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Biomedical subjects

H Kawano

Publications and source records attributed to H Kawano.

At least 127 records · Page 7Linked to original sources
PubMed1999

Improved RNA analysis for immediate autopsy of temporal bone soft tissues.

RNA analysis is essential for understanding biological activities of a cell or tissue. Unfortunately, retrieval of RNA from existing archives of human temporal bones has proven extremely difficult due to degradation of RNA molecules. The major factors that contribute to degradation of RNA in specimens from autopsied temporal bones are tissue autolysis due to time elapsed before autopsy, and technical problems in processing the bones after harvest. We therefore focused on improving the survival of RNA in human temporal bones by shortening the time to autopsy and through modification of the processing technique by removing targeted tissues directly from the temporal bones and by avoiding time-consuming decalcification and celloidin-embedding. Eight temporal bones collected at immediate autopsies were used in this study. Representative mRNAs, ranging from high (MUC5B, physically unstable) to low (beta-actin, physically stable) molecular weights, and from abundant (MUC5B) to non-abundant (MUC1) RNA, were studied by in situ hybridization, Northern blot technique, or both. Using this modified protocol in autopsies performed up to 6 h after death, the existence of mRNAs was demonstrated in all bones studied. This improved method demonstrates the feasibility of the use of autopsied temporal bone tissues for RNA analysis.

Autopsy↗
PubMed1999

The usefulness of Tc-99m MIBI for evaluating brain tumors: comparative study with Tl-201 and relation with P-glycoprotein

PURPOSE: This study was undertaken to determine the usefulness of Tc-99m methoxyisobutylisonitrile (MIBI) in brain tumors compared with TI-201 imaging. The authors evaluated the correlation between MIBI uptake and the presence of P-glycoprotein, and also the relation between MIBI uptake in response to combined radiotherapy and chemotherapy in glioblastoma. MATERIALS AND METHODS: Thirty-four brain tumors composed of 15 glioblastoma multiforme (GBM), 5 anaplastic astrocytomas, 5 low-grade astrocytomas, and 9 metastases were evaluated. Early and delayed images were obtained for MIBI and Tl-201 scintigraphy. P-glycoprotein status in all GBM, 2 anaplastic astrocytomas, 2 low-grade astrocytomas, and 2 metastases were evaluated immunohistochemically. Patients with GBM were divided into an effective and a noneffective group according to the change in tumor size. MIBI uptake indices were compared for these two groups. RESULTS: Both radiopharmaceuticals accumulated in all GBM and anaplastic astrocytomas. In low-grade astrocytomas, only one case showed tracer uptake. In metastasis, two cases showed high uptake on early images and marked washout on delayed images. Uptake ratio values (early uptake ratio and delayed uptake ratio) in all tumors were significantly higher in MIBI than in Tl-201. Immunohistochemical studies showed that the metastases were positive for P-glycoprotein but the GBM were not. In low-grade astrocytomas, a few cells were positively stained. In relation to the therapeutic outcome of GBM, both the early and delayed uptake ratios of MIBI were significantly greater in the noneffective group. CONCLUSIONS: Although diagnostic ability was comparable in MIBI and Tl-201, the imaging quality was better in MIBI. Both radiopharmaceuticals are useful in differentiating low-grade glioma from high-grade glioma. MIBI delayed imaging could also reflect the presence of P-glycoprotein. Intense MIBI uptake was also predictive of a poor clinical outcome in GBM.

Journal Article↗
PubMed1999

PPAR gamma-ligands inhibit migration mediated by multiple chemoattractants in vascular smooth muscle cells.

The purpose of this study was to determine the effect of the peroxisome proliferator-activated receptor gamma-(PPAR gamma) ligands troglitazone (TRO), rosiglitazone (RSG), and 15-deoxy-delta prostaglandin J2 (15d-PGJ2) on vascular smooth muscle cell (VSMC) migration directed by multiple chemoattractants. Involvement of mitogen-activated protein kinase (MAPK) in migration also was examined, because TRO was previously shown to inhibit nuclear events stimulated by this pathway during mitogenic signaling in VSMCs. Migration of rat aortic VSMCs was induced 5.4-fold by PDGF, 4.6-fold by thrombin, and 2.3-fold by insulin-like growth factor I (IGF-I; all values of p < 0.05). The PPAR gamma ligands 15d-PGJ2, RSG, or TRO all inhibited VSMC migration with the following order of potency: 15d-PGJ2 > RSG > TRO. Inhibition of MAPK signaling with PD98059 completely blocked PDGF-, thrombin-, and IGF-I-induced migration. All chemoattractants induced MAPK activation. PPAR gamma ligands did not inhibit MAPK activation, suggesting a nuclear effect of these ligands downstream of MAPK. The importance of nuclear events was confirmed because actinomycin D also blocked migration. We conclude that PPAR gamma ligands are potent inhibitors of VSMC migration pathways, dependent on MAPK and nuclear events. PPAR gamma ligands act downstream of the cytoplasmic activation of MAPK and appear to exert their effects in the nucleus. Because VSMC migration plays an important role in the formation of atherosclerotic lesions and restenosis, PPAR gamma ligands like TRO and RSG, which ameliorate insulin resistance in humans, also may protect the vasculature from diabetes-enhanced injury.

Animals↗
PubMed1999

TNF-alpha-induced migration of vascular smooth muscle cells is MAPK dependent.

-Migration of vascular smooth muscle cells (VSMC) is a key event in neointimal formation and atherosclerosis that may be linked to the accumulation of inflammatory cells and release of chemotactic cytokines. Tumor necrosis factor-alpha (TNF-alpha) induces chemotaxis of inflammatory cells and fibroblasts, but little is known about chemotactic signaling by TNF-alpha in VSMC. The aim of this study was to investigate the role of TNF-alpha in VSMC migration and to elucidate the chemotactic signaling pathways mediating this action. TNF-alpha (50 to 400 U/mL) induced migration of cultured rat aortic VSMC in a dose-dependent manner. Because activation of the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (MAPK) is known to be required in platelet-derived growth factor-directed and angiotensin II-directed migration of these cells, we used the MAPK-inhibitor PD98059 to determine if chemotactic signaling by TNF-alpha involves the MAPK pathway as well. We found that TNF-alpha-directed migration was substantially inhibited by PD98059. TNF-alpha (100 U/mL) transiently activated MAPK with a maximal induction 10 minutes after stimulation that returned to baseline levels by 2 hours after treatment. Only a single peak of increased MAPK activity was seen. PD98059 also blocked TNF-alpha-stimulated MAPK activation in a concentration-dependent manner, which is consistent with its inhibition of TNF-alpha-directed migration. To identify which TNF-alpha receptor is involved in TNF-alpha-induced MAPK activation, antibodies against the p55 TNF-alpha receptor-1 (TNF-R1) and the p75 TNF-alpha receptor-2 (TNF-R2) were used. VSMC express both receptors, but TNF-alpha-induced MAPK activation was inhibited only by the TNF-R1 antibody. The TNF-R2 antibody had no effect. Thiazolidinediones are known to inhibit TNF-alpha signaling in adipose tissue and attenuate platelet-derived growth factor-directed and angiotensin II-directed migration in VSMC. We therefore investigated the effects of the thiazolidinediones troglitazone (TRO) and rosiglitazone (RSG) on TNF-alpha-induced migration. Both TRO and RSG inhibited migration, but neither attenuated TNF-alpha-induced MAPK activation, indicating that their antimigration activity was exerted downstream of MAPK. These experiments provide the first evidence that early activation of MAPK is a crucial event in TNF-alpha-mediated signal transduction leading to VSMC migration. Moreover, inhibition of TNF-alpha-directed migration by the insulin sensitizers TRO and RSG underscores their potential as vasculoprotective agents.

Analysis of Variance↗
PubMed1999

MRI of arachnoid granulations within the dural sinuses using a FLAIR pulse sequence.

The purpose of the study was to assess the signal intensities of arachnoid granulations within the dural sinuses using the FLAIR sequence for differentiation of space-occupying lesions in and adjacent to the dural sinuses. We retrospectively reviewed MR images of the brain of 1118 consecutive subjects, ranging in age from 0 to 93 years (mean 57.2 years). Nodules within the dural sinuses with signal intensities similar to that of cerebrospinal fluid (CSF) on both T1 and T2 weighted images were defined as arachnoid granulations. The location, signal intensity on T1 weighted spin echo (SE), T2 weighted fast SE and FLAIR images, the impression on the inner table of the skull, and the size of the lesion were assessed. 112 subjects (10.0%), age range 4-89 years old (mean 58.9 years), were found to have 134 arachnoid granulations. The commonest location was the transverse sinus, with 115 granulations (85.8%). The prevalence of the granulations showed a peak in the sixth decade of age. All granulations were isointense relative to CSF on T2 weighted images and almost all lesions were isointense relative to CSF on T1 weighted images. On FLAIR images, 90.3% of the granulations were isointense relative to CSF and the other 9.7% granulations were slightly hyperintense compared with the CSF. 21 (15.7%) subjects showed impressions on the inner table; one case involved the outer table. In conclusion, arachnoid granulations were isointense or slightly hyperintense relative to CSF on FLAIR. FLAIR images are helpful in differentiating arachnoid granulations from other dural sinus lesions or skull lesions which have an intensity similar to that of CSF on T1 weighted and T2 weighted images.

Adolescent↗
PubMed1999

Relationship between serum biochemical values and marbling scores in Japanese Black steers.

In order to obtain available biochemical parameters related to the marbling score (MS), by which the meat was graded from 1 to 12 in Japan, serum biochemical values were examined in 13 Japanese Black steers during the fattening stages. The steers were divided into high MS (8-11) and low MS (4-5) groups and the fattening stage was also divided into 4 stages according to their feed contents; Stage I (11-13 month-old; 0-4 months after the fattening (af)), II (5-9 months af), III (10-14 months af), and IV (15-20 months af). High MS group showed significantly higher levels in glucose and urea nitrogen (at Stage I), albumin/globulin ratio (at Stage II), and magnesium (at Stage I and III), and lower level in vitamin A (at Stage III) than low MS group. These biochemical parameters, indicating conditions of steers during the fattening stages, are considered to have a possibility related to MS in fattening steers.

Animals↗
PubMed1999

MR imaging of Tornwaldt's cysts.

OBJECTIVE: The purpose of this study was to assess the characteristics of Tornwaldt's cysts as revealed by routine MR studies. MATERIALS AND METHODS: We retrospectively reviewed MR images of the brain in 1208 consecutive subjects who ranged in age from 3 weeks to 93 years (mean, 57.1 years). The signal intensity, shape, and size of Tornwaldt's cysts were assessed. Patients with Tornwaldt's cysts were then questioned about the presence of persistent nasal discharge, occipital headaches, and halitosis and an unpleasant taste in the mouth and about a history of adenoidectomy. RESULTS: Tornwaldt's cysts were found in 23 patients (1.9%) who ranged in age from 39 to 78 years (mean, 57.3 years). Of the 23 Tornwaldt's cysts, all were isointense to CSF on T2-weighted images and hyperintense to gray matter on the fluid-attenuated inversion-recovery images. The cysts showed high signal intensity compared with muscle on T1-weighted images. Nineteen cysts were round and four were oval. The mean size of the lesions was 6.0 mm in the major axis and 5.5 mm in the minor axis. Two patients with Tornwaldt's cysts had persistent nasal discharge and occipital headaches, and another patient had occipital headaches alone. None of the patients had undergone an adenoidectomy. CONCLUSION: Lesions consistent with Tornwaldt's cysts were found in 1.9% of the routine MR studies of the brain. The cysts had high signal intensity on T1-weighted, T2-weighted, and fluid-attenuated inversion-recovery images.

Adolescent↗
PubMed1999

Intraoperative transesophageal echocardiography for evaluation of mitral valve repair.

BACKGROUND AND AIM OF THE STUDY: Although mitral valve repair is a well-established procedure, incorrect assessment of the repaired valve may occasionally lead to the need for reoperation. This study was performed to evaluate the accuracy of color Doppler in assessing the competence of the repaired mitral valve. METHODS: Transesophageal echocardiography (TEE) and left ventriculography were each performed in 72 patients to compare the two techniques and a semi-quantitative index derived. Using this relationship, post bypass intraoperative TEE was then performed in 34 patients who underwent mitral valve repair, in order to assess the competence of the repaired valve. RESULTS: Significant differences were apparent in maximal regurgitant mosaic area between angiographic grade 0, and grades 1+ (p = 0.0006), 1+ and 2+ (p < 0.0001) and 2+ and 3+ (p = 0.0010). A maximal regurgitant area < 2 cm2 predicted angiographic grade as 0 (sensitivity 100%, specificity 95%), an area of 2-4 cm2 as 1+ (sensitivity 82%, specificity 100%), an area of 4-7 cm2 as 2+ (sensitivity 78%, specificity 90%), and an area > 7 cm2 as grade 3+ or 4+ (sensitivity 79%, specificity 93%). All 34 patients completed valve repair with the maximal regurgitant mosaic area < 2.5 cm2. Postoperative left ventriculography showed grade +1 in only five patients; four of these completed mitral valve repair with a maximal mosaic area > 2.0 cm2 as assessed by post bypass intraoperative TEE. During follow up, transthoracic echocardiography (TTE) detected recurrent mitral regurgitation which required mitral valve replacement in one patient, and rapid progression of mitral regurgitation in three patients. CONCLUSIONS: It is important that mitral valve repair should be completed with a maximal mosaic area < 2.0 cm2 as assessed by intraoperative TEE, in order to reduce the need for reoperation.

Adult↗
PubMed1999

[Molecular mechanisms of the pathway formation in the fetal rat cerebral neocortex].

Neural cell adhesion molecules (NCAMs), L1 and TAG-1, which are prominently expressed in the developing nervous system, have been shown to promote axonal growth and bundle formation of central neurons in vitro. In the cerebral neocortex of fetal rats, immunoreactions of L1 and TAG-1 were specifically localized on thalamic afferent axons and cortical efferent axons, respectively. L1-bearing thalamocortical axons preferentially extended in the subplate of the cortical anlage where neurocan, a brain-specific chondroitin sulfate proteoglycan (CSPG), was prominently expressed. In contrast, cortical efferent axons immunoreactive for TAG-1 did not enter the subplate and run in the intermediate zone where neurocan expression was less abundant. In addition, TAG-1-bearing axons extensively invaded regions expressing another type of brain-specific CSPG, phosphacan. In the cell culture system, neurite outgrowth of TAG-1-transfected PC 12 D cells was remarkably inhibited on the neurocan substrate, while the outgrowth on phosphacan substrate was significantly promoted. Although both L1 and TAG-1 have been reported to bind both neurocan and phosphacan in vitro, interactions between NCAMs and CSPGs in vivo indicate more complicated patterns than previously thought. Thus, the present results suggest that various patterns of functional correlation between NCAMs and CSPGs play important roles in the pathway formation of the rat cerebral neocortex.

Animals↗
PubMed1999

Natriuretic peptides regulate the expression of tissue factor and PAI-1 in endothelial cells.

In the present study, we demonstrate that brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) interact with angiotensin II (Ang II) in regulative blood coagulation and fibrinolysis by suppressing the expressions of both tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) induced by Ang II. The expressions of TF and PAI-1 mRNA were analyzed by northern blotting methods, and the activities of TF on the surface of rat aortic endothelial cells (RAECs) and PAI-1 in the culture media were respectively measured by chromogenic assay. Both BNP and CNP suppressed the expressions of TF and PAI-1 mRNA induced by Ang II in a time- and concentration-dependent manner via cGMP cascade, which suppressions were accompanied by respective decrease in activities of TF and PAI-1. However, neither the expression of tissue factor pathway inhibitor (TFPI) nor tissue-type plasminogen activator (TPA) mRNA was affected by the treatment of BNP and CNP.

Angiotensin II↗
PubMed1999

The effects of angiotensin metabolites on the regulation of coagulation and fibrinolysis in cultured rat aortic endothelial cells.

Not only angiotensin II (Ang II) but also other angiotensin metabolites such as angiotensin I (Ang I), angiotensin III (Ang III), angiotensin IV, or angiotensin 1-7 have recently been reported to have various activities. Few data, however, are available on the regulation of thrombus formation. In this study, we investigated the effects of angiotensin metabolites on the mRNA expression of tissue factor (TF), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1), and tissue type plasminogen activator (TPA) in cultured rat aortic endothelial cells. None of the used angiotensin metabolites altered TFPI or TPA mRNA expression levels. Ang I, Ang II, and Ang III made TF and PAI-1 mRNA inductions which were inhibited by an selective antagonist of angiotensin II type 1 receptors. These metabolites made TF predominant to TFPI or PAI-1 to TPA, and could render endothelial cells thrombogenic.

Angiotensin I↗
PubMed1998

Vitamin E administration improves impairment of endothelium-dependent vasodilation in patients with coronary spastic angina.

OBJECTIVES: We examined the effects of oral administration of vitamin E, an antioxidant, on endothelium-dependent vasodilation in patients with coronary spastic angina. BACKGROUND: We have recently reported that endothelium-dependent vasodilation is impaired in patients with coronary spastic angina (CSA). Furthermore, it is known that oxidative stress may play an important role in the impairment of endothelium-dependent vasodilation in cardiovascular diseases. METHODS: With the ultrasound technique, flow-dependent vasodilation of the brachial arteries during reactive hyperemia was examined before and after treatment for a month with either oral administration of vitamin E (alpha-tocopherol acetate, 300 mg/day) or placebo, which is randomly assigned, in patients with CSA (n=60). RESULTS: Before treatment, patients with CSA had impaired flow-dependent vasodilation, lower plasma levels of alpha-tocopherol and higher plasma levels of thiobarbituric acid reactive substances (TBARS), as compared with age- and sex-matched control subjects (n=60) (flow-dependent vasodilation: 3.1+/-1.8 vs. 7.1+/-2.5%, p < 0.001; alpha-tocopherol levels: 8.9+/-1.8 vs. 10.8+/-1.8 microg/ml, p < 0.001). In patients with CSA, treatment with vitamin E restored flow-dependent vasodilation (3.1+/-1.7 vs. 8.3+/-2.0%, p < 0.001), and this improvement was associated with the decreases in plasma TBARS levels and anginal attacks. CONCLUSIONS: The results indicate that vitamin E treatment improved endothelium-dependent vasodilation and decreased plasma TBARS levels in patients with CSA. Thus, increased oxidative stress may contribute to endothelial dysfunction and anginal attacks in patients with CSA.

Adult↗
PubMed1998

Up-regulation of vascular endothelial growth factor induced by hepatocyte growth factor/scatter factor stimulation in human glioma cells.

Recent findings suggest that hepatocyte growth factor/scatter factor (HGF/SF) contributes to the malignant progression of human gliomas. We investigated the effect of HGF/SF on vascular endothelial growth factor (VEGF) expression of c-Met/HGF receptor-positive human glioma cell lines. Treatment of the glioma cells with various concentrations of HGF/SF resulted in an enhanced secretion of VEGF proteins accompanying increased transcription of VEGF mRNA in a dose-dependent fashion. Since malignant gliomas frequently co-express HGF/SF and its receptor, these results suggest that HGF/SF could act as an indirect angiogenic factor through autocrine induction of VEGF expression and secretion in malignant gliomas.

Endothelial Growth Factors↗
PubMed1998

Evaluation of molecular strategies to develop a live dengue vaccine.

BACKGROUND: Millions of individuals are estimated to become infected with dengue virus each year, particularly in tropical and subtropical regions. Mortality is low but infection can lead to a severe form of dengue, characterised by haemorrhage and shock. A safe and effective vaccine against dengue is still not available. OBJECTIVE: To use the successful construction of dengue type 4 virus (DEN4) cDNA, which yields infectious RNA transcripts, to provide a new approach to the development of safe and effective dengue vaccines. STUDY DESIGN: The 3' and 5' noncoding (NC) regions of the genome were targeted to construct DEN4 deletion mutants, because the sequences in these regions are thought to play an important role in the regulation of viral replication. DEN4 cDNA was also employed to construct a viable chimeric virus with dengue type 1, 2 or 3 antigenicity, by substitution of heterotypic structural protein genes. RESULTS: Most viable mutants, recovered from the cDNA constructs, were partially restricted for growth in simian cells as analysed by plaque morphology assay and viral yield analysis. Several 3' NC deletion mutants which exhibited a range of growth restriction in cell culture were further evaluated for infectivity and immunogenicity in rhesus monkeys. Occurrence and duration of viraemia were reduced for these deletion mutants, compared to the wild type DEN4. Analysis of antibody response to infection in rhesus monkeys also indicated that some of these mutants were attenuated. These DEN4 deletion mutants represent promising live dengue vaccine candidates that merit further clinical evaluation. Chimera DEN1/DEN4 or DEN2/DEN4 which expresses DEN1 or DEN2 antigenicity were also used to infect monkeys. Most monkeys immunised with these chimeric viruses, singly or in combination, developed high titres of neutralising antibodies and were protected against homotypic wild type DEN1 or DEN2 challenge. CONCLUSIONS: DEN4 and its derived chimeric viruses of other three dengue serotype specificity, that contain appropriate attenuating mutations, have a potential use in a tetravalent live vaccine against dengue.

Animals↗
PubMed1998

Association of remnant lipoprotein levels with impairment of endothelium-dependent vasomotor function in human coronary arteries.

BACKGROUND: It remains undetermined whether triglyceride-rich lipoproteins are an independent risk factor for atherosclerosis. METHODS AND RESULTS: The correlation of responses of coronary arterial diameter (quantitative coronary angiography) and coronary blood flow (intracoronary flow wire technique) to intracoronary infusion of acetylcholine (10 and 50 microg/min) with coronary risk factors including remnant lipoprotein levels was statistically analyzed in 106 consecutive subjects with normal coronary angiograms. Remnant lipoproteins were isolated from fasting blood with an immunoaffinity mixed gel containing anti-apolipoprotein (apo) A-1 and anti-apoB-100 monoclonal antibodies. In multivariate stepwise regression analysis, remnant lipoprotein levels had the most significant correlation with abnormal epicardial coronary vasomotor responses to acetylcholine infusion, reflected by impaired dilation or constriction of the epicardial coronary arteries, and the levels also had an inverse and independent correlation with the coronary blood flow increase in response to acetylcholine. In a subgroup of 53 consecutive subjects, constrictor responses of epicardial coronary diameters to intracoronary infusion of NG-monomethyl-L-arginine (50 micromol/min for 4 minutes) at baseline, reflecting the presence of coronary nitric oxide bioactivity, had an inverse and independent correlation with remnant lipoprotein levels by use of multivariate analysis. CONCLUSIONS: Remnant lipoprotein levels were independently associated with abnormal endothelium-dependent vasomotor function in large and resistance coronary arteries in humans, indicating that remnant lipoproteins may impair endothelial vasomotor function in human coronary arteries. The decrease in coronary nitric oxide bioactivity may be responsible in part for the inhibitory effects of remnant lipoproteins.

Acetylcholine↗
PubMed1998

Coordinate expression of L1 and 6B4 proteoglycan/phosphacan is correlated with the migration of mesencephalic dopaminergic neurons in mice.

Mesencephalic dopaminergic (DA) neurons of mice are generated from embryonic day 10 to 12 (E10-12) in the ventricular zone of the mesencephalon. They first migrate toward the ventral mesencephalon, and then turn laterally, or tangentially, in the basal part of the mesencephalon. With immunohistochemical analysis of E10-E15 ICR mice, we found that cell adhesion molecule L1 was transiently expressed on the median part of tangential fibers coincident with the lateral migration of DA neurons from E11 to E13, when neurons move along the tangential fibers toward their final destinations: the reticular formation, the substantia nigra pars compact, and the ventral tegmental area. While L1 expression was not observed in DA neurons, they expressed a chondroitin sulfate proteoglycan, 6B4 proteoglycan/phosphacan, which has been shown to bind to L1/Ng-CAM in vitro. These results suggest that the heterophilic interaction between 6B4 proteoglycan on the neurons and L1 on the fibers is involved in the lateral migration of mesencephalic DA neurons in mice.

Animals↗