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Biomedical subjects

K Yoshida

Publications and source records attributed to K Yoshida.

At least 145 records · Page 8Linked to original sources

Validity of the Framingham risk model applied to Japanese men.

OBJECTIVES: To examine whether the Framingham Risk Model can appropriately predict coronary heart disease (CHD) events detected by electrocardiography (ECG) in Japanese men. METHODS: Using the annual health examination database of a Japanese company 5611 male workers, between the ages of 30 to 59, who were free of cardiovascular disease, were followed up to observe the occurrence of CHD events detected by ECG over a period of five to seven years. The probability of CHD was calculated for each individual from the equations of the Framingham risk model (with total cholesterol). RESULTS: The incidence of CHD increased with the estimated CHD risk. The Hosmer-Lemeshow goodness of fit test showed an adequate fit of the risk model to the data of the study subjects. In the receiver operating characteristic analysis, the area under the curve reached 0.67 which indicated an acceptable discriminatory accuracy of the risk model. CONCLUSIONS: The Framingham risk model provides useful information on future CHD events in Japanese men.

Adult↗

Standard protocol for exchange of health-checkup data based on SGML: the Health-checkup Data Markup Language (HDML).

OBJECTIVES: To develop a health/medical data interchange model for efficient electronic exchange of data among health-checkup facilities. RESULTS: A Health-checkup Data Markup Language (HDML) was developed on the basis of the Standard Generalized Markup Language (SGML), and a feasibility study carried out, involving data exchange between two health checkup facilities. The structure of HDML is described. RESULTS: The transfer of numerical lab data, summary findings and health status assessment was successful. CONCLUSIONS: HDML is an improvement to laboratory data exchange. Further work has to address the exchange of qualitative and textual data.

Computer Communication Networks↗

[Thrombus entrapped in a patent foramen ovale of the atrial septum].

A 59-year-old women was referred to our hospital due to severe dyspnea and shock status 12 days after intracranial hematoma evacuation for the hypertensive right putaminal hemorrhage. Transthoracic echocardiography revealed right ventricular dilatation and floating structures in the right atrium. Transesophageal echocardiography demonstrated a large, snake-like structure crossing her foramen ovale of the interatrial septum, and impending paradoxical embolism was diagnosed. She did not receive any anticoagulation and surgery due to recent cerebral hemorrhage. Follow-up TEE showed complete disappearance of the thrombus in the atrium two weeks after the onset. Phlebogram of deep vein demonstrated several thrombus in her leg. She underwent placement of inferior vena cava filter and was discharged from our hospital without any symptom of paradoxical embolism.

Echocardiography, Transesophageal↗

[Resection for pulmonary metastasis of gastrointestinal stromal tumor of the stomach at 10 years after gastrectomy; report of a case].

A 70-years-old male, who had received gastrectomy for leiomyosarcoma of the stomach 10 years ago, was found to have a left lung tumor on chest X-ray and computed tomography (CT). The tumor was diagnosed to be a pulmonary metastasis of gastric leiomyosarcoma. On admission, another tumor was detected at left occipital region by brain CT and was thought to be meningioma. Left lower lobectomy and brain tumor resection were performed serially. The histologic and immunohistochemical findings showed that both tumors were metastases of gastrointestinal stromal tumor (GIST) of the stomach after long disease-free interval. Compared with the primary tumor, cellular density, mitotic figures, bizarre nuclei, and necrotic foci were prominent in the metastatic tumors. This case suggest that GIST may recurrent as pulmonary metastasis after long disease-free interval and should be follow up longer after resection. Patient prognosis with pulmonary metastases is considered to be reflected more exactly in biological malignant potential of metastatic tumor rather than that of primary tumor.

Aged↗

Chemoprevention of large bowel carcinogenesis; the role of control of cell proliferation and significance of beta-catenin-accumulated crypts as a new biomarker.

Control of cell proliferation is important for cancer prevention since cell proliferation has essential roles in carcinogenesis in the processes of both initiation and promotion. In large bowel carcinogenesis, carcinogens produce hyperproliferation of cells in the target sites and the cell proliferation persists even after the cessation of carcinogen exposure. Chemopreventive agents principally control the increased cell proliferation when given in the initiation as well as post-initiation phases. Aberrant crypt foci (ACF) which appear soon after carcinogen exposure in large bowel carcinogenesis in rodents have been used as a reliable biomarker for screening of potential chemopreventive agents. Recently, our group demonstrated the presence of probable premalignant lesions with frequent beta-catenin gene mutations and accumulation of the corresponding protein in the colonic epithelium of rats given a large bowel carcinogen. Such early-appearing lesions lack the morphological appearance of ACF. Expression of these beta-catenin-accumulated crypts (BCAC) is markedly suppressed by a chemopreventive cyclooxygenase-2 inhibitor, celecoxib. BCAC are suggested to be more reliable biomarkers than ACF for screening effective chemopreventive agents for colorectal cancer and for investigating the mode of action of the agents.

Animals↗

Characterization of stage progression in chronic myeloid leukemia by DNA microarray with purified hematopoietic stem cells.

Chronic myeloid leukemia (CML) is characterized by the clonal expansion of hematopoietic stem cells (HSCs). Without effective treatment, individuals in the indolent, chronic phase (CP) of CML undergo blast crisis (BC), the prognosis for which is poor. It is therefore important to clarify the mechanism underlying stage progression in CML. DNA microarray is a versatile tool for such a purpose. However, simple comparison of bone marrow mononuclear cells from individuals at different disease stages is likely to result in the identification of pseudo-positive genes whose change in expression only reflects the different proportions of leukemic blasts in bone marrow. We have therefore compared with DNA microarray the expression profiles of 3456 genes in the purified HSC-like fractions that had been isolated from 13 CML patients and healthy volunteers. Interestingly, expression of the gene for PIASy, a potential inhibitor of STAT (signal transducer and activator of transcription) proteins, was down-regulated in association with stage progression in CML. Furthermore, forced expression of PIASy has induced apoptosis in a CML cell line. These data suggest that microarray analysis with background-matched samples is an efficient approach to identify molecular events underlying the stage progression in CML.

AC133 Antigen↗

Lipid peroxidation in the rat brain after CO inhalation is temperature dependent.

We reported previously that 7-hydroperoxycholesterols, 7 alpha- and 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 alpha-OOH and 7 beta-OOH), indicated lipid peroxidation. In the present study, we measured not only 7-hydroperoxycholesterols but also oxysterols (7 alpha- and 7 beta-hydroxycholesterol, 7 alpha-OH, and 7 beta-OH) and 3 beta-hydroxycholest-5-en-7-one (7-keto) in the brains of rats that underwent either a sham operation (control), hypoxia, or CO inhalation (1005 ppm) at 37 degrees C for 90 min followed by 48 h of recovery. The levels of 7-hydroperoxycholesterols, 7 beta-OH, and 7-keto were low in the hypoxia group, while the levels were unaltered in the CO group compared with the controls. Among the three groups of CO inhalation, these levels were high in the hyperthermia group (39 degrees C), and the 7-hydroperoxycholesterols were low in the hypothermia group (32 degrees C), compared with the control group. The blood O(2) saturation was almost normal in the hypothermia group, while it was similarly low in the hyperthermia and normothermia groups. The temperature-dependent lipid peroxidation in the brain after CO inhalation and recovery can not be explained by hypoxia due to CO-hemoglobin formation, but may contribute to the delayed neuronal death following CO inhalation. Hypothermia may be applicable to treat patients after CO inhalation.

Administration, Inhalation↗

Influence of angiogenetic factors and matrix metalloproteinases upon tumour progression in non-small-cell lung cancer.

We attempted to investigate immunohistochemical expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PD-ECGF), c-erbB-2, matrix metalloproteinase-2 (MMP-2), and MMP-9 using surgical specimens of 119 non-small-cell lung carcinoma (NSCLC) cases and to evaluate the relationship between the expression levels of each molecule and clinicopathological factors or prognosis. VEGF expression levels were significantly associated with the local invasion (P = 0.0001), lymph node involvement (pN-factor) (P = 0.0019), pathological stage (p-stage) (P = 0.0027) and lymphatic permeation (P = 0.0389). PD-ECGF expression levels were associated with pN-factor (P = 0.0347). MMP-2 expression levels were associated with pN-factor (P = 0.004) and lymphatic permeation (P = 0.0056). Also, MMP-9 expression levels showed a significant correlation to local invasion (P = 0.0012), pN-factor (P = 0.0093) and p-stage (P = 0.0142). Multivariate analysis showed VEGF to be the most related to local invasion (P = 0.0084), and MMP-2 was the only factor with significant independent impact on lymphatic permeation (P = 0.0228). Furthermore, log-rank analysis showed significant association with poor survival by VEGF, bFGF, MMP-2 and MMP-9. Especially, combined overexpression of VEGF and MMP-2 revealed poor prognosis, our study might provide a basis for the better evaluation of biological characteristics and a new therapeutic strategy based on chemotherapy.

Adult↗

Double-stranded RNA-induced interferon regulatory factor-1 gene expression in FRTL-5 rat thyroid cells.

Double-stranded RNA (dsRNA) plays a role in the regulation of cell growth and apoptosis as well as in the cellular antiviral responses. However, it remains unknown if dsRNA-activated signaling systems are functional in the thyroid. Here we report the presence of the dsRNA-dependent protein kinase (PKR) in FRTL-5 rat thyroid cells. In poly(I)-poly(C) (pIC)-stimulated cells, activation of nuclear factor-kappa B (NF kappa B) binding was clearly induced. Incubation of FRTL-5 cells with pIC resulted in a marked increase in interferon regulatory factor-1 (IRF-1) mRNA and phosphorylated signal transducer and activator of transcription-1 (STAT1) levels. Addition of pIC to cells led to type I interferon (IFN) gene expression, especially IFN beta, which can induce STAT1 phosphorylation, suggesting that dsRNA indirectly induced STAT1 phosphorylation through expression of type I IFN. Thus, our results suggest that the dsRNA-activated signaling pathway may be involved in the regulation of IFN-inducible genes in the thyroid.

Animals↗

Separation methods applicable to prostate cancer diagnosis and monitoring therapy.

During the last decade, significant research has been conducted using prostate-specific antigen (PSA) in the basic and clinical sciences and many advances have occurred in the clinical use of PSA for detecting and monitoring prostate cancer (PCa). Separation methods including gel-permeation chromatography, isoelectric focusing, lectin-affinity chromatography, polyacrylamide gel electrophoresis and high-performance liquid chromatography have made significant contributions to the discovery and identification of different molecular forms of PSA. Furthermore, the measurement of free and total PSA has improved the ability of PSA to detect early PCa. However, unnecessary biopsies are still needed for men with slightly elevated PSA values. On the other hand, PSA is not adequate for staging newly diagnosed PCa and prognosticating the course in individual cases. The possible application of separation methods in the basic science of prostate cancer may be associated with identification of more cancer-specific forms of PSA and discoveries of other serum proteins useful not only for detecting, but also for staging and prognosticating PCa. Such novel markers might lead to a better understanding of PCa aggressiveness and to developments in the clinical field of treatment.

Carbohydrate Sequence↗

Noninvasive detection of total occlusion of the left anterior descending coronary artery with transthoracic Doppler echocardiography.

OBJECTIVES: The purpose of this study was to evaluate the value of transthoracic Doppler echocardiography (TTDE) for the noninvasive detection of total left anterior descending coronary artery (LAD) occlusion. BACKGROUND: Total coronary occlusion is associated with an adverse long-term prognosis, and mechanical revascularization may be required for the patient with total coronary occlusion. However, a noninvasive diagnosis of total coronary occlusion before coronary angiography (CAG) has been difficult, especially in patients without clinical signs. METHODS: We studied 103 consecutive patients who underwent CAG for the evaluation of coronary artery disease. The study group consisted of 16 patients with total LAD occlusion (group A) and 87 patients without total LAD occlusion (group B). Coronary flow velocity in the mid-portion of the LAD was recorded by TTDE. RESULTS: Adequate spectral Doppler recordings of diastolic flow in the LAD were obtained in 98 study patients (95%; 15 patients in group A and 83 patients in group B). In group A, retrograde LAD flow was obtained in 14 (93%) of 15 patients. The mean diastolic velocity of the retrograde flow was 21.0 +/- 6.1 cm/s. In group B, antegrade LAD flow was obtained in all 83 patients (100%). The mean diastolic velocity of the antegrade flow was 21.5 +/- 7.1 cm/s. Retrograde LAD flow by TTDE had a sensitivity of 93% and a specificity of 100% for the detection of total LAD occlusion. CONCLUSIONS: Retrograde flow in the LAD by TTDE is a highly sensitive and specific finding that can be used to noninvasively diagnose total LAD occlusion.

Aged↗

Sodium butyrate induces growth arrest and senescence-like phenotypes in gynecologic cancer cells.

We demonstrated here the growth-suppressing effects of sodium butyrate (NaB) on human endometrial and ovarian cancer cells. The arrest of cells at the G1 checkpoint accounted for this effect. NaB-mediated p21 might arrest endometrial and ovarian cancer cells at the G0/G1 phase by eliciting pRb unphosphorylation. To demonstrate the role of pRb regulation by p21, we measured the sensitivity to NaB of cervical cancer cells in which pRb had been inactivated by HPV E7. The cervical cancer cells displayed a sensitivity in NaB-mediated G2/M arrest in addition to their sensitivity in G0/G1 arrest. Arrest at G0/G1 and G2/M accompanied induction of senescence-like phenotypes (SLPs). Most importantly, the effect of NaB on senescence induction was not coupled with the predominance of hypophosphorylated pRb forms in the cervical cancer cells. This suggested that NaB had the potential to elicit SLPs through p21-mediated withdrawal from cell cycle progression. The consequences of p21 induction were manifold. The effects of NaB on gynecologic cancer cell growth indicated its potential use in cancer treatment. NaB was effective even in the cancer cells with mutant p53 and/or Rb genes by eliciting cell senescence.

Animals↗

A dot-blot-immunoassay for semen identification using a polyclonal antibody against semenogelin, a powerful seminal marker.

Among various seminal plasma proteins, semenogelin (Sg), produced in the seminal vesicle, has been considered a candidate for demonstrating the presence of semen. Sg consists of two proteins, one 52 kDa (Sg-I) in size, and the other a mixture of 71 and 76 kDa proteins (Sg-II). Recombinant Sg-I and Sg-II proteins were obtained using a baculovirus system and then injected into a rabbit to produce the respective antibodies [Characterization of recombinant precursor proteins of the human seminal plasma sperm motility inhibitor synthesized in insect cells, Int. J. Mol. Med. 2 (1998) 693]. When liquefied seminal plasma was immunoblotted with the anti-Sg-I and Sg-II antibodies, the anti-Sg-II antibody identified a wider range of the polypeptides originating from Sg than did the anti-Sg-I antibody. A dot-blot-immunoassay using anti-Sg-II antibody revealed a clear immunoreactive spot even when the semen was diluted 6400-fold. However, this assay showed that the Sg antigen was undetectable in saliva, urine, vaginal secretions, sweat, nasal secretions and serum. To determine the stability of Sg antigenic activity, filter paper with dried semen stains were kept at 37, 4 and 22 degrees C for 1, 6 and 18 months, respectively, and the Sg antigenic activity was examined. The activity was detectable in an area not less than 0.5 cm x 0.5 cm under all of the above environmental conditions during each period. Finally, semen was mixed with saliva or blood at various volumetric ratios, and used as a source of dried stains. The Sg antigenic activity was detectable in the stains until the ratio of semen to saliva or blood reached 1:8. These results suggest that Sg may be useful as a marker for semen identification.

Adult↗

Arg660Ser mutation in Thermus aquaticus DNA polymerase I suppresses T-->C transitions: implication of wobble base pair formation at the nucleotide incorporation step.

We examined the replication fidelity of an Arg660Ser (R660S) mutant of Thermus aquaticus DNA polymerase I (Taq pol I). In a forward mutation assay, R660S showed a marked reduction in T-->C transitions, one of the most frequent errors made by the wild-type enzyme. Steady-state kinetics showed that R660S discriminates against dGTP incorporation at a template T 13-fold better than the wild-type. R660S was also 3.2-fold less efficient than the wild-type at extending a T:dG mismatch. These results indicate that R660S has enhanced fidelity during incorporation and extension, which reduces its T-->C transition frequency. Interestingly, R660S also discriminated correct from incorrect nucleotides at the incorporation step of C:dATP, A:dATP, G:dATP and C:8-OH-dGTP mispairs 28-, 6.0-, 4.1- and 6.8-fold better, respectively, than the wild-type, although it may not always be as accurate as the wild-type at the extension step. A structural model suggests that Arg660 may participate in two interactions that influence fidelity; the guanidinium group of Arg660 might interact with the incoming guanine base at the major groove and it might compete for forming another interaction with the primer terminus. Substituting Arg with Ser may eliminate or alter these interactions and destabilize the closed complex with incorrect substrates. Our data also suggest that T:dGTP and C:dATP base pairs form 'wobble' structures at the incorporation step of Taq pol I.

Arginine↗

Enhanced immune responses in transgenic mice expressing a truncated form of the lymphocyte semaphorin CD100.

CD100/Sema4D is a 150-kDa transmembrane protein that belongs to the semaphorin family. Binding of CD100 to CD72 enhances the immune response by turning off the negative signaling effects of CD72. To investigate the physiological functions of CD100 in vivo, we generated transgenic mice expressing a truncated form of CD100. A large amount of the soluble form of CD100 was detected in the sera of mice expressing a truncated form of CD100, although the amount of CD100 was only slightly elevated on the surface of B cells. In the mutant mice the development of conventional B and T cells appeared normal in terms of the surface marker phenotypes, while the number of CD5(+) B-1 cells in the peritoneal cavity increased in comparison with wild-type mice. In vitro proliferation and Ig production of B cells in response to CD40 stimulation were considerably enhanced in mice expressing a truncated form of CD100. Additionally, in vivo both Ab responses against T cell-dependent Ags and generation of Ag-specific T cells were enhanced. Furthermore, introduction of the CD100-transgene could restore in vitro B cell responses as well as in vivo Ab production against T cell-dependent Ag in CD100-deficient mice. Collectively, these results not only indicate that CD100 has an important role in the immune system, but also that the soluble form of CD100 released from the cell surface can exert functions in vivo.

Animals↗

Angiogenesis in pancreatic carcinoma: thymidine phosphorylase expression in stromal cells and intratumoral microvessel density as independent predictors of overall and relapse-free survival.

BACKGROUND: Recently, the usefulness of intratumoral microvessel density (IMD) and expression of several angiogenic factors as prognostic indicators have been demonstrated in several human solid tumors. METHODS: One hundred four patients with pancreatic ductal adenocarcinoma were examined retrospectively. The investigated clinicopathologic and immunohistologic data included staining for vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP), basic fibroblast growth factor (bFGF), CD34 (for calculating IMD), p53, and Ki-67. RESULTS: Multivariate analysis for both overall and relapse-free survival revealed two independent variables, IMD and TP staining in stromal cells (TPs, P < 0.02). Whereas the frequency of hepatic metastasis was correlated significantly with cytoplasmic expression of TP or bFGF in tumor cells (TPc, bFGFc), IMD, and p53 status, local recurrence was significantly more common in patients with positive staining for TPs, bFGF in stromal cells (bFGFs), and for the pM category (P < 0.05). TPc, bFGFc, VEGF, and p53 expression correlated with IMD (P < 0.01), although TPs and bFGFs expression did not. VEGF and IMD status correlated with p53 expression (P < 0.001), although TP, bFGF, and Ki-67 status did not. CONCLUSIONS: TPs expression and IMD were revealed to be valuable tools for predicting overall and relapse-free survival in patients with pancreatic adenocarcinoma. Whereas TPc and bFGFc are likely to participate in hepatic metastasis by means of their angiogenic properties, TPs and bFGFs may be related to local tumor progression. Angiogenesis in human pancreatic carcinoma may be dependent on VEGF, TP, and bFGF. p53 abnormality is likely to take part in VEGF-related angiogenesis.

Adenocarcinoma↗

Autoreactive CD4(+) T-cell clones to beta2-glycoprotein I in patients with antiphospholipid syndrome: preferential recognition of the major phospholipid-binding site.

Autoreactive CD4(+) T cells to beta2-glycoprotein I (beta2GPI) that promote antiphospholipid antibody production were recently identified in patients with antiphospholipid syndrome (APS). To further examine antigen recognition profiles and T-cell helper activity in beta2GPI-reactive T cells, 14 CD4(+) T-cell clones specific to beta2GPI were generated from 3 patients with APS by repeated stimulation of peripheral blood T cells with recombinant beta2GPI. At least 4 distinct T-cell epitopes were identified, but the majority of the beta2GPI-specific T-cell clones responded to a peptide encompassing amino acid residues 276 to 290 of beta2GPI (KVSFFCKNKEKKCSY; single-letter amino acid codes) that contains the major phospholipid-binding site in the context of the DRB4*0103 allele. Ten of 12 beta2GPI-specific T-cell clones were able to stimulate autologous peripheral blood B cells to promote anti-beta2GPI antibody production in the presence of recombinant beta2GPI. T-cell helper activity was exclusively found in T-cell clones capable of producing interleukin 6 (IL-6). In vitro anti-beta2GPI antibody production induced by T-cell clones was inhibited by anti-IL-6 or anti-CD40 ligand monoclonal antibody. In addition, exogenous IL-6 augmented anti-beta2GPI antibody production in cultures of the T-cell clone lacking IL-6 expression. These results indicate that beta2GPI-specific CD4(+) T cells in patients with APS preferentially recognize the antigenic peptide containing the major phospholipid-binding site and have the capacity to stimulate B cells to produce anti-beta2GPI antibodies through IL-6 expression and CD40-CD40 ligand engagement. These findings are potentially useful for clarifying the pathogenesis of APS and for developing therapeutic strategies that suppress pathogenic antiphospholipid antibody production in these patients.

Adult↗