Biomedical subjects

M Yoneyama

Publications and source records attributed to M Yoneyama.

At least 37 records · Page 2Linked to original sources

PubMed1996

Effect of 4G-beta-D-galactosylsucrose (lactosucrose) on fecal microflora in patients with chronic inflammatory bowel disease.

Metabolic interaction between the intestinal microflora and the host has been suggested to play a role in the pathogenesis of chronic inflammatory bowel disease. Elemental or low-fat, low-residual diets in patients with Crohn's disease or ulcerative colitis are reported to decrease anaerobic bacteria and to change the composition of the intestinal microflora. We examined the effect of an indigestible agent, 4G-beta-D-galactosylsucrose (lactosucrose), which is selectively utilized by intestinal Bifidobacterium, on the composition of the intestinal microflora. After the administration of lactosucrose to two patients with Crohn's disease and five patients with ulcerative colitis for 2 weeks, significant induction of the growth of Bifidobacterium was observed, and significant reduction in the population level of Bacteroidaceae was seen. Bowel movements improved in four patients. The intestinal environment, estimated by measuring fecal pH, fecal levels of short-chain fatty acids and putrid products, and the urinary secretion of indican, also improved in these patients. These results suggest that lactosucrose may be useful for patients with chronic inflammatory bowel disease.

Adolescent↗

PubMed1996

Subchronic toxicity of thiabendazole (TBZ) in ICR mice.

The subchronic toxic effects of thiabendazole (TBZ) administered in the diet at levels of 0 (control), 0.8 and 1.6% for 13 wk to male and female ICR mice were investigated. Mean body weights of male mice fed 0.8 or 1.6% TBZ showed a significant decrease compared with controls, except for wk 3 and 8 for mice fed 0.8% TBZ. Red blood cell parameters in male mice of treated groups were significantly lower than controls. Biochemistry showed increased concentrations of GOT and GPT in male and female mice of the 1.6% TBZ groups. Relative spleen or liver weights were significantly increased in male and female mice of treated groups. Relative kidney weights of treated mice tended to be increased in comparison with controls. Histological findings showed a marked haemosiderosis and extramedullary haematopoiesis in the spleen of treated mice. In the liver, sinusoidal dilatation and enlargement of liver cells were found in treated mice. In the kidney, atrophy of tubules with peritubular fibrosis, cell infiltration and some tubular necrosis were found in treated mice. Slight hyperplasia was found in the urinary bladder of treated mice. The findings in the present study indicate that TBZ caused a slight anaemia and liver or kidney injury at both levels tested, under these conditions.

Administration, Oral↗

PubMed1996

Structure of mouse interferon stimulated gene factor 3 gamma (ISGF3 gamma/p48) cDNA and chromosomal localization of the gene.

Interferon stimulated gene factor 3 (ISGF3) is a trimeric transcription factor activated on treatment of cells with interferon-alpha and beta (type I IFNs). Upon stimulation, the regulatory subunits, p84/91 and p113, present in the cytoplasm are phosphorylated at specific tyrosine residues and assemble with the DNA binding subunit, ISGF3 gamma, into the active ISGF3 in the nucleus. Thus, ISGF3 plays a primary role in the transmission of a signal from the cell surface to the nucleus. In this report, we describe the cloning of a mouse cDNA encoding a polypeptide homologous to human ISGF3 gamma. Comparison of the deduced amino acid sequences revealed the middle region was significantly different between mouse and man. The mouse cDNA was shown to encode a functional ISGF3 subunit by means of an in vitro reconstitution assay. Furthermore, the locus of the ISGF3 gamma gene, designated as Isgf3g, was mapped to distal mouse chromosome 14 by linkage analysis using an intersubspecific backcross typing panel.

Amino Acid Sequence↗

PubMed1996

Autocrine amplification of type I interferon gene expression mediated by interferon stimulated gene factor 3 (ISGF3).

Interferon regulatory factor (IRF)-1 and IRF-2 have been implicated for the virus-induced expression of the interferon-alpha and beta (type I IFN) genes. However, recent gene disruption studies in mice suggested the presence of other factor(s) interacting with overlapping promoter elements. In the present paper, we describe the characterization of a DNA binding factor which is strongly induced after virus infection and recognizes these promoter elements. After extensive purification, the factor was revealed to be identical to IFN-stimulated gene factor 3 (ISGF3), a transcription factor complex activated by IFN treatment. ISGF3 binds to the promoter element of IFN-beta, positive regulatory domain I (PRDI), with significantly higher affinity than IRF-1, 2, and mutational analysis of PRDI showed that the gene expression and binding of ISGF3, but not of IRF-1, 2, are highly correlated. Furthermore, our functional analysis involving a dominant negative inhibitor for ISGF3 activation and an anti-IFN neutralizing antibody clearly demonstrated the presence of a positive feedback path way for type I IFN genes mediated by ISGF3.

Animals↗

PubMed1995

Thermodynamic parameters to predict stability of RNA/DNA hybrid duplexes.

The thermodynamic parameters (delta H degree, delta S degree, and delta G degree 37) for 16 nearest-neighbor sets and one initiation factor are presented here in order to predict stability of RNA/DNA hybrid duplexes. To determine the nearest-neighbor parameters, thermodynamics for 68 different hybrid sequences (136 single-stranded oligonucleotides) with 5-13 nucleotide length including several duplexes with identical nearest-neighbors were measured by UV melting procedure. These sequences were selected to have many different combinations of nearest-neighbor pairs, and so that the number of the 16 nearest-neighbor sequences in the oligomers were as equal as possible. The structures of the hybrids were also investigated by measuring circular dichroism spectra. Comparing delta G degree 37 values of the hybrids with DNA/DNA and RNA/RNA parameters reported previously (Breslauer, K.J., Frank, R., Blöcker, H., & Marky, L.A. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 3746-3750; Freier, S.M., Kierzek, R., Jaeger, J.A., Sugimoto, N., Caruthers, M.H., Neilson, T., & Turner, D.H. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 9373-9377), RNA/RNA double helix is the most stable of the three kinds of helixes with the same nearest-neighbor sequences. Which is more stable between DNA/DNA and RNA/DNA hybrid duplexes depends on its sequence. Calculated thermodynamic values of hybrid formation with the present parameters reproduce the experimental values within reasonable errors.

Base Sequence↗

PubMed1995

Two-dimensional domain shape transitions in photosensitive monolayer assemblies.

Bubble-stripe shape transitions of gaseous domains are observed in Langmuir monolayers of porphyrin/arachidic acid and porphyrin/spiropyran mixtures using fluorescence microscopy. Characteristics of the transition such as critical bubble size are found to be controllable by subphase pH or UV/visible irradiation. These features are discussed in terms of a balance between dipolar repulsions and line tension in the monolayer.

Benzopyrans↗

PubMed1995

Optical neural device based on memory-type organic photoconductors.

A variable-sensitivity organic-photoconductive device has been developed by using a memory-type organic photoconductor. The device is composed of an input layer and a memory layer acting as a charge generation and a charge transport layer, respectively. A persistent high-sensitivity state, which corresponds to a modulation of synaptic weights in a neuron model, was obtained by blue light illumination. A photochemical reaction of thiomichler's ketone (TMK) in the memory layer was found to be responsible for the memory formation. As a potential application of this memory-type organic photoconductor to an optical neural device, 2-D pattern storage and calculations were performed successfully.

Animals↗

PubMed1995

Collaborative work to determine an optimal administration period and optimal parameters for detection of effects on male fertility in rats--male reproductive toxicity study of haloperidol.

Haloperidol, a neuroleptic, was orally administered at 0, 3, 10, 30 and 60 mg/kg/day in a 4-week dosing study, and 0, 3, 10 and 30 mg/kg/day in a 9-week dosing study, to Sprague-Dawley male rats which were then sacrificed for histopathological examination or mated with untreated females. The males in the mating groups were continuously treated during the mating period. Sperm positive females were sacrificed on day 20 of gestation. The males in the histopathology groups were sacrificed after 4- or 9-week dosing and their testes were fixed in Bouin's fluid and sections stained with HE or PAS. The mated males were sacrificed and reproductive organ weights were determined. At 3 mg/kg or more, reduced spontaneous motor activity was observed and body weights were lowered. The absolute weight of testes was decreased with 60 mg/kg in the 4-week dosing study, and was decreased with 10 and 30 mg/kg in the 9-week dosing study. However, the relative weight was increased or showed a tendency to increase. In the 4-week dosing study, decrease in the fertility index with 60 mg/kg and increase in pre-implantation loss with 30 mg/kg or more were noted. However, there were no adverse effects on the copulation index in any of the treated groups. The males given 60 mg/kg showed slight changes in the testes (necrosis of pachytene spermatocytes in seminiferous tubules of stage VII, exfoliation of round spermatids in the lumina and atrophy of Leydig cells) and seminal vesicles (atrophy of epithelial cells). Atrophy of Leydig cells was also observed at 30 mg/kg in the 4-week dosing study. In the 9-week dosing study, neither male reproductive ability nor histopathological parameters were affected by haloperidol up to 30 mg/kg. From the results detailed above, it may be concluded that 4-weeks dosing before mating is suitable for detection of effects of haloperidol on male reproductive ability, and that histopathological changes together provide an optimal parameter for predicting male reproductive disorders.

Animals↗

PubMed1994

Chronic toxicity studies of piperonyl butoxide in F344 rats: induction of hepatocellular carcinoma.

Male and female F344 rats (30-33 rats/group) were administered piperonyl butoxide (alpha-[2-(2-butoxyethoxy)ethoxy]-4,5-methylenedioxy-2-propylto luene) in the diet at levels of 0 (control), 0.6, 1.2, and 2.4% for nearly 2 years. Beginning at about 40 weeks, 10 rats in the 1.2% treated male group died due to cecal hemorrhages. Piperonyl butoxide induced hepatocellular carcinoma in both sexes in a dose-dependent manner. Hepatocellular carcinoma was found even in the 1.2% treated male group (incidence, 26.7%), and incidences in the 2.4% groups of males and females were 80.0 and 57.7% respectively of all those surviving. Piperonyl butoxide also caused essential thrombocythemia with a dose-response relationship. Hemorrhages in stomach and cecum, anemia, degenerative lesions of alveoli, and nephrotoxicity were also observed related to exposure. These results indicate that piperonyl butoxide is a hepatocarcinogen to the rat.

Animals↗

PubMed1994

Piperonyl butoxide induces hepatocellular carcinoma in male CD-1 mice.

Male CD-1 mice in groups of 52, 53 or 100 were administered piperonyl butoxide (alpha-[2-(2-butoxyethoxy)ethoxy-4,5-methylenedioxy-2-propyltol uene) in the diet at levels of 0 (control), 0.6 and 1.2% for 12 months. Hepatocellular carcinoma was induced in treated groups in a dose-dependent manner but not in the control group. The incidences of hepatocellular carcinoma were 11.3 and 52.0% in mice given 0.6 and 1.2% piperonyl butoxide, indicating that piperonyl butoxide can cause hepatocellular carcinoma in mice as it is known to do in rats.

Animals↗

PubMed1993

Hepatotoxicity of piperonyl butoxide in male F344 rats.

Male F344 rats were given 0, 0.6, 1.2 or 2.4% of piperonyl butoxide in the diet. At 1, 2, 4 or 12 weeks after the beginning of the experiment, liver and kidney weight and serum clinical parameters were determined and livers and kidneys were examined with light microscopy. From 1 or 2-12 weeks, distinct increase of liver weight, changes in serum clinical parameters for liver damage, oval cell proliferation, bile duct hyperplasia, single cell necrosis, enlarged and vacuolated hepatocytes, enlarged nuclei and anisonucleosis were seen in treated rats. From 4-12 weeks, cell infiltration, focal necrosis, multinucleated hepatocytes and prominent nucleoli of hepatocytes were seen in treated rats. At 12 weeks microgranulomas were seen in treated rats. Especially in rats of the 2.4% group at 12 weeks, severe enlargement of hepatocytes, severe enlargement of nuclei and multinucleated hepatocyte were seen, suggesting preneoplastic alteration. Relative kidney weights and serum urea nitrogen levels were increased in treated rats from 1 or 2-12 weeks and at 12 weeks, atrophy of proximal tubules, dilation of tubules, cell infiltration, fibrosis and accumulation of yellow-brown pigment in the proximal tubular cells were seen.

Administration, Oral↗

PubMed1993

Subacute toxicity of piperonyl butoxide in ICR mice.

Piperonyl butoxide, alpha-[2-(2-butoxyethoxy)ethoxy]-4,5-methylenedioxy-2-propyltol uene, is a pesticide synergist. ICR mice of both sexes were maintained on diet containing 0, 0.1, 0.3 or 0.9% of piperonyl butoxide for 20 days. At the end of the experimental period, they were necropsied. Selected organs were weighed and serum chemistries were analyzed. In male and female mice of the 0.9% group, body weight, kidney and spleen weight were depressed in comparison to those of control group. Liver weight of the 0.3 and 0.9% group of both sexes were significantly higher than those of control group. Mice of the 0.9% group of both sexes had increased serum levels of cholesterol, total protein, gamma-glutamyl transpeptidase. Histological examination of livers from mice of the 0.9% group by light microscopy showed enlarged hepatocytes, anisonucleosis and single cell necrosis. The results indicated that subacute toxicity of piperonyl butoxide in ICR mice was directed primarily at liver.

Animals↗

PubMed1992

The crystal structure and physicochemical properties of L-ascorbic acid 2-glucoside.

The stable L-ascorbic acid glucoside produced by the action of the cyclomaltodextrin glucanotransferase (CGTase, EC 2.4.1.19) from Bacillus stearothermophilus was crystallized from an aqueous solution. Determination of the molecular structure by single crystal X-ray analysis showed the compound to be 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G). The crystals are orthorhombic, space group P2(1)2(1)2(1), with unit-cell dimensions a = 11.929 A, b = 24.351 A, and c = 4.864 A. The D-glucopyranose residue has the 4C1 conformation. These conclusions are in good agreement with those based on the 13C-NMR spectrum. The general physicochemical properties of crystalline AA-2G are reported.

Ascorbic Acid↗

PubMed1992

IL-2 and EGF receptors stimulate the hematopoietic cell cycle via different signaling pathways: demonstration of a novel role for c-myc.

Stimulation via cytokine receptors such as IL-2 and IL-3 receptors, but not by the EGF receptor (EGFR), induces cells of the BAF-B03 hematopoietic cell line to transit the cell cycle. We demonstrate that the IL-2 receptor beta chain (IL-2R beta) is linked to at least two intracellular signaling pathways. One pathway may involve a protein tyrosine kinase of the src family, which leads to the induction of the c-jun and c-fos genes, among others. A second pathway, involving an as yet unknown mechanism, leads to c-myc gene induction. Stimulation of the EGFR, expressed following transfection of an appropriate recombinant construct, can activate the former, but not the latter, pathway in this cell line and cause the cells to enter S phase but not progress further. This deficiency can be rescued by ectopic expression of the c-myc gene, indicating a novel role for this proto-oncogene in the S to G2/M transition of the cell cycle.

Animals↗

PubMed1992

Acute renal toxicity of thiabendazole (TBZ) in ICR mice.

The acute toxic effects of thiabendazole [2-(4'-thiazolyl)benzimidazole; TBZ] on the kidneys of ICR mice were investigated. The mice were given 0, 250, 500 or 1000 mg TBZ/kg body weight by gavage (using olive oil as a vehicle), and the kidneys were subjected to pathological examination at 1, 3, 5 or 24 hr after dosing. Gross findings were slight enlargement and the presence of whitish areas (white maculae) in kidneys of treated mice at 3, 5 or 24 hr after dosing. Histological findings were desquamation of degenerated cells in proximal tubules of treated mice at 1 hr. Dilation of proximal, distal and collecting tubules was apparent in treated mice at 3, 5 and 24 hr. TBZ-induced renal injury was reduced by pretreatment with inducers of the microsomal monooxygenase system (sodium phenobarbital, beta-naphthoflavone and 3-methylcholanthrene) and were enhanced by pretreatment with inhibitors of that system (2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride and piperonyl butoxide). The concentration of TBZ in blood at 1 or 5 hr after dosing was lower in mice pretreated with microsomal monooxygenase system inducers and was higher in those pretreated with the inhibitors, than in those given TBZ alone. These results suggest that TBZ-induced renal injury may be attributable to the parent compound rather than its metabolites. Measurement of organic ion uptake into renal slices revealed significant depression of [1-14C]tetraethylammonium bromide (TEA) uptake in treated mice at 1 or 5 hr, whereas uptake of p-[glycyl-2-3H]aminohippurate (PAH) was not depressed at 1 or 5 hr after dosing. The reduction in uptake of TEA is interpreted as the result of competitive suppression of the tubular transport of TEA by TBZ. TBZ-induced renal injury was reduced by organic cation transport inhibitors [N'-methylnicotinamide (NMN) or thiamine] but not by organic anion transport inhibitor [p-(dipropylsulphamyl)benzoic acid probenecid], suggesting that the reduction of TBZ-induced renal injury is the result of competitive suppression of the tubular transport of TBZ by NMN or thiamine.

Administration, Oral↗

PubMed1991

New metabolites of thiabendazole and the metabolism of thiabendazole by mouse embryo in vivo and in vitro.

Thiabendazole [2-(4'-thiazolyl)benzimidazole; TBZ], a teratogen in ICR mice, is known to be mainly metabolized to 5-hydroxy-TBZ (5-OH-TBZ) and its conjugates in domestic and laboratory animals. Besides the known metabolites of TBZ, 4-hydroxy-TBZ and 2-acetylbenzimidazole (ABI) were identified as new metabolites of TBZ in the urine of F344 rats and ICR mice. 5-OH-TBZ and ABI, as well as TBZ, were found in the embryos of ICR mice given TBZ orally on day 10 of gestation. In the whole-embryo culture system, 5-OH-TBZ and ABI in the medium, and TBZ, 5-OH-TBZ and ABI in the embryo were detected after 24 hr of culture in 25 or 50 micrograms TBZ ml. However, the amount of metabolites in the embryo in vitro was very small compared with that detected in vivo, whereas the amount of TBZ was comparable. Furthermore, the mouse embryo homogenate, at organogenesis, metabolized TBZ to 5-OH-TBZ or ABI. The specific activity required by this homogenate to form 5-OH-TBZ or ABI was less than 1/1000 of that of the liver microsomal fraction. The results suggested that mouse embryos at organogenesis could metabolize TBZ, although most of the metabolites in the embryo in vivo came from the dam.

Animals↗

PubMed1991

Relationship of HBsAg subtypes with HBeAg/anti-HBe status and chronic liver disease. Part I: Analysis of 1744 HBsAg carriers.

A total of 1744 HBsAg carriers were investigated to determine whether there are clinical differences among HBsAg subtypes or not. Although adr was more predominant than adw in 1078 asymptomatic carriers as well as in 666 carriers with liver dysfunction, the adr carriers had liver dysfunction more frequently than the adw carriers (p = 0.005). In addition, the adr carriers were more often positive for HBeAg and less often positive for anti-HBe than the adw carriers (p less than 0.001). Multivariate analyses indicated that the HBsAg subtypes were associated with liver dysfunction not directly but through the relationship between the HBsAg subtypes and HBeAg/anti-HBe status. HBeAg/anti-HBe status of each age bracket in the adr carriers and in the adw carriers suggested that adr carriers are seroconverted later than adw carriers. In conclusion, HBsAg subtypes may affect the development of chronic liver disease, through their association with HBeAg/anti-HBe status.

Adult↗

PubMed1991

Relationship of HBsAg subtypes with HBeAg/anti-HBe status and chronic liver disease. Part II: Evaluation of epidemiological factors and suspected risk factors of liver dysfunction.

In this study, we examined a possibility that epidemiological factors or suspected risk factors of liver dysfunction could account for the different HBeAg/anti-HBe status or the different prevalence of liver dysfunction between the adr and adw carriers. A total of 428 HBsAg carriers were surveyed of their age, sex, racial background, socioeconomic status, place of residence, birthplace, alcohol consumption, smoking habit, and history of blood transfusion as epidemiological factors or suspected risk factors of liver dysfunction. Adjustment for those variables using multivariate analyses did not substantially affect the association of the HBsAg subtypes with either prevalence of liver dysfunction or HBeAg/anti-HBe status. HBsAg subtypes seem to directly affect HBeAg/anti-HBe status and consequently influence development of chronic liver disease.

Adult↗