Biomedical subjects

M Goto

Publications and source records attributed to M Goto.

At least 37 records · Page 2Linked to original sources

PubMed2005

Beta defensin-3 engineered epidermis shows highly protective effect for bacterial infection.

Defensins are small cationic proteins that harbor broad-spectrum microbicidal activity against bacteria, fungi and viruses. This study examines the effects on pathogens of the epidermis engineered to express human beta-defensin 3 (HBD3) to combat bacterial infections. First, we examined the localization of HBD3 in the epidermis and observed HBD3 in the intercellular spaces and lamellar bodies of the upper epidermal layers. This result showed HBD3 expressed and assembled in the outer layers of the epidermis was suspected to counter the invading microorganisms. Next, we established a keratinocyte cell line that stably expressed HBD3 and found that the culture medium showed antibacterial activity. Furthermore, we prepared an epidermal sheet of these cells with the HBD3 gene and grafted this onto a dermal wound on a nude rat. The HBD3 engineered epidermis demonstrated significant antimicrobial activity. Skin ulcers without epidermis are constantly exposed to invading microorganisms. Biopsy samples of re-epithelizing epidermis from patients with skin ulcers were collected, and HBD3 mRNA level measured in the epidermis. The epidermal samples from the ulcer skin expressed 2.5 times higher levels of HBD3 transcript than those in the control skin. These results, taken together, indicate that the therapeutic introduction of the HBD3 gene into somatic cells may provide a new gene therapy strategy for intractable infectious diseases.

Animals↗

PubMed2005

Little effects of low dosage of levomepromazine on plasma risperidone levels.

In the present study, we investigated the effects of levomepromazine on plasma risperidone concentrations in a steady state. Twenty patients taking risperidone at a stable dose for more than 2 weeks who were considered to require levomepromazine coadministration were selected. The scores of excitement in BPRS significantly decreased 2 weeks after the coadministration of levomepromazine. Plasma risperidone concentrations and the ratio of risperidone and 9-hydroxyrisperidone (risperidone/9-hydroxyrisperidone) did not change between before and 2 weeks after the coadministration of levomepromazine. The extrapyramidal symptoms were not worsened by the coadministration of levomepromazine. These results suggest that a low dosage of levomepromazine, use as a sedative adjuvant to risperidone treatment, have no statistically significant effect on the trough plasma concentrations of risperidone.

Adolescent↗

PubMed2005

Comparative study of two Japanese rhinoconjunctivitis quality-of-life questionnaires.

CONCLUSION: Two questionnaires were used to assess quality of life (QOL) in allergic rhinitis: the Japanese translation of the Rhino-conjunctivitis Quality of Life Questionnaire (RQLQJ) and an original Japanese QOL questionnaire (JRQLQ). Either questionnaire may be used to assess QOL depending on differences in target domains. OBJECTIVES: Although pollinosis is a common disease which has a major impact on patient QOL, no internationally standardized questionnaire has been available in Japan until now. The aim of this study was to compare two currently available QOL questionnaires for allergic rhinitis in Japan-the RQLQJ and JRQLQ-in terms of their appropriateness for clinical use and their psychometric properties. MATERIAL AND METHODS: A multicenter, inter-group, cross-sectional study was conducted in 187 adult symptomatic patients with Japanese cedar pollinosis in 2003. Patient scores on the two questionnaires were compared in terms of both overall and comparable domains. We also examined the acceptability, construct and reliability of both questionnaires. RESULTS: The questionnaires were highly correlated in terms of both overall and comparable domain scores. In addition, both questionnaires had equal and satisfactory psychometric validity, demonstrating that they are both useful tools for assessing QOL in rhinitis. However, when compared with each other, the JRQLQ focuses mainly on activities of daily life and is simpler, while the RQLQJ focuses mainly on rhinitis-related health and is more responsive.

Adult↗

PubMed2005

Temporal diet changes recorded by stable isotopes in Asiatic black bear (Ursus thibetanus) hair.

Carbon and nitrogen stable isotope ratios were measured in hair samples of the Asiatic black bear (Ursus thibetanus) inhabiting the Northern Japanese Alps (NJA) (n = 20) and the periphery of Nagano City (NC) (n = 6), in Nagano Prefecture, Japan. The hair of NJA bears, which did not have access to anthropogenic foods, showed lower values of d13C and d15N than that of NC bears which had access to garbage and corn fields, especially during the summer. These results reflect somewhat differing diets between the NJA and NC bears. We attempted to assess the feeding history during the hair growth cycle using the growth section analysis method. Each hair sample had been cut into 3?mm lengths from root to tip, labeled, and analyzed along the hair growth. We measured the carbon and nitrogen stable isotope ratios of each 3?mm length of hair sample from one NC bear which had been killed while raiding a corn field. The sections showed wide ranges of isotope ratios, from -23.2% to -14.6% for delta13C, and from 0.3% to 4.6% for delta15N. It was shown that the diet of this bear shifted dramatically from principally C3 plants to more C4 plants and to foods of animal origin. An analysis of the whole hair reflects just the average feeding habit during hair growth, but the present method can trace its diet history. This method can contribute to obtain precise ecological information of wildlife.

Animal Feed↗

PubMed2005

Effects of high-intensity intermittent swimming on PGC-1alpha protein expression in rat skeletal muscle.

AIM: The aim of the present investigation was to elucidate the effects of exercise intensity on exercise-induced expression of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) protein in rat skeletal muscle. METHODS: We measured PGC-1alpha content in the skeletal muscles of male Sprague-Dawley rats (age: 5-6 weeks old; body weight: 150-170 g) after a single session of high-intensity intermittent exercise (HIE) or low-intensity prolonged swimming exercise (LIE). During HIE, the rats swam for fourteen 20-s periods carrying a weight (14% of body weight), and the periods of swimming were separated by a 10-s pause. LIE rats swam with no load for 6 h in two 3-h sessions, separated by 45 min of rest. RESULTS: After HIE, the PGC-1alpha protein content in rat epitrochlearis muscle had increased by 126, 140 and 126% at 2, 6 and 18 h, respectively, compared with that of the age-matched sedentary control rats' muscle. Immediately, 6 and 18-h after LIE, the PGC-1alpha protein content in the muscle was significantly elevated by 84, 95 and 67% respectively. The PGC-1alpha protein content observed 6 h after HIE tended to be higher than that observed after LIE. However, there was no statistically significant difference between the two values (P = 0.12). CONCLUSION: The present investigation suggests that irrespective of the intensity of the exercise, PGC-1alpha protein content in rat skeletal muscle increases to a comparable level when stimuli induced by different protocols are saturated. Further, HIE is a potent stimulus for enhancing the expression of PGC-1alpha protein, which may induce mitochondrial biogenesis in exercise-activated skeletal muscle.

Adenylate Kinase↗

PubMed2005

Detection of 1733insC mutations in an Asian family with Birt-Hogg-Dubé syndrome.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant genodermatosis characterized by skin tumours, including multiple fibrofolliculomas, trichodiscomas and acrochordons. BHD patients also may suffer from associated renal and colonic carcinomas. The defective gene in BHD has been recently identified and is suspected of being a tumour suppressor gene. Several mutations of the BHD gene have been reported only in Caucasian patients. OBJECTIVES: This study reports the first Asian family that has been demonstrated to carry a BHD mutation. PATIENTS/METHODS: The proband was a 26-year-old Japanese man with multiple asymptomatic, soft skin-coloured papules on his face, neck and trunk, which were clinically thought to be acrochordon. His father was also affected. Histopathologically, the papules revealed a fibrofolliculoma that had a circumscribed proliferation of fibroblasts and collagen fibres surrounding an abnormal hair follicle. RESULTS: Mutational analysis of the BHD gene of the proband and the father detected 1733insC, a cytosine insertion mutation in an eight-cytosine tract (nucleotides 1733-1740) in exon 11. Analysis of fibrofolliculoma in the proband showed heterozygous 1733insC mutation, suggesting the absence of loss of heterozygosity. Interestingly, previous mutational analysis in Caucasian patients revealed that both1733insC and 1733delC mutations were hot spots. CONCLUSIONS: This study is the first to find the same hot-spot 1733insC mutation in Asian kindred. The mutations in this polycytosine tract may have a wide, global distribution despite their arising from a different ethnic background.

Adult↗

PubMed2005

Effect of specific antigen stimulation on intraepithelial lymphocyte migration to small intestinal mucosa.

Migration of intraepithelial lymphocytes (IELs) into intestinal epithelium is not yet well understood. We established an IEL-cell line from ovalbumin (OVA) 23-3 transgenic (Tg) mice and investigated the effect of antigen stimulation on the dynamic process of IEL migration into small intestinal mucosa. The cell line was a T cell receptor (TCR) alphabeta(+) CD4(+) CD8(-) phenotype, expressing alphaEbeta7 integrin in 90% of cells. Under intravital microscopy, the lined IELs adhered selectively to the microvessels of the intestinal villus tip of the Tg mice. The accumulation of IELs was significantly inhibited by an antibody against beta7-integrin and MAdCAM-1. When IELs were stimulated with OVA, the accumulation was attenuated compared to that of resting cells, with decreased expression of alphaEbeta7 integrin. In Tg mice fed with OVA, the number of IELs which migrated in the villus mucosa was significantly smaller than in the non-fed controls. The preferential migratory capacity of IELs to villus mucosa may be altered by specific antigen stimulations.

Animals↗

PubMed2005

A novel STK11 germline mutation in two siblings with Peutz-Jeghers syndrome complicated by primary gastric cancer.

Patients with Peutz-Jeghers syndrome (PJS) are known to be at risk of gastric cancer (GC), and the STK11 gene is a susceptibility gene for PJS. However, as no cases of PJS with GC in which a STK11 germline mutation has been identified have ever been reported and other susceptibility genes have also been suggested to be involved in PJS, the relation between STK11 germline mutations and GC in PJS is still unknown. In this study, we used sequencing analysis to investigate the STK11, CDH1, and TP53 loci for a germline mutation in two siblings with PJS with primary GC. A novel type of the STK11 germline mutation, c.890delG, encoding a truncated protein (p.Arg297fsX38) was identified, but no germline mutations of the CDH1 and TP53 genes were detected. No inactivation of the wild-type allele by somatic mutation or chromosomal deletion or hypermethylation at the 5'-CpG site of STK11 was detected in the GC. This is the first report of a STK11 germline mutation in a PJS patient with GC and should contribute to establishing correlations between the STK11 germline mutations and GC in PJS patients.

AMP-Activated Protein Kinase Kinases↗

PubMed2005

MUC4 expression is a novel prognostic factor in patients with invasive ductal carcinoma of the pancreas.

BACKGROUND: Many patients with invasive ductal carcinoma of the pancreas (IDC) have a poor outcome. MUC4 expression has been implicated as a marker for diagnosis and progression of IDC, but there are no studies of the relation between MUC4 expression and patient prognosis in IDC. AIMS: To investigate the prognostic significance of MUC4 expression in IDC. METHODS: The expression profiles of MUC4, ErbB2, p27, and MUC1 were investigated in IDC tissues from 135 patients by means of immunohistochemistry. RESULTS: MUC4 was expressed in 43 of the 135 patients with IDC (31.9%). The survival of 21 patients with high MUC4 expression (>20% of neoplastic cells stained) was significantly worse than that of the 114 patients with low MUC4 expression (<20% of neoplastic cells stained) (p = 0.0043). Univariate analysis showed that high MUC4 expression (p = 0.0061), large primary tumour status (>T2) (p = 0.0436), distant metastasis (p = 0.0383), lymphatic invasion (p = 0.0243), and surgical margins (p = 0.0333) were significant risk factors affecting the outcome of patients with IDC. Backward stepwise multivariate analysis showed that MUC4 expression (p = 0.0121), lymph node metastasis (p = 0.0245), and lymphatic invasion (p = 0.0239) were significant independent risk factors. ErbB2, p27, and MUC1 were not independent risk factors. CONCLUSIONS: This study shows that MUC4 expression in IDC is a new independent factor for poor prognosis and predicts the outcome of patients with IDC.

Adult↗

PubMed2004

Low-molecular weight dextran sulfate abrogates the instant blood-mediated inflammatory reaction induced by adult porcine islets both in vitro and in vivo.

BACKGROUND: One of the main obstacles to clinical application of islet xenotransplantation is the injurious inflammatory reaction elicited by porcine islets when they are exposed to fresh human blood in vitro and in vivo. This instant blood-mediated inflammatory reaction (IBMIR) causes rapid binding of platelets to the islet surface, activation of the coagulation and complement systems, and leukocyte infiltration of the islets. As a consequence of IBMIR, morphological destruction of porcine islets occurs within the first few hours after transplantation. MATERIALS AND METHODS: In the present study, by analyzing the plasma samples and performing immunohistochemical investigation, we assessed the effect of adding low-molecular weight dextran sulfate (LMW-DS) at 0.01-1 mg/mL to an in vitro tubing loop assay in which porcine islets were exposed to fresh human blood. The effect of LMW-DS also was investigated in an in vivo model using diabetic athymic mice, which provides an innate inflammatory milieu without influence of T cells. The possible toxicity of LMW-DS was assessed by culturing pig islets in the presence or absence of LMW-DS for 3 days. RESULTS: In the in vitro study, in the presence of LMW-DS at 0.01 mg/mL, platelet consumption, coagulation, and complement activation were reduced, and, at 0.1 mg/mL, LMW-DS totally prevented IBMIR. Immunohistochemical investigation showed that leukocyte infiltration was totally abrogated at the highest dose. A similar finding was observed in the in vivo study. No adverse effect of LMW-DS was observed on the quality of the islets. CONCLUSIONS: LMW-DS appears to be an effective drug candidate that is able to control the strong innate immune response induced by pig islets in contact with human blood.

Animals↗

PubMed2004

Association between patient education and health-related quality of life in patients with Parkinson's disease.

BACKGROUND: Providing patients with disease- and treatment-related information is an important role of medical staff and is now reimbursed in Japan by the national health insurance system under the rubric 'patient education'. Evaluation of the effectiveness of patient education programs is necessary to ensure that limited health care resources are used efficiently. OBJECTIVE: The objective is to determine whether educating patients with Parkinson's disease (PD) is related to better health-related quality of life (HRQOL). DESIGN: A cross-sectional study was conducted. SETTING: Members of the Japan Association of Patients with Parkinson's disease were randomly selected. PARTICIPANTS: A total of 1200 patients with PD were asked to fill in written questionnaires and replies from 762 (63.5%) were analyzed. MEASUREMENTS: The questionnaire inquired about clinical characteristics, comorbidity, symptoms of PD, complications of therapy, HRQOL, and patient education. SF-36 was used to assess HRQOL. The section on patient education comprised one question each on patient-perceived satisfaction with information provided on (1) disease condition and pathophysiology, (2) effectiveness of drug therapy, (3) adverse drug reactions, (4) publicly available financial and social resources, and (5) rehabilitation and daily activities. Patient education score was defined as the sum of the individual scores for these five questions. The relationships between scores on the SF-36 subscales and the patient education score were examined. RESULTS: More satisfaction with patient education was associated with higher scores in all SF-36 subscales except physical functioning and bodily pain. The difference in score between the most satisfied and the least satisfied patients ranged from 8.4 points on the subscales of general health and 16.7 points on the subscale of role limitation due to emotional problems. CONCLUSION: The conclusion that patient education is associated with better HRQOL in patients with PD is drawn.

Aged↗

PubMed2004

Viscoelastic properties of the small intestinal and caecal contents of the chicken.

We measured the coefficients of viscosity, shear rates and shear stresses of chicken small intestinal and caecal contents, including solid particles, using a tube-flow viscometer. The coefficients of viscosity of chicken small intestinal and caecal contents were correlated negatively with their shear rates, a characteristic typical of non-Newtonian fluids. The coefficient of viscosity of the small intestinal contents was lower than that of the caecal contents at a shear rate of 1 s(-1). Chicken caecal contents were more viscous than pig caecal contents. The exponential relationship between shear stress and shear rate showed that chicken small intestinal and caecal contents had an apparent Herschel-Bulkley fluid nature. These results indicate that solid particles, including uric acid crystals, are mainly responsible for the viscosity of the digesta in the chicken.

Animal Feed↗

PubMed2004

CT-based evaluation of axillary sentinel lymph node status in breast cancer: value of added contrast-enhanced study.

PURPOSE: To evaluate the diagnostic reliability of CT-based sentinel lymph node (SLN) size criteria for selecting the candidates for direct axillary dissection without SLN biopsy and to determine the value of added contrast-enhanced study. MATERIAL AND METHODS: Breast cancer patients (n = 107) underwent triple phasic (1-min, 3-min, 8-min) contrast-enhanced 5 mm-computed tomography (CT) of the breasts and axillae. In the CT image, the most inferior lymph node in the axilla was designated the SLN. Axillary status was judged based on SLN size criteria. CT density, enhancement rate, and peak enhancement time of each SLN were correlated with histopathological results. RESULTS: SLN size criteria demonstrated a sensitivity of 76% and a positive predictive value of 95% in predicting SLN metastasis. The density values at each scanning time-point were significantly different for metastatic and non-metastatic SLN. However, their enhancement rates differed significantly only at 1 min. Their peak enhancement occurred primarily at 1 min. The use of contrast-enhancement criteria improved the predictive sensitivity, but failed to decrease the false-positive rate of the SLN size criteria. CONCLUSION: The enhancement rate at 1 min proved to be the most useful parameter in contrast-enhanced CT studies; however, it failed in improving the accuracy of the SLN size criteria.

Adult↗

PubMed2004

Combined status of MUC1 mucin and surfactant apoprotein A expression can predict the outcome of patients with small-size lung adenocarcinoma.

AIM: Lung cancer is still a disease of high mortality, despite advanced diagnostic techniques. Here, we aim to report a unique method to predict the recurrence and outcome of patients with pulmonary adenocarcinomas. METHODS AND RESULTS: Immunohistochemical expression of MUC1 mucin and surfactant apoprotein A (SP-A) was examined in 185 cases of surgically removed lung adenocarcinomas of non-bronchioloalveolar type smaller than 30 mm. Staining results were evaluated semiquantitatively, and the expression of MUC1 and SP-A was compared in each case. There were 140/185 (76%) cases showing MUC1 expression higher than SP-A expression (MUC1>SP-A), and 45/185 (24%) cases showing MUC1 expression lower than or equal to SP-A expression (MUC1 SP-A pattern, but in 7% (3/45) of the patients with a MUC1< or =SP-A pattern after the median observation period of 41 months (1-99 months) (P < 0.01). The MUC1>SP-A group showed higher recurrence and worse survival than the MUC1<or =SP-A group by Kaplan-Meier's method (P < 0.01 and P < 0.005). Even in the patients with apparently favourable prognostic factors (well-differentiated adenocarcinoma or no lymph node metastasis), recurrence and survival were different between the two groups. CONCLUSIONS: A high MUC1/SP-A ratio is strongly associated with a poor outcome in patients with small-size lung adenocarcinoma.

Adenocarcinoma↗

PubMed2004

Mucin expression in pleomorphic adenoma of salivary gland: a potential role for MUC1 as a marker to predict recurrence.

BACKGROUND: Pleomorphic adenoma of the salivary gland (PA) is essentially a benign neoplasm. However, patients with recurrent PA are difficult to manage. There are rare reports on useful immunohistochemical markers to detect a high risk of recurrence when the primary lesions are resected. AIMS: To find a new marker to predict the recurrence of PA. METHODS: Primary lesions of PA were collected from nine patients showing subsequent recurrence and from 40 patients without recurrence during at least 10 years of follow up of the disease. Paraffin wax embedded tumour samples of the two groups were examined for the expression profiles of MUC1 (differentially glycosylated forms), MUC2, MUC4, MUC5AC, and MUC6 using immunohistochemistry. Several clinicopathological factors were also examined. RESULTS: In univariate analysis of the factors examined, MUC1/DF3 high expression (more than 30% of the neoplastic cells stained) in the primary lesions was seen more frequently in patients with recurrence (four of nine) than in those without recurrence (three of 40; p = 0.011). Larger tumour size (more than 3.0 cm) of the primary PA was also a significant (p = 0.035) risk factor for the recurrence of PA. In multivariate analysis, only high expression of MUC1/DF3 was found to be a significant independent risk factor for the recurrence of PA (p = 0.021). CONCLUSIONS: Expression of MUC1/DF3 in PA is a useful marker to predict its recurrence. Those patients with PA showing positive MUC1/DF3 expression should be followed up carefully.

Adenoma, Pleomorphic↗

PubMed2004

Persistent gene expression in mouse vagina exposed neonatally to diethylstilbestrol.

Developmental exposure to a synthetic estrogen, diethylstilbestrol (DES), induces carcinogenesis in human and laboratory animals. In mice, neonatal DES treatment induces persistent proliferation and keratinization of the vaginal epithelium, even in the absence of the ovaries, resulting in cancerous lesions later in life. To understand the mechanisms underlying this persistent cell proliferation and differentiation, we characterized the gene expression patterns in the neonatally DES-exposed mouse vagina using DNA microarray and real-time quantitative RT-PCR. We found that genes related to cellular signaling, which are candidates for mediating the persistent proliferation and differentiation, were altered, and genes related to the immune system were decreased in the neonatally DES-exposed mouse vagina. We also noted high expression of interleukin-1 (IL-1)-related genes accompanied by phosphorylation of JNK1. In addition, expression IGF-I and its binding proteins was modulated and led to phosphorylation of IGF-I receptor and Akt, which is one of the downstream factors of IGF-I signaling. This led us to characterize the expression as well as the phosphorylation status of IL-1 and IGF-I signaling pathway components which may activate the phosphorylation cascade in the vagina of mice exposed neonatally to DES. These findings give insight into persistent activation in the vagina of mice exposed neonatally to DES.

Animals↗

PubMed2004

Tissue-specific estrogenic and non-estrogenic effects of a xenoestrogen, nonylphenol.

Alkylphenols perturb the endocrine system and are considered to have weak estrogenic activities. Although it is known that nonylphenol can bind weakly to the estrogen receptor, it is unclear whether all reported effects of nonylphenol are attributable to its estrogen receptor-binding activity. In order to examine whether alkylphenols have similar effects to the natural hormone, estradiol, we used a mouse model to examine the effects of nonylphenol on gene expression and compared it with estradiol. DNA microarray analysis revealed that, in the uterus, most of the genes activated by this alkylphenol at a high dose (50 mg/kg) were also activated by estradiol. At lower doses, nonylphenol (0.5 mg/kg and 5 mg/kg) had little effect on the genes that were activated by estradiol. Thus, we concluded that the effects of nonylphenol at a high dose (50 mg/kg) were very similar to estradiol in uterine tissue. Moreover, since evaluation of estrogenic activity by gene expression levels was comparable with the uterotrophic assay, it indicated that analysis of gene expression profiles can predict the estrogenic activities of chemicals. In contrast to the similar effects of nonylphenol and estradiol observed in the uterus, in the liver, gene expression was more markedly affected by nonylphenol than by estradiol. This indicated that, in the liver, nonylphenol could activate another set of genes that are distinct from estrogen-responsive genes. These results indicated that nonylphenol has very similar effects to estradiol on gene expression in uterine but not in liver tissue, indicating that tissue-specific effects should be considered in order to elucidate the distinct effects of alkylphenols.

Animals↗

PubMed2004

Comparative uterine gene expression analysis after dioxin and estradiol administration.

The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) adversely affects many organisms. TCDD exposure is known to be associated with abnormal development, hepatotoxicity and endocrine effects. It has also been reported to have antiestrogenic activity in addition to estrogenic activity. In order to clarify the effects of TCDD in the uterus, we evaluated the patterns of gene expression after TCDD and estradiol administration. Of the 10 000 arrayed genes, only a few were affected by both estradiol and TCDD. Although the subset of genes that responded to estrogen was also activated by TCDD, the response to TCDD was more limited than that observed in response to estradiol. Therefore, according to our analysis of gene expression patterns, TCDD had partial and weak estrogenic activity in the uterus.

Animals↗