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Biomedical subjects

F Sato

Publications and source records attributed to F Sato.

At least 181 records · Page 10Linked to original sources
PubMed1996

Detection of transcripts of Marek's disease virus serotype 1 iCP4 homologue (MDV1 ICP4) by in situ hybridization.

Homologues of herpes simplex virus ICP4 are important genes for the activation of many herpesviruses. We detected transcripts of the Marek's disease virus serotype 1 homologue of ICP4 (MDV1 ICP4) by in situ hybridization (ISH). Using a digoxigenin-labeled-RNA (DIG-RNA) probe, MDV1 ICP4 transcripts were detected in c.a. 90% of MDV1-infected chicken embryo fibroblasts (CEF) cells when cytopathic effect was reached to 90% of the CEF cells and in 0.35% of MDCC-MSB-1 (MSB-1) cells, at a frequency similar to that for MD antigen-positive MSB-1 cells. Using the same in situ procedure, we detected abundant MDV1 ICP4 transcripts in the feather follicle epithelium (FFE) and some lymphoid cells in the liver, kidney and peripheral nerve of infected chickens. The subcellular localization of the transcripts appeared to vary: MSB-1 cells had them in the nucleus, infected CEF cells and FFE had them in the nucleus and cytoplasm, and lymphoid cells contained them in the cytoplasm. The MDV1 ICP4 transcripts were also detected in the FFE and lymphoid cells in the liver by reverse-transcriptase polymerase chain reaction (RT-PCR). Detection of MDV1 ICP4 transcripts by RT-PCR indicated the existance of MDV1 ICP4 transcripts-positive cells in these tissues. And these data suggested that DIG-RNA-ISH can detect MDV transcripts on paraffin sections and provide information about their subcellular localization.

Animals↗
PubMed1996

Lipid peroxide levels and superoxide-scavenging abilities of Sera obtained from hotbred (Thoroughbred) horses.

Hotbred (Thoroughbred) horses were grouped into three classes according to the levels of constant physical exercise (foals, 6 months old; racing horses, 5 years old; horses for breeding, 6-10 years old), and lipid peroxide levels in their sera were measured as thiobarbituric acid-reactive substances. No significant differences were observed among them. The superoxide-scavenging abilities of sera were measured next; to examine the antioxidative properties of hotbreds, and were found to be highest in the racing horses. The higher scavenging ability of the racing horses might contribute to keep their lipid peroxide levels as low as those of the other two groups. HPLC analysis of substances in sera suggested that the presence of albumin-bound bilirubin was one of the reasons for the high superoxide-scavenging ability of sera of the racing horses. When the hotbreds were compared with coldbred (crossbred) horses, the lipid peroxide levels of hotbreds was higher (7.0 +/- 1.2 nmol/ml) than that of coldbreds (2.6 +/- 0.7 nmol/ml). Comparison of the superoxide-scavenging abilities of sera between hotbreds and coldbreds showed that the hotbreds possessed higher scavenging ability than the coldbreds. These results indicated that the lipid peroxide level in sera of hotbreds was higher than that of coldbreds regardless of the higher superoxide-scavenging abilities of sera.

Animals↗
PubMed1996

[Carotid screening with duplex scanning before coronary artery bypass].

Seventy-one patients undergoing scheduled coronary artery bypass were preoperatively evaluated for the presence of carotid stenosis by duplex scanning. Prevalence of a moderate degree of stenosis (peak systolic flow velocity of internal carotid artery > 130 cm/sec) or a high degree of stenosis (peak systolic flow velocity > 250 or < 25 cm/sec) was 12.7% (nine patients). Predictive risk factors for carotid stenosis were diabetes mellitus and history of stroke. Compared with carotid angiogram, hemodynamically critical stenosis greater than 90% was found in three patients, severe stenosis (75-90%) in four, moderate stenosis (50-75%) in two. Bilateral carotid occlusion, complete occlusion of an internal carotid artery with contralateral 99% stenosis, was found in one patient. In the critical stenosis group (n = 3), simultaneous carotid endarterectomy and coronary artery bypass were performed in two and coronary artery bypass alone in one patient with unilateral complete occlusion of the internal carotid artery. There was neither operative death nor postoperative stroke in this series of patients. In conclusion, carotid screening with a duplex scan is very helpful to evaluate the presence of carotid occlusive disease in coronary artery bypass candidates. When significant carotid stenosis is detected, further examination should be done to clarify the carotid hemodynamics and brain protection during the operation should be employed.

Adult↗
PubMed1995

The suppression of age-related accumulation of lipid peroxides in rat brain by administration of Rooibos tea (Aspalathus linearis).

The protective effects of Rooibos tea (RT), Aspalathus linearis, against damage to the central nervous system (CNS) accompanying aging were examined by both the thiobarbituric acid reaction (TBA) and magnetic resonance imaging (MRI) methods in brains of chronically RT-treated rats. Ad libitum administration of RT was begun with 3-month-old Wistar female rats and continued for 21 months. The contents of TBA reactive substances (TBARS) in the frontal cortex, occipital cortex, hippocampus and cerebellum in 24-month-old rats after administration with water were significantly higher than those in young rats (5 weeks old). However, no significant increase of TBARS was observed in RT-administered aged rats. When MR images of the brains of 24-month-old rats with and without RT as well as 5-week-old rats were taken, a decrease of the signal intensity was observed in the cerebral cortex, hippocampus and cerebellum in MR images of aged rats without RT, whereas little change of the signal intensity was observed in MR images of the same regions of 24-month-old rats treated with RT, whose images were similar to those of young rats. These observations suggested that (1) the age-related accumulation of lipid peroxides in the brain was closely related to the morphological changes observed by MRI, and (2) chronic RT-administration prevented age-related accumulation of lipid peroxides in several regions of rat brain.

Administration, Oral↗
PubMed1995

Synthesis and secretion of tobacco neutral PR-5 protein by transgenic tobacco and yeast.

Tobacco neutral osmotin-like protein was expressed in both homologous and heterologous expression systems. Osmotin-like protein was retained in tobacco cells when expressed as the prepro-form, whereas deletion of the carboxyl-terminal propeptide of 22 amino acids induced its secretion into the extracellular fluid. Without the amino-terminal signal peptide, there was no accumulation of osmotin-like protein. When the construct with both the amino- and carboxyl-terminal peptides was introduced to methylotrophic yeast, divergent osmotin-like protein forms were found in the cell and medium. Results suggest that the amino-terminal signal of the osmotin-like protein is essential for the transport of protein to the endoplasmic reticulum both in tobacco and yeasts but that the carboxyl-terminal propeptide signal is effective only for intracellular retention in tobacco.

Amino Acid Sequence↗
PubMed1995

(Piperidinylalkoxy)chromones: novel antihistamines with additional antagonistic activity against leukotriene D4.

A series of novel chromone derivatives, in which the chromone moiety is connected to a (diphenylmethylene)-, (diphenylmethyl)-, or (diphenylmethoxy)piperidine via an alkyloxy spacer, were synthesized as antiallergic and antiasthmatic agents. In addition to their potent antihistaminic activity, the compounds also inhibit contraction in guinea pig ileum induced by leukotriene D4. When analyzed by radioligand binding assays in guinea pig lung membranes, one of the compounds, 7-[[3-[4-(diphenylmethylene)piperidin-1- yl]propyl]oxy]-2-(5-tetrazolyl)-4-oxo-4H-1-benzopyran, showed dissociation constants (KD) of 5.62 nM and 2.34 microM for H1- and LTD4-receptors, respectively. In vivo at the dose of 10 mg/kg, the compound inhibited the histamine- and LTD4-induced increase of vascular permeability in guinea pigs by 95 and 30%, respectively. The inhibition of LTD4-induced increase in vascular permeability by the compound was increased to 56% when a dose of 50 mg/kg was employed. Similar to terfenadine, the compound does not readily occupy the brain H1-receptors when given intraperitoneally to mice, implying no sedating side effects.

Animals↗
PubMed1995

In vitro insulinotropic action of a new non-sulfonylurea hypoglycemic agent, calcium (2s)-2-benzyl-3-(cis-hexahydro-2-isoindolinyl-carbonyl) propionate dihydrate (KAD-1229), in rat pancreatic B-cells.

We examined the in vitro insulinotropic action of a novel non-sulfonylurea compound, calcium (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinyl-carbonyl) propionate dihydrate (KAD-1229), which is a succinate derivative, using rat pancreatic islets and perfused pancreas. The sodium salt of KAD-1229 free acid (KAD-1229-Na) stimulated insulin secretion from isolated rat islets and perfused rat pancreas in a concentration-dependent manner at 0.1 to 10 microM. It produced a predominant first phase and a less prominent second phase response in the presence of 5.55 mM glucose. An ATP-sensitive K+ (K+ATP) channel activator, diazoxide, eliminated the insulinotropic effect of KAD-1229-Na. Glucose primed the B-cell in the perfused pancreas, but KAD-1229-Na did not. When the insulinotropic effects of 16.7 mM glucose on isolated rat islets were inhibited submaximally by 1 microM norepinephrine, the addition of 1 microM KAD-1229-Na reversed this inhibition. All of these insulinotropic effects of KAD-1229-Na were qualitatively indistinguishable from those of sulfonylurea compounds. We conclude that KAD-1229-Na acts on K+ATP channels of pancreatic B-cells despite its non-sulfonylurea structure.

Animals↗
PubMed1995

1,1,1,2-Tetrafluoroethane: repeat exposure inhalation toxicity in the rat, developmental toxicity in the rabbit, and genotoxicity in vitro and in vivo.

Subchronic and chronic studies were carried out in the rat and a developmental toxicity study in the rabbit with exposures to 1,1,1,2-tetrafluoroethane (HFC 134a) by inhalation. In the rat repeated exposure to 50,000 ppm HFC 134a for 13, 52, and 104 weeks elicited no effect on clinical condition, growth, and survival, or on a variety of hematological, clinical chemistry, and urinary parameters. Treatment-related pathological changes were seen only at study termination at 2 years and were confined to increased incidence of Leydig cell hyperplasia and adenoma in male rats exposed to 50,000 ppm. The tumors, which were also seen in control animals, were benign and not life-threatening. A battery of in vitro and in vivo tests gave no evidence of genotoxic activity. With exposure to pregnant rabbits, the only treatment-related effects were of minimal maternal toxicity at high exposure concentrations; there were no effects on fetal development. It is concluded that HFC 134a is of very low toxicity and should be an acceptable alternative to CFCs.

Administration, Inhalation↗
PubMed1995

Antitumor effects of oral administration of an interferon-inducing pyrimidinone, Bropirimine, on murine renal-cell carcinoma.

Bropirimine [2-amino-5-bromo-6-phenyl-4-(3H)-pyrimidinone] is a low-molecular-weight compound that acts as an inducer of interferon in several animal species. Experiments were designed to explore the possibility of using this drug for the treatment of renal-cell carcinoma (RCC). Euthymic BALB/c mice were inoculated with murine RCC (Renca) cells and given graded doses of Bropirimine p.o. for 5 consecutive days beginning on day 1 following tumor inoculation. These mice were killed and tumors were excised on day 21. Bropirimine significantly (P < 0.01) inhibited the tumor growth at a daily dose of 1,000 or 2,000 mg/kg. No adverse effect or toxicity was noted at 1,000 mg/kg, and at 2,000 mg/kg there was only a marginal body-weight reduction without any other appreciable side effect. In addition to the inhibition of tumor growth, there was a small yet significant (P < 0.05) increase in the duration of survival (in days) in the Bropirimine-treated animals. When the treatment was delayed to begin on day 6 following tumor inoculation, Bropirimine did not suppress tumor growth in euthymic mice, pointing to the importance of the timing of the treatment. In athymic nude BALB/c mice lacking T-cells or T-cell function, Bropirimine also inhibited tumor growth (P < 0.01). The antitumor effect of this drug was abolished by pretreatment with anti-asialo GM1 serum, which eliminated natural killer (NK) activity in euthymic mice. In vivo treatment with Bropirimine augmented the cytotoxicity of lymphocytes isolated from the spleens or lungs of the tumor-bearing mice, which were active against Renca and YAC-1 cells in vitro. This activity was NK-cell-dependent as judged on the basis of the results of the in vitro complement-dependent cytotoxicity assay. Since Bropirimine induced interferon (IFN)-alpha/beta production, significantly (P < 0.05) elevating its serum concentration, and since this drug mimics the effects of IFN-alpha/beta, it seemed likely that the Bropirimine-induced NK cell augmentation we found was mediated by IFN-alpha/beta. These results suggest that Bropirimine, a booster of NK activity, may have potential as an adjunct to other therapeutic modalities in the treatment of human RCC.

Administration, Oral↗
PubMed1995

Subchronic toxicity of 3-phenylamino alanine, an impurity in L-tryptophan reported to be associated with eosinophilia-myalgia syndrome.

Consumption of certain product lots of L-tryptophan (LT) has been reported to be epidemiologically associated with an outbreak of eosinophilia-myalgia syndrome (EMS) in the United States. Since the production lots were found to contain 3-phenylamino alanine (PAA) as an impurity, its effects were studied by administering the substance orally by gavage to 5-week-old Sprague-Dawley rats. Groups of animals were given PAA for 13 consecutive weeks at dose levels of 1, 10 and 100 mg/kg per day. The animals were killed at 4 or 8 weeks. Hematological and blood biochemical tests were performed and detailed histopathological observations were made. No significant abnormalities were observed in the test animals and in particular no EMS-like conditions. A brief summary of other animal studies using several species of rats and mice performed in our laboratory since 1989 on various LT related substances is also presented. No EMS-like effects were observed in these studies.

Administration, Oral↗
PubMed1995

Insulinotropic action of (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl) propionate. I. Secretory and cationic aspects.

1. Sodium (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl) propionate (KAD-1229) is a newly introduced non-sulphonylurea insulinotropic agent. 2. It failed to affect insulin release by rat islets incubated in the absence of D-glucose, slightly increased insulin output at 2.8 mM D-glucose and markedly enhanced secretion at 6.0 and 11.1 mM D-glucose. At the latter hexose concentration, the threshold concentration for the insulinotropic action of KAD-1229 was below 0.1 microM and a close-to-maximal response recorded with 1.0 microM KAD-1229. Even at 16.7 mM D-glucose, KAD-1229 (10 microM) still augmented insulin output. 3. At 6.0 mM D-glucose, KAD-1229 (0.1-1.0 microM) caused a concentration-related increase in 45Ca uptake. This coincided, in prelabelled islets, with a rapid and dual change in 86Rb outflow and dramatic increase in 45Ca outflow. 4. KAD-1229 also increased insulin release evoked by 2-ketoisocaproate (10 mM), albeit to a lesser extent than observed at a D-glucose concentration of comparable insulinotropic efficiency. 14C-labelled KAD-1229 was poorly oxidized by the islets. 5. These findings support the view that the mode of action of KAD-1229 displays analogy with that of hypoglycemic sulphonylurea.

Animals↗
PubMed1995

Insulinotropic action of (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl) propionate. II. Ionophoretic and conformational aspects.

1. The non-sulphonylurea insulinotropic agent sodium (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl) propionate (KAD-1229) was found to display calcium ionophoretic activity in an artificial membrane model. 2. Conformation analysis indicated that a complex between calcium and KAD-1229, with a 1:2 stoichiometry, indeed displays favourable attributes for ionophoretic activity across a hydrophobic environment. 3. It is speculated that the ionophoretic property of KAD-1229 might participate to the remodelling of cationic fluxes evoked by this insulinotropic agent in pancreatic islet cells.

Animals↗
PubMed1995

An immunohistochemical study of Ca2+/calmodulin-dependent protein kinase IV in the rat central nervous system: light and electron microscopic observations.

We observed the distribution pattern of Ca2+/calmodulin-dependent protein kinase IV in rat brain and spinal cord using an immunohistochemical method by light and electron microscopy. Particularly strong immunoreactivity was detected in the telencephalic structures such as the olfactory bulb, cerebral cortex, hippocampal formation, caudate-putamen, most nuclei of the dorsal thalamus and the granule cell layer of the cerebellum. Relatively weak staining was observed in the amygdaloid body, some neuron groups of the brainstem reticular formation, the inferior olivary nucleus and the posterior horn of the spinal cord. Immunohistochemical reactivity was not detected in the globus pallidus, substantia nigra, sensory and motor nuclei of the cranial nerves, or in the spinal cord anterior horn. Overall, the distribution of Ca2+/calmodulin-dependent protein kinase IV-like immunoreactivity broadly paralleled the sites of expression of signals for messenger RNA of this enzyme. At the subcellular level, Ca2+/calmodulin-dependent protein kinase IV-like immunoreactivity appeared exclusively in the nuclei of neurons in the various brain regions, and immunopositive reactivity, although less strong, was also observed in dendritic processes, as well as on the granular endoplasmic reticulum in neuronal somata in these areas. Axon terminals, however, did not show immunoreactivity. These studies demonstrate that Ca2+/calmodulin-dependent protein kinase IV-like immunoreactivity is distributed widely in the central nervous system. The significance of the localization of this enzyme in nuclei is discussed in relation to gene expression.

Animals↗
PubMed1995

Surgical treatment of renal cell carcinoma extending into the vena cava.

BACKGROUND: Renal cell carcinoma has a tendency to invade the vasculature and the prognostic implications of intravena caval tumor thrombectomy remains controversial. We reviewed our clinical experience with RCC patients who underwent tumor thrombectomy and radical nephrectomy. METHODS: Surgery was carried out in 13 renal cell carcinoma patients with inferior vena cava extension over the past seven years. Diagnosis of intracaval tumor extension and thrombus formation was made by imaging techniques including ultrasonography and computed tomography. Cavography and magnetic resonance imaging were also performed in some cases. RESULTS: The level of the tumor thrombus was infrahepatic (V2a) in nine cases and retrohepatic (V2b) in four. Ultrasound and magnetic resonance imaging were extremely useful in defining the extent of the thrombus in addition to detecting its presence. The caval thrombi were reached simply by ligation and division of the short hepatic veins in the V2a cases, but liver mobilization was required in the V2b cases. There were no operative deaths. Two patients who had metastases on surgery died of the disease eight and 13 months after surgery. Four of the 11 patients in whom no evidence of metastasis was found on surgery also died of the disease between nine and 16 months postoperatively. The remaining seven patients are still alive at periods of 6-74 months after surgery, with or without residual tumors. The nature of the intracaval tumor thrombi seems to affect the overall prognosis for survival. Elevated levels of acute phase reactants and immunosuppressive acidic protein were associated with short survival times. CONCLUSIONS: Our experience suggests that aggressive surgery should be considered in selected patients with non-metastatic renal cell carcinoma extending into the vena cava.

Aged↗
PubMed1995

Normalization of impaired glucose tolerance by the short-acting hypoglycemic agent calcium (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionate dihydrate (KAD-1229) in non-insulin-dependent diabetes mellitus rats.

We have investigated the hypoglycemic effects of the newly synthesized short-acting nonsulphonylurea hypoglycemic agent calcium (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl)-propionate dihydrate (KAD-1229) in non-insulin-dependent diabetes mellitus (NIDDM) rats. NIDDM rats that were given a neonatal injection of 60 mg/kg streptozotocin showed a dose-dependent but attenuated response to oral administration of KAD-1229 and gliclazide, and their impaired glucose tolerance was improved but not normalized. We next produced, using a neonatal injection of 30 mg/kg streptozotocin, a mild type of NIDDM rat with less impaired glucose tolerance. These rats responded well to these insulinotropic hypoglycemic agents. Their impaired glucose and meal tolerance were completely normalized by oral administration of 3 mg/kg KAD-1229. The efficacy of KAD-1229 in this NIDDM rat model 1-3 h after oral glucose administration was comparable with similar doses of gliclazide, despite its shorter hypoglycemic action (compared with gliclazide), in fasting normal rats. In meal tolerance tests (20 kcal/kg; 1 cal = 4.2 J), KAD-1229 reduced abnormally enhanced plasma glucose levels 1-3 h after administration. This effect disappeared by 5 h. In contrast, gliclazide showed sustained hypoglycemic effects until 5 h after oral administration, with a lower postprandial (0.5-1 h) effect. These data indicated that the rapid- and short-acting efficacy of KAD-1229 would be beneficial and sufficient to control postprandial plasma glucose in NIDDM rats.

Animals↗
PubMed1995

Hb Gunma (beta Gunma) with pulmonary embolism.

A 67-year-old woman with pulmonary embolism was suspected to have beta-thalassemia based on microcytosis, hemolysis and a negative red cell stability test. The DNA sequencing analysis of beta-globin gene, however, revealed the deletion of three nucleotides within codon 127-128, leading to substitution of glutamine and alanine residues at 127 and 128 by proline, namely Hb Gunma. This mutant is characterized by the fact that no abnormal hemoglobin is detected in the circulating blood, and is classified as a thalassemic hemoglobinopathy. The present case showed a relatively hemolytic manifestation.

Aged↗
PubMed1995

Molecular cloning and characterization of S-adenosyl-L-methionine:scoulerine-9-O-methyltransferase from cultured cells of Coptis japonica.

S-Adenosyl-L-methionine:scoulerine-9-O-methyltransferase (SMT) catalyzes the transfer of the S-methyl group of S-adenosyl-L-methionine to the 9-hydroxyl group of scoulerine during the biosynthesis of berberine. We have isolated functionally active cDNA clones (pCJSMTs) from a cDNA library prepared from cultured cells of Coptis japonica. The longest cDNA insert (pCJSMT1) had an open reading frame that encoded 351 amino acids, but the calculated molecular mass (38,364 Da) of the deduced product was slightly lower than the experimentally determined molecular mass of purified SMT. Rapid amplification of the 5' end of the cDNA indicated that the full-length cDNA of SMT consisted of 1,458 nucleotides that encoded 381 amino acids. When the full-length cDNA was expressed in E. coli, the molecular mass of the expressed SMT was greater than that of native SMT in Coptis cells. This result suggests that SMT might be produced in a pre-mature form and processed post-translationally. SMT was also found to exhibit sequence homology to other O-methyltransferases from plants and N-terminal region of the SMT polypeptide appeared to be necessary for enzymatic activity.

Amino Acid Sequence↗