was resistant to inhibition by the antiandrogen 5-hydroxyflutamide. Cyclin E was shown to bind directly to the AB domain of the AR, and to enhance its AF-1 transactivation function. These results suggest that cyclin E functions as a coactivator of the AR, and that aberrant expression of cyclin E in tumors may contribute persistent activation of AR function, even during androgen ablation therapy.

Antineoplastic Agents, Hormonal↗
PubMed2000

Enhanced tumorigenicity caused by truncation of the extracellular domain of GP125/CD98 heavy chain.

GP125/CD98 is a heterodimeric 125-kDa glycoprotein, which consists of an 85-kDa heavy chain (hc) and a 40-kDa light chain (lc), and is strongly expressed on the cell surface of various tumor cells, irrespective of their tissue of origin. We have recently demonstrated that overexpression of the CD98hc cDNA causes malignant transformation of NIH3T3 cells. To investigate the function of the extracellular domain of CD98hc in cell proliferation and malignant transformation, we established two NIH3T3-derived clones transfected with human truncated CD98hc cDNAs, and compared their characteristics with parental NIH3T3 and clones transfected with full-length CD98hc cDNA. Truncated as well as full-length CD98hc-transfected clones grew to a higher saturation density than control cells. Efficiency of colony formation in soft agar was augmented in all CD98hc-transfected clones, and the degrees of augmented colony formation of the transfectants expressing full-length CD98hc of 529 a.a. or truncated CD98hc of 418 a.a. were reduced by anti-human CD98hc antibodies, while that of the transfectant expressing truncated CD98hc of 237 a.a. lacking the epitopes recognized by anti-human CD98hc antibodies was not affected by the addition of antibodies. CD98hc-transfected clones developed tumors in athymic mice, and tumor growth of truncated CD98hc-transfected clones was faster than that of full-length CD98hc-transfected clones.

3T3 Cells↗
PubMed2000

Neuronal cell apoptosis by a receptor-binding domain peptide of ApoE4, not through low-density lipoprotein receptor-related protein.

Since an apolipoprotein E4 (ApoE4) peptide composed of the low-density lipoprotein (LDL) receptor-related protein (LRP)-binding domain [ApoE4(141-149)(2) or ApoE(141-155)(2)] exerts neurotoxicity in primary neurons and neuronal cell lines, it has been controversial whether these effects are mediated by LRP. Here, we examined whether ApoE4(141-149)(2)-induced toxicity is mediated by LRP in a neuronal cell system where ApoE4 toxicity is mediated by LRP: serum-deprived F11 neuronal cells. In these cells, where ApoE4 exerted toxicity by apoptosis in a manner sensitive to both caspase inhibitors and pertussis toxin (PTX), ApoE4(141-149)(2) also caused cell death by apoptosis but in a caspase-inhibitor-resistant, PTX-resistant manner. ApoE4(141-149)(2)-induced death was not inhibited by antisense oligonucleotides to LRP. Therefore, we conclude that ApoE4(141-149)(2) is able to exert neurotoxicity without involving LRP.

Amino Acid Sequence↗
PubMed2000

Neuronal apoptosis by apolipoprotein E4 through low-density lipoprotein receptor-related protein and heterotrimeric GTPases.

The epsilon4 genotype of apolipoprotein E (apoE4) is the most established predisposing factor in Alzheimer's disease (AD); however, it remains unclear how apoE4 contributes to the pathophysiology. Here, we report that the apoE4 protein (ApoE4) evokes apoptosis in neuronal cells through the low-density lipoprotein receptor-related protein (LRP) and heterotrimeric GTPases. We examined neuron/neuroblastoma hybrid F11 cells and found that these cells were killed by 30 microg/ml ApoE4, but not by 30 microg/ml ApoE3. ApoE4-induced death occurred with typical features for apoptosis in time- and dose-dependent manners, and was observed in SH-SY5Y neuroblastomas, but not in glioblastomas or non-neuronal Chinese hamster ovary cells. Activated, but not native, alpha2-macroglobulin suppressed this ApoE4 toxicity. Suppression by the antisense oligonucleotide to LRP and inhibition by low nanomolar concentrations of LRP-associated protein RAP provided evidence for the involvement of LRP. The involvement of heterotrimeric GTPases was demonstrated by the findings that (1) ApoE4-induced death was suppressed by pertussis toxin (PTX), but not by heat-inactivated PTX; and (2) transfection with PTX-resistant mutant cDNAs of Galpha(i) restored the toxicity of ApoE4 restricted by PTX. We thus conclude that one of the neurotoxic mechanisms triggered by ApoE4 is to activate a cell type-specific apoptogenic program involving LRP and the G(i) class of GTPases and that the apoE4 gene may play a direct role in the pathogenesis of AD and other forms of dementia.

Animals↗
PubMed2000

Multiple mechanisms underlie neurotoxicity by different types of Alzheimer's disease mutations of amyloid precursor protein.

We examined a neuronal cell system in which single-cell expression of either familial Alzheimer's disease (FAD) gene V642I-APP or K595N/M596L-APP (NL-APP) in an inducible plasmid was controlled without affecting transfection efficiency. This system revealed that (i) low expression of both mutants exerted toxicity sensitive to both Ac-DEVD-CHO (DEVD) and glutathione ethyl ester (GEE), whereas wild-type APP (wtAPP) only at higher expression levels caused GEE/DEVD-resistant death to lesser degrees; (ii) toxicity by the V642I mutation was entirely GEE/DEVD sensitive; and (iii) toxicity by higher expression of NL-APP was GEE/DEVD resistant. The GEE/DEVD-sensitive death was sensitive to pertussis toxin and was due to G(o)-interacting His(657)-Lys(676) domain. The GEE/DEVD-resistant death was due to C-terminal Met(677)-Asn(695). APP mutants lacking either domain unraveled elaborate intracellular cross-talk between these domains. E618Q-APP, responsible for non-AD type of a human disease, only exerted GEE/DEVD-resistant death at higher expression. Therefore, (i) different FAD mutations in APP cause neuronal cell death through different cytoplasmic domains via different sets of mechanisms; (ii) expression levels of FAD genes are critical in activating specific death mechanisms; and (iii) toxicity by low expression of both mutants most likely reflects the pathogenetic mechanism of FAD.

Alzheimer Disease↗
PubMed2000

Mutant mouse lysozyme carrying a minimal T cell epitope of hen egg lysozyme evokes high autoantibody response.

Self proteins including foreign T cell epitope induce autoantibodies. We evaluated the relationship between the size of foreign Ag introduced into self protein and the magnitude of autoantibody production. Mouse lysozyme (ML) was used as a model self protein, and we prepared three different ML derivatives carrying T cell epitope of hen egg white lysozyme (HEL) 107-116, i.e, heterodimer of ML and HEL (ML-HEL), chimeric lysozyme that has residue 1-82 of ML and residue 83-130 of HEL in its sequence (chiMH), and mutant ML that has triple mutations rendering the most potent T cell epitope of HEL (sequence 107-116). Immunization of BALB/c mice with these three ML derivatives induced anti-ML autoantibody responses, whereas native ML induced no detectable response. In particular, mutML generated a 10(4) times higher autoantibody titer than did ML-HEL. Anti-HEL107-116 T cell-priming activities were almost similar among the ML derivatives. The heterodimerization of mutant ML and HEL led to significant reduction of the autoantibody response, whereas the mixture did not. These results show that size of the nonself region in modified self Ag has an important role in determining the magnitude of the autoantibody response, and that decrease in the foreign region in a modified self protein may cause high-titered autoantibody response.

Animals↗
PubMed2000

Sequence analysis of the Plutella xylostella granulovirus genome.

The Plutella xylostella granulovirus (PxGV) genome DNA was sequenced and the predicted open reading frames (ORFs) were compared to genes of the first-sequenced GV, Xestia c-nigrum GV (XcGV), and those from other baculoviruses and organisms. PxGV DNA has a size of 100,999 bp with a G + C content of 40.7%. The analysis predicted 120 ORFs with a size of 150 nucleotides or larger that showed minimal overlap. Blast searches followed by a comparison of ORF arrangement with those of completely sequenced baculovirus genomes showed the presence of 102 homologs to other genes in the database. Among them, 74 and 100 were homologous to genes of Autographa californica NPV (AcMNPV) and XcGV, respectively. A striking feature of the relationship between the genomes of PxGV and XcGV was the conservation of the order and orientation of homologous genes. Even though the XcGV genome is much larger than that of PxGV (178 vs 101 kb) and had many more predicted ORFs (181 vs 120) with an average amino acid sequence relatedness of 42%, the order and orientation of almost all homologous genes was conserved. The PxGV genome contained four homologous regions (hrs), each with 10 to 23 repeated sequences of 101 to 105 nucleotides containing a 15-bp imperfect palindrome in the center of the repeats.

Amino Acid Sequence↗
PubMed2000

On the antioxidant mechanism of curcumin: classical methods are needed to determine antioxidant mechanism and activity.

[reaction: see structure] The antioxidant activity of curcumin (1, 7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) was determined by inhibition of controlled initiation of styrene oxidation. Synthetic nonphenolic curcuminoids exhibited no antioxidant activity; therefore, curcumin is a classical phenolic chain-breaking antioxidant, donating H atoms from the phenolic groups not the CH(2) group as has been suggested (Jovanovic et al. J. Am. Chem. Soc. 1999, 121, 9677). The antioxidant activities of o-methoxyphenols are decreased in hydrogen bond accepting media.

Antioxidants↗
PubMed2000

Cyclin E as a coactivator of the androgen receptor.

Androgens play an important role in the growth of prostate cancer, but the molecular mechanism that underlies development of resistance to antiandrogen therapy remains unknown. Cyclin E has now been shown to increase the transactivation activity of the human androgen receptor (AR) in the presence of its ligand dihydrotestosterone. The enhancement of AR activity by cyclin E was resistant to inhibition by the antiandrogen 5-hydroxyflutamide. Cyclin E was shown to bind directly to the COOH terminus portion of the AB domain of the AR, and to enhance its AF-1 transactivation function. These results suggest that cyclin E functions as a coactivator of the AR, and that aberrant expression of cyclin E in tumors may contribute to persistent activation of AR function, even during androgen ablation therapy.

Cell Line↗