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Biomedical subjects

S Satoh

Publications and source records attributed to S Satoh.

At least 433 records · Page 24Linked to original sources

Production of two phosphoproteins from the NS5A region of the hepatitis C viral genome.

Hepatitis C virus produces about 12 viral proteins by proteolytic cleavage of the viral polyprotein precursor produced from the largest open reading frame in the viral genome. We have analyzed the production of viral nonstructural proteins with an in vivo transient expression system using COS-1 cells. Two proteins, a 56-kDa protein and a 58-kDa protein, were produced from the nonstructural region 5A (NS5A), which has the potential to produce a 49 kDa protein. We showed that these proteins are phosphorylated at the serine residues. The presence of the two proteins was reflected by different degrees of phosphorylation. Moreover, the hyper-phosphorylation of p58 was shown to depend on the presence of NS4A, another hepatitis C virus protein.

Animals↗

Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1.

Insulin receptor substrate-1 (IRS-1) is the major substrate of insulin receptor and IGF-1 receptor tyrosine kinases; it has an apparent relative molecular mass of 160-190,000 (M(r), 160-190K) on SDS polyacrylamide gel. Tyrosine-phosphorylated IRS-1 binds the 85K subunit of phosphatidylinositol 3-kinase which may be involved in the translocation of glucose transporters and the abundant src homology protein (ASH)/Grb2 which may be involved in activation of p21ras and MAP kinase cascade. IRS-1 also has binding sites for Syp and Nck and other src homology 2 (SH2) signalling molecules. To clarify the physiological roles of IRS-1 in vivo, we made mice with a targeted disruption of the IRS-1 gene locus. Mice homozygous for targeted disruption of the IRS-1 gene were born alive but were retarded in embryonal and postnatal growth. They also had resistance to the glucose-lowering effects of insulin, IGF-1 and IGF-2. These data suggest the existence of both IRS-1-dependent and IRS-1-independent pathways for signal transduction of insulin and IGFs.

Animals↗

Monoclonal antibodies distinctively recognizing the subtypes of inositol 1,4,5-trisphosphate receptor: application to the studies on inflammatory cells.

Monoclonal antibodies were raised that specifically recognize the COOH-terminal sequences and the loop sequences between the fifth and the sixth transmembrane spanning regions of human inositol 1,4,5-trisphosphate receptor (IP3R) type 1, 2 and 3. Western blot analysis using Jurkat cells, mouse cerebellum, COS-7 expressing IP3R type 3 cDNA showed that those monoclonal antibodies reacted specifically with each of these three IP3R subtypes and that they do not cross-react. These antibodies could be used for the specific immunoprecipitation of IP3Rs. Using these monoclonal antibodies, the expression profiles of IP3R-subtype proteins were found to be different among inflammatory cells such as macrophages, polymorphonuclear cells, mast cells, eosinophils, splenocytes, thymocytes and megakaryocytic cells. Usually, more than one type of IP3R were expressed in a cell simultaneously. The observation of CMK cells under immunofluorescence confocal microscopy revealed that IP3R type 1 and type 2 are located at different subcellular fractions.

Amino Acid Sequence↗

Inhibition by omega-conotoxin GVIA of adrenal catecholamine release in response to endogenous and exogenous acetylcholine.

Effects of the N-type voltage-dependent Ca2+ channel (VDCC) blocker, omega-conotoxin GVIA, and the L-type VDCC blockers, nifedipine and verapamil, on adrenal catecholamine release were examined in anesthetized dogs. These blockers were infused into the adrenal gland through the phrenicoabdominal artery. Splanchnic nerve stimulation at 1 and 3 Hz produced frequency-dependent increases in epinephrine and norepinephrine output determined from adrenal venous blood. Infusion of omega-conotoxin GVIA (0.4 micrograms/min) significantly inhibited the splanchnic nerve stimulation-evoked increases in epinephrine and norepinephrine output. Furthermore, increases in epinephrine and norepinephrine output induced by intraarterial injection of acetylcholine (3 micrograms) into the adrenal gland also were inhibited by omega-conotoxin GVIA (0.4 micrograms/min). Further inhibition of splanchnic nerve stimulation- or exogenous acetylcholine-induced increases in catecholamine output was observed even after the cessation of omega-conotoxin GVIA infusion. Neither nifedipine (1 microgram/min) nor verapamil (10 micrograms/min) affected the splanchnic nerve stimulation-evoked increases in catecholamine output, whereas they inhibited the exogenous acetylcholine-evoked catecholamine release. These results suggest that N-type VDCCs located in adrenal medullary cells may contribute to the release of adrenal catecholamines in response to endogenous and exogenous acetylcholine in the dog.

Acetylcholine↗

What is the minimum number of heart rates necessary to evaluate fetal conditions at different gestational ages?

Our objective was to determine the minimum number of fetal heart rates (FHRs) needed to assess various fetal conditions adequately, focusing on FHR changes in relation to gestational age. We used probability distribution matrices previously derived from 10,934,604 FHRs of 743 uncomplicated fetuses. These matrices were made at nine consecutive 2-week intervals between 23 and 40 weeks' gestation, from which samples were taken after assigning random numbers to FHRs in sequence. As a variable, the difference rate (%) between the sample probability distribution matrix and its corresponding age-group probability distribution matrix was calculated. Scattergrams of difference rates vs. a given number of FHR samplings were analyzed using piecewise linear regression. One critical point per age-group emerged, ranging between 9000 and 10,000 beats, for all age-groups. A linear decrease in the difference rate was noted with a step-by-step increase in random sampling size of FHRs until reaching the critical point, beyond which the difference rate remained constant between 25-33%. The critical points indicate that the minimum number of FHRs for assessment of the fetus at 23-40 weeks' gestation is almost the same, between 9000 and 10,000, with 67-75% baseline variability (so called beat-to-beat variability) and 25-33% long-term variability regardless of advance in gestation.

Evaluation Studies as Topic↗

Cholecystokinin is not a major regulator in the digestive system in the chicken.

To find out whether physiological concentrations of cholecystokinin (CCK), a gastrointestinal hormone in mammals, are also active in chickens, the pancreatic amylase secretory response to CCK-8 was investigated in vitro. Rat pancreatic acini responded to the physiological concentration of CCK-8, but in chickens amylase release was induced at a concentration of CCK-8 1000 times higher than that observed in rats. In another experiment, biliary flow was tested with several doses of CCK-8. The bile flow was stimulated in a dose-dependent fashion, but a significant enhancement was not obtained at a concentration of 0.5 micrograms CCK-8/kg body weight, which was considerably higher than physiological ones. It is concluded that endogenous CCK does not have an important role in the digestive system in the chicken.

Amylases↗

T cell activation-associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6.

This study investigates the molecular mechanisms underlying the induction of and protection from T cell activation-associated hepatic injury. When BALB/c mice were given a single intravenous injection of concanavalin A (Con A) (> or = 0.3 mg/mouse), they developed acute hepatic injury as assessed by a striking increase in plasma transaminase levels within 24 h. Histopathologically, only the liver was injured while moderate infiltration of T cells and polymorphonuclear cells occurred in the portal areas and around the central veins. The induction of hepatic injury was dependent on the existence as well as the activation of T cells, as untreated BALB/c nu/nu mice or BALB/c mice pretreated with a T cell-specific immunosuppressive drug, FK506, failed to develop disease. Significant increases in the levels of various cytokines in the plasma were detected before an increase in plasma transaminase levels. Within 1 h after Con A injection, tumor necrosis factor (TNF) levels peaked, this being followed by production of two other inflammatory cytokines, interleukin 6 (IL-6) and IL-1. Passive immunization with anti-TNF but not with anti-IL-1 or anti-IL-6 antibody, conferred significant levels of protection. Moreover, administration of rIL-6 before Con A injection resulted in an IL-6 dose-dependent protection. A single administration of a given dose of rIL-6 completely inhibited the release of transaminases, whereas the same regimen induced only 40-50% inhibition of TNF production. More than 80% inhibition of TNF production required four consecutive rIL-6 injections. These results indicate that: (a) TNFs are critical cytokines for inducing T cell activation-associated (Con A-induced) hepatitis; (b) the induction of hepatitis is almost completely controlled by rIL-6; and (c) rIL-6 exerts its protective effect through multiple mechanisms including the reduction of TNF production.

Animals↗

[CT findings of sinonasal and orbital Wegener's granulomatosis].

We reviewed the CT findings of four cases of Wegener's granulomatosis that presented as inflammatory masses in the sinonasal cavity or orbit. In the present study, an infiltrative nature and homogeneous texture with contrast enhancement were typical of the masses. In addition, the masses were frequently accompanied by infiltration of the pterygopalatine fossa or destruction of adjacent bone. However, no pathognomonic findings were observed.

Adult↗

Molecular cloning of P-type ATPases on intracellular membranes of the marine alga Heterosigma akashiwo.

Two cDNA clones (HAA13 and HAA1) which include conserved regions of genes of P-type ATPases were isolated from the marine alga Heterosigma akashiwo by a method that included the polymerase chain reaction. The longer cDNA (3286 bp), HAA13, consisted of an open reading frame that encoded a 106 kDa polypeptide of 977 amino acids with several possible transmembrane domains and conserved regions of eukaryotic P-type ATPases. One transmembrane domain had a leucine zipper structure. HAA1 was not a full-length gene (2054 bp) and lacked the 5' region, but it also included the conserved regions and putative transmembrane domains. Antibodies against the regions and putative transmembrane domains. Antibodies against the polypeptides encoded by HAA13 and HAA1 that have been expressed in Escherichia coli reacted with 100 kDa and 95 kDa polypeptides, respectively, on intracellular membranes of H. akashiwo cells. Immunostaining of H. akashiwo cells revealed that the HAA13 antigen was distributed on membranes around chloroplasts and the HAA1 antigen was located on small vesicles.

Adenosine Triphosphatases↗

Endogenous cholecystokinin is not a major regulator of food intake in the chicken.

This study investigated whether or not endogenous cholecystokinin exerts satiety effects in chickens. After several doses (0, 1, 2 and 4 micrograms.kg body weight-1) of intravenous injection of caerulein, the bile flow was increased in a dose-dependent fashion. However, the pharmacological level of caerulein failed to suppress the food intake of chickens. Two potent stimulators of endogenous cholecystokinin, i.e., soybean trypsin inhibitor and phenylalanine were administered to chickens before feeding and food intake was determined over 2 h. The soybean trypsin inhibitor and phenylalanine did not alter food intake. Devazepide, a cholecystokinin-A receptor antagonist, significantly decreased amylase release from the dispersed chicken pancreatic acini stimulated by caerulein. However, devazepide did not improve food intake of the chicken. The results obtained suggest that endogenous cholecystokinin may not act as a satiety signal in chickens.

Animals↗

The combination of lovastatin and enalapril in a model of progressive renal disease.

Puromycin-induced nephrotic syndrome is an animal model of progressive renal disease. Both angiotensin converting enzyme inhibitors and lipid-lowering agents have been used to preserve renal structure and function in this model, although neither completely prevents progression. We tested the hypothesis that the combination of the two agents would be more protective than either alone. Rats were divided into five groups; all were uninephrectomized. Four groups were given puromycin at a dose of 10 mg/100 g body weight (BW) with additional doses of 4 mg/100 g BW given intraperitoneally at 4, 5, and 6 weeks thereafter. One group was given enalapril (EN) 50 mg/l dissolved in the drinking water; the second received lovastatin (L) 15 mg/kg given daily by gavage; the third received both agents; the fourth was left untreated, and the final group received no puromycin and served as the control group. Eight weeks after the initial dose of puromycin, glomerular filtration rate (GFR), as inulin clearance, and protein excretion were determined and blood was collected for cholesterol and triglycerides. Blood pressure was not different between any of the groups. At the end of the study period, serum cholesterol [mean +/- SD, 252 +/- 185 mg/dl (L), 135 +/- 101 mg/dl (L + EN)] and triglycerides (239 +/- 200, 148 +/- 158 mg/dl) were significantly lower (P < 0.001) in the lovastatin-treated groups than in the untreated puromycin group (535 +/- 255 mg/dl and 579 +/- 561 mg/dl, cholesterol and triglyceride, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Reconstruction of an iliac crest defect with a bioactive ceramic prosthesis.

Between June 1987 and December 1990, an iliac crest prosthesis made of bioactive apatite- and wollastonite-containing glass ceramic (A-W.GC) was used in 60 patients for the reconstruction of the iliac crest defect after harvesting autogenous tricortical iliac bone graft. The clinical results of this prosthesis were satisfactory. No patients felt spontaneous pain in the reconstructed area, and 93% of the patients had no tenderness there. In the radiological evaluation at the final follow-up, no apparent "radiolucent clear zone" was detected at the prosthesis-iliac bone junction in 98% of the patients. Excellent new bone formation between the prosthesis and the iliac crest was also noticed in 96% of the patients. The A-W.GC iliac crest prosthesis was beneficial for reconstruction of the iliac crest defect.

Adolescent↗

Interleukin 6-producing gastric carcinoma with fever, hypergammaglobulinemia, and plasmacytosis in bone marrow.

A 42-year-old man with a remittent fever was found to have both para-aortic and hepatic tumors with generalized lymphadenopathy. The pathological findings from biopsy specimens from the para-aortic lymph node and hepatic tumor by laparotomy and from left supraclavicular lymphadenectomy showed undifferentiated carcinoma. However, the location of the primary lesion could not be determined. Chemotherapy temporarily reduced the size of the metastatic lymph nodes and the hepatic tumor and also suppressed the remittent fever. Fifteen months after onset, massive polyclonal hypergammapathy developed together with plasmacytosis (30% plasmacytes) in bone marrow, consisting of normal mature plasmacytes. Among cytokines, including interleukin (IL) 1 beta, IL-3, IL-4, IL-6, and tumor necrosis factor alpha, a high value of IL-6 was detected in the serum. Postmortem pathological examination showed the scirrhous type of gastric carcinoma with specific staining by polyclonal antibody against human IL-6. To our knowledge, this is the first report of a gastric carcinoma producing IL-6 associated with fever, hypergammaglobulinemia, and plasmacytosis in bone marrow.

Adenocarcinoma, Scirrhous↗

Fetal heart rate variation described using a probability distribution matrix.

We devised a new method using a probability distribution matrix to simultaneously describe variation in the characteristics of fetal heart rate (FHR) and beat-to-beat difference (DFHR) between the present and the immediately following FHR. The FHRs were plotted in columns, DFHRs in rows and probabilities in the corresponding elements of the matrix. The age-related changes of FHR data obtained from 743 fetuses at 23-40 weeks gestation were analysed using a pulsed Doppler cardiotocograph with an autocorrelation system. While keeping an almost symmetrical spread around 0 beats/min of DFHR, three particular probability distribution patterns of FHR versus DFHR emerged with advance in gestation: (i) oval with a monomodal peak from 23/24 to 29/30 weeks, (ii) ellipsoid with a monomodal peak and plateau from 31/32 to 33/34 weeks and (iii) elongated ellipsoid with bimodal peaks from 35/36 weeks of gestation onwards. The probability distribution matrix presented enables one to condense any amount of FHR data into one uniform description. This allows analysis of data, en bloc, achieving a quantitative inter-group comparison, on an equivalent scale.

Age Factors↗

Supporting, microporous, elastomeric, degradable prostheses to improve the arterialization of autologous vein grafts.

Arterial reconstructions with vein grafts fail more frequently than with arterial grafts. One of the causes of graft failure is damage due to overstretching of the graft wall. Overstretching is caused because the vein graft, which has a poorly developed medium, cannot withstand the arterial blood pressures. The aim of this study is to evaluate whether damage due to overstretching can be prevented and a gradual adaptation of the vein graft to the arterial blood pressures can be induced by applying a microporous, elastomeric, degradable prosthesis around the vein graft. Therefore, autologous vein grafts (length 1.0 cm) with and without supporting prostheses (composite vein grafts and control vein grafts, respectively) were interposed into both carotid arteries of rabbits. Microporous, elastomeric, biofragmentable polyurethane-based prostheses and microporous, elastomeric, biodegradable prostheses made of poly-epsilon-caprolactone or a copolymer of epsilon-caprolactone and 3.6-dimethyl-1,4-morpholine-2,5-dione with a monomer ratio of 95.5:4.5 were prepared. The grafts were evaluated up to 6 wk after implantation. The control vein grafts showed severe destructive changes such as de-endothelialization, disruption of the media with oedema, degradation of the elastic laminae and infiltration of polymorphonuclear leucocytes into the vein graft wall, leading eventually to a fibrotic wall. In contrast, the composite vein grafts showed a preservation of the smooth muscle cell layers and the elastic laminae with only few polymorphonuclear leucocytes infiltrated into the vein graft wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Vasopressin mediated vasodilation of cerebral arteries.

The bolus injection of vasopressin into the vertebral artery produced a dose-dependent vasodilation in the major cerebral arteries, detected angiographically, while it elicited a decrease in vertebral blood flow. One nanomol of vasopressin was the optimal dose for producing maximal vasodilation. The basilar, posterior communicating, and internal carotid arteries showed the most dilatation, followed by the middle cerebral, the intracranial portion of the vertebral artery and the anterior spinal artery. The extracranial portion of the vertebral artery was less sensitive to vasopressin. The vasodilation was inhibited by a V1-antagonist and NG-monomethyl-L-arginine. These results suggest that the arteries of the circle of Willis at the base of the brain are more sensitive to nitric oxide release induced by vasopressin compared with other intracranial and extracranial arteries.

Anesthesia↗

Promotion of sleep by prostaglandin D2 in rats made insomniac by pretreatment with para-chlorophenylalanine.

The correlation between the somnogenic effect of prostaglandin (PG) D2 and the serotoninergic system was examined in freely-moving rats (n = 64) by use of a continuous infusion method. Rats pretreated with para-chlorophenylalanine (PCPA: 450 mg/kg body weight, i.p.) or non-PCPA-pretreated rats received infusion of PGD2, serotonin, or its direct precursor, 5-hydroxytryptophan (5HTP), into their third cerebral ventricle at a rate of 100 pmol/0.2 microliter/min between 11:00 and 17:00 h. In the PCPA-pretreated insomniac rats, PGD2 infusion resulted in an immediate increase in slow-wave sleep (SWS) and an increase with a 2-h latency in paradoxical sleep (PS). The total amounts of SWS and PS during the PGD2-infusion period were 151% and 154% of the respective control values. These results indicate that inhibition of the biosynthesis of serotonin and 5HTP by PCPA marginally affects the sleep-promoting effect of PGD2. The transient sleep restoration produced by 5HTP infusion into PCPA-pretreated rats was hardly affected by the simultaneous infusion (200 pmol/0.2 microliter/min; 07:00-17:00 h) of diclofenac sodium, an inhibitor of cyclo-oxygenase, suggesting that PGD2 production is not critically involved in the sleep restoration by 5HTP. The sleep-promoting property of PGD2 is thus probably independent of the serotoninergic modulation of sleep-wake activity.

5-Hydroxytryptophan↗

The relationship between age-related heart rate changes and developing brain function: a model of anencephalic human fetuses in utero.

We attempted to identify the brain segment which controls heart rate changes in human fetuses with advancing gestation. Twelve anencephalic and 165 normal fetuses (control-group fetuses) between 25-32 weeks' gestation were studied. The instantaneous fetal heart rate (FHR) data were obtained from each fetus for a continuous 90-120 min period, using an external cardiotocograph. Calculations included the 'individual probability distribution matrices' in which the FHRs at 1 beat/min intervals between 110 and 180 beats/min, the beat-to-beat differences (DFHRs) between +/- 5 beats/min and the probability values were arranged in rows, columns and the corresponding elements, respectively. Using 2-gestational-week intervals probability distribution matrices (age-group probability distribution matrices) obtained from 335 normal fetuses in our previous study as a reference, the difference between a given 'individual probability distribution matrix' and the corresponding age-group probability distribution matrix' was quantified as the 'difference rate' according to the formula in the text. From 25-26 to 27-28 weeks' gestation, the 'difference rates' in four anencephalic fetuses, with only the spinal cord preserved, were significantly higher in value than those of control-group fetuses, whereas the rates in four fetuses with both the spinal cord and medulla oblongata preserved, indicated no significant differences. From 29-30 to 31-32 weeks' gestation, the rates of the four fetuses with the spinal cord and medulla oblongata preserved, showed significant differences from the control-group fetuses. These findings suggest that there is a critical period between 27-28 and 29-30 weeks' gestation with regard to the developing brain function pertaining to FHR changes. In the early stage, the medulla oblongata plays a role in FHR changes, whereas, in the latter stage, the brain cephalad to the medulla also appears to take on the role of FHR regulator.

Anencephaly↗