Search PubMed⌕ Search

Biomedical subjects

A Sato

Publications and source records attributed to A Sato.

At least 487 records · Page 27Linked to original sources
PubMed1995

Diagnostic usefulness of postexercise systolic blood pressure response for detection of coronary artery disease in patients with electrocardiographic left ventricular hypertrophy.

Patients with left ventricular (LV) hypertrophy often have a positive result on exercise testing despite a normal coronary arteriogram. This indicates that exercise-induced ST depression is not always an accurate indicator of the presence of coronary artery disease (CAD) in such patients. We evaluated the usefulness of the postexercise systolic blood pressure (BP) response for detection of CAD in 51 patients with both electrocardiographic evidence of LV hypertrophy and positive ST depression on treadmill exercise testing. Coronary cineangiograms showed normal coronary arteries in 23 patients (45%) (group 1) and significant CAD in 28 patients (55%) (group 2). The systolic BP ratio (systolic BP at 3 minutes of recovery divided by systolic BP at peak exercise) was significantly higher in group 2 than in group 1 (1.01 +/- 0.19 vs 0.80 +/- 0.09; p < 0.001). Analysis of the relative cumulative frequency revealed that a systolic BP ratio of 0.86 was the cutoff point for distinguishing a patient with CAD from one with normal coronary arteries. The sensitivity, specificity, and accuracy of a systolic BP ratio > or = 0.86 for detection of CAD in patients with LV hypertrophy were 79%, 83%, and 82%, respectively. Our results suggest that the use of an abnormal BP ratio, in combination with ST depression, improves the accuracy of treadmill exercise testing for detecting CAD in patients with electrocardiographic evidence of LV hypertrophy.

Adult↗
PubMed1995

c-Src phosphorylates epidermal growth factor receptor on tyrosine 845.

In the previous study [Sato et al. (1995) Biochem. Biophys. Res. Commun. 210, 844-851], we found that c-Src was associated with epidermal growth factor (EGF) receptor and activated upon EGF treatment in A431 cells. In the present study, we investigated the phosphorylation of EGF receptor by c-Src in the c-Src-EGF receptor complex. We have focused our attention to tyrosine residue 845 (Y845) of EGF receptor as a candidate for the phosphorylation site. A synthetic peptide containing Y845, named Y845 peptide, which corresponds to residue 837 to 856 of EGF receptor, was found to be phosphorylated by c-Src and used to provide the standard phosphopeptide. In addition to the autophosphorylated peptide of 25 kDa, a phosphopeptide of 7 kDa was detected in the cyanogen bromide-digested fragments of the c-Src-associated EGF receptor phosphorylated in vitro in an EGF-dependent manner. In phosphopeptide mapping, tryptic digest of the 7-kDa phosphopeptide was shown to co-migrate with that of the phosphorylated Y845 peptide. The 7-kDa phosphopeptide was found to be phosphorylated exclusively on tyrosine. These results suggest that c-Src can phosphorylate EGF receptor on Y845 in an EGF-dependent manner. Furthermore, we confirmed that the same site of the c-Src-associated EGF receptor was phosphorylated in EGF-treated A431 cells.

Amino Acid Sequence↗
PubMed1995

Leukoencephalopathy in childhood hematopoietic neoplasm caused by moderate-dose methotrexate and prophylactic cranial radiotherapy--an MR analysis.

PURPOSE: The main purpose of this study was to determine influential factors related to minor leukoencephalopathy (LEP) caused by moderate-dose methotrexate (MTX) and prophylactic cranial radiotherapy (CRT) in childhood hematopoietic malignancies. We also compared the incidence of LEP following this treatment to that reported in the literature following treatment with high-dose MTX alone. METHODS AND MATERIALS: Thirty-eight pediatric patients of hematopoietic malignancies (37 acute lymphoblastic leukemias, 1 non-Hodgkin lymphoma) who were given CRT (18-24 Gy) as well as prophylactic intrathecal and per os MTX were studied for leukoencephalopathy by magnetic resonance (MR) imaging. All the patients were free from grave neuropsychiatric disturbances. The data were examined to elucidate the influential ones of five factors (patients' age, doses of intrathecal and per os MTX, dose of CRT, interval between treatment, and MR study) to develop LEP using multiple regression analysis. To compare the effect of moderate-dose MTX and prophylactic CRT on LEP to that of high-dose MTX alone, we conducted literature review. RESULTS: Seven out of 38 patients (18%) developed LEP. From multiple regression analysis and partial correlation coefficients, the age and CRT dose seemed influential in the subsequent development of LEP. The incidence of LEP following treatment with moderate-dose MTX and prophylactic CRT appears to be less than that reported in the literature following treatment with intravenous high-dose MTX. However, even moderate-dose MTX in combination with CRT can result in a significant incidence of MR-detectable LEP, particularly in children 6 years of age or younger receiving 24 Gy. CONCLUSION: Leukoencephalopathy was caused by moderate-dose MTX and prophylactic CRT in pediatric patients, probably less frequently than by high-dose MTX treatment alone. The influential factors were patient's age and CRT dose.

Adolescent↗
PubMed1995

Superoxide generation by alveolar macrophages from aged rats: improvement by in vitro treatment with IFN-gamma.

Alveolar macrophages (AM) from aged rats show an impaired oxidative response, but it is unclear whether or not this is due to the inability of these cells to be activated. To elucidate this, we investigated the capacity of AM from young (16-week-old) and aged (100-week-old) rats to become primed with recombinant rat interferon-gamma (IFN-gamma) for increased phorbol myristate acetate (PMA)-elicited O2- production, utilizing an MCLA-dependent chemiluminescent assay. We also compared concanavalin A- or Bacillus Calmette Guerin (BCG)-induced IFN-gamma production by the spleen cells of young and aged animals. The data indicated that AM freshly harvested from non-sensitized aged rats produced less O2- than those from young animals. A similar result was obtained in BCG-sensitized rats. However, AM from aged rats were primed with in vitro treatment with IFN-gamma for increased rate of O2- production to an equivalent level of that by AM from young animals. In addition, the ability of spleen cells to produce IFN-gamma was well maintained in aged rats. These results suggest that AM function is suppressed in the lungs of aged animals. Our observation that the decreased AM function in aged rats can be reversed is important because it suggests that appropriate treatment may reduce the incidence and mortality of respiratory infections in the elderly.

Aging↗
PubMed1995

Site-specific association of c-Src with epidermal growth factor receptor in A431 cells.

We have examined the interaction between c-Src and epidermal growth factor (EGF) receptor in A431 cells. c-Src was found exclusively in the Triton X-100-solubilized particulate fraction and activated up to 3-fold within 1 min after EGF treatment of the cells. Association between c-Src and EGF receptor was detected by immunoprecipitation of c-Src followed by immunoblotting with anti-EGF receptor antibody. The c-Src-EGF receptor complex was found in both EGF-treated and untreated cells, but an augmented complex formation was observed in EGF-treated cells. We have isolated the complex by DEAE-cellulose column chromatography and found that a site-specific anti-c-Src antibody, which was raised against a synthetic peptide corresponding to residues 413 to 431 of human c-Src, did not recognize the c-Src protein in the complex, while other c-Src-specific antibodies tested did. Incubation of the complex with this synthetic peptide resulted in a partial dissociation of the complex. These results suggest that the specific region of c-Src is involved in the association with EGF receptor.

Amino Acid Sequence↗
PubMed1995

Inhibition of nitric oxide synthesis potentiates the responsiveness of carotid chemoreceptors to systemic hypoxia in the rat.

Carotid sinus nerve afferent activity was recorded in the peripheral end of the cut carotid sinus nerves in rats anesthetized with urethane, paralyzed and artificially ventilated with pure oxygen in order to abolish any resting chemoreceptor activity. Hypoxic stimuli were applied by switching pure oxygen to a nitrogen/oxygen gas mixture in the inspiratory line, reducing end-tidal oxygen concentrations to 10% FETO2, 8% FETO2 and 6% FETO2 respectively. Each stimulus was applied for 60 s and ventilation was switched again to pure oxygen. Increases in the carotid sinus nerve activities were due to chemo- and not to baroreceptor stimulation as arterial blood pressure decreased during hypoxia. After administration of nitric oxide synthase blocker L-NG-nitroarginine methyl ester, 30 mg/kg weight i.v., chemoreceptor excitatory response to all hypoxic stimuli increased significantly. Subsequent administration of L-arginine, 300 mg/kg weight i.v., restored chemoreceptor response to hypoxia to initial magnitude. It is concluded that NO is generated in the carotid body and attenuates chemoreceptor responsiveness in rats in vivo, as reported on isolated carotid bodies in cats in vitro.

Afferent Pathways↗
PubMed1995

Increased procoagulant and antifibrinolytic activities in the lungs with idiopathic pulmonary fibrosis.

To elucidate the pathophysiology of idiopathic pulmonary fibrosis (IPF), we examined procoagulant (tissue factor:TF), fibrinolytic (tissue type plasminogen activator:t-PA and urokinase type plasminogen activator:u-PA) and antifibrinolytic (plasminogen activator inhibitor-1:PAI-1 and PAI-2) activities in bronchoalveolar lavage (BAL) supernatant fluids and BAL cell lysates obtained from IPF patients. The results indicated that TF levels in BAL supernatant fluids from IPF patients were higher than those of normal subjects, especially in patients with progressive disease, suggesting that TF levels in the lung correlate with disease activity. PAI-1 levels in BAL supernatant fluids were significantly higher in IPF patients than in normal subjects (1.7 +/- 4.1 vs 0 ng/mg protein). PAI-2 levels in BAL cell lysates were also significantly higher in IPF patients than those in normal subjects (14.4 +/- 12.2 vs 3.0 +/- 3.0 ng/mg protein). However, u-PA levels in both BAL supernatant fluids and BAL cell lysates did not differ between the two groups. These observations suggest that u-PA inhibition exceeded u-PA activity in alveolar lining fluid resulting in an antifibrinolytic condition. Immunohistochemical analysis showed that TF was intensely stained in cuboidal epithelial cells and PAIs were positively stained in alveolar macrophages (AMs) and cuboidal epithelial cells, suggesting that cuboidal epithelial cells as well as AMs contribute to the increased procoagulant and antifibrinolytic activities in the lungs of IPF patients.

Aged↗
PubMed1995

The oxytocin antagonist 1-deamino-2-D-Tyr-(Oet)-4-Thr-8-Orn-oxytocin reverses the increase in the withdrawal response latency to thermal, but not mechanical nociceptive stimuli following oxytocin administration or massage-like stroking in rats.

In this study the effect of exogenous oxytocin and of massage-like stroking on the withdrawal latency responses to heat and mechanical nociceptive stimulation were investigated in rats. A hot-plate test and the Randall-Selitto test were used to assess the withdrawal responses. Exogenous oxytocin (0.1-1 mg/kg) and stroking (a low frequency mechanical stimulation) significantly increased the withdrawal latencies in response to mechanical and to thermal nociceptive stimuli. The effect of oxytocin and of stroking in the hot-plate test was reversed by the oxytocin antagonist (1-deamino-2-D-Tyr-(Oet)-4-Thr-8-Orn-oxytocin) directed against the uterine receptor. In contrast, the antagonist did not affect the prolonged response latency in the mechanical nociceptive stimulation test following either exogenous oxytocin or stroking. These results support the view that (1) oxytocin administration affects directly or indirectly nociceptive related behaviour in response to heat stimulation, and (2) massage-like stroking may have an anti-nociceptive effect via activation of oxytocinergic mechanisms. Since the response to mechanical stimulation was not blocked by the antagonist the mechanisms mediating the withdrawal latency to heat and mechanical stimulation could be different.

Animals↗
PubMed1995

The structure of chicken liver xanthine dehydrogenase. cDNA cloning and the domain structure.

The amino acid sequence of chicken liver xanthine dehydrogenase (EC 1.1.1.204) was determined by cDNA cloning and partial amino acid sequencing of the purified enzyme. The enzyme consisted of 1358 amino acids with calculated molecular mass of 149,633 Da. In order to compare the structure of the chicken and rat enzymes, limited proteolysis was performed with the purified chicken liver xanthine dehydrogenase. When the enzyme was digested with subtilisin, it was not converted from the NAD-dependent dehydrogenase type to the O2-dependent oxidase type, in contrast with the mammalian enzyme. However, the enzyme was cleaved mainly into three fragments in a manner similar to that for the rat enzyme at pH 8.2 (20, 37, and 84 kDa) and retaining a full complement of redox centers. The cleavage sites were identified by determination of amino-terminal sequences of the produced fragments. It was concluded that the 20-kDa fragment was amino-terminal, the 84-kDa fragment carboxyl-terminal, and the 37-kDa fragment an intermediate portion in the enzyme protein. On the other hand, when the enzyme was digested with the same protease at pH 10.5, the sample contained only the 20- and 84-kDa portions and lacked the 37-kDa portion. The resultant sample possessed xanthine dichlorophenol indophenol reductase activity, indicating that the molybdenum center remained intact. The absorption spectrum showed the sample was very similar to deflavo-enzyme. From these results and sequence analyses, the domain structure of the enzyme is discussed.

Amino Acid Sequence↗
PubMed1995

Quantitation of anti-hepatitic C virus antibodies in interferon-treated patients by S29-1/S4 ELISA.

In 23 patients with chronic hepatitis C who have undergone interferon (IFN) treatment, quantitation of anti-hepatitis C virus IgG antibodies by a second-generation assay S29-1/S4 ELISA [Sato et al. (1993): Microbiology and Immunology 37: 295-304]. (anti-S29-1/S4) was compared with that of anti-HCV core IgG antibodies (C22-3, anticore) and the presence of viral RNA confirmed by the reverse transcription-nested polymerase chain reaction (RT-nested PCR). In 12 complete responders with loss of HCV-RNA and normal alanine aminotransferase (ALT) levels at 6 months after therapy, IgG antibodies quantified by a second-generation assay have decreased significantly at the end of treatment (P < 0.05). Further significant reduction of anti-S29-1/S4 titers was observed at 6 months after therapy (P < 0.01) as well as anti-core antibodies (P < 0.01). On the other hand, in 11 non-responders with persistent or intermittent viremia at 6 months after therapy, no significant change in the level of anti-S29-1/S4 titers was observed, whereas anti-core titers have decreased at the end of therapy (P < 0.01). In contrast, both levels of anti-S29-1/S4 and anti-core have increased at 6 months after treatment (P < 0.05). It is concluded that, although it appears difficult to monitor the effect of virus clearance during IFN therapy, changes in anti-S29-1/S4 titers after IFN treatment correlate with virus clearance and with anti-core titers.

Chronic Disease↗
PubMed1995

m-xylene toxicokinetics in phenobarbital-treated rats: comparison among inhalation exposure, oral administration, and intraperitoneal administration.

Rats, pretreated with phenobarbital (PB) for 3 days (80 mg/kg/day), were challenged with m-xylene orally or intraperitoneally at a small (0.01 ml/kg or 0.081 mmol/kg) or a large (0.10 ml/kg or 0.814 mmol/kg) dose, or by 6-hr inhalation exposure at a low (40 ppm) or a high (400 ppm) concentration. The concentrations of m-xylene and its major metabolite, m-methyl hippuric acid (m-MHA), were measured over time in the blood and urine, respectively. PB treatment, which increased the hepatic metabolism of m-xylene in vitro about sixfold, had a significant effect on the metabolism of inhaled m-xylene (decreased blood m-xylene concentration together with increased urinary excretion of m-MHA) only at a high exposure concentration (400 ppm). On the other hand, the enzyme induction had a significant effect on the metabolism of orally administered m-xylene either at a small (0.081 mmol/kg) or a large (0.814 mmol/kg) dose, due to the first-pass metabolism that plays a great role in this route. When m-xylene was administered intraperitoneally, the effect of enzyme induction was shown only at the large dose, a finding which suggests that intraperitoneal administration is more similar to inhalation exposure than oral administration. However, in agreement with oral administration but in contrast to inhalation exposure, PB treatment increased the urinary excretion of m-MHA only shortly after intraperitoneal administration of m-xylene, with no significant increase occurring in the total amount of m-MHA excreted in the urine, despite the great difference in the blood m-xylene concentration between PB-treated and control rats.

Administration, Inhalation↗
PubMed1995

Dose- and route-dependent alteration of metabolism and toxicity of chloroform in fed and fasting rats.

Effects of overnight food deprivation on the metabolism and toxicity of chloroform (CHCl3) administered to rats per os (po), intraperitoneally (ip), or by inhalation (inh) at different doses were investigated. Rats that had been either deprived of food overnight or normally fed were challenged with CHCl3 either po (0, 100, 200, or 400 mg/kg), ip (0, 100, 200, or 400 mg/kg), or inh (0, 50, 100, or 500 ppm for 6 hr). Overnight fasting increased CHCl3 metabolism in vitro about threefold with a decrease of liver glutathione content to 67%. The fasting caused route- and dose-dependent alteration in the metabolism and toxicity of CHCl3. The area-under-the-curve (AUC) of blood CHCl3 concentration was invariably smaller following po than ip administration, and CHCl3 administered po caused more severe hepatic damage than did the same amount of CHCl3 administered ip. With po administration, the AUC (toxicity) of CHCl3 in fasting rats was significantly smaller (higher) than that of fed rats at a dose as small as 100 mg/kg, whereas, with ip administration at such a small dose, fasting caused no significant alteration in the AUC (toxicity). When rats were exposed by inhalation to CHCl3 vapor, food deprivation had little or no effect on either the blood concentration or the toxicity until the exposure concentration was raised to 500 ppm. The present study indicates that po administration is different from both ip and inh administration with regard to the effect of enzyme induction on the toxicokinetics of CHCl3, mainly due to the first-pass metabolism unique to po administration.

Administration, Inhalation↗
PubMed1995

Modulation of somatocardiac sympathetic reflexes mediated by opioid receptors at the spinal and brainstem level.

Modulation of somatosympathetic reflexes at the spinal cord and the brainstem was studied by administering opioid receptor agonists into the intrathecal space of the lumbar spinal cord and into the subarachnoid space of the cisterna magna in rats anesthetized with alpha-chloralose and urethane. Somatocardiac sympathetic A- and C-reflexes were elicited by electrical stimulation of myelinated (A) and unmyelinated (C) afferent fibers of the tibial nerve, respectively. Intrathecal administration of the mu-opioid receptor agonist DAMGO selectively depressed the C-reflex in a dose-dependent manner (minimum effective dose 10 ng), whereas the intrathecal injection of the delta-opioid receptor agonist DPDPE and the kappa-opioid receptor agonist U-50,488H only at doses of 10 micrograms and 100 micrograms, respectively, led to a significant depression of the C-reflex. Injection of DAMGO into the cisterna magna enhanced both A- and C-reflexes in a dose-dependent manner (minimum effective dose 1 ng). The administration of neither DPDPE nor U-50,488H into the cisterna magna affected A- or C-reflexes. It is concluded that the activation of mu-opioid receptors is mainly or exclusively responsible for suppressing somatosympathetic C-reflexes at the spinal cord and for enhancing them at the brainstem.

Adrenergic Fibers↗
PubMed1995

Characteristic antitumor activity of cytarabine ocfosfate against human colorectal adenocarcinoma xenografts in nude mice.

The antitumor activity of cytarabine ocfosfate (SPAC) was tested against human colorectal, gastric and lung adenocarcinoma xenografts in nude mice in comparison with the activities of various antitumor drugs used clinically. SPAC showed higher therapeutic efficacy against human colorectal adenocarcinoma xenografts than against human gastric and lung adenocarcinoma xenografts. SPAC was effective against three of four human colorectal adenocarcinoma xenografts, with efficacy higher than that of 1-beta-D-arabinofuranosylcytosine, fluorouracil, cisplatin, doxorubicin, pirarubicin and vindesine sulfate, but lower than that of mitomycin C and cyclophosphamide. These results indicate that SPAC may be useful for induction and/or postoperative chemotherapy against colorectal adenocarcinomas.

Adenocarcinoma↗
PubMed1995

Induction of MHC class II antigens on rat bronchial epithelial cells by interferon-gamma and its effect on antigen presentation.

Recent studies have found aberrant expression of class II antigens by bronchial epithelial cells (BECs), suggesting that these cells may also be involved in airway mucosal immunity. However, the regulation of class II antigen expression on BECs by cytokines and the functional capacity of such cells bearing class II molecules remain unknown. We investigated the effect of IFN-gamma on class II antigen expression by cultured rat BECs, as well as the ability of these cells to present intact protein antigens to specifically sensitized T cells. Although primary BECs did not express class II antigens, IFN-gamma readily induced their expression in a dose-dependent manner. More than 85% of the BECs treated with 1000 U/ml of IFN-gamma were positive for class II antigens. In addition, when IFN-treated BECs bearing class II molecules were pulsed with ovalbumin (OVA), they significantly stimulated the proliferation of OVA-sensitized T cells, whereas cells that were not treated with IFN-gamma but were pulsed with OVA did not do so. Our findings indicate that BECs bearing class II molecules are capable of presenting OVA to OVA-sensitized T cells. These results suggest that various pathological conditions causing the local production of IFN-gamma may increase class II antigen expression on BECs, which in turn may modulate the airway mucosal immune response by the presentation of antigens to T cells.

Animals↗
PubMed1995

Hyperuricemia in patients with hyperthyroidism due to Graves' disease.

The effects of hyperthyroidism on uric acid metabolism were investigated. First, the serum uric acid level was measured in 92 patients with hyperthyroidism due to Graves' disease, eight patients with subacute thyroiditis, six patients with hypothyroidism, and 70 sex- and age-matched controls. Second, the correlation between serum thyroxine (T4) and serum uric acid was obtained in hyperthyroid Graves' disease patients before and during antithyroid drug therapy. Finally, uric acid clearance (CUA) was determined in untreated patients with hyperthyroidism due to Graves' disease. Serum uric acid was significantly elevated in patients with hyperthyroidism, and the elevation correlated well with serum T4 before treatment as a group and during treatment in each patient. A significant elevation of serum uric acid was not present in patients with a transient mild thyrotoxicosis due to subacute thyroiditis. Serum uric acid was significantly decreased in patients with hypothyroidism. Renal excretion of uric acid clearly increased in hyperthyroid patients, and CUA also increased. The increase in CUA corresponded to the increase in renal plasma flow (RPF), which was measured by p-aminohippuric acid clearance. The fractional excretion of uric acid as determined by CUA/glomerular filtration rate (GFR) was similar and within the normal range in hyperthyroid patients and normal controls. A significant inverse correlation between CUA and serum uric acid concentration was present in hyperthyroid patients as in normal controls, indicating that the renal handling of uric acid in the tubule affected uric acid excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

A case of uterine cervical adenoid cystic carcinoma: immunohistochemical study for basement membrane material.

BACKGROUND: Adenoid cystic carcinoma is a rare neoplasm of the cervix. Only two reports of immunohistochemical studies for basement membrane material in adenoid cystic carcinoma of the cervix have been reported. CASE: An 80-year-old Japanese woman complained of atypical vaginal bleeding and underwent removal of a cervical polyp; the biopsy specimen revealed a solid variant of adenoid cystic carcinoma. The tumor was composed of nests and nodules of small carcinoma cells, and there were few characteristic cribriform patterns. Immunohistochemical findings for type IV collagen and laminin revealed intercellular cylinders composed of basement membrane material in the solid area without a cribriform pattern. CONCLUSION: The immunohistochemical finding of intercellular cylinders that reacted for type IV collagen was useful for the diagnosis of a solid variant of adenoid cystic carcinoma.

Aged↗