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Biomedical subjects

S Sugiyama

Publications and source records attributed to S Sugiyama.

At least 55 records · Page 3Linked to original sources
PubMed2000

Lysophosphatidylcholine induces urokinase-type plasminogen activator and its receptor in human macrophages partly through redox-sensitive pathway.

Urokinase-type plasminogen activator (uPA) and its cell surface receptor (uPAR) have been shown to be expressed in macrophages in atherosclerotic arterial walls, but the regulatory mechanisms of their expression remain unclear. The present study was performed to examine the effects of lysophosphatidylcholine (lysoPC), an important atherogenic lipid, on the expression of uPA and uPAR in human monocyte-derived macrophages. LysoPC upregulated the mRNA expression of uPA and uPAR, and it increased the protein expression of uPA in the culture medium and bound to the cell surface and of uPAR in the particulate fraction of the cells. LysoPC significantly increased the binding of the amino-terminal fragment of uPA to the treated cells and the cell-associated plasminogen activator activity. LysoPC stimulated superoxide anion production and increased intracellular oxidant levels in the cells. The combined incubation with reduced glutathione diethyl ester or N-acetylcysteine, antioxidants, suppressed the upregulation of uPA and uPAR mRNA and the increase in plasminogen activator activity by lysoPC. uPA and uPAR mRNA expression was also induced by the incubation with xanthine and xanthine oxidase, a superoxide anion-generating system. The results suggest that lysoPC increased the expression of uPA and uPAR and their functional activities in human monocyte-derived macrophages, at least in part through a redox-sensitive mechanism. This coordinate increase in the expression of uPA and uPAR in human macrophages by lysoPC could play an important role in plaque formation and disruption, arterial remodeling, and angiogenesis in atherosclerotic arterial walls.

Acetylcysteine↗
PubMed2000

[A study on coordination of occupational and community health--a survey of occupational health nurses].

The survey was conducted on occupational health nurses to find out their awareness of the issue, levels of coordination practiced at work and contributing factors. Based on the results, measures to facilitate the coordination of the two areas were examined. The major findings are as follows: 1. Cooperation between occupational and community health nurses: More than 40% of the occupational health nurses surveyed were aware of the necessity for cooperation with community health nurses. However, less than 7% of those surveyed actually practiced it at work. The deciding factors included the use of a support system in the community, previous training in community health, and work experience in health centers in the community. To facilitate the cooperation between the two sectors, it is suggested that occupational health nurses acquire more knowledge of community health issues. 2. Coordination through focusing on the employee's life in the community: More than 85% of those surveyed were aware of the necessity of coordinating occupational and community health issues through focusing on the lives of the employees in the community. However, less than 30% practiced it at work. Awareness and practice of occupational health planning scored the lowest. The deciding factors included completion of a public health nursing course and the number of employees assigned to each nurse, the use of a support system in the community, and previous training in community health. To facilitate coordination of occupational and community health issues, it is suggested that occupational health nurses acquire more knowledge of community health issues, the number of employees assigned be carefully considered, and that activities focusing on community health be incorporated into occupational health planning.

Community Health Nursing↗
PubMed1999

Interdependence of Anion and Cation Exchanges in Calcium Hydroxyapatite: Pb(2+) and Cl(-).

The ion exchange of Pb(2+) and Cl(-) into calcium hydroxyapatite from aqueous solutions is studied at 293 K. Although the exchange of Cl(-) into CaHAp and PbHAp was not observed, in the presence of both Pb(2+) and Cl(-) in aqueous solution the exchange of both Pb(2+) and Cl(-) into CaHAp occurred, and, at least at intermediate concentrations of HCl, a proportionality between the sorbed quantities of these two ions was observed. The dissolution of CaHAp is shown to be dependent upon the pH, while the quantity of Pb(2+) exchanged into the solid is not a function of the proton content; consequently, the exchange is not primarily a dissolution-precipitation process. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Circulating levels of secretory type II phospholipase A(2) predict coronary events in patients with coronary artery disease.

Background-The circulating levels of secretory nonpancreatic type II phospholipase A(2) (sPLA(2)) are increased in various chronic inflammatory diseases and the increase in the levels correlates with the disease severity. sPLA(2) may possibly play a role in atherogenesis and is highly expressed in atherosclerotic arterial walls that are known to have inflammatory features. Thus, this study prospectively examined whether circulating levels of sPLA(2) may have a significant risk and prognostic values in patients with coronary artery disease (CAD). Methods and Results-Plasma levels of sPLA(2) were measured in 142 patients with CAD and in 93 control subjects by a radioimmunoassay. The sPLA(2) levels had a significant and positive relations with serum levels of C-reactive protein, a marker of systemic inflammation, and with the number of the traditional coronary risk factors associated with individuals. Multivariate logistic regression analysis showed that higher levels of sPLA(2) (>246 ng/dL; 75th percentile of sPLA(2) distribution in controls) were a significant and independent risk factor for the presence of CAD. In multivariate Cox hazard analysis, the higher levels of sPLA(2) were a significant predictor of developing coronary events (ie, coronary revascularization, myocardial infarction, coronary death) during a 2-year follow-up period in patients with CAD independent of other risk factors, including CRP levels, an established inflammatory predictor. Conclusions-The increase in circulating levels of sPLA(2) is a significant risk factor for the presence of CAD and predicts clinical coronary events independent of other risk factors in patients with CAD; these results may reflect possible relation of sPLA(2) levels with inflammatory activity in atherosclerotic arteries.

Aged↗
PubMed1999

Dietary lipid lowering reduces tissue factor expression in rabbit atheroma.

BACKGROUND: The mechanisms by which lipid lowering reduces the incidence of acute thrombotic complications of coronary atheroma in clinical trials remains unknown. Tissue factor (TF) overexpressed in atheroma may accelerate thrombus formation at the sites of plaque disruption. A cell surface cytokine CD40 ligand (CD40L) enhances TF expression in vitro. METHODS AND RESULTS: To test the hypothesis that lipid lowering reduces TF expression and activity, we produced atheroma in rabbit aortas by balloon injury and cholesterol feeding for 4 months (Baseline group, n=15), followed by either a chow diet (Low group, n=10) or a continued high-cholesterol diet for 16 months (High group, n=5). Immunolocalization of TF, CD40L, and its receptor CD40 was quantified by computer-assisted color image analysis. Macrophages in atheroma of the Baseline and High groups strongly expressed TF. Intimal smooth muscle cells and endothelial cells also contained immunoreactive TF. Regions of expression of CD40L and CD40 colocalized with TF. Protein expression of TF diminished substantially in the Low group in association with reduced expression of CD40L and CD40. In situ binding of TF to factors VIIa and X, detected by digoxigenin-labeled factors VIIa and X, colocalized with TF protein in atheroma and decreased after lipid lowering. We also determined reduced TF biological activity in the Low group by use of a chromogenic assay. The level of TF mRNA detected by reverse transcription-polymerase chain reaction also decreased after lipid lowering. CONCLUSIONS: These results suggest decreased expression and activity of TF as a novel mechanism of reduced incidence of thrombotic complications of atherosclerosis by lipid lowering.

Animals↗
PubMed1999

Remnant lipoprotein levels in fasting serum predict coronary events in patients with coronary artery disease.

BACKGROUND: Remnant lipoproteins are atherogenic, but assays of remnants have not been available in routine clinical laboratories because of the lack of practical and validated methods. A simple and reliable method for such an assay, using an immunochemical approach, has recently been developed. This study prospectively examined whether remnant lipoprotein levels in fasting serum, measured by our method, may have prognostic value in patients with coronary artery disease (CAD). METHODS AND RESULTS: Remnant lipoprotein levels in fasting serum were measured in 135 patients with CAD by an immunoaffinity mixed gel containing anti-apolipoprotein (apo) A-1 and anti-apoB-100 monoclonal antibodies. Patients were followed up for </=36 months until occurrence of 1 of the following clinical coronary events: recurrent or refractory angina pectoris requiring coronary revascularization, nonfatal myocardial infarction, or cardiac death. Kaplan-Meier analysis demonstrated a significantly higher probability of developing coronary events in patients with the highest tertile of remnant levels (>5.1 mg cholesterol/dL; 75th percentile of distribution of remnant levels) than in those with the lowest tertile of remnant levels (</=3.3 mg cholesterol/dL; 50th percentile of the distribution). Higher levels of remnants were a significant and independent predictor of developing coronary events in multivariate Cox hazard analysis including the following covariates: extent of coronary artery stenosis, age, sex, smoking, hypertension, diabetes mellitus, hypercholesterolemia, low HDL cholesterol, and hypertriglyceridemia. CONCLUSIONS: Higher levels of remnant lipoproteins in fasting serum predict future coronary events in patients with CAD independently of other risk factors. Thus, measurement of fasting remnant levels, assessed by the current immunoseparation method, may be helpful in assessment of CAD risk.

Adult↗
PubMed1999

Lung carcinoma in patients age younger than 30 years.

BACKGROUND: To the authors' knowledge, no study regarding lung carcinoma patients age <30 years has been published. Therefore, this study was undertaken to define the characteristics of lung carcinoma patients age <30 years. METHODS: Information regarding 26 patients with primary lung carcinoma who were age <30 years was obtained from 10 medical institutions and reviewed retrospectively. For comparison, 304 patients age > or = 30 years who were admitted to the First Department of Internal Medicine at Toyama Medical and Pharmaceutical University between 1980-1996 were studied. RESULTS: Among the characteristics observed in the group of lung carcinoma patients age <30 years was a high incidence of female gender, no history of smoking, so-called "low grade malignancy," American Joint Committee on Cancer Stage I disease, and previous surgical resection. In addition, a low incidence of squamous cell carcinoma was noted, and a more favorable prognosis was observed. CONCLUSIONS: The current study noted clinical features that could be defined clearly in lung carcinoma patients age <30 years.

Adolescent↗
PubMed1999

Suppression of atherosclerotic development in Watanabe heritable hyperlipidemic rabbits treated with an oral antiallergic drug, tranilast.

BACKGROUND: Inflammatory and immunological responses of vascular cells have been shown to play a significant role in the progression of atheromatous formation. Tranilast [N-(3,4-dimethoxycinnamoyl) anthranillic acid] inhibits release of cytokines and chemical mediators from various cells, including macrophages, leading to suppression of inflammatory and immunological responses. This study tested whether tranilast may suppress atheromatous formation in Watanabe heritable hyperlipidemic (WHHL) rabbits. METHODS AND RESULTS: WHHL rabbits (2 months old) were given either 300 mg x kg-1 x d-1 of tranilast (Tranilast, n=12) or vehicle (Control, n=13) PO for 6 months. Tranilast treatment was found to suppress the aortic area covered with plaque. Immunohistochemical analysis showed that there was no difference in the percentage of the RAM11-positive macrophage area and the frequency of CD5-positive cells (T cells) in intimal plaques between Tranilast and Control. Major histocompatibility complex (MHC) class II expression in macrophages and interleukin-2 (IL-2) receptor expression in T cells, as markers of the immunological activation in these cells, was suppressed in atheromatous plaque by tranilast treatment. Flow cytometry analysis of isolated human and rabbit peripheral blood mononuclear cells showed that an increase in expression both of MHC class II antigen on monocytes by incubation with interferon-gamma and of IL-2 receptor on T cells by IL-2 was suppressed by the combined incubation with tranilast. CONCLUSIONS: The results indicate that tranilast suppresses atherosclerotic development partly through direct inhibition of immunological activation of monocytes/macrophages and T cells in the atheromatous plaque.

Administration, Oral↗
PubMed1999

Shortened elastase infusion time in the elastase-induced rat aneurysm model.

OBJECTIVE: This study was performed to determine whether it would be possible to shorten the elastase infusion time in the elastase-induced rat aneurysm model. METHODS: The abdominal aortas of 76 male Sprague-Dawley rats were dissected and infused for 10, 20, 30, 60, or 120 min with a solution containing 14 U of elastase or for 30 min with saline solution (control). After infusion, the rats were evaluated every day for calculation of the mortality rate. On day 7, the surviving rats underwent laparotomy. The diameter of the aorta was measured, and the aortic tissue was excised for histologic examination. RESULTS: There were no deaths among the rats infused for 10, 20, or 30 min. The mortality rate was 64% in the 60-min and 90% in 120-min groups. There were no significant differences in the diameters of the 30-min saline-infused aortas and the 10- or 20-min elastase-infused aortas. The diameter of the 30-min elastase-infused aortas (6.2 +/- 2.1 mm) was significantly larger (P < 0.01) than the diameters of the 10- and 20-min elastase-infused aortas. There were no significant differences between the 30-min and the 60- and 120-min elastase-infused aortas. Microscopically, there was total or subtotal loss of elastic tissue and marked inflammatory cell infiltration of the aortic wall in the 30-, 60-, and 120-min elastase-infused aortas. CONCLUSIONS: It is possible to shorten the elastase infusion time from 120 to 30 min in the elastase-induced rat aneurysm model. This shortening of infusion time reduces the experimental time and mortality rate.

Animals↗
PubMed1999

Superoxide dismutase in normal cycling human ovaries: immunohistochemical localization and characterization.

OBJECTIVE: To investigate the expression of manganese (Mn) and copper-zinc (Cu,Zn) superoxide dismutase (SOD) in normal cycling human ovaries throughout the menstrual cycle. DESIGN: Descriptive, controlled study. SETTING: Tohoku University School of Medicine. PATIENT(S): Twenty-four normal cycling human ovaries were obtained from patients who underwent oophorectomy and hysterectomy for squamous cell carcinoma of the uterine cervix. INTERVENTION(S): Immunohistochemistry for Mn-SOD and Cu,Zn-SOD. MAIN OUTCOME MEASURE(S): Immunostaining. RESULT(S): In the follicular stage, Mn-SOD immunoreactivity was detected in granulosa and theca interna cells of steroid-producing follicles, that is, preantral, nondominant, dominant, and atretic follicles, whereas Cu,Zn-SOD was detected in theca interna cells of these follicles and in granulosa cells of dominant follicles. In the luteal stage, immunoreactivity for Mn-SOD and Cu,Zn-SOD was observed in both luteinized granulosa and theca cells of the functioning corpus luteum. In the early degenerating corpus luteum, both Mn-SOD and Cu,Zn-SOD were positive in steroid-producing luteinized theca cells. Mn-SOD immunoreactivity was also detected in nonsteroid-producing luteinized granulosa cells and macrophages. CONCLUSION(S): Our results suggest that the expression of Mn-SOD and Cu,Zn-SOD closely correlates with steroidogenesis in the human ovary. In addition, Mn-SOD may play an important role in the process of luteal regression.

Adult↗
PubMed1999

Burst production of superoxide anion in human endothelial cells by lysophosphatidylcholine.

This study examined whether lysophosphatidylcholine (lysoPC), an atherogenic lipid, may stimulate production of O2*-, in cultured human endothelial cells. Production of O2*- was detected by bis-N-methylacridinium nitrate (lucigenin)-elicited chemiluminescence. LysoPC was found to induce burst production of O2*-, peaked at 2-4 min after the stimulation, in intact endothelial cells. LysoPC also stimulated NADH-dependent production of O2*- in particulate fraction of the cells, and the action of lysoPC was inhibited by diphenyliodonium. The results suggested that lysoPC stimulated production of O2*- partly through membrane-associated NADH-dependent O2*- production systems.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed1999

Improvement of endothelial vasomotor dysfunction by treatment with alpha-tocopherol in patients with high remnant lipoproteins levels.

OBJECTIVES: This study sought to examine whether oral intake of alpha-tocopherol, an antioxidant, could improve endothelium-dependent vasorelaxation in patients with high remnant lipoproteins levels. BACKGROUND: Remnant lipoproteins are known to be atherogenic and impair endothelium-dependent arterial relaxation, but the underlying mechanisms remain unclear. Oxidative stress is a common feature of various risk factors for atherosclerosis. METHODS: Flow-mediated vasodilation of the brachial artery during reactive hyperemia was examined by high resolution ultrasound technique before and at the end of 4 weeks treatment with oral administration of alpha-tocopherol acetate (300 IU/day) or placebo, which was randomly assigned, in 40 patients with high serum levels of remnants and in 30 patients with low remnants levels in the fasting state (>75th percentile and <25th percentile, respectively, of the distribution of remnants levels in 150 consecutive hospitalized patients). RESULTS: Before treatment, flow-mediated vasodilation was lower in patients with high remnants levels than in those with low levels (4.1 +/- 0.3% vs. 6.0 +/- 0.5%, p < 0.01). Treatment with alpha-tocopherol but not with placebo significantly increased flow-mediated dilation in patients with high remnants levels (7.5 +/- 0.4% after alpha-tocopherol vs. 4.2 +/- 0.4% after placebo, p < 0.01). In patients with low remnants levels, alpha-tocopherol was not effective. The beneficial effect with alpha-tocopherol in high remnants patients was associated with decrease in plasma levels of thiobarbituric acid reactive substances, an indicator of lipid peroxidation (6.6 +/- 0.3 nmol/ml before alpha-tocopherol vs. 4.6 +/- 0.3 after alpha-tocopherol, p < 0.05). CONCLUSIONS: Alpha-tocopherol improved impairment of endothelium-dependent vasodilation in patients with high remnants levels. The increase in oxidative stress may at least partly contribute to endothelial vasomotor dysfunction, in patients with high remnants levels.

Adult↗
PubMed1999

Presumption of a suspect based on the skin fragment attached the rope.

An eight-year-old girl (second-year of elementary school) was strangled in an irrigation canal near her house and was left unconscious. The body of a male who hanged himself to death was discovered on the next day. The hanging mark on the neck of the man and the ligature mark on the neck of the girl were caused by double nooses of a rope, the width of the rope mark was nearly the same, and similar Zwischenkammblutung (subcutaneous bleeding in the middle of the rope mark) was observed in both cases. Therefore, we evaluated whether the marks were caused by the same rope. As a result, the DNA type of the skin fragment (keratinized epithelial cells) attached to the rope used by the man to hang himself was identical to that of the girl. On the basis of this evidence, the man who hanged himself to death was presumed to be the suspect who strangled the girl.

Journal Article↗
PubMed1999

Estimation of age by epidermal image processing.

Small pieces of human precordial skin were obtained from 266 individuals during autopsy performed in Osaka Prefecture. The area from the stratum corneum to the stratum basale in a unit area of the epidermal cross-section was extracted as a segmented area of white image by image processing. The number of pixels surrounding this area was measured in individuals of various ages, and the age-associated changes were evaluated. The number of pixels around this binary image in the epidermal cross-section showed a strong correlation with age. The number tended to decrease with an increase in age in individuals aged 20 years and above, which could be closely approximated by an exponential function. A formula for estimating age was obtained as an inverse function of the number of pixels and age, and the accuracy of estimation using this formula was examined by comparing the estimated age with the actual age. Such age-associated changes in the epidermis were considered to be closely related with increased roughening of the stratum basale, flattening of dermal papillae, and a decreased percentage of the stratum granulosum per unit area of epidermis observed by light microscopy or scanning electron microscopy.

Journal Article↗
PubMed1999

A sudden death case of laryngocele accompanied by infarction of the dorso-lateral portion of the medulla oblongata.

A 70-year-old man, who had a laryngeal tumor discovered by otolaryngological examination during admission for suspicion of facial nerve paralysis was found dead in his bed on the seventh hospital day. Clinical doctors aspirated a large amount of mucous sputum from his larynx during their attempt at resuscitation. Although the direct cause of death was clinically unknown, an autopsy revealed an internal type laryngocele, a type of laryngeal cyst, in the right larynx and infarction of the left dorso-lateral portion of the medulla oblongata. Suffocation resulted from mucous sputum filling his larynx, which had been narrowed by a laryngocele from the right, in an unfortunate association with movement disturbance of the left larynx caused by the infarction of the left dorso-lateral portion of the medulla oblongata. We assumed this to be the direct cause of death, because the heart and lungs showed no remarkable changes that could be ascribed to it. This case offers important suggestions concerning the risks of suffocation due to laryngeal cysts, especially in patients with complications.

Journal Article↗
PubMed1999

Mediastinal lymph node metastasis model by orthotopic intrapulmonary implantation of Lewis lung carcinoma cells in mice.

This study is designed to establish a pulmonary tumour model to investigate the biology and therapy of lung cancer in mice. Current methods for forming a solitary intrapulmonary nodule and subsequent metastasis to mediastinal lymph nodes are not well defined. Lewis lung carcinoma (LLC) cell suspensions were orthotopically introduced into the lung parenchyma of C57/BL6 mice via a limited skin incision without thoracotomy followed by direct puncture through the intercostal space. The implantation process was performed within approximately 50 s per mouse, and the operative mortality was less than 5%. Single pulmonary nodules developed at the implanted site in 93% of animals and subsequent mediastinal lymph node metastasis was observed in all mice that formed a lung nodule after intrapulmonary implantation. The size of tumour nodule and the weight of mediastinal lymph node increased in a time-dependent manner. The mean survival time of mice implanted successfully with LLC cells was 21+/-2 days (range 19-24 days). Histopathological analysis revealed that no metastatic tumour was detectable in the mediastinal lymph nodes on day 11, but metastatic foci at mediastinal lymph nodes were clearly observed on days 17 and 21 after implantation. Other metastases in distant organs or lymph nodes were not observed at 21 days after the implantation. Comparative studies with intrapleural and intravenous injections of LLC cells suggest that the mediastinal lymph node metastasis by intrapulmonary implantation is due to the release of tumour cells from the primary nodule, and not due to extrapulmonary leakage of cells. An intravenous administration of cis-diamine dichloro platinum on day 1 after tumour implantation tended to suppress the primary tumour nodule and significantly inhibited lymph node metastasis. Thus, a solitary pulmonary tumour nodule model with lymph node metastasis approximates clinical lung cancer and may provide a useful basis for lung cancer research.

Animals↗
PubMed1999

Sulfur containing tyrosine analogs can cause selective melanocytotoxicity involving tyrosinase-mediated apoptosis.

Sulfur-containing tyrosine analogs such as 4-S-cysteaminylphenol (4-S-CAP) and its N-acetyl derivative, N-acetyl-4-S-CAP, are tyrosinase substrates and can cause selective cytotoxicity or cell death of melanocytes and melanoma cells. It is not clear, however, if the cytotoxicity derives from a cytostatic or cytocidal effect. The latter can also be either apoptotic or necrotic. This paper summarizes our attempt to clarify the nature of melanocytotoxicity and cell death by using a new derivative of 4-S-CAP, N-propionyl-4-S-CAP (NPr-CAP). The i.p. administration of NPr-CAP caused marked depigmentation of black hair follicles in C57 mice. At 12 h postadministration of NPr-CAP, follicular melanocytes showed histochemical and morphologic features indicative of apoptosis by TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining and electron microscopy. The agarose gel electrophoresis of DNA from drug-treated melan a2 cells, an immortal melanocyte line of C57 black mice, showed the nucleosomal DNA ladder pattern. NPr-CAP caused irreversible cytotoxicity in melan a2 and the effect was inhibited by a tyrosinase inhibitor, phenylthiocarbamide. The tyrosinase-mediated cytotoxicity of NPr-CAP was further confirmed by the decreased viability of COS 7 monkey-kidney cells, which expressed a level of high tyrosinase activity through transfection of human tyrosinase cDNA. NPr-CAP, however, also transiently inhibited the proliferation of melan c cells, a control tyrosinase-negative albino melanocyte line, and vector-transfected COS 7 cells. Thus, the major process of NPr-CAP-mediated melanocytotoxicity involves cytocidal apoptosis associated with active tyrosinase. In addition, there is transient, nontyrosinase-mediated cytostatic cytotoxicity.

Animals↗