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Biomedical subjects

T Satoh

Publications and source records attributed to T Satoh.

At least 523 records · Page 29Linked to original sources
PubMed1996

Functional CD86 (B7-2/B70) on cultured human Langerhans cells.

CD86 (B70/B7-2) has recently been identified as an alternative CD28/CTLA-4 ligand on activated B cells. CD86 has also been demonstrated as possibly serving as a primary costimulatory molecule in the initial immune response. Since the human Langerhans cell is one of the most potent antigen-presenting cells, we examined whether CD86 expression and function are found on organ-cultured skin, freshly isolated Langerhans cells, and cultured Langerhans cells in normal human epidermis. Immunohistochemical study in situ revealed that CD86 was expressed on dendritic cells with CD1a antigen in organ-cultured but not fresh skin. Fluorescence-activated cell sorter analysis revealed that no staining for either CD80 or CD86 was observed in freshly isolated Langerhans cells but that both CD80 and CD86 were expressed on cultured Langerhans cells. The actual expression of CD86 on cultured Langerhans cells was further confirmed by the detection of 70-kDa glycoprotein on Western blot analysis. Analysis of polymerase chain reaction demonstrated that both CD80 and CD86 were specifically amplified from purified cultured and freshly isolated Langerhans cells but not from Langerhans cell-depleted epidermal cells, indicating that both CD80 and CD86 genes were expressed by Langerhans cells. The functional importance of CD86 on Langerhans cells was confirmed by the allogeneic CD4 T cell proliferative responses with enriched Langerhans cells. A monoclonal antibody against CD86 caused 81% inhibition in contrast with 29% inhibition produced by anti-CD80 monoclonal antibody. This inhibitory effect was enhanced to 85.3% inhibition when a combination of anti-CD86 and anti-CD80 was administered. These results indicate that CD86 is predominantly expressed on the surface of cultured Langerhans cells and may transduce a primordial costimulatory signal in the interaction of Langerhans cells and T cells.

Antibodies, Monoclonal↗
PubMed1996

Giant retroperitoneal cyst in an adult male.

This paper presents a case of a symptomatic giant retroperitoneal cyst in an adult male. The unilocular cyst was excised successfully with resolution of the attendant symptoms. Histological findings of the cyst wall suggested a lymphangiomatous etiology. Any good risk patient found to harbor such a cyst should undergo complete excision in view of the potential for the development of symptoms and complications.

Cysts↗
PubMed1996

Unequal atrial stretch in dogs increases dispersion of refractoriness conducive to developing atrial fibrillation.

INTRODUCTION: We have shown previously that acute atrial dilation prolonged atrial refractoriness. We hypothesized that this increase in refractoriness might be heterogeneous and could create an electrophysiologic substrate leading to atrial fibrillation. The purpose of the present study was to test that hypothesis. METHODS AND RESULTS: We studied 23 anesthetized open chest dogs. Bipolar plunge electrodes were placed in the medial free wall of the right atrium (thin region) and in the lower crista terminalis of the right atrium (thick region). Two bipolar plunge electrodes were also placed in the left ventricular apex to stimulate and record. Atrial effective refractory period (ERP) was measured in a group of nine dogs using the atrial extrastimulus method (A1A2) in two ways: during atrial pacing (AP) and during simultaneous atrioventricular (AV) pacing that achieved and AV interval of 0 msec (AV = 0). One liter/hour of normal saline was infused intravenously to elevate right atrial pressure and produce right atrial stretch. Atrial ERPs were measured before and after the normal saline infusion. To compare the extent of atrial stretch produced by volume overload, two pairs of sonomicrometer transducers were implanted in the thick and thin regions in a separate group of six dogs. The area encompassed by sonomicrometers was measured before and after saline infusion. The inducibility of atrial fibrillation was compared before and after saline infusion using rapid AP in another group of five dogs. Atrial pressure during sinus rhythm increased from 5.1 +/- 0.96 mmHg to 6.3 +/- 0.93 mmHg after normal saline infusion (P < 0.01). ERP increased in the thin free wall from 151 +/- 14.3 to 172 +/- 14.7 msec (AV = 0), and from 169 +/- 12.0 to 170 +/- 14.3 msec (AP). ERP increased in the thick crista terminalis from 134 +/- 9.9 to 147 +/- 10.2 msec (AV = 0), and from 133 +/- 7.9 to 146 +/- 9.8 msec (AV) (P < 0.01). The increase in ERP in the thin free wall exceeded that in the thick crista terminalis (P < 0.01), increasing the dispersion of atrial ERP. After 500-mL saline infusion for 30 minutes, the increase of area in the thin region was 12.8% +/- 3.7%, and that in the thick was 3.5% +/- 3.2%. The increase of the area in the thin region after 1000 mL for 1 hour was 18.8% +/- 6.2%, and that in the thick region was 6.3 +/- 5.1% (P < 0.01). Atrial fibrillation was not induced in any dog before infusion, but induced in all five dogs after saline infusion. CONCLUSIONS: Atrial ERP in the thin right atrial free wall exceeds the ERP of the thick crista terminalis, and an increase in atrial pressure produced by saline infusion exaggerates this difference by stretching thin segments of the atrial myocardium more than it stretches thick regions. Thus, atrial stretch, by increasing the dispersion of atrial ERP, may be conducive to the development of atrial fibrillation.

Action Potentials↗
PubMed1996

Localization of hyaluronan in human liver sinusoids: a histochemical study using hyaluronan-binding protein.

Circulating hyaluronan is mostly derived from lymph, fibroblast and Ito cells in the liver, and more than 90% of hyaluronan is degraded in hepatic sinusoidal endothelial cells. Thus, elevated serum hyaluronan is regarded as an indication of hepatic fibrosis with activated Ito cells and dysfunctional sinusoidal endothelial cells. We studied the distribution of hyaluronan in human liver sinusoids to determine the influences on elevated hyaluronan levels in sera. Histochemical examination was made using hyaluronan-binding protein (HABP) and serial sections of liver tissue for staining of alpha-smooth muscle actin (ASMA) (an indicator of activated Ito cells) and of ulex europaeus agglutinin I lectin (UEA-1) (closely related to hepatic sinusoidal capillarization). Positive staining, indicating the presence of hyaluronan, was noted in fibrous regions around the portal tracts, areas of focal necrosis in the liver parenchyma, and walls of the sinusoids in chronic hepatitis. In this group, hyaluronan-positive areas corresponded to positive ASMA staining and faint staining of UEA-1. On the contrary, in liver cirrhosis, UEA-1-positive areas were essentially identical to hyaluronan-positive areas and to ASMA-negative areas in sinusoidal walls. Hyaluronan and ASMA could be detected in the same areas of sinusoidal walls in chronic hepatitis, but not in liver cirrhosis. Hyaluronan appears to be mainly related to the staining of activated Ito cells in chronic hepatitis. Therefore, we concluded that in chronic hepatitis, the production of hyaluronan was accelerated in Ito cells; however, degradation of hyaluronan by sinusoidal endothelial cells continued. On the contrary, in liver cirrhosis, hyaluronan production decreased in Ito cells, and a marked transformation of sinusoidal endothelial cells with hepatic sinusoidal capillarization indicated loss of the ability to degrade hyaluronan. These different mechanisms in chronic hepatitis and liver cirrhosis may operate in the sinusoidal walls and may cause the elevation of hyaluronan in sera.

Biomarkers↗
PubMed1996

Pharmacological analysis of local anaesthetic tolycaine-induced convulsions by modification of monoamines in rat brain.

The effects of a local anaesthetic, tolycaine, on brain monoamine levels were investigated during the convulsive process in rats. The influence of central monoamine modifications on tolycaine-induced convulsions was also examined. Tolycaine (140 mg/kg, intraperitoneally) produced a significant elevation of noradrenaline and 5-hydroxytryptamine levels in all brain regions in the convulsive state from the levels in the non-convulsive state. Their levels returned to normal during the postconvulsive state. Dopamine levels were depleted in the cerebral cortex, the striatum, and the ponsmedulla oblongata during the convulsive process and increased in the cerebellum. Pretreatment with alpha-methyl-p-tyrosine, which depletes brain catecholamine, suppresses the tolycaine-induced convulsions, as shown by a decrease in the incidence; L-3,4-dihydroxyphenylalanine and bis-(1-methyl-4-homopiperazinyl-thiocarbonyl)-disulfide, which increase brain catecholamine, intensified the convulsions, as shown by shortening of the latency and increase in the mortality. Antagonists of beta-adrenergic and dopamine receptors, such as propranolol, chlorpromazine and pimozide, markedly suppressed the convulsions, but an antagonist of alpha-adrenergic receptor, phenoxybenzamine, had no effect. Furthermore, 5-hydroxytryptophan, which increases brain 5-hydroxytryptamine, suppressed the convulsions, and DL-p-chlorophenylalanine, which depletes brain 5-hydroxytryptamine, intensified them. Antagonists of 5-hydroxytryptamine receptor, methysergide and methiothepin, suppressed the convulsions. These results suggest that brain noradrenaline and 5-hydroxytryptamine are major regulators in the tolycaine-induced convulsive process and that central catecholaminergic neurones act in a stimulatory way on the tolycaine-induced convulsions, while serotonergic neurones act suppressively.

Adrenergic Agents↗
PubMed1996

Inhibition of the accumulation of uremic toxins in the blood and their precursors in the feces after oral administration of Lebenin, a lactic acid bacteria preparation, to uremic patients undergoing hemodialysis.

The plasma levels of phenol, p-cresol, and indican are markedly increased in uremic patients, and cannot be efficiently reduced by hemodialysis. Such uremic toxins, which are produced in the intestine as bacterial putrefactive metabolites, accumulate to a great degree in the feces of hemodialysis patients. Oral administration of Lebenin, a preparation consisting of antibiotic-resistant lactic acid bacteria, reduced the levels of fecal putrefactive metabolites to levels comparable with those of healthy subjects. Moreover, the plasma level of indican also significantly decreased in these Lebenin-treated patients. An analysis of the fecal microflora revealed that a disturbed composition of the microflora characterized by an overgrowth of aerobic bacteria is restored to normal by oral administration of Lebenin in hemodialysis patients. These results thus demonstrate that oral administration of lactic acid bacteria in uremic patients is effective in reducing the levels of uremic toxins, especially that of indican, in the blood by inhibiting bacterial production by means of correcting the intestinal microflora.

Administration, Oral↗
PubMed1996

Pharmaceutical properties of freeze-dried formulations of egg albumin, several drugs and olive oil.

The freeze-dried ternary formulations of meclizine (MZ, an anti-motion sickness drug), prednisolone (PRED, an anti-inflammatory drug) and norfloxacin (NFLX, an anti-microbial drug) which are poorly water-soluble and are low bioavailability drugs, were prepared using egg albumin and olive oil. The powder X-ray diffractions, the dissolution rate and the bioavailabilities in vivo of these formulations were studied in comparison with each drug alone. By forming ternary formulations of these drugs, the dissolution rates of the drugs from the formulations were significantly improved compared with each drug alone. The results of their powder X-ray diffraction measurements showed that these drugs in the ternary formulations presented in an amorphous form, indicating increased dissolution rates. On the other hand, the plasma concentrations of these drugs increased significantly after oral administration in formulations to rats, except for the NFLX formulation, and the areas under the concentration-time curves (AUC) of the ternary formulations of MZ, PRED and NFLX were 2.1, 1.6 and 1.3 times those of the drugs alone, respectively. From these results, it was proven that formulations consisting of egg albumin, olive oil and poorly water-soluble drugs were useful preparations for improving the drug's disadvantageous pharmaceutical properties.

Administration, Oral↗
PubMed1996

Differences in the induction of carboxylesterase RL4 in rat liver microsomes by various perfluorinated fatty acids, metabolically inert derivatives of fatty acids.

Differences in the ability of metabolically inert peroxisome proliferators [perfluoro-n-decanoic acid (PFDA, C10), perfluoro-n-octanoic acid (PFOA, C8), perflorooctane sulfonic acid (PFOS, C8) and 1H,1H-pentadecafluoro-n-octanol (PFOL, C8)] to induce liver microsomal carboxylesterase RL4 in male rats were studied by evaluating changes in the RL4 content by immunoblot analysis with a specific antibody. The administration of PFOA, PFOS and PFOL markedly increase the content of carboxylesterase RL4. On the other hand, PFDA decreases PNPA, BUTA, and ISOC hydrolase activity, and slightly increases the carboxylesterase RL4 content.

Alkanesulfonic Acids↗
PubMed1996

[Studies on solid phase extraction of bile acids from biological matrix].

To quantify bile acids in biological samples, a solid phase extraction method was examined. This method is known as simpler procedures with less contamination compared with solvent extraction methods. Rat bile, feces and urine were used as biological samples. Since Bond Elut C18 and C8 were proved to be more suitable than the other phases (CH and SAX) so far examined using standard bile acids, Bond Elut C18 was used for biological samples. Quantification of biological sample was carried out by gas chromatography after the extracted sample was derivatized to methyl ester by treatment with trimethylsilyldiazomethane then to trifluoroacetyl ester by trifluoroacetic anhydride. On the gas chromatography, two columns (Rtx-50 and Rtx-200) were connected to the injector with Y-tube for elimination of interference. Except for a few bile acids, high recovery with less biological contamination was obtained by this solid phase extraction method.

Animals↗
PubMed1996

Activity immediately before the onset of non-fatal myocardial infarction and sudden cardiac death.

To investigate triggers for the occurrence of acute myocardial infarction (AMI) and sudden cardiac death (SCD), we examined the activities immediately before the time of onset in 149 cases of non-fatal AMI and 110 cases of SCD. All of the cases in which death occurred within 24 h from the onset of the underlying cause were considered SCD as long as the cause of death was of cardiac origin or unknown. We calculated the average time which is spent on each activity in the life cycle of Japanese people and estimated the number of incidence of each activity assuming a uniform distribution. Estimated values and actual values were compared. The results were as follows: 1) The incidence of non-fatal AMI and SCD was low while sleeping or resting or doing light work, and was high while using the toilet or doing sport or heavy work. 2) the incidence of SCD was also high even during moderate exertion, such as taking a bath or, walking or cycling, and it was significantly higher than that in the group of non-fatal AMI. 3) The incidence of non-fatal AMI was high while eating or drinking. 4) Many of the patients with SCD had past histories of circulatory diseases, compared to those with non-fatal AMI. This difference in past histories may account for the high incidence of SCD during moderate exertion.

Activities of Daily Living↗
PubMed1996

Influence of cholesterol feeding on bile acid metabolism in young and aged germ-free rats.

The effects of cholesterol feeding on serum and liver cholesterol levels, fecal and biliary bile acid levels, bile acid pool size and bile acid composition were examined in 2-, 12- and 24-month-old male germ-free rats. The major bile acids in these animals were cholic and beta-muricholic acids. Cholesterol feeding increased synthesis of bile acids by 3- to 4-fold, especially that of chenodeoxycholic acid (mainly beta-muricholic acid in the rat), decreasing the cholic acid/chenodeoxycholic acid (CA/CDCA) ratio in all rats regardless of age, even though the CA/CDCA ratio increased as a linear function of age in both diet groups. Cholesterol feeding increased the serum cholesterol level markedly in aged rats. This hypercholesterolemia may be produced by the increase in CA/CDCA ratio in aged rats.

Aging↗
PubMed1996

Telomere position on the cat chromosome.

The telomere in the cat chromosome was detected by the fluorescence in situ hybridization method using all human telomere as a probe. In the metaphase chromosomes of cultured peripheral lymphocytes, telomere spots were observed in the terminal portions of the chromosomes. Although telomeres were confirmed in all chromosomes, the fluorescence intensity varied between the two homologues in some chromosomes.

Animals↗
PubMed1996

Specificity of substrate and inhibitor probes for cytochrome P450s: evaluation of in vitro metabolism using cDNA-expressed human P450s and human liver microsomes.

1. We evaluated the specificity of 15 substrates and 14 inhibitors of the cytochrome P450s using nine human P450 forms expressed in HepG2 cells using a recombinant vaccinia virus and also in human liver microsomes. 2. Coumarin, 7-ethoxyresorufin, 7-benzyloxyresorufin, tolbutamide, aniline and diazepam were form-selective substrates towards CYP2A6, the CYP1A subfamily, CYP2B6, the CYP2C subfamily, CYP2E1 and the CYP3A subfamily respectively. However, a selective substrate for CYP2D6 was not found among the chemicals tested. 3. SKF-525A inhibited > 40% of the metabolic activity of all substrates tested, and the inhibitory effects differed among P450 forms. Sulphaphenazole, 7,8-benzoflavone, quinidine and troleandomycin were selective inhibitors of the CYP2C subfamily (except CYP2C19), the CYP1A subfamily, CYP2D6 and the CYP3A subfamily respectively. Methoxsalen (CYP2A6 inhibitor) inhibited the metabolic activity of CYP1A2 as well as that of CYP2A6. Diethyldithiocarbamate (CYP2E1 inhibitor) inhibited the metabolic activities of CYP2A6 and CYP2C19 in addition to that of CYP2E1. 4. Our results indicated that substrates and inhibitors reported as P450 selective probes are not necessarily specific for individual human P450 forms. These results may provide useful information regarding human P450 substrates and inhibitors in vitro using human liver microsomal samples.

Blotting, Western↗
PubMed1996

Human liver microsomal diazepam metabolism using cDNA-expressed cytochrome P450s: role of CYP2B6, 2C19 and the 3A subfamily.

1. We have examined the metabolism of diazepam by ten human cytochrome P450 forms (CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4 and 3A5) expressed in HepG2 cells using a recombinant vaccinia virus system. 2. Among the P450 forms tested, diazepam was significantly demethylated by CYP2B6, 2C9, 2C19, 3A4 and 3A5, with 2C19 exhibiting the highest rate at concentrations < 0.1 mM, and hydroxylated only by the latter three enzymes, with 3A5 being the most active. The N-demethylation activity of diazepam by 2C19 at a concentration of 20 microM was six times of that by 3A4. However, that by 2C9 was detected at only a trace level. 3. CYP2C19, 3A4 and 3A5 of the ten human P450s catalysed the 3-hydroxylation of nordiazepam, and 2B6, the 2C subfamily and the 3A subfamily catalysed the N-demethylation of temazepam. CYP3A4 exhibited the highest activity of nordiazepam 3-hydroxylation and temazepam N-demethylation. 4. Diazepam N-demethylation by human liver microsomes correlated with diazepam 3-hydroxylation, but not S-mephenytoin 4'-hydroxylation. 5. Our results suggest that in the human liver, the metabolism of diazepam to nordiazepam is mediated by CYP3A4, which has been reported as the most abundant P450 form in human liver as well as 2C19, which has been reported as a polymorphic enzyme.

Anti-Anxiety Agents↗
PubMed1996

Altered bile acid metabolism related to atherosclerosis in alloxan diabetic rats.

Normal and alloxan diabetic rats were kept on a 0.25% cholesterol diet for 12 months and the changes in serum cholesterol levels, and fecal excretion of sterols and bile acids were examined to elucidate the influence of changes in bile acid metabolism on manifestations of hypercholesterolemia and development of atheromatous lesions. Diabetic rats fed the cholesterol diet showed increases in bile acid synthesis and in the cholic acid group/chenodeoxycholic acid group (CA/CDCA) ratio, and developed significant hypercholesterolemia and atheromatous lesions. In contrast, normal rats showed increased bile acids synthesis but a decreased CA/CDCA ratio after feeding with the cholesterol diet, and developed neither hypercholesterolemia nor atheromatous lesions. Fecal sterol excretion and the cholesterol/sitosterol ratio decreased in diabetic rats. Positive correlations were found between the cumulative serum cholesterol level and the atheromatous lesion area, and between the fecal CA/CDCA ratio and the serum cholesterol level, in the latter of which the correlation was higher in rats on the cholesterol diet than in those on the standard diet. These findings suggest that alteration of bile acid metabolism with increases in cholic acid synthesis and CA/CDCA ratio in diabetic rats enhances cholesterol absorption to produce significant hypercholesterolemia, which in turn leads to development of atheromatous lesions.

Alloxan↗
PubMed1996

[Endobronchial malignant lymphoma of mucosa-associated lymphoid tissue].

A 56-year-old man presented with pulmonary infiltrates. A chest roentgenogram revealed infiltrates in the left upper lobe and a tomogram showed obstruction of the left upper lobe bronchus. Computed tomography of the chest confirmed the presence these infiltrates, and no lymphadenopathy or mediastinal involvement was detected. At bronchoscopic examination, endobronchial masses were found. These masses almost completely obstructed the distal portion of the left upper lobe bronchus and partly obstructed the right upper lobe bronchus. A left upper sleeve lobectomy was done. Macroscopically, the tumor mass looked like a polypoid growth in the bronchial lumen. Microscopic examination showed that the tumor was composed mainly of small cleaved cells. These cells were observed to have infiltrated the epithelium to form lymphoepithelial lesions. Their B-cell origin was shown by the positive CD19 stain. Monoclonality of tumor cells was shown immunohistochemically and by hybridization techniques. Evidence of monoclonal B-cell proliferation was found in the rearrangement of Ig heavy- and light-chain genes, with Bam HI and Hind III digests. The final diagnosis was distinctive B-cell lymphoma (diffuse, small cell type) of mucosa-associated lymphoid tissue.

Bronchial Neoplasms↗