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Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 307 records · Page 17Linked to original sources
PubMed1996

In vivo microdialysis to determine the relative pharmacokinetics of drugs.

The purpose of this study was to evaluate a simultaneous microdialysis method in blood and brain striatum to determine the relative pharmacokinetics and metabolism of L-3,4-dihydroxypenylalanine (L-dopa). L-Dopa (250 mumol/kg) was administered to rats with or without the aromatic amino acid decarboxylase (AADC) inhibitor carbidopa (25 mumol/kg) or benserazide (25 or 62.5 mumol/kg). L-Dopa, its metabolites, and AADC inhibitors in dialysates were analyzed by high performance liquid chromatography with an electrochemical detector. A moment analysis was also made to obtain pharmacokinetic parameters. After administration of L-dopa alone, it and its related metabolites were detected in both dialysates of blood and brain striatum. Coadministration of carbidopa (25 mumol/kg) or benserazide (62.5 mumol/kg) significantly enhanced the striatal amount of L-dopa by 8.0 and 6.1 times, respectively. Carbidopa and benserazide also increased striatal amounts of L-dopa metabolites, such as 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylethyleneglycol. Inhibition effect of benserazide on an extracerebral decarboxylation of L-dopa to dopamine (DA) was stronger than that of carbidopa. Carbidopa showed a higher striatal level of DA than benserazide. These results suggest a different effect of the two inhibitors on the DA formations in blood and brain striatum, and on the L-dopa transport through the blood-brain barrier (BBB). Thus, microdialysis is an easy and available method for simultaneously assessing the in vivo relative pharmacokinetics and metabolism of drugs in systemic circulation and a target organ.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Forskolin derivatives. I. Synthesis, and cardiovascular and adenylate cyclase-stimulating activities of water-soluble forskolins.

Water-soluble forskolin and 7-deacetylforskolin derivatives with an aminoacetyl, a 3-aminopropionyl, or a 4-aminobutyryl group at the 6- or 7-position were prepared, and their positive inotropic as well as vasodilative activities were evaluated in anesthetized dogs. 7-Deacetylforskolin (2) and 7-deacetyl-1-silylforskolin (6) were converted to the corresponding 7-chloroacylderivatives (3, 7, 10), which were reacted with amines to obtain 7-aminoacyl-7-deacetylforskolins (4a-f, 9a, b, 11). The 7-acyl substituents migrated to the 6-position with sodium hydroxide in acetonitrile-water to afford 6-aminoacyl-7-deacetylforskolins (12a-f). The 7-position of 12a, d-f was selectively acetylated with acetyl chloride to obtain the corresponding 6-aminoacylforskolins (13a-d). Among the 6-aminoacylforskolins, 6-(3-dimethylaminopropionyl)forskolin (13b) and 6-(4-dimethylaminobutyryl)forskolin (13d) exhibited potent positive inotropic and vasodilative activities comparable to those of forskolin (1). The activities of 13b and 13d were approximately ten times more potent than those of 7-aminoacyl- and 6-aminoacyl-7-deacetylforskolins (4a-f, 9a, 12a-c, f). 6-Dimethylaminoacetylforskolin (13a) and 6-(3-diethylaminopropionyl)forskolin (13c) were less potent than 1. The effects of the soluble forskolins on adenylate cyclase activity were also examined in vitro. 6-Aminoacylforskolins (13a-d) exhibited potent adenylate cyclase-stimulating activity, comparable to that of 1.

Adenylyl Cyclases↗
PubMed1996

[Effect of human serum albumin on transport of drugs through human erythrocyte membranes].

The binding properties to human serum albumin (HSA) and the transport of drugs through human erythrocyte membranes were examined with benzoic acid or its twenty-five derivatives (o-, m-, or p-hydroxybenzoic acid, o-, m-, or p-aminobenzoic acid, o-, m-, or p-nitrobenzoic acid, o-, m-, or p-toluic acid, o-, m-, or p-fluorobenzoic acid, o-, m-, or p-chlorobenzoic acid, o-, m-, or p-bromobenzoic acid, aspirin, salicyluric acid, alpha-resorcylic acid and gamma-resorcylic acid) and with glycosides (arbutin, salicin, glycyrrhizin and four p-nitrophenylglycosides) or their aglycons (hydroquinone, saligenin, glycyrretinic acid and p-nitrophenol). The drugs having hydroxyl group and amino group to o-site and those having nitro group, methyl group and halogen group to m- or p-site showed higher affinity with HSA and the plasma hindered the permeability of these drugs. The glycosides bind to each site (1, 2, and 3) of HSA more weakly than do their aglycons and they were difficult for plasma to hinder membrane permeation. The binding constants of each drug to HSA (Kb-site 1, Kb-site 2, Kb-site 3 and Kb-total) and the inhibition ratio (IR) related to the partition coefficient (P): Kb-site 1 (M-1) = 2.1479 x 10(3).square root of P - 5.2824.P + 2.0985 x 10(3) (R = 0.9371), Kb-site 2 (M-1) = 4.3741 x 10(3).square root of P - 15.2068.P + 6.5660 x 10(3) (R = 0.6788), Kb-site 3 (M-1) = 2.2176 x 10(4).log P + 1.2022 x 10(4) (R = 0.5227), Kb-total (M-1) = 1.0214 x 10(4).square root of P - 33.3721.P + 1.6919 x 10(4) (R = 0.7413), IR (%) = 19.885.log P + 17.916 (R = 0.8605). IR obtained from predictive equations (IR = 17.837.log P - 13.286. log Kb-site 1 + 0.175.square root of Kb-site 2 + 0.074.square root of K b-site 3 + 37.355, R = 0.9642, F = 71.4937***, ***; p < 0.001) by multiple regression analysis was compatible with experimental IR.

Benzoates↗
PubMed1996

A case of adenosine-sensitive ventricular tachycardia in a very elderly male.

The best-known type of adenosine-sensitive ventricular tachycardia is idiopathic and of right ventricular outflow origin; however, there is little information about other types of adenosine-sensitive ventricular tachycardia. Idiopathic adenosine-sensitive ventricular tachycardia is common in the young. An 87-year-old man with ventricular tachycardia was admitted to our hospital. His ventricular tachycardia was sensitive to adenosine triphosphate, edrophonium, verapamil, and Valsalva's maneuver. He had experienced no anginal episodes. His ventricular tachycardia was thought to be idiopathic. We report this very rare case of adenosine-sensitive ventricular tachycardia, which was not derived from the right ventricular outflow tract, in a very elderly male.

Adenosine↗
PubMed1996

Purification and activity of recombinant chicken stem cell factor produced by using a baculovirus vector.

Stem cell factor is a pleiotropic cytokine that plays an essential role in the development of hematopoietic cells, germ cells, and melanocytes. To obtain recombinant soluble chicken stem cell factor (chSCF), a baculovirus containing the cDNA encoding chSCF polypeptide from amino acids -25 to 170 was constructed. The chSCF produced in insect cells infected with the virus was purified by ion exchange column chromatography. The ability of the purified protein to induce the outgrowth of neurites from chicken dorsal root ganglia cultured in vitro was demonstrated.

Animals↗
PubMed1996

The production of arthritis in beagles by an immunological reaction to bovine serum albumin.

Arthritis was produced in beagles by the immunological reaction to bovine serum albumin (BSA). Dogs immunized with BSA showed the development of delayed type-hypersensitivity response to BSA and the significant increase in the titer of serum anti-BSA antibodies. The development of arthritis and the increase in a number of nucleated cells in synovial fluid were observed by the injection with BSA into the knee joints of immunized dogs. The synovial membrane of BSA-injected joints revealed a remarkable villous hyperplasia of membrane, and an infiltration of lymphocytes and plasma cells around vessels, resulting in a lymphoid nodule-like formation. The depositions of IgG and C3 on the surface of the synovial membrane were also observed in BSA-injected joints. Histopathological and immunopathological findings indicated that the immune response to BSA in the knee joints could induce a rheumatoid arthritis like chronic synovitis in dogs.

Animals↗
PubMed1996

Is the intracellular pH threshold an anaerobic threshold from the view point of intracellular events?: a brief review.

Intracellular biochemical changes could be monitored noninvasivery and continuously by using nuclear magnetic resonance (NMR). In about the last decade, intracellular behavior of phosphorus compounds and pH during muscle contraction in man have been studied by 31P nuclear magnetic resonance spectroscopy (31P-MRS). During incremental load, lactic acidosis was followed by a decline in intracellular pH. 31P-MRS studies has been definitely proved that this change in intracellular pH shows the threshold behavior. Some reports discussed the intracellular pH threshold (pHT) as an anaerobic threshold (AT) from the view point of intracellular events. However, our studies revealed that pHT did not reflect the onset of lactate production. In this article, studies of intracellular pH of working muscle were reviewed in relation to an anaerobic threshold.

Anaerobiosis↗
PubMed1996

Water fraction of lumbar vertebral bone marrow estimated from chemical shift misregistration on MR imaging: normal variations with age and sex.

OBJECTIVE: Our objective was to use the chemical-shift misregistration effect of MR imaging to measure the variation in the water fraction in vertebral bone marrow with respect to patient age and sex. SUBJECTS AND METHODS: We examined prospectively 211 subjects (5-84 years old; 108 male and 103 female subjects) who had no history of hematologic disorders. We obtained midsagittal proton density-weighted spin-echo images (2500/22 [TR/TE]) with a narrow sampling bandwidth (6250 Hz). Misregistered signals from lipid protons of 6-10 mm (upward shift in the readout direction) were obtained with the chemical-shift effect. By measuring the mean signal intensities of the water voxels and the water-plus-lipid voxels, we calculated a region of interest in each vertebral body for L1 to L3. The water fraction of bone marrow was then calculated as 100 x (signal intensity of water voxels/signal intensity of water-plus-lipid voxels). Individual water fractions were calculated from the average values for the water fractions of the L1-L3 bodies. RESULTS: In the male subjects, the water fraction showed a rapid decrease in the older patients in the 5- to 34-year-old group. (Mean water fractions for male patients who were 5-14, 15-24, and 25-34 years old were 75.2%, 69.0%, and 53.7%, respectively.) For male patients more than 25 years old, the water fraction remained almost constant (approximately 50%). In female subjects who were 5-44 years old, the water fraction exceeded 69% and remained almost constant. However, the water fraction rapidly decreased in women more than 45 years old. (Mean water fractions for female patients who were 35-44, 45-54, and 55-64 years old were 70.9%, 61.1%, and 49.7%, respectively.) A comparison between male subjects and female subjects showed that the water fraction for women who were 25-54 years old exceeded the water fraction for men in the same age group (25-34 years old, p < .0001; 35-44 years old, p < .001; 45-54 years old, p < .05). CONCLUSION: MR imaging showed that male and female subjects convert hematopoietic marrow to fatty marrow in the lumbar vertebral bodies in significantly different ways. The data obtained for the normal water fraction of bone marrow may prove useful for evaluating diseases that affect marrow.

Adolescent↗
PubMed1996

Treatment with recombinant interferon-alpha 2a for patients with chronic hepatitis C: predictive factors for biochemical and virologic response. Osaka Liver Disease Study Group.

BACKGROUND: The heterogeneity of the hepatitis C virus (HCV) genome has been reported to be associated with the effectiveness of interferon therapy. We investigated the correlation of the viral and host factors, including the degree of sequence complexity of the HCV genome for responses to interferon-alpha in patients with chronic hepatitis C. METHODS: Ninety-seven patients received a 26-week course of recombinant interferon-alpha 2a therapy. The sequence complexity of the envelope 1-2 region was evaluated by polymerase chain reaction-mediated single-strand conformation polymorphism (PCR-SSCP) analysis. RESULTS: Of the 85 patients who completed the treatment, 31 (36%) achieved a sustained response, and 28 (33%) showed a sustained loss of HCV RNA. A low HCV RNA level, determined by the branched DNA probe assay, and serotype group 2 HCV correlated with a sustained response. In patients with serotype group 1 HCV of more than the threshold of the branched DNA probe assay, a band number on PCR-SSCP analysis of more than 2 could be associated with inefficacy of interferon therapy. Multivariate analysis in the 50 patients whose sera were available for all the virologic tests showed that only the HCV RNA level is independently predictive of a sustained response. CONCLUSIONS: Determination of the HCV RNA level is most important for predicting the response before interferon therapy. PCR-SSCP analysis may be useful as an additional test for patients with a high HCV RNA level of serotype group 1 HCV.

Adult↗
PubMed1996

Heterogeneous effects of G-CSF and GM-CSF on cell growth and ara-C cytotoxicity in childhood leukemias which express myeloid markers.

It is uncertain if acute lymphoblastic leukemia (ALL) cells expressing myeloid makers can respond to granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF). We investigated the effects of G-CSF (0.01 microgram/ml) and GM-CSF (0.01 microgram/ml) on [3H]thymidine (TdR) uptake, and the cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C) in leukemia cells from 17 pediatric patients. ALL cells without myeloid markers did not respond to G-CSF or GM-CSF. On the other hand, these cytokines enhanced the [3H]TdR uptake and cell growth, not only of AML cells but also of ALL cells expressing myeloid antigens. However, G-CSF and GM-CSF did not always enhance the growth inhibitory effect of the cell cycle specific drug ara-C when the cells were co-cultured with the drug. There was no relationship between cell growth and the amount of [3H]TdR incorporation or the intracellular ara-CTP level. These results indicate the heterogeneous effects of G-CSF and GM-CSF on cell growth and ara-C sensitivity in childhood leukemia cells.

Adolescent↗
PubMed1996

Relationship between hepatic iron deposits and response to interferon in chronic hepatitis C.

OBJECTIVES: The response to interferon in chronic hepatitis C is believed to be affected by hepatic iron content. We histopathologically examined liver biopsy specimens from patients with chronic hepatitis C to determine whether the presence or absence of hepatic iron deposits correlated with the response to interferon. METHODS: Sixty-three patients with hepatitis C treated with interferon-alpha were examined. Liver biopsy specimens obtained just before treatment were sliced and stained with Perls' Prussian blue. Twenty patients had complete responses, 24 patients had transient responses, and 19 patients had no response. RESULTS: Iron deposits stained by Prussian blue were seen in hepatocytes, sinusoidal cells, and portal mesenchymal cells. The degree of hepatocytic and sinusoidal iron deposits did not correlate with the response to interferon. However, the degree of portal iron deposits did correlate with hepatic inflammation activity (tau = 0.55, p < 0.001) and the severity of liver fibrosis (tau = 0.60, p < 0.001), and it correlated negatively to the response to interferon (tau = -0.49, p < 0.001). CONCLUSIONS: The results suggest that portal iron deposits are a factor in the response to interferon. The presence of portal iron deposits seems to be related to a poor response.

Adult↗
PubMed1996

Development of intralobular bile ductules after spontaneous hepatitis in Long-Evans mutant rats.

Oval cell proliferation occurs during spontaneous hepatitis in Long-Evans cinnamon (LEC) rats. It has been reported that oval cells undergo differentiation into mature hepatocytes via small hepatocytes during carcinogenesis. This study was designed to demonstrate in vivo differentiation of oval cells into typical bile ductular cells in the liver lobule and the characteristic feature of intralobular bile ductule formation in LEC rats. We have examined kinetics, intralobular distribution, and morphology of oval cells, small hepatocytes, and bile ductular cells in LEC rat livers at prehepatitic, acute hepatitic, chronic hepatitic, and precancerous stages by conventional light and electron microscopy, immunostaining for cytokeratin, and 3-dimensional reconstruction analysis. Our results indicate that oval cells proliferated and extended into the periportal zone of the liver lobule during acute hepatitis at 20 to 23 weeks after birth. They exhibited tubular structures with a poorly defined lumen and incomplete basement membrane. After remission of the jaundice, small hepatocytes proliferated in association with oval cells and predominated in the periportal zone at 26 weeks. In a chronic hepatitic stage at 28 to 30 weeks, tubular structures were transformed into typical bile ductules, which had a well defined lumen and complete basement membrane, and small hepatocytes became a normal size. Intralobular bile ductules originated from the interlobular bile ducts, ran in the space of Disse, giving rise to several branches in the course, and were terminated at the hepatocytes. The present results indicate that oval cells that proliferate in the liver lobule of LEC rats after spontaneous hepatitis not only differentiate into small hepatocytes but also into typical bile ductular cells. This study suggests that intralobular bile ductules may play roles in maintaining the bile excretion during and after the disorganized proliferation of oval cells and small hepatocytes.

Animals↗
PubMed1996

[Results of patch tests with mite components in atopic dermatitis patients].

House dust mite lipids were investigated in atopic dermatitis (AD) patients. The analysis showed that eicosapentaenoic acid (EPA) was present at 0.88% in total lipid of Dermatophagoides farinae (Df). In the patch tests with crushed 3 live Dfs, the difference of positive rates between AD patients and controls was statistically significant. In the patch test with secretions from opisthonotal glands of mites, 2% citral contained in both D. pteronyssinus (Dp)s and Dfs showed higher rate of positivity with AD patients than controls without statistically significance. In the patch test with the fatty acids of house dust mites, EPA showed higher rate of positivity with AD patients than controls. There was a statistical significance with 100% (as is) EPA. Histopathological findings by hematoxylin and eosin staining with the skin lesions of AD patients and the positive reactions of patch test with crushed 3 live mites and EPA revealed spongiosis in the epidermis and infiltration of mononuclear cells in the upper dermis. The positive subsets of the mononuclear cells were mostly CD4, HLA-DR and ICAM 1, while CD8 positive cells were rare. Based on these findings, not only mite protein but also mite lipids including secretions from mites should be investigated as mite contact allergens in AD.

Animals↗
PubMed1996

Intracellular localization of antigens recognized by anti-vimentin monoclonal antibodies (mAbs): cross-reactivities of anti-vimentin mAbs with other cellular components.

Monoclonal antibodies were raised against immunoaffinity-purified fusion regulatory protein (FRP)-1 complex from membrane fraction of HeLa cells. Immunoblotting and immunoprecipitation studies showed all ten antibodies reacted with a 55 kDa band of cell lysate and purified vimentin. Interestingly, one of the antibodies (mAb57) cross-reacted with purified tropomyosin and myosin. Further analyses using vimentin chemically cleaved by 2-nitro-5-thio-cyanobenzoic acid, and lambda gt 11 cDNA which encoded a partial sequence of vimentin indicated that six mAbs recognized epitopes between amino acids 1 and 313 and the other four mAbs recognized epitopes in the area between residues 314 and 326. Indirect immunofluorescence microscopy using 3% formalin-fixed, 0.1% Triton X-100 treated HeLa cells revealed that seven antibodies stained various intracellular components other than vimentin, while three antibodies stained vimentin filaments alone. Furthermore, flow cytometric analysis showed one of the antibodies (mAb25) clearly stained the surface of unfixed HeLa cells. All immunofluorescent findings were the same when HeLa, baby hamster kidney (BHK) and murine L229 cells were examined. These results indicate that we could obtain unique anti-vimentin mAbs which show cross-reactivities with previously undescribed cell surface and intracellular molecules including tropomyosin and myosin. Taken together, there are two possibilities that explain our findings: (1) The unknown molecules may have structural similarity to vimentin. (2) Our anti-vimentin mAbs can react specifically with structurally distinct epitopes present on both unknown molecules and vimentin. In either case, our cross-reactive mAbs, which recognized undescribed epitopes on vimentin, maybe provide useful tools for studying intermediate filaments and related cellular components.

Animals↗
PubMed1996

Rhabdomyolysis following administration of cyclophosphamide: a case report in a BMT recipient.

Massive rhabdomyolysis followed by myocardial necrosis was observed in a 14-year-old patient undergoing allogeneic bone marrow transplantation for severe aplastic anemia. Rhabdomyolysis was preceded by the administration of cyclophosphamide as part of a preparative regimen for transplantation Although the specific etiology of this rhabdomyolysis is still unknown, an association with high-dose cyclophosphamide should be noted.

Bone Marrow Transplantation↗
PubMed1996

[Optimum dose study of cefozopran in the pediatric field].

Cefozopran (SCE-2787, CZOP) was administered to patients with pediatric infections three to four times daily by intravenous injection or 30-minute intravenous drip infusion, and investigations were made in individual cases, on relationships among doses, pharmacokinetics, effects on pathogenic bacteria and MIC against them, and clinical effects. The following results on optimal doses of CZOP were obtained. 1. Clinical cases in which CZOP was administered at a dose of 10 mg (potency)/kg The subjects were 7 patients including 4 patients with pneumonia. Severities of the diseases were severe in one of the patients with pneumonia, and moderate in the other patients. The MIC against pathogenic bacteria (4 strains) isolated from these cases ranged from 0.2 to 1.56 micrograms/ml. The serum concentrations were in a range between 1.4 and 7.6 micrograms/ml at 4 hours after administration. In some cases, the serum concentrations were lower than the MICs, though slightly. In the clinical evaluation, CZOP was excellent in 3 cases, good in 2 cases and fair in 1 case. The evaluation was impossible in 1 case. The efficacy rate was 83.3% (5/6). In bacteriological evaluation, 3 out of the 4 strains disappeared. Adverse reactions and abnormal laboratory test values were not observed. 2. Cases in which CZOP was administered at a dose of 20 mg (potency)/kg The subjects were 5 patients including 2 with pneumonia, and severities were severe in one of the patients with pneumonia, and moderate in the other patients. The MICs against the pathogenic bacteria (3 strains) isolated from these cases ranged from 0.1 to 1.56 micrograms/ml. While, serum concentrations at 4 hours after administration were in a range between 3.0 and 7.7 micrograms/ml sufficiently exceeding the MICs. In the clinical evaluation, CZOP was excellent in 1 case and good in four cases, with an efficacy rate of 100% (5/5). In the bacteriological evaluation, all the 3 strains disappeared. No adverse reactions were observed, but an abnormal laboratory test value showing eosinophilia was noted in one case. 3. Cases in which CZOP was administered at a dose of 40 mg (potency)/kg The subjects were 5 patients including 3 with pneumonia. The severity was moderate in 2 of the pneumonia patients, and severe in the other three cases. The MICs against the pathogenic bacteria (4 strains) isolated from these cases were in a range between 0.1 and 0.78 micrograms/ml. The serum concentrations at 4 hours after administration ranged from 6.5 to 21.9 micrograms/ml, sufficiently exceeding the MICs. In the clinical evaluation, CZOP was excellent in 4 cases and good in 1 case, with an efficacy rate of 100% (5/5). The efficacy rate in the bacteriological evaluation was also 100%. As adverse reaction, red urine was observed in one case. Eosinophlia was noted in one case in the laboratory tests. When CZOP was administered to patients with pediatric infections at a dose of 10 mg (potency)/kg, the clinical effect of the drug was insufficient in a case in which serum concentration of CZOP at 4 hours after administration was lower than the MICs against the pathogenic bacteria. When CZOP was administered at a dose of 20 mg (potency)/kg, sufficient concentrations were obtained, and the drug efficacies were found to be excellent or good in all cases. Therefore, the effective dose normally used is considered to be 20 mg (potency)/kg. When CZOP was administered at a dose of 40 mg (potency)/kg, the drug was found to be excellent or good in all of the cases although the severities were high in more than half of the cases tested. In addition, the rate of excellent efficacies was 80% (4/5). Furthermore, no severe adverse reactions were observed. It was, therefore, confirmed that CZOP should be administered at a dose of 40 mg (potency)/kg in severe or intractable cases.

Bacterial Infections↗
PubMed1996

Recurrent cold hemagglutinin disease following allogeneic bone marrow transplantation successfully treated with plasmapheresis, corticosteroid and cyclophosphamide.

A 10-year-old male with severe aplastic anemia following allogeneic BMT developed a hemolytic crisis on post-BMT day 67. The diagnosis of cold hemagglutinin disease was made based on the findings of anemia, reticulocytosis, positive direct Coombs test, and markedly elevated cold agglutinins. Anti-nuclear antibody and anti-DNA antibody were also increased. Plasmapheresis was effective as an emergency measure. Corticosteroid after plasmapheresis had a transient effect. At the second episode of hemolysis 6 months after BMT, immunosuppressive therapy with cyclophosphamide plus corticosteroid was successfully administered without negative effect on engraftment.

Anemia, Aplastic↗