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1.
J Gastroenterol ; 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31240436

RESUMO

BACKGROUND: Gastric cancer (GC) is one of the most common causes of cancer deaths worldwide; however, reliable and non-invasive screening methods for GC are not established. Therefore, we conducted this study to develop a biomarker for GC detection, consisting of urinary microRNAs (miRNAs). METHODS: We matched 306 participants by age and sex [153 pairs consisting of patients with GC and healthy controls (HCs)], then randomly divided them across three groups: (1) the discovery cohort (4 pairs); (2) the training cohort (95 pairs); and (3) the validation cohort (54 pairs). RESULTS: There were 22 urinary miRNAs with significantly aberrant expressions between the two groups in the discovery cohort. Upon multivariate analysis of the training cohort, urinary expression levels of miR-6807-5p and miR-6856-5p were significantly independent biomarkers for diagnosis of GC, in addition to Helicobacter pylori (H. pylori) status. A diagnostic panel that combined these 2 miRNAs and H. pylori status distinguished between HC and GC samples with an area under the curve (AUC) = 0.736. In the validation cohort, urinary miR-6807-5p and miR-6856-5p showed significantly higher expression levels in the GC group, and the combination biomarker panel of miR-6807-5p, miR-6856-5p, and H. pylori status also showed excellent performance (AUC = 0.885). In addition, this biomarker panel could distinguish between HC and stage I GC patients with an AUC = 0.748. Urinary expression levels of miR-6807-5p and miR-6856-5p significantly decreased to undetectable level after curative resection of GC. CONCLUSIONS: This novel biomarker panel enables early and non-invasive detection of GC.

2.
Sleep ; 42(6)2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-30810208

RESUMO

Usual sleep duration has substantial heritability and is associated with various physical and psychiatric conditions as well as mortality. However, for its genetic locus, only PAX8 and VRK2 have been replicated in previous genome-wide association studies (GWAS). We conducted a GWAS meta-analysis of self-reported usual sleep duration using three population-based cohorts totaling 31 230 Japanese individuals. A genome-wide significant locus was identified at 12q24 (p-value < 5.0 × 10-8). Subsequently, a functional variant in the ALDH2 locus, rs671, was replicated in an independent sample of 5140 Japanese individuals (p-value = 0.004). The association signal, however, disappeared after adjusting for alcohol consumption, indicating the possibility that the rs671 genotype modifies sleep duration via alcohol consumption. This hypothesis explained a modest genetic correlation observed between sleep duration and alcohol consumption (rG = 0.23). A Mendelian randomization analysis using rs671 and other variants as instrumental variables confirmed this by showing a causal effect of alcohol consumption, but not of coffee consumption on sleep duration. Another genome-wide significant locus was identified at 5q33 after adjusting for drinking frequency. However, this locus was not replicated, nor was the PAX8 and VRK2. Our study has confirmed that a functional ALDH2 variant, rs671, most strongly influences on usual sleep duration possibly via alcohol consumption in the Japanese population, and presumably in East Asian populations. This highlights the importance of considering the involvement of alcohol consumption in future GWAS of usual sleep duration, even in non-East Asian populations, where rs671 is monomorphic.

3.
Public Health Nutr ; 22(8): 1351-1360, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30803461

RESUMO

OBJECTIVE: We aimed to examine missing data in FFQ and to assess the effects on estimating dietary intake by comparing between multiple imputation and zero imputation. DESIGN: We used data from the Okazaki Japan Multi-Institutional Collaborative Cohort (J-MICC) study. A self-administered questionnaire including an FFQ was implemented at baseline (FFQ1) and 5-year follow-up (FFQ2). Missing values in FFQ2 were replaced by corresponding FFQ1 values, multiple imputation and zero imputation. SETTING: A methodological sub-study of the Okazaki J-MICC study.ParticipantsOf a total of 7585 men and women aged 35-79 years at baseline, we analysed data for 5120 participants who answered all items in FFQ1 and at least 50% of items in FFQ2. RESULTS: Among 5120 participants, the proportion of missing data was 3·7%. The increasing number of missing food items in FFQ2 varied with personal characteristics. Missing food items not eaten often in FFQ2 were likely to represent zero intake in FFQ1. Most food items showed that the observed proportion of zero intake was likely to be similar to the probability that the missing value is zero intake. Compared with FFQ1 values, multiple imputation had smaller differences of total energy and nutrient estimates, except for alcohol, than zero imputation. CONCLUSIONS: Our results indicate that missing values due to zero intake, namely missing not at random, in FFQ can be predicted reasonably well from observed data. Multiple imputation performed better than zero imputation for most nutrients and may be applied to FFQ data when missing is low.

4.
Transl Oncol ; 12(3): 539-544, 2019 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-30611902

RESUMO

Since a fecal occult blood test for colorectal cancer (CRC) does not offer sufficient diagnostic power for CRC, novel non-invasive biomarkers are hopeful for CRC screening. We conducted the current study to discover non-invasive urinary biomarkers for diagnosing CRC. Among urine samples from 258 patients (CRC, n = 148; healthy controls, n = 110), a cohort of 176 patients composed of 88 patients with GC and 88 healthy controls was selected after age- and sex-matching using propensity score. This cohort was then randomly divided into 2 groups: 53 pairs (106 patients) in the training cohort, and 35 pairs (70 patients) in the validation cohort. No significant differences were found for baseline characteristics between the CRC and healthy control groups in both training and validation cohorts. On multivariate analysis in the training cohort, urinary levels of cysteine-rich protein 61 (uCyr61) and trefoil factor 3 (uTFF3) were identified as independent significant diagnostic markers for CRC. Moreover, uCyr61 alone and the combination of uCyr61 and uTFF3 allowed significant differentiation between healthy controls and CRC groups in the training set (uCyr61: area under the curve (AUC) = 0.745 [95% CI, 0.653-0.838]; uCyr61 + uTFF3: AUC = 0.753 [95% CI, 0.659-0.847]). In the validation cohort, uCyr61 and uTFF3 were significantly higher in the CRC group than in the healthy control group, and they also allowed significant differentiation between healthy control and CRC groups (uCyr61: AUC = 0.696 [95% CI, 0.571-0.822]; uTFF3: AUC = 0.639 [95% CI, 0.508-0.770]; uCyr61 + uTFF3: AUC = 0.720 [95% CI, 0.599-0.841]), as in the training cohort. A panel combining uCyr61 and uTFF3 offers a promising non-invasive biomarker for diagnosing CRC.

5.
J Epidemiol ; 2018 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-30249943

RESUMO

BACKGROUND: It is known that physical activity affects glucose metabolism. However, there have been no reports on the influence of physical activity earlier in life on subsequent glucose metabolism. Therefore, we analyzed the influence of physical activity in earlier decades of life on insulin resistance in middle aged and older residents in Japan. METHODS: The subjects were 6,883 residents of Okazaki City between the ages of 40 and 79 years who underwent physical examinations at the Okazaki City Medical Association Public Health Center from April 2007 through August 2011. They gave informed consent for participation in the study. Data on individual characteristics were collected via a questionnaire and from the health examination records. Fasting blood glucose and insulin levels were used to calculate the homeostatic model assessment of insulin resistance (HOMA-IR). HOMA-IR >1.6 was considered to indicate insulin resistance for the purpose of logistic regression models. RESULTS: The study sample included 3,683 men and 3,200 women for whom complete information was available. For those who exercised regularly throughout their teens to their 30s-40s, the odds ratio for having insulin resistance was 0.75 (95% confidence interval [CI], 0.58-0.96) for men and 0.76 (95% CI, 0.58-0.99) for women after adjusting for other variables, including age, body mass index, and present physical activity. A linear trend was also observed in both men and women. CONCLUSIONS: Subjects who have exercised regularly in the early decades of life are less likely to have insulin resistance later in life.

6.
Oncotarget ; 8(17): 29247-29257, 2017 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28418926

RESUMO

The current imaging modalities are not sufficient to identify inoperable tumor factors, including distant metastasis and local invasion. Hence, we conducted this study using urine samples to discover non-invasive biomarkers for the incurability of gastric cancer (GC). Urine samples from 111 GC patients were analyzed in this study. The GC cohort was categorized and analyzed according to disease stage and operability. In the discovery phase, protease protein array analysis identified 3 potential candidate proteins that were elevated in the urine of advanced GC patients compared to early GC patients. Among them, urinary kallikrein 10 (KLK10) was positively associated with tumor stage progression. Moreover, the urinary level of KLK10 (uKLK10) was significantly elevated in the urine of patients with inoperable GC compared to operable GC patients (median, 118 vs. 229; P=0.014). The combination of uKLK10, tumor location and tumor size distinguished operability of GC with an area under the curve of 0.859, 82.4% sensitivity and 86.2% specificity. Disease-free survival (DFS) was significantly shorter in GC patients with high uKLK10 compared to those with low uKLK10 (hazard ratio: 3.30 [95% confidence interval, 1.58-6.90] P<0.001). Immunohistochemical analyses also demonstrated a positive correlation between tumor stage and KLK10 expression in GC tissues (r=0.426, P<0.001). In addition, GC patients with high expression of pathological KLK10 (pKLK10) showed a significantly shorter DFS compared to those with low pKLK10 (hazard ratio: 3.79 [95% confidence interval, 1.27-11.24] P=0.010). uKLK10 is a promising non-invasive biomarker for the inoperability and incurability of GC.


Assuntos
Neoplasias Gástricas/diagnóstico , Calicreínas Teciduais/urina , Idoso , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
7.
J Dermatol ; 43(11): 1350-1353, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27458049

RESUMO

Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa of unknown etiology. Clinically, the erosive type of OLP (erosive OLP) can show features similar to those of pemphigus vulgaris (PV), an autoimmune blistering disorder in which desmoglein (Dsg)3 is targeted. In addition to clinical and histopathological findings, immunological studies, including direct immunofluorescence (IF), indirect IF and enzyme-linked immunosorbent assay (ELISA) that detect autoantibodies to Dsg3, are helpful in differentiating erosive OLP from PV. Here, we show two cases of erosive OLP with autoantibodies to Dsg3. Patient 1 was a 68-year-old woman with chronic erosions of the oral mucosa, in which elevated levels of immunoglobulin (Ig)G autoantibodies to Dsg1 and Dsg3 were detected by ELISA. Patient 2 was an 85-year-old woman with white striae with erosions on the lateral sides of the buccal mucosa with elevated levels of IgG autoantibodies to Dsg3 detected by ELISA. Histopathological findings from both cases showed lichenoid dermatitis, and both direct and indirect IF showed no tissue-bound IgG autoantibodies. From these findings, the diagnosis of erosive OLP was made. Immunological assays revealed both cases to have IgG-directing calcium-independent linear epitopes on Dsg3, which are suggestive of non-pathogenic autoantibodies. In addition, autoantibodies to Dsg3 in patient 2 reacted with a prosequence-possessing precursor form of Dsg3 but not with the mature form of the molecule. The present study suggests that erosive OLP may develop anti-Dsg3 autoantibodies, which should be carefully assessed.


Assuntos
Autoanticorpos/imunologia , Desmogleína 3/imunologia , Líquen Plano Bucal/imunologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Líquen Plano Bucal/patologia , Mucosa Bucal/patologia
8.
Sci Rep ; 6: 23545, 2016 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-27009236

RESUMO

Cellular interactions with the extracellular matrix play critical roles in tumor progression. We previously reported that receptor activator of NF-κB ligand (RANKL) specifically facilitates head and neck squamous cell carcinoma (HNSCC) progression in vivo. Here, we report a novel role for RANKL in the regulation of cell adhesion. Among the major type I collagen receptors, integrin α2 was significantly upregulated in RANKL-expressing cells, and its knockdown suppressed cell adhesion. The mRNA abundance of integrin α2 positively correlated with that of RANKL in human HNSCC tissues. We also revealed that RANK-NF-κB signaling mediated integrin α2 expression in an autocrine/paracrine manner. Interestingly, the amount of active integrin ß1 on the cell surface was increased in RANKL-expressing cells through the upregulation of integrin α2 and endocytosis. Moreover, the RANK-integrin α2 pathway contributed to RANKL-dependent enhanced survival in a collagen gel and inhibited apoptosis in a xenograft model, demonstrating an important role for RANKL-mediated cell adhesion in three-dimensional environments.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , Integrina alfa2/genética , NF-kappa B/metabolismo , Ligante RANK/genética , Ligante RANK/metabolismo , Animais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Adesão Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Integrina alfa2/metabolismo , Camundongos , Transplante de Neoplasias , Transdução de Sinais
9.
Histol Histopathol ; 31(12): 1315-26, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26984199

RESUMO

In order to provide a clue to understand the interplay between leptin and estrogen, we have examined femoral metaphyses of ovariectomized db/db mice carrying a mutated leptin receptor. We performed ovariectomy (OVX) or sham-operation (sham) on 12-week old female wild-type and db/db mice, and then, after 8 weeks, divided the animals into four groups: wild-type sham, wild-type OVX, db/db sham and db/db OVX. Samples from all groups were prepared for histochemical and ultrastructural examinations. As a result, db/db sham mice showed a reduced number and thickness of metaphyseal trabeculae and excessive adipose tissue when compared to wild-type sham mice. The wild-type OVX group exhibited markedly diminished trabecular number, as well as lower populations of osteoblasts and osteoclasts in comparison to wild-type sham group. On the other hand, trabecular numbers were similar for the two db/db groups, suggesting that the effect of the ovariectomy, i.e., estrogen deficiency may be lessened in this animal model. Leptin receptor was mainly found in osteoblasts and in bone marrow stromal cells including adipocytes. In addition, the expression of estrogen receptor did not seem to change after OVX in wild-type mice and in db/db mice. Both db/db sham and OVX mice featured many adipocytes close to the metaphyseal chondro-osseous junction, while osteoblasts accumulated glycogen granules and lipid droplets. Therefore, it seems likely that the disruption of leptin signaling in db/db mice shifts the cell differentiation cascade towards the adipocyte lineage, resulting in an osteoporotic bone independently of estrogen deficiency.


Assuntos
Fêmur/patologia , Obesidade/fisiopatologia , Osteoporose/fisiopatologia , Receptores para Leptina/genética , Tecido Adiposo/patologia , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Mutantes , Microscopia Eletrônica de Transmissão , Osteoporose/patologia , Ovariectomia , Reação em Cadeia da Polimerase , Receptores para Leptina/metabolismo , Transcriptoma
10.
Acta Histochem Cytochem ; 48(3): 95-101, 2015 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-26160988

RESUMO

To elucidate the fate of the epithelial root sheath during initial cellular cementogenesis, we examined developing maxillary first molars of rats by immunohistochemistry for keratin, vimentin, and tissue non-specific alkaline phosphatase (TNALP) and by TdT-mediated dUTP nick end labeling (TUNEL). The advancing root end was divided into three sections, which follow three distinct stages of initial cellular cementogenesis: section 1, where the epithelial sheath is intact; section 2, where the epithelial sheath becomes fragmented; and section 3, where initial cellular cementogenesis begins. After fragmentation of the epithelial sheath, many keratin-positive epithelial sheath cells were embedded in the rapidly growing cellular cementum. A few unembedded epithelial cells located on the cementum surface. Dental follicle cells, precementoblasts, and cementoblasts showed immunoreactivity for vimentin and TNALP. In all three sections, there were virtually no cells possessing double immunoreactivity for vimentin-keratin or TNALP-keratin and only embedded epithelial cells showed TUNEL reactivity. Taken together, these findings suggest that: (1) epithelial sheath cells divide into two groups; one group is embedded in the cementum and thereafter dies by apoptosis, and the other survives on the cementum surface as epithelial cell rests of Malassez; and (2) epithelial sheath cells do not undergo epithelial-mesenchymal transition during initial cellular cementogenesis.

11.
Cancer Prev Res (Phila) ; 8(3): 240-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25591790

RESUMO

Although the early diagnosis of gastric cancer provides the opportunity for curative endoscopic resection, comprehensive screening endoscopy would be invasive and expensive. To date, there is a complete absence of clinically useful gastric cancer biomarkers. With the goal of discovering noninvasive biomarkers for the early diagnosis of gastric cancer, we have conducted a case-control study using urine samples from individuals with gastric cancer versus healthy control samples. Of the enrolled 106 patients from September, 2012 to April, 2013, a cohort of 70 patients composed of 35 patients with gastric cancer and 35 age- and sex-matched healthy controls was analyzed. The gastric cancer group was composed of stage IA of 62.9% (22/35). The urinary levels of MMP-9/NGAL complex (uMMP-9/NGAL) and ADAM12 (uADAM12) were significantly higher in the gastric cancer group compared with the healthy control group as determined by monospecific ELISAs (uMMP-9/NGAL: median, 85 pg/mL vs. 0 pg/mL; P = 0.020; uADAM12: median, 3.35 ng/mL vs. 1.44 ng/mL; P < 0.001). Multivariate analysis demonstrated that both uMMP-9/NGAL and uADAM12 were significant, independent diagnostic biomarkers for gastric cancer. Moreover, MMP-9/NGAL activity was significantly elevated as determined by gelatin zymography. The combination of uMMP-9/NGAL with uADAM12 distinguished between control samples and gastric cancer samples with an AUC of 0.825 (P < 0.001) in an ROC analysis. Significantly, immunohistochemical analyses demonstrated a high coexpression of MMP-9 and NGAL (P < 0.001) and high expression of ADAM12 (P < 0.001) in gastric cancer tissues compared with adjacent normal tissues (N = 35). In summary, uMMP-9/NGAL and uADAM12 are potential noninvasive biomarkers for gastric cancer, including early-stage disease.


Assuntos
Proteínas ADAM/urina , Proteínas da Fase Aguda/urina , Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/urina , Lipocalinas/urina , Metaloproteinase 9 da Matriz/urina , Proteínas de Membrana/urina , Proteínas Proto-Oncogênicas/urina , Neoplasias Gástricas/diagnóstico , Proteína ADAM12 , Adenocarcinoma/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Lipocalina-2 , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Análise Serial de Proteínas , Curva ROC , Neoplasias Gástricas/urina , Adulto Jovem
12.
Histochem Cell Biol ; 142(5): 489-96, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24859538

RESUMO

This study was designed to examine developing acellular cementum in rat molars by immunohistochemistry, to elucidate (1) how Hertwig's epithelial root sheath disintegrates and (2) whether epithelial sheath cells transform into cementoblasts through epithelial-mesenchymal transition (EMT). Initial acellular cementogenesis was divided into three developmental stages, which can be seen in three different portions of the root: portion 1, where the epithelial sheath is intact; portion 2, where the epithelial sheath becomes fragmented; and portion 3, where acellular cementogenesis begins. Antibodies against three kinds of matrix proteinases, which degrade epithelial sheath-maintaining factors, including basement membrane and desmosomes, were used to investigate proteolytic activity of the epithelial sheath. Tissue non-specific alkaline phosphatase (TNALP) and keratin were used to investigate EMT. Epithelial sheath cells showed immunoreactivity for all three enzymes at fragmentation, which suggests that epithelial sheath disintegration is enzymatically mediated. Dental follicle cells and cementoblasts showed intense immunoreactivity for TNALP, and from portion 1 through to 3, the reaction extended from the alveolar bone-related zone to the root-related zone. Cells possessing keratin/TNALP double immunoreactivity were virtually absent. Keratin-positive epithelial sheath cells showed negligible immunoreactivity for TNALP, and epithelial cells did not appear to migrate to the dental follicle. Together, these findings suggest that a transition phenotype between epithelial cells and cementoblasts does not exist in the developing dental follicle and hence that epithelial sheath cells do not undergo EMT during initial acellular cementogenesis. In brief, this study supports the notion that cementoblasts derive from the dental follicle.


Assuntos
Cementogênese , Células Epiteliais/citologia , Dente Molar/citologia , Raiz Dentária/citologia , Animais , Células Epiteliais/metabolismo , Masculino , Dente Molar/metabolismo , Ratos , Ratos Wistar , Raiz Dentária/metabolismo
13.
Histol Histopathol ; 29(6): 731-42, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24352874

RESUMO

Verifying whether periostin affects the distribution of type I collagen, fibronectin and tenascin C in the periodontal ligament (PDL) is important to contribute to a more thorough understanding of that protein's functions. In this study, we have histologically examined incisor PDL of mandibles in 20 week-old male wild-type and periostin-deficient (periostin-/-) mice, by means of type I collagen, fibronectin, tenascin C, proliferating cell nuclear antigen, matrix metallo-proteinase (MMP)-1 and F4/80-positive monocyte/macrophage immunostaining, transmission electron microscopy and quantitative analysis of cell proliferation. Wild-type PDL featured well-arranged layers of collagen bundles intertwined with PDL cells, whose longitudinal axis ran parallel to the collagen fibers. However, cells in the periostin-/- PDL were irregularly distributed among collagen fibrils, which were also haphazardly arranged. Type I collagen and fibronectin reactivity was seen throughout the wild-type PDL, while in the periostin-/- PDL, only focal, uneven staining for these proteins could be seen. Similarly, tenascin C staining was evenly distributed in the wild-type PDL, but hardly seen in the periostin-/- PDL. MMP-1 immunoreactivity was uniformly distributed in the wild-type PDL, but only dotted staining could be discerned in the periostin-/- PDL. F4/80-positive monocyte/macrophages were found midway between tooth- and bone-related regions in the wild-type PDL, a pattern that could not be observed in the periostin-/- PDL. In summary, periostin deficiency may not only cause PDL collagen fibril disorganization, but could also affect the distribution of other major extracellular matrix proteins such as fibronectin and tenascin C.


Assuntos
Moléculas de Adesão Celular/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Matriz Extracelular/metabolismo , Ligamento Periodontal/metabolismo , Animais , Antígenos de Diferenciação/metabolismo , Moléculas de Adesão Celular/genética , Proliferação de Células/fisiologia , Colágeno Tipo I/metabolismo , Fibronectinas/metabolismo , Masculino , Metaloproteinase 1 da Matriz/metabolismo , Camundongos , Camundongos Knockout , Antígeno Nuclear de Célula em Proliferação/metabolismo , Tenascina/metabolismo
14.
Cancer Imaging ; 14: 11, 2014 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-25608450

RESUMO

BACKGROUND: Previous studies have reported that the signal attenuation of diffusion-weighted magnetic resonance imaging (DWI) for normal breast tissue and tumor were well fitted by a monoexponential and a biexponential function, respectively. The aim of this study was to investigate the optimal b-value to detect breast tumors from DWI signal attenuations. METHODS: Sixty-four subjects with breast cancer underwent DWI using six b-values up to 3500 s/mm2. The signal attenuations of normal breast and tumor were fitted by mono- and biexponential functions, respectively. The maximum contrast b-values were estimated and compared in terms of frequency. RESULTS: In almost all cases, the contrast increased with a b-value from 0 to approximately 1500 s/mm2. For b > 1500 s/mm2, the contrast decreased. The highest contrast b-value in the range of 0 to 2500 s/mm2 most frequently was b = 1500 and the next most frequent was 1400 s/mm2. Comparing sensitivity and specificity between b = 700 and b = 1400 s/mm2, b =1400 s/mm2 was slightly superior. CONCLUSION: Based on these results, DWI with a b-value of approximately 1400-1500 s/mm2 is recommended for optimizing breast tumor detectability.


Assuntos
Neoplasias da Mama/diagnóstico , Imagem de Difusão por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade
15.
Bone ; 57(1): 206-19, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23954506

RESUMO

In an attempt to identify the histological properties of the klotho-deficient (kl/kl) bone matrix, bone mineralization and the localization of Ca(2+)-binding bone matrix proteins - osteocalcin, dentin matrix protein-1 (DMP-1) and matrix Gla protein (MGP) - were examined in kl/kl tibiae. While a widespread osteocalcin staining could be verified in the wild-type bone matrix, localization of the same protein in the kl/kl tibiae seemed rather restricted to osteocytes with only a faint staining of the whole bone matrix. In wild-type mice, MGP immunoreactivity was present at the junction between the epiphyseal bone and cartilage, and at the insertion of the cruciate ligaments. In kl/kl mice, however, MGP was seen around the cartilaginous cores of the metaphyseal trabeculae and in the periphery of some cells of the bone surface. DMP-1 was identified in the osteocytic canalicular system of wild-type tibiae, but in the kl/kl tibiae this protein was mostly found in the osteocytic lacunae and in the periphery of some cells of the bone surface. Mineralization of the kl/kl bone seemed somewhat defective, with broad unmineralized areas within its matrix. In these areas, mineralized osteocytes along with their lacunae and osteocytic cytoplasmic processes were found to have intense osteocalcin and DMP-1 staining. Taken together, it might be that the excessive production of Ca(2+)-binding molecules such as osteocalcin and DMP-1 by osteocytes concentrates mineralization around such cells, disturbing the completeness of mineralization in the kl/kl bone matrix.


Assuntos
Osteocalcina/metabolismo , Osteócitos/metabolismo , Fosfatase Ácida/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Proteínas da Matriz Extracelular/metabolismo , Glucuronidase/deficiência , Glucuronidase/genética , Imuno-Histoquímica , Isoenzimas/metabolismo , Masculino , Camundongos , Microscopia Imunoeletrônica , Osteopontina/metabolismo , Fosfatase Ácida Resistente a Tartarato
16.
Biomed Res ; 34(3): 119-28, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23782745

RESUMO

We have histologically examined vascular invasion and calcification of the hypertrophic zone during endochondral ossification in matrix metalloproteinase (MMP)-9 deficient (MMP-9-/-) mice and in their littermates at 3 days, 3 weeks and 6 weeks after birth. Capillaries and osteoclasts at the chondro-osseous junction showed an intense MMP-9 immunopositivity, suggesting that they recognize chemical properties of cartilaginous matrices, and then release MMP-9 for cartilage degradation. CD31-positive capillaries and tartrate-resistant acid phosphatase-reactive osteoclasts could be found in the close proximity in the region of chondro-osseous junction in MMP-9-/- mice, while in wild-type mice, vascular invasion preceded osteoclastic migration into the epiphyseal cartilage. Although MMP-9-/- mice revealed larger hypertrophic zones, the index of calcified area was significantly smaller in MMP-9-/- mice. Interestingly, the lower layer of the MMP-9-/- hypertrophic zone showed intense MMP-13 staining, which could not be observed in wild-type mice. This indicates that MMP-13 may compensate for MMP-9 deficiency at that specific region, but not to a point at which the deficiency could be completely rescued. In conclusion, it seems that MMP-9 is the optimal enzyme for cartilage degradation during endochondral ossification by controlling vascular invasion and subsequent osteoclastic migration.


Assuntos
Células Endoteliais/citologia , Lâmina de Crescimento/irrigação sanguínea , Lâmina de Crescimento/citologia , Metaloproteinase 9 da Matriz/genética , Osteoclastos/citologia , Osteogênese , Animais , Animais Recém-Nascidos , Calcificação Fisiológica , Movimento Celular , Condrócitos/citologia , Condrócitos/enzimologia , Células Endoteliais/enzimologia , Expressão Gênica , Lâmina de Crescimento/enzimologia , Lâmina de Crescimento/crescimento & desenvolvimento , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/deficiência , Camundongos , Camundongos Knockout , Neovascularização Fisiológica , Osteoclastos/enzimologia
17.
Biomed Res ; 34(3): 153-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23782749

RESUMO

Sclerostin, an osteocyte-derived molecule, has been reported to serve as a negative regulator of osteoblastic activity as well as bone remodeling. However, there is no report that verified the regional difference for sclerostin synthesis, and in this study we have investigated immunolocalization of sclerostin by comparing dentin matrix protein (DMP) 1, an osteocyte-derived factor broadly expressed in tibial metaphyses and cortical bone. In metaphyseal primary trabecules, a site of bone modeling, strong DMP1-reactivity was observed in osteocytic lacunar-canalicular system (OLCS), while faint staining for sclerostin was visible only in a few osteocytes. In secondary trabecules, in which bone remodeling begins, some osteocytes showed intense sclerostin-immunopositivity, though there were many DMP1-positive osteocytes. In cortical bone, there were more osteocytes reactive for sclerostin, when compared with those in the secondary trabecules. Silver impregnation verified that immature, primary trabecules contained randomly-oriented OLCS, while mature, cortical bone showed geometrically well-arrangement of OLCS. Taken together, though DMP1 is broadly synthesized in bone, sclerostin appears to be abundantly synthesized in regular OLCS of cortical bone, but less produced in irregular OLCS as seen in primary trabecules, indicating the regional difference for sclerostin synthesis.


Assuntos
Proteínas da Matriz Extracelular/genética , Glicoproteínas/genética , Osteócitos/metabolismo , Osteogênese/genética , Tíbia/metabolismo , Animais , Remodelação Óssea , Proteínas da Matriz Extracelular/metabolismo , Expressão Gênica , Glicoproteínas/metabolismo , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos ICR , Osteócitos/citologia , Tíbia/citologia
18.
Kaibogaku Zasshi ; 88(1-2): 25-8, 2013 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-23600319

RESUMO

The School of Dental Medicine in Japan nurtures well-trained professionals who are at the cutting edge of the present knowledge in the fields of Dentistry and Dental Technology. As an important part of its mission, many Schools of Dental Medicine in Japan, including Hokkaido University, also encourages dental students to pursue basic research in the many aspects of Dentistry. It is of importance to cultivate research-minded students in Dental Medicine. Laboratory assignment conducted by the School of Dental Medicine, Hokkaido University, is one process of education curriculum to assign students in the fifth and sixth grade to laboratories of basic sciences. Every dental student should belong to one laboratory, which accepts the fixed number of the students. By means of the research activity of the laboratory assignments, some students obtain new insights on their research projects, and will often have an opportunity for presenting their findings in some academic meetings. Meanwhile, many academic meetings in Japan, including The Japanese Association of Anatomists, often feature special sessions where undergraduate students can present their findings under the guidance of their mentors. Such initiatives led by the Dental School and the academic meetings are geared towards raising interest in research and preparing young investigators for the future.


Assuntos
Pesquisa Biomédica , Educação em Odontologia , Estudantes de Odontologia , Avaliação Educacional , Humanos , Japão , Faculdades de Odontologia , Estudantes de Odontologia/estatística & dados numéricos
19.
J Electron Microsc (Tokyo) ; 61(5): 309-20, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22802488

RESUMO

This study aimed at elucidating whether estrogen deficiency would affect the synthesis of an osteocyte-derived factor, sclerostin, in the mesial region of alveolar bone. Eight 9-week-old Wistar female rats were ovariectomized (OVX) and eight other rats were Sham-operated (Sham). After 4 weeks, the interradicular septa of mandibular first molar were embedded in paraffin and then histochemically examined. Sclerostin-positive osteocytes were located in the superficial layer of the mesial region of Sham bones, whereas the OVX mesial region showed less sclerostin-reactive osteocytes. There was no significant difference in the distribution of estrogen receptor α and terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling -positive cells in the groups studied. The Sham mesial region featured many osteoclasts, and OVX specimens showed numerous osteoclasts in association with intense immunolabeling of the receptor activator of the nuclear factor kB ligand. Contrary to the observations in Sham specimens, a complex meshwork of cement lines was seen in the OVX mesial region, accompanied by an irregularly distributed osteocytic lacunar-canalicular system. In conclusion, estrogen deficiency appears to inhibit osteocyte-derived sclerostin synthesis in the mesial region of the interradicular septum, in a process that seems to be mediated by accelerated bone remodeling rather than by direct effects on osteocytes.


Assuntos
Proteínas Morfogenéticas Ósseas/biossíntese , Remodelação Óssea/efeitos dos fármacos , Osteoclastos/metabolismo , Osteócitos/efeitos dos fármacos , Osteócitos/metabolismo , Fosfatase Ácida/metabolismo , Animais , Proteínas Morfogenéticas Ósseas/genética , Osso e Ossos/metabolismo , Catepsina K/genética , Catepsina K/metabolismo , Estrogênios/deficiência , Estrogênios/farmacologia , Feminino , Marcadores Genéticos/genética , Marcação In Situ das Extremidades Cortadas , Isoenzimas/metabolismo , Ovariectomia , Ratos , Ratos Wistar , Receptores Estrogênicos/genética , Receptores Estrogênicos/metabolismo , Fosfatase Ácida Resistente a Tartarato
20.
Clin Calcium ; 22(3): 373-9, 2012 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-22370304

RESUMO

Parathyroid hormone (PTH) -driven anabolism in bone appears to involve the osteoblastic activation and the increased population of preosteoblastic lineages. Given that the activities of osteoclasts and osteoblasts are intertwined during normal bone remodeling, it is plausible that the anabolic action of PTH is either directly or indirectly related to the osteoclast. We have recently reported that the absence of osteoclasts in c-fos( - / - ) mice might hinder PTH-driven bone anabolism, and that osteoclastic presence may be necessary for full osteoblastic differentiation and enhanced bone formation seen after intermittent PTH administration. Alternatively, it was suggested that PTH administration inhibits sclerostin synthesis by osteocytes, thereby allowing for active bone formation. Taken together, PTH affects bone cells in a dual pathway - mediating osteoblastic (preosteoblastic) activities or osteocytic synthesis of sclerostin -.


Assuntos
Osso e Ossos/metabolismo , Osteoblastos/citologia , Osteogênese/efeitos dos fármacos , Hormônio Paratireóideo/administração & dosagem , Hormônio Paratireóideo/farmacologia , Animais , Proteínas Morfogenéticas Ósseas/biossíntese , Remodelação Óssea , Diferenciação Celular , Marcadores Genéticos , Humanos , Camundongos , Osteoclastos/fisiologia , Osteócitos/metabolismo , Hormônio Paratireóideo/fisiologia
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