Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 271 records · Page 15Linked to original sources

PubMed2000

New imaging findings in a patient with central nervous system dysfunction after bone marrow transplantation.

Central nervous system disorders are an important complication of bone marrow transplantation (BMT). We have recently performed cerebral angiography to examine central nervous system dysfunction in a 22-year-old woman with acute lymphoblastic leukaemia who had undergone BMT. Angiography demonstrated multiple stenoses and occlusions in the peripheral branches of the anterior and middle cerebral arteries, a pattern similar to that seen in vasculitis. She was thought to most likely have cytomegalovirus (CMV) vasculitis, but other forms of vasculitis, such as angiitis-like-syndrome-associated graft-versus-host disease could not be excluded. This case suggests that CMV vasculitis may cause central nervous system dysfunction after BMT and that imaging studies may provide useful information about central nervous system disorders in these patients.

Adult↗

PubMed2000

Acute promyelocytic leukemia with marrow fibrosis at initial presentation: possible involvement of transforming growth factor-beta(1).

Although the occurrence of marrow fibrosis in acute myeloid leukemia has been described, there have been no reports of acute promyelocytic leukemia (APL) associated with marrow fibrosis. Here we describe an APL patient with severe marrow fibrosis at initial presentation. He had the typical manifestations of APL, except for marrow fibrosis. Complete remission was achieved by treatment with all-trans retinoic acid plus chemotherapy, and his marrow fibrosis gradually improved concomitantly with the decrease in leukemic cells. To clarify the mechanism of marrow fibrosis in this patient, we investigated the expression of genes for several cytokines promoting fibrosis by the reverse transcriptase polymerase chain reaction methods. An overexpression of transforming growth factor-beta(1) was noted in his leukemic cells at initial presentation, whereas no increase in expression was observed at the time of relapse when he no longer had marrow fibrosis. These findings suggest that overexpression of transforming growth factor-beta(1) was involved in the development of marrow fibrosis in this APL patient.

Adult↗

PubMed2000

Bezafibrate increases prebeta 1-HDL at the expense of HDL2b in hypertriglyceridemia.

Prebeta1-high density lipoprotein (prebeta1-HDL), the initial acceptor of cell-derived cholesterol, can be generated from HDL(2) by hepatic lipase. Because bezafibrate elevates lipase activity, it may increase prebeta1-HDL at the expense of HDL(2). To answer this question, we determined the apolipoprotein A-I (apoA-I) distribution in 20 hypertriglyceridemics (triglycerides>2.26 mmol/L) and 20 sex-matched normolipidemics by native 2-dimensional gel electrophoresis. At baseline, prebeta1-HDL was 70% higher in hypertriglyceridemics than in normolipidemics (123.5+/-49.9 versus 72.5+/-34.1 mg/L apoA-I, P<0.01). Prebeta1-HDL was positively correlated with triglyceride (r=0.624, P<0.0001). A 4-week bezafibrate treatment (400 mg daily) increased prebeta1-HDL by 30% (160.2+/-64.5 mg/L apoA-I, P<0.05) but decreased HDL(2b) by 31% (from 188.8+/-94.9 to 129.3+/-78.7 mg/L apoA-I, P<0.05). Hepatic lipase activity increased by 24% (P<0.005). Prebeta1-HDL was generated either from ultracentrifugally isolated HDL(2) or from plasma during incubation with triglyceride lipase. In conclusion, bezafibrate increases prebeta1-HDL at the expense of HDL(2). We speculate that such an effect might partly contribute to the antiatherogenic action of bezafibrate.

Adult↗

PubMed2000

Role of p38 mitogen-activated protein kinase in neointimal hyperplasia after vascular injury.

p38 mitogen-activated protein kinase (MAPK) is involved in intracellular signals that regulate a variety of cellular responses during inflammation. However, the role of p38 MAPK in atherosclerosis, a chronic inflammatory disorder, remains uncertain. The aim of the present study was to examine the role of p38 MAPK in the development of neointimal hyperplasia in balloon-injured rat carotid arteries. Immunohistochemical studies indicated that p38 MAPK was rapidly activated in the majority of medial cells in injured arterial walls. Rats treated with FR167653, a selective inhibitor of p38 MAPK, at a dosage of 10 mg x kg(-1) x d(-1), had a 29.4% lower intima-to-media ratio than the untreated controls at 14 days after balloon injury (P:<0.05). The percentage of proliferating nuclear antigen-positive cells in the media at 48 hours was significantly lower in the FR167653-treated group than in the control group. Quantitative competitive reverse transcription-polymerase chain reaction analysis revealed that interleukin-1beta mRNA expression in arteries was significantly inhibited by FR167653 (to 18.1% of control, P:<0.05) at 8 hours after balloon injury. Moreover, p38 MAPK activation and interleukin-1beta production by lipopolysaccharide-stimulated vascular smooth muscle cells were inhibited by FR167653 in a concentration-dependent manner in vitro. These results indicate that p38 MAPK is activated in vascular walls after injury and promotes neointimal formation and suggest that selective inhibition of p38 MAPK may be effective in the prevention of restenosis after percutaneous transluminal coronary angioplasty.

Angioplasty, Balloon, Coronary↗

PubMed2000

A role for heterologous gap junctions between melanoma and endothelial cells in metastasis.

F10 and BL6 sublines of B16 mouse melanoma cells are metastatic after intravenous injection, but only BL6 cells are metastatic after subcutaneous injection. We found that connexin (Cx) 26 is upregulated in BL6 cells. To examine gap junction formation, we devised a coculture system, in which an opened vein segment was placed at the bottom of a culture dish and then dye-labeled melanoma cells were seeded onto it. Immunohistochemistry indicated that the vein segment preserved the integrity of the endothelial monolayer. In this system, BL6 cells could transfer dye into endothelial cells but F10 cells could not. Transfection with wild-type Cx26 rendered F10 cells competent for coupling with endothelial cells and as spontaneously metastatic as BL6 cells. Conversely, transfection with a dominant-negative form of Cx26 rendered BL6 cells deficient in coupling and less metastatic. In human melanoma lesions, the level of Cx26 expression was low in melanoma cells residing in the basal layer, but significantly upregulated in melanoma cells invading the dermis. The results suggested that Cx26 plays a role in intravasation and extravasation of tumor cells through heterologous gap junction formation with endothelial cells.

Animals↗

PubMed2000

Clinical assessment of vascular thrombosis using indium-111 platelet scintigraphy.

The authors reviewed the clinical value of platelet scintigraphy by using autologous platelets labeled with indium-111-oxine to detect thrombotic activity at vascular thrombosis sites. Thirty-nine patients with deep vein thrombosis, 28 with arteriosclerosis obliterans, and 10 with pulmonary embolism were the subjects of this study. Platelet accumulation on scintigrams had a tendency to correlate with aggravation of acute thrombotic symptoms in deep vein thrombosis and arteriosclerosis obliterans. In addition, appropriate thrombolytic and anticoagulant therapy resulted in reduced platelet accumulation in conjunction with improvement of acute symptoms. On the other hand, this type of scintigraphy was not so sensitive for assessment of pulmonary embolism. Platelet scintigraphy could facilitate the assessment of thrombotic activity and might be useful for determining the optimal indication of thrombolytic and anticoagulant therapy for acute vascular thrombosis.

Adult↗

PubMed2000

Intravenous leiomyomatosis extending into the right ventricular cavity: one-stage radical operation using cardiopulmonary bypass--a case report.

The authors describe a 47-year-old woman with intravenous leiomyomatosis (IVL) extending into the right ventricular cavity. This rare entity is a neoplasm originating from smooth muscle of the uterus, with vermiform extensions into the inferior vena cava. The patient underwent a one-stage operation under simultaneous sternotomy and laparotomy, and radical excision of the tumor was successfully achieved with use of normothermic cardiopulmonary bypass. Although this tumor is histologically benign, it sometimes extends into the cardiac cavity and causes sudden death due to incarceration into the atrioventricular orifice. Moreover, recurrence or lung metastasis of IVL has been reported. The authors recommend a one stage-radical resection of the tumor or a two-staged operation within a short interval. In the literature, 24 surgical cases of the intravenous leiomyomatosis with intracardiac extension have been reported. The diagnosis and surgical treatment of this tumor are reviewed and discussed.

Cardiac Surgical Procedures↗

PubMed2000

Oxytocin stimulates the translocation of oxytocinase of human vascular endothelial cells via activation of oxytocin receptors.

Oxytocinase (OTase) degrades several small peptides such as oxytocin (OT), and thus plays important roles in fetal development and maintenance of human homeostasis during pregnancy. The physiological effects of OT are mediated via its receptor (OTR). Although the interactions between OT and OTR have studied extensively, the relationship to OTase remains to be clarified. It is known that human umbilical vascular endothelial cells express OTR messenger RNA; therefore, they were selected for examination of this question in the present study. RT-PCR experiments confirmed the existence of messenger RNA for OTase, and assessment of protein levels and activity clarified that OT increases the activity of OTase at the cell surface via binding to OTR. This stimulation appears to involve translocation of OTase from cytosolic to the cell surface in response to cellular signal transduction pathways linked to the OTR. Protein kinase C stimulation significantly increased the cell surface activity of OTase, whereas its inhibition resulted in reduction. In summary, our findings provide clear evidence that OT triggers directly OTase translocation in human umbilical vascular endothelial cells via a protein kinase C-dependent pathway coupled to OTR.

Biological Transport↗

PubMed2000

The anxiolytic effect of two oriental herbal drugs in Japan attributed to honokiol from magnolia bark.

An improved elevated plus-maze test in mice revealed that seven daily treatments with two different traditional Chinese medicines, known as Kampo medicines in Japan, Hange-koboku-to (composed of extracts of 5 plants) and Saiboku-to (composed of extracts of 10 plants), produced an anxiolytic effect, and the effect was mainly due to the presence of honokiol derived from magnolia. This study was carried out to evaluate the anxiolytic potential of honokiol, Hange-koboku-to and Saiboku-to, which were prescribed with two different magnolia samples: Kara-koboku (Magnoliae officinalis) (KA) or Wa-koboku (Magnoliae obovata) (WA). The doses of test samples were adjusted to ensure a constant dose of honokiol at 0.2 mg kg(-1). Although the doses of magnolol (an isomer of honokiol), as well as those of undetermined chemicals, varied among samples, the seven daily treatments with 9 out of 10 test samples produced an anxiolytic effect almost equivalent to that produced by 0.2 mg kg(-1) honokiol. The only exception was the sample containing the lowest amount of honokiol. Magnolia-free preparations of Hange-koboku-to or Saiboku-to did not have any anxiolytic effect. These results confirm that honokiol derived from magnolia is the causal chemical of the anxiolytic effect of Hange-koboku-to and Saiboku-to.

Animals↗

PubMed2000

Circulating hepatocyte growth factor as a marker of thrombus formation in unstable angina pectoris.

A new enzyme-linked immunosorbent assay can detect 10 pg/ml of human hepatocyte growth factor (HGF). Circulating HGF was significantly higher in patients with unstable angina (296+/-184 pg/ml, mean+/-SD, n=36) than in healthy volunteers (201+/-64 pg/ml, n=250, p<0.0001). Individual concentrations exceeded the mean control value +2 SD (329 pg/ml) in 12 of the 36 (33%) patients with unstable angina. The present study indicates that this new, sensitive HGF assay can successfully detect thrombosis in patients with unstable angina.

Adolescent↗

PubMed2000

Antiplatelet and antithrombotic effects of a novel selective phosphodiesterase 3 inhibitor, NSP-513, in mice and rats.

We investigated the effects of NSP-513, (R)-4,5-dihydro-5-methyl-6-[4-(2-propyl-3-oxo-1-cyclohexenyl)amino] phenyl-3(2H)-pyridazinone, on phosphodiesterase (PDE) isozyme activities, in vitro platelet aggregation and in vivo thrombus formation. NSP-513 selectively inhibited human platelet PDE 3 isozyme with an IC50 value of 0.039 microM. In an in vitro human platelet aggregation assay, the IC50 values (microM) of NSP-513 for platelet aggregation induced by collagen, U-46619, arachidonic acid, adenosine diphosphate (ADP), epinephrine and thrombin were 0.31, 0.25, 0.082, 0.66, 0.23 and 0.73, respectively. In a mouse pulmonary thromboembolism model, orally administered NSP-513 showed in vivo antithrombotic effects that were 320 to 470 times more potent than those of cilostazol. In a rat carotid arterial thrombosis model, intraduodenally administered NSP-513 (0.1 mg/kg), cilostazol (30 mg/kg) and aspirin (30 mg/kg) reduced thrombus formation by 75%, 66% and 48%, respectively. However, intravenously administered dipyridamole (10 mg/kg) did not significantly prevent thrombus formation. These results demonstrate that NSP-513 has the potential to prevent not only in vitro platelet aggregation but also in vivo thrombus formation and indicate that the highly selective PDE 3 inhibitory effect of NSP-513 may make this compound useful for assessing the physiological role of PDE 3.

Adenosine Diphosphate↗

PubMed2000

Capillary isotachophoretic analysis of serum lipoproteins using a carrier ampholyte as spacer ion.

We have developed a novel analytical method for serum lipoproteins using a commercially available capillary electrophoresis apparatus, BioFocus 3000 (Bio-Rad Laboratories Co Ltd, USA). The analytical principle is isotachophoresis (ITP), using a carrier ampholyte, BioLyte 7/9, as a spacer ion. The method allows a much higher resolution of lipoproteins than of amino acid mixtures. Serum lipoproteins are normally separated into 13-15 peaks, including some shoulder peaks. The reproducibility of repeated analysis within a day was relatively good with the coefficient of variation within the range 0.9-1.1%. VLDL, LDL and HDL prepared by discontinuous density ultracentrifugation could be further separated by capillary ITP. This high-resolving ability of our method enabled detection of small amounts of abnormal lipoprotein species. For example, small dense LDL, which is thought to be an atherogenic lipoprotein, could be detected within the LDL group peak. Moreover, an abnormal HDL, apolipoprotein E-rich HDL, was also detected by a single analysis. These findings suggest that our capillary ITP method is a useful means for detailed analysis of lipoproteins and thus for clinical diagnosis of hyperlipoproteinaemic subjects.

Ampholyte Mixtures↗

PubMed2000

Dietary beta- and gamma-cyclodextrins stimulation of hepatic metallothionein gene expression in rats.

This study investigated whether hepatic metallothionein gene expression is affected by dietary cyclodextrins. Young male Wistar rats were fed a basal diet or cyclodextrin-supplemented (50 g of cyclodextrin per kg diet) diets for 7 d. Copper content in the liver did not show any significant changes among rats fed the basal, beta- and gamma-cyclodextrin diets. There were no differences in liver or serum zinc among groups. Copper content in serum was markedly decreased in rats fed the gamma-cyclodextrin-supplemented diet. Liver metallothionein mRNA levels were significantly elevated in both beta- and gamma-cyclodextrins-fed rats, but not in alpha-cyclodextrin-fed rats. Thus, the increase in hepatic metallothionein mRNA levels might be due to this mechanism except for the contents of copper and zinc in the liver.

Animals↗

PubMed2000

Binding affinity of the methyl ester of AK-toxin I to membrane fractions from Japanese pear leaves.

The binding site of AK-toxin, a host-specific toxin against Japanese pear, was searched for in the membrane fractions of the pear leaves, using 3H-labeled AK-toxin I methyl ester. Binding activity, which was displaceable by the unlabeled ligand, was observed for microsomal fraction from a toxin-susceptible cultivar, Nijisseiki. However, the binding was also observed for those from toxin-resistant cultivars, Kosui and Hosui. Detection of the specific binding failed for the plasma membrane fraction which was prepared from microsomal fraction of the toxin-susceptible cultivar by aqueous two-phase separation, and the hitherto presumed model of the AK-toxin receptor in the plasma membrane could not be verified.

Binding, Competitive↗

PubMed2000

In vitro and in vivo suppression of osteoclast function by adenovirus vector-induced csk gene.

The proto-oncogene c-src, which encodes a non-receptor-type tyrosine kinase c-Src, has been shown to be essential for osteoclastic bone resorption by the finding that the targeted disruption of the c-src gene induced osteopetrosis in mice. The csk (C-terminal Src family kinase) gene encodes a cytoplasmic protein-tyrosine kinase that specifically phosphorylates the negative regulatory site of c-Src (Tyr-527), thereby inhibiting its kinase activity. To regulate osteoclast function by modulating the kinase activity of c-Src, we constructed an adenovirus vector that carries this gene. The recombinant adenovirus vector carrying csk cDNA induced Csk expression in mouse osteoclast-like cells formed in vitro and clearly reduced c-Src kinase activity in a dose-dependent manner. The expression of Csk caused cytoskeletal disorganization of osteoclast-like cells and strongly suppressed pit-forming activity of the cells in vitro. In addition, the viral vector carrying csk gene dramatically suppressed interleukin-1 alpha-induced bone resorption in vivo. Conversely, kinase-inactive Csk caused an increase in c-Src kinase activity and bone resorbing activity of the cells both in vitro and in vivo, acting as a dominant negative molecule against intrinsic Csk. These findings indicate that the inhibition of c-Src activity by adenovirus vector-mediated csk expression offers an efficient means for inhibiting pathological bone resorption by suppressing osteoclast function.

Adenoviridae↗

PubMed2000

Induction therapy for non-small cell lung cancer with involved mediastinal nodes in multiple stations.

BACKGROUND: Metastasis to multiple stations of mediastinal nodes is associated with a poor prognosis. OBJECTIVE: : We prospectively examined the efficacy of induction therapy plus surgery in patients with non-small cell lung cancer and metastases at multiple stations of mediastinal (N2) lymph nodes. METHODS: Among the 1,085 patients who underwent surgery for primary non-small cell lung carcinoma from 1985 to 1997, those with clinical N2 disease of involved multiple stations, defined as bulky, mediastinal, lymph node metastases on CT scans, received induction therapy, consisting of cisplatin-based chemotherapy and radiation of 40 Gy. RESULTS: Of the 88 eligible patients entered into the study, 51 (58%) had multiple stations of N2 nodes affected preoperatively, as demonstrated by pathologic examination. Neither operative mortality nor fatal, treatment-related complications occurred during hospitalization. Patients who underwent complete resection had significantly longer survivals than did those who underwent incomplete resection (p = 0. 001). Among patients who underwent complete resection, the survival rate for patients with pathologically downstaged disease was significantly higher than that for patients whose disease was not downstaged (p = 0.009). Among patients with multiple stations of pN2 nodes involved who had undergone complete resection, those who received induction therapy for bulky N2 disease had a significantly better prognosis than did those undergoing surgery alone for nonbulky N2 disease (p = 0.03). CONCLUSIONS: Induction therapy prolonged the survival of patients with non-small cell lung cancer and mediastinal nodes involved at multiple stations. Survival was better when complete resection and downstaging of the disease were achieved after induction therapy.

Adult↗

PubMed2000

Autoantibodies against oxidized low-density lipoprotein correlate with Achilles tendon xanthomas.

Although there is increasing evidence for anti-oxidized low-densitiy lipoprotein (LDL) autoantibodies in human sera, their diagnostic utility remains controversial. We examined the difference in autoantibody titers between patients with Achilles tendon xanthoma and control subjects. Fifteen hyperlipidemic patients with Achilles tendon xanthoma (group A+) and 94 hyperlipidemic patients without Achilles tendon xanthoma (group A-) were studied. Quantification of anti-oxidized LDL and anti-native LDL autoantibodies was performed using an ELISA method. To calculate antibody titers, we used the ratio between the spectrophotometric reading of anti-oxidized LDL and anti-native LDL wells. Using oxidized LDL that was purified by gel-permeation chromatography as antigen, immunoglobulin G level differed significantly between groups A+ and A- (p < 0.01). In contrast, using native and oxidized LDL as antigens without chromatographical purification revealed no significant difference between the two groups. Furthermore, immunoglobulin autoantibody titer did not correlate with age, body mass index, total cholesterol, high-density lipoprotein cholesterol, LDL cholesterol, or triglyceride in the entire group of subjects. Thus, immunoglobulin G autoantibody values appear to correlate with Achilles tendon xanthoma.

Achilles Tendon↗

PubMed2000

Possible risk factors of carotid artery atherosclerosis in the Japanese population: a primary prevention study in non-diabetic subjects.

OBJECTIVE: Hyperinsulinemia has been associated with the risk of coronary heart disease, stroke, and renal disease in nondiabetic subjects. However, direct evidence that hyperinsulinemia per se is directly associated with atherosclerosis has been conflicting. The present study was designed to investigate the cross-sectional association of carotid artery atherosclerosis with insulin, independent of well-known cardiovascular risk factors, in nondiabetic subjects. METHODS AND SUBJECTS: Between 1996 and 1997, 1,335 subjects (620 men and 715 women) were recruited from one Japanese community, interviewed, and examined. Clinical measurements in the study included intimal-medial thickness (IMT) of the carotid artery, fasting plasma insulin, serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), hemoglobin type HbA1c, systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI). We divided the subjects of both genders into three subgroups according to age (40-49 years of age; 50-59; and 60-69). RESULTS: Using simple regression analysis, we found that IMT was significantly correlated with at least one of TC, LDL-C, HbA1c, SBP, DBP, and BMI in each subgroup. The results of multivariate analysis showed that IMT was independently correlated with TC, HDL-C, LDL-C, SBP and BMI in males and with TC, TG, HDL-C, LDL-C, HbA1c, SBP, DBP, and BMI in females. Insulin levels showed no correlation with IMT in either males or females. CONCLUSION: Fasting hyperinsulinemia does not appear to be correlated with carotid artery atherosclerosis based on the present cross-sectional results.

Adult↗