Biomedical subjects

Kyoko Fujiwara

Publications and source records attributed to Kyoko Fujiwara.

12 recordsLinked to original sources

PubMed2006

Beneficial effect of antioxidants in purified neurons derived from rat cortical culture.

Brain cell suspensions obtained from cerebrum of fetal rats were cultured and after 5 days neurons were separated from the residual cells. These purified neurons, which were replated on the dish, started to die within 24 h in culture. Glutathione content of these neurons decreased rapidly to less than one-tenth of the initial level after 24 h. In the presence of alpha-tocopherol, a well-known antioxidant, the neurons survived for at least 3 days, though glutathione content remained very low. Butylated hydroxyanisol had similar effect, but ascorbic acid and uric acid had no or very little effect. Serotonin, which is assumed to have an antioxidant activity, kept the neurons alive for 3 days. These results suggest that neurons separated from the other types of cells cannot survive due to the oxidative stress, which may otherwise be neutralized by a mechanism involving glutathione, and that antioxidants including serotonin has a beneficial effect on these purified neurons.

Animals↗

PubMed2006

Two-dimensional structure control by molecular width variation with metal coordination.

The self-assembled monolayer of bipyridine derivative 1, which has two alkyl chains on each end, at the HOPG/1-phenyloctane interface was studied by in situ scanning tunneling microscopy (STM). The detailed mechanism of a spontaneous change in the monolayer packing pattern by Pd coordination was studied. Uncomplexed 1 existed in a bent form in the monolayer, and the alkyl chains were interdigitated, whereas Pd-complexed 1 was in a straight form and the alkyl chains were not interdigitated. An intermediate state of 1 was successfully observed during metal coordination. The structure was the bent form with noninterdigitated alkyl chains. Equilibrium intermolecular distances reported from ab initio calculations indicate that the molecular width of the central aromatic part of uncomplexed 1 (7.5 A) is substantially smaller than that of the peripheral alkyl chain part (9.2 A). The bent form was suitable for covering up the surface to maximize the packing density. However, the molecular width of the aromatic unit of Pd-complexed 1 (9.1 A) was almost identical to that of the alkyl chain unit (9.2 A). Therefore, Pd-complexed 1 took the straight form in the monolayer. The observation of surface coverage by STM suggests that the bent form increases the packing density by as much as 16% compared with that of the straight form. These results indicate that the control of molecular width can be used to design molecular templates for nanostructure formation.

Journal Article↗

PubMed2005

Frequent trefoil factor 3 (TFF3) overexpression and promoter hypomethylation in mouse and human hepatocellular carcinomas.

Expression profiling analysis revealed ectopic high expression of mouse TFF3 in non-tumor liver tissues from the hepatocellular carcinoma (HCC) susceptible PWK/Rbrc strain. TFF3 is a member of the trefoil factor family peptides, which are small secreted proteins regulating mucosal regeneration and repair, and which are overexpressed during inflammatory processes and cancer progression. We, therefore, analyzed the TFF3 expression extensively in mouse and human HCCs. Expression of the mouse TFF3 gene was significantly increased in 6 out of 7 HCCs from a PWK spontaneous tumor model and in all 7 HCCs from an SV40T antigen-induced transgenic MT-D2C57BL/6 model. In humans, 8 of 20 HCCs (40%) had overexpression of TFF3 in both mRNA level and protein level. We then analyzed DNA methylation patterns of the TFF3 promoter region to evaluate expression regulation of promoter methylation. In mouse HCCs, we demonstrated that two CpGs, at positions -992 and +109, were hypomethylated in 13 of 14 mouse HCCs. In human HCCs, hypomethylation at CpG -260 was associated with TFF3 overexpression (p=0.04). These results indicate that TFF3 overexpression may be a critical process in mouse and human hepatocellular carcinogenesis, and the specific promoter CpG hypomethylation may be one of the regulation mechanisms of TFF3 overexpression in HCCs.

Animals↗

PubMed2004

Global gene expression analysis of rat colon cancers induced by a food-borne carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

Colon cancers develop after accumulation of multiple genetic and epigenetic alterations in colon epithelial cells. To shed light on global changes in gene expression of colon cancers and to gain further insight into the molecular mechanisms underlying colon carcinogenesis, we have conducted a comprehensive microarray analysis of mRNA using a rat colon cancer model with the food-borne carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Of 8749 genes or ESTs on a high density oligonucleotide microarray, 27 and 46 were over- and underexpressed, respectively, by > or =3-fold in colon cancers in common in two rat strains with distinct susceptibility to PhIP carcinogenesis. For example, genes involved in inflammation and matrix proteases and a cell cycle regulator gene, cyclin D2, were highly expressed in colon cancers. In contrast, genes encoding structural proteins, muscle-related proteins, matrix-composing and mucin-like proteins were underexpressed. Interestingly, a subset of genes whose expression is characteristic of Paneth cells, i.e. the defensins and matrilysin, were highly overexpressed in colon cancers. The presence of defensin 3 and defensin 5 transcripts in cancer cells could also be confirmed by in situ mRNA hybridization. Furthermore, Alcian blue/periodic acid Schiff base (AB-PAS) staining and immunohistochemical analysis with an anti-lysozyme antibody demonstrated Paneth cells in the cancer tissues. AB-PAS-positive cells were also observed in high grade dysplastic aberrant crypt foci, which are considered to be preneoplastic lesions of the colon. Our results suggest that Paneth cell differentiation in colon epithelial cells could be an early morphological change in cryptic cells during colon carcinogenesis.

Alcian Blue↗

PubMed2004

Urinary catecholamines and salivary cortisol on workdays and days off in relation to job strain among female health care providers.

OBJECTIVES: This study examined the effects of psychosocial job strain on the excretion of neuroendocrine stress hormones (adrenaline, noradrenaline, and cortisol) on workdays and days off. METHODS: Japanese female health care providers (N=16) filled out Karasek's job content questionnaire and had their neuroendocrine excretions (ie, urinary catecholamines and salivary cortisol) measured on a day off and on two workdays (one day shift and one night shift). After control for age and job experience as covariates, a repeated-measures analysis of variance was carried out. RESULTS: Noradrenaline excretion was significantly greater over time in the high-strain group than in the low-strain group, and that of the high-demand group was significantly greater over time than that of the low-demand group. Adrenaline excretion did not significantly differ between the groups. The group with high supervisory support had significantly higher adrenaline excretion than the group with low supervisory support. The concentration of salivary cortisol on a dayshift was significantly lower, but marginally, in the high-strain group than in the low-strain group. CONCLUSIONS: Psychosocial job strain is associated with greater noradrenaline excretion over time. This finding suggests unwinding sympathetic nervous activity. The low cortisol levels of the high-strain group may indicate circadian rhythm disturbance induced by job strain. Supervisory relationships may have a particular influence for the studied occupation because the participants had more administrative contact with supervisors than support at the worksite; therefore, supervisory support may increase adrenaline excretion.

Adult↗

PubMed2003

Characterization of dysplastic aberrant crypt foci in the rat colon induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

The multistage model of colon carcinogenesis is well established in both humans and experimental animals, and aberrant crypt foci (ACF) are generally assumed to be putative preneoplastic lesions of the colon. However, morphological analyses of ACF have suggested that they are highly heterogeneous in nature and their role in tumorigenesis is still controversial. To better understand the biological significance of ACF in carcinogenesis, morphological and genetic analyses were performed using a rat colon cancer model induced by a food-borne colon carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). ACF of different sizes were collected at weeks 6, 18, 25, and 32 after three cycles of 2-week PhIP feeding (400 ppm in diet) with 4-week intervals on a high-fat diet, and a total of 110 ACF, representing approximately three-quarters of the total ACF, were subjected to histological evaluation. Thirty (27%) were diagnosed as dysplastic ACF, based on cytological and structural abnormalities of crypts. Dysplastic ACF were detected even at week 6 (0.4 per rat), and the numbers increased slightly at later time points, being 0.8, 1.4, and 0.8 per rat at weeks 18, 25, and 32, respectively. The sizes of these dysplastic ACF varied widely from 1 to 16 crypts and 50% (15 of 30) were composed of less than 4 crypts. Immunohistochemical analysis revealed that 83% (25 of 30) of dysplastic ACF demonstrated beta-catenin accumulation; 22 only in the cytoplasm and 3 in both the cytoplasm and nucleus, the latter manifesting a higher grade of dysplasia as compared with the former. Seven dysplastic ACF harbored beta-catenin mutations at codon 32, 34, or 36 in exon 2, and one had an Apc mutation at the boundary of intron 10 and exon 11. Mutations at these sites were also commonly found in colon tumors induced by PhIP. The results of our present study indicate that dysplastic ACF, which accounted for approximately one-fourth of the total ACF, are preneoplastic lesions of colon cancers induced by PhIP in rats.

Adenocarcinoma↗

PubMed2003

Visual dysfunction in workers exposed to a mixture of organic solvents.

The aim of this study was to investigate the relationship between the workers occupationally exposed to a mixture of organic solvents and their visual functions. Here the visual functions included color vision (CV), visual contrast sensitivity (CS) and visual evoked potentials (VEP). Test subjects were 182 workers at 53 furniture factories in the same industrial area of Japan. As control, a group consisted of 96 workers without exposure to any organic solvent was also tested. Exposure assessments were made both by the environmental concentration and biological monitoring. CV and CS tests were carried out for all the subjects. VEP was measured for 21 exposed subjects who were considered to have impaired CV and CS. In the results, the color confusion index (CCI) values of the exposed subjects were significantly higher than that of the age-matched controls (P<0.01). Their CS values were significantly lower than those in the controls at spatial frequencies of 6 and 12 cycles per degree (cpd) (P<0.01 and <0.05, respectively). A significant correlation between the concentration of urinary methylhippuric acid and contrast sensitivity was found by a multiple regression analysis (P<0.05). CCI showed a negative correlation at all spatial frequencies of CS in a simple regression analysis, no abnormal data were found by the VEP test in the exposed subjects who were found to have impaired CV and CS. The results suppose that a low concentration of the mixed organic solvents might affect the retina and optic nerve. However, it needs to be further researched if such an impact affects the Brodmann's areas of visual cortex in the brain.

Adult↗

PubMed2003

Differential gene expression profiles in colon epithelium of two rat strains with distinct susceptibility to colon carcinogenesis after exposure to PhIP in combination with dietary high fat.

Colon cancers develop through accumulation of multiple genetic and epigenetic alterations in colon epithelial cells, and the environment of the genetically altered epithelial cells may also have a substantial impact on their further development to cancer. In the present study, groups of 6-week-old F344 and ACI male rats, the former strain being susceptible to colon carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and the latter being relatively resistant, were subjected to a long-term carcinogenesis experiment using our intermittent feeding protocol of PhIP in combination with a high-fat diet, which serves as a relevant risk factor that promotes the development of colon cancers. Animals were sacrificed at 60 weeks, and global gene expression analyses of normal parts of colon epithelial tissues were conducted using a high-density oligonucleotide microarray to elucidate the differential gene expression profile (environment) in normal colonic regions between F344 and ACI strains. Of 8799 entries on the RatU34A array, 74 genes exhibited 3-fold or greater variation. A subset of genes encoding ribosomal RNAs and proteins were highly preferentially expressed in the F344 strain. In addition, genes encoding fatty acid binding proteins and the peroxisome membrane protein 70 appeared up-regulated in the susceptible F344 strain. In the ACI strain, a mismatch repair gene, Msh2, was preferentially expressed, at approximately 20-fold the F344 level, along with a gene encoding a detoxification enzyme, catechol-O-methyltransferase. The combined effects of the repertoire of these differentially expressed genes in normal colon epithelial tissues may account for the distinct susceptibilities of F344 and ACI strains to colon carcinogenesis.

Animals↗

PubMed2003

Interpersonal conflict, social support, and burnout among home care workers in Japan.

To examine associations between interpersonal relationships in work settings and burnout, a cross-sectional survey was conducted on home care workers in Sapporo, Japan, by using the Maslach Burnout Inventory (MBI) and scales of interpersonal conflict and social support developed by the authors. Questionnaires were distributed among 303 subjects and returned by 243 subjects (80%). Complete answers were obtained from 106 subjects and were used for analysis. In multiple regression analyses, conflict with clients and their families significantly related to emotional exhaustion and depersonalization of the MBI (p<.05). Supervisory conflict significantly related to emotional exhaustion (p<.05), whereas coworker conflict significantly associated with depersonalization (p<.01). It is suggested that conflicts with clients' families, as well as clients, are important indicators for emotional exhaustion and depersonalization of home care workers.

Adult↗

PubMed2003

[Job characteristics and problems related to home care services for the elderly. A comparison among employment categories in Sapporo].

OBJECTIVE: The aims of this study were to describe job characteristics for daytime and shift workers in home care services for the elderly and to clarify health care in the work setting, social support, and job satisfaction and possibilities. METHODS: A self-reported questionnaire was given to 433 home care workers, both full time and part time (more than 15 hours), at 35 institutions that provide home care services to residents of Sapporo (return rate; 80.2%). The following issues were investigated: job content (physical care, assistance with housework, and advice), specialty, job satisfaction, possibilities, job training, health care and social support. The results were compared among employed types: full-time and part-time daytime and shift workers using the t-test or the Fisher's test. RESULTS: The participants demonstrated high dissatisfaction with wages, physical uneasiness themselves and limited social support from their supervisors. Especially full-time workers were dissatisfied with the payment, whereas part-time workers complained about insufficient attention to the prevention of lumbago. It was found that part-time daytime workers were given insufficient on-job-training and education for prevention of infection, and that full-time shift workers greatly wished to leave the employment. However, the home care workers were satisfied with their job itself and expected to continue their work. Furthermore, half of the part-time workers hoped to work full time. CONCLUSIONS: Health management and educational training for part-time workers may be necessary to improve the quality of care services and protection of health. Promotion of full time employment and reconsideration of working condition might be necessary to provide sufficient home care services.

Adult↗

PubMed2002

A rat colon cancer model induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, PhIP.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most abundant heterocyclic amines contained in cooked meat and fish, and induces aberrant crypt foci (ACF), putative preneoplastic lesions of the colon, and colon cancers in male rats when administered orally. As has been reported previously, F344 rats are susceptible to induction of ACF by PhIP, while ACI rats being relatively resistant. Approximately one-fourth of ACF induced by PhIP in F344 rats are dysplastic; exhibiting lesions with structural distortion of the crypt, decrease of goblet cells, nuclear stratification and enlargement of nuclei. Dysplastic ACF demonstrate beta-catenin accumulation, mainly in the cytoplasm, and increased cell proliferation in crypts. These dysplastic ACF are, therefore, strongly considered to be putative preneoplastic lesions of the colon.A genetic trait affecting the susceptibility to colon carcinogenesis in F344 rats was mapped to chromosome 16, between D16Rat17 and D16Wox3, using the number of ACF as a surrogate biomarker for colon carcinogenesis. Since the number of dysplastic lesions is well correlated with the total number of ACF, being approximately one-fourth of the total ACF as described above in F344 rats and will be described elsewhere in ACI rats, the gene involved in the susceptibility to ACF induction may possibly be partly responsible for the susceptibility to colon carcinogenesis by PhIP. We, thus, tentatively referred the name of the candidate susceptibility gene on rat chromosome 16 as susceptibility to colon tumor (Sct). In the present study, the colonic lesions induced by PhIP were well refined histologically and genetically, and the multi-step profiles of colon cancer development by PhIP were well characterized and revealed to be similar to the multi-step model of colon carcinogenesis in humans. The PhIP-induced colon cancer model in rats, thus contributes as a relevant tool to elucidate genetic factors responsible for susceptibility to colon carcinogenesis in human. Other unknown genetic or epigenetic alterations, which are essential for the development of early lesions of colon carcinogenesis, could also be clarified using this system.

Animals↗

PubMed2002

Hague (Hag). A new mouse hair mutation with an unstable semidominant allele.

A spontaneous mouse hair mutation was identified in a C3H/HeN colony. The mode of inheritance of the mutation was semidominant, with incomplete penetrance when heterozygous. The trait is controlled by a single locus hague (Hag), which was mapped to the telomeric region of chromosome 15. This mutation was shown to be unstable, since its transmission could be switched from semidominant to recessive. To identify the causative gene and the nature of the mutation, hague was introduced into a high-resolution and high-density molecular genetic map. Over 2000 meioses were analyzed and the mutation was mapped to the keratin 2 complex genes. A YAC and BAC physical map of the critical region was then constructed and the gene involved was located in a 600- to 800-kb-long segment. Fourteen genes were mapped to this region; of these, 11 were expressed in the skin (5 epidermic cytokeratin and 6 hard keratin genes), but none were mutated in hague mice.

Animals↗