Biomedical subjects

M Koyama

Publications and source records attributed to M Koyama.

At least 37 records · Page 2Linked to original sources

PubMed2001

Granulomatous and cytokine responses to pulmonary Cryptococcus neoformans in two strains of rats.

The present study was undertaken to elucidate the participation of Th1 and Th2 responses in granulomatous inflammation induced by Cryptococcus neoformans using Lewis and Brown Norway rats which have Th1-polarized and Th2-polarized innate immunity, respectively. Both strains demonstrated granulomatous inflammation in the lung, and the lesions were composed mainly of mononuclear phagocytes and surrounded by lymphocytes. Lewis rats demonstrated tuberculoid epithelioid cell granulomas with a central necrosis resembling caseation, and increased transcription of Th1 relevant cytokines. On the other hand, Brown Norway rats showed mature granulomas including eosinophils with increased transcription of IL-12 without increased transcription of not only IFN-gamma and IL-2 but also Th2 cytokines such as IL-4, IL-5, and IL-10, unexpectedly. The colony-forming unit of the lung was decreased exponentially in both strains, and that of Brown Norway rats was significantly lower than that of Lewis rats 10 days after the inoculation. This indicated that Brown Norway rats demonstrated more fungicidal activity than Lewis rats in the early stage of the infection. The role of eosinophils with humoral immunity may be considered to be resistant in Brown Norway rats in addition of the function of macrophages.

Animals↗

PubMed2001

Histological diversity of vasculitic lesions in MPO-ANCA-positive autopsy cases.

To investigate the variety of histological features of vasculitic lesions in myeloperoxidase-specific antineutrophil cytoplasmic antibody (pANCA)-related vasculitis, retrospective pathological analysis was done on 13 autopsy cases, collected from 1990 to 1998 at five hospitals. These cases were classified into three groups: (i) pulmonary-renal syndrome characterized by capillaritis of lung and glomeruli with occasional small-vessel arteritis and/or phlebitis; (ii) glomerular capillaritis without pulmonary involvement associated with significant small-vessel arteritis; and (iii) extensive distribution of small-vessel arteritis with no capillary involvement. The results suggest that pANCA-related vasculitis encompasses a wide variety of vasculitic syndromes, including pulmonary-renal syndrome, microscopic polyarteritis nodosa, and classic polyarteritis nodosa. pANCA may contribute to pathogenesis in all of these cases.

Aged↗

PubMed2001

Long-term follow-up study of Lennox-Gastaut syndrome in patients with severe motor and intellectual disabilities: with special reference to the problem of dysphagia.

A long-term follow-up study of Lennox-Gastaut syndrome (LGS) ( > 10 years) was conducted with 38 patients with severe motor and intellectual disabilities (SMID) to clarify the relationship between the rapid development of dysphagia and epileptic seizures, and to elucidate the long-term evolution of LGS in patients with SMID. Those who showed a relatively favourable seizure outcome were compared to those with a poor seizure outcome. Poor seizure outcome correlated strongly with: (a) an early appearance of dysphagia and additional deterioration of the already retarded mental function; (b) a predominance of atypical absence seizures; and (c) persistent frequent epileptiform discharges during electroencephalographic evaluations. Neither age at seizure onset nor intelligence level at the time of the last examination was correlated with seizure prognosis. Further, seizure prognosis was not related to the aetiology of LGS. Repeated seizures apparently caused development of progressive epileptic encephalopathy, in addition to the underlying severe brain damage. Since development of dysphagia burdens an already severely handicapped patient with intensive medical care, efforts to reduce the seizures and design a long-term care plan are of great importance.

Adult↗

PubMed2001

Production of secretory leukocyte protease inhibitor by human amniotic membranes and regulation of its concentration in amniotic fluid.

Secretory leukocyte protease inhibitor (SLPI) is a potent inhibitor of human leukocyte elastase. SLPI is a protein found in various human fluids, including parotid secretions, cervical mucus, seminal plasma and ascites. Western blot analysis revealed that SLPI protein is detected as a 12 kDa band in both the amniotic fluid and the amniotic membrane. The amniotic fluid concentrations of SLPI were assayed by enzyme-linked immunosorbent assay. SLPI concentrations in the amniotic fluid of women in the third trimester were higher than those in the second trimester. Immunohistochemistry using an anti-SLPI polyclonal antibody revealed positive staining in epithelial cells in amniotic membranes. Reverse transcription-polymerase chain reaction demonstrated that SLPI transcripts could be detected in the amniotic membranes. To determine the mechanism of SLPI production by amniotic cells, purified amniotic cells were stimulated with various cytokines. Amniotic cells produced SLPI in a dose-dependent manner when stimulated with interleukin (IL)-1alpha, IL-1beta, and tumour necrosis factor-alpha. The present findings show that SLPI is produced by the amniotic membranes in response to cytokine concentrations. The SLPI in the amniotic fluid may contribute to immunodefence mechanisms during pregnancy.

Amniotic Fluid↗

PubMed2001

Effects of recombinant human macrophage colony-stimulating factor on atherosclerotic lesions established in the aorta of high cholesterol-fed rabbits.

Anti-atherosclerotic effects of human macrophage colony-stimulating factor were investigated using rabbits fed a high cholesterol diet. Rabbits fed a diet containing 2% cholesterol for 59 days developed hyperlipidemia and atheromatous aortic plaques. They were then administered 80 microg/kg/day of either macrophage colony-stimulating factor or human serum albumin, as a control, for the next 12 weeks. Compared with the control group, rabbits treated with macrophage colony-stimulating factor had significantly fewer plaques on the inner surface of the thoracic and abdominal aortae, and half the sectional area of thickened intima in the aortic arch, as well as in the thoracic and abdominal aortae. Macrophage colony-stimulating factor also decreased the cholesterol content of the atherosclerotic lesions. Serobiochemical analyses revealed that macrophage colony-stimulating factor increased the levels of high density lipoprotein-cholesterol significantly, without influencing other lipid parameters such as the level of low density lipoproteins. The effects of macrophage colony-stimulating factor were evident until the fourth week of drug injection, at which time anti-human macrophage colony-stimulating factor antibodies were clearly induced in the serum. These results indicate that exogenously administered macrophage colony-stimulating factor suppresses atherosclerotic lesions induced by a high cholesterol diet by activating lipid metabolism in vivo.

Animals↗

PubMed2001

Pulmonary involvement in mixed connective tissue disease: high-resolution CT findings in 41 patients.

The objective of this study was to describe the pulmonary abnormalities on high-resolution computed tomography (CT) in patients with mixed connective tissue disease (MCTD). The study included 41 patients who met the diagnostic criteria for MCTD and showed abnormal findings on high-resolution CT. The presence, extent, and distribution of various high-resolution CT findings were evaluated. The predominant abnormalities included areas of ground-glass attenuation (n = 41), subpleural micronodules (n = 40), and nonseptal linear opacities (n = 32). Other common findings included peripheral predominance (n = 40), lower lobe predominance (n = 39), intralobular reticular opacities (n = 25), architectural distortion (n = 20), and traction bronchiectasis (n = 18). Less common findings included honeycombing, ill-defined centrilobular nodules, airspace consolidation, interlobular septal thickening, thickening of bronchovascular bundles, bronchial wall thickening, bronchiectasis, and emphysema. Pulmonary involvement of MCTD is characterized by the presence of ground-glass attenuation, nonseptal linear opacities, and peripheral and lower lobe predominance. Ill-defined centrilobular opacities were uncommonly seen.

Adult↗

PubMed2001

Pulmonary involvement in primary Sjögren's syndrome: spectrum of pulmonary abnormalities and computed tomography findings in 60 patients.

The purpose of this study was to describe the high-resolution computed tomography (HRCT) findings of pulmonary involvement in primary Sjögren's syndrome. The study included 60 patients who met the diagnostic criteria for primary Sjögren's syndrome. The authors retrospectively reviewed the presence, extent, and distribution of various HRCT findings. Results showed that the most common HRCT findings were areas with ground-glass attenuation (92%), followed by subpleural small nodules (78%), non-septal linear opacity (75%), interlobular septal thickening (55%), bronchiectasis (38%), and cysts (30%).

Adult↗

PubMed2001

Recurrent cerebral embolism in a familial amyloid polyneuropathy patient who received partial liver transplantation from a living donor.

Cerebral embolism in relation to cardiac amyloidosis has not been widely noted. A 47-year-old woman who had been suffering from familial amyloid polyneuropathy (FAP) for 7 years was treated with partial liver transplantation from a living donor and her early postoperative course was uneventful. During the 391st to 613th postoperative day she experienced recurrent cerebral infarctions, but clinical examinations revealed no disorders capable of producing cerebral embolism. At autopsy splenic infarction and intracardiac thrombi adhering to the mitral valve and left atrium were found, and these areas showed severe amyloid deposition. Amyloid heart is considered to be one possible cause of systemic embolism.

Amyloid Neuropathies↗

PubMed2001

High-resolution CT using multidetector CT equipment: evaluation of image quality in 11 cadaveric lungs and a phantom.

OBJECTIVE: The aim of this study was to evaluate the image quality and diagnostic efficacy of multidetector high-resolution CT (HRCT) by comparing it with single-detector HRCT and by comparing the noise and artifact of multidetector HRCT images with a phantom. SUBJECTS AND METHODS: Multidetector HRCT with six parameters and single-detector HRCT were performed on cadaveric lungs. The image quality and diagnostic efficacy of multidetector HRCT were evaluated in comparison with those of single-detector HRCT. A phantom was scanned, and image artifact and noise were investigated. RESULTS: . The image quality of multidetector HRCT with axial 1.25 mm x 4i (four images per gantry rotation) mode was equal to that of single-detector HRCT. The image quality of multidetector HRCT with other modes was worse than that on single-detector HRCT. The diagnostic efficacy of multidetector HRCT with high-quality mode (pitch, 3:1) and axial mode was equal to that of single-detector HRCT. The diagnostic efficacy on multidetector HRCT with high-speed mode (pitch, 6:1) was worse than that on single-detector HRCT. In the phantom study, images made in high-speed mode had strong artifacts. Noise in the axial mode was milder than that in high-speed mode but more severe than that in high-quality mode. CONCLUSION: The image quality of axial HRCT with multidetector CT is equal to that on single-detector HRCT. Axial HRCT with multidetector CT is appropriate for evaluating subtle lung abnormalities, but high-speed mode is unsuitable. Using the high-quality mode degrades image quality but is still worthwhile.

Cadaver↗

PubMed2001

Three-dimensional anisotropy contrast magnetic resonance axonography to predict the prognosis for motor function in patients suffering from stroke.

OBJECT: The purpose of this study was to assess how early wallerian degeneration in the corticospinal tracts of patients who had suffered from stroke was detected using three-dimensional anisotropy contrast (3D-AC) magnetic resonance (MR) axonography and to explore the possibility of predicting the prognosis for motor function in these patients. METHODS: Ten healthy volunteers and 16 stroke patients with hemiparesis were studied using MR images including 3D-AC MR axonography images obtained using a 1.5-tesla MR imaging system. The axonography was performed using an echoplanar imaging method. All patients underwent MR studies 2, 3, and 10 weeks after stroke onset. To detect wallerian degeneration, the diffusion anisotropy in the corticospinal tracts at the level of the upper pons was evaluated on axial images. These MR findings were compared with the patients' motor functions, which were classified according to the Brunnstrom criteria 12 weeks after the onset of stroke. In all patients with poor recovery (Brunnstrom Stages I-IV), wallerian degeneration, which was demonstrated as a reduction in diffusion anisotropy on axonography images, could be observed in the corticospinal tracts; this degeneration was not found in patients with good recovery (Stages V and VI). Axonography could be used to detect degeneration between 2 and 3 weeks after stroke onset. On conventional T2-weighted MR images, hyperintense areas indicating wallerian degeneration were not detected until 10 weeks after stroke onset. CONCLUSIONS: With the aid of 3D-AC MR axonography, wallerian degeneration can be detected in the corticospinal tracts during the early stage of stroke (2-3 weeks after onset), much earlier than it can be detected using T2-weighted MR imaging. The procedure of 3D-AC MR axonography may be useful in predicting motor function prognosis in stroke patients.

Adult↗

PubMed2001

Expression of vascular endothelial growth factor in human monocyte/macrophages stimulated with lipopolysaccharide.

Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells. We have studied the production of VEGF by human macrophages in response to lipopolysaccharide (LPS). Macrophages stimulated with LPS expressed VEGF mRNA and protein in concentration- and time-dependent manners. The LPS-induced expression of VEGF was inhibited by cycloheximide pretreatment, which suggested that synthesis of certain factor(s) is required for the LPS activity. The induction of VEGF was also suppressed by SB203580, an inhibitor of p38 mitogen-activated protein (MAP) kinase. These results suggest that the LPS-induced VEGF expression depends on the p38-mediated expression of c-Jun, which constitutes the AP-1 complex and binds to the AP-1 site in the VEGF promoter. Pretreatment of the cells with dexamethasone did not affect the LPS-induced upregulation of VEGF mRNA but strongly inhibited VEGF protein production, and the involvement of posttranscriptional regulation on VEGF expression by dexamethasone was suggested. The conditioned medium of LPS-stimulated macrophages enhanced the growth of cultured endothelial cells and it was inhibited by an antibody against VEGF. We conclude that macrophages produce VEGF in response to the stimulation with LPS, which may be partly mediated by the p38 MAP kinase pathway.

Cells, Cultured↗

PubMed2001

[Surgical treatment of infectious endocarditis complicated by discrete subaortic stenosis: report of a case].

A 39-year-old male with a history of cardiac murmur from early childhood was diagnosed as having infectious endocarditis (IE) complicated by discrete subaortic stenosis (DSS). Echocardiography revealed severe aortic regurgitation, subaortic membranous structure and mild mitral regurgitation. The pressure gradient across the subaortic stenosis was 105 mmHg according to continuous Doppler wave ultrasonography. Aortic valve replacement and resection of subaortic membranous tissue and mitral annuloplasty were performed. Postoperative cardiac catheterization demonstrated that the hemodynamic data were remarkably improved, and the patient was free of symptoms. He is currently well at 6 months after the operation.

Adult↗

PubMed2001

[Experimental study of pharmacological hypothermia: enhanced neuroprotective effect of a novel 5-HT 1 A agonist SUN N4057 by the pharmacological hypothermia].

PURPOSE: 5-hydroxytryptamine(5-HT) 1 A receptor agonists have a potentially marked neuroprotective reaction by both neuroprotective and hypothermic effects. We previously reported (1) the neuroprotective effect against the cerebral ischemia under normothermic condition, and (2) the hypothermic effect of the novel compound of 5-HT 1 A agonist, SUN N4057. The present investigation was designed to examine the enhancement of the neuroprotective effect by its pharmacological hypothermia. METHODS: In 24 anesthetized cats(body weight 1.9-4.6 kg), the left middle cerebral artery(MCA) occlusion was performed via the transorbital approach. Just after MCA occlusion, SUN N4057(6 micrograms/kg/min) was infused. Physiological parameters were measured continuously, and arterial blood gas was analyzed hourly for 6 hours and maintained within the normal ranges. Animals were randomly allocated to the following three groups: (1) ischemic controls infused with sterile saline(Group A, n = 8), (2) SUN N4057 under normothermic condition(Group B, n = 8), (3) SUN N4057 (Group C, n = 8). Then, brain coronal sections of 3 mm in thickness were stained with 1% triphenyltetrazolium chloride(TTC) solution, and hemispheric infarct volumes were calculated by using a computerized image analysis system. RESULTS: There were no significant differences in any physiological parameters among 3 groups. In Group C, brain temperature decreased significantly starting 1 hour after MCA occlusion and dropped by 2.1 +/- 0.7 degrees C 5 hours. Infarct volumes were 35.6 +/- 6.9% (Group A), 23.3 +/- 5.8% (Group B) and 12.3 +/- 11.3% (Group C), respectively. There were significant differences among three groups(p < 0.05). CONCLUSION: On the basis of these data, we conclude that SUN N4057 provides more effective neuroprotection by the combination of hypothermic and neuroprotective effects. Chemical hypothermia may lead to a new therapeutic approaches for treatment of brain ischemia.

Animals↗

PubMed2000

Phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by protein kinase N.

CPI-17 is a phosphorylation-dependent inhibitory protein for smooth muscle myosin phosphate. Phosphorylation at Thr(38), in vitro, by protein kinase C or Rho-kinase enhances the inhibitory potency toward myosin phosphatase. Phosphorylation of CPI-17 by protein kinase N (PKN), a fatty acid- and Rho-activated serine/threonine kinase, and its effect on smooth muscle myosin phosphatase activity were investigated. CPI-17 was phosphorylated by GST-PKN-CAT, a constitutively active GST-fusion fragment of PKN, to 1.46 mol of P/mol of CPI-17, in vitro. The K(m) value of CPI-17 for PKN was 0.96 microM. Phosphorylation of PKN dramatically increased the inhibitory effect of CPI-17 on myosin phosphatase activity. The major and inhibitory phosphorylation site was identified as Thr(38) using a point mutant of CPI-17 and a phosphorylation-state specific antibody. Thus, CPI-17 is a substrate of PKN and might be involved in the Ca(2+) sensitization of smooth muscle contraction as a downstream effector of Rho and/or arachidonic acid.

Animals↗

PubMed2000

Phosphorylation of CPI-17, an inhibitory phosphoprotein of smooth muscle myosin phosphatase, by Rho-kinase.

Phosphorylation of CPI-17 by Rho-associated kinase (Rho-kinase) and its effect on myosin phosphatase (MP) activity were investigated. CPI-17 was phosphorylated by Rho-kinase to 0.92 mol of P/mol of CPI-17 in vitro. The inhibitory phosphorylation site was Thr(38) (as reported previously) and was identified using a point mutant of CPI-17 and a phosphorylation state-specific antibody. Phosphorylation by Rho-kinase dramatically increased the inhibitory effect of CPI-17 on MP activity. Thus, CPI-17 as a substrate of Rho-kinase could be involved in the Ca(2+) sensitization of smooth muscle contraction as a downstream effector of Rho-kinase.

Animals↗

PubMed2000

Identification of a 1-Mb common region at 16q24.1-24.2 deleted in hepatocellular carcinoma.

To identify the location of one or more putative tumor suppressor genes that may be involved in hepatocellular carcinoma (HCC), we examined 96 such tumors for their patterns of allelic loss at 21 microsatellite marker loci distributed along chromosome arm 16q. Allelic loss at one or more loci was observed in 58 (60%) of these tumors. Detailed deletion mapping identified a distinct commonly deleted region located within an interval flanked by D16S534 and D16S3091 at 16q24.1-24.2. By constructing a physical map consisting of a YAC contig across the region, the extent of the deleted region was determined to be less than 1 Mb. Among the tumors for which clinical data were available, allelic loss at 16q24.1-24.2 was more frequent in tumors arising from liver cirrhosis compared to HCCs arising from chronic hepatitis (30/42, 71%, vs. 13/33, 39%; P = 0. 0054). Additionally, allelic loss at 16q24.1-24.2 was frequently observed in small tumors and early-stage tumors as well as in tumors of more advanced phenotype.

Carcinoma, Hepatocellular↗

PubMed2000

Nafamostat mesilate modulates the release of platelet-activating factor during left ventricular assistance with hemofiltration in canine heart failure.

OBJECTIVE: The enhanced generation of various chemical mediators is regarded as one of the mechanisms by which severe heart failure progresses to multiple organ failure. Platelet-activating factor is a phospholipid mediator which plays an important role in inflammatory reactions and circulatory shock. We studied the changes in platelet-activating factor levels in a canine heart failure model treated with a left ventricular assist device and hemofiltration, and assessed the effect of a protease inhibitor, nafamostat mesilate. METHODS: Twenty dogs underwent multiple coronary ligations, and at 2 hours after the ligations they were maintained on left ventricular assist device support with continuous hemofiltration. The animals were divided into two groups: a nafamostat group (n = 10) that received nafamostat mesilate (2 mg/kg/hr), and a control group (n = 10) that received vehicle only. RESULTS: The blood platelet-activating factor level, before coronary ligations, in the control and nafamostat groups was 2.3 +/- 0.4 and 2.0 +/- 0.7 ng/ml, respectively, and the coronary ligations had little effect on the platelet-activating factor. However, after the initiation of left ventricular assist device, the platelet-activating factor in the control group (5.6 +/- 2.2) was significantly higher (p < 0.05) than that in the nafamostat group (1.1 +/- 0.3). Nafamostat administration was also effective in controlling the increase in the blood lactate level. Hemofiltration did not change the platelet-activating factor. CONCLUSIONS: We concluded that platelet-activating factor may play a critical role in the development of severe heart failure with left ventricular assistance, and nafamostat administration is likely to be beneficial in such a critical condition by suppressing the platelet-activating factor level.

Animals↗

PubMed2000

Atherosclerosis and omega-3 fatty acids in the populations of a fishing village and a farming village in Japan.

The effect of different dietary habits on atherosclerosis was investigated by examining the content of ordinary diets and relevant risk factors through a mass health survey on two village populations in Japan. In total, 261 inhabitants in the fishing village and 209 in the farming village were examined for body build, blood pressure, and blood chemistry. Information on smoking habits and food consumption was obtained using a semi-quantitative item-frequency questionnaire. Pulse wave velocity of the aorta, intima-media thickness of the carotid artery, and atherosclerotic plaques as obtained by ultrasonography were used as measures of atherosclerosis. All measures of atherosclerosis are lower in the fishing village than in the farming village in both men and women. There is a striking 5-8-fold difference in the number of atherosclerotic plaques (P < 0.0001) between the populations. The observed differences in atherosclerosis parallels differences in dietary habits and differences in the serum essential fatty acids. Evaluation of the omega-3 fatty acids over the combined populations reveals a negative association with the number of plaques in the common carotid while the omega-6 fatty acids shows a weak positive association with plaques.

Adult↗