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H Shiono

Publications and source records attributed to H Shiono.

At least 37 records · Page 2Linked to original sources
PubMed2000

N-methylation ability for azaheterocyclic amines is higher in Parkinson's disease: nicotinamide loading test.

The discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) leads to the hypothesis that Parkinson's disease (PD) is may be initiated or precipitated by endogenous toxins by the mechanism similar to that of MPTP in genetically-predisposed individuals. The higher cerebrospinal fluid levels of N-methylated azaheterocyclic amines, such as beta-carboline and tetrahydroisoquinoline, have been found in parkinsonian patients compared with age-matched controls. To estimate the N-methylation ability for azaheterocyclic amines in parkinsonian patient, nicotinamide was dosed with 100 mg to 26 parkinsonians and 20 controls consisted of 16 other neurogenic disease patients and 4 healthy volunteers. The urine was collected for 4 h, and then analyzed urinary its metabolites by an improved HPLC method. Nicotinamide has a pyridine ring in its structure and may be metabolized through the pathways similar to those for the endogenous neurotoxins. The urinary excretions of nicotinamide metabolites were significantly affected by aging. The excretion of N1-methylnicotinamide decreased along with aging both in PD patients and controls. In younger (65 years old or younger) PD patients, the excretion amount of N1-methylnicotinamide was significantly higher than that in younger controls. The decline rate of N1-methylnicotinamide excretion in parkinsonians was significantly greater than that in controls; the rate is more than 2-fold higher in parkinsonian patients. The age-associated decrease in 1-methyl-2-pyridone-5-carboxyamide excretion was observed only in parkinsonian patients, but not in controls. The total excreted amount of N-methylated metabolites (N1-methylnicotinamide plus 1-methyl-2-pyridone-5-carboxyamide) was also observed the age-related decline in both groups. The urinary excretions of nicotinamide and nicotinamide-N-oxide were not influenced by aging. These results would indicate that the excess N-methylation ability for azaheterocyclic amines before the onset had been implicated in PD. On the other hand, the present results suggested that the contribution of aberrant cytochrome P450 or aldehyde oxidase activity acting on the pyridine ring, that could act as detoxification routes of endogenous neurotoxins, would be small in the etiology of PD.

Aged↗
PubMed2000

The tissue distribution of lidocaine in acute death due to overdosing.

A 78-year-old woman committed double suicide with a bolus injection of 1 g of lidocaine hydrochloride. The tissue distribution of lidocaine in this fatal poisoning was investigated using an improved gas chromatographic method. The blood level was 42 microg/ml and the brain concentration was 70 miccro/g. Thus, the cause of death in this case was clearly diagnosed as lidocaine overdosing. The blood level of 42 microg/ml was higher than that calculated using the standard pharmacokinetic parameters. Lower blood/tissue ratios were also detected compared with the data described in the literature. These results indicated that the cardiac failure should have occurred immediately after the lidocaine injection. The present data show the distribution of lidocaine after acute death due to overdosing.

Journal Article↗
PubMed2000

Altered T cell development in human thymoma is related to impairment of MHC class II transactivator expression induced by interferon-gamma (IFN-gamma).

Thymoma is known to contain CD4+CD8+ T cells, indicating that neoplastic epithelial cells of thymoma have a function as thymic cortical epithelium. However, it has been shown that there is an impairment of CD4+ T cell development in thymoma and that IFN-gamma-induced HLA-DR expression on cultured thymic epithelial cells (TEC) derived from thymoma is decreased when compared with the normal thymus. MHC class II transactivator (CIITA) is known to play a critical role in IFN-gamma-induced MHC II expression. In this study, we attempted to elucidate whether CIITA is responsible for the impaired up-regulation of MHC II molecules in response to IFN-gamma in thymoma TEC. A quantitative reverse transriptase-polymerase chain reaction examination revealed that the induced level of CIITA was significantly lower in thymoma TEC than in normal TEC. The induced levels of invariant chain (Ii) and HLA-DR in thymoma TEC were correlated with CIITA expression. The proportion of CD3+ cells in the CD4+CD8- subset in thymoma was also correlated with CIITA expression. A gel mobility shift assay however, revealed translocation of STAT1 to the nucleus in thymoma as well as normal TEC. Intercellular adhesion molecule-1 was up-regulated in the thymoma TEC to a level similar to normal TEC in response to IFN-gamma. These results indicate that impaired up-regulation of HLA-DR in response to IFN-gamma results from insufficient induction of CIITA, but not from the signal from IFN-gamma receptor to the nucleus. The abnormal regulation of HLA-DR expression caused by impaired induction of CIITA may affect CD4+ T cell development in thymoma.

Adolescent↗
PubMed2000

Effect of intramammary infusion of tumour necrosis factor-alpha on milk protein composition and induction of acute-phase protein in the lactating cow.

The present study was designed to evaluate the effects of tumour necrosis factor-alpha (TNF-alpha) on lactating bovine mammary functions such as milk protein secretion and the integrity of the milk-blood barrier. The effect on the induction of the systemic inflammatory response was also examined using concentrations of serum haptoglobin (Hp), a major inflammatory acute-phase protein, as an index. One hundred micrograms per mammary gland of recombinant bovine (rBo) TNF-alpha or placebo saline was individually infused into a rear mammary gland of each of four lactating cows, and milk and blood samples were collected before and 4, 8, 24, 32, 48, 96 and 168 h after infusion. In the rBoTNF-alpha-infused gland, increases of somatic cell counts were observed at 4-48 h. Although concentrations of total milk protein were not changed, compositions of milk proteins varied following rBoTNF-alpha infusion. Concentrations of caseins, alpha-lactalbumin and beta-lactoglobulin were significantly decreased at 4 and 8 h. Lactoferrin concentrations were significantly increased at 4 h. Significant infiltrations of serum albumin, immunoglobulin G1 (IgG1) and IgG2 were observed at 4 and 8 h. Elevations of the serum concentration of Hp were detected at 8-32 h, but were very small in comparison with those reported in inflammatory diseases. Changes in rectal temperature and white blood cell counts were not significant. These results show that single rBoTNF-alpha infusion into the lactating mammary gland suppresses the lactogenic function of the gland and influences the function of the milk-blood barrier, with little effect on the generalized inflammatory response.

Acute-Phase Proteins↗
PubMed2000

Classification of standard alleles of the MN blood group system.

BACKGROUND AND OBJECTIVES: We had classified the M alleles of the MN blood group system into two subtypes, M(G) (standard M) and M(T), based on a G/T substitution in intron 1 of the glycophorin A (GPA) gene. This study provides further study on nucleotide sequences of M(G), M(T) and N alleles to profile the new allele, M(T). MATERIALS AND METHODS: M(G), M(T) and N alleles of the GPA gene were amplified using GPA gene-specific primers to avoid co-amplification of the genes of glycophorins B and E. Then the 5'-flanking region, exons 1-7 and introns 1-4 of the alleles were analyzed by DNA sequencing. RESULTS: There were 17 nucleotide substitutions and deletions between M(G) (standard M) and N alleles. Ten of the M(T) nucleotides were M(G)-type but the other 7 were N-type. M(T) allele also showed one base change and one deletion that were observed in neither the M(G) nor the N allele. Moreover, we found nucleotide substitutions within each allele, allowing further classification of the alleles. CONCLUSION: By the sequence data of M(G), M(T) and N alleles, the three alleles could be further classified into M101 and M102, M201 and M202, and N101 and N102, respectively.

Alleles↗
PubMed2000

Nitration of manganese superoxide dismutase in cerebrospinal fluids is a marker for peroxynitrite-mediated oxidative stress in neurodegenerative diseases.

Peroxynitrite can nitrate tyrosine residues of proteins. We examined nitrotyrosine-containing proteins in cerebrospinal fluid of 66 patients with neurogenic disease by immunoblot analysis. Nitrated tyrosine residue-containing protein was observed in the cerebrospinal fluid and was concluded to be manganese superoxide dismutase (Mn-SOD). The nitrated Mn-SOD level was strikingly elevated in amyotrophic lateral sclerosis patients and was slightly increased in Alzheimer's and Parkinson's disease patients, whereas an elevated Mn-SOD level was observed only in progressive supranuclear palsy group.

Adult↗
PubMed1999

Nitric oxide production by bronchoalveolar cells during allograft rejection in the rat.

BACKGROUND: We reported the increased nitric oxide (NO) level in exhaled air of rat lung transplant recipients during acute rejection (AR). The aim of this study was to determine the site and level of NO production in the rejected graft. METHODS: Rat lung transplantation was performed in isografts and allografts. RESULTS: In isografts, no AR and no significant increase in NO production was identified. In allografts, grades I-II of AR was seen on postoperative day (POD) 3 and grade III on POD 5. NO produced by BAL cells increased on both POD 3 (11.8+/-2.0 parts per billion [ppb]) and POD 5 (115.3+/-66.9 ppb). There was a highly significant correlation between the level of NO and the severity of AR (p=0.862, P<0.005). BAL cells from allografts expressed iNOS mRNA. Among them, macrophages, lymphocytes and neutrophils were immunostained for iNOS. CONCLUSION: NO produced by BAL cells was detected in the early stages of rejection. Therefore, it may serve as a sensitive indicator of AR in lung transplantation.

Animals↗
PubMed1999

The polymorphisms of DYS388 and DYS392 on the Y chromosome in Japanese and German populations.

The analysis of a genotype survey in Japanese and German populations at the loci DYS388 and DYS392 located on the Y chromosome is reported. The gene diversities of DYS388 were 0.34 and 0.30 in the Japanese and German males, respectively, and six alleles were found in both groups. The gene diversities of DYS392 were 0.65 and 0.64 and the number of alleles was 8 and 9, respectively in the two populations. The distribution of DYS388 alleles in the Japanese population was different from the German population. The allele distribution of DYS392 showed significant differences among Asian populations.

Asian People↗
PubMed1999

T-cell development in human thymoma.

Human thymoma is derived from thymic epithelial cells and often associated with a large number of cortical thymocytes. Since thymic epithelial cells play key roles in T-cell development in the normal thymus, we hypothesized that the neoplastic epithelial cells of thymoma may support T-cell differentiation. We attempted to reconstitute the T-cell development in vitro by using neoplastic epithelial cells isolated from thymoma. CD34, a stem cell marker, was expressed on a proportion of CD4-CD8- cells in thymoma. These CD34+CD4-CD8- cells also expressed both IL-7R alpha-chain and common gamma-chain. Purified CD4-CD8- cells from thymomas were cultured with the neoplastic epithelial cells, and their differentiation into CD4+CD8+ cells via CD4 single positive intermediates was observed within 9 days' co-culture in the presence of recombinant IL-7. The CD34+CD4-CD8- cells purified from a normal thymus also differentiated to CD4+CD8+ cells in an allogeneic co-culture with the neoplastic epithelial cells of thymoma. In addition, a pleural dissemination from thymoma contained a large amount of cortical thymocytes. These results suggest that the neoplastic epithelial cells retain the function of thymic epithelium and can support T-cell development in thymomas.

Adult↗
PubMed1999

Forensic diagnosis of death from cold.

To clarify the forensic diagnosis of hypothermia, the postmortem changes in the bodies of 211 cases of hypothermia (partly including death from diseases) encountered between January 1990 and January 1999 were studied as follows:i) The rectal temperature had been measured in 83 cases in which the time after death was known relatively clearly, and the rate of decrease in the rectal temperature per hour was evaluated. The rate of decrease in the rectal temperature was 2.3 +/- 1.2 degrees C, 2.7 +/- 1.5 degrees C and 3.6 +/- 1.9 degrees C per hour (mean +/- SD) when the ambient temperature was > or = 0 degrees C, 0 degrees C > to >-10 degrees C and -10 degrees C > or =, respectively. ii) The color of blood collected from the right and left hearts was different in 43 (33.6%) of the 128 cases of death from cold that underwent inquest and in 20 (87.0%) of the 23 cases that underwent forensic autopsy. This color difference was useful for the diagnosis of fatal hypothermia. iii) Gastric or duodenal submucosal bleeding (Wishnewski's spots) was noted in 10 (43.5%) of the 23 cases that underwent forensic autopsy. iv) Paradoxical undressing was observed in 35 (21.3%) of the 164 cases that underwent inquest.

Journal Article↗
PubMed1999

Impaired expression of MHC class II molecules in response to interferon-gamma (IFN-gamma) on human thymoma neoplastic epithelial cells.

A human thymoma is a neoplasm derived from the thymic epithelial cell, and is well known for its association with autoimmune diseases, especially myasthenia gravis. The neoplastic epithelial cells of thymoma clearly retain thymic epithelial functions, but the development of T cells in thymoma is somewhat impaired. In this study, we quantified by flow cytometry the in vitro expression of MHC molecules on neoplastic epithelial cells precultured with IFN-gamma. While MHC class I expression was comparable with that on normal thymic epithelial cells, the level of MHC class II molecules on neoplastic epithelial cells was lower than in controls, and also varied greatly from case to case. Additionally, there was a significant positive correlation between the expression level of MHC class II and the proportion of mature CD3+ cells in the CD4+CD8- subset. Thus, accumulation of CD3-CD4+CD8- cells in thymoma may result from impaired expression of the MHC class II molecules, suggesting that the function of the neoplastic epithelial cells might determine the maturation and the positively selected repertoire of T cells in thymomas.

Adult↗
PubMed1999

Preparation of chylomicrons and VLDL with monoacid-rich triacylglycerol and characterization of kinetic parameters in lipoprotein lipase-mediated hydrolysis in chickens.

To identify the substrate specificity of lipoprotein lipase (LPL) for triacylglycerol-rich lipoproteins with monoacid-rich triacylglycerols, monoacid-rich lipoproteins were prepared and kinetic parameters of LPL were characterized. Male broiler chickens were fed 8 g/100 g fat diets differing only in the fat source: palm oil (tripalmitin-rich), olive oil (triolein-rich), safflower oil (trilinolein-rich) and linseed oil (trilinolenin-rich). After diets were fed for 3 d, chickens were starved for 2 d and then force-fed emulsions containing one of the monoacid-triacylglycerols: tripalmitin, triolein, trilinolein or trilinolenin. The triacylglycerols in chylomicrons and very low density lipoprotein (VLDL) of chickens force-fed tripalmitin, triolein or trilinolein contained the corresponding acid at more than 70% of total acids. Linolenic acid was incorporated into chylomicrons and VLDL to a lower extent (51.2 and 57.2%, respectively) in chickens force-fed trilinolein. Major apolipoproteins and lipid compositions were not significantly different among all lipoproteins isolated from chickens fed the different fats. Vmax of LPL was significantly higher (P < 0.05) for palmitic acid-rich chylomicrons and VLDL and decreased with increasing chain length and unsaturation of monoacid: 16:0>18:1>18:2>18:3. The electron spin resonance analysis, order parameter (S), decreased with monoacid chain length and unsaturation. In addition, the Vmax of LPL increased linearly (P < 0.01, r = 0. 912) with an increase in the palmitic acid content of the lipoprotein triacylglycerols. These findings suggest that lipoprotein catalysis by LPL is modulated by the palmitic acid content of the lipoprotein triacylglycerol, which affects the fluidity of lipoproteins.

Animals↗
PubMed1999

Characterization of the carrier-mediated transport of levofloxacin, a fluoroquinolone antimicrobial agent, in rabbit cornea.

The cornea presents a formidable barrier to drug penetration. The fluoroquinolone levofloxacin, which is an effective antimicrobial agent, has the potential to be used in the topical treatment of ocular disease. Thus, we sought to characterize how levofloxacin penetrates the cornea. To perform this characterization, we measured the time dependent permeation of levofloxacin across the isolated rabbit cornea using a diffusion chamber, and compared it with antipyrine fluxes. Levofloxacin permeation into the receiver epithelial-side bathing solution (pH = 6.5) from the donor endothelial-side (pH = 7.4) reached 3.00 nmolcm(-2) cornea after 2h, whereas in the opposite direction permeation was 1.89 nmolcm(-2) cornea. Based on the temperature-dependent effects on permeation, the calculated energy of activation for permeation, Ea, was 31.3 kcal mol(-1), whereas Ea for antipyrine, a marker of diffusion, was 11.0 kcalmol(-1). The transport of levofloxacin from epithelium to endothelium was concentration-dependent and had both a linear and saturable component. Evaluation of the kinetic parameters, Jmax, apparent Km and k(d) showed that they were 38.78 pmol min(-1) cm(-2), 3.83 mM and 0.0135 microL min(-1) cm(-2), respectively. These results, coupled with the fact that levofloxacin permeation reached a maximum value at pH 6.5, suggest that levofloxacin transport across the cornea is carrier mediated. However, at present, it cannot be ascertained whether such a system is localized in either the corneal epithelial or the endothelial layer.

Animals↗
PubMed1998

Immaturity of lymphocytes in the metastatic lesions of thymoma.

Thymoma is a thymic epithelial tumor which often contains a large number of immature T cells. Although the metastatic lesions are also associated with abundant lymphocytes, their characteristics have not been assessed in detail. In this study, the phenotype was analyzed and compared with those in their primary lesions. Nine metastatic thymomas were obtained from seven patients. In the metastatic lesions, CD1a+ cells and CD4(+)CD8(+) cells accounted for 77.7 +/- 10.6 and 52.3 +/- 15.8% of all the lymphocytes, respectively. In five primary lesions and their metastatic lesions, CD3(-)CD4(+)CD8(-) cells accounted for 23.9 +/- 16.9 and 45.2 +/- 15. 5% of the CD4(+)CD8(-) cells, respectively. CD69 was expressed on 70. 9 +/- 9.5 and 53.1 +/- 11.8% of the CD4(+)CD8(-) cells, respectively. These results indicate that the metastatic lesions of thymoma are associated with abundant immature T cells which are phenotypically less mature than those in their primary lesions.

Adult↗
PubMed1998

Reduced dorsal hippocampal glutamate release significantly correlates with the spatial memory deficits produced by benzodiazepines and ethanol.

Memory deficits frequently occur after taking benzodiazepines and ethanol. We studied in vivo hippocampal presynaptic glutamate transmission in conjunction with memory deficits induced by benzodiazepines and ethanol in rats as an animal model of amnesia. These drugs potently impaired spatial memory formation as evaluated by the Morris water maze task, the rank order among tested treatments being the combination of triazolam (20 micrograms/kg) with ethanol (2 g/kg) > or = triazolam (100 micrograms/kg) > ethanol (2 g/kg) > or = triazolam (20 micrograms/kg) > rilmazafone (20 micrograms/kg). On the other hand, these drug treatments also reduced glutamate release in the dorsal hippocampus but not in the cerebellum measured by microdialysis: the combined administration of triazolam with ethanol potently inhibited glutamate release to 60% of basal output in the dorsal hippocampus. These decreases in hippocampal glutamate transmission closely correlated with the extent of impairment of spatial memory performance (r = 0.990). Thus, the present results strongly indicated that presynaptic dysfunction in dorsal hippocampal glutamatergic neurons would be critical for spatial memory deficits induced by benzodiazepines and ethanol.

Animals↗
PubMed1998

Neoplastic thymic epithelial cells of human thymoma support T cell development from CD4-CD8- cells to CD4+CD8+ cells in vitro.

Human thymoma is a thymic epithelial cell tumour which often contains a large number of immature T cells and is frequently associated with autoimmune diseases. Since thymic epithelial cells play key roles in the development and selection of T cells in the normal thymus, we hypothesized that the neoplastic thymic epithelial cells of thymoma may support T cell differentiation in the tumour. We characterized CD4-CD8- cells in thymoma and applied an in vitro reconstitution culture system using the CD4-CD8- cells and the neoplastic epithelial cells isolated from thymoma. CD34, a stem cell marker, was expressed on 29.9 +/- 12.2% of CD4-CD8- cells in thymoma. TCRgammadelta was expressed on 27.4 +/- 15.1% of CD4-CD8- cells and CD19, a B cell marker, was expressed on 14.1 +/- 23.1% of CD4-CD8- cells. CD4-CD8- cells expressed both IL-7R alpha-chain and common gamma-chain. Purified CD4-CD8- cells from thymomas were cultured with the neoplastic epithelial cells, and their differentiation into CD4+CD8+ cells via CD4 single-positive intermediates was observed within 9 days' co-culture in the presence of recombinant IL-7. Furthermore, we examined the reconstitution culture using CD34+CD4-CD8- cells purified from normal infant thymus. The CD34+CD4-CD8- cells in normal thymus also differentiated to CD4+CD8+ cells in the allogeneic co-culture with the neoplastic epithelial cells of thymoma. These results indicate that the tumour cells of thymoma retain the function of thymic epithelial cells and can induce differentiation of T cells in thymoma.

Adult↗
PubMed1998

Beta adrenergic antagonist permeation across cultured rabbit corneal epithelial cells grown on permeable supports.

PURPOSE: To determine whether cultured rabbit corneal epithelial cells (RCEC), grown on permeable supports, provide a suitable in vivo model for characterizing transcellular drug permeation and metabolism. METHODS: Primary rabbit corneal epithelial cells grown in DMEM-F12 were seeded on Transwell-COL inserts coated with fibronectin. The epithelial barrier integrity was evaluated, based on measurements of 14C-mannitol and 3H-PEG900, and their transepithelial electrical resistance (TEER). Ultrastructure evaluation was based on scanning electron microscopy and transmission electron microscopy, which were performed 8 days after seeding. Measurements of beta adrenergic antagonist permeability were performed to assess transcellular permeability. RESULTS: Eight days after seeding, the TEER reached a peak of 144 omega.cm2 and the 14C-mannitol and 3H-PEG900 permeabilities were 6.8 x 10(-6) and 2.9 x 10(-6) cm/sec, respectively. Ultrastructural analysis revealed a multilayered structure with numerous microplicae and typical cytoplasmic organelles along with desmosomes. The relationship between permeation of beta-blockers and lipophilicity resembled the intact isolated cornea. CONCLUSIONS: This is the first description of cultured RCEC grown on permeable support. Many of its properties mimic those described in the intact corneal epithelium. Even though its electrical tightness is less than that of the intact cornea, the transcellular permeability to lipophilic beta-antagonists is comparable to the isolated preparation. Therefore, this model will facilitate characterization of ocular permeation mechanisms of hydrophobic drugs whose route of permeation is transcellular.

Adrenergic beta-Antagonists↗