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T Satoh

Publications and source records attributed to T Satoh.

At least 199 records · Page 11Linked to original sources
PubMed2000

Effects of alpha adrenoreceptor antagonists, prazosin and. yohimbine, on intrathecal lidocaine-induced antinociception in mice.

BACKGROUND: The precise mechanisms involved in the spinal analgesic effect of lidocaine are not yet clear. We previously found that lidocaine releases noradrenaline, a modulator of nociception, in rat spinal cord. Here, we attempted to clarify whether or not the noradrenaline release contributes to spinal analgesia by lidocaine. METHODS: The effects of intrathecal injections of the alpha adrenoreceptor antagonists, prazosin (0.01-0.3 nmol) and yohimbine (0.1-3 nmol), on intrathecal 2% lidocaine were assessed using the tail-flick (TF) test in mice. RESULTS: Lidocaine significantly increased the TF latency for 15 min. Prazosin (0.03, 0.1 or 0.3 nmol) and yohimbine (0.3, 1.0 or 3.0 nmol) significantly reduced the lidocaine-induced increase of the TF latency 10 min after injection, although both drugs showed a ceiling effect. CONCLUSION: These results suggest that stimulation of the noradrenergic systems plays an important role in spinal analgesia by lidocaine.

Adrenergic alpha-Antagonists↗
PubMed2000

Multiple minute digitate hyperkeratoses.

A familial case of multiple minute digitate hyperkeratoses is reported. Hundreds of tiny, spiked, keratotic papules were scattered on the trunk and limbs. Microscopically, the lesions showed digitiform orthohyperkeratosis with tenting of the epidermis. Neither atypical epidermal cells nor a dermal infiltrate were observed. This disease has three types: familial, sporadic and postinflammatory. We have analysed the histopathological features of all the cases reported to date. While the familial and sporadic types are similar, the lesions in the postinflammatory type are composed of parakeratotic columns with an invaginated epidermis. Although morphological analysis may not provide any clues to pathogenetic differences, it seems reasonable to assume that the postinflammatory type is an entity different from the other two forms.

Aged↗
PubMed2000

Pathogenic roles of eosinophils in guinea-pig contact sensitivity: regulation of dermal eosinophilia with remotely administered IL-5.

Eosinophils have a variety of functions. Although increasing evidence links the presence of eosinophils to airway damage, studies have not examined in detail if, and how, eosinophils affect skin inflammation. The purpose of this study was to determine whether eosinophil infiltration augments the contact sensitivity reaction in vivo. Guinea-pigs were sensitized with 2, 4-dinitrochlorobenzene and challenged on the dorsal skin or on the right ear lobe. The number of eosinophils and macroscopic changes of the skin lesion in the presence or absence of human recombinant IL-5 (rIL-5) administered at the remote site was assessed. The reaction on the dorsal skin was acutely eczematous with considerable basophil infiltration. In contrast, eosinophils had extensively infiltrated the right ear lobe and major basic protein was deposited in the dermis. A subcutaneous injection of rIL-5 (10 pmol/kg) at the remote site (left ear lobe) 12 h after challenge induced transient blood eosinophilia and enhanced eosinophil accumulation in the challenged ear lobe. These changes were accompanied by increased ear swelling and severe erythema. In contrast, eosinophil infiltration was significantly inhibited by rIL-5 administered at the time of challenge. Ear thickness, as well as the erythema and oedema, were also reduced. These data suggest that marked eosinophil infiltration enhances skin inflammation in allergic contact dermatitis. Moreover, locally administered IL-5 functions remotely by controlling eosinophil recruitment into the skin. The guinea-pig model of contact sensitivity may be useful for evaluating therapies and pharmaceuticals targeted at eosinophil infiltration.

Animals↗
PubMed2000

Small dose midazolam or droperidol reduces the hypnotic dose of propofol at the induction of anaesthesia.

We investigated the effect of a small dose of midazolam, ketamine, droperidol or lidocaine on the propofol dose required for hypnosis during induction of general anaesthesia. These drugs were randomly administered to 100 patients about to undergo scheduled surgery. Propofol was then infused at a rate of 250 microg kg-1 min-1 and the hypnotic dose to produce hypnosis was evaluated. Midazolam (20 microg kg-1) and droperidol (20 microg kg-1) significantly reduced the mean hypnotic dose of propofol (mean) S.D.) compared with the placebo (43.7 +/- 17.8 mg, 61.9 +/- 10.6 mg and 72.5 +/- 27.7 mg after pretreatment with midazolam, droperidol and placebo, respectively), whereas ketamine (0.1 mg kg-1) and lidocaine (1 mg kg-1) did not significantly affect the hypnotic dose of propofol (63. 1 +/- 25.6 mg and 65.1 +/- 24.8 mg, respectively). Only midazolam when compared with saline administration, (176 +/- 66 s and 298 +/- 126 s, respectively), shortened the time to achieve hypnosis. The changes in blood pressure (non-invasive) and heart rate were not significantly different in all groups during the induction of anaesthesia and oro-tracheal intubation. These results raise the possibility that new combinations of central nervous system drugs, such as droperidol and propofol, have a potential to reduce the dose of intravenous anaesthetics, including propofol, that produce hypnosis without significant adverse effects.

Adjuvants, Anesthesia↗
PubMed2000

Interaction between hyaluronan and CD44 in the development of dimethylnitrosamine-induced liver cirrhosis.

BACKGROUND: A significant increase in serum hyaluronan (HA) levels has been reported in patients with liver cirrhosis. This mechanism is not yet clear, and receptors for HA have not been characterized. In this study, we examined the expression of both HA and its receptors, CD44 and intercellular adhesion molecule-1 (ICAM-1), in dimethylnitrosamine-induced liver cirrhosis. METHODS AND RESULTS: Using biotinylated HA binding protein, HA was detected in the area of periportal fibrosis and around the sinusoidal wall where hepatic fibrosis was developing. Electron microscopy revealed that HA was localized on Ito cells and sinusoidal endothelial cells (SEC). Conversely, CD44, which was only expressed weakly in normal liver, was present in large amounts in cirrhotic liver. The distribution pattern of CD44 was similar to that of HA, however, CD44 was mainly localized on the infiltrating lymphocytes and Kupffer cells. Moreover, CD44 was detected on part of factor VIII-positive SEC. Intercellular adhesion molecule-1, another receptor for HA, was detected on the surface of hepatocytes and around the sinusoidal wall in cirrhotic liver, but its distribution was not accompanied by expression of HA. With respect to CD44 isoforms, the standard form m-RNA predominated in both normal and cirrhotic liver. Variant pMeta-1 mRNA was detected at low levels. CONCLUSIONS: An interaction between HA and CD44 may play a role in the recruitment of numerous infiltrating cells and HA accumulation in hepatic sinusoids. Together with phenotypic changes in the SEC, these results may lead to a disturbance in the elimination of HA during the progression of liver cirrhosis.

Animals↗
PubMed2000

Abnormal distribution of collagen type IV in extrahepatic bile duct carcinoma.

The present study investigated the pathogenesis of desmoplastic stroma formation, which is characteristic of most bile duct carcinomas and other scirrhous carcinomas. Using immunohistochemical analysis, the expression of collagen types I and IV, laminin and TGF-beta1 was examined in human extrahepatic bile duct carcinoma and compared with gastric and colon carcinoma. In addition to delineating the basement membranes of carcinoma nests and blood vessels, collagen type IV was present along the thick bundles of collagenous fibers in the stroma of extrahepatic bile duct carcinoma and scirrhous gastric carcinoma. The immunoreactivity of collagen type IV was strong in the adjacent or surrounding interstitium of tumor cell nests, but was absent or weak in older, more central portions of the tumor that contained sclerotic collagen. In situ hybridization demonstrated active expression of collagen alpha1(IV) mRNA in extrahepatic bile duct carcinoma and scirrhous gastric carcinoma cells. These results suggest that, although collagen type IV is typically a component of the basement membrane, it is expressed in the interstitial stroma of extrahepatic bile duct carcinoma and scirrhous gastric carcinoma where it may play a role in desmoplastic stroma formation.

Adenocarcinoma↗
PubMed2000

Facilitatory roles of novel compounds designed from cyclopentenone prostaglandins on neurite outgrowth-promoting activities of nerve growth factor.

Cyclopentenone prostaglandins (PGs) are known to arrest the cell cycle at the G(1) phase in vitro and to suppress tumor growth in vivo. However, their effects on neurons are unclear. Here, we report that some cyclopentenone PGs function as neurite outgrowth-promoting factors. They promoted neurite outgrowth from PC12 cells and from dorsal root ganglion explants but only in the presence of nerve growth factor (NGF). We refer to these PGs as neurite outgrowth-promoting PGs (NEPPs). Through study of the structure-function relationship of NEPP1-10 and related compounds, we found that the cross-conjugated dienone moiety of NEPPs was essential for promoting neurite outgrowth, and NEPP10 was concluded to be the best candidate for drug development. We also investigated the intracellular mechanism of the promotion by NEPPs and obtained evidence that immunoglobulin heavy chain binding protein/glucose-regulated protein 78 (BiP/GRP78) plays a role in the promotion, based on the following observations: Antisense nucleotides for BiP/GRP78 gene blocked the promotion of neurite outgrowth; BiP/GRP78 protein level increased in response to NEPPs; and overexpression of BiP/GRP78 protein by adenoviral gene transfer promoted the neurite outgrowth by NGF.

Adenoviridae↗
PubMed2000

Glucocorticoids augment the chemically induced production and gene expression of interleukin-1alpha through NF-kappaB and AP-1 activation in murine epidermal cells.

To clarify the mechanism of the glucocorticoid-induced augmentation of skin response, we attempted to demonstrate the modulatory effect of glucocorticoids on the regulation of cytokines produced by keratinocytes stimulated with various chemicals in vitro. Haptens, irritants, and a superantigen (staphylococcal enterotoxin B) induced a significant release of interleukin-1alpha and tumor necrosis factor alpha, but not interleukin-10, from a murine keratinocyte cell line, Pam 212 cells. Glucocorticoids (10(-6)-10(-12) M) significantly augmented the production of interleukin-1alpha by Pam 212 cells at both the protein and mRNA levels when stimulated by either haptens or irritants, but not by staphylococcal enterotoxin B, whereas glucocorticoids alone had no effect. In contrast, glucocorticoids had no effect on the production of tumor necrosis factor alpha and interleukin-10 by chemically stimulated Pam 212 cells. Electrophoretic mobility shift assays revealed that chemical stimulation induced NF-kappaB activation in Pam 212 cells; however, augmented NF-kappaB activation by 10(-6)-10(-8) M of glucocorticoids was observed in Pam 212 cells stimulated by both haptens and irritants, but not by staphylococcal enterotoxin B. Furthermore, pyrrolidine dithiocarbamate inhibited the hapten-induced interleukin-1alpha production and NF-kappaB expression by Pam 212 cells. Pyrrolidine dithiocarbamate did not completely abrogate the hapten-induced interleukin-1alpha production augmented by glucocorticoids, however. To determine the effect on transcription factors other than NF-kappaB, AP-1 activity was examined by electrophoretic mobility shift assays. Hapten was founded to induce AP-1 activation in Pam 212 cells. In addition, AP-1 activation was augmented in the hapten-stimulated Pam 212 cells in the presence of 10(-8)-10(-10) M of glucocorticoids. The augmented inflammatory reaction by glucocorticoids may therefore reflect the augmentation of interleukin-1alpha production by keratinocytes mediated through the NF-kappaB and AP-1 pathway.

Animals↗
PubMed2000

Simple hemostatic procedure for hemorrhagic duodenal ulcer: two cases of arterial hemorrhage quickly controlled by balloon compression.

We utilized balloon compression in two cases of arterial hemorrhage from duodenal ulcers. The bleeding was quickly controlled in both cases. The advantages of this technique are its simplicity and ease of performance, and the fact that it does not require precise identification of the bleeding point in the duodenal bulb. No serious complications, such as perforation or stenosis, are associated with this technique. During the healing of the ulcer, balloon expansion may result in decreased duodenal bulb deformity. The following points, however, should be clarified in future studies: a) the stability of the duodenal bulb after longer-term balloon compression, and b) the optimum amount of cold water to be injected into the balloon and the optimum compression time.

Adult↗
PubMed2000

Interleukin-6 and interleukin-8 levels in serum and synovial fluid of patients with osteoarthritis.

Concentrations of interleukin (IL)-6 and IL-8 in serum and synovial fluid obtained from patients with osteoarthritis (OA) of the knee were determined by the chemiluminescence-ELISA (CL-ELISA) method, the sensitivity of which is 100-1,000 times greater than that of the conventional ELISA method. The results were compared with those obtained from patients with rheumatoid arthritis (RA) and from healthy subjects. The mean IL-6 and IL-8 levels in synovial fluid indicated higher concentrations in RA than in OA. The IL-6 and IL-8 levels in serum were significantly higher in RA and OA relative to controls. Among OA patients in whom remarkable improvement was noted in hydrarthrosis, the synovial fluid IL-6 and IL-8 levels at the initial examination were relatively higher, and were markedly decreased after treatment with sodium hyaluronate (NaHA). Among those in whom no improvement was noted in hydrarthrosis, the synovial fluid IL-6 and IL-8 levels at the time of initial examination were relatively lower, and hydrarthrosis was not significantly improved even after treatment with NaHA. In addition, there was a tendency for the synovial fluid IL-6 and IL-8 levels to decrease as HA levels increased. Evaluation of X-ray findings revealed that the IL-6 levels in synovial fluid at the initial examination in low-grade cases tended to be significantly higher than in high-grade cases. In low-grade cases, as determined by X-ray findings, there was a significant decrease in IL-6 levels in synovial fluid after treatment with NaHA.

Adjuvants, Immunologic↗
PubMed2000

Compound A concentrations during low-flow sevoflurane anesthesia correlate directly with the concentration of monovalent bases in carbon dioxide absorbents.

UNLABELLED: Sevoflurane degrades to Compound A, which is nephrotoxic in rats. Potassium hydroxide (KOH) and sodium hydroxide (NaOH) are primary determinants of this degradation reaction. To address this, new carbon dioxide absorbents, such as Amsorb((R)) (A; Armstrong Medical, Coleraine, Northern Ireland), which contains neither KOH nor NaOH, Drägersorb 800 Plus((R)) (D; Dräger, Luebeck, Germany), and Medisorb((R)) (M; Datex-Ohmeda, Bromma, Sweden), which contain some NaOH (1% to 2%) and only trace amounts of KOH (0.003%), were recently developed. We compared Compound A concentrations using these three CO(2) absorbents during low-flow (1 L/min) sevoflurane anesthesia in surgical patients, with those using a conventional CO(2) absorbent, Drägersorb 800 (C). The mean Compound A concentrations +/- SD using C, A, D, and M were 18.7 +/- 2.5, 1.8 +/- 0.7, 13.3 +/- 3.5, and 11.2 +/- 2.6 ppm, respectively, with significant differences (P < 0.001; A versus C, A versus D, A versus M, C versus D, C versus M). Amsorb prevented the degradation of sevoflurane to Compound A, whereas Drägersorb 800 Plus and Medisorb decreased the degradation to Compound A. IMPLICATIONS: Sevoflurane degradation to Compound A is decreased by lowering the concentration of monovalent bases in the carbon dioxide absorbent (Drägersorb 800 Plus) [Dräger, Luebeck, Germany] and Medisorb) [Datex-Ohmeda, Bromma, Sweden]) and is virtually eliminated in the absence of these bases (Amsorb) [Armstrong Medical, Coleraine, Northern Ireland]).

Absorption↗
PubMed2000

The effect on intracuff pressure of various nitrous oxide concentrations used for inflating an endotracheal tube cuff.

UNLABELLED: We sought to determine the optimal concentration of nitrous oxide (N(2)O) for inflating endotracheal tube cuffs, to avoid overinflation and air leaks. Female patients undergoing endotracheal intubation (inner diameter 7.5 mm) during anesthesia with 67% N(2)O were randomly assigned to five groups of 25 subjects each, in which cuffs were inflated with 0% (Air), 30% (N30), 40% (N40), 50% (N50), or 67% (N67) N(2)O. The cuff pressure and the N(2)O concentration in the cuff were measured. In an additional 15 patients (N40-a group), pilot balloons were replaced with metal tubes, and the mouths and noses of the patients were wrapped with tape, to minimize N(2)O efflux into the air. Postoperative sore throats were evaluated in double-blinded interviews. Cuff pressures increased significantly in the Air and N30 groups but decreased in the N67 group. Cuff pressures were <22 mm Hg in the N40 and N50 groups, but the N50 group had air leaks. The N(2)O concentration in the cuff in the N40 group was significantly smaller than that in the N40-a group, suggesting N(2)O rediffusion. The incidence of sore throats (40% in the Air group) was reduced significantly in the N40 and N50 groups. Therefore, 40% N(2)O is optimal for filling the cuff during anesthesia with 67% N(2)O. IMPLICATIONS: Nitrous oxide (N(2)O) diffuses into the cuff, equilibrating at a smaller concentration than the gas mixture with which patients are ventilated. Our data indicate that inflation of the cuff with 40% N(2)O is recommended to prevent both excessive endotracheal cuff pressure and air leaks during anesthesia with 67% N(2)O, reducing postoperative sore throats.

Adolescent↗
PubMed2000

Structure of cytochrome c6 from the red alga Porphyra yezoensis at 1. 57 A resolution.

The crystal structure of cytochrome c(6) from the red alga Porphyra yezoensis has been determined at 1.57 A resolution. The crystal is tetragonal and belongs to space group P4(3)2(1)2, with unit-cell parameters a = b = 49.26 (3), c = 83.45 (4) A and one molecule per asymmetric unit. The structure was solved by the molecular-replacement method and refined with X-PLOR to an R factor of 19.9% and a free R factor of 25.4%. The overall structure of cytochrome c(6) follows the topology of class I c-type cytochromes in which the heme prosthetic group covalently binds to Cys14 and Cys17, and the iron has an octahedral coordination with His18 and Met58 as the axial ligands. The sequence and the structure of the eukaryotic red algal cytochrome c(6) are very similar to those of a prokaryotic cyanobacterial cytochrome c(6) rather than those of eukaryotic green algal c(6) cytochromes.

Amino Acid Sequence↗
PubMed2000

Hematin polymerization assay as a high-throughput screen for identification of new antimalarial pharmacophores.

Hematin polymerization is a parasite-specific process that enables the detoxification of heme following its release in the lysosomal digestive vacuole during hemoglobin degradation, and represents both an essential and a unique pharmacological drug target. We have developed a high-throughput in vitro microassay of hematin polymerization based on the detection of (14)C-labeled hematin incorporated into polymeric hemozoin (malaria pigment). The assay uses 96-well filtration microplates and requires 12 h and a Wallac 1450 MicroBeta liquid scintillation counter. The robustness of the assay allowed the rapid screening and evaluation of more than 100, 000 compounds. Random screening was complemented by the development of a pharmacophore hypothesis using the "Catalyst" program and a large amount of data available on the inhibitory activity of a large library of 4-aminoquinolines. Using these methods, we identified "hit" compounds belonging to several chemical structural classes that had potential antimalarial activity. Follow-up evaluation of the antimalarial activity of these compounds in culture and in the Plasmodium berghei murine model further identified compounds with actual antimalarial activity. Of particular interest was a triarylcarbinol (Ro 06-9075) and a related benzophenone (Ro 22-8014) that showed oral activity in the murine model. These compounds are chemically accessible and could form the basis of a new antimalarial medicinal chemistry program.

Animals↗
PubMed2000

Geranylgeranyltransferase I of Candida albicans: null mutants or enzyme inhibitors produce unexpected phenotypes.

Geranylgeranyltransferase I (GGTase I) catalyzes the transfer of a prenyl group from geranylgeranyl diphosphate to the carboxy-terminal cysteine of proteins with a motif referred to as a CaaX box (C, cysteine; a, usually aliphatic amino acid; X, usually L). The alpha and beta subunits of GGTase I from Saccharomyces cerevisiae are encoded by RAM2 and CDC43, respectively, and each is essential for viability. We are evaluating GGTase I as a potential target for antimycotic therapy of the related yeast, Candida albicans, which is the major human pathogen for disseminated fungal infections. Recently we cloned CaCDC43, the C. albicans homolog of S. cerevisiae CDC43. To study its role in C. albicans, both alleles were sequentially disrupted in strain CAI4. Null Cacdc43 mutants were viable despite the lack of detectable GGTase I activity but were morphologically abnormal. The subcellular distribution of two GGTase I substrates, Rho1p and Cdc42p, was shifted from the membranous fraction to the cytosolic fraction in the cdc43 mutants, and levels of these two proteins were elevated compared to those in the parent strain. Two compounds that are potent GGTase I inhibitors in vitro but that have poor antifungal activity, J-109,390 and L-269,289, caused similar changes in the distribution and quantity of the substrate. The lethality of an S. cerevisiae cdc43 mutant can be suppressed by simultaneous overexpression of RHO1 and CDC42 on high-copy-number plasmids (Y. Ohya et al., Mol. Biol. Cell 4:1017, 1991; C. A. Trueblood, Y. Ohya, and J. Rine, Mol. Cell. Biol. 13:4260, 1993). Prenylation presumably occurs by farnesyltransferase (FTase). We hypothesize that Cdc42p and Rho1p of C. albicans can be prenylated by FTase when GGTase I is absent or limiting and that elevation of these two substrates enables them to compete with FTase substrates for prenylation and thus allows sustained growth.

Alkyl and Aryl Transferases↗
PubMed2000

Haemodynamic correlates and prognostic significance of serum uric acid in adult patients with Eisenmenger syndrome.

OBJECTIVE: To assess haemodynamic correlates and prognostic significance of serum uric acid in adult patients with Eisenmenger syndrome. DESIGN: Retrospective observational study. SETTING: Tertiary referral centre. PATIENTS: 94 adult patients with Eisenmenger syndrome who were diagnosed between September 1982 and July 1998. MAIN OUTCOME MEASURES: Serum uric acid was measured in all patients, together with clinical and haemodynamic variables related to mortality. RESULTS: Serum uric acid was raised in patients with Eisenmenger syndrome compared with age and sex matched control subjects (7.0 v 4.7 mg/dl, p < 0.0001) and increased in proportion to the severity of New York Heart Association functional class. Serum uric acid was positively correlated with mean pulmonary arterial pressure (r = 0.30, p = 0.0052) and total pulmonary resistance index (r = 0.55, p < 0.0001), and negatively correlated with cardiac index (r = -0.50, p < 0.0001). During a mean follow up period of 97 months, 38 patients died of cardiopulmonary causes. Among various clinical, echocardiographic, and laboratory variables, serum uric acid remained predictive in multivariate analysis. Kaplan-Meier survival curves based on median serum uric acid showed that patients with high values had a significantly worse survival rate than those with low values (log-lank test: p = 0.0014 in male patients, p = 0.0034 in female patients). CONCLUSIONS: Serum uric acid increases in proportion to haemodynamic severity in adult patients with Eisenmenger syndrome and is independently associated with long term mortality.

Adolescent↗
PubMed2000

Haemodynamic and hormonal effects of adrenomedullin in patients with pulmonary hypertension.

OBJECTIVE: To investigate whether infusion of adrenomedullin, a potent vasorelaxant peptide, has beneficial haemodynamic and hormonal effects in patients with pulmonary hypertension. PATIENTS AND DESIGN: The haemodynamic and hormonal responses to intravenous infusion of adrenomedullin (0.05 microgram/kg/min) or placebo were examined in 13 patients with precapillary pulmonary hypertension. RESULTS: Infusion of adrenomedullin produced a 44% increase in cardiac index (mean (SD) 1.8 (0.2) to 2.6 (0.3) l/min/m(2), p < 0. 05) and a 32% decrease in pulmonary vascular resistance (19.7 (1.4) to 13.4 (1.3) units, p < 0.05), with a 4% reduction in mean pulmonary arterial pressure (62 (4) to 59 (4) mm Hg, NS). Adrenomedullin also decreased mean systemic arterial pressure (81 (3) to 72 (4) mm Hg, p < 0.05) and increased heart rate (73 (4) to 79 (4) beats/min, p < 0.05). Adrenomedullin decreased plasma aldosterone (9.8 (2.5) to 7.1 (1.5) ng/dl, p < 0.05) without significant changes in plasma renin activity. Plasma atrial and brain natriuretic peptides tended to decrease with adrenomedullin, although these changes did not reach significance. The haemodynamic and hormonal variables remained unchanged during placebo infusion. CONCLUSIONS: Intravenous adrenomedullin has beneficial haemodynamic and hormonal effects in patients with precapillary pulmonary hypertension.

Adrenomedullin↗