PubMed Health⌕ Search

Biomedical subjects

Makoto Watanabe

Publications and source records attributed to Makoto Watanabe.

At least 19 recordsLinked to original sources
PubMed2026

Crosstalk mediators implicated in the Stevens-Johnson Syndrome through gene regulatory network analysis.

Stevens-Johnson syndrome (SJS) is a rare and severe mucocutaneous disorder often triggered by medications or infections. Our previous research identified that four key genes, Ikzf1, Ptger3, Mavs, and Tlr3 are involved in SJS susceptibility and the conjunctival epithelial innate immune response, demonstrating their role in regulating interferon-stimulated genes. However, the interplay among these regulatory factors remains unclear. This study aimed to elucidate the crosstalk mechanisms between the pathways regulated by these four genes in conjunctival epithelial cells. We constructed a comprehensive gene regulatory network using transcriptomic data from murine conjunctival epithelial cells under 16 distinct conditions, including polyI:C stimulation across wild-type, knockout, and transgenic backgrounds for the key genes. A targeted network analysis systematically identified numerous candidate genes mediating the crosstalk between the regulatory pathways initiated by Ikzf1, Ptger3, Mavs, and Tlr3. The identified candidates suggest the involvement of diverse signaling pathways previously unlinked to SJS pathology. Our findings suggest that the pathogenesis of SJS may arise not from the dysfunction of isolated genes but from the disruption of a balance maintained by intricate pathway crosstalk.

Animals↗
PubMed2007

Enhanced expression of adipocyte-type fatty acid binding protein in murine lymphocytes in response to dexamethasone treatment.

Fatty acids have a great influence on the process of lymphocyte apoptosis which is considered as a modulating factor of immune response in both humans and animals. However the mechanism underlying the function of fatty acids in the process of lymphocyte apoptosis is not fully understood. In this study we show that the appearance of adipocyte-type fatty acid binding protein (A-FABP) is induced upon administration of dexamethasone (DEX) in both in vivo and cultured lymphocytes, and its distinct nuclear localization occurs in close relation to the DEX-induced apoptosis process. In immunohistochemistry of mouse spleen, A-FABP-immunoreactivity starts to occur 3 h after DEX stimulation, and it massively localizes in the nucleus 8 h after the treatment, while no A-FABP-immunoreactivity is discerned in the lymphocytes of normal as well as 24 h post-injection spleen. In the murine T-cell leukemia CTLL-2 cells, A-FABP-immunoreactivity is also induced in both of the cytoplasm and nucleus when the apoptosis is induced by IL-2 retrieval together with DEX treatment, while in the presence of IL-2 A-FABP-immunoreactivity is confined to the cytoplasm with DEX treatment. On the other hand, A-FABP-immunoreactivity is not detected by IL-2 retrieval alone. The present findings altogether suggest that A-FABP and its ligands, fatty acids, play an important role in the process of apoptosis and the immune modulation induced by DEX.

Adipocytes↗
PubMed2007

Geographic difference of mortality of Creutzfeldt-Jakob disease in Japan.

BACKGROUND: The geographic mortality difference of Creutzfeldt-Jakob disease is still unclear in Japan. METHODS: Using vital statistics of Japan for 6 year period between 1999 and 2004 officially published by the government, we observed the mortality from Creutzfeldt-Jakob disease (ICD-10th: A81.0 and A81.8) by prefecture. Standardized mortality ratios were calculated for the 47 prefectures. RESULTS: For the observed 6 years, a total of 792 deaths from Creutzfeldt-Jakob disease were observed whole in Japan. Two prefectures, Akita and Yamanashi, presented significantly high standardized mortality ratios. In addition, Tochigi, Kochi, and Nagasaki showed standardized mortality rates higher than 1.5 without significance. No prefecture had significantly low standardized mortality ratios. CONCLUSION: Some prefectures with high mortality rate from Creutzfeldt-Jakob disease existed in Japan. Some of them had high incidence rate in a survey conducted in 1996 as well.

Adolescent↗
PubMed2006

Chimeric VEGF-ENZ7/PlGF specifically binding to VEGFR-2 accelerates skin wound healing via enhancement of neovascularization.

OBJECTIVE: VEGF-E(NZ7)/PlGF molecules composed of Orf virus-derived VEGF-E(NZ7) and human PlGF1 were previously proven to be potent angiogenic factors stimulating angiogenesis without significant enhancement of vascular leakage and inflammation in vivo. For its future clinical application, there is a pressing need to better understand the beneficial effects of VEGF-E(NZ7)/PlGF during wound healing in adulthood. METHODS AND RESULTS: In this study, several angiogenic factors were administrated to skin punched wounds of both wild-type and diabetic mice. The treatment with VEGF-E(NZ7)/PlGF accelerated wound closure accompanied with enhanced angiogenesis, the process was occurring slightly faster than that in VEGF-A164 group. Moreover, the macrophage infiltration and lymphangiogenesis level in healed wounds were strikingly lower in VEGF-E(NZ7)/PlGF group than VEGF-A164 group, suggesting that the increased inflammation was the key issue preventing speedy wound healing of VEGF-A164-treated skin. Considering clinical safety, we further examined the antigenicity of chimeric VEGF-E(NZ7)/PlGF. Compared with the original VEGF-E(NZ7), the immunogenicity of VEGF-E(NZ7)/PlGF molecules was markedly decreased in mice and squirrel monkeys with the increase of PlGF1 humanized ratio. CONCLUSION: These results indicate that VEGF-E(NZ7)/PlGF molecules are superior to VEGF-A for the acceleration of either normal or delayed skin wound healing and might be regarded as potential drugs in therapeutic angiogenesis.

Animals↗
PubMed2006

Flexible ex vivo phantoms for validation of diffusion tensor tractography on a clinical scanner.

PURPOSE: The aim of this study was to develop ex vivo diffusion tensor (DT) flexible phantoms. MATERIALS AND METHODS: Materials were bundles of textile threads of cotton, monofilament nylon, rayon, and polyester bunched with spiral wrapping bands and immersed in water. DT images were acquired on a 1.5-Tesla clinical magnetic resonance scanner using echo planar imaging sequences with 15 motion probing gradient directions. DT tractography with seeding and a line-tracking method was carried out by software originally developed on a PC-based workstation. RESULTS: We observed relatively high fractional anisotropy on the polyester phantom and were able to reconstruct tractography. Straight tracts along the bundle were displayed when it was arranged linearly. It was easy to bend arcuately or bifurcate at one end; and tracts followed the course of the bundle, whether it was curved or branched and had good agreement with direct visual observation. Tractography with the other fibers was unsuccessful. CONCLUSION: The polyester phantom revealed a diffusion anisotropic structure according to its shape and would be utilizable repeatedly under the same conditions, differently from living central neuronal system. It would be useful to validate DT sequences and to optimize an algorithm or parameters of DT tractography software. Additionally, the flexibility of the phantom would enable us to model human axonal projections.

Anisotropy↗
PubMed2006

[Change in awareness of waste reduction as observed among female students attending a college of nursing].

We conducted a survey from 1999 to 2004 of female students attending a college of nursing, regarding their awareness of the municipal waste reduction policy as well as the problems caused by dioxins. The questionnaire survey showed that over the six years a majority of students supported a stricter waste-sorting policy. The students were willing to sort waste in more minute details. Only a handful of students was aware of the municipal government's waste-reduction campaign. Furthermore, the students' awareness regarding problems caused by dioxins was high, but decreased from 94.7% in 1999 to 76.5% in 2004, with more than 90.0% of the students recognizing that it is necessary to reduce the total amount of waste in order to decrease dioxin emission from incineration plants.

Adolescent↗
PubMed2006

Epidermal-type fatty acid binding protein as a negative regulator of IL-12 production in dendritic cells.

Fatty acids and their metabolites have recently been shown to modulate various functions of dendritic cells (DCs) including their differentiation and cytokine production, although the mechanisms underlying their cellular functions are not fully understood. In view of our previous finding that epidermal-type fatty acid binding protein (E-FABP) was exclusively expressed in splenic DCs among FABP family, we examined the phenotype of E-FABP-null mutant mice in order to elucidate the functional significance of E-FABP expression in DCs. Although E-FABP-null mutant mice showed no apparent abnormalities in the population density and subset distribution of DCs as well as the microscopic morphology in the spleen, DCs isolated from E-FABP-null spleen showed enhanced production of IL-12p70, a key cytokine for innate immune responses, in response to appropriate stimuli as compared with wild-type. In real-time PCR, the expression level of IL-12p35 mRNA after LPS stimuli was much higher in mutant DCs when compared with wild-type, while no apparent change of IL-12p40 mRNA level was detected. Phosphorylated forms of p38 mitogen-activated protein kinase (p38MAPK) and IkappaB-alpha, molecules critical for IL-12 production, were detected at higher levels in E-FABP-null-mutant DCs after LPS stimuli when compared with wild-type counterparts. Collectively, it is suggested that E-FABP may be a novel negative regulator of IL-12 production in DCs, and this regulation may be exerted via its involvement in the p38MAPK-mediated transcription of IL-12p35.

Animals↗
PubMed2006

Prevalence and risk factors for hepatitis C virus infection in Mongolian children: Findings from a nationwide survey.

Although the hepatitis C virus (HCV) infection is one of the major causes of chronic hepatitis and hepatocellular carcinoma (HCC) in Mongolia, its prevalence among children and routes of transmission are largely unknown. The aim of the study was to determine the prevalence of anti-HCV antibodies and the possible risk factors for transmission among school children using representative national data. A nationwide cross-sectional survey among elementary school children was conducted in four main geographical regions and the metropolitan area of Mongolia, through multistage, stratified, random cluster sampling. Serum samples from 1,145 children (response rate, 93%; 592 boys and 553 girls; age range, 7-12 years), which represented nearly 2% of the second grade population in Mongolia, were tested for HCV antibodies with a third-generation immunoradiometric assay (IRMA). Positive samples were further evaluated by a third-generation immunoblot assay (RIBA). A standardized questionnaire concerning the socio-demographic characteristics and potential risk factors was used. Overall, seven subjects were confirmed to be anti-HCV seropositive, giving a prevalence of 0.6% (95% CI: 0.15-1.0%). The prevalence of anti-HCV increased with age. In the multivariate logistic regression analysis, adjusted for age, sex, and residence, the history of dental manipulation (odds ratio [OR] = 15.4; 95% CI: 1.4-164.8) and surgery (OR = 8.3; 95% CI: 1.5-45.6) were associated independently with the presence of anti-HCV. These findings suggest that contaminated equipment used in the dental and surgical manipulations probably played a predominant role in HCV transmission among Mongolian children. Strict guidelines on disinfection and sterilization procedures of medical instruments have to be introduced and should be followed to improve the control of HCV infection in Mongolia.

Child↗
PubMed2006

Selective detection of 2-nitrobenzenesulfenyl-labeled peptides by matrix-assisted laser desorption/ionization-time of flight mass spectrometry using a novel matrix.

The 2-nitrobenzenesulfenyl (NBS) method, which is useful for quantitative proteome analysis, is based on stable isotope labeling of tryptophan residues with NBS chloride ((12)C(6)-NBSCl or (13)C(6)-NBSCl). We found that 3-hydroxy-4-nitrobenzoic acid (3H4NBA) is a more suitable matrix than 2,5-dihydroxybenzoic acid (DHB) for detecting NBS-labeled peptides by MALDI-quadrupole IT (QIT)-TOF MS . Furthermore, NBS-labeled peptides were selectively ionized and detected in a mixture of NBS-labeled and unlabeled peptides. Labeled paired peaks were easily detected without enrichment, nonpaired labeled peaks were clearly distinguished from unlabeled contaminating peptides, and nitrotyrosine-containing peptides were also selectively detected on the 3H4NBA matrix, while by-product-peaks arising from nitrobenzene moieties were suppressed. The use of 3H4NBA as a comatrix with CHCA improved the sensitivity of detection while substantially retaining the selectivity of 3H4NBA. The 3H4NBA matrix offers great advantages in terms of simplicity, sensitivity, and usability when used for the NBS method and for MALDI-TOF MS analysis applied to compounds having a nitrobenzene ring.

Amino Acid Sequence↗
PubMed2006

Improved 2-nitrobenzenesulfenyl method: optimization of the protocol and improved enrichment for labeled peptides.

We have developed the NBS (2-nitrobenzenesulfenyl) method, a quantitative proteome analysis method utilizing stable isotope labeling followed by mass spectrometry. The potential of this method was reported previously, and the procedure has now been further optimized. Here, we describe a procedure utilizing urea or guanidine hydrochloride as a protein denaturant, in conjunction with an improved chromatographic enrichment method for the NBS-labeled peptides using a phenyl resin column. By using this new protocol, both sample loss throughout the protocol and the elution of unwanted unlabeled peptides can be minimized, improving the efficiency of the analysis significantly.

Animals↗
PubMed2006

Augmentation of osteopontin expression in renal tubuli is independent of a histopathological type of glomerular lesions in mouse lupus nephritis.

Augmentation of osteopontin (OPN) expression in renal tubuli is often observed in lupus nephritis. To investigate whether this might depend on histopathological type of glomerular lesions, comparative studies of the distribution and levels of OPN expression in kidneys were performed by in situ hybridization and real-time polymerase chain reaction in mouse lupus nephritis manifesting inflammatory (endocapillary proliferative) and deposit (wire loop) types of glomerular lesions. These glomerular lesions were developed in C.B-17/Inc-scid/scid mice by injection of IgG3 antibody producing hybridoma clones, 2B11.3 and 7B6.8, respectively, which are derived from an MRL/Mp-lpr/lpr (MRL/lpr) lupus mouse. Both clones significantly augmented OPN expression in renal tubuli, but a non-nephritogenic IgG3 clone, 1G3, derived from the same MRL/lpr mouse, did not. The OPN augmentation was prominent in the renal cortex and the inner stripe of the outer medulla. These results indicate that OPN augmentation in renal tubuli is not associated with a histopathological type of glomerular lesion in lupus nephritis, at least not with an inflammatory or a deposit type.

Animals↗
PubMed2006

Usefulness of 16-slice multislice spiral computed tomography for follow-up study of coronary stent implantation.

BACKGROUND: Although multislice spiral computed tomography (MSCT) is a promising technique for non-invasive coronary angiography, its usefulness in patients with stent implantation remains unclear. The aim of the present study was to compare the usefulness of MSCT with that of invasive coronary angiography for evaluating coronary stent patency. METHODS AND RESULTS: Thirty-one patients were enrolled after coronary stent implantation. Sixteen-slice MSCT scans were performed (39.0+/-21.8 days) before follow-up coronary angiography. After assigning an image score based on luminal visibility (1= poor, 2= fair, 3= good), factors determing image quality were analyzed. Among 42 implanted stents, 33 (78%) were assigned an image score of 3, 2 (5%) a score of 2, and 7 (17%) a score of 1. Image scores among stents with diameters >or=3.5 mm were significantly (p<0.05) higher than among smaller stents (<or=3.0 mm). Stent strut thickness did not affect image quality, but coronary calcification significantly (p<0.01) hampered the image quality. After excluding 7 stents with image scores of 1, the sensitivity, specificity, positive and negative predictive values of MSCT to identify patent stents were 83%, 90%, 63% and 96%, respectively. CONCLUSIONS: MSCT can provide useful and valuable clinical information for assessing stent patency during the follow-up period when patients are treated with relatively large diameter coronary stents.

Aged↗
PubMed2006

Continuation of smoking cessation and following weight change after intervention in a healthy population with high smoking prevalence.

Smoking prevalence among males is conspicuously high in Asian countries including Japan. There are few prospective intervention studies on the duration of smoking cessation within regions with a high prevalence of smokers, such as Asia. We investigated the extent to which subjects continued abstaining from smoking after receiving smoking cessation support provided for all smokers in an occupational setting, regardless of their willingness to quit smoking. The subjects were 251 male workers who were smokers and had received a smoking cessation intervention in 1997 in an occupational setting. Smoking cessation rates and body mass index (BMI) at 10, 18, 30, 42, 54, and 66 months after the initial intervention were confirmed during annual health check-ups. Those who quit smoking following the intervention and continuously abstained from smoking throughout the study period were separately examined for BMI. After five years, 10.6% of the smokers continued smoking cessation. Of the abstainers who quit following the intervention, the abstinence rate decreased in the first and second year, but it stabilized at approximately 45% after the third year. High nicotine dependence and a self-reported lack of willingness to quit smoking did not lower long-term abstinence rates. Abstainers initially gained 1.55 BMI on average, but decreased the weight gain to 0.96 BMI over six years. Introducing smoking cessation support without nicotine replacement therapy is an effective long-term strategy in a healthy population with a high smoking prevalence. Abstainers maintain their smoking cessation if they refrain from smoking for three years.

Adult↗
PubMed2006

Social class inequalities in self-rated health and their gender and age group differences in Japan.

BACKGROUND: Few studies have examined social inequalities in self-rated health in Japan, and the issue of gender differences related to social inequalities in self-rated health remains inconclusive. METHODS: The data derived from interviews with 2987 randomly selected Japanese adults in four prefectures in Japan who completed the cross-national World Mental Health survey from 2002 through 2005. We calculated odds ratios (ORs) of having poor self-rated physical and mental health by two social class indicators independently with multivariate logistic regression models, adjusted for age, gender, marital status, and area. Stratified analyses by gender and age group were also conducted. RESULTS: The adjusted ORs of the lowest educational attainment category having poor self-rated physical and mental health were 1.42 (95% confidence interval [CI]: 1.15-1.76) and 1.37 (95% CI: 1.10-1.70), respectively. Among females, educational attainment had significant linear associations with self-rated physical and mental health. Adjusted household income was also significantly associated with self-rated physical health among female respondents. No associations were found among males. While educational attainment was associated with self-rated health among the young age group, adjusted household income was associated with self-rated physical health in the middle and old age group. CONCLUSION: These results indicated social inequalities in self-rated health and prominent social inequalities in self-rated health among females in Japan. Social inequalities in self-rated health seemed to exist across age groups. However, the mechanism of social inequalities in self-rated health could be different depending on the age group.

Adult↗
PubMed2006

Hepatitis delta virus infection in mongolia: analyses of geographic distribution, risk factors, and disease severity.

The prevalence and risk factors for hepatitis delta virus (HDV) infection among Mongolian school children were assessed by detecting the antibody against HDV and HDV RNA, and through structured interviews. The study subjects consisted of 181 children with the past or ongoing hepatitis B virus infection who were investigated during the nationwide serosurvey conducted in 2004. The prevalence of antibody to HDV was 6.1%, with the proportion of 13.6% among hepatitis B surface antigen (HBsAg)-positive subjects, all of whom had HDV RNA. Multivariate logistic regression analyses showed that injections (> 11 times) (odds ratio [OR] = 8.31, 95% confidence interval [CI] = 1.28-54.07) and blood sampling (> 3 times) (OR = 5.34, 95% CI = 1.12-25.53) in health care settings, hospitalization (> 3 times) (OR = 6.20, 95% CI = 1.18-32.71), and cohabitating with patients with chronic hepatitis (OR = 4.57, 95% CI = 1.26-16.55) predicted the seropositivity for antibody to HDV. These results suggest that parenteral exposures in health care settings and household transmission are the main routes of HDV transmission among Mongolian children.

Antibodies, Viral↗
PubMed2006

[Combination chemotherapy with S-1 plus CPT-11 for patients with advanced or recurrent colorectal cancer].

Various kinds of combination chemotherapies with 5-FU as a base agent have been performed for patients with advanced or recurrent colorectal cancer. S-1 was a newly developed 5-FU derivative and was orally administered. One of the combination therapies with S-1 plus irinotecan (CPT-11) has also been expected to have a better therapeutic value. Recently this combination therapy has been undertaken by our department, and its clinical use and toxicities are described in this article.

Administration, Oral↗