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Biomedical subjects

Y Hirai

Publications and source records attributed to Y Hirai.

At least 37 records · Page 2Linked to original sources
PubMed2001

Somatic mutations of the PTEN/NMAC1 gene associated with frequent chromosomal loss detected using comparative genomic hybridization in endometrial cancer.

OBJECTIVES: We analyzed the mutational status of the transforming growth factor-beta type II receptor (TGF beta RII), BAX, and PTEN/MMAC1 genes as well as microsatellite instability (MI) in 29 consecutive cases of endometrial carcinoma operated on at the Cancer Institute Hospital (Tokyo, Japan). To identify chromosomal loss associated with significant somatic mutations, we conducted comparative genomic hybridization (CGH) analysis. METHODS: We conducted a direct sequence for mutational analysis of these genes. To examine copy number loss at the chromosomal regions bearing these genes, we used CGH analysis. CGH analysis may provides a genome-wide overview about tumor-associated genomic imbalances. RESULTS: Among nine tumors that showed the MI+ phenotype, four (44%) demonstrated a significant mutation with a definite amino acid change in the PTEN/MMAC1 gene. CGH analysis demonstrated that all four tumors (100%) showed chromosomal copy number loss around the locus of this gene, whereas four (57%) of seven tumors with PTEN/MMAC1 mutations showed chromosomal loss or double mutations in MI- carcinomas. The role of TGF beta RII and BAX genes is limited as a target gene of MI+ phenotype in endometrial cancer, because several mutations of these genes were detected but a chromosomal loss was demonstrated by CGH in only one tumor in MI+ endometrial cancers with mutation. CONCLUSIONS: This report reveals, by using CGH, that most MI+ endometrial cancers with PTEN/MMAC1 mutations as well as MI- tumors showed inactivation of both alleles of this gene, which strongly suggested the involvement of this gene in carcinogenesis.

Adenocarcinoma↗
PubMed2001

Effects of ipriflavone on bone loss following a bilateral ovariectomy and menopause: a randomized placebo-controlled study.

A randomized placebo controlled study was undertaken to evaluate the effect of ipriflavone (IP) against the bone loss in premenopausal ovariectomized women and postmenopausal women. Thirty-seven Japanese women who underwent premenopausal bilateral ovariectomy within 3 months (early stage group) and 52 Japanese women who were ovariectomized or who had undergone menopause more than 3 years before the start of the study (late stage group) were enrolled. The patients were randomly allocated into two groups: those who received IP (600 mg/day) and those who received placebo. The bone mineral density (BMD) of the lumbar vertebrae was measured by dual energy X-ray absorptiometry, and the markers of bone metabolism were measured at the same time that BMD was measured. In the early stage group, the IP group showed a 6.7% decrease in BMD from baseline levels, whereas the placebo group showed a 10.7% decrease (P < 0.01) at 12 months of treatment, and 7.1% and 12.6% decrease at 24 months of treatment, respectively (P < 0.01). In the late stage group, there was a 0.3% increase in BMD in the IP group and a 2.3% decrease in the placebo group at 6 months of treatment (P < 0.01), and similar changes were seen at 18 months (1.4% increase and 3.9% decrease; P < 0.01). IP suppressed bone loss compared with placebo, however, did not prevent acute bone loss in the early stage following ovariectomy. The effect of IP alone on bone loss in the early stage is not sufficient to reduce the risk of osteoporosis in later life.

Bone Density↗
PubMed2001

Malignant potential of positive peritoneal cytology in endometrial cancer.

OBJECTIVE: To investigate the malignant potential of positive peritoneal cytology in endometrial cancer. METHODS: Fifty patients with clinical stage I-II endometrial cancer in whom the disease was completely surgically resected and positive peritoneal smears were found at surgery formed the study population. In these patients, a tube for cytologic analyses was inserted into the peritoneal cavity when closing the abdomen. The peritoneal cavity was irrigated with physiologic saline, and washings were obtained through the tube 7 and 14 days after the operation. RESULTS: Persistence of positive peritoneal cytology was observed in four of seven patients with adnexal metastasis, zero of nine patients with nodal disease, and one of 34 patients with disease confined to the uterus, for a total of 10% (5 of 50). In the remaining 45 (90%) patients, no malignant cells were found in any of the washings. CONCLUSION: The current series suggests that endometrial cancer cells found in the peritoneal cavity usually disappear within a short time and seem to have a low malignant potential. It also seems that only malignant cells from special cases, such as adnexal metastasis, may be capable of independent growth, and are possibly associated with intraperitoneal recurrence.

Adenocarcinoma↗
PubMed2001

Is insulin resistance or diabetes mellitus associated with stroke? An 18-year follow-up study.

Insulin resistance and/or diabetes are risk factors for coronary artery disease. However, it is still controversial whether they are associated with the development of stroke. A total of 304 Japanese men and women, aged 20-69 years, were selected on the basis of casual high blood glucose concentrations from 2732 participants of a population-based health examination in 1980. They all underwent a 50 g oral glucose tolerance test in 1981. Homa IR (index of insulin resistance) and Homa beta-cells (index of beta-cell function) were calculated from their fasting insulin and glucose using the formulas for the homeostasis model. They were followed-up for 18 years. Incidence of stroke was investigated by computed tomography. During 18 years, 28 subjects had a stroke; 21 had ischemic and nine had hemorrhagic strokes (two had both). Baseline variables, which showed an independent association with the incidence of stroke in the Cox proportional hazard model, were blood pressure, use of anti-hypertensive medications, and Homa beta-cell index (inversely) after adjustments for age and sex. After further adjustment for blood pressure using a step-forward method, Homa beta-cell was significantly related to the incidence of stroke (Hazard ratio: 0.65, 95% confidence interval: 0.44-0.95). In addition to hypertension, diabetes but not insulin resistance, is a risk factor for stroke.

Adult↗
PubMed2001

An anatomic study of the extensor tendons of the human hand.

A total of 548 upper limbs (276 right and 272 left hands) from Japanese cadavers were dissected. The arrangements of extensor indicis proprius, extensor digitorum communis (EDC), and extensor digiti minimi tendons and the intertendinous connections were studied. The most common pattern of extensor tendons was as follows: the index finger had a single EDC tendon, the middle finger had a single EDC tendon, the ring finger had a single EDC tendon, and the small finger had a single EDC tendon or a single common EDC tendon distributed to the ring and small finger. A single extensor indicis proprius tendon ran along the ulnar side of the EDC, and the extensor digiti minimi tendon consisted of 2 slips. Intertendinous connections were classified into 3 types: type 1 with a filamentous band, type 2 with a fibrous band, and type 3 with a tendinous band subdivided to r-shaped and y-shaped. The most common patterns were type 1 in the second intermetacarpal space (IMCS), type 3r in the third IMCS, and type 3y in the fourth IMCS.

Cadaver↗
PubMed2001

Heart rate and mortality in a Japanese general population: an 18-year follow-up study.

The predictive power of elevated heart rate for total mortality was evaluated in a Japanese general population. A total of 573 male participants, aged 40 to 64, who underwent a health examination in 1977, were followed until 1994. Heart rate (beats per minute; bpm) was measured using an electrocardiogram. During the 18 years, 82 subjects died; 18 from cerebro-cardiovascular diseases and 36 from cancer. In a multivariate proportional hazards regression model, age, elevated systolic and diastolic blood pressures, antihypertensive medication, heart rate, uric acid, vital capacity (inversely), and serum cholesterol (inversely) were significantly associated with all-cause death. Of these variables, elevated heart rate was the strongest predictor of all-cause death after adjustment for age. Resting heart rate levels were classified into five groups: < 60 (G1), 60-69 (G2), 70-79 (G3), 80-89 (G4), and > or = 90 (G5) bpm. Heart rates of 60-69 (G2) bpm showed the lowest death rate (14.3%) and heart rate > or = 90 (G5) bpm showed the highest death rate (38.2%) after adjustments for age and other confounding factors. The relative risk of G2 versus G5 was 2.68. An increased mortality risk was shown in men whose heart rate was > or = 90 bpm. Moreover, a continuous model suggested a graded increase in risk, so that risk is likely elevated even for heart rates less than 90 bpm, and lowest risk may be around 60 bpm.

Adult↗
PubMed2001

Resin bonding to Er: YAG laser-irradiated dentin: combined effects of pre-treatments with citric acid and glutaraldehyde.

The purpose of this study was to evaluate the combined effects of citric acid and glutaraldehyde (GA) on the resin bonding to Er: YAG laser-irradiated dentin. Bovine dentin was prepared with 180- to 600-grit SiC paper and then uniformly irradiated with an Er: YAG laser (laser-irradiated group) or immersed in water at 60 degrees C for 15 min (heated group). The samples were then acid-conditioned with 10% citric acid (10-0) or 10% citric acid/3% ferric chloride (10-3) for 15 s and treated with GA for 10 min before bonding to an acrylic rod with 4-META/MMA-TBB resin. These samples were trimmed to prepare miniaturized dumbbell-shaped specimens. After storage in water at 37C for 1 d, the tensile bond strength was measured, and the fractured surface was evaluated using a scanning electron microscope (SEM). In the laser-irradiated and heated groups, the 10-3+GA-treated specimen had higher bond strength than that of 10-0+GA. On the other hand, the tensile bond strength of 10-3 +GA in the non-irradiated group was lower that that of 10-0+GA. In conclusion, the combination of 10-3 and GA for bonding with 4-META/MMA-TBB resin was the most effective for Er: YAG laser-irradiated dentin and heated dentin, but it was not effective for the non-irradiated dentin.

Acid Etching, Dental↗
PubMed2001

Expression of membrane-type 1 matrix metalloproteinase in rheumatoid synovial cells.

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is thought to be a putative regulator of pro-gelatinase A (MMP-2) in the rheumatoid synovium. In this study, we examined the effects of IL-1beta, one of the inflammatory cytokines, on the expression of MT1-MMP and the activation of pro-MMP-2 using rheumatoid synovial cells. We also studied the effects of KE-298 (2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid), a new disease-modifying anti-rheumatic drug (DMARD), on MT1-MMP expression of rheumatoid synovial cells. Type B synovial cells (fibroblast-like synovial cells) were cultured with KE-298 (25-100 microg/ml) in the presence of IL-1beta for 48 h. Activation of pro-MMP-2 secreted from synovial cells was analysed by gelatin zymography. Reverse transcription-polymerase chain reaction (RT-PCR) methods were used to detect MT1-MMP mRNA. MT1-MMP protein expression on synovial cells was examined by anti-MT1-MMP immunoblot. An active form of MMP-2 was demonstrated in the culture media conditioned by IL-1beta-stimulated synovial cells. In addition, MT1-MMP mRNA and protein expression of rheumatoid synovial cells were increased by IL-1beta treatment. KE-298 blocked this IL-1beta-induced pro-MMP-2 activation and MT1-MMP expression, but did not affect IL-1beta-induced tissue inhibitor of metalloproteinase-2 (TIMP-2) secretion from rheumatoid synovial cells. These findings indicate that activation of rheumatoid synovial cells by IL-1beta results in the induction of MT1-MMP expression. Given that MT1-MMP promotes matrix degradation by activating pro-MMP-2, these results suggest a novel mechanism whereby cytokine may contribute to articular destruction in rheumatoid arthritis (RA). KE-298 may prevent this process by down-regulating MT1-MMP expression.

Antirheumatic Agents↗
PubMed2001

Sexual isolation and cuticular hydrocarbons in Drosophila elegans.

In Drosophila elegans, partial sexual isolation has developed between the brown and black morphs, which are distributed allopatrically. The present study aims to understand how they discriminate between potential mates. Mating experiments show that the females of the two morphs differ in sexual signal(s) and the males discriminate using these differences. Body colouration is not used as a sexual cue in this species. Between the females of the two morphs, a large difference was observed in the percentages of 7-pentacosene and 9-pentacosene on the cuticle. Genetical analysis using recombinant inbred lines supported the possibility that the concentration of these pentacosenes plays a role in mate discrimination of these two morphs. However, males did not respond to killed females at all, suggesting that cuticular hydrocarbons of females are not the only cue for the induction of male courtship behaviour. It may be that unknown signals or substances are essential to induce male courtship and pentacosenes modulate the attractiveness of females, positively in the black morph and negatively in the brown morph. Drosophila elegans F1 offspring had intermediate characteristics in mate discrimination and hydrocarbon composition between the parental brown and black morph strains. The number of loci responsible for the differences in the concentration of pentacosenes and the male and female components in the mate recognition between these two morphs is suggested to be more than one.

Animals↗
PubMed2001

X-irradiation induces up-regulation of ATM gene expression in wild-type lymphoblastoid cell lines, but not in their heterozygous or homozygous ataxia-telangiectasia counterparts.

Ataxia-telangiectasia (AT) is an autosomal recessive disease. The relevant gene has been cloned and designated ATM. We studied the expression of both ATM mRNA and the ATM protein in unirradiated and X-irradiated EBV (Epstein-Barr virus)-transformed lymphoblastoid cell lines (LCLs) derived from donors who were normal (ATM + / + ), AT heterozygotes (ATM + / - ), or AT homozygotes (ATM - / - ), respectively. In ATM + / + LCLs, the levels of ATM mRNA were found to have increased by approximately 1.5-fold within 1 h of exposure to 10 Gy of X-rays, while the ATM protein levels had increased by 1.5- to 2.0-fold within 2 to 3 h of irradiation. The wild-type mRNA and protein levels both returned to their basal values fairly quickly after this time. The results obtained with the ATM + / - LCLs were quite different, however: neither the mRNA nor protein levels were found to have increased as a consequence of X-irradiation in any ATM + / - LCL. Twelve of the mutations in the ATM - / - LCLs we used were truncating mutations, and we suspected that the corresponding truncated ATM proteins would be too labile to be detected by western blot analysis. However, five of the ATM - / - LCLs produced mutant ATM proteins that were identical in molecular weight to the wild-type ATM protein. When cells from three of these five clones were exposed to X-rays, transcription of the mutant ATM genes appeared to reduce somewhat, as were the levels of protein being produced. These results suggest that the normal ATM gene responds to ionizing radiation by up-regulating its activity, whereas none of the mutant ATM genes we studied were able to respond in this way.

Ataxia Telangiectasia↗
PubMed2001

[Evaluation of immunochromatography based rapid detection kit of rotavirus and adenovirus].

We investigated the usefulness of Rapidtesta Rota-Adeno (Daiichi Pure Chemicals Co., Ltd., Japan) for rapid detection of group A rotavirus and adenovirus simultaneously using immunochromatography with clinical samples. In investigation of the reaction of the kit to 5 strains of group A rotavirus, 13 strains of adenovirus and other intestinal viruses, specific lines were formed in red to group A rotavirus and blue to adenovirus. No cross reaction was observed with other intestinal virus. In measurement of detection limit, group A rotavirus (SA11) was detected at 10(4.4)TCID50/ml, serotype 3 adenovirus at 10(4.45)TCID50/ml. The detection limit of the kit was similar to other immunochromatographic assay or enzyme immnoassay kits and approximately 10 times higher than that of kits using latex agglutination test. In comparison with other testing kits in clinical samples, the concordance with other immunochromatographic assay was 99.2% (121/122) in group A rotavirus and 98.6% (138/140) in adenovirus. The rate of concordance with latex agglutination test kit was 94.5% (69/73) in group A rotavirus and 92.3% (84/91) in adenovirus. The kit had high rates of concordance with other immunochromatographic assay kits and higher virus detection rates than those of latex agglutination test kits. Rapidtesta Rota-Adeno is able to detect group A rotavirus and adenovirus simply and rapidly. In addition, the two kinds of virus can be easily differentiated by color difference in reaction lines, suggesting that the kit is useful in clinical diagnosis.

Adenoviridae↗
PubMed2001

Immunoglobulin G1 antibody response to Helicobacter pylori heat shock protein 60 is closely associated with low-grade gastric mucosa-associated lymphoid tissue lymphoma.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is related to Helicobacter pylori infection. Specifically, it has been pointed out that pathogenesis of MALT lymphoma involves the 60-kDa heat shock protein (hsp60). To investigate humoral immune responses to the H. pylori hsp60 in patients with gastroduodenal diseases and patients with MALT lymphoma, the hsp60 of H. pylori was expressed with a glutathione S-transferase fusion protein and was purified (recombinant hsp60). Sera were obtained from H. pylori-positive patients with gastroduodenal diseases (MALT lymphoma, n = 13; gastric ulcer, n = 20; duodenal ulcer, n = 20; gastritis, n = 20) and from H. pylori-negative healthy volunteers (n = 9). Sera from patients with MALT lymphoma were also obtained at two times: before and after eradication therapy. Antibodies to hsp60 and H. pylori were assessed by enzyme-linked immunosorbent assay. The levels of immunoglobulin G (IgG) antibodies to the hsp60 of H. pylori-positive patients with gastroduodenal diseases were significantly elevated compared to those in the controls. The levels of IgG1 antibodies to hsp60 were elevated and correlated with the levels of anti-H. pylori antibodies in patients with MALT lymphoma. Humarol immunity against hsp60 may be important and relevant to gastroduodenal diseases induced by H. pylori infection.

Adult↗
PubMed2001

Lipopolysaccharide of Burkholderia cepacia and its unique character to stimulate murine macrophages with relative lack of interleukin-1beta-inducing ability.

Lipopolysaccharide (LPS) of Burkholderia cepacia was purified by the conventional phenol-water extraction method (preparation BcLPS-1), followed by enzymatic treatments with DNase, RNase, trypsin, and proteinase K (preparation BcLPS-2), and finally by deoxycholate-phenol-water extraction (preparation BcLPS-3). Cells of LPS-hyporesponsive C3H/HeJ mice were activated by both the BcLPS-1 and the BcLPS-2 preparations but barely activated by BcLPS-3. When LPS-responsive C3H/HeN mice were used as targets, endotoxic activities such as lethal toxicity to galactosamine-sensitized mice, mitogenicity to spleen cells, and activation of macrophages to induce tumor necrosis factor alpha and interleukin-6 (IL-6) were strongly exhibited even by highly purified BcLPS-3 at levels comparable to those of the highly active enterobacterial LPS of Salmonella enterica serovar Abortus-equi (SaeLPS), used as the control. The ability of BcLPS-3 to activate murine macrophages for induction of IL-1beta was, however, much weaker than that of SaeLPS. Both accumulation of pro-IL-1beta protein and expression of IL-1beta mRNA in macrophages by stimulation with BcLPS-3 were much weaker than by stimulation with SaeLPS. These results indicate that LPS of B. cepacia has the potential to play a role as a pathogenic factor with strong activity comparable to that of usual enterobacterial LPS, but unlike the latter, this LPS has a relative lack of ability in the activation of murine macrophages to induce IL-1beta. The lack of IL-1beta-inducing ability appears to be caused by incomplete signal transduction somewhere in the upstream step(s) of IL-1beta gene transcription.

Animals↗
PubMed2001

Importance of NF-kappaB in rheumatoid synovial tissues: in situ NF-kappaB expression and in vitro study using cultured synovial cells.

OBJECTIVES: To examine whether inhibition of NF-kappaB induces apoptosis of human synovial cells stimulated by tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), and anti-Fas monoclonal antibody (mAb). METHODS: The expression of proliferating cell nuclear antigen (PCNA), NF-kappaB, and the presence of apoptotic synovial cells were determined in synovial tissues. Apoptosis of cultured synovial cells was induced by inhibition of NF-kappaB nuclear translocation by Z-Leu-Leu-Leu-aldehyde (LLL-CHO). The activation of caspase-3 and expression of XIAP and cIAP2 in synovial cells in LLL-CHO induced apoptosis was also examined. RESULTS: Abundant PCNA+ synovial cells were found in rheumatoid arthritis (RA) synovial tissue, though a few apoptotic synovial cells were also detected in the RA synovial tissues. Nuclear NF-kappaB was expressed in RA synovial cells. Electrophoretic mobility shift assay showed that treatment of cells with TNFalpha or IL1beta significantly stimulated nuclear NF-kappaB activity. A small number of apoptotic synovial cells expressing intracellular active caspase-3 were found after treatment of cells with LLL-CHO. Although treatment of RA synovial cells with TNFalpha or IL1beta alone did not induce apoptosis, apoptosis induced by LLL-CHO and caspase-3 activation were clearly enhanced in TNFalpha or IL1beta stimulated synovial cells compared with unstimulated synovial cells. Furthermore, induction of apoptosis of synovial cells with caspase-3 activation by anti-Fas mAb was clearly increased by LLL-CHO. The expression of cIAP2 and XIAP in synovial cells may not directly influence the sensitivity of synovial cells to apoptosis induced by LLL-CHO. CONCLUSION: The results suggest that NF-kappaB inhibition may be a potentially important therapeutic approach for RA by correcting the imbalance between apoptosis and proliferation of synovial cells in RA synovial tissue.

Antibodies, Monoclonal↗
PubMed2001

The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells.

The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth factor 7, fibroblast growth factor 2 and hepatocyte growth factor was strongly reduced by inhibitors of MMPs, indicating the requirement of MMPs for three-dimensional growth involved in morphogenesis. Recombinant stromelysin 1/MMP3 alone was sufficient to drive branching in the absence of growth factors in the organoids. Plasmin also stimulated branching; however, plasmin-dependent branching was abolished by both inhibitors of plasmin and MMPs, suggesting that plasmin activates MMPs. To differentiate between signals for proliferation and morphogenesis, we used a cloned mammary epithelial cell line that lacks epimorphin, an essential mammary morphogen. Both epimorphin and MMPs were required for morphogenesis, but neither was required for epithelial cell proliferation. These results provide direct evidence for a crucial role of MMPs in branching in mammary epithelium and suggest that, in addition to epimorphin, MMP activity is a minimum requirement for branching morphogenesis in the mammary gland.

Actins↗
PubMed2001

[Gastric mucosal immunity induced by H. pylori infection].

H. pylori infection induces various humoral and cellular immunities in gastric mucosa. Some reports indicate predominant CD4+ cells infiltrate in H. pylori infected gastric mucosa, and these cells express the T helper 1 phenotype. Local humoral immunity is also induced. Gastric plasma cells produce anti-H. pylori antibodies, however, their protective immunity is not enough to eradicate bacteria in human. We found heat shock protein 60 kDa (hsp60) may be closely associated with pathogenesis in MALT lymphoma. IgG1 antibodies to hsp60 were significantly correlated with the antibodies to H. pylori whole cell in patients with MALT lymphoma. CD40-CD40L dependent B cell proliferation was induced by cytokine and/or hsp60 stimulations in those patients. Cytotoxicity of gastric epithelial cells which is associated with host immunity induced by H. pylori infection is still unclear. We found that lymphocytes from patients with peptic ulcer showed cytotoxicity to gastric cell line HGC-27 in vitro. Cytotoxicity was enhanced by cytokine stimulus to T-lymphocytes and by heat stress and/or patients' antibodies treatment of HGC-27 cells. The pathogenicity of H. pylori may involve not only bacterial virulence factor but also host immunity. Studies of mucosal local immunity will help explain the mechanisms of H. pylori induced gastrodoudenal diseases.

Antibody Formation↗
PubMed2001

[Prediction of the need for mechanical ventilation after transsternal thymectomy in patients with myasthenia gravis].

Between June 1992 and May 2000, transsternal extended thymectomy was performed for 70 patients with myasthenia gravis in our hospital. We were able to evaluate 64 of them in terms of prediction of the need for postoperative mechanical ventilation using the score systems reported by Leventhal et al., Kimura et al. and the criteria of Adachi et al.. For these systems, the rates of agreement between predictions and results were 85.9%, 82.8%, and 64.1%, respectively. The two former systems had some false negative cases (i.e., they predicted that ventilation would not be needed when in fact it was), but the last one gave no false negatives. We recommend Adachi's criteria for clinical safety. In our cases the patients whose value of %VC multiplied by FEV1.0% was less than 7,000 (Adachi's criterion is less in 8,300), especially, needed careful management with regard to respiratory crisis.

Adolescent↗