Biomedical subjects

T Asano

Publications and source records attributed to T Asano.

At least 253 records · Page 14Linked to original sources

PubMed1998

Localization of a G protein Gi2 in the cilia of rat ependyma, oviduct and trachea.

In previous studies, the localization of a pertussis toxin-sensitive G protein was demonstrated in ependymal cilia, but the identification of the subtype of G protein was inconsistent. To clarify this issue, we studied the localization of Goalpha, Gi1alpha, Gi3alpha and Gi2alpha in the ciliated ependymal cells and in the cilia of some other tissues of rats using specific antibodies. The cilia of the ependymal cells that line the ventricular cavity of the brain were intensely immunoreactive for Gi2alpha, but not for Goalpha, Gi1alpha or Gi3alpha. Immunoblot analysis demonstrated higher levels of Gi2alpha in the ependymal cilia-rich pellet than in the motor area of the parietal cortex. At the ultrastructural level, the immunoreactivity specific for Gi2alpha was found predominantly in the cilia, but rarely in the microvilli or the basal bodies of ependymal cells. In cross-sections, the immunoreactivity specific for Gi2alpha was observed only in cell membranes, in particular, in the inner electron-dense leaflet of the trilaminar structure. In addition to that in the ependymal cilia, such specific localization of Gi2alpha was observed in the motile cilia in other tissues, including the oviduct and trachea. By contrast, the stereocilia in the ductus deferens were not immunopositive for Gi2alpha. These findings suggest that Gi2 might play an important role in the signal transduction in ciliary membrane-associated function(s) of the ependymal cells, oviduct and trachea.

Animals↗

PubMed1998

Anaplastic transformation of a papillary carcinoma of the thyroid in a patient with Graves' disease with varied activity of thyrotropin receptor antibodies.

We describe a 75-year-old man who had had a lump in his neck for about 15 years. At his first visit to our hospital, poorly differentiated papillary carcinoma of the thyroid was diagnosed by means of aspiration cytology; x-rays revealed the presence of lung metastases. He was thyrotoxic with positive thyroid stimulating antibody (TSAb). He was reluctant to undergo surgery. In an early stage of the treatment for Graves' disease, he became hypothyroid with decreased TSAb activity and strongly positive thyroid stimulation blocking antibody (TSBAb), and rapid growth of the thyroid carcinoma with anaplastic transformation was observed. The increase in the size of the transformed thyroid carcinoma was shown to be exponential by ultrasonography. This is a rare case in which anaplastic transformation of the thyroid papillary carcinoma became apparent during treatment of Graves' disease with varied activity of thyrotropin receptor antibodies.

Aged↗

PubMed1998

G protein gamma subunits coimmunoprecipitated with antibodies against alpha subunits: identification of major isoforms in cultured cells by silver stain and immunoblotting with conventional transfer procedure.

The betagamma subunits of G proteins were coimmunoprecipitated with antibodies against various alpha subunits, and analyzed by silver stain and immunoblotting with conventional transfer procedure and membrane-blocking buffer containing 2% BSA. Multiple isoforms of gamma were coimmunoprecipitated with no significant difference in form or ratio among the antibodies against alpha subunits used, suggesting antibodies against any alpha subunit could coimmunoprecipitate all forms of gamma. Therefore, this method was applicable to analyze gamma subunits in various cells, especially to clarify what forms of gamma subunits are major components. The major isoforms were: gamma5 in C6, NG108-15, HeLa, HEK293, and F9 cells; gamma12 in Swiss 3T3 and BRL-3A cells; and gamma3 in PC12 cells. In addition to most gamma subunits identified, unidentified gamma subunits were present in PC12, NG108-15, and BRL-3A cells. Furthermore, the method was applied to examine changes of isoforms of gamma during differentiation of HL-60 cells. Undifferentiated cells mainly contained gamma5, but retinoic acid treatment of cells replaced most gamma5 with gamma2. Thus, this method is useful to determine the major isoforms which seem to be the more important in cells.

Amino Acid Sequence↗

PubMed1998

Cytokine levels in cystic renal masses associated with renal cell carcinoma.

PURPOSE: We compared cytokine levels in fluid from renal cysts with and without renal cell carcinoma. MATERIALS AND METHODS: Fluid was aspirated from 18 renal cysts without (benign) and 21 with renal cell carcinoma (malignant). Serum from patients with renal cell carcinoma and healthy controls was collected and cytokines were measured by enzyme-linked immunosorbent assay. RESULTS: Interleukin-6 (IL-6) and basic fibroblast growth factor concentrations were higher in malignant than benign cysts or serum (p <0.006). Epidermal growth factor levels were significantly higher in malignant cysts and serum than in benign cysts (p <0.01). IL-6 levels in malignant cysts positively correlated with the erythrocyte sedimentation rate (R=0.80) and C-reactive protein (R=0.86), and they were higher in grade 3 than in grade 2 tumors. Basic fibroblast growth factor levels were significantly higher in malignant cysts associated with hypervascular than hypovascular tumors (p=0.029). CONCLUSIONS: Cytokine levels in aspirated fluid may help to identify malignant renal cysts and indicate the characteristics of coexisting tumors.

Adult↗

PubMed1998

Neuroprotective effect of an antioxidant, ebselen, in patients with delayed neurological deficits after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: The effect of ebselen, a seleno-organic compound with antioxidant activity through a glutathione peroxidase-like action, on the outcome of subarachnoid hemorrhage was evaluated in a multicenter placebo-controlled double-blind clinical trial. METHODS: Patients who suffered aneurysmal subarachnoid hemorrhages of Hunt and Kosnik Grades II through IV at admission and were able to start drug treatment within 96 hours of the ictus were enrolled. Early surgery was performed whenever possible. Oral administration of ebselen granules suspended in water (150 mg, twice a day) or placebo was started immediately after admission and continued for 2 weeks. The major end points were the Glasgow Outcome Scale at 2 weeks, 1 month, and 3 months after the start of treatment. The incidence of delayed ischemic neurological deficits clinically diagnosed as resulting from vasospasm and the incidence and extent of low-density areas on postoperative computed tomographic scans were also studied as secondary outcome measures. RESULTS: Intent-to-treat analysis of the 286 patients enrolled in the trial (145 patients administered ebselen and 141 administered placebo) revealed that the incidence of clinically diagnosed delayed ischemic neurological deficits was unaltered. There were 52 (receiving ebselen) and 58 (receiving placebo) patients with delayed deficits; however, a significantly better outcome was observed after ebselen treatment than after placebo (P = 0.005, chi2 test). There was a corresponding decrease in the incidence and extent of low-density areas (P = 0.032, Wilcoxon rank sum test). CONCLUSION: Ebselen reduced brain damage in patients with delayed neurological deficits after subarachnoid hemorrhage and may be a promising neuroprotective agent.

Aged↗

PubMed1998

Expression of MRP and cMOAT in childhood neuroblastomas and malignant liver tumors and its relevance to clinical behavior.

Advanced neuroblastoma and malignant liver tumor are representative childhood cancers for which combined chemotherapy including cisplatin and doxorubicin is routinely performed. The prognosis of patients with tumors which develop multiple drug resistance (MDR) is unfavorable. To elucidate the role of multidrug resistance-associated protein (MRP) and canalicular multispecific organic anion transporter (cMOAT) in the clinical behavior of the tumors, we examined 42 neuroblastomas and 10 malignant liver tumors for the expressions of MRP and cMOAT by quantitative RNA-polymerase chain reaction (PCR). The amplification and expression of N-myc oncogene in the neuroblastomas were also investigated. We found a close association between MRP and N-myc expression in each neuroblastoma sample but no significant relationship between MRP expression and the patients' outcome. The forced expression of N-myc failed to enhance the expression of MRP in N-myc transfected neuroblastoma cell lines. cMOAT was rarely expressed in the neuroblastomas, but was frequently expressed in the malignant liver tumors. The expression of MRP and cMOAT in the childhood liver tumors was more common and higher, especially in advanced cases with a poor outcome, than that observed in normal liver or in 9 hepatocellular carcinomas from adult patients. The enhanced expression of these genes might be characteristic of childhood malignant liver tumors and related to their clinical chemoresistance.

ATP-Binding Cassette Transporters↗

PubMed1998

Incidence of thrombocytopenia in infants born to mothers with idiopathic thrombocytopenic purpura.

Neonatal thrombocytopenia related to maternal idiopathic thrombocytopenic purpura (ITP) is reportedly uncommon but may have severe complications. The present report reviews records of 15 infants born to mothers with ITP during a 10-year period, and the incidence of neonatal thrombocytopenia and the risk of hematological complications is examined. Severe thrombocytopenia (platelets < 50,000/microL) was seen in three infants despite successful therapy with high-dose gamma globulin prior to delivery, which elevated maternal platelet counts. Although the platelet counts of these three infants fell to < 10,000/microL, none had severe complications. Moreover, no infants required treatment such as adrenocorticosteroids, platelets transfusion, or high doses of gamma globulin. No maternal markers predicted the degree of neonatal thrombocytopenia. The risk of complications arising from neonatal thrombocytopenia is low, but careful observation is required for the thrombocytopenic newborn of ITP mothers even when the infant has no bleeding complications at delivery.

Adult↗

PubMed1998

Changes in the duration of the urinary abnormality of purpura nephritis over the past 5 years.

BACKGROUND: The clinical features of patients with anaphylactoid purpura who were admitted to the National Tosei Hospital over the past 15 years were investigated to confirm whether the prognosis of renal involvement had improved. RESULTS: Of the 107 patients admitted to hospital, 43 (40.2%) had urinary abnormalities. The patients with renal involvement were older (P < 0.05) compared to patients without nephritis. Over the last 5 years (1991-95), the duration of urinary abnormalities was significantly shorter than in the period from 1981 to 1990 (P < 0.05). CONCLUSIONS: The duration of the urinary abnormality of nephritis complicating anaphylactoid purpura appears to be changing.

Age of Onset↗

PubMed1998

Simultaneous presentation of malignant lymphoma of the kidney and multiple myeloma of the bone marrow.

We report a case of coexisting renal lymphoma and multiple myeloma. A 77-year-old man was referred to our hospital with a diagnosis of cancer in his right kidney. Biopsies of the renal mass and bone marrow were performed because of hyperproteinemia and biclonal gammopathy. Immunohistochemical staining and Southern blot analysis of the tumor's DNA were diagnostic for renal lymphoma. To our knowledge, this is the first time the coexistence of malignant renal lymphoma and multiple myeloma has been reported.

Aged↗

PubMed1998

A case of gallbladder adenomyomatosis with pancreaticobiliary maljunction and an anomaly of the cystic duct joined the common channel.

A 46-yr-old woman was admitted to our hospital with mild epigastric pain. Ultrasonography and computed tomography revealed an extremely thickened gallbladder wall. Endoscopic retrograde cholangiopancreatography demonstrated that the main pancreatic duct joined the nondilated common bile duct at the outer point of the duodenal wall (P-C type of pancreaticobiliary maljunction), and the cystic duct joined the common channel directly. The intraoperative amylase levels of the bile juices both in the common bile duct and the cystic duct were high. A cholecystectomy was performed. The wall of the gallbladder was markedly thick, yellowish, elastic, and soft. Histologically, Rokitansky-Aschoff sinus proliferation, hypertrophy of smooth muscles, and fibrosis were seen. The diagnosis was a generalized type of adenomyomatosis. The pathogenesis of the adenomyomatosis was believed to result from chronic stimulation as a result of pancreatic juice reflux. The etiology of this unusual type of junction was considered to be the result of the combination of pancreaticobiliary maljunction and an anomaly of lower junction of the cystic duct.

Adenomyoma↗

PubMed1998

Expression of receptors for basic fibroblast growth factor on human periodontal ligament cells.

Basic fibroblast growth factor (FGF-2; bFGF) is a major mitogen for connective tissue cells, and participates in the healing process. It has already been reported that FGF-2 could be applicable to enhance periodontal regeneration. In the present study, we examined FGF receptor (FGFR) expression on human periodontal ligament (PDL) cells. The binding of [125I]-labeled FGF-2 to human PDL cells was studied by radioreceptor assay. The binding of [125I]-FGF-2 to PDL cells reached a plateau after 2.5 h incubation at 4 degrees C and was inhibited by the addition of unlabeled FGF-2 and acidic FGF (FGF-1; aFGF), but not insulin-like growth factor-I, platelet-derived growth factor and transforming growth factor-beta 1. Scatchard analysis revealed the presence of approximately 1.0 x 10(5) FGF-2 binding sites per cell with an apparent Kd of 1.2 x 10(-10) M. Interestingly, the binding of [125I]-FGF-2 on PDL cells reached its maximum at d 6 of the culture and then gradually decreased. Scatchard analysis also demonstrated that the number of FGFRs on a PDL cell was altered during the course of the culture, while the affinity between FGF-2 and its receptor was not. The responsiveness of PDL cells to FGF-2, which was monitored by the inhibitory effect on alkaline phosphatase activity, was reduced in proportion to the decrease in the number of FGFRs on the PDL cells. The present study suggests that PDL cells alter the responsiveness to FGF-2 during the course of the culture by changing the density of its receptor, and that the density of FGFR expression might be a marker of the cytodifferentiation of PDL cells into mineralized tissue forming cells.

Alkaline Phosphatase↗

PubMed1998

Hypotensive mechanism of [Leu13]motilin in dogs in vivo and in vitro.

The effects of [Leu13]motilin were examined in vivo after its intravenous administration into anesthetized dogs and in vitro with isolated preparations of canine mesenteric artery. [Leu13]Motilin (0.1-10 nmol x kg(-1), i.v.) induced both strong and clustered phasic contractions in the gastric antrum and duodenum. At doses of over 1 nmol x kg(-1), [Leu13]motilin also produced transient decreases in arterial blood pressure, left ventricular pressure, maximum rate of rise of left ventricular pressure, and total peripheral resistance, and an increase in aortic blood flow and heart rate. A selective motilin antagonist, GM-109 (Phe-cyclo[Lys-Tyr(3-tBu)-betaAla] trifluoroacetate), completely abolished the gastric antrum and duodenal motor responses induced by [Leu13]motilin. In contrast, hypotension induced by [Leu13]motilin (1 nmol x kg(-1)) was unchanged in the presence of GM-109. In isolated mesenteric artery preparations precontracted with U-46619 (10(-7) M), [Leu13]motilin (10(-8)-10(-5) M) induced an endothelium-dependent relaxation, and this was inhibited by a pretreatment with N(omega)-nitro-L-arginine, a competitive inhibitor of NO synthase (10(-4) M). A high dose (10(-4) M) of GM-109 slightly decreased [Leu13]motilin-induced relaxation, and shifted the concentration-response curve of [Leu13]motilin to the right. However, the pA2 value (4.09) of GM-109 for [Leu13]motilin in the present study was conspicuously lower than that previously demonstrated in the rabbit duodenum (7.37). These results suggest that [Leu13]motilin induces hypotension via the endothelial NO-dependent relaxation mechanism and not through the receptor type that causes upper gastrointestinal contractions.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1998

Does light stimulus at eye opening of the developing rat influence retinal expression of GTP-binding protein (G(0))?

We previously hypothesized that light stimulus at eye opening of rats on postnatal days (P) 13 or 14 has an effect on the expression of GTP-binding proteins (G(0) in the retina) because the concentration of G(0) alpha increased rapidly between P10 and P15. This hypothesis was also supported by the findings that the distribution of G(0) alpha in the retina was almost the same as that of adult rats between P10 and P15. In this study, pregnant rats were kept in a dark room after vaginal plugs were identified; they gave birth to their pups in the dark, and their pups were reared by their mothers in the dark. The postnatal rats were sacrificed at P10, P15, P18, P22, P24, P27, and P30. Their retinas were investigated immunochemically and immunohistochemically, using G(0) alpha antibody, and these results were compared with those of the rat pups reared normally. Only G(0) alpha immunoreactivity in the inner nuclear layer of rats reared in the dark room was weaker than in the controls; the distribution of G(0) alpha in the retina did not change, as compared with pups reared in normal conditions. In addition, in pups reared in the dark, G(0) alpha increased rapidly from P10 to P15. However, the concentration of G(0) alpha in the retina of rat pups reared in the dark was significantly low at P22 (p < 0.01) and P30 (p < 0.05), as compared with pups reared in normal conditions. Although the function of G(0) in the retina may have something to do with the light stimulus after eye opening, it appeared that the expression of G(0) was not influenced by light stimulus at eye opening.

Animals↗

PubMed1998

Ebselen in acute ischemic stroke: a placebo-controlled, double-blind clinical trial. Ebselen Study Group.

BACKGROUND AND PURPOSE: The effect of ebselen, a seleno-organic compound with antioxidant activity through a glutathione peroxidase-like action, on the outcome of acute ischemic stroke was evaluated in a multicenter, placebo-controlled, double-blind clinical trial. METHODS: Patients diagnosed as having acute ischemic stroke who could receive drug treatment within 48 hours of stroke onset were enrolled. Oral administration of ebselen granules suspended in water (150 mg BID) or placebo was started immediately after admission and was continued for 2 weeks. The major end points were the Glasgow Outcome Scale scores at 1 month and 3 months after the start of treatment. The modified Mathew Scale and modified Barthel Index scores at 1 month and 3 months were also studied as secondary outcome measures. RESULTS: Three hundred two patients were enrolled in the trial. Intent-to-treat analysis of 300 patients (151 given ebselen and 149 given placebo) revealed that ebselen treatment achieved a significantly better outcome than placebo at 1 month (P = .023, Wilcoxon rank sum test) but not at 3 months (P = .056, Wilcoxon rank sum test). The improvement was significant in patients who started ebselen within 24 hours of stroke onset but not in those who started treatment after 24 hours. There was a corresponding improvement in the modified Mathew Scale and modified Barthel Index scores. CONCLUSIONS: Early treatment with ebselen improved the outcome of acute ischemic stroke. Ebselen may be a promising neuroprotective agent.

Acute Disease↗

PubMed1998

Vascular alpha1-adrenoceptor subtype selectivity and alpha1-blocker-induced orthostatic hypotension.

Newly developed alpha1-adrenoceptor antagonists including naftopidil are free from the "prazosin-like" side effect of orthostatic hypotension and associated symptoms. We investigated the mechanism for the differential effects of naftopidil and prazosin on the development of postural hypotension, with special attention on their selectivity for the alpha1-adrenoceptor subtype. We observed that head-up tilt caused a similar extent of drop in mean arterial pressure in control, naftopidil (1 mg/kg)- or prazosin (10 microg/kg)-treated rats; however, the tilt-induced postural hypotension was recovered within 2 min in the naftopidil-treated group, but not in the prazosin-treated group. Comparing an inhibitory effect on noradrenaline-induced contraction in the rat aorta and portal vein, we found that naftopidil was sixfold less potent in the portal vein, while prazosin showed similar potency in both tissues. Reverse transcription-polymerase chain reaction analysis showed that the expression of alpha1d-adrenoceptor mRNA predominated in the aorta, while that of alpha1b-adrenoceptor mRNA predominated in the portal vein. Using cloned rat alpha1-adrenoceptor subtypes, we found that naftopidil was selective for the alpha1d-subtype with approximately ninefold higher affinity than at the other subtypes. These results show that the pharmacological character of naftopidil, combined with the differential expression of the alpha1-adrenoceptor subtype in the artery and the vein, may partly explain the differential effect of naftopidil and prazosin on head-up tilt-induced hemodynamic responses.

Adrenergic alpha-Antagonists↗

PubMed1998

Contamination of mouse-adapted influenza virus with Sendai virus.

In our laboratory animal facility, Sendai virus (HVJ) contamination occurred in a negative flow rack used for experimental infection with 4 strains of mouse-adapted influenza virus (Inf.V). Anti-HVJ antibody (Ab) was detected in 35/42 mice in the rack. To specify the strain of Inf.V contaminated with HVJ, experimental infection was performed by using A, B and D strains of Inf.V in each vinyl isolator. Anti-HVJ Ab was detected in all mice infected with A strain at day 28 post-infection. As a result of experimental infection with A strain of Inf.V which was treated with anti-HVJ mouse serum, the virus suspension was determined not to contain HVJ and allowed for experimental use in our facility, Since then, HVJ contamination has not occurred in our facility.

Animals↗

PubMed1998

Altered expression levels and impaired steps in the pathway to phosphatidylinositol 3-kinase activation via insulin receptor substrates 1 and 2 in Zucker fatty rats.

To elucidate the mechanism of obesity-related insulin resistance, we investigated the impaired steps in the processes of phosphatidylinositol (PI) 3-kinase activation through binding with insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) in liver and muscle of Zucker fatty rats. The expressions of IRS-1 and IRS-2 were shown to be downregulated in both liver and muscle in fatty rats (hepatic IRS-1, 83%; hepatic IRS-2, 45%; muscle IRS-1, 60%; muscle IRS-2, 78%), resulting in decreased tyrosine phosphorylation in response to insulin stimulation. Despite the decrease in the tyrosine phosphorylation levels of hepatic IRS-1 and IRS-2 being mild to moderate, associated PI 3-kinase activities were dramatically decreased in fatty rats (IRS-1, 14%; IRS-2, 10%), which may suggest alteration in the sites of phosphorylated tyrosine residues of hepatic IRS-1 and IRS-2. In addition, we demonstrated that the expressions of p85alpha and p55alpha regulatory subunits of PI 3-kinase were reduced (p85alpha, 67%; p55alpha, 54%), and that the p50alpha regulatory subunit was markedly upregulated (176%) in the livers of fatty rats without apparent alterations in expressions of the catalytic subunits p110alpha and p110beta. These alterations may reflect the obesity-related insulin resistance commonly observed in human NIDDM.

Albumins↗

PubMed1998

Induction of antitumor effect on human esophageal carcinoma cells by the retroviral expression of granulocyte macrophage-colony stimulating factor gene.

We have examined antitumor effect of human esophageal carcinoma cells (T.Tn) which were retrovirally transduced to express mouse granulocyte macrophage-colony stimulating factor (mGM-CSF) gene. Nude mice inoculated with T.Tn cells secreting mGM-CSF developed small tumors but the tumors regressed spontaneously, although the proliferation in vitro of transduced cells was not different from that of wild-type cells. In contrast, the tumor of T.Tn cells transduced with human GM-CSF grew as that of wild-type cells, since murine GM-CSF receptors do not bind to human GM-CSF. Histological examination of the regressing tumor of mGM-CSF-producing T.Tn cells revealed predominant infiltration of inflammatory cells including macrophages. In addition, local injection of mGM-CSF-producing T.Tn cells into the established wild-type tumors significantly induced the retardation of subsequent wild-type tumor growth, suggesting that T-cell independent local response plays a crucial role in destroying tumor cells.

Animals↗