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Biomedical subjects

K Aoyagi

Publications and source records attributed to K Aoyagi.

At least 37 records · Page 2Linked to original sources

Stiffness index of the calcaneus measured by quantitative ultrasound and menopause among Japanese women: The Hizen-Oshima Study.

Quantitative ultrasound (QUS) is a recently developed technique for evaluating fracture risk that can assess both bone mass and architecture. Although numerous studies have shown that menopause is associated with accelerated loss of bone mineral density, there are only a few studies on the association of QUS parameter (stiffness index) with menopausal status, especially among Japanese population. We examined age-specific changes in stiffness index, and relation with age, body mass index (BMI) and menopausal status among 506 community-dwelling Japanese women aged 40-89 years. Mean age at menopause (standard deviation) among 459 women with natural menopause was 49.4 (4.0) years. Stiffness index significantly decreased with increasing age. Stiffness index among 80-89 years age group was 40% lower, compared with that of 40-49 years age group. The greatest decline among adjacent ten-year age groups in stiffness index (15%) was found between 40-49 and 50-59 years of age. Multiple regression analysis showed that menopause related with decreased stiffness index, independent of age and BMI. Our findings indicate that menopause influences loss of bone mass and induces deterioration of bone trabecular microstructure.

Adult↗

Evaluation of the epidermal growth factor receptor (EGFR) and c-erbB-2 in superspreading-type and penetrating-type gastric carcinoma.

The expression of epidermal growth factor (EGF), epidermal growth factor receptor (EGFR), transforming growth factor alpha (TGF alpha), and of c-erbB-2 was immunohistochemically investigated in resected gastric carcinoma (in 39 cases of superspreading type and in 11 cases of penetrating type), to understand the differential biological features of these two types of gastric carcinoma. EGF, EGFR and c-erbB-2 positive cases were preferentially found in penetrating type rather than in superspreading type (p < 0.05, p < 0.01, and p < 0.05, respectively). The positive rates of EGFR and c-erbB-2 were significantly higher in submucosal gastric carcinoma than in intramucosal gastric carcinoma (p < 0.01, p < 0.05, respectively). These results suggested that the autocrine mechanism of the growth factors and the expression of c-erbB-2 were correlated to the degree of gastric wall invasion.

Adult↗

Advanced gastric cancer effectively treated by neoadjuvant continuous low-dosage 5-fluorouracil and cisplatin (FP regimen): a case report.

We have experienced a case of advanced gastric cancer with para-aortic lymph node metastasis effectively treated by neoadjuvant continuous low dosage 5-fluorouracil and cisplatin (FP regimen). The patient was a 67-year-old man diagnosed as having advanced gastric cancer type 4 with para-aortic lymph node metastasis. This patient was treated by continuous infusion of 5-fluorouracil (5-FU) 500 mg/day, for 28 days, and infusion of cisplatin 10 mg/day over 1 hr on days 1-5, 8-12, 15-19, and 22-26. At 4 weeks later, a CT revealed that swelling in the para-aortic lymph node had disappeared, and the thickening in the stomach wall had diminished. This patient underwent a curative operation, and both the serum level of carcinoembryonal antigen (CEA) and carbohydrate antigen (CA 19-9) decreased to normal. These results suggested that the FP regimen was an effective neoadjuvant treatment for advanced gastric cancer with para-aortic lymph node metastasis.

Aged↗

Long-term survival after gastric cancer with liver metastasis: a report of two cases.

We have experienced two cases of long-term survival after surgery for gastric cancer case with liver metastasis. One case was of a 66-year-old male patient diagnosed as having type 1 advanced gastric cancer located in the posterior wall of the lower body with liver metastasis. The stage of this case was P0H1N1T2M0 stage IV. This patient underwent distal gastrectomy with D2 lymph node resection, partial hepatectomy of the S3 region including the metastatic liver tumor and coagulation of metastatic liver tumors in the S6 and S7 regions. This patient was treated by intra-hepatic arterial infusion of 5-FU, CDDP and peroral administration of UFT after surgery. This patient has died at 3 years and 7 months after surgery. The other case was of a 55-year-old male patient diagnosed as having type 2 advanced gastric cancer located in the lesser curvature of the cardia with liver metastasis. The stage of this case was P0H1N1T3 M0 stage IV. This patient underwent total gastrectomy with D2 lymph node dissection, wedge resection of the S8 region including the metastatic liver tumor and coagulation of a metastatic liver tumor in the S4 region. This patient was treated by obstruction of the hepatic artery using coils, peroral administration of UFT, lentinan, MMC, and continuous low-dosage 5-FU and CDDP after surgery. This patient has died at 3 years and 6 months after surgery. These results suggest that for long-term survival in cases of gastric cancer with liver metastasis, hepatectomy or coagulation of the metastatic tumor with postoperative chemotherapy are indicated in cases that have no non-curative factors and only a few metastatic tumors.

Aged↗

Performance of a conventional enzyme immunoassay for hepatitis C virus core antigen in the early phases of hepatitis C infection.

There are periods within the early phase of hepatitis C virus (HCV) infection in which the anti-HCV antibody test is unable to confirm HCV viremia. To reduce the risk of transmitting HCV through transfusions, we developed a simple and highly sensitive enzyme immunoassay (EIA) which detects the core antigen of HCV (HCVcAg). This assay employed a conventional colorimetric EIA system, and was based on a two-step sandwich assay, using a 96- well microplate. The reproducibility of the results was very high. When the cutoff values were set to 30 fmol of recombinant HCVcAg/L, as determined by the distribution of healthy subject sera (n=223), 99.6% of healthy subject sera and 100% of hepatitis B patient sera (n=50) were negative for HCVcAg. The clinical performance of this EIA was examined using 14 commercially available seroconversion panels. In every panel, HCVcAg could be detected at points preceding the seroconversion of anti-HCV antibodies. The points at which HCVcAg was detected were the same as those at which it was detected by an AMPLICOR HCV Monitor test. The EIA's window period for detecting the HCVcAg in all panels was on average 26 days shorter than that of the anti-HCV antibody test. In three panels where the first sample is negative for HCV RNA, the window period was shortened 50 days by this EIA for HCVcAg. There was a positive correlation between the concentration of HCVcAg and HCV RNA in anti-HCV antibody negative specimens. This assay was simpler to perform than assays based on gene amplification technology for the detection of HCV RNA, and the window period was shortened to that of the AMPLICOR HCV Monitor test. Thus, the EIA for HCVcAg would be useful in screening seroconverting donors and could reduce the residual risk of secondary HCV infections through transfusions.

Case-Control Studies↗

Significance of cysteine rich transcription factor (CRTF) in the synthesis of tissue inhibitor of metalloproteinases 1 (TIMP-1) in gastrointestinal cancers.

We previously reported that a novel promoter enhancer element "human tissue inhibitors of metalloproteinases 1 (TIMP-1) enhancer" (HTE) and a novel transacting protein "cysteine rich transcription factor" (CRTF) induced TIMP-1 synthesis in prostate cancer cells 2xN.I.PC-3. In the present study, to clarify the significance of CRTF in gastrointestinal cancers we measured the binding activity of CRTF to HTE using an electrophoretic mobility shift assay (EMSA), and the TIMP-1 concentration by ELISA after various stimulation of six cancer cell lines (KE-3, TE-9, MKN-28, MKN-45, KM12SM, SW620). In three cell lines (KE-3, MKN-45, SW620), both the binding activity of CRTF and TIMP-1 concentration significantly increased after IL-10 stimulation. Fetal bovine serum (FBS) did not affect the binding activity of CRTF, whereas FBS induced TIMP-1 synthesis in all cell lines. In KE-3 esophageal cancer cells and SW620 colon cancer cells, both the binding activity of CRTF and TIMP-1 concentration increased in the presence of a conditioned medium (CM) of fibroblasts which was isolated from human colon cancer tissues, but did not increase in MKN-45 cells. Moreover, in the fibroblasts, both the binding activity of CRTF and the TIMP-1 concentration increased in the presence of CM from KM12SM, SW620, and TE-9 cancer cell lines. These results suggested that IL-I0, and unknown factors in addition to IL-10, induced TIMP-1 synthesis via an increase in the binding activity of CRTF in gastrointestinal cancers, and that interaction between cancer cells and fibroblasts may play an important role in TIMP-1 synthesis through a signal transduction pathway consisting of CRTF phosphorylation and HTE activation.

Cells, Cultured↗

Primary biliary cirrhosis associated with ulcerative colitis.

A rare case of concurrent primary biliary cirrhosis and ulcerative colitis is described in a 61 year-old Japanese male. Primary biliary cirrhosis was diagnosed on the basis of characteristic histologic findings and a positive serum mitochondrial antibody test. Ulcerative colitis was diagnosed from typical findings on colonoscopy and the histologic features of a sigmoid colon biopsy specimen. This is the 12th report of a patient presenting with the combination of primary biliary cirrhosis and ulcerative colitis. The potential autoimmune relationships on the basis of these conditions are discussed.

Colitis, Ulcerative↗

[Prevalence of disabilities of the upper and lower extremities among community-dwelling middle-aged and elderly women].

OBJECTIVE: In order to obtain baseline data for designing programs aimed at promoting physical function among elderly people in Japan, we determined the prevalence of disabilities affecting upper and lower extremities and their impact on function in community-dwelling middle-aged and elderly Japanese women. METHODS: Subjects were 580 women aged 40 years and over, living in Oshima town, Nagasaki, Japan. Information on disabilities affecting all four extremities was collected by questionnaire. Subjects were asked about the extent of disability in each extremity (no disability, some, moderate, cannot or very difficult to use extremity) and the reason for the disability. The functional level was defined using a disability score, calculated by summing the disabilities for upper or lower extremities (no disability, 0; some, 1; moderate, 2; cannot or very difficult to use, 3). Women who scored 0 were classified as 'good', women who scored 1-2 'fair', and who scored 3-6 as 'poor'. RESULTS: Prevalence of disability affecting the upper extremities increased significantly with age (11.9% with some or greater, and 4.3% with moderate or worse). Disabilities of the lower extremities also increased significantly with age (27.2% with some or greater, and 12.9% with moderate or worse), affecting a larger proportion of individuals. With regard to the upper extremities, the women classified a 'fair' and 'poor' increased significantly with age (9.5% with 'fair', and 2.4% with 'poor'), and function decreased (p = 0.003). The same was the case for the lower extremities (19.0% with 'fair', and 8.3% with 'poor') (P < 0.001). The most frequently cited cause of disability was arthritis, both in the upper (20%) and lower (40%) extremities, followed by stroke (10%), fracture (10%) and trauma not associated with fracture (10%). CONCLUSIONS: In middle aged and elderly women, disabilities of the upper and lower extremities become more prevalent and are associated with further functional impairment with aging. Such disabilities are more common in the lower extremities, and arthritis seems to be the most frequent cause.

Adult↗

Impact of Helicobacter pylori infection on gastric cancer incidence in a general Japanese population: the Hisayama study.

BACKGROUND: Several nested case-control studies have reported the potentially causal relationship between Helicobacter pylori infection and the development of gastric cancer. However, there has been no prospective study evaluating this issue. The purpose of this study is to examine the impact of H pylori infection on gastric cancer occurrence in a general Japanese population (Hisayama, Japan) stratified according to sex, using a prospective study design. METHODS: A total of 2602 subjects aged 40 years or older (1070 men; mean age, 57 years; 1532 women; mean age, 59 years) without a history of gastrectomy or gastric cancer were classified according to the status of the serum IgG antibodies to H pylori and observed prospectively for 9 years from 1988. RESULTS: Infection of H pylori was more common in men (71.5%) than in women (62.5%; P<.001). The age-adjusted incidence of gastric cancer for men (5.3 per 1000 person-years) was 4-fold higher than that for women (1.3; P<.001). In men, the age-adjusted incidence of gastric cancer was significantly higher in the subjects with H pylori infection than in those without it (6.2 vs 2.5; relative risk, 2.59 [95% confidence interval, 1.03-6.50]), whereas no significant difference was observed in women (1.2 vs 1.1; relative risk, 0.99 [95% confidence interval, 0.36-2.68]). These results were similar even after controlling for other risk factors in multivariate analysis. It was estimated that 40.1% of gastric cancers for men in this cohort were attributable to H pylori infection. CONCLUSION: A significant relationship exists between infection with H pylori and subsequent occurrence of gastric cancer for men but not for women in this Japanese population.

Adult↗

Alternative splicing of protein 4.1R exon 16: ordered excision of flanking introns ensures proper splice site choice.

Alternative splicing plays a major role in regulating tissue-specific expression of cytoskeletal protein 4.1R isoforms. In particular, expression of the protein's functionally critical spectrin-actin binding domain, essential for maintenance of red cell membrane mechanical properties, is governed by a developmentally regulated splicing switch involving alternative exon 16. Using a model 3-exon 4.1R pre-messenger RNA (pre-mRNA), we explored the sequence requirements for excision of the introns flanking exon 16. These studies revealed that splicing of this alternative exon occurs preferentially in an ordered fashion. The first step is excision of the downstream intron to join exons 16 and 17, followed by excision of the upstream intron. Constructs designed to test the converse pathway were spliced less efficiently and with less fidelity, in part due to activation of a cryptic 5' splice site in exon 16. This downstream-first model for ordered splicing is consistent with the hypothesis that regulated alternative splicing requires cooperation between multiple exonic and/or intronic regulatory elements whose spatial organization is critical for recruitment of appropriate splicing factors. Our results predict that exon 16 splicing is regulated at the first step-excision of the downstream intron-and that cells unable to catalyze this step will exhibit exon 16 skipping. In cells that include exon 16, adherence to an ordered pathway is important for efficient and accurate production of mature 4.1R mRNA encoding an intact spectrin-actin binding domain. (Blood. 2000;95:692-699)

Alternative Splicing↗

Calcaneus bone mineral density is lower among men and women with lower physical performance.

Fracture risk is influenced by both bone strength and by falls. Measures of physical function and performance are predictors of falls. However, the interrelationships among bone mineral density (BMD), regular physical activity, and measures of physical performance are not well known. We studied 447 community-dwelling Japanese people aged 40 years and over (96 men and 351 women) to examine the association of calcaneus BMD with measures of physical performance (grip strength, walking speed, chair stand, and functional reach) and regular physical activity. Calcaneus BMD decreased with age by approximately 25% in men and 42% in women. Measures of physical performance decreased with age by approximately 30% in both genders, however, performance on the chair stand test declined by approximately 60%. There were only minimal differences in performance measures and calcaneus BMD between people with and those without regular physical activity in both genders, and most differences were not significant. However, there were significant BMD increases of 3-6% per standard deviation (SD) increase in all performance measures for women and a 7% increase in BMD per SD increase in grip strength for men, after adjusting for age. These associations remained after additional adjustment for body mass index and regular physical activity. These findings suggest that bone density and physical function decline markedly in both men and women with age, and that low BMD and poor function tend to occur together, which would increase fracture risk more than either risk factor alone.

Absorptiometry, Photon↗

Evaluation of a new enzyme immunoassay for hepatitis C virus (HCV) core antigen with clinical sensitivity approximating that of genomic amplification of HCV RNA.

The aim of this study was to analyze the clinical performance of a new enzyme immunoassay (EIA) for hepatitis C virus (HCV) core antigen in comparison with the reverse transcription polymerase chain reaction (RT-PCR). A total of 310 patients with acute or chronic hepatitis C, and 132 HCV-negative controls were studied. Chemiluminescence EIA with monoclonal anti-HCV core antigen was used, and qualitative and quantitative commercial RT-PCRs and an in-house nested RT-PCR were performed. Compared with nested RT-PCR, the core antigen assay showed 97% sensitivity and 100% specificity in 75 patients with chronic hepatitis C and 132 controls. HCV core antigen was positive in 16 (94%) of 17 patients with acute hepatitis C at initial consultation. In 3 persons prospectively followed, core antigen was detected in the first available (1-3 weeks) post-transfusion sample. In 167 anti-HCV-positive individuals, 129 (77%) were viremic; core antigen was detected in 126 (98%) compared with 129 (100%) for nested RT-PCR and 121 (94%) for the commercial RT-PCR. In 48 patients with chronic hepatitis C treated with interferon alfa, the concentration of core antigen before treatment was significantly (P <.002) lower in patients with sustained response than in nonresponders. All responders had a sustained loss of core antigen, whereas all nonresponders remained core antigen positive. The concentrations of HCV core antigen and HCV RNA correlated significantly (n = 48, r =.627, P <.001). In conclusion, the HCV core antigen assay is useful for the diagnosis of acute and chronic hepatitis C, and for predicting and monitoring the effect of interferon alfa treatment.

Acute Disease↗

Endoscopic ultrasound features of protein-losing gastropathy with hypertrophic gastric folds.

BACKGROUND AND STUDY AIMS: We aim to clarify the endoscopic ultrasound (EUS) features of protein-losing gastropathy with hypertrophic gastric folds (PLGH), including Ménétrier's disease. PATIENTS AND METHODS: We analyzed the EUS and histologic findings in five patients who underwent both endoscopic ultrasonography and endoscopic resection. RESULTS: Histologically, we diagnosed one patient as having acute gastritis, three patients as having Ménétrier's disease, and the remaining patient as having hypertrophic lymphocytic gastritis (HLG). Helicobacter pylori was recognized in all but one patient. At EUS every patient was found to have giant gastric folds (13 to 20 mm in diameter), resulting from echogenic thickening of the mucosal layer with or without cystic components. Two patients who underwent eradication therapy of H. pylori showed both clinical and morphologic resolution. CONCLUSIONS: Echogenic thickening of the mucosal layer may be a characteristic EUS feature of protein-losing gastropathy with hypertrophic gastric folds, and H. pylori may be one of the causative agents.

Adolescent↗

Creatol, an oxidative product of creatinine in hemodialysis patients.

Creatol (CTL) is a product resulting from the reaction of creatinine (Cr) with the hydroxyl radical and is identified as a precursor of methylguanidine (MG), a uremic toxin. In this study, we investigated serum CTL levels together with those of Cr and MG in 66 patients who were on maintenance hemodialysis (HD). Prior to dialysis, the mean serum levels of Cr, CTL and MG were 967 (= 11.1 mg/dl)+/-267 microM, 11.1+/-4.8 microM and 5.8+/-2.9 microM, respectively. The mean CTL level was about 1.1% that of Cr, and the CTL plus MG level was about 1.4% that of the Cr level. The reduction rates of Cr, CTL and MG by a single HD were 62.6 6.1%, 71.0+/-10.3% and 51.9+/-11.6%, respectively. The CTL level at 0.5, 1 and 6 h after HD increased rapidly by 20.7+/-8.7%, 31.7+/-14.7% and 80.1+/-27.3%, respectively. There was a significant correlation between CTL or CTL/Cr and parathyroid hormone in patients who had just undergone parathyroidectomy. No significant correlation was found between CTL or CTL/Cr and those factors which seems to be related to the predialysis levels of reactive oxygen. Therefore, because of the good clearance of CTL and its rapid conversion to MG, its usefulness for the estimation of hydroxyl radical generation in HD patients is limited.

Adult↗

The role of protein kinase C in the increased generation in isolated rat hepatocytes of the hydroxyl radical by puromycin aminonucleoside.

Puromycin aminonucleoside (PAN) has been known to induce proteinuria. The increased generation of reactive oxygen species (ROS) has been implicated in this toxicity of PAN. We have reported that PAN increases the synthesis of methylguanidine (MG) and creatol which are the products of the reaction of creatinine and the hydroxyl radical in isolated rat hepatocytes. However, the mechanism for the increased ROS induced by PAN is still unclear. In this paper, we investigate the role of protein kinase C (PKC) on the PAN induced reactive oxygen generation in isolated rat hepatocytes. Isolated hepatocytes were incubated in Krebs-Henseleit bicarbonate buffer containing 3% BSA, 16.6 mM creatinine and tested reagents. MG and creatol were determined by high-performance liquid chromatography using 9,10-phenanthrenequinone for the post-labeling. PAN increased MG and creatol synthesis in isolated rat hepatocytes by 60%. 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), a PKC inhibitor, at 10 and 100 microM significantly inhibited MG and creatol synthesis with or without PAN. The inhibition rate is dose dependent from 10 to 100 microM. H1004, a reagent used as control for H-7, did not affect (at 10 microM) or increased little (at 100 microM) the synthesis of MG and creatol. Ro31-8425, a potent PKC inhibitor, significantly inhibited (at 10 microM) MG synthesis in the presence of PAN. PKC in the membrane fraction, a marker of PKC activation, increased over the initial concentration by a factor of 1.65-fold at 60 min incubation and 2.16-fold at 120 min with PAN, while it changed little without PAN. These results indicate that PAN activates PKC resulting in increased hydroxyl radical generation in isolated rat hepatocytes.

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

Knowledge and attitudes toward AIDS among female college students in Nagasaki, Japan.

This study assesses knowledge and attitudes concerning HIV infection and individuals with AIDS among 383 female students attending colleges in Nagasaki, Japan. A structured questionnaire containing questions concerning knowledge about AIDS, sources of information, beliefs and attitudes toward people with HIV/AIDS was administered during sessions set up for that purpose. The mean age of participants was 18.8 +/- 0.8 years (+/- SD). The main source of information for AIDS awareness as reported by the students was the mass media. Good knowledge about AIDS was positively associated with ease of acceptance of living in the same house with a person diagnosed with AIDS [odds ratio (OR): 1.90; 95% confidence interval (CI): 1.07-3.38]. However, residing at home (OR: 0.64; 95% CI: 0.42-0.98) and involvement in nurse education programmes (OR: 0.59; 95% CI: 0.37-0.95) showed a negative association. Students demonstrated a high level of knowledge concerning AIDS and HIV, but had considerable misconceptions and prejudices about people having HIV/AIDS. Our results suggest that a more appropriate education programme in colleges in Japan may be necessary to reduce the discrepancy between general knowledge and desirable attitude regarding HIV/AIDS.

Acquired Immunodeficiency Syndrome↗

Cytokines and T-cell responses in superantigen-related glomerulonephritis following methicillin-resistant Staphylococcus aureus infection.

BACKGROUND: We have previously reported that 10 patients who developed glomerulonephritis (GN) in association with methicillin-resistant Staphylococcus aureus (MRSA) infection showed a marked increase in DR+CD4+ and DR+CD8+ subsets of T cells and in T cells expressing several T-cell receptor (TCR) V beta+cells, perhaps representing V beta-specific T-cell activation by MRSA-derived superantigens (Kidney Int 1995; 47: 207-216). In this study we examine cytokine levels, T-lymphocyte subsets, natural killer NK cells, memory T cells, and the expression of IL-2 receptors in order to better understand the role of bacterial superantigens and cytokines in the pathogenesis of MRSA-associated GN. METHODS: Twenty-two patients with MRSA infection who later developed GN caused by staphylococcal enterotoxin were evaluated immunologically in comparison with patients whose MRSA infection was not followed by GN (non-GN group) and normal individuals. RESULTS: Among peripheral lymphocytes, the frequency of T cells expressing several TCR V betas, especially V beta 5-family TCR, was higher in the GN group than in both the non-GN group and the normal healthy control group. GN patients also showed increased serum levels of several cytokines, including tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-2, IL-6, IL-8, and IL-10, which have been implicated in the onset of nephritis. Memory cells, and IL-2 receptors also were elevated in the GN group. CONCLUSION: These results suggest that T cells activated by MRSA-derived staphylococcal enterotoxins and subsequent production of cytokines may play an important role in the pathogenesis of MRSA-associated GN.

Adult↗

Detection of hepatitis C core antigen in the antibody negative 'window' phase of hepatitis C infection.

BACKGROUND AND OBJECTIVES: Despite improvements in assays for anti-HCV, there remains a significant delay before the appearance of antibodies following infection, during which, circulating viral RNA is present. We have evaluated a prototype assay for the serological detection of hepatitis C virus (HCV) core antigen with specimens derived from the early phase of HCV infection. MATERIALS AND METHODS: Serial specimens from 24 individuals undergoing HCV seroconversion were tested for the presence of anti-HCV, HCV RNA and HCV core antigen. RESULTS: HCV antigen was detected at the same time as HCV RNA in 83% (20/24) cases. The mean time to the first detection of HCV antigen was approximately 1 day later than HCV RNA. Overall, 87% of HCV-RNA-positive specimens contained detectable HCV core antigen. CONCLUSION: These results indicate that HCV core antigen can be identified by routine serological ELISA in specimens from the early antibody-negative phase of HCV infection. A test for HCV core antigen may be a useful test for identifying window phase blood donations from antibody negative donors infected with HCV.

Enzyme-Linked Immunosorbent Assay↗