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Sample records for cd44 occupancy prevents

  1. Downregulation of CD44 reduces doxorubicin resistance of CD44+CD24- breast cancer cells

    Phuc PV

    2011-06-01

    Full Text Available Pham Van Phuc, Phan Lu Chinh Nhan, Truong Hai Nhung, Nguyen Thanh Tam, Nguyen Minh Hoang, Vuong Gia Tue, Duong Thanh Thuy, Phan Kim NgocLaboratory of Stem Cell Research and Application, University of Science, Vietnam National University, Ho Chi Minh, VietnamBackground: Cells within breast cancer stem cell populations have been confirmed to have a CD44+CD24- phenotype. Strong expression of CD44 plays a critical role in numerous types of human cancers. CD44 is involved in cell differentiation, adhesion, and metastasis of cancer cells.Methods: In this study, we reduced CD44 expression in CD44+CD24- breast cancer stem cells and investigated their sensitivity to an antitumor drug. The CD44+CD24- breast cancer stem cells were isolated from breast tumors; CD44 expression was downregulated with siRNAs followed by treatment with different concentrations of the antitumor drug.Results: The proliferation of CD44 downregulated CD44+CD24- breast cancer stem cells was decreased after drug treatment. We noticed treated cells were more sensitive to doxorubicin, even at low doses, compared with the control groups.Conclusions: It would appear that expression of CD44 is integral among the CD44+CD24- cell population. Reducing the expression level of CD44, combined with doxorubicin treatment, yields promising results for eradicating breast cancer stem cells in vitro. This study opens a new direction in treating breast cancer through gene therapy in conjunction with chemotherapy.Keywords: antitumor drugs, breast cancer stem cells, CD44, CD44+CD24- cells, doxorubicin

  2. Dual role of CD44 isoforms in ampullary adenocarcinoma: CD44s predicts poor prognosis in early cancer and CD44ν is an indicator for recurrence in advanced cancer

    Wu, Cheng-Lin; Chao, Ying-Jui; Yang, Ta-Ming; Chen, Yi-Ling; Chang, Kung-Chao; Hsu, Hui-Ping; Shan, Yan-Shen; Lai, Ming-Derg

    2015-01-01

    Although postoperative adjuvant chemoradiotherapies prevent recurrence for some patients with ampullary cancer, the recurrence rate is as high as 29 % in patients with stage I cancer. In an effort to identify predictors of recurrence in patients with ampullary adenocarcinoma, we investigated the clinical value of assessing standard and variant forms of CD44. Immunohistochemistry staining and reverse-transcription polymerase chain reaction (RT-PCR) was used to detect standard and variant forms of CD44 in samples of ampullary adenocarcinoma. The cDNA microarray analysis comparing tumors with or without pancreatic invasion was undertaken and analyzed by Ingenuity Pathway Analysis. The standard CD44 (CD44s) isoform was detected in 76 of 98 patients with ampullary adenocarcinoma, and the negative or weak expression of CD44s was correlated with pancreatic invasion, lymphovascular invasion, advanced stage and bone metastasis. Moderate to dense expression of CD44s was correlated with shorter overall survival in patients with localized cancer (T1 or T2 disease, P = 0.0268). The patients with advanced cancer (T3 or T4 disease) and moderate or dense CD44s expression had a trend toward better survival. Alternative splicing of CD44 was confirmed using RT-PCR, which revealed that the CD44ν3-10 isoform was only expressed in patients with cancer recurrence. Fold change of CD44ν6-10 was also increased. In addition, networks containing CD44, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), transforming growth factor-β (TGF-β), matrix metalloproteinase 2 (MMP2), AKT, extracellular signal-regulated protein kinase 1 and 2 (ERK1/2), p38 MAPK, activated protein 1 (AP1)‚ and CTNNB1 were constructed after comparing microarray data from patients with and without pancreatic invasion. Whereas CD44s functions as tumor-promoting oncoprotein in early localized ampullary adenocarcinoma, CD44 variants are expressed in advanced cancer and patients with

  3. CD44v10, osteopontin and lymphoma growth retardation by a CD44v10-specific antibody.

    Megaptche, Amelie Pajip; Erb, Ulrike; Büchler, Markus Wolfgang; Zöller, Margot

    2014-09-01

    Blockade of CD44 is considered a therapeutic option for the elimination of leukemia-initiating cells. However, the application of anti-panCD44 can be burdened by severe side effects. We determined whether these side effects could be avoided by replacing anti-panCD44 with CD44 variant isoform (CD44v)-specific antibodies in CD44v-positive hematological malignancies using the EL4 thymoma and CD44v10-transfected EL4 (EL4-v10) as models. Subcutaneous growth of EL4 and EL4-v10 was equally well inhibited by the anti-panCD44 and anti-CD44v10 antibodies, respectively. Ex vivo analysis indicated that natural killer cytotoxicity and antibody-dependent cellular cytotoxicity were the main effector mechanisms. Under local inflammation, the efficacy of anti-CD44v10 prolonged the survival time twofold compared with untreated, EL4-v10 tumor-bearing mice, and this was due to inflammation-induced expression of osteopontin (OPN). A high level of OPN in EL4-v10 tumors supported leukocyte recruitment and tumor-infiltrating T-cell activation. Taken together, in hematological malignancies expressing CD44v, anti-panCD44 can be replaced by CD44v-specific antibodies without a loss in efficacy. Furthermore, CD44v10-specific antibodies appear particularly advantageous in cutaneous leukemia therapy, as CD44v10 binding of OPN drives leukocyte recruitment and activation.

  4. CRISPR-Cas9-Mediated Silencing of CD44 in Human Highly Metastatic Osteosarcoma Cells

    Tang Liu

    2018-04-01

    Full Text Available Background/Aims: Metastasis is the major cause of death in patients with osteosarcoma. There is an urgent need to identify molecular markers that promote metastasis. Cluster of differentiation 44 is a receptor for hyaluronic acid (HA and HA-binding has been proven to participate in various biological tumor activities, including tumor progression and metastasis. Methods: We performed a meta-analysis to investigate the relationship between CD44 expression, survival, and metastasis in patients with osteosarcoma. We then utilized the CRISPR-Cas9 system to specifically silence CD44 in highly metastatic human osteosarcoma cells (MNNG/HOS and 143B and further determined the functional effects of CD44 knockout in these cells. Results: The meta-analysis demonstrated that a high level of CD44 may predict poor survival and higher potential of metastasis in patients with osteosarcoma. The expression of CD44 in highly metastatic human osteosarcoma cell lines was efficiently blocked by CRISPR-Cas9. When CD44 was silenced, the proliferation and spheroid formation of these osteosarcoma cells was inhibited under 3-D culture conditions. Furthermore, the migratory and invasive functions were also impaired in these highly metastatic osteosarcoma cells. Conclusion: These results suggest that developing new strategies to target CD44 in osteosarcoma may prevent metastasis and improve the clinical outcome of osteosarcoma patients.

  5. PREVENTION OF OCCUPATIONAL ACCIDENTS

    Jovica Jovanovic

    2004-01-01

    Full Text Available Medical services, physicians and nurses play an essential role in the plant safety program through primary treatment of injured workers and by helping to identify workplace hazards. The physician and nurse should participate in the worksite investigations to identify specific hazard or stresses potentially causing the occupational accidents and injuries and in planning the subsequent hazard control program. Physicians and nurses must work closely and cooperatively with supervisors to ensure the prompt reporting and treatment of all work related health and safety problems. Occupational accidents, work related injuries and fatalities result from multiple causes, affect different segments of the working population, and occur in a myriad of occupations and industrial settings. Multiple factors and risks contribute to traumatic injuries, such as hazardous exposures, workplace and process design, work organization and environment, economics, and other social factors. With such a diversity of theories, it will not be difficult to understand that there does not exist one single theory that is considered right or correct and is universally accepted. These theories are nonetheless necessary, but not sufficient, for developing a frame of reference for understanding accident occurrences. Prevention strategies are also varied, and multiple strategies may be applicable to many settings, including engineering controls, protective equipment and technologies, management commitment to and investment in safety, regulatory controls, and education and training. Research needs are thus broad, and the development and application of interventions involve many disciplines and organizations.

  6. CD44 is involved in mineralization of dental pulp cells.

    Chen, Kuan-Liang; Huang, Yu-Yuan; Lung, Jrhau; Yeh, Ying-Yi; Yuan, Kuo

    2013-03-01

    CD44 is a transmembrane glycoprotein with various biological functions. Histologic studies have shown that CD44 is strongly expressed in odontoblasts at the appositional stage of tooth development. We investigated whether CD44 is involved in the mineralization of dental pulp cells. Ten human third molars with incomplete root formation were collected and processed for immunohistochemistry of CD44. Dental pulp cells isolated from another 5 human third molars were assayed for their viability, alkaline phosphatase activity, and alizarin red staining in vitro after silencing stably their expression of CD44 by using the short hairpin RNA technique. The CD44 knockdown cells were cultured on a collagen sponge and transplanted subcutaneously into the dorsal surfaces of immunocompromised mice. After 6 weeks, the subcutaneous tissues were processed for alizarin red staining and immunohistochemistry of human specific antigen. The dental pulp cells transduced with control short hairpin RNA were used as the control in all assays. CD44 is expressed in odontogenic cells with active mineral deposition during tooth development. Odontoblasts in the root ends of immature teeth express a stronger CD44 signal compared with those in the crown portion. When CD44 expression was stably suppressed in dental pulp cells, their mineralization activities were substantially decreased in both in vitro and in vivo assays. CD44 may play a crucial role in the initial mineralization of tooth-associated structures. However, further studies are required to clarify the underlying mechanisms. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  7. Transforming growth factor-β-mediated CD44/STAT3 signaling contributes to the development of atrial fibrosis and fibrillation.

    Chang, Shang-Hung; Yeh, Yung-Hsin; Lee, Jia-Lin; Hsu, Yu-Juei; Kuo, Chi-Tai; Chen, Wei-Jan

    2017-09-04

    Atrial fibrillation (AF) is associated with atrial fibrosis. Inhibition of atrial fibrosis might be a plausible approach for AF prevention and therapy. This study is designed to evaluate the potential role of CD44, a membrane receptor known to regulate fibrosis, and its related signaling in the pathogenesis of atrial fibrosis and AF. Treatment of cultured rat atrial fibroblasts with transforming growth factor-β (TGF-β, a key mediator of atrial fibrosis) led to a higher expression of hyaluronan (HA), CD44, STAT3, and collagen (a principal marker of fibrosis) than that of ventricular fibroblasts. In vivo, TGF-β transgenic mice and AF patients exhibited a greater expression of HA, CD44, STAT3, and collagen in their atria than wild-type mice and sinus rhythm subjects, respectively. Treating TGF-β transgenic mice with an anti-CD44 blocking antibody resulted in a lower expression of STAT3 and collagen in their atria than those with control IgG antibody. Programmed stimulation triggered less AF episodes in TGF-β transgenic mice treated with anti-CD44 blocking antibody than in those with control IgG. Blocking CD44 signaling with anti-CD44 antibody and mutated CD44 plasmids attenuated TGF-β-induced STAT3 activation and collagen expression in cultured atrial fibroblasts. Deletion and mutational analysis of the collagen promoter along with chromatin immunoprecipitation demonstrated that STAT3 served as a vital transcription factor in collagen expression. TGF-β-mediated HA/CD44/STAT3 pathway plays a crucial role in the development of atrial fibrosis and AF. Blocking CD44-dependent signaling may be a feasible way for AF management.

  8. Advances and advantages of nanomedicine in the pharmacological targeting of hyaluronan-CD44 interactions and signaling in cancer.

    Skandalis, Spyros S; Gialeli, Chrisostomi; Theocharis, Achilleas D; Karamanos, Nikos K

    2014-01-01

    Extensive experimental evidence in cell and animal tumor models show that hyaluronan-CD44 interactions are crucial in both malignancy and resistance to cancer therapy. Because of the intimate relationship between the hyaluronan-CD44 system and tumor cell survival and growth, it is an increasingly investigated area for applications to anticancer chemotherapeutics. Interference with the hyaluronan-CD44 interaction by targeting drugs to CD44, targeting drugs to the hyaluronan matrix, or interfering with hyaluronan matrix/tumor cell-associated CD44 interactions is a viable strategy for cancer treatment. Many of these methods can decrease tumor burden in animal models but have yet to show significant clinical utility. Recent advances in nanomedicine have offered new valuable tools for cancer detection, prevention, and treatment. The enhanced permeability and retention effect has served as key rationale for using nanoparticles to treat solid tumors. However, the targeted and uniform delivery of these particles to all regions of tumors in sufficient quantities requires optimization. An ideal nanocarrier should be equipped with selective ligands that are highly or exclusively expressed on target cells and thus endow the carriers with specific targeting capabilities. In this review, we describe how the hyaluronan-CD44 system may provide such an alternative in tumors expressing specific CD44 variants. © 2014 Elsevier Inc. All rights reserved.

  9. Expression of two isoforms of CD44 in human endometrium.

    Behzad, F; Seif, M W; Campbell, S; Aplin, J D

    1994-10-01

    The distribution of the cell-surface adhesion glycoprotein CD44 in human endometrium was examined by immunofluorescence using six monoclonal antibodies to epitopes common to all forms of the molecule, and by reverse transcription-polymerase chain reaction (RT-PCR). Immunoreactivity was observed throughout the menstrual cycle in stroma, vessels, glandular, and luminal epithelium. Variations in staining intensity were observed, especially in the epithelial compartment. CD44 was also expressed strongly by decidualized stromal cells of first-trimester pregnancy. No systematic variation of immunoreactivity was observed with stages of the normal cycle, but a fraction (25%) of the specimens lacked reactivity in the epithelium. To determine the molecular size of the epithelial isoform, an immunoprecipitation technique was developed using surface-radioiodinated, detergent-extracted glands. This indicated the presence at the cell surface of a single dominant CD44E species with an approximate molecular mass of 130 kDa. RT-PCR was used to investigate the isoforms present in whole endometrial tissue, isolated gland fragments, and Ishikawa endometrial carcinoma cells. Complementary DNA produced from total endometrial mRNA was PCR-amplified across the splice junction between exons 5 and 15. Transcripts corresponding to the hyaluronate receptor CD44H as well as a larger isoform were identified. CD44H was absent, or very scarce, in cDNA from purified gland epithelium. In contrast, Ishikawa cells expressed this form abundantly. The glands and Ishikawa cells also expressed CD44E containing sequences encoded by exons 12, 13, and 14. These data demonstrate the presence of CD44 in human endometrium and decidua, and show that different isoforms of CD44 are associated with tissue compartments in which different functional roles can be anticipated.

  10. CD44 standard and CD44v10 isoform expression on leukemia cells distinctly influences niche embedding of hematopoietic stem cells

    Erb, Ulrike; Megaptche, Amelie Pajip; Gu, Xiaoyu; Büchler, Markus W; Zöller, Margot

    2014-01-01

    Background A blockade of CD44 is considered a therapeutic option for the elimination of leukemia initiating cells. However, anti-panCD44 can interfere with hematopoiesis. Therefore we explored, whether a CD44 variant isoform (CD44v)-specific antibody can inhibit leukemia growth without attacking hematopoiesis. As a model we used CD44v10 transfected EL4 thymoma cells (EL4-v10). Methods The therapeutic efficacy of anti-panCD44 and anti-CD44v10 was evaluated after intravenous application of EL4/...

  11. CD44 expression in IgA nephropathy

    Florquin, Sandrine; Nunziata, Raffaele; Claessen, Nike; van den Berg, Frank M.; Pals, Steven T.; Weening, Jan J.

    2002-01-01

    Immunoglobulin A (IgA) nephropathy is a frequent, chronic renal disease characterized by a broad spectrum of clinical presentations and pathologic findings. CD44, a family of type I transmembrane glycoproteins: involved in cell-cell and cell-matrix interactions, may orchestrate partially the cascade

  12. Effect of Three Calmodulin Antagonists on Subpopulations of CD44 ...

    Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus,. International Pharmaceutical ... cancer stem cells. It is not known, however, whether targeting CD44 can alter the fate of cancer stem cells themselves. In this study, the effect of the calmodulin antagonists (N-(10-.

  13. Atomistic fingerprint of hyaluronan-CD44 binding

    Vuorio, Joni; Vattulainen, Ilpo; Martinez-Seara, Hector

    2017-01-01

    that hyaluronan can bind CD44 with three topographically different binding modes that in unison define an interaction fingerprint, thus providing a plausible explanation for the disagreement between the earlier studies. Our results confirm that the known crystallographic mode is the strongest of the three binding...

  14. Lipid raft association restricts CD44-ezrin interaction and promotion of breast cancer cell migration.

    Donatello, Simona

    2012-12-01

    Cancer cell migration is an early event in metastasis, the main cause of breast cancer-related deaths. Cholesterol-enriched membrane domains called lipid rafts influence the function of many molecules, including the raft-associated protein CD44. We describe a novel mechanism whereby rafts regulate interactions between CD44 and its binding partner ezrin in migrating breast cancer cells. Specifically, in nonmigrating cells, CD44 and ezrin localized to different membranous compartments: CD44 predominantly in rafts, and ezrin in nonraft compartments. After the induction of migration (either nonspecific or CD44-driven), CD44 affiliation with lipid rafts was decreased. This was accompanied by increased coprecipitation of CD44 and active (threonine-phosphorylated) ezrin-radixin-moesin (ERM) proteins in nonraft compartments and increased colocalization of CD44 with the nonraft protein, transferrin receptor. Pharmacological raft disruption using methyl-β-cyclodextrin also increased CD44-ezrin coprecipitation and colocalization, further suggesting that CD44 interacts with ezrin outside rafts during migration. Conversely, promoting CD44 retention inside lipid rafts by pharmacological inhibition of depalmitoylation virtually abolished CD44-ezrin interactions. However, transient single or double knockdown of flotillin-1 or caveolin-1 was not sufficient to increase cell migration over a short time course, suggesting complex crosstalk mechanisms. We propose a new model for CD44-dependent breast cancer cell migration, where CD44 must relocalize outside lipid rafts to drive cell migration. This could have implications for rafts as pharmacological targets to down-regulate cancer cell migration.

  15. CD44 standard and CD44v10 isoform expression on leukemia cells distinctly influences niche embedding of hematopoietic stem cells.

    Erb, Ulrike; Megaptche, Amelie Pajip; Gu, Xiaoyu; Büchler, Markus W; Zöller, Margot

    2014-03-31

    A blockade of CD44 is considered a therapeutic option for the elimination of leukemia initiating cells. However, anti-panCD44 can interfere with hematopoiesis. Therefore we explored, whether a CD44 variant isoform (CD44v)-specific antibody can inhibit leukemia growth without attacking hematopoiesis. As a model we used CD44v10 transfected EL4 thymoma cells (EL4-v10). The therapeutic efficacy of anti-panCD44 and anti-CD44v10 was evaluated after intravenous application of EL4/EL4-v10. Ex vivo and in vitro studies evaluated the impact of anti-panCD44 and anti-CD44v10 as well as of EL4 and EL4-v10 on hematopoietic stem cells (HSC) in cocultures with bone marrow stroma cells with a focus on adhesion, migration, cell cycle progression and apoptosis resistance. Intravenously injected EL4-v10 grow in bone marrow and spleen. Anti-panCD44 and, more pronounced anti-CD44v10 prolong the survival time. The higher efficacy of anti-CD44v10 compared to anti-panCD44 does not rely on stronger antibody-dependent cellular cytotoxicity or on promoting EL4-v10 apoptosis. Instead, EL4 compete with HSC niche embedding. This has consequences on quiescence and apoptosis-protecting signals provided by the stroma. Anti-panCD44, too, more efficiently affected embedding of HSC than of EL4 in the bone marrow stroma. EL4-v10, by catching osteopontin, migrated on bone marrow stroma and did not or weakly interfere with HSC adhesion. Anti-CD44v10, too, did not affect the HSC--bone marrow stroma crosstalk. The therapeutic effect of anti-panCD44 and anti-CD44v10 is based on stimulation of antibody-dependent cellular cytotoxicity. The superiority of anti-CD44v10 is partly due to blocking CD44v10-stimulated osteopontin expression that could drive HSC out of the niche. However, the main reason for the superiority of anti-CD44v10 relies on neither EL4-v10 nor anti-CD44v10 severely interfering with HSC--stroma cell interactions that, on the other hand, are affected by EL4 and anti-panCD44. Anti-panCD44

  16. Conditional expression of CD44 isoforms in lymphoma cells: influence on hyaluronate binding and tumor growth

    Fu, J.

    2002-03-01

    CD44 describes a family of surface proteins consisting of many isoforms due to alternative splice of ten 'variant' exons. Members of this family are involved in various processes including hematopoiesis, lymphocyte activation and homing, limb development, wound healing and tumor progression. Clinically, CD44 has been shown to be a prognostic factor for several human cancers. To answer the question which isoform might be relevant for tumor progression and to gain an insight into the mechanism of its function, I established transfectants of the LB lymphoma cell line in which the expression of four CD44 isoforms, namely CD44v3-10, CD44v4-10, CD44v8-10 and CD44s, was controlled by the Tet-off promoter. In the presence of Doxycycline, the expression was repressed. Removal of Doxycycline switched on expression and the maximal CD44 amount was obtained within two days. The transfectants were characterized regarding their ability to bind to the extracellular matrix component hyaluronate (HA). Overexpression of all four CD44 isoforms conferred the ability to bind HA on LB cells. Other glycosaminoglycans (GAGs) were bound in an isotype-specific fashion. CD44v3-10, CD44v4-10 and CD44v8-10 showed high binding affinity to chondroitin A, B and C, and low affinity to heparin, heparan sulfate and keratan sulfate. CD44s could not bind to these GAGs. Among these three variants, the binding ability of CD44v3-10 was the strongest. CD44 clustering seemed to play a crucial role for HA binding. Both CD44s and CD44v8-10 formed reduction-sensitive complexes in LB cells. The complexes are homooligomers or heterooligomers composed of different isoforms. Cys286 in CD44 transmember domain was not responsible for the formation of reduction-sensitive oligomer or for the enhanced HA binding in LB cell line. Using a conditional dimerization system the requirement of CD44 oligomerization for HA binding was directly demonstrated. The induction of oligomerization increased HA binding

  17. Conditional expression of CD44 isoforms in lymphoma cells: influence on hyaluronate binding and tumor growth

    Fu, J.

    2002-03-01

    CD44 describes a family of surface proteins consisting of many isoforms due to alternative splice of ten 'variant' exons. Members of this family are involved in various processes including hematopoiesis, lymphocyte activation and homing, limb development, wound healing and tumor progression. Clinically, CD44 has been shown to be a prognostic factor for several human cancers. To answer the question which isoform might be relevant for tumor progression and to gain an insight into the mechanism of its function, I established transfectants of the LB lymphoma cell line in which the expression of four CD44 isoforms, namely CD44v3-10, CD44v4-10, CD44v8-10 and CD44s, was controlled by the Tet-off promoter. In the presence of Doxycycline, the expression was repressed. Removal of Doxycycline switched on expression and the maximal CD44 amount was obtained within two days. The transfectants were characterized regarding their ability to bind to the extracellular matrix component hyaluronate (HA). Overexpression of all four CD44 isoforms conferred the ability to bind HA on LB cells. Other glycosaminoglycans (GAGs) were bound in an isotype-specific fashion. CD44v3-10, CD44v4-10 and CD44v8-10 showed high binding affinity to chondroitin A, B and C, and low affinity to heparin, heparan sulfate and keratan sulfate. CD44s could not bind to these GAGs. Among these three variants, the binding ability of CD44v3-10 was the strongest. CD44 clustering seemed to play a crucial role for HA binding. Both CD44s and CD44v8-10 formed reduction-sensitive complexes in LB cells. The complexes are homooligomers or heterooligomers composed of different isoforms. Cys286 in CD44 transmember domain was not responsible for the formation of reduction-sensitive oligomer or for the enhanced HA binding in LB cell line. Using a conditional dimerization system the requirement of CD44 oligomerization for HA binding was directly demonstrated. The induction of oligomerization increased HA binding. Finally, I

  18. Effects of CD44 Ligation on Signaling and Metabolic Pathways in Acute Myeloid Leukemia

    Madhoun, Nour Y.

    2017-01-01

    Acute myeloid leukemia (AML) is characterized by a blockage in the differentiation of myeloid cells at different stages. CD44-ligation using anti-CD44 monoclonal antibodies (mAbs) has been shown to reverse the blockage of differentiation

  19. CD44 regulates cell migration in human colon cancer cells via Lyn kinase and AKT phosphorylation.

    Subramaniam, Venkateswaran; Vincent, Isabella R; Gardner, Helena; Chan, Emily; Dhamko, Helena; Jothy, Serge

    2007-10-01

    Colon cancer is among the leading causes of cancer death in North America. CD44, an adhesion and antiapoptotic molecule is overexpressed in colon cancer. Cofilin is involved in the directional motility of cells. In the present study, we looked at how CD44 might modulate cell migration in human colon cancer via cofilin. We used a human colon cancer cell line, HT29, which expresses CD44, HT29 where CD44 expression was knocked down by siRNA, SW620, a human colon cancer cell line which does not express CD44, stably transfected exons of CD44 in SW620 cells and the colon from CD44 knockout and wild-type mouse. Western blot analysis of siRNA CD44 lysates showed increased level of AKT phosphorylation and decreased level of cofilin expression. Similar results were also observed with SW620 cells and CD44 knockout mouse colon lysates. Experiments using the AKT phosphorylation inhibitor LY294002 indicate that AKT phosphorylation downregulates cofilin. Immunoprecipitation studies showed CD44 complex formation with Lyn, providing an essential link between CD44 and AKT phosphorylation. LY294002 also stabilized Lyn from phosphorylated AKT, suggesting an interaction between Lyn and AKT phosphorylation. Immunocytochemistry showed that cofilin and Lyn expression were downregulated in siRNA CD44 cells and CD44 knockout mouse colon. siRNA CD44 cells had significantly less migration compared to HT29 vector. Given the well-defined roles of CD44, phosphorylated AKT in apoptosis and cancer, these results indicate that CD44-induced cell migration is dependent on its complex formation with Lyn and its consequent regulation of AKT phosphorylation and cofilin expression.

  20. Expression of CD44 splice variants in human primary brain tumors

    Kaaijk, P.; Troost, D.; Morsink, F.; Keehnen, R. M.; Leenstra, S.; Bosch, D. A.; Pals, S. T.

    1995-01-01

    Expression of CD44, particularly of certain splice variants, has been linked to tumor progression and metastatic potential in a number of different animal and human cancers. Although differential expression of CD44 standard epitopes (CD44s) in human brain tumors has been reported, the expression of

  1. Expression of CD44v6 and Its Association with Prognosis in Epithelial Ovarian Carcinomas

    Dang-xia Zhou

    2012-01-01

    Full Text Available The aim of this study was to evaluate CD44v6 protein expression and its prognostic value of CD44v6 in ovarian carcinoma. The expression of CD44v6 was analyzed in 62 patients with ovarian carcinoma by immunohistochemical method. The data obtained were analyzed by univariate and multivariate analyses. The present study clearly demonstrates that tumor tissues from 41 (66.1% patients showed positive expression with CD44v6. The expression of CD44v6 was significantly correlated with histological type, FIGO stage and histological grade of ovarian carcinomas. Concerning the prognosis, the survival period of patients with CD44v6 positive was shorter than that of patients with CD44v6 negative (36.6% versus 66.7%, 5-year survival, P<0.05. Univariate analysis showed that CD44v6 expression, histological type, FIGO stage and histological grade were associated with 5-year survival, and CD44v6 expression was associated with histological type, FIGO stage and histological grade and 5-year survival. In multivariate analysis, using the COX-regression model, CD44v6 expression was important prognostic factor. In conclusion, these results suggest that CD44v6 may be related to histological type, FIGO stage and histological grade of ovarian carcinomas, and CD44v6 may be an important molecular marker for poor prognosis in ovarian carcinomas.

  2. Occupational injury insurance - A strategy for prevention?

    Jacobsen, Thomas

    1993-01-01

    Can compulsory occupational injury insurance be used as a strategy for prevention in the work place? This is discussed on the basis of two different insurance systems - the Danish and the French.......Can compulsory occupational injury insurance be used as a strategy for prevention in the work place? This is discussed on the basis of two different insurance systems - the Danish and the French....

  3. Alternatively spliced CD44 isoforms containing exon v10 promote cellular adhesion through the recognition of chondroitin sulfate-modified CD44

    Chiu, R K; Droll, A; Dougherty, S T; Carpenito, C; Cooper, D L; Dougherty, G J

    1999-01-01

    Correlations have been noted between the expression of certain alternatively spliced CD44 isoforms and the metastatic propensity of various histologically distinct tumor cell types. The precise mechanism by which particular CD44 isoforms contribute to the metastatic process is, however, unclear. In

  4. MicroRNA miR-328 regulates zonation morphogenesis by targeting CD44 expression.

    Wang, Chia-Hui; Lee, Daniel Y; Deng, Zhaoqun; Jeyapalan, Zina; Lee, Shao-Chen; Kahai, Shireen; Lu, Wei-Yang; Zhang, Yaou; Yang, Burton B

    2008-06-18

    Morphogenesis is crucial to initiate physiological development and tumor invasion. Here we show that a microRNA controls zonation morphogenesis by targeting hyaluronan receptor CD44. We have developed a novel system to study microRNA functions by generating constructs expressing pre-miRNAs and mature miRNAs. Using this system, we have demonstrated that expression of miR-328 reduced cell adhesion, aggregation, and migration, and regulated formation of capillary structure. Protein analysis indicated that miR-328 repressed CD44 expression. Activities of luciferase constructs harboring the target site in CD44, but not the one containing mutation, were repressed by miR-328. Zonation morphogenesis appeared in cells transfected by miR-328: miR-328-transfected cells were present on the surface of zonating structures while the control cells stayed in the middle. MiR-328-mediated CD44 actions was validated by anti-CD44 antibody, hyaluronidase, CD44 siRNA, and CD44 expression constructs. In vivo experiments showed that CD44-silencing cells appeared as layers on the surfaces of nodules or zonating structures. Immuno-histochemistry also exhibited CD44-negative cells on the surface layers of normal rat livers and the internal zones of Portal veins. Our results demonstrate that miR-328 targets CD44, which is essential in regulating zonation morphogenesis: silencing of CD44 expression is essential in sealing the zonation structures to facilitate their extension and to inhibit complex expansion.

  5. Occupational Stress: Preventing Suffering, Enhancing Wellbeing.

    Quick, James Campbell; Henderson, Demetria F

    2016-04-29

    Occupational stress is a known health risk for a range of psychological, behavioral, and medical disorders and diseases. Organizations and individuals can mitigate these disorders through preventive stress management and enhanced wellbeing. This article addresses, first, the known health risk evidence related to occupational stress; second, the use of preventive stress management in organizations as the framework for intervention; and third, the emerging domain of enhancing wellbeing, which strengthens the individual. Premature death and disability along with chronic suffering from occupational stress are not inevitable, despite being known outcome risks.

  6. MAP kinase pathways and calcitonin influence CD44 alternate isoform expression in prostate cancer cells

    Robbins, Eric W; Travanty, Emily A; Yang, Kui; Iczkowski, Kenneth A

    2008-01-01

    Dysregulated expression and splicing of cell adhesion marker CD44 is found in many types of cancer. In prostate cancer (PC) specifically, the standard isoform (CD44s) has been found to be downregulated compared with benign tissue whereas predominant variant isoform CD44v7-10 is upregulated. Mitogen-activated protein kinase pathways and paracrine calcitonin are two common factors linked to dysregulated expression and splicing of CD44 in cancer. Calcitonin has been found to increase proliferation and invasion in PC acting through the protein kinase A pathway. In androgen-independent PC with known high CD44v7-10 expression, CD44 total and CD44v7-10 RNA or protein were assessed in response to exogenous and endogenous calcitonin and to inhibitors of protein kinase A, MEK, JNK, or p38 kinase. Benign cells and calcitonin receptor-negative PC cells were also tested. MEK or p38 but not JNK reduced CD44 total RNA by 40%–65% in cancer and benign cells. Inhibition of protein kinase A reduced CD44 total and v7-10 protein expression. In calcitonin receptor-positive cells only, calcitonin increased CD44 variant RNA and protein by 3 h and persisting to 48 h, apparently dependent on an uninhibited p38 pathway. Cells with constitutive CT expression showed an increase in CD44v7-10 mRNA but a decrease in CD44 total RNA. The MEK pathway increases CD44 RNA, while calcitonin, acting through the protein kinase A and p38 pathway, facilitates variant splicing. These findings could be used in the formulation of therapeutic methods for PC targeting CD44 alternate splicing

  7. HA/CD44 interactions as potential targets for cancer therapy

    Misra, Suniti; Heldin, Paraskevi; Hascall, Vincent C.; Karamanos, Nikos K.; Skandalis, Spyros S.; Markwald, Roger R.; Ghatak, Shibnath

    2011-01-01

    It is becoming increasingly clear that signals generated in tumor microenvironments are crucial to tumor cell behavior, such as, survival progression, and metastasis. The establishment of these malignant behaviors requires that tumor cells acquire novel adhesion and migration properties to detach from their original sites for localizing into distant organs. CD44, an adhesion/homing molecule is a major receptor for the glycosaminoglycan hyaluronan, which is one of the major components of the tumor extracellular matrix (ECM). CD44, a multi structural and multifunctional molecule, detects changes in ECM components, and thus is well positioned to provide appropriate responses to changes in the microenvironment, i.e. engagement in cell-cell and cell-ECM interactions, cell traffic, lymph node homing, and presentation of growth factors/cytokines/chemokines to co-ordinate signaling events that enable the cell responses that change in the tissue environment. The potential involvement of CD44variants (CD44v), especially CD44v4-v7 and CD44v6-v9 in tumor progression was confirmed for many tumor types in numerous clinical studies. Down regulation of the standard CD44 isoform (CD44s) in colon cancer is postulated to result in increased tumorigenicity. CD44v-specific functions could be due to their higher binding affinity for hyaluronan than CD44s. Alternatively, CD44v-specific functions could be due to differences in associating molecules, which may bind selectively to the CD44v exon. This review summarizes how the interaction between hyaluronan and CD44v can serve as a potential target for cancer therapy, in particular how silencing the CD44v can target multiple metastatic tumors. PMID:21362138

  8. Lipid Raft Association Restricts CD44-Ezrin Interaction and Promotion of Breast Cancer Cell Migration

    Donatello, Simona; Babina, Irina S.; Hazelwood, Lee D.; Hill, Arnold D.K.; Nabi, Ivan R.; Hopkins, Ann M.

    2012-01-01

    Cancer cell migration is an early event in metastasis, the main cause of breast cancer-related deaths. Cholesterol-enriched membrane domains called lipid rafts influence the function of many molecules, including the raft-associated protein CD44. We describe a novel mechanism whereby rafts regulate interactions between CD44 and its binding partner ezrin in migrating breast cancer cells. Specifically, in nonmigrating cells, CD44 and ezrin localized to different membranous compartments: CD44 predominantly in rafts, and ezrin in nonraft compartments. After the induction of migration (either nonspecific or CD44-driven), CD44 affiliation with lipid rafts was decreased. This was accompanied by increased coprecipitation of CD44 and active (threonine-phosphorylated) ezrin-radixin-moesin (ERM) proteins in nonraft compartments and increased colocalization of CD44 with the nonraft protein, transferrin receptor. Pharmacological raft disruption using methyl-β-cyclodextrin also increased CD44-ezrin coprecipitation and colocalization, further suggesting that CD44 interacts with ezrin outside rafts during migration. Conversely, promoting CD44 retention inside lipid rafts by pharmacological inhibition of depalmitoylation virtually abolished CD44-ezrin interactions. However, transient single or double knockdown of flotillin-1 or caveolin-1 was not sufficient to increase cell migration over a short time course, suggesting complex crosstalk mechanisms. We propose a new model for CD44-dependent breast cancer cell migration, where CD44 must relocalize outside lipid rafts to drive cell migration. This could have implications for rafts as pharmacological targets to down-regulate cancer cell migration. PMID:23031255

  9. Priority Setting for Occupational Cancer Prevention

    Cheryl E. Peters

    2018-06-01

    Full Text Available Background: Selecting priority occupational carcinogens is important for cancer prevention efforts; however, standardized selection methods are not available. The objective of this paper was to describe the methods used by CAREX Canada in 2015 to establish priorities for preventing occupational cancer, with a focus on exposure estimation and descriptive profiles. Methods: Four criteria were used in an expert assessment process to guide carcinogen prioritization: (1 the likelihood of presence and/or use in Canadian workplaces; (2 toxicity of the substance (strength of evidence for carcinogenicity and other health effects; (3 feasibility of producing a carcinogen profile and/or an occupational estimate; and (4 special interest from the public/scientific community. Carcinogens were ranked as high, medium or low priority based on specific conditions regarding these criteria, and stakeholder input was incorporated. Priorities were set separately for the creation of new carcinogen profiles and for new occupational exposure estimates. Results: Overall, 246 agents were reviewed for inclusion in the occupational priorities list. For carcinogen profile generation, 103 were prioritized (11 high, 33 medium, and 59 low priority, and 36 carcinogens were deemed priorities for occupational exposure estimation (13 high, 17 medium, and 6 low priority. Conclusion: Prioritizing and ranking occupational carcinogens is required for a variety of purposes, including research, resource allocation at different jurisdictional levels, calculations of occupational cancer burden, and planning of CAREX-type projects in different countries. This paper outlines how this process was achieved in Canada; this may provide a model for other countries and jurisdictions as a part of occupational cancer prevention efforts. Keywords: cancer prevention, carcinogen exposure, occupational health

  10. Occupational Accidents And Preventive Measures

    Fassnacht, V

    2006-01-01

    This report presents the 2005 statistics concerning occupational accidents involving members of the CERN personnel and contractors' personnel. It sets out the accident frequency and severity rates and provides a breakdown of accidents by cause and injury. It also contains a summary analysis of the most serious accidents and the associated recommendations.

  11. Effect of curcumin on the cell surface markers CD44 and CD24 in breast cancer.

    Calaf, Gloria M; Ponce-Cusi, Richard; Abarca-Quinones, Jorge

    2018-04-20

    Human breast cell lines are often characterized based on the expression of the cell surface markers CD44 and CD24. CD44 is a type I transmembrane glycoprotein that regulates cell adhesion and cell-cell, as well as cell-extracellular matrix interactions. CD24 is expressed in benign and malignant solid tumors and is also involved in cell adhesion and metastasis. The aim of the present study was to investigate the effects of curcumin on the surface expression of CD44 and CD24 in breast epithelial cell lines. An established breast cancer model derived from the MCF-10F cell line was used. The results revealed that curcumin decreased CD44 and CD24 gene and protein expression levels in MCF-10F (normal), Alpha5 (premalignant) and Tumor2 (malignant) cell lines compared with the levels in their counterpart control cells. Flow cytometry revealed that the CD44+/CD24+ cell subpopulation was greater than the CD44+/CD24- subpopulation in these three cell lines. Curcumin increased CD44+/CD24+ to a greater extent and decreased CD44+/CD24- subpopulations in the normal MCF-10F and the pre-tumorigenic Alpha5 cells, but had no significant effect on Tumor2 cells compared with the corresponding control cells. Conversely, curcumin increased CD44 and decreased CD24 gene expression in MCF-7 breast cancer cells, and decreased CD44 gene expression in MDA-MB-231 cell line, while CD24 was not present in these cells. Curcumin did not alter the CD44+/CD24+ or CD44+/CD24- subpopulations in the MCF-7 cell line. However, it increased CD44+/CD24+ and decreased CD44+/CD24- subpopulations in MDA-MB-231 cells. In breast cancer specimens from patients, normal tissues were negative for CD44 and CD24 expression, while benign lesions were positive for both markers, and malignant tissues were found to be negative for CD44 and positive for CD24 in most cases. In conclusion, these results indicated that curcumin may be used to improve the proportion of CD44+/CD24+ cells and decrease the proportion of CD44

  12. Analysis of human articular chondrocyte CD44 isoform expression and function in health and disease.

    Salter, D M; Godolphin, J L; Gourlay, M S; Lawson, M F; Hughes, D E; Dunne, E

    1996-08-01

    Interactions between articular chondrocytes and components of the extracellular matrix are of potential importance in the normal function of cartilage and in the pathophysiology of arthritis. Little is known of the basis of these interactions, but cell adhesive molecules such as CD44 are likely to be involved. Immunohistology using six well-characterized anti-CD44 monoclonal antibodies demonstrated standard CD44 isoform (CD44H) expression by all chondrocytes in normal and osteoarthrotic (OA) cartilage but absence of the CD44E variant. Polymerase chain reaction (PCR) of reverse transcribed mRNA from monolayer cultures of normal and OA chondrocytes using primer sequences which span the region containing variably spliced exons produced a predominant band representing the standard form of CD44, which lacks the variable exons 6-15 (v1-v10). No product was seen at the expected size of the epithelial variant of CD44 (CD44v8-10). Use of exon-specific primers, however, showed expression of variant exons resulting in multiple minor isoforms. Standard CD44 was also shown to be the predominantly expressed isoform identified by immunoprecipitation, but human articular chondrocytes did not adhere to hyaluronan in vitro. Chondrocyte CD44 may function as an adhesion receptor for other matrix molecules such as fibronectin or collagen.

  13. Can CD44 Be a Mediator of Cell Destruction? The Challenge of Type 1 Diabetes

    Assayag-Asherie, Nathalie; Sever, Dror; Bogdani, Marika; Johnson, Pamela; Weiss, Talya; Ginzberg, Ariel; Perles, Sharon; Weiss, Lola; Sebban, Lora Eshkar; Turley, Eva A.; Okon, Elimelech; Raz, Itamar; Naor, David

    2015-01-01

    CD44 is a multi-functional receptor with multiple of isoforms engaged in modulation of cell trafficking and transmission of apoptotic signals. We have previously shown that injection of anti-CD44 antibody into NOD mice induced resistance to type 1 diabetes (T1D). In this communication we describe our efforts to understand the mechanism underlying this effect. We found that CD44-deficient NOD mice develop stronger resistance to T1D than wild-type littermates. This effect is not explained by the involvement of CD44 in cell migration, because CD44-deficient inflammatory cells surprisingly had greater invasive potential than the corresponding wild type cells, probably owing to molecular redundancy. We have previously reported and we show here again that CD44 expression and hyaluronic acid (HA, the principal ligand for CD44) accumulation are detected in pancreatic islets of diabetic NOD mice, but not of non-diabetic DBA/1 mice. Expression of CD44 on insulin-secreting β cells renders them susceptible to the autoimmune attack, and is associated with a diminution in β-cells function (e.g., less insulin production and/or insulin secretion) and possibly also with an enhanced apoptosis rate. The diabetes-supportive effect of CD44 expression on β cells was assessed by the TUNEL assay and further strengthened by functional assays exhibiting increased nitric oxide release, reduced insulin secretion after glucose stimulation and decreased insulin content in β cells. All these parameters could not be detected in CD44-deficient islets. We further suggest that HA-binding to CD44-expressing β cells is implicated in β-cell demise. Altogether, these data agree with the concept that CD44 is a receptor capable of modulating cell fate. This finding is important for other pathologies (e.g., cancer, neurodegenerative diseases) in which CD44 and HA appear to be implicated. PMID:26624007

  14. Can CD44 Be a Mediator of Cell Destruction? The Challenge of Type 1 Diabetes.

    Nathalie Assayag-Asherie

    Full Text Available CD44 is a multi-functional receptor with multiple of isoforms engaged in modulation of cell trafficking and transmission of apoptotic signals. We have previously shown that injection of anti-CD44 antibody into NOD mice induced resistance to type 1 diabetes (T1D. In this communication we describe our efforts to understand the mechanism underlying this effect. We found that CD44-deficient NOD mice develop stronger resistance to T1D than wild-type littermates. This effect is not explained by the involvement of CD44 in cell migration, because CD44-deficient inflammatory cells surprisingly had greater invasive potential than the corresponding wild type cells, probably owing to molecular redundancy. We have previously reported and we show here again that CD44 expression and hyaluronic acid (HA, the principal ligand for CD44 accumulation are detected in pancreatic islets of diabetic NOD mice, but not of non-diabetic DBA/1 mice. Expression of CD44 on insulin-secreting β cells renders them susceptible to the autoimmune attack, and is associated with a diminution in β-cells function (e.g., less insulin production and/or insulin secretion and possibly also with an enhanced apoptosis rate. The diabetes-supportive effect of CD44 expression on β cells was assessed by the TUNEL assay and further strengthened by functional assays exhibiting increased nitric oxide release, reduced insulin secretion after glucose stimulation and decreased insulin content in β cells. All these parameters could not be detected in CD44-deficient islets. We further suggest that HA-binding to CD44-expressing β cells is implicated in β-cell demise. Altogether, these data agree with the concept that CD44 is a receptor capable of modulating cell fate. This finding is important for other pathologies (e.g., cancer, neurodegenerative diseases in which CD44 and HA appear to be implicated.

  15. Epigenetic regulation of CD44 in Hodgkin and non-Hodgkin lymphoma

    Eberth, Sonja; Schneider, Björn; Rosenwald, Andreas; Hartmann, Elena M; Romani, Julia; Zaborski, Margarete; Siebert, Reiner; Drexler, Hans G; Quentmeier, Hilmar

    2010-01-01

    Epigenetic inactivation of tumor suppressor genes (TSG) by promoter CpG island hypermethylation is a hallmark of cancer. To assay its extent in human lymphoma, methylation of 24 TSG was analyzed in lymphoma-derived cell lines as well as in patient samples. We screened for TSG methylation using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in 40 lymphoma-derived cell lines representing anaplastic large cell lymphoma, Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), Hodgkin lymphoma and mantle cell lymphoma (MCL) as well as in 50 primary lymphoma samples. The methylation status of differentially methylated CD44 was verified by methylation-specific PCR and bisulfite sequencing. Gene expression of CD44 and its reactivation by DNA demethylation was determined by quantitative real-time PCR and on the protein level by flow cytometry. Induction of apoptosis by anti-CD44 antibody was analyzed by annexin-V/PI staining and flow cytometry. On average 8 ± 2.8 of 24 TSG were methylated per lymphoma cell line and 2.4 ± 2 of 24 TSG in primary lymphomas, whereas 0/24 TSG were methylated in tonsils and blood mononuclear cells from healthy donors. Notably, we identified that CD44 was hypermethylated and transcriptionally silenced in all BL and most FL and DLBCL cell lines, but was usually unmethylated and expressed in MCL cell lines. Concordant results were obtained from primary lymphoma material: CD44 was not methylated in MCL patients (0/11) whereas CD44 was frequently hypermethylated in BL patients (18/29). In cell lines with CD44 hypermethylation, expression was re-inducible at mRNA and protein levels by treatment with the DNA demethylating agent 5-Aza-2'-deoxycytidine, confirming epigenetic regulation of CD44. CD44 ligation assays with a monoclonal anti-CD44 antibody showed that CD44 can mediate apoptosis in CD44 + lymphoma cells. CD44 hypermethylated, CD44 - lymphoma cell lines were consistently

  16. Regulation of proximal tubular epithelial cell CD44-mediated binding and internalisation of hyaluronan.

    Jones, Stuart George; Ito, Takafumi; Phillips, Aled Owain

    2003-09-01

    Increased expression of the connective tissue polysaccharide hyaluronan (HA) in the renal corticointerstitium is associated with progressive renal fibrosis. Numerous studies have demonstrated involvement proximal tubular epithelial cells in the fibrotic process and in the current study we have characterised their expression of the HA receptor, CD44, and examined changes in CD44 expression and function in response to either IL-1beta or glucose. Characterisation of CD44 splice variant expression was carried out in primary cultures of human proximal tubular cells (PTC) and HK2 cells. Binding and internalisation HA was examined by addition of exogenous of fluorescein-HA (fl-HA), and expression of CD44 examined by immunoblot analysis and flow cytometry. Alteration in "functional" CD44 was determined by immunoprecipitation of CD44 following stimulation in the presence of fl-HA. PTC, both primary culture and the PTC cell line, HK2, express at least 5 CD44 splice variants, the expression of which are not altered by addition of either IL-1beta or 25mM D-glucose. Addition of either stimulus increased cell surface binding and internalisation of fl-HA and increased expression of functionally active CD44. Increased binding and internalisation of fl-HA, was blocked by anti-CD44 antibody, and by the inhibition of O-glycosylation. The data demonstrate that stimuli inducing PTC HA synthesis also regulate PTC-HA interactions. Furthermore increased HA binding and internalisation is the result of post-translational modification of CD44 by O-glycosylation, rather than by alteration in expression of CD44 at the cell surface, or by alternate use of CD44 splice variants.

  17. Virtual screening-driven repositioning of etoposide as CD44 antagonist in breast cancer cells

    Aguirre-Alvarado, Charmina; Segura-Cabrera, Aldo; Velázquez-Quesada, Inés; Hernández-Esquivel, Miguel A.; García-Pérez, Carlos A.; Guerrero-Rodríguez, Sandra L.; Ruiz, Angel J.; Rodríguez-Moreno, Andrea; Pérez-Tapia, Sonia M.; Velasco-Velázquez, Marco A.

    2016-01-01

    CD44 is a receptor for hyaluronan (HA) that promotes epithelial-to-mesenchymal transition (EMT), induces cancer stem cell (CSC) expansion, and favors metastasis. Thus, CD44 is a target for the development of antineoplastic agents. In order to repurpose drugs as CD44 antagonists, we performed consensus-docking studies using the HA-binding domain of CD44 and 11,421 molecules. Drugs that performed best in docking were examined in molecular dynamics simulations, identifying etoposide as a potential CD44 antagonist. Ligand competition and cell adhesion assays in MDA-MB-231 cells demonstrated that etoposide decreased cell binding to HA as effectively as a blocking antibody. Etoposide-treated MDA-MB-231 cells developed an epithelial morphology; increased their expression of E-cadherin; and reduced their levels of EMT-associated genes and cell migration. By gene expression analysis, etoposide reverted an EMT signature similarly to CD44 knockdown, whereas other topoisomerase II (TOP2) inhibitors did not. Moreover, etoposide decreased the proportion of CD44+/CD24− cells, lowered chemoresistance, and blocked mammosphere formation. Our data indicate that etoposide blocks CD44 activation, impairing key cellular functions that drive malignancy, thus rendering it a candidate for further translational studies and a potential lead compound in the development of new CD44 antagonists. PMID:27009862

  18. Chondroitin sulfate addition to CD44H negatively regulates hyaluronan binding

    Ruffell, Brian; Johnson, Pauline

    2005-01-01

    CD44 is a widely expressed cell adhesion molecule that binds hyaluronan, an extracellular matrix glycosaminoglycan, in a tightly regulated manner. This regulated interaction has been implicated in inflammation and tumor metastasis. CD44 exists in the standard form, CD44H, or as higher molecular mass isoforms due to alternative splicing. Here, we identify serine 180 in human CD44H as the site of chondroitin sulfate addition and show that lack of chondroitin sulfate addition at this site enhances hyaluronan binding by CD44. A CD44H-immunoglobulin fusion protein expressed in HEK293 cells, and CD44H expressed in murine L fibroblast cells were modified by chondroitin sulfate, as determined by reduced sulfate incorporation after chondroitinase ABC treatment. Mutation of serine 180 or glycine 181 in CD44H reduced chondroitin sulfate addition and increased hyaluronan binding, indicating that serine 180 is the site for chondroitin sulfate addition in CD44H and that this negatively regulates hyaluronan binding

  19. [Preventing occupational eye trauma (Geneva, Switzerland)].

    Ngondi, C Emole; Chastonay, P; Dosso, A

    2010-01-01

    Occupational eye trauma causes injuries with often serious socioprofessional, medical-legal, and economic consequences, not only for workers themselves, but also for employers. In spite of today's legislation and the efforts to encourage prevention, the frequency of occupational ocular accidents remains relatively high despite how easy it is to protect the eyes. In this study, the reasons that these accidents persist despite the progress made in preventive measures was investigated. From January to July 2005, we analyzed the parameters related to 175 occupational eye injuries. All patients agreed to take part in this study, which was carried out in the emergency unit of the Ophthalmology Clinic at Geneva University Hospital. Additional data was collected in companies. Construction workers were the most exposed (41.1%). The activity with the greatest risk was grinding (19.4%). The most affected structure of the eye was the cornea (84%), 72.6% patients were not equipped with ocular protection at the time of the accident, and 17.4% wore poorly adapted eye protection. This can be explained by negligence, lack of awareness, etc. Overall, workers, employers, and the legislation in force are all responsible. Our results are comparable with those found in the literature, with certain particularities because heavy industry was underrepresented in our sample. Analysis of the law on the prevention of occupational accidents and diseases shows that the worker is not sufficiently aware of his responsibilities. To our knowledge, the legal aspects treated herein have not been studied. As done in certain studies, we emphasize the importance of preventive ophthalmologic examinations as well as improvement of both working conditions and worker awareness in the workplace. Primary prevention must be reinforced. Information campaigns within the workplace aimed at workers and revision of the laws on occupational safety are some of the recommendations that are proposed to control

  20. CD44 antibodies and immune thrombocytopenia in the amelioration of murine inflammatory arthritis.

    Patrick J Mott

    Full Text Available Antibodies to CD44 have been used to successfully ameliorate murine models of autoimmune disease. The most often studied disease model has been murine inflammatory arthritis, where a clear mechanism for the efficacy of CD44 antibodies has not been established. We have recently shown in a murine passive-model of the autoimmune disease immune thrombocytopenia (ITP that some CD44 antibodies themselves can induce thrombocytopenia in mice, and the CD44 antibody causing the most severe thrombocytopenia (IM7, also is known to be highly effective in ameliorating murine models of arthritis. Recent work in the K/BxN serum-induced model of arthritis demonstrated that antibody-induced thrombocytopenia reduced arthritis, causing us to question whether CD44 antibodies might primarily ameliorate arthritis through their thrombocytopenic effect. We evaluated IM7, IRAWB14.4, 5035-41.1D, KM201, KM114, and KM81, and found that while all could induce thrombocytopenia, the degree of protection against serum-induced arthritis was not closely related to the length or severity of the thrombocytopenia. CD44 antibody treatment was also able to reverse established inflammation, while thrombocytopenia induced by an anti-platelet antibody targeting the GPIIbIIIa platelet antigen, could not mediate this effect. While CD44 antibody-induced thrombocytopenia may contribute to some of its therapeutic effect against the initiation of arthritis, for established disease there are likely other mechanisms contributing to its efficacy. Humans are not known to express CD44 on platelets, and are therefore unlikely to develop thrombocytopenia after CD44 antibody treatment. An understanding of the relationship between arthritis, thrombocytopenia, and CD44 antibody treatment remains critical for continued development of CD44 antibody therapeutics.

  1. MicroRNA miR-328 regulates zonation morphogenesis by targeting CD44 expression.

    Chia-Hui Wang

    Full Text Available Morphogenesis is crucial to initiate physiological development and tumor invasion. Here we show that a microRNA controls zonation morphogenesis by targeting hyaluronan receptor CD44. We have developed a novel system to study microRNA functions by generating constructs expressing pre-miRNAs and mature miRNAs. Using this system, we have demonstrated that expression of miR-328 reduced cell adhesion, aggregation, and migration, and regulated formation of capillary structure. Protein analysis indicated that miR-328 repressed CD44 expression. Activities of luciferase constructs harboring the target site in CD44, but not the one containing mutation, were repressed by miR-328. Zonation morphogenesis appeared in cells transfected by miR-328: miR-328-transfected cells were present on the surface of zonating structures while the control cells stayed in the middle. MiR-328-mediated CD44 actions was validated by anti-CD44 antibody, hyaluronidase, CD44 siRNA, and CD44 expression constructs. In vivo experiments showed that CD44-silencing cells appeared as layers on the surfaces of nodules or zonating structures. Immuno-histochemistry also exhibited CD44-negative cells on the surface layers of normal rat livers and the internal zones of Portal veins. Our results demonstrate that miR-328 targets CD44, which is essential in regulating zonation morphogenesis: silencing of CD44 expression is essential in sealing the zonation structures to facilitate their extension and to inhibit complex expansion.

  2. Increased Toxicity of Chemotherapeutic Drugs by All-Trans Retinoic Acid in Cd44 Cells

    A Abbasi

    2016-03-01

    Full Text Available BACKGROUND AND OBJECTIVE: In recent studies, undifferentiated CD44 cells have been introduced as the major cause of chemotherapeutic drug resistance in esophageal cancer. In this study, we aimed to evaluate the effects of all-trans retinoic acid on reducing chemotherapeutic drug resistance and improving the associated toxic effects. METHODS: In this clinical study, CD44+ and CD44- cells were separated from KYSE-30 cell line, using magnetic-activated cell sorting (MACS method. The cytotoxic effects of retinoic acid treatment, combined with cisplatin and 5-fluorouracil, were separately evaluated in two cell groups, i.e., CD44+ and CD44-. Cytotoxicity was determined by identifying cellular metabolic activity, acridine orange/ethidium bromide staining, and flow cytometry. FINDINGS: In this study, CD44 marker was expressed in 6.25% of the cell population in KYSE-30 cell line. The results of flow cytometry revealed that treatment with a combination of retinoic acid and chemotherapeutic drugs could improve cell cycle arrest in CD44+ cells (p<0.05, unlike CD44- cells. Determination of cellular metabolic activity, increased cell apoptosis along with decreased half maximal inhibitory concentration (IC50, and acridine orange/ethidium bromide staining were indicative of the increased percentage of primary and secondary apoptotic CD44+ cells. However, in CD44- cells, these effects were only observed by using a combination of retinoic acid and cisplatin (p<0.05. CONCLUSION: The present results showed that all-trans retinoic acid could increase the toxicity of cisplatin and 5-fluorouracil in CD44+ cells.

  3. CD44-engineered mesoporous silica nanoparticles for overcoming multidrug resistance in breast cancer

    Wang, Xin; Liu, Ying; Wang, Shouju; Shi, Donghong; Zhou, Xianguang; Wang, Chunyan; Wu, Jiang; Zeng, Zhiyong; Li, Yanjun; Sun, Jing; Wang, Jiandong; Zhang, Longjiang; Teng, Zhaogang; Lu, Guangming

    2015-01-01

    Graphical abstract: - Highlights: • CD44-engineered mesoporous silica nanoparticles are synthesized. • The mechanism of CD44-engineered mesoporous silica nanoparticles is revealed. • This new delivery system increased the drug accumulation in vitro and in vivo. • This new delivery system offers an effective approach to treat multidrug resistance. - Abstract: Multidrug resistance is a major impediment for the successful chemotherapy in breast cancer. CD44 is over-expressed in multidrug resistant human breast cancer cells. CD44 monoclonal antibody exhibits anticancer potential by inhibiting proliferation and regulating P-glycoprotein-mediated drug efflux activity in multidrug resistant cells. Thereby, CD44 monoclonal antibody in combination with chemotherapeutic drug might be result in enhancing chemosensitivity and overcoming multidrug resistance. The purpose of this study is to investigate the effects of the CD44 monoclonal antibody functionalized mesoporous silica nanoparticles containing doxorubicin on human breast resistant cancer MCF-7 cells. The data showed that CD44-modified mesoporous silica nanoparticles increased cytotoxicity and enhanced the downregulation of P-glycoprotein in comparison to CD44 antibody. Moreover, CD44-engineered mesoporous silica nanoparticles provided active target, which promoted more cellular uptake of DOX in the resistant cells and more retention of DOX in tumor tissues than unengineered counterpart. Animal studies of the resistant breast cancer xenografts demonstrated that CD44-engineered drug delivery system remarkably induced apoptosis and inhibited the tumor growth. Our results indicated that the CD44-engineered mesoporous silica nanoparticle-based drug delivery system offers an effective approach to overcome multidrug resistance in human breast cancer

  4. Occupational ergonomics and injury prevention.

    Stobbe, T J

    1996-01-01

    Ergonomics is the study of people at work. The current focus is on the prevention of work-induced musculoskeletal injuries through the application of sound ergonomic principles. This chapter has briefly outlined ergonomics and its history, has described low back pain and upper extremity cumulative trauma disorders from an ergonomic perspective, and has discussed control and prevention approaches for a few scenarios. Ergonomic principles are based on a combination of science and engineering and a thorough understanding of human capabilities and limitations. When these principles are applied to the design of a job, task, process, or procedure, the incidence and severity of musculoskeletal injuries decrease. In many cases productivity and morale also improve. Workers are spared suffering, and employers are spared costs. It is hoped that this discussion will encourage more health, safety, and business professionals to learn about and apply ergonomics in their workplaces for the improvement of the worker, product, and business. Finally, many additional epidemiologic studies on the individual and joint effects of the CTD risk factors are needed. The knowledge gained from these studies will promote the more effective application of ergonomic principles to reduce worker suffering, improve products, and reduce costs.

  5. CD44 deficiency enhanced Streptococcus equi ssp. zooepidemicus dissemination and inflammation response in a mouse model.

    Fu, Qiang; Xiao, Pingping; Chen, Yaosheng; Wei, Zigong; Liu, Xiaohong

    2017-12-01

    Streptococcus equi ssp. zooepidemicus (S. zooepidemicus) is responsible for peritonitis, septicemia, meningitis, arthritis and several other serious diseases in various species. Recent studies have demonstrated that CD44 is implicated in the process of host defense against pathogenic microorganisms. In the present study, the role of CD44 in the host response to S. zooepidemicus infection was investigated in a mouse model. Upon intraperitoneal infection with S. zooepidemicus, the expression of CD44 on the peritoneal exudate cells from wild-type (WT) mice was increased. CD44 deficiency accelerated mortality, which was accompanied by increased peritoneal bacterial growth and dissemination to distant body sites. CD44 knock-out (KO) mice showed enhanced early inflammatory cell recruitment into the peritoneal fluid on S. zooepidemicus infection. In line with this, the expression of proinflammatory cytokines, chemokines in peritoneal exudate cells and peritoneal macrophages of CD44 KO mice were increased compared with those of WT mice. In addition, CD44 deficiency was associated with reduced expression of A20, a negative regulator in TLR signaling. Overall, the present study suggests that CD44 plays a protective role in antibacterial defense against S. zooepidemicus in mice. Copyright © 2017. Published by Elsevier Ltd.

  6. Evaluation of Stem Cell Markers, CD44/CD24 in Breast Cancer Cell Lines

    Masoud Hashemi Arabi

    2014-05-01

    Four breast cancer cell lines, MCF-7 ، T47D ، MDA-MB231 and MDA-MB468 were purchased from National cell Bank of Iran based in Iran Pasture Institute and were cultured in high glucose DMEM supplemented with 10% FCS. Cells were stained with antiCD44-PE and antiCD24-FITC antibodies and Status of CD44 and CD24 as markers of breast cancer stem cells were evaluated using flow cytometer and fluorescent microscopy.Evaluation of CD44 and CD24 as markers of breast cancer stem cells showed that MDA-MB231 with 97±1.2% CD44+/CD24-/low cells is significantly different from the others that they were mainly CD44 and CD24 positive cells(p

  7. Intracellular targeting of CD44+ cells with self-assembling, protein only nanoparticles.

    Pesarrodona, Mireia; Ferrer-Miralles, Neus; Unzueta, Ugutz; Gener, Petra; Tatkiewicz, Witold; Abasolo, Ibane; Ratera, Imma; Veciana, Jaume; Schwartz, Simó; Villaverde, Antonio; Vazquez, Esther

    2014-10-01

    CD44 is a multifunctional cell surface protein involved in proliferation and differentiation, angiogenesis and signaling. The expression of CD44 is up-regulated in several types of human tumors and particularly in cancer stem cells, representing an appealing target for drug delivery in the treatment of cancer. We have explored here several protein ligands of CD44 for the construction of self-assembling modular proteins designed to bind and internalize target cells. Among five tested ligands, two of them (A5G27 and FNI/II/V) drive the formation of protein-only, ring-shaped nanoparticles of about 14 nm that efficiently bind and penetrate CD44(+) cells by an endosomal route. The potential of these newly designed nanoparticles is evaluated regarding the need of biocompatible nanostructured materials for drug delivery in CD44-linked conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Cleavage of Hyaluronan and CD44 Adhesion Molecule Regulate Astrocyte Morphology via Rac1 Signalling.

    Anna Konopka

    Full Text Available Communication of cells with their extracellular environment is crucial to fulfill their function in physiological and pathophysiological conditions. The literature data provide evidence that such a communication is also important in case of astrocytes. Mechanisms that contribute to the interaction between astrocytes and extracellular matrix (ECM proteins are still poorly understood. Hyaluronan is the main component of ECM in the brain, where its major receptor protein CD44 is expressed by a subset of astrocytes. Considering the fact that functions of astrocytes are tightly coupled with changes in their morphology (e.g.: glutamate clearance in the synaptic cleft, migration, astrogliosis, we investigated the influence of hyaluronan cleavage by hyaluronidase, knockdown of CD44 by specific shRNA and CD44 overexpression on astrocyte morphology. Our results show that hyaluronidase treatment, as well as knockdown of CD44, in astrocytes result in a "stellate"-like morphology, whereas overexpression of CD44 causes an increase in cell body size and changes the shape of astrocytes into flattened cells. Moreover, as a dynamic reorganization of the actin cytoskeleton is supposed to be responsible for morphological changes of cells, and this reorganization is controlled by small GTPases of the Rho family, we hypothesized that GTPase Rac1 acts as a downstream effector for hyaluronan and CD44 in astrocytes. We used FRET-based biosensor and a dominant negative mutant of Rac1 to investigate the involvement of Rac1 activity in hyaluronidase- and CD44-dependent morphological changes of astrocytes. Both, hyaluronidase treatment and knockdown of CD44, enhances Rac1 activity while overexpression of CD44 reduces the activity state in astrocytes. Furthermore, morphological changes were blocked by specific inhibition of Rac1 activity. These findings indicate for the first time that regulation of Rac1 activity is responsible for hyaluronidase and CD44-driven morphological

  9. Cleavage of Hyaluronan and CD44 Adhesion Molecule Regulate Astrocyte Morphology via Rac1 Signalling.

    Konopka, Anna; Zeug, Andre; Skupien, Anna; Kaza, Beata; Mueller, Franziska; Chwedorowicz, Agnieszka; Ponimaskin, Evgeni; Wilczynski, Grzegorz M; Dzwonek, Joanna

    2016-01-01

    Communication of cells with their extracellular environment is crucial to fulfill their function in physiological and pathophysiological conditions. The literature data provide evidence that such a communication is also important in case of astrocytes. Mechanisms that contribute to the interaction between astrocytes and extracellular matrix (ECM) proteins are still poorly understood. Hyaluronan is the main component of ECM in the brain, where its major receptor protein CD44 is expressed by a subset of astrocytes. Considering the fact that functions of astrocytes are tightly coupled with changes in their morphology (e.g.: glutamate clearance in the synaptic cleft, migration, astrogliosis), we investigated the influence of hyaluronan cleavage by hyaluronidase, knockdown of CD44 by specific shRNA and CD44 overexpression on astrocyte morphology. Our results show that hyaluronidase treatment, as well as knockdown of CD44, in astrocytes result in a "stellate"-like morphology, whereas overexpression of CD44 causes an increase in cell body size and changes the shape of astrocytes into flattened cells. Moreover, as a dynamic reorganization of the actin cytoskeleton is supposed to be responsible for morphological changes of cells, and this reorganization is controlled by small GTPases of the Rho family, we hypothesized that GTPase Rac1 acts as a downstream effector for hyaluronan and CD44 in astrocytes. We used FRET-based biosensor and a dominant negative mutant of Rac1 to investigate the involvement of Rac1 activity in hyaluronidase- and CD44-dependent morphological changes of astrocytes. Both, hyaluronidase treatment and knockdown of CD44, enhances Rac1 activity while overexpression of CD44 reduces the activity state in astrocytes. Furthermore, morphological changes were blocked by specific inhibition of Rac1 activity. These findings indicate for the first time that regulation of Rac1 activity is responsible for hyaluronidase and CD44-driven morphological changes of

  10. Myosin 1g Contributes to CD44 Adhesion Protein and Lipid Rafts Recycling and Controls CD44 Capping and Cell Migration in B Lymphocytes

    Orestes López-Ortega

    2017-12-01

    Full Text Available Cell migration and adhesion are critical for immune system function and involve many proteins, which must be continuously transported and recycled in the cell. Recycling of adhesion molecules requires the participation of several proteins, including actin, tubulin, and GTPases, and of membrane components such as sphingolipids and cholesterol. However, roles of actin motor proteins in adhesion molecule recycling are poorly understood. In this study, we identified myosin 1g as one of the important motor proteins that drives recycling of the adhesion protein CD44 in B lymphocytes. We demonstrate that the lack of Myo1g decreases the cell-surface levels of CD44 and of the lipid raft surrogate GM1. In cells depleted of Myo1g, the recycling of CD44 was delayed, the delay seems to be caused at the level of formation of recycling complex and entry into recycling endosomes. Moreover, a defective lipid raft recycling in Myo1g-deficient cells had an impact both on the capping of CD44 and on cell migration. Both processes required the transportation of lipid rafts to the cell surface to deliver signaling components. Furthermore, the extramembrane was essential for cell expansion and remodeling of the plasma membrane topology. Therefore, Myo1g is important during the recycling of lipid rafts to the membrane and to the accompanied proteins that regulate plasma membrane plasticity. Thus, Myosin 1g contributes to cell adhesion and cell migration through CD44 recycling in B lymphocytes.

  11. CD44 Promotes intoxication by the clostridial iota-family toxins.

    Wigelsworth, Darran J; Ruthel, Gordon; Schnell, Leonie; Herrlich, Peter; Blonder, Josip; Veenstra, Timothy D; Carman, Robert J; Wilkins, Tracy D; Van Nhieu, Guy Tran; Pauillac, Serge; Gibert, Maryse; Sauvonnet, Nathalie; Stiles, Bradley G; Popoff, Michel R; Barth, Holger

    2012-01-01

    Various pathogenic clostridia produce binary protein toxins associated with enteric diseases of humans and animals. Separate binding/translocation (B) components bind to a protein receptor on the cell surface, assemble with enzymatic (A) component(s), and mediate endocytosis of the toxin complex. Ultimately there is translocation of A component(s) from acidified endosomes into the cytosol, leading to destruction of the actin cytoskeleton. Our results revealed that CD44, a multifunctional surface protein of mammalian cells, facilitates intoxication by the iota family of clostridial binary toxins. Specific antibody against CD44 inhibited cytotoxicity of the prototypical Clostridium perfringens iota toxin. Versus CD44(+) melanoma cells, those lacking CD44 bound less toxin and were dose-dependently resistant to C. perfringens iota, as well as Clostridium difficile and Clostridium spiroforme iota-like, toxins. Purified CD44 specifically interacted in vitro with iota and iota-like, but not related Clostridium botulinum C2, toxins. Furthermore, CD44 knockout mice were resistant to iota toxin lethality. Collective data reveal an important role for CD44 during intoxication by a family of clostridial binary toxins.

  12. In situ identification of CD44+/CD24- cancer cells in primary human breast carcinomas.

    Giuseppe Perrone

    Full Text Available Breast cancer cells with the CD44+/CD24- phenotype have been reported to be tumourigenic due to their enhanced capacity for cancer development and their self-renewal potential. The identification of human tumourigenic breast cancer cells in surgical samples has recently received increased attention due to the implications for prognosis and treatment, although limitations exist in the interpretation of these studies. To better identify the CD44+/CD24- cells in routine surgical specimens, 56 primary breast carcinoma cases were analysed by immunofluorescence and confocal microscopy, and the results were compared using flow cytometry analysis to correlate the amount and distribution of the CD44+/CD24- population with clinicopathological features. Using these methods, we showed that the breast carcinoma cells displayed four distinct sub-populations based on the expression pattern of CD44 and CD24. The CD44+/CD24- cells were found in 91% of breast tumours and constituted an average of 6.12% (range, 0.11%-21.23% of the tumour. A strong correlation was found between the percentage of CD44+/CD24- cells in primary tumours and distant metastasis development (p = 0.0001; in addition, there was an inverse significant association with ER and PGR status (p = 0.002 and p = 0.001, respectively. No relationship was evident with tumour size (T and regional lymph node (N status, differentiation grade, proliferative index or HER2 status. In a multivariate analysis, the percentage of CD44+/CD24- cancer cells was an independent factor related to metastasis development (p = 0.004. Our results indicate that confocal analysis of fluorescence-labelled breast cancer samples obtained at surgery is a reliable method to identify the CD44+/CD24- tumourigenic cell population, allowing for the stratification of breast cancer patients into two groups with substantially different relapse rates on the basis of CD44+/CD24- cell percentage.

  13. Prognostic significance of CD44s expression in resected non-small cell lung cancer

    Ko Yoon

    2011-08-01

    Full Text Available Abstract Background CD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether CD44s is involved in clinical outcomes of patients with resected non-small cell lung cancer (NSCLC. Methods Using immunohistochemical staining, we investigated CD44s protein expression using tissue array specimens from 159 patients with resected NSCLC (adenocarcinoma (AC; n = 82 and squamous cell carcinoma (SCC; n = 77. Additionally, the immunoreactivity of cyclooxygenase (COX-2 was also studied. The clinicopathological implications of these molecules were analyzed statistically. Results High CD44s expression was detected more frequently in NSCLC patients with SCC (66/72; 91.7% than in those with AC histology (P 0.001. Additionally, high CD44s expression was significant correlated with more advanced regional lymph node metastasis (P = 0.021. In multivariate analysis of survival in NSCLC patients with AC histology, significant predictors were lymph node metastasis status (P P = 0.046, and high CD44s expression (P = 0.014. For NSCLC patients with SCC histology, the significant predictor was a more advanced tumor stage (P = 0.015. No significant association was found between CD44s and clinical outcome (P = 0.311. Conclusions High CD44s expression was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with AC histology, and was independent of tumor stage.

  14. Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy

    Pham Phuc V

    2011-12-01

    Full Text Available Abstract Background Breast cancer stem cells (BCSCs are the source of breast tumors. Compared with other cancer cells, cancer stem cells show high resistance to both chemotherapy and radiotherapy. Targeting of BCSCs is thus a potentially promising and effective strategy for breast cancer treatment. Differentiation therapy represents one type of cancer stem-cell-targeting therapy, aimed at attacking the stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs. Methods We isolated a breast cancer cell population (CD44+CD24- cells from primary cultures of malignant breast tumors. These cells were sorted into four sub-populations based on their expression of CD44 and CD24 surface markers. CD44 knockdown in the BCSC population was achieved using small hairpin RNA lentivirus particles. The differentiated status of CD44 knock-down BCSCs was evaluated on the basis of changes in CD44+CD24- phenotype, tumorigenesis in NOD/SCID mice, and gene expression in relation to renewal status, metastasis, and cell cycle in comparison with BCSCs and non-BCSCs. Results Knockdown of CD44 caused BCSCs to differentiate into non-BCSCs with lower tumorigenic potential, and altered the cell cycle and expression profiles of some stem cell-related genes, making them more similar to those seen in non-BCSCs. Conclusions Knockdown of CD44 is an effective strategy for attacking the stemness of BCSCs, resulting in a loss of stemness and an increase in susceptibility to chemotherapy or radiation. The results of this study highlight a potential new strategy for breast cancer treatment through the targeting of BCSCs.

  15. Mineralization Effect of Hyaluronan on Dental Pulp Cells via CD44.

    Chen, Kuan-Liang; Yeh, Ying-Yi; Lung, Jrhau; Yang, Yu-Chi; Yuan, Kuo

    2016-05-01

    CD44 is a cell-surface glycoprotein involved in various cellular functions. Recent studies have suggested that CD44 is involved in early mineralization of odontoblasts. Hyaluronic acid (HA) is the principal ligand for receptor CD44. Whether and how HA regulated the mineralization process of dental pulp cells were investigated. The effects of high-molecular-weight HA on differentiation and mineral deposition of dental pulp cells were tested by using alkaline phosphatase (ALP) activity assay and alizarin red S staining. Osteogenesis real-time polymerase chain reaction array, quantitative polymerase chain reaction, and Western blotting were performed to identify downstream molecules involved in the mineralization induction of HA. CD44 was knocked down and examined to confirm whether the mineralization effect of HA was mediated by receptor CD44. Immunohistochemistry was used to understand the localization patterns of CD44 and the identified downstream proteins in vivo. Pulse treatment of HA enhanced ALP activity and mineral deposition in dental pulp cells. Tissue-nonspecific ALP, bone morphogenetic protein 7 (BMP7), and type XV collagen (Col15A1) were upregulated via the HA-CD44 pathway in vitro. Immunohistochemistry of tooth sections showed that the staining pattern of BMP7 was very similar to that of CD44. Results of this study indicated that high-molecular-weight HA enhanced early mineralization of dental pulp cells mediated via CD44. The process involved important mineralization-associated molecules including tissue-nonspecific ALP, BMP7, and Col15A1. The findings may help develop new strategies in regenerative endodontics. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  16. Prognostic significance of CD44s expression in resected non-small cell lung cancer

    Ko, Yoon Ho; Won, Hye Sung; Jeon, Eun Kyoung; Hong, Sook Hee; Roh, Sang Young; Hong, Young Seon; Byun, Jae Ho; Jung, Chan-Kwon; Kang, Jin Hyoung

    2011-01-01

    CD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether CD44s is involved in clinical outcomes of patients with resected non-small cell lung cancer (NSCLC). Using immunohistochemical staining, we investigated CD44s protein expression using tissue array specimens from 159 patients with resected NSCLC (adenocarcinoma (AC; n = 82) and squamous cell carcinoma (SCC; n = 77). Additionally, the immunoreactivity of cyclooxygenase (COX)-2 was also studied. The clinicopathological implications of these molecules were analyzed statistically. High CD44s expression was detected more frequently in NSCLC patients with SCC (66/72; 91.7%) than in those with AC histology (P <0.001). Additionally, high CD44s expression was significant correlated with more advanced regional lymph node metastasis (P = 0.021). In multivariate analysis of survival in NSCLC patients with AC histology, significant predictors were lymph node metastasis status (P < 0.001), high-grade tumor differentiation (P = 0.046), and high CD44s expression (P = 0.014). For NSCLC patients with SCC histology, the significant predictor was a more advanced tumor stage (P = 0.015). No significant association was found between CD44s and clinical outcome (P = 0.311). High CD44s expression was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with AC histology, and was independent of tumor stage

  17. Effects of CD44 Ligation on Signaling and Metabolic Pathways in Acute Myeloid Leukemia

    Madhoun, Nour Y.

    2017-04-01

    Acute myeloid leukemia (AML) is characterized by a blockage in the differentiation of myeloid cells at different stages. CD44-ligation using anti-CD44 monoclonal antibodies (mAbs) has been shown to reverse the blockage of differentiation and to inhibit the proliferation of blasts in most AML-subtypes. However, the molecular mechanisms underlying this property have not been fully elucidated. Here, we sought to I) analyze the effects of anti-CD44 mAbs on downstream signaling pathways, including the ERK1/2 (extracellular signal-regulated kinase 1 and 2) and mTOR (mammalian target of rapamycin) pathways and II) use state-of-the-art Nuclear Magnetic Resonance (NMR) technology to determine the global metabolic changes during differentiation induction of AML cells using anti-CD44 mAbs and other two previously reported differentiation agents. In the first objective (Chapter 4), our studies provide evidence that CD44-ligation with specific mAbs in AML cells induced an increase in ERK1/2 phosphorylation. The use of the MEK inhibitor (U0126) significantly inhibited the CD44-induced differentiation of HL60 cells, suggesting that ERK1/2 is critical for the CD44-triggered differentiation in AML. In addition, this was accompanied by a marked decrease in the phosphorylation of the mTORC1 and mTORC2 complexes, which are strongly correlated with the inhibition of the PI3K/Akt pathway. In the second objective (Chapter 5), 1H NMR experiments demonstrated that considerable changes in the metabolic profiles of HL60 cells were induced in response to each differentiation agent. These most notable metabolites that significantly changed upon CD44 ligation were involved in the tricarboxylic acid (TCA) cycle and glycolysis such as, succinate, fumarate and lactate. Therefore, we sought to analyze the mechanisms underlying their alterations. Our results revealed that anti-CD44 mAbs treatment induced upregulation in fumarate hydratase (FH) expression and its activity which was accompanied by a

  18. Occupational Injury Prevention Research in NIOSH

    Hongwei Hsiao

    2010-12-01

    Full Text Available This paper provided a brief summary of the current strategic goals, activities, and impacts of the NIOSH (National Institute for Occupational Safety and Health occupational injury research program. Three primary drivers (injury database, stakeholder input, and staff capacity were used to define NIOSH research focuses to maximize relevance and impact of the NIOSH injury-prevention-research program. Injury data, strategic goals, program activities, and research impacts were presented with a focus on prevention of four leading causes of workplace injury and death in the US: motor vehicle incidents, falls, workplace violence, and machine and industrial vehicle incidents. This paper showcased selected priority goals, activities, and impacts of the NIOSH injury prevention program. The NIOSH contribution to the overall decrease in fatalities and injuries is reinforced by decreases in specific goal areas. There were also many intermediate outcomes that are on a direct path to preventing injuries, such as new safety regulations and standards, safer technology and products, and improved worker safety training. The outcomes serve as an excellent foundation to stimulate further research and worldwide partnership to address global workplace injury problems.

  19. CD44 Interacts with HIF-2α to Modulate the Hypoxic Phenotype of Perinecrotic and Perivascular Glioma Cells

    Johansson, Elinn; Grassi, Elisa S.; Pantazopoulou, Vasiliki

    2017-01-01

    Hypoxia-inducible factors enhance glioma stemness, and glioma stem cells have an amplified hypoxic response despite residing within a perivascular niche. Still, little is known about differential HIF regulation in stem versus bulk glioma cells. We show that the intracellular domain of stem cell...... marker CD44 (CD44ICD) is released at hypoxia, binds HIF-2α (but not HIF-1α), enhances HIF target gene activation, and is required for hypoxia-induced stemness in glioma. In a glioma mouse model, CD44 was restricted to hypoxic and perivascular tumor regions, and in human glioma, a hypoxia signature...... correlated with CD44. The CD44ICD was sufficient to induce hypoxic signaling at perivascular oxygen tensions, and blocking CD44 cleavage decreased HIF-2α stabilization in CD44-expressing cells. Our data indicate that the stem cell marker CD44 modulates the hypoxic response of glioma cells and that the pseudo-hypoxic...

  20. The Expression and Regulation of the Cell Adhesion Molecule CD44 in Human Breast Cancer

    Ge, Lisheng

    1997-01-01

    ... alternative splicing signals of CD44 variant exons as control elements in CEPT. In our colon cancer metastasis to liver model, we developed dual modulation vectors to increase tissue-specific expression of cytosine deaminase (CD...

  1. CD44: molecular interactions, signalling and functions in the nervous system.

    Grzegorz Marek Wilczynski

    2015-05-01

    Full Text Available CD44 is the major surface hyaluronan receptor implicated in intercellular and cell-matrix adhesion, cell migration and signalling. It is a transmembrane, highly glycosylated protein with several isoforms resulting from alternative gene splicing. The CD44 molecule consists of several domains serving different functions: the N-terminal extracellular domain, the stem region, the transmembrane domain and the C-terminal tail. In the nervous system, CD44 expression occurs in both glial and neuronal cells. The role of CD44 in the physiology and pathology of the nervous system is not entirely understood, however, there exists evidence suggesting it might be involved in the axon guidance, cytoplasmic Ca2+ clearance, dendritic arborization, synaptic transmission, epileptogenesis, oligodendrocyte and astrocyte differentiation, post-traumatic brain repair and brain tumour development.

  2. CD44v6 regulates growth of brain tumor stem cells partially through the AKT-mediated pathway.

    Mayumi Jijiwa

    Full Text Available Identification of stem cell-like brain tumor cells (brain tumor stem-like cells; BTSC has gained substantial attention by scientists and physicians. However, the mechanism of tumor initiation and proliferation is still poorly understood. CD44 is a cell surface protein linked to tumorigenesis in various cancers. In particular, one of its variant isoforms, CD44v6, is associated with several cancer types. To date its expression and function in BTSC is yet to be identified. Here, we demonstrate the presence and function of the variant form 6 of CD44 (CD44v6 in BTSC of a subset of glioblastoma multiforme (GBM. Patients with CD44(high GBM exhibited significantly poorer prognoses. Among various variant forms, CD44v6 was the only isoform that was detected in BTSC and its knockdown inhibited in vitro growth of BTSC from CD44(high GBM but not from CD44(low GBM. In contrast, this siRNA-mediated growth inhibition was not apparent in the matched GBM sample that does not possess stem-like properties. Stimulation with a CD44v6 ligand, osteopontin (OPN, increased expression of phosphorylated AKT in CD44(high GBM, but not in CD44(low GBM. Lastly, in a mouse spontaneous intracranial tumor model, CD44v6 was abundantly expressed by tumor precursors, in contrast to no detectable CD44v6 expression in normal neural precursors. Furthermore, overexpression of mouse CD44v6 or OPN, but not its dominant negative form, resulted in enhanced growth of the mouse tumor stem-like cells in vitro. Collectively, these data indicate that a subset of GBM expresses high CD44 in BTSC, and its growth may depend on CD44v6/AKT pathway.

  3. Exosomes Promote Ovarian Cancer Cell Invasion through Transfer of CD44 to Peritoneal Mesothelial Cells.

    Nakamura, Koji; Sawada, Kenjiro; Kinose, Yasuto; Yoshimura, Akihiko; Toda, Aska; Nakatsuka, Erika; Hashimoto, Kae; Mabuchi, Seiji; Morishige, Ken-Ichirou; Kurachi, Hirohisa; Lengyel, Ernst; Kimura, Tadashi

    2017-01-01

    Epithelial ovarian cancer (EOC) cells metastasize within the peritoneal cavity and directly encounter human peritoneal mesothelial cells (HPMC) as the initial step of metastasis. The contact between ovarian cancer cells and the single layer of mesothelial cells involves direct communications that modulate cancer progression but the mechanisms are unclear. One candidate mediating cell-cell communications is exosomes, 30-100 nm membrane vesicles of endocytic origin, through the cell-cell transfer of proteins, mRNAs, or microRNAs. Therefore, the goal was to mechanistically characterize how EOC-derived exosomes modulate metastasis. Exosomes from ovarian cancer cells were fluorescently labeled and cocultured with HPMCs which internalized the exosomes. Upon exosome uptake, HPMCs underwent a change in cellular morphology to a mesenchymal, spindle phenotype. CD44, a cell surface glycoprotein, was found to be enriched in the cancer cell-derived exosomes, transferred, and internalized to HPMCs, leading to high levels of CD44 in HPMCs. This increased CD44 expression in HPMCs promoted cancer invasion by inducing the HPMCs to secrete MMP9 and by cleaning the mesothelial barrier for improved cancer cell invasion. When CD44 expression was knocked down in cancer cells, exosomes had fewer effects on HPMCs. The inhibition of exosome release from cancer cells blocked CD44 internalization in HPMCs and suppressed ovarian cancer invasion. In ovarian cancer omental metastasis, positive CD44 expression was observed in those mesothelial cells that directly interacted with cancer cells, whereas CD44 expression was negative in the mesothelial cells remote from the invading edge. This study indicates that ovarian cancer-derived exosomes transfer CD44 to HPMCs, facilitating cancer invasion. Mechanistic insight from the current study suggests that therapeutic targeting of exosomes may be beneficial in treating ovarian cancer. Mol Cancer Res; 15(1); 78-92. ©2016 AACR. ©2016 American

  4. Immunohistochemical expression of CD44s in renal cell carcinoma lacks independent prognostic significance

    Walter Henriques da Costa

    2012-08-01

    Full Text Available PURPOSE: To analyze the immunohistochemical expression of the standard isoform of CD44 (CD44s adhesion molecule in clear cell renal cell carcinoma (CCRCC and its impact on clinical outcomes. MATERIALS AND METHODS: Ninety-nine consecutive patients treated surgically for RCC between 1992 and 2009 were selected. A single pathologist reviewed all cases to effect a uniform reclassification and determine the most representative tumor areas for construction of a tissue microarray. The same pathologist, who was blinded to the outcome of the cases, semi-quantitatively scored the staining intensity of CD44s in all specimens. The counting was done using the H-Score algorithm. RESULTS: Of the 99 immunostained RCC specimens, 57(57.7% showed low expression, and 42(42.4% showed high expression levels of CD44s. The expression of CD44s was directly associated with tumor size (p = 0.03, clinical stage (p = 0.02 and Fuhrman grade (p = 0.02. Disease specific survival (DSS rates for patients whose specimens expressed low and high levels of CD44s was 88.1% and 67.5%, respectively (p = 0.009. Progression free survival (PFS rates in patients with low and high expression of CD44s were 78.8% and 61.7%, respectively (p = 0.05. Classical features such as the presence of metastasis and clinical stage remained isolated predictors of survival. CONCLUSIONS: Immunohistochemical expression of CD44s was associated with important clinical variables such as stage and Fuhrman grade. However, it was not an independent predictor of survival. Therefore, we believe it has a limited role as a prognostic marker in patients with CCRCC.

  5. Kaempferol regulates OPN–CD44 pathway to inhibit the atherogenesis of apolipoprotein E deficient mice

    Xiao, Hong-Bo; Lu, Xiang-Yang; Sun, Zhi-Liang; Zhang, Heng-Bo

    2011-01-01

    Recent studies show that osteopontin (OPN) and its receptor cluster of differentiation 44 (CD44) are two pro-inflammatory cytokines contributing to the development of atherosclerosis. The objective of this study was to explore the inhibitory effect of kaempferol, a naturally occurring flavonoid compound, on atherogenesis and the mechanisms involved. The experiments were performed in aorta and plasma from C57BL/6J control and apolipoprotein E-deficient (ApoE −/− ) mice treated or not with kaempferol (50 or 100 mg/kg, intragastrically) for 4 weeks. Kaempferol treatment decreased atherosclerotic lesion area, improved endothelium-dependent vasorelaxation, and increased the maximal relaxation value concomitantly with decrease in the half-maximum effective concentration, plasma OPN level, aortic OPN expression, and aortic CD44 expression in ApoE −/− mice. In addition, treatment with kaempferol also significantly decreased reactive oxygen species production in mice aorta. The present results suggest that kaempferol regulates OPN–CD44 pathway to inhibit the atherogenesis of ApoE −/− mice. -- Graphical abstract: Kaempferol regulates OPN–CD44 pathway to inhibit the atherogenesis of ApoE −/− mice. Highlights: ► OPN–CD44 pathway plays a critical role in the development of atherosclerosis. ► We examine lesion area, OPN and CD44 changes after kaempferol treatment. ► Kaempferol treatment decreased atherosclerotic lesion area in ApoE −/− mice. ► Kaempferol treatment decreased aortic OPN and CD44 expressions in ApoE −/− mice. ► Kaempferol regulates OPN–CD44 pathway to inhibit the atherogenesis.

  6. Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of apolipoprotein E deficient mice

    Xiao, Hong-Bo, E-mail: xhbzhb@yahoo.com [College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128 (China); Lu, Xiang-Yang; Sun, Zhi-Liang [Hunan Agricultural University, Changsha 410128 (China); Zhang, Heng-Bo [Furong District Red Cross Hospital, Changsha 410126 (China)

    2011-12-15

    Recent studies show that osteopontin (OPN) and its receptor cluster of differentiation 44 (CD44) are two pro-inflammatory cytokines contributing to the development of atherosclerosis. The objective of this study was to explore the inhibitory effect of kaempferol, a naturally occurring flavonoid compound, on atherogenesis and the mechanisms involved. The experiments were performed in aorta and plasma from C57BL/6J control and apolipoprotein E-deficient (ApoE{sup -/-}) mice treated or not with kaempferol (50 or 100 mg/kg, intragastrically) for 4 weeks. Kaempferol treatment decreased atherosclerotic lesion area, improved endothelium-dependent vasorelaxation, and increased the maximal relaxation value concomitantly with decrease in the half-maximum effective concentration, plasma OPN level, aortic OPN expression, and aortic CD44 expression in ApoE{sup -/-} mice. In addition, treatment with kaempferol also significantly decreased reactive oxygen species production in mice aorta. The present results suggest that kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of ApoE{sup -/-} mice. -- Graphical abstract: Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of ApoE{sup -/-} mice. Highlights: Black-Right-Pointing-Pointer OPN-CD44 pathway plays a critical role in the development of atherosclerosis. Black-Right-Pointing-Pointer We examine lesion area, OPN and CD44 changes after kaempferol treatment. Black-Right-Pointing-Pointer Kaempferol treatment decreased atherosclerotic lesion area in ApoE{sup -/-} mice. Black-Right-Pointing-Pointer Kaempferol treatment decreased aortic OPN and CD44 expressions in ApoE{sup -/-} mice. Black-Right-Pointing-Pointer Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis.

  7. Occupational risks prevention in colombian companies

    Leonardo Briceño

    2003-06-01

    Full Text Available We assessed the preventive activitiesperformed in 120 Colombian workplacesin Bogotá and El Valle delCauca, Colombia.The results were analyzed by level of interventionconsidering the primary, secondary andtertiary levels, and by size of the workplace.It was established that those enterprisesaffiliated to the Professional Risk insurancesystem –part of the Social security system– withhigher levels of premiums paid to the insurancecompanies, had more prevention activities thanthose with lower payments–75% vs. 16%.The Professional risks administrators –Insurancecompanies– gave more services to thoseworkplaces with high premiums than thoseprovided to enterprises with low premiums.75% of the big factories had a commitmentsigned by the insurance company related toprevention services, while only 19% of the littleenterprises had one. The enterprises with less than20 employees had less prevention activities thanthose with more than 100 employees.None of the evaluated workplaces with lessthan 100 workers had a licensed occupationalhealth counselor.Primary prevention activities like IndustrialHygiene studies in specific risks factors are scarce–24% of the workplaces had any evaluation aboutnoise levels, illumination, temperatures or anyother occupational risks factor 22.5% of theworkplaces show any activity of risk control.It was concluded that the preferential servicesprovided to the biggest enterprises carry a lossof cross subsidies in the social security systembetween big and little factories. Finally, the governmentmust create an information systemregarding the preventive services surveillance inthe highest risks factories.

  8. ALDH/CD44 identifies uniquely tumorigenic cancer stem cells in salivary gland mucoepidermoid carcinomas.

    Adams, April; Warner, Kristy; Pearson, Alexander T; Zhang, Zhaocheng; Kim, Hong Sun; Mochizuki, Daiki; Basura, Gregory; Helman, Joseph; Mantesso, Andrea; Castilho, Rogério M; Wicha, Max S; Nör, Jacques E

    2015-09-29

    A small sub-population of cells characterized by increased tumorigenic potential, ability to self-renew and to differentiate into cells that make up the tumor bulk, has been characterized in some (but not all) tumor types. These unique cells, namedcancer stem cells, are considered drivers of tumor progression in these tumors. The purpose of this work is to understand if cancer stem cells play a functional role in the tumorigenesis of salivary gland mucoepidermoid carcinomas. Here, we investigated the expression of putative cancer stem cell markers (ALDH, CD10, CD24, CD44) in primary human mucoepidermoid carcinomas by immunofluorescence, in vitro salisphere assays, and in vivo tumorigenicity assays in immunodeficient mice. Human mucoepidermoid carcinoma cells (UM-HMC-1, UM-HMC-3A, UM-HMC-3B) sorted for high levels of ALDH activity and CD44 expression (ALDHhighCD44high) consistently formed primary and secondary salispheres in vitro, and showed enhanced tumorigenic potential in vivo (defined as time to tumor palpability, tumor growth after palpability), when compared to ALDHlowCD44low cells. Cells sorted for CD10/CD24, and CD10/CD44 showed varying trends of salisphere formation, but consistently low in vivo tumorigenic potential. And finally, cells sorted for CD44/CD24 showed inconsistent results in salisphere formation and tumorigenic potential assays when different cell lines were evaluated. Collectively, these data demonstrate that salivary gland mucoepidermoid carcinomas contain a small population of cancer stem cells with enhanced tumorigenic potential and that are characterized by high ALDH activity and CD44 expression. These results suggest that patients with mucoepidermoid carcinoma might benefit from therapies that ablate these highly tumorigenic cells.

  9. CD44-positive cells are candidates for astrocyte precursor cells in developing mouse cerebellum.

    Cai, Na; Kurachi, Masashi; Shibasaki, Koji; Okano-Uchida, Takayuki; Ishizaki, Yasuki

    2012-03-01

    Neural stem cells are generally considered to be committed to becoming precursor cells before terminally differentiating into either neurons or glial cells during neural development. Neuronal and oligodendrocyte precursor cells have been identified in several areas in the murine central nervous system. The presence of astrocyte precursor cells (APCs) is not so well understood. The present study provides several lines of evidence that CD44-positive cells are APCs in the early postnatal mouse cerebellum. In developing mouse cerebellum, CD44-positive cells, mostly located in the white matter, were positive for the markers of the astrocyte lineage, but negative for the markers of mature astrocytes. CD44-positive cells were purified from postnatal cerebellum by fluorescence-activated cell sorting and characterized in vitro. In the absence of any signaling molecule, many cells died by apoptosis. The surviving cells gradually expressed glial fibrillary acidic protein, a marker for mature astrocytes, indicating that differentiation into mature astrocytes is the default program for these cells. The cells produced no neurospheres nor neurons nor oligodendrocytes under any condition examined, indicating these cells are not neural stem cells. Leukemia inhibitory factor greatly promoted astrocytic differentiation of CD44-positive cells, whereas bone morphogenetic protein 4 (BMP4) did not. Fibroblast growth factor-2 was a potent mitogen for these cells, but was insufficient for survival. BMP4 inhibited activation of caspase-3 and greatly promoted survival, suggesting a novel role for BMP4 in the control of development of astrocytes in cerebellum. We isolated and characterized only CD44 strongly positive large cells and discarded small and/or CD44 weakly positive cells in this study. Further studies are necessary to characterize these cells to help determine whether CD44 is a selective and specific marker for APCs in the developing mouse cerebellum. In conclusion, we succeeded in

  10. Hyaluronate fragments reverse skin atrophy by a CD44-dependent mechanism.

    Gürkan Kaya

    2006-12-01

    Full Text Available BACKGROUND: Skin atrophy is a common manifestation of aging and is frequently accompanied by ulceration and delayed wound healing. With an increasingly aging patient population, management of skin atrophy is becoming a major challenge in the clinic, particularly in light of the fact that there are no effective therapeutic options at present. METHODS AND FINDINGS: Atrophic skin displays a decreased hyaluronate (HA content and expression of the major cell-surface hyaluronate receptor, CD44. In an effort to develop a therapeutic strategy for skin atrophy, we addressed the effect of topical administration of defined-size HA fragments (HAF on skin trophicity. Treatment of primary keratinocyte cultures with intermediate-size HAF (HAFi; 50,000-400,000 Da but not with small-size HAF (HAFs; 400,000 Da induced wild-type (wt but not CD44-deficient (CD44-/- keratinocyte proliferation. Topical application of HAFi caused marked epidermal hyperplasia in wt but not in CD44-/- mice, and significant skin thickening in patients with age- or corticosteroid-related skin atrophy. The effect of HAFi on keratinocyte proliferation was abrogated by antibodies against heparin-binding epidermal growth factor (HB-EGF and its receptor, erbB1, which form a complex with a particular isoform of CD44 (CD44v3, and by tissue inhibitor of metalloproteinase-3 (TIMP-3. CONCLUSIONS: Our observations provide a novel CD44-dependent mechanism for HA oligosaccharide-induced keratinocyte proliferation and suggest that topical HAFi application may provide an attractive therapeutic option in human skin atrophy.

  11. Hyaluronan functionalizing QDs as turn-on fluorescent probe for targeted recognition CD44 receptor

    Zhou, Shang; Huo, Danqun; Hou, Changjun; Yang, Mei; Fa, Huanbao

    2017-09-01

    The recognition of tumor markers in living cancer cells has attracted increasing interest. In the present study, the turn-on fluorescence probe was designed based on the fluorescence of thiolated chitosan-coated CdTe QDs (CdTe/TCS QDs) quenched by hyaluronan, which could provide the low background signal for sensitive cellular imaging. This system is expected to offer specific recognition of CD44 receptor over other substances owing to the specific affinity of hyaluronan and CD44 receptor ( 8-9 kcal/mol). The probe is stable in aqueous and has little toxicity to living cells; thus, it can be utilized for targeted cancer cell imaging. The living lung cancer cell imaging experiments further demonstrate its value in recognizing cell-surface CD44 receptor with turn-on mode. In addition, the probe can be used to recognize and differentiate the subtypes of lung cancer cells based on the difference of CD44 expression on the surface of lung cancer cells. And, the western blot test further confirmed that the expression level of the CD44 receptor in lung cancer cells is different. Therefore, this probe may be potentially applied in recognizing lung cancer cells with higher contrast and sensitivity and provide new tools for cancer prognosis and therapy. [Figure not available: see fulltext.

  12. CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers

    Olsson, Eleonor; Lövgren, Kristina; Fernö, Mårten; Grabau, Dorthe; Borg, Åke; Hegardt, Cecilia; Honeth, Gabriella; Bendahl, Pär-Ola; Saal, Lao H; Gruvberger-Saal, Sofia; Ringnér, Markus; Vallon-Christersson, Johan; Jönsson, Göran; Holm, Karolina

    2011-01-01

    The CD44 cell adhesion molecule is aberrantly expressed in many breast tumors and has been implicated in the metastatic process as well as in the putative cancer stem cell (CSC) compartment. We aimed to investigate potential associations between alternatively spliced isoforms of CD44 and CSCs as well as to various breast cancer biomarkers and molecular subtypes. We used q-RT-PCR and exon-exon spanning assays to analyze the expression of four alternatively spliced CD44 isoforms as well as the total expression of CD44 in 187 breast tumors and 13 cell lines. ALDH1 protein expression was determined by IHC on TMA. Breast cancer cell lines showed a heterogeneous expression pattern of the CD44 isoforms, which shifted considerably when cells were grown as mammospheres. Tumors characterized as positive for the CD44 + /CD24 - phenotype by immunohistochemistry were associated to all isoforms except the CD44 standard (CD44S) isoform, which lacks all variant exons. Conversely, tumors with strong expression of the CSC marker ALDH1 had elevated expression of CD44S. A high expression of the CD44v2-v10 isoform, which retain all variant exons, was correlated to positive steroid receptor status, low proliferation and luminal A subtype. The CD44v3-v10 isoform showed similar correlations, while high expression of CD44v8-v10 was correlated to positive EGFR, negative/low HER2 status and basal-like subtype. High expression of CD44S was associated with strong HER2 staining and also a subgroup of basal-like tumors. Unsupervised hierarchical cluster analysis of CD44 isoform expression data divided tumors into four main clusters, which showed significant correlations to molecular subtypes and differences in 10-year overall survival. We demonstrate that individual CD44 isoforms can be associated to different breast cancer subtypes and clinical markers such as HER2, ER and PgR, which suggests involvement of CD44 splice variants in specific oncogenic signaling pathways. Efforts to link CD44 to

  13. CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers

    Vallon-Christersson Johan

    2011-09-01

    Full Text Available Abstract Background The CD44 cell adhesion molecule is aberrantly expressed in many breast tumors and has been implicated in the metastatic process as well as in the putative cancer stem cell (CSC compartment. We aimed to investigate potential associations between alternatively spliced isoforms of CD44 and CSCs as well as to various breast cancer biomarkers and molecular subtypes. Methods We used q-RT-PCR and exon-exon spanning assays to analyze the expression of four alternatively spliced CD44 isoforms as well as the total expression of CD44 in 187 breast tumors and 13 cell lines. ALDH1 protein expression was determined by IHC on TMA. Results Breast cancer cell lines showed a heterogeneous expression pattern of the CD44 isoforms, which shifted considerably when cells were grown as mammospheres. Tumors characterized as positive for the CD44+/CD24- phenotype by immunohistochemistry were associated to all isoforms except the CD44 standard (CD44S isoform, which lacks all variant exons. Conversely, tumors with strong expression of the CSC marker ALDH1 had elevated expression of CD44S. A high expression of the CD44v2-v10 isoform, which retain all variant exons, was correlated to positive steroid receptor status, low proliferation and luminal A subtype. The CD44v3-v10 isoform showed similar correlations, while high expression of CD44v8-v10 was correlated to positive EGFR, negative/low HER2 status and basal-like subtype. High expression of CD44S was associated with strong HER2 staining and also a subgroup of basal-like tumors. Unsupervised hierarchical cluster analysis of CD44 isoform expression data divided tumors into four main clusters, which showed significant correlations to molecular subtypes and differences in 10-year overall survival. Conclusions We demonstrate that individual CD44 isoforms can be associated to different breast cancer subtypes and clinical markers such as HER2, ER and PgR, which suggests involvement of CD44 splice variants in

  14. Detection of high CD44 expression in oral cancers using the novel monoclonal antibody, C44Mab-5

    Shinji Yamada

    2018-07-01

    Full Text Available CD44 is a transmembrane glycoprotein that regulates a variety of genes related to cell-adhesion, migration, proliferation, differentiation, and survival. A large number of alternative splicing isoforms of CD44, containing various combinations of alternative exons, have been reported. CD44 standard (CD44s, which lacks variant exons, is widely expressed on the surface of most tissues and all hematopoietic cells. In contrast, CD44 variant isoforms show tissue-specific expression patterns and have been extensively studied as both prognostic markers and therapeutic targets in cancer and other diseases. In this study, we immunized mice with CHO-K1 cell lines overexpressing CD44v3-10 to obtain novel anti-CD44 mAbs. One of the clones, C44Mab-5 (IgG1, kappa, recognized both CD44s and CD44v3-10. C44Mab-5 also reacted with oral cancer cells such as Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4 using flow cytometry. Moreover, immunohistochemical analysis revealed that C44Mab-5 detected 166/182 (91.2% of oral cancers. These results suggest that the C44Mab-5 antibody may be useful for investigating the expression and function of CD44 in various cancers.

  15. Detection of high CD44 expression in oral cancers using the novel monoclonal antibody, C44Mab-5.

    Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Yanaka, Miyuki; Kaneko, Mika K; Kato, Yukinari

    2018-07-01

    CD44 is a transmembrane glycoprotein that regulates a variety of genes related to cell-adhesion, migration, proliferation, differentiation, and survival. A large number of alternative splicing isoforms of CD44, containing various combinations of alternative exons, have been reported. CD44 standard (CD44s), which lacks variant exons, is widely expressed on the surface of most tissues and all hematopoietic cells. In contrast, CD44 variant isoforms show tissue-specific expression patterns and have been extensively studied as both prognostic markers and therapeutic targets in cancer and other diseases. In this study, we immunized mice with CHO-K1 cell lines overexpressing CD44v3-10 to obtain novel anti-CD44 mAbs. One of the clones, C 44 Mab-5 (IgG 1 , kappa), recognized both CD44s and CD44v3-10. C 44 Mab-5 also reacted with oral cancer cells such as Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4 using flow cytometry. Moreover, immunohistochemical analysis revealed that C 44 Mab-5 detected 166/182 (91.2%) of oral cancers. These results suggest that the C 44 Mab-5 antibody may be useful for investigating the expression and function of CD44 in various cancers.

  16. Lung cancer tumorigenicity and drug resistance are maintained through ALDH(hi)CD44(hi) tumor initiating cells.

    Liu, Jing; Xiao, Zhijie; Wong, Sunny Kit-Man; Tin, Vicky Pui-Chi; Ho, Ka-Yan; Wang, Junwen; Sham, Mai-Har; Wong, Maria Pik

    2013-10-01

    Limited improvement in long term survival of lung cancer patients has been achieved by conventional chemotherapy or targeted therapy. To explore the potentials of tumor initiating cells (TIC)-directed therapy, it is essential to identify the cell targets and understand their maintenance mechanisms. We have analyzed the performance of ALDH/CD44 co-expression as TIC markers and treatment targets of lung cancer using well-validated in vitro and in vivo analyses in multiple established and patient-derived lung cancer cells. The ALDH(hi)CD44(hi) subset showed the highest enhancement of stem cell phenotypic properties compared to ALDH(hi)CD44(lo), ALDH(lo)CD44(hi), ALDH(lo)CD44(lo) cells and unsorted controls. They showed higher invasion capacities, pluripotency genes and epithelial-mesenchymal transition transcription factors expression, lower intercellular adhesion protein expression and higher G2/M phase cell cycle fraction. In immunosuppressed mice, the ALDH(hi)CD44(hi)xenografts showed the highest tumor induction frequency, serial transplantability, shortest latency, largest volume and highest growth rates. Inhibition of sonic Hedgehog and Notch developmental pathways reduced ALDH+CD44+ compartment. Chemotherapy and targeted therapy resulted in higher AALDH(hi)CD44(hi) subset viability and ALDH(lo)CD44(lo) subset apoptosis fraction. ALDH inhibition and CD44 knockdown led to reduced stemness gene expression and sensitization to drug treatment. In accordance, clinical lung cancers containing a higher abundance of ALDH and CD44-coexpressing cells was associated with lower recurrence-free survival. Together, results suggested theALDH(hi)CD44(hi)compartment was the cellular mediator of tumorigenicity and drug resistance. Further investigation of the regulatory mechanisms underlying ALDH(hi)CD44(hi)TIC maintenance would be beneficial for the development of long term lung cancer control.

  17. Expression of CD44 and P53 in renal cell carcinoma: Association with tumor subtypes

    Farahnaz Noroozinia

    2014-01-01

    Full Text Available Renal cell carcinoma (RCC is a common malignancy of the kidney and accurate prediction of prognosis is valuable for the design of adjuvant therapy and counseling and effective scheduling of follow-up visits. Molecular genetic investigations of CD44 and P53 in RCC may be helpful in this regard. We studied the CD44 and P53 expressions semi-quantitatively on paraffin-embedded specimens of 64 RCC patients (37 male/27 female who underwent surgery from 2003 to 2008 by immunohistochemistry and analyzed the correlation of P53 and CD44 expression in RCC and outcome. Thirteen of 64 (20.3% specimens were P53 positive, 30/64 (46.9% were CD44 positive and five tumors with positive P53 expressed CD44 protein (P = 0.5. A statistically significant correlation was not found between CD44 and P53 expression (P = 0.5 and age (P = 0.07, sex (P= 0.3, tumor size (P = 0.7, grade (P = 0.23, vascular invasion (P = 1.00 and ureteral invasion (P = 1.00. Furthermore, a significant correlation was not found between P53 expression with age (P = 0.3, sex (P = 0.7, tumor size (P = 0.7, grade (P = 0.1, vascular inva-sion (P = 1.00 and ureteral invasion (P = 1.00. According to our findings, only P53 expression is generally accompanied by non-conventional subtype tumor.

  18. CD44 plays a functional role in Helicobacter pylori-induced epithelial cell proliferation.

    Nina Bertaux-Skeirik

    2015-02-01

    Full Text Available The cytotoxin-associated gene (Cag pathogenicity island is a strain-specific constituent of Helicobacter pylori (H. pylori that augments cancer risk. CagA translocates into the cytoplasm where it stimulates cell signaling through the interaction with tyrosine kinase c-Met receptor, leading cellular proliferation. Identified as a potential gastric stem cell marker, cluster-of-differentiation (CD CD44 also acts as a co-receptor for c-Met, but whether it plays a functional role in H. pylori-induced epithelial proliferation is unknown. We tested the hypothesis that CD44 plays a functional role in H. pylori-induced epithelial cell proliferation. To assay changes in gastric epithelial cell proliferation in relation to the direct interaction with H. pylori, human- and mouse-derived gastric organoids were infected with the G27 H. pylori strain or a mutant G27 strain bearing cagA deletion (∆CagA::cat. Epithelial proliferation was quantified by EdU immunostaining. Phosphorylation of c-Met was analyzed by immunoprecipitation followed by Western blot analysis for expression of CD44 and CagA. H. pylori infection of both mouse- and human-derived gastric organoids induced epithelial proliferation that correlated with c-Met phosphorylation. CagA and CD44 co-immunoprecipitated with phosphorylated c-Met. The formation of this complex did not occur in organoids infected with ∆CagA::cat. Epithelial proliferation in response to H. pylori infection was lost in infected organoids derived from CD44-deficient mouse stomachs. Human-derived fundic gastric organoids exhibited an induction in proliferation when infected with H. pylori that was not seen in organoids pre-treated with a peptide inhibitor specific to CD44. In the well-established Mongolian gerbil model of gastric cancer, animals treated with CD44 peptide inhibitor Pep1, resulted in the inhibition of H. pylori-induced proliferation and associated atrophic gastritis. The current study reports a unique

  19. High Expression of Osteopontin and CD44v6 in Odontogenic Keratocysts

    Yi-Ping Wang

    2009-04-01

    Conclusion: Binding of OPN to osteoclast cell membrane receptor integrin αv can activate the osteoclasts and increase their osteolytic activity. In addition, binding of OPN to OKC lining epithelial cell membrane receptor CD44v6 can enhance the motility, migration, invasion and spread of lining epithelial cells into the surrounding cancellous bone. Therefore, we suggest that the local aggressive behavior and high osteolytic ability of OKCs in the jawbone can be explained at least partially by high expression of OPN and CD44v6 in lining epithelial cells of OKCs and high expression of integrin αv in osteoclasts.

  20. Non-Small Cell Lung Cancer Cells Expressing CD44 Are Enriched for Stem Cell-Like Properties

    Leung, Elaine Lai-Han; Fiscus, Ronald R.; Tung, James W.; Tin, Vicky Pui-Chi; Cheng, Lik Cheung; Sihoe, Alan Dart-Loon; Fink, Louis M.; Ma, Yupo; Wong, Maria Pik

    2010-01-01

    Background The cancer stem cell theory hypothesizes that cancers are perpetuated by cancer stem cells (CSC) or tumor initiating cells (TIC) possessing self-renewal and other stem cell-like properties while differentiated non-stem/initiating cells have a finite life span. To investigate whether the hypothesis is applicable to lung cancer, identification of lung CSC and demonstration of these capacities is essential. Methodology/Principal Finding The expression profiles of five stem cell markers (CD34, CD44, CD133, BMI1 and OCT4) were screened by flow cytometry in 10 lung cancer cell lines. CD44 was further investigated by testing for in vitro and in vivo tumorigenecity. Formation of spheroid bodies and in vivo tumor initiation ability were demonstrated in CD44+ cells of 4 cell lines. Serial in vivo tumor transplantability in nude mice was demonstrated using H1299 cell line. The primary xenografts initiated from CD44+ cells consisted of mixed CD44+ and CD44− cells in similar ratio as the parental H1299 cell line, supporting in vivo differentiation. Semi-quantitative Real-Time PCR (RT-PCR) showed that both freshly sorted CD44+ and CD44+ cells derived from CD44+-initiated tumors expressed the pluripotency genes OCT4/POU5F1, NANOG, SOX2. These stemness markers were not expressed by CD44− cells. Furthermore, freshly sorted CD44+ cells were more resistant to cisplatin treatment with lower apoptosis levels than CD44− cells. Immunohistochemical analysis of 141 resected non-small cell lung cancers showed tumor cell expression of CD44 in 50.4% of tumors while no CD34, and CD133 expression was observed in tumor cells. CD44 expression was associated with squamous cell carcinoma but unexpectedly, a longer survival was observed in CD44-expressing adenocarcinomas. Conclusion/Significance Overall, our results demonstrated that stem cell-like properties are enriched in CD44-expressing subpopulations of some lung cancer cell lines. Further investigation is required to clarify

  1. Inversed relationship between CD44 variant and c-Myc due to oxidative stress-induced canonical Wnt activation

    Yoshida, Go J.; Saya, Hideyuki

    2014-01-01

    Highlights: •CD44 variant8–10 and c-Myc are inversely expressed in gastric cancer cells. •Redox-stress enhances c-Myc expression via canonical Wnt signal. •CD44v, but not CD44 standard, suppresses redox stress-induced Wnt activation. •CD44v expression promotes both transcription and proteasome degradation of c-Myc. •Inversed expression pattern between CD44v and c-Myc is often recognized in vivo. -- Abstract: Cancer stem-like cells express high amount of CD44 variant8-10 which protects cancer cells from redox stress. We have demonstrated by immunohistochemical analysis and Western blotting, and reverse-transcription polymerase chain reaction, that CD44 variant8-10 and c-Myc tend to show the inversed expression manner in gastric cancer cells. That is attributable to the oxidative stress-induced canonical Wnt activation, and furthermore, the up-regulation of the downstream molecules, one of which is oncogenic c-Myc, is not easily to occur in CD44 variant-positive cancer cells. We have also found out that CD44v8-10 expression is associated with the turn-over of the c-Myc with the experiments using gastric cancer cell lines. This cannot be simply explained by the model of oxidative stress-induced Wnt activation. CD44v8-10-positive cancer cells are enriched at the invasive front. Tumor tissue at the invasive area is considered to be composed of heterogeneous cellular population; dormant cancer stem-like cells with CD44v8-10 high / Fbw7 high / c-Myc low and proliferative cancer stem-like cells with CD44v8-10 high / Fbw7 low / c-Myc high

  2. Inversed relationship between CD44 variant and c-Myc due to oxidative stress-induced canonical Wnt activation

    Yoshida, Go J., E-mail: medical21go@yahoo.co.jp; Saya, Hideyuki

    2014-01-10

    Highlights: •CD44 variant8–10 and c-Myc are inversely expressed in gastric cancer cells. •Redox-stress enhances c-Myc expression via canonical Wnt signal. •CD44v, but not CD44 standard, suppresses redox stress-induced Wnt activation. •CD44v expression promotes both transcription and proteasome degradation of c-Myc. •Inversed expression pattern between CD44v and c-Myc is often recognized in vivo. -- Abstract: Cancer stem-like cells express high amount of CD44 variant8-10 which protects cancer cells from redox stress. We have demonstrated by immunohistochemical analysis and Western blotting, and reverse-transcription polymerase chain reaction, that CD44 variant8-10 and c-Myc tend to show the inversed expression manner in gastric cancer cells. That is attributable to the oxidative stress-induced canonical Wnt activation, and furthermore, the up-regulation of the downstream molecules, one of which is oncogenic c-Myc, is not easily to occur in CD44 variant-positive cancer cells. We have also found out that CD44v8-10 expression is associated with the turn-over of the c-Myc with the experiments using gastric cancer cell lines. This cannot be simply explained by the model of oxidative stress-induced Wnt activation. CD44v8-10-positive cancer cells are enriched at the invasive front. Tumor tissue at the invasive area is considered to be composed of heterogeneous cellular population; dormant cancer stem-like cells with CD44v8-10 {sup high}/ Fbw7 {sup high}/ c-Myc {sup low} and proliferative cancer stem-like cells with CD44v8-10 {sup high}/ Fbw7 {sup low}/ c-Myc {sup high}.

  3. Molecular mechanism for the action of the anti-CD44 monoclonal antibody MEM-85

    Škerlová, Jana; Král, Vlastimil; Kachala, M.; Fábry, Milan; Bumba, Ladislav; Svergun, D.I.; Tosner, Z.; Veverka, V.; Řezáčová, Pavlína

    2015-01-01

    Roč. 191, č. 2 (2015), s. 214-223 ISSN 1047-8477 R&D Projects: GA ČR(CZ) GA15-11851S EU Projects: European Commission 264257 Institutional support: RVO:68378050 ; RVO:61388971 Keywords : CD44 * Epitope mapping * Monoclonal antibody * MEM-85 * SAXS * NMR Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.570, year: 2015

  4. Molecular mechanism for the action of the anti-CD44 monoclonal antibody MEM-85

    Škerlová, Jana; Král, V.; Kachala, M.; Fábry, M.; Bumba, L.; Svergun, D. I.; Tošner, Z.; Veverka, Václav; Řezáčová, Pavlína

    2015-01-01

    Roč. 191, č. 2 (2015), s. 214-223 ISSN 1047-8477 R&D Projects: GA MŠk(CZ) LK11205; GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 Keywords : CD44 * epitope mapping * monoclonal antibody * MEM-85 * NMR * SAXS Subject RIV: CE - Biochemistry Impact factor: 2.570, year: 2015

  5. A bioengineered murine model using CD24+CD44+ pancreatic cancer stem cells for chemotherapy study

    Qin, Shengqi; Li, Jianshe; Zhang, Zhongtao; Deng, Yiming

    2015-01-01

    In this work we first developed a murine pancreatic tumor model using CD24 + CD44 + pancreatic cancer stem cells (CSC) supported by an electrospun scaffold. Unlike conventional models, the use of CSC and the scaffold, which were biologically and chemically defined, afforded scientists a reliable platform to evaluate novel chemotherapy regimens. CD24 + CD44 + CSC successfully initiated tumorigenesis in vitro on the scaffold without suffering apoptosis, evidencing the lack of cytotoxicity of scaffolding materials. Also, the scaffold contributed to the acceleration of in vivo tumorigenesis and increased the likelihood of tumor formation. Using this model, we set out to explore the effectiveness of irinotecan/gemcitabine (IRIN-GEM), a chemotherapy regimen, for pancreatic cancer. Our study showed that IRIN-GEM induced a tumor regression whereas gemcitabine alone could only arrest the tumor growth. Further study suggested that the superior performance of IRIN-GEM could be attributed to its capacity to demolish the CD24 + CD44 + CSC sub-population by inducing a large-scale apoptosis. The use of highly proliferative yet homogenous CD24 + CD44 + CSC along with a chemically defined scaffold accelerated the tumor formation and significantly reduced the variability associated with conventional murine models. Armed with this new model, we discovered that IRIN-GEM would be a promising chemotherapy candidate for patients with advanced pancreatic cancer. (paper)

  6. Urothelial CD44 facilitates Escherichia coli infection of the murine urinary tract

    Rouschop, Kasper M. A.; Sylva, Marc; Teske, Gwendoline J. D.; Hoedemaeker, Inge; Pals, Steven T.; Weening, Jan J.; van der Poll, Tom; Florquin, Sandrine

    2006-01-01

    Escherichia coli is the most common pathogen found in urinary tract infections (UTIs), mainly affecting children and women. We report that CD44, a hyaluronic acid (HA) binding protein that mediates cell-cell and cell-matrix interactions, facilitates the interaction of E. coli with urothelial cells

  7. Rb suppresses collective invasion, circulation and metastasis of breast cancer cells in CD44-dependent manner.

    Kui-Jin Kim

    Full Text Available Basal-like breast carcinomas (BLCs present with extratumoral lymphovascular invasion, are highly metastatic, presumably through a hematogenous route, have augmented expression of CD44 oncoprotein and relatively low levels of retinoblastoma (Rb tumor suppressor. However, the causal relation among these features is not clear. Here, we show that Rb acts as a key suppressor of multiple stages of metastatic progression. Firstly, Rb suppresses collective cell migration (CCM and CD44-dependent formation of F-actin positive protrusions in vitro and cell-cluster based lymphovascular invasion in vivo. Secondly, Rb inhibits the release of single cancer cells and cell clusters into the hematogenous circulation and subsequent metastatic growth in lungs. Finally, CD44 expression is required for collective motility and all subsequent stages of metastatic progression initiated by loss of Rb function. Altogether, our results suggest that Rb/CD44 pathway is a crucial regulator of CCM and metastatic progression of BLCs and a promising target for anti-BLCs therapy.

  8. Aggravation of Allergic Airway Inflammation by Cigarette Smoke in Mice Is CD44-Dependent.

    Smitha Kumar

    Full Text Available Although epidemiological studies reveal that cigarette smoke (CS facilitates the development and exacerbation of allergic asthma, these studies offer limited information on the mechanisms involved. The transmembrane glycoprotein CD44 is involved in cell adhesion and acts as a receptor for hyaluronic acid and osteopontin. We aimed to investigate the role of CD44 in a murine model of CS-facilitated allergic airway inflammation.Wild type (WT and CD44 knock-out (KO mice were exposed simultaneously to house dust mite (HDM extract and CS. Inflammatory cells, hyaluronic acid (HA and osteopontin (OPN levels were measured in bronchoalveolar lavage fluid (BALF. Proinflammatory mediators, goblet cell metaplasia and peribronchial eosinophilia were assessed in lung tissue. T-helper (Th 1, Th2 and Th17 cytokine production was evaluated in mediastinal lymph node cultures.In WT mice, combined HDM/CS exposure increased the number of inflammatory cells and the levels of HA and OPN in BALF and Th2 cytokine production in mediastinal lymph nodes compared to control groups exposed to phosphate buffered saline (PBS/CS, HDM/Air or PBS/Air. Furthermore, HDM/CS exposure significantly increased goblet cell metaplasia, peribronchial eosinophilia and inflammatory mediators in the lung. CD44 KO mice exposed to HDM/CS had significantly fewer inflammatory cells in BALF, an attenuated Th2 cytokine production, as well as decreased goblet cells and peribronchial eosinophils compared to WT mice. In contrast, the levels of inflammatory mediators were similar or higher than in WT mice.We demonstrate for the first time that the aggravation of pulmonary inflammation upon combined exposure to allergen and an environmental pollutant is CD44-dependent. Data from this murine model of concomitant exposure to CS and HDM might be of importance for smoking allergic asthmatics.

  9. Occupational skin diseases and prevention among sanitation ...

    Background: Little research has been focused on the health status or the occupational protection awareness of sanitation workers. The policy recommendations on the occupational safety and health of sanitation workers based on the scientific research are also insufficient in developing countries like China. Objective: To ...

  10. Preventing occupational stress in healthcare workers

    Jani H. Ruotsalainen

    Full Text Available ABSTRACT: BACKGROUND: Healthcare workers can suffer from occupational stress which may lead to serious mental and physical health problems. OBJECTIVES: To evaluate the effectiveness of work and person-directed interventions in preventing stress at work in healthcare workers. METHODS: Search methods: We searched the Cochrane Depression Anxiety and Neurosis Group trials Specialised Register, MEDLINE, PsychInfo and Cochrane Occupational Health Field database. Selection criteria: Randomised controlled clinical trials (RCT of interventions aimed at preventing psychological stress in healthcare workers. For work-directed interventions interrupted time series and prospective cohort were also eligible. Data collection and analysis: Two authors independently extracted data and assessed trial quality. Meta-analysis and qualitative synthesis were performed where appropriate. MAIN RESULTS: We identified 14 RCTs, three cluster-randomised trials and two crossover trials, including a total of 1,564 participants in intervention groups and 1,248 controls. Two trials were of high quality. Interventions were grouped into 1 person-directed: cognitive-behavioural, relaxation, music-making, therapeutic massage and multicomponent; and 2 work-directed: attitude change and communication, support from colleagues and participatory problem solving and decision-making, and changes in work organisation. There is limited evidence that person-directed interventions can reduce stress (standardised mean difference or SMD -0.85; 95% CI -1.21, -0.49; burnout: Emotional Exhaustion (weighted mean difference or WMD -5.82; 95% CI -11.02, -0.63 and lack of Personal Accomplishment (WMD -3.61; 95% CI -4.65, -2.58; and anxiety: state anxiety (WMD -9.42; 95% CI -16.92, -1.93 and trait anxiety (WMD -6.91; 95% CI -12.80, -1.01. One trial showed that stress remained low a month after intervention (WMD -6.10; 95% CI -8.44, -3.76. Another trial showed a reduction in Emotional Exhaustion (Mean

  11. Significance of CD44 expression in head and neck cancer: a systemic review and meta-analysis

    Chen, Jianqiang; Zhou, Jianding; Lu, Jie; Xiong, Hua; Shi, Xueli; Gong, Liang

    2014-01-01

    CD44 has been reported to be involved with tumor growth and metastasis and has also been implicated as a CSC marker in head and neck squamous cell cancer (HNSCC). However, the prognostic value of CD44 still remains controversial; hence, we investigated the correlation between CD44 and the clinicopathological features of HNSCC by meta-analysis. A comprehensive search was performed using PubMed, ISI web of Science and China National Knowledge Infrastructure (CNKI) up to April 2013. Only studies with immunohistochemical staining of HNSCC were considered. Data on TNM classification, tumor grade, disease free survival and 3- or 5-year overall survival rate were extracted. Thirty studies with 2102 patients met the inclusion criteria for the meta-analysis. Fifteen studies used anti-pan-CD44 antibody, 9 used anti-CD44-v6 antibody, 2 used anti-CD44-v3 and 2 used anti-CD44s antibody, 1 used anti-CD44-v9, and 1 used anti-CD44-v6,-v3 and -v4-5 simultaneously. The total percentage of CD44 expression was 57.8%, with 49.3% in oral cancer patients, 66.4% in pharynx and 54.7% in larynx cancer patients expressing CD44. No significant correlation between clinical features and CD44 expression was revealed for oral cancer patients, but CD44 was shown to be associated with advanced T categories (larynx: RR = 1.33, 95% CI 1.01-1.76; larynx & pharynx RR = 1.21, 95% CI 1.08-1.35), worse N categories (larynx: RR = 2.53, 95% CI 1.99-3.21; larynx & pharynx RR = 1.95, 95% CI 1.35-2.82), higher tumor grades (larynx & pharynx RR = 1.71, 95% CI 1.04-2.79) and 5-year OS rates (larynx: RR = 0.62, 95% CI 0.47-0.83; larynx & pharynx RR = 0.66, 95% CI 0.47-0.94) in patients with laryngeal and pharyngolaryngeal cancer. In stratified analysis, pan-CD44 and CD44-v6 expression were both correlated with 5-year OS rate of patients with laryngeal (CD44: RR = 0.66, 95% CI 0.46-0.95; CD44-v6 RR = 0.53, 95% CI 0.37-0.77) and pharyngolaryngeal cancer (CD44: RR = 0.56, 95% CI 0.34-0.93; CD44-v6 RR = 0.53, 95% CI

  12. Alcohol and drug screening of occupational drivers for preventing injury

    Cashman, Clodagh M.; Ruotsalainen, Jani H.; Greiner, Birgit A.; Beirne, Paul V.; Verbeek, Jos H.

    2009-01-01

    BACKGROUND: Workforce alcohol and drug testing is commonplace but its effect in reducing occupational injuries remains unclear. OBJECTIVES: To assess the effects of alcohol and drug screening of occupational drivers (operating a motorised vehicle) in preventing injury or work-related effects such as

  13. 76 FR 62093 - Preventing Occupational Hearing Loss: Stakeholder Meeting

    2011-10-06

    ... Loss: Stakeholder Meeting AGENCY: Occupational Safety and Health Administration (OSHA), Labor. ACTION... stakeholder meeting on preventing occupational hearing loss. Every year, between 20,000 and 25,000 workers... controls. OSHA is holding this stakeholder meeting as part of its commitment to work with stakeholders on...

  14. Aberrant Splicing of Estrogen Receptor, HER2, and CD44 Genes in Breast Cancer

    Kazushi Inoue

    2015-01-01

    Full Text Available Breast cancer (BC is the most common cause of cancer-related death among women under the age of 50 years. Established biomarkers, such as hormone receptors (estrogen receptor [ER]/progesterone receptor and human epidermal growth factor receptor 2 (HER2, play significant roles in the selection of patients for endocrine and trastuzumab therapies. However, the initial treatment response is often followed by tumor relapse with intrinsic resistance to the first-line therapy, so it has been expected to identify novel molecular markers to improve the survival and quality of life of patients. Alternative splicing of pre-messenger RNAs is a ubiquitous and flexible mechanism for the control of gene expression in mammalian cells. It provides cells with the opportunity to create protein isoforms with different, even opposing, functions from a single genomic locus. Aberrant alternative splicing is very common in cancer where emerging tumor cells take advantage of this flexibility to produce proteins that promote cell growth and survival. While a number of splicing alterations have been reported in human cancers, we focus on aberrant splicing of ER , HER2 , and CD44 genes from the viewpoint of BC development. ERα36 , a splice variant from the ER1 locus, governs nongenomic membrane signaling pathways triggered by estrogen and confers 4-hydroxytamoxifen resistance in BC therapy. The alternative spliced isoform of HER2 lacking exon 20 (Δ16HER2 has been reported in human BC; this isoform is associated with transforming ability than the wild-type HER2 and recapitulates the phenotypes of endocrine therapy-resistant BC. Although both CD44 splice isoforms ( CD44s , CD44v play essential roles in BC development, CD44v is more associated with those with favorable prognosis, such as luminal A subtype, while CD44s is linked to those with poor prognosis, such as HER2 or basal cell subtypes that are often metastatic. Hence, the detection of splice variants from these loci

  15. Tumor-Endothelial Interaction Links the CD44+/CD24- Phenotype with Poor Prognosis in Early-Stage Breast Cancer

    Martin Buess

    2009-10-01

    Conclusions Our results suggest that the interaction of endothelial cells with tumor cells that express the CD44+/CD24- signature, which indicates a low proliferative potential, might explain the unexpected and paradoxical association of the CD44+/CD24- signature with highly proliferative tumors that have an unfavorable prognosis.

  16. CD44 Binding to Hyaluronic Acid Is Redox Regulated by a Labile Disulfide Bond in the Hyaluronic Acid Binding Site.

    Helena Kellett-Clarke

    Full Text Available CD44 is the primary leukocyte cell surface receptor for hyaluronic acid (HA, a component of the extracellular matrix. Enzymatic post translational cleavage of labile disulfide bonds is a mechanism by which proteins are structurally regulated by imparting an allosteric change and altering activity. We have identified one such disulfide bond in CD44 formed by Cys77 and Cys97 that stabilises the HA binding groove. This bond is labile on the surface of leukocytes treated with chemical and enzymatic reducing agents. Analysis of CD44 crystal structures reveal the disulfide bond to be solvent accessible and in the-LH hook configuration characteristic of labile disulfide bonds. Kinetic trapping and binding experiments on CD44-Fc chimeric proteins show the bond is preferentially reduced over the other disulfide bonds in CD44 and reduction inhibits the CD44-HA interaction. Furthermore cells transfected with CD44 no longer adhere to HA coated surfaces after pre-treatment with reducing agents. The implications of CD44 redox regulation are discussed in the context of immune function, disease and therapeutic strategies.

  17. The depletion of ATM inhibits colon cancer proliferation and migration via B56γ2-mediated Chk1/p53/CD44 cascades.

    Liu, Rui; Tang, Jiajia; Ding, Chaodong; Liang, Weicheng; Zhang, Li; Chen, Tianke; Xiong, Yan; Dai, Xiaowei; Li, Wenfeng; Xu, Yunsheng; Hu, Jin; Lu, Liting; Liao, Wanqin; Lu, Xincheng

    2017-04-01

    Ataxia-telangiectasia mutated (ATM) protein kinase is a major guardian of genomic stability, and its well-established function in cancer is tumor suppression. Here, we report an oncogenic role of ATM. Using two isogenic sets of human colon cancer cell lines that differed only in their ATM status, we demonstrated that ATM deficiency significantly inhibits cancer cell proliferation, migration, and invasion. The tumor-suppressive function of ATM depletion is not modulated by the compensatory activation of ATR, but it is associated with B56γ2-mediated Chk1/p53/CD44 signaling pathways. Under normal growth conditions, the depletion of ATM prevents B56γ2 ubiquitination and degradation, which activates PP2A-mediated Chk1/p53/p21 signaling pathways, leading to senescence and cell cycle arrest. CD44 was validated as a novel ATM target based on its ability to rescue cell migration and invasion defects in ATM-depleted cells. The activation of p53 induced by ATM depletion suppresses CD44 transcription, thus resulting in epithelial-mesenchymal transition (EMT) and cell migration suppression. Our study suggests that ATM has tumorigenic potential in post-formed colon neoplasia, and it supports ATM as an appealing target for improving cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. WNT5A inhibits metastasis and alters splicing of Cd44 in breast cancer cells.

    Wen Jiang

    Full Text Available Wnt5a is a non-canonical signaling Wnt. Low expression of WNT5A is correlated with poor prognosis in breast cancer patients. The highly invasive breast cancer cell lines, MDA-MB-231 and 4T1, express very low levels of WNT5A. To determine if enhanced expression of WNT5A would affect metastatic behavior, we generated WNT5A expressing cells from the 4T1 and MDA-MB-231 parental cell lines. WNT5A expressing cells demonstrated cobblestone morphology and reduced in vitro migration relative to controls. Cell growth was not altered. Metastasis to the lung via tail vein injection was reduced in the 4T1-WNT5A expressing cells relative to 4T1-vector controls. To determine the mechanism of WNT5A action on metastasis, we performed microarray and whole-transcriptome sequence analysis (RNA-seq to compare gene expression in 4T1-WNT5A and 4T1-vector cells. Analysis indicated highly significant alterations in expression of genes associated with cellular movement. Down-regulation of a subset of these genes, Mmp13, Nos2, Il1a, Cxcl2, and Lamb3, in WNT5A expressing cells was verified by semi-quantitative RT-PCR. Significant differences in transcript splicing were also detected in cell movement associated genes including Cd44. Cd44 is an adhesion molecule with a complex genome structure. Variable exon usage is associated with metastatic phenotype. Alternative spicing of Cd44 in WNT5A expressing cells was confirmed using RT-PCR. We conclude that WNT5A inhibits metastasis through down-regulation of multiple cell movement pathways by regulating transcript levels and splicing of key genes like Cd44.

  19. CD44+ cancer stem-like cells in EBV-associated nasopharyngeal carcinoma.

    Samantha Wei-Man Lun

    Full Text Available Nasopharyngeal carcinoma (NPC is a unique EBV-associated epithelial malignancy, showing highly invasive and metastatic phenotype. Despite increasing evidence demonstrating the critical role of cancer stem-like cells (CSCs in the maintenance and progression of tumors in a variety of malignancies, the existence and properties of CSC in EBV-associated NPC are largely unknown. Our study aims to elucidate the presence and role of CSCs in the pathogenesis of this malignant disease. Sphere-forming cells were isolated from an EBV-positive NPC cell line C666-1 and its tumor-initiating properties were confirmed by in vitro and in vivo assays. In these spheroids, up-regulation of multiple stem cell markers were found. By flow cytometry, we demonstrated that both CD44 and SOX2 were overexpressed in a majority of sphere-forming C666-1 cells. The CD44+SOX2+ cells was detected in a minor population in EBV-positive xenografts and primary tumors and considered as potential CSC in NPC. Notably, the isolated CD44+ NPC cells were resistant to chemotherapeutic agents and with higher spheroid formation efficiency, showing CSC properties. On the other hand, microarray analysis has revealed a number of differentially expressed genes involved in transcription regulation (e.g. FOXN4, GLI1, immune response (CCR7, IL8 and transmembrane transport (e.g. ABCC3, ABCC11 in the spheroids. Among these genes, increased expression of CCR7 in CD44+ CSCs was confirmed in NPC xenografts and primary tumors. Importantly, blocking of CCR7 abolished the sphere-forming ability of C666-1 in vitro. Expression of CCR7 was associated with recurrent disease and distant metastasis. The current study defined the specific properties of a CSC subpopulation in EBV-associated NPC. Our findings provided new insights into developing effective therapies targeting on CSCs, thereby potentiating treatment efficacy for NPC patients.

  20. CD44+ Cancer Stem-Like Cells in EBV-Associated Nasopharyngeal Carcinoma

    Lun, Samantha Wei-Man; Cheung, Siu Tim; Cheung, Phyllis Fung Yi; To, Ka-Fai; Woo, John Kong-Sang; Choy, Kwong-Wai; Chow, Chit; Cheung, Chartia Ching-Mei; Chung, Grace Tin-Yun; Cheng, Alice Suk-Hang; Ko, Chun-Wai; Tsao, Sai-Wah; Busson, Pierre; Ng, Margaret Heung-Ling; Lo, Kwok-Wai

    2012-01-01

    Nasopharyngeal carcinoma (NPC) is a unique EBV-associated epithelial malignancy, showing highly invasive and metastatic phenotype. Despite increasing evidence demonstrating the critical role of cancer stem-like cells (CSCs) in the maintenance and progression of tumors in a variety of malignancies, the existence and properties of CSC in EBV-associated NPC are largely unknown. Our study aims to elucidate the presence and role of CSCs in the pathogenesis of this malignant disease. Sphere-forming cells were isolated from an EBV-positive NPC cell line C666-1 and its tumor-initiating properties were confirmed by in vitro and in vivo assays. In these spheroids, up-regulation of multiple stem cell markers were found. By flow cytometry, we demonstrated that both CD44 and SOX2 were overexpressed in a majority of sphere-forming C666-1 cells. The CD44+SOX2+ cells was detected in a minor population in EBV-positive xenografts and primary tumors and considered as potential CSC in NPC. Notably, the isolated CD44+ NPC cells were resistant to chemotherapeutic agents and with higher spheroid formation efficiency, showing CSC properties. On the other hand, microarray analysis has revealed a number of differentially expressed genes involved in transcription regulation (e.g. FOXN4, GLI1), immune response (CCR7, IL8) and transmembrane transport (e.g. ABCC3, ABCC11) in the spheroids. Among these genes, increased expression of CCR7 in CD44+ CSCs was confirmed in NPC xenografts and primary tumors. Importantly, blocking of CCR7 abolished the sphere-forming ability of C666-1 in vitro. Expression of CCR7 was associated with recurrent disease and distant metastasis. The current study defined the specific properties of a CSC subpopulation in EBV-associated NPC. Our findings provided new insights into developing effective therapies targeting on CSCs, thereby potentiating treatment efficacy for NPC patients. PMID:23285037

  1. Novel Dual Mitochondrial and CD44 Receptor Targeting Nanoparticles for Redox Stimuli-Triggered Release

    Wang, Kaili; Qi, Mengjiao; Guo, Chunjing; Yu, Yueming; Wang, Bingjie; Fang, Lei; Liu, Mengna; Wang, Zhen; Fan, Xinxin; Chen, Daquan

    2018-02-01

    In this work, novel mitochondrial and CD44 receptor dual-targeting redox-sensitive multifunctional nanoparticles (micelles) based on oligomeric hyaluronic acid (oHA) were proposed. The amphiphilic nanocarrier was prepared by (5-carboxypentyl)triphenylphosphonium bromide (TPP), oligomeric hyaluronic acid (oHA), disulfide bond, and curcumin (Cur), named as TPP-oHA-S-S-Cur. The TPP targeted the mitochondria, the antitumor drug Cur served as a hydrophobic core, the CD44 receptor targeting oHA worked as a hydrophilic shell, and the disulfide bond acted as a connecting arm. The chemical structure of TPP-oHA-S-S-Cur was characterized by 1HNMR technology. Cur was loaded into the TPP-oHA-S-S-Cur micelles by self-assembly. Some properties, including the preparation of micelles, morphology, redox sensitivity, and mitochondrial targeting, were studied. The results showed that TPP-oHA-S-S-Cur micelles had a mean diameter of 122.4 ± 23.4 nm, zeta potential - 26.55 ± 4.99 mV. In vitro release study and cellular uptake test showed that TPP-oHA-S-S-Cur micelles had redox sensibility, dual targeting to mitochondrial and CD44 receptor. This work provided a promising smart multifunctional nanocarrier platform to enhance the solubility, decrease the side effects, and improve the therapeutic efficacy of anticancer drugs.

  2. Expression and distribution of hyaluronic acid and CD44 in unphonated human vocal fold mucosa.

    Sato, Kiminori; Umeno, Hirohito; Nakashima, Tadashi; Nonaka, Satoshi; Harabuchi, Yasuaki

    2009-11-01

    The tension caused by phonation (vocal fold vibration) is hypothesized to stimulate vocal fold stellate cells (VFSCs) in the maculae flavae (MFe) to accelerate production of extracellular matrices. The distribution of hyaluronic acid (HA) and expression of CD44 (a cell surface receptor for HA) were examined in human vocal fold mucosae (VFMe) that had remained unphonated since birth. Five specimens of VFMe (3 adults, 2 children) that had remained unphonated since birth were investigated with Alcian blue staining, hyaluronidase digestion, and immunohistochemistry for CD44. The VFMe containing MFe were hypoplastic and rudimentary. The VFMe did not have a vocal ligament, Reinke's space, or a layered structure, and the lamina propria appeared as a uniform structure. In the children, HA was distributed in the VFMe containing MFe. In the adults, HA had decreased in the VFMe containing MFe. In both groups, the VFSCs in the MFe and the fibroblasts in the lamina propria expressed little CD44. This study supports the hypothesis that the tensions caused by vocal fold vibration stimulate the VFSCs in the MFe to accelerate production of extracellular matrices and form the layered structure. Phonation after birth is one of the important factors in the growth and development of the human VFMe.

  3. Preventing occupational stress in healthcare workers.

    Ruotsalainen, Jani H; Verbeek, Jos H; Mariné, Albert; Serra, Consol

    2015-04-07

    Healthcare workers can suffer from occupational stress as a result of lack of skills, organisational factors, and low social support at work. This may lead to distress, burnout and psychosomatic problems, and deterioration in quality of life and service provision. To evaluate the effectiveness of work- and person-directed interventions compared to no intervention or alternative interventions in preventing stress at work in healthcare workers. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, NIOSHTIC-2 and Web of Science up to November 2013. Randomised controlled trials (RCTs) of interventions aimed at preventing psychological stress in healthcare workers. For organisational interventions, interrupted time-series and controlled before-and-after (CBA) studies were also eligible. Two review authors independently extracted data and assessed trial quality. We used Standardised Mean Differences (SMDs) where authors of trials used different scales to measure stress or burnout. We combined studies that were similar in meta-analyses. We used the GRADE system to rate the quality of the evidence. In this update, we added 39 studies, making a total of 58 studies (54 RCTs and four CBA studies), with 7188 participants. We categorised interventions as cognitive-behavioural training (CBT) (n = 14), mental and physical relaxation (n = 21), combined CBT and relaxation (n = 6) and organisational interventions (n = 20). Follow-up was less than one month in 24 studies, one to six in 22 studies and more than six months in 12 studies. We categorised outcomes as stress, anxiety or general health.There was low-quality evidence that CBT with or without relaxation was no more effective in reducing stress symptoms than no intervention at one month follow-up in six studies (SMD -0.27 (95% Confidence Interval (CI) -0.66 to 0.13; 332 participants). But at one to six months follow-up in seven studies (SMD -0.38, 95% CI -0.59 to -0

  4. How to permanently build up the prevention of occupational cancers

    Hery, Michel; Goutet, Pierre; Calvez, Olivier; Fontaine, Bernard; Bastos, Henri; Guseva-Canu, Irina; Telle-Lamberton, Maylis; Pourquet, Michel; Fontaine, Jean-Raymond; Silvente, Eric; Malenfer, Marc; Risse-Fleury, Mathilde; Lepocreau, Antoine; Guimon, Michele; Laine, Patrick; Fares, Nadim; Hermouet, Christine; Chauvet, Claire; Haeflinger, Raphael; Vogel, Laurent; Counil, Emilie; Bertin, Melanie; Thebaud-Mony, Annie; Certin, Jean-Francois; Goutet, Pierre; Brixi, Omar

    2015-01-01

    As about 2 millions of workers are exposed to carcinogenic agents in different industrial sectors, this expert opinion proposes a presentation of the state of the art of the prevention of carcinogenic risks. The different parts address the contribution of experimental and epidemiologic studies to the knowledge and prevention of occupational cancers (sure and possible factors, classifications and regulations), the knowledge of exposures in working environments (exposure modalities and principle of assessment of exposures, traceability and retrospective assessment), the risk management within a company (identification, suppression and substitution, design of work equipment, prevention of exposure for the personnel of subcontracting companies and in the waste and recycling sectors), the evolution from risk perception to risk prevention, the various strategies for action and professional sectors (general regime, prevention policy of the French national fund of prevention for territorial and hospital public services, the taking into charge of cancers as occupational disease by agriculture regimes of social protection), and the taking into care and restorative actions (medical and legal follow up and remedy, taking inequities into account, acknowledgement of occupational cancers in Europe, critical discussion of the European policy on occupational cancer prevention, lessons learned from Giscop93 inquiry)

  5. Work Disability Prevention: A Primer for Occupational Therapists.

    McDougall, Alicia; Nowrouzi-Kia, Behdin

    An estimated 313 million workplace accidents resulting in injury occur worldwide every year. Therefore, the burden of workplace injury and disability is present at the individual and the societal level and involves several stakeholders. There has been a shift in paradigm from workplace disability and injury treatment to workplace disability prevention. Occupational therapy practitioners are well positioned to address this multifaceted societal issue. Opening communication lines among stakeholders allows for a more holistic, collaborative, and comprehensive approach to disability, injury, and pain management. The positive results researchers have found at the individual level when using a holistic approach translate to benefits for all of the stakeholders involved. Occupational therapy practitioners may espouse a work disability prevention approach to reduce work disability rates and provide timely return-to-work outcomes for clients. The transition to the preventative model requires collaboration among stakeholders but would be beneficial to all stakeholders involved in the workplace. Copyright © 2017 by the American Occupational Therapy Association, Inc.

  6. CD44 staining of cancer stem-like cells is influenced by down-regulation of CD44 variant isoforms and up-regulation of the standard CD44 isoform in the population of cells that have undergone epithelial-to-mesenchymal transition.

    Adrian Biddle

    Full Text Available CD44 is commonly used as a cell surface marker of cancer stem-like cells in epithelial tumours, and we have previously demonstrated the existence of two different CD44(high cancer stem-like cell populations in squamous cell carcinoma, one having undergone epithelial-to-mesenchymal transition and the other maintaining an epithelial phenotype. Alternative splicing of CD44 variant exons generates a great many isoforms, and it is not known which isoforms are expressed on the surface of the two different cancer stem-like cell phenotypes. Here, we demonstrate that cancer stem-like cells with an epithelial phenotype predominantly express isoforms containing the variant exons, whereas the cancer stem-like cells that have undergone an epithelial-to-mesenchymal transition down-regulate these variant isoforms and up-regulate expression of the standard CD44 isoform that contains no variant exons. In addition, we find that enzymatic treatments used to dissociate cells from tissue culture or fresh tumour specimens cause destruction of variant CD44 isoforms at the cell surface whereas expression of the standard CD44 isoform is preserved. This results in enrichment within the CD44(high population of cancer stem-like cells that have undergone an epithelial-to-mesenchymal transition and depletion from the CD44(high population of cancer stem-like cells that maintain an epithelial phenotype, and therefore greatly effects the characteristics of any cancer stem-like cell population isolated based on expression of CD44. As well as effecting the CD44(high population, enzymatic treatment also reduces the percentage of the total epithelial cancer cell population staining CD44-positive, with potential implications for studies that aim to use CD44-positive staining as a prognostic indicator. Analyses of the properties of cancer stem-like cells are largely dependent on the ability to accurately identify and assay these populations. It is therefore critical that

  7. Galunisertib suppresses the staminal phenotype in hepatocellular carcinoma by modulating CD44 expression.

    Rani, Bhavna; Malfettone, Andrea; Dituri, Francesco; Soukupova, Jitka; Lupo, Luigi; Mancarella, Serena; Fabregat, Isabel; Giannelli, Gianluigi

    2018-03-07

    Cancer stem cells (CSCs) niche in the tumor microenvironment is responsible for cancer recurrence and therapy failure. To better understand its molecular and biological involvement in hepatocellular carcinoma (HCC) progression, one can design more effective therapies and tailored then to individual patients. While sorafenib is currently the only approved drug for first-line treatment of advanced stage HCC, its role in modulating the CSC niche is estimated to be small. By contrast, transforming growth factor (TGF)-β pathway seems to influence the CSC and thus may impact hallmarks of HCC, such as liver fibrosis, cirrhosis, and tumor progression. Therefore, blocking this pathway may offer an appealing and druggable target. In our study, we have used galunisertib (LY2157299), a selective ATP-mimetic inhibitor of TGF-β receptor I (TGFβI/ALK5) activation, currently under clinical investigation in HCC patients. Because the drug resistance is mainly mediated by CSCs, we tested the effects of galunisertib on stemness phenotype in HCC cells to determine whether TGF-β signaling modulates CSC niche and drug resistance. Galunisertib modulated the expression of stemness-related genes only in the invasive (HLE and HLF) HCC cells inducing a decreased expression of CD44 and THY1. Furthermore, galunisertib also reduced the stemness-related functions of invasive HCC cells decreasing the formation of colonies, liver spheroids and invasive growth ability. Interestingly, CD44 loss of function mimicked the galunisertib effects on HCC stemness-related functions. Galunisertib treatment also reduced the expression of stemness-related genes in ex vivo human HCC specimens. Our observations are the first evidence that galunisertib effectiveness overcomes stemness-derived aggressiveness via decreased expression CD44 and THY1.

  8. Gaps in Workplace Education For Prevention of Occupational Skin Disease.

    Gupta, Tanya; Arrandale, Victoria H; Kudla, Irena; Holness, D Linn

    2018-02-13

    Occupational contact dermatitis (OCD) is a common occupational disease. Evidence suggests that education and training are effective prevention strategies. In spite of these known prevention strategies, workers continue to develop OCD. Little is reported regarding the actual training experience of workers. To examine the training experience of workers with contact dermatitis to identify areas for improvement. Participants were workers being assessed for contact dermatitis in an occupational health clinic. The anonymous survey collected demographics, workplace characteristics, and education and prevention practices. Approximately 80% reported general occupational health and safety training; however, only 49% reported skin-specific training (SST). For workers reporting SST, most received information regarding exposure avoidance, hand washing, and glove use. This content was reported as helpful by at least 50%. Workers who did not receive SST indicated the most important content would be warning signs of skin problems, how to avoid exposure and skin care while using gloves. While the study was anonymous and used self-reported of training experience, the study suggests there are gaps in skin protection training. Addressing these gaps may lead to improved prevention and reduction in OCD. © The Author(s) 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  9. Lipid-Based Nanovectors for Targeting of CD44-Overexpressing Tumor Cells

    Silvia Arpicco

    2013-01-01

    Full Text Available Hyaluronic acid (HA is a naturally occurring glycosaminoglycan that exists in living systems, and it is a major component of the extracellular matrix. The hyaluronic acid receptor CD44 is found at low levels on the surface of epithelial, haematopoietic, and neuronal cells and is overexpressed in many cancer cells particularly in tumour initiating cells. HA has been therefore used as ligand attached to HA-lipid-based nanovectors for the active targeting of small or large active molecules for the treatment of cancer. This paper describes the different approaches employed for the preparation, characterization, and evaluation of these potent delivery systems.

  10. Assessing Specific Oligonucleotides and Small Molecule Antibiotics for the Ability to Inhibit the CRD-BP-CD44 RNA Interaction

    Thomsen, Dana; Lee, Chow H.

    2014-01-01

    Studies on Coding Region Determinant-Binding Protein (CRD-BP) and its orthologs have confirmed their functional role in mRNA stability and localization. CRD-BP is present in extremely low levels in normal adult tissues, but it is over-expressed in many types of aggressive human cancers and in neonatal tissues. Although the exact role of CRD-BP in tumour progression is unclear, cumulative evidence suggests that its ability to physically associate with target mRNAs is an important criterion for its oncogenic role. CRD-BP has high affinity for the 3′UTR of the oncogenic CD44 mRNA and depletion of CRD-BP in cells led to destabilization of CD44 mRNA, decreased CD44 expression, reduced adhesion and disruption of invadopodia formation. Here, we further characterize the CRD-BP-CD44 RNA interaction and assess specific antisense oligonucleotides and small molecule antibiotics for their ability to inhibit the CRD-BP-CD44 RNA interaction. CRD-BP has a high affinity for binding to CD44 RNA nts 2862–3055 with a Kd of 645 nM. Out of ten antisense oligonucleotides spanning nts 2862–3055, only three antisense oligonucleotides (DD4, DD7 and DD10) were effective in competing with CRD-BP for binding to 32P-labeled CD44 RNA. The potency of DD4, DD7 and DD10 in inhibiting the CRD-BP-CD44 RNA interaction in vitro correlated with their ability to specifically reduce the steady-state level of CD44 mRNA in cells. The aminoglycoside antibiotics neomycin, paramomycin, kanamycin and streptomycin effectively inhibited the CRD-BP-CD44 RNA interaction in vitro. Assessing the potential inhibitory effect of aminoglycoside antibiotics including neomycin on the CRD-BP-CD44 mRNA interaction in cells proved difficult, likely due to their propensity to non-specifically bind nucleic acids. Our results have important implications for future studies in finding small molecules and nucleic acid-based inhibitors that interfere with protein-RNA interactions. PMID:24622399

  11. CD44+CD24+ subset of PANC-1 cells exhibits radiation resistance via decreased levels of reactive oxygen species.

    Wang, Lei; Li, Pengping; Hu, Wei; Xia, Youyou; Hu, Chenxi; Liu, Liang; Jiang, Xiaodong

    2017-08-01

    Emerging evidence has suggested that pancreatic adenocarcinoma is sustained by pancreatic cancer stem cells. The present study aimed to investigate the expression patterns of the pancreatic cancer stem cell surface markers cluster of differentiation CD44 and CD24 in a pancreatic adenocarcinoma cell line, and to investigate the possible mechanisms for their radiation resistance. Flow cytometry was used to analyze the expression patterns of CD44 and CD24 in the pancreatic adenocarcinoma PANC-1 cell line. In addition, a multi-target click model was used to fit cell survival curves and determine the sensitizer enhancement ratio. The apoptosis and cycle distribution of the four cell subsets was determined using flow cytometry, and the level of reactive oxygen species (ROS) was determined using the 2',7'-dichlorofluorescin diacetate probe. The present results identified that the ratios of CD44 + and CD24 + in the sorted PANC-1 cell line were 92.0 and 4.7%, respectively. Prior to radiation, no statistically significant differences were observed among the four groups. Following treatment with 6 MV of X-rays, the rate of apoptosis was decreased in the CD44 + CD24 + group compared with other subsets. The percentage of G0/G1 cells was highest in the CD44 + CD24 + group compared with the three other groups, which exhibited increased radiosensitivity. In addition, the level of ROS in the CD44 + CD24 + group was reduced compared with the other groups. In summary, the results of the present study indicated that CD44 + CD24 + exhibited stem cell properties. The lower level of ROS and apoptosis in CD44 + CD24 + cells may contribute to their resistance to radiation in pancreatic adenocarcinoma.

  12. Preparation and bioevaluation of {sup 177}Lu-labelled anti-CD44 for radioimmunotherapy of colon cancer

    Lee, So Young; Hong, Young Don; Jung, Sung Hee; Choi, Sun Ju [Radioisotope Research Division, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-12-15

    CD44 is a particular adhesion molecule and facilitates both cell-cell and cell-matrix interactions. In particular, splice variants of CD44 are particularly overexpressed in a large number of malignancies and carcinomas. In this study, the {sup 177}Lu-labelled CD44 targeting antibody was prepared and bioevaluated in vitro and in vivo. Anti-CD44 was immunoconjugated with the equivalent molar ratio of cysteine-based dtPA-ncS and radioimmunoconjugated with {sup 177}Lu at room temperature within 15 minutes. the stability was tested in human serum. An in vitro study was carried out in Ht-29 human colon cancer cell lines. For the biodistribution study {sup 177}Lu-labelled anti-CD44 was injected in xenograft mice. Anti-CD44 was immunoconjugated with cysteinebased dtPA-ncS and purified by a centricon filter system having a molecular cut-off of 50 kda. radioimmunoconjugation with {sup 177}Lu was reacted for 15 min at room temperature. the radiolabeling yield was >99%, and it was stable in human serum without any fragmentation or degradation. The radioimmunoconjugate showed a high binding affinity on HT-29 colon cancer cell surfaces. In a biodistribution study, the tumor-to-blood ratio of the radioimmunoconjugate was 43 : 1 at 1 day post injection (p.i) in human colon cancer bearing mice. the anti-CD44 monoclonal antibody for the targeting of colon cancer was effectively radioimmunoconjugated with {sup 177}Lu. the in vitro high immunoactivity of this radioimmunoconjugate was determined by a cell binding assay. In addition, the antibody's tumor targeting ability was demonstrated with very high uptake in tumors. this radioimmunoconjugate is applicable to therapy in human colon cancer with highly expressed CD44.

  13. An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells

    Ali, Amal J.; AbuElela, Ayman; Merzaban, Jasmeen

    2017-01-01

    -selectin ligands, to CD44, a ligand that has not previously been characterized as an E-selectin ligand on activated human T-cells. We showed that CD44 acts as a functional E-selectin ligand when expressed on both CD4+ and CD8+ T-cells. Moreover, the CD44 protein

  14. Expression of CD44 3′-untranslated region regulates endogenous microRNA functions in tumorigenesis and angiogenesis

    Jeyapalan, Zina; Deng, Zhaoqun; Shatseva, Tatiana; Fang, Ling; He, Chengyan; Yang, Burton B.

    2011-01-01

    The non-coding 3′-untranslated region (UTR) plays an important role in the regulation of microRNA (miRNA) functions, since it can bind and inactivate multiple miRNAs. Here, we show the 3′-UTR of CD44 is able to antagonize cytoplasmic miRNAs, and result in the increased translation of CD44 and downstream target mRNA, CDC42. A series of cell function assays in the human breast cancer cell line, MT-1, have shown that the CD44 3′-UTR inhibits proliferation, colony formation and tumor growth. Furthermore, it modulated endothelial cell activities, favored angiogenesis, induced tumor cell apoptosis and increased sensitivity to Docetaxel. These results are due to the interaction of the CD44 3′-UTR with multiple miRNAs. Computational algorithms have predicted three miRNAs, miR-216a, miR-330 and miR-608, can bind to both the CD44 and CDC42 3′-UTRs. This was confirmed with luciferase assays, western blotting and immunohistochemical staining and correlated with a series of siRNA assays. Thus, the non-coding CD44 3′-UTR serves as a competitor for miRNA binding and subsequently inactivates miRNA functions, by freeing the target mRNAs from being repressed. PMID:21149267

  15. Expression of CD44 3'-untranslated region regulates endogenous microRNA functions in tumorigenesis and angiogenesis.

    Jeyapalan, Zina; Deng, Zhaoqun; Shatseva, Tatiana; Fang, Ling; He, Chengyan; Yang, Burton B

    2011-04-01

    The non-coding 3'-untranslated region (UTR) plays an important role in the regulation of microRNA (miRNA) functions, since it can bind and inactivate multiple miRNAs. Here, we show the 3'-UTR of CD44 is able to antagonize cytoplasmic miRNAs, and result in the increased translation of CD44 and downstream target mRNA, CDC42. A series of cell function assays in the human breast cancer cell line, MT-1, have shown that the CD44 3'-UTR inhibits proliferation, colony formation and tumor growth. Furthermore, it modulated endothelial cell activities, favored angiogenesis, induced tumor cell apoptosis and increased sensitivity to Docetaxel. These results are due to the interaction of the CD44 3'-UTR with multiple miRNAs. Computational algorithms have predicted three miRNAs, miR-216a, miR-330 and miR-608, can bind to both the CD44 and CDC42 3'-UTRs. This was confirmed with luciferase assays, western blotting and immunohistochemical staining and correlated with a series of siRNA assays. Thus, the non-coding CD44 3'-UTR serves as a competitor for miRNA binding and subsequently inactivates miRNA functions, by freeing the target mRNAs from being repressed.

  16. Effects of CD44 and E-cadherin overexpression on the proliferation, adhesion and invasion of ovarian cancer cells.

    Mao, Meiya; Zheng, Xiaojiao; Jin, Bohong; Zhang, Fubin; Zhu, Linyan; Cui, Lining

    2017-12-01

    CD44 is a prognostic indicator of shorter survival time in ovarian cancer. E-cadherin fragmentation promotes the progression of ovarian cancer. However, the effects of CD44 and E-cadherin overexpression on ovarian cancer cells have remained elusive. The present study aimed to investigate the effects of overexpression of CD44 and E-cadherin on cell proliferation, adhesion and invasion of SKOV-3 and OVCAR-3 ovarian cancer cells. Overexpression of CD44 and E-cadherin was achieved by transfecting SKOV-3 and OVCAR-3 cells with viruses carrying the CD44 or E-cadherin gene, respectively. Expression of CD44 and E-cadherin was detected by western blot analysis. The proliferation of SKOV-3 and OVCAR-3 cells was measured by a Cell Counting Kit-8 at 0, 24 and 48 h after viral transfection. The adhesion ability of SKOV-3 and OVCAR-3 cells to the endothelial layer was detected. A Transwell invasion assay was utilized to assess the invasion ability of the cells. Overexpression of CD44 and E-cadherin in SKOV-3 and OVCAR-3 cells was confirmed by western blot. Compared with the blank or negative control groups, the CD44 overexpression groups of SKOV-3 and OVCAR-3 cells exhibited an increased cell proliferation rate at 24 and 48 h, whereas overexpression of E-cadherin did not alter the proliferation of these cells. Furthermore, compared with the blank and negative control groups, the cell adhesion and invasion ability in the CD44 overexpression groups of SKOV-3 and OVCAR-3 cells was markedly higher. There were no significant differences in adhesion ability between the E-cadherin overexpression group and the blank/negative control group. Of note, overexpression of E-cadherin decreased the invasive ability of SKOV-3 and OVCAR-3 cells. In conclusion, Overexpression of CD44 increased the proliferation, adhesion and invasion of ovarian cancer cells, while overexpression of E-cadherin decreased the invasion of ovarian cancer cells.

  17. Expression of Bmi-1, P16, and CD44v6 in Uterine Cervical Carcinoma and Its Clinical Significance

    Weng, Mei-ying; Li, Lin; Feng, Shu-ying; Hong, Shun-jia

    2012-01-01

    Bmi-1, a putative proto-oncogene, is a core member of the polycomb gene family, which is expressed in many human tumors. The p16 protein negatively regulated cell proliferation, whereas CD44v6 is associated with proliferation as an important protein. Additionally, CD44v6 is an important nuclear antigen closely correlated to tumor metastasis. The present study aims to investigate the expression and significance of Bmi-1, p16, and CD44v6 in uterine cervical carcinoma (UCC). A total of 62 UCC, 30 cervical neoplasic, and 20 normal cervical mucosal tissues were used in the current study. The expression of Bmi-1, p16, and CD44v6 in these tissues was determined using immunohistochemical assay. The relationships among the expression of these indices, the clinicopathologic features of UCC, and the survival rate of UCC patients were also discussed. The correlation between Bmi-1 protein expression and p16 or CD44v6 protein in UCC was analyzed. The expression of Bmi-1, p16, and CD44v6 was significantly high in cervical carcinoma compared with that in the cervical neoplasia and normal colorectal mucosa (P<0.05). The over-expression of Bmi-1 protein in UCC was apparently related to the distant metastasis (P<0.01) and the tumor, nodes and metastasis-classification, i.e. the TNM staging, World Health Organization (P<0.05). Nevertheless, the positive expression of p16 protein in UCC was not significantly associated with the clinicopathologic features (P>0.05). The Kaplan–Meier survival analysis showed that the over-expression of Bmi-1 significantly decreased the survival rate of UCC patients (P<0.05). A strong correlation indicated that there was statistical significance between the expression of Bmi-1 and CD44V6 proteins in UCC (r=0.419, P=0.001). The over-expression of Bmi-1 and CD44v6 protein closely correlate to the tumorigenesis, metastasis, and prognosis of UCC. Bmi-1 and CD44v6 may be used to predict the prognosis of cervical carcinoma. Bmi-1 may indirectly regulate the

  18. The role of a new CD44st in increasing the invasion capability of the human breast cancer cell line MCF-7

    Fang, Xin Jian; Jiang, Hua; Zhao, Xv Peng; Jiang, Wei Mei

    2011-01-01

    CD44, a hyaluronan (HA) receptor, is a multistructural and multifunctional cell surface molecule involved in cell proliferation, cell differentiation, cell migration, angiogenesis, presentation of cytokines, chemokines and growth factors to the corresponding receptors, and docking of proteases at the cell membrane, as well as in signaling for cell survival. The CD44 gene contains 20 exons that are alternatively spliced, giving rise to many CD44 isoforms, perhaps including tumor-specific sequences. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were used to detect CD44st mRNA and CD44 protein in sensitive MCF-7, Lovo, K562 and HL-60 cell lines as well as their parental counterparts, respectively. The full length cDNA encoding CD44st was obtained from the total RNA isolated from MCF-7/Adr cells by RT-PCR, and subcloned into the pMD19-T vector. The CD44st gene sequence and open reading frame were confirmed by restriction enzyme analysis and nucleotide sequencing, and then inserted into the eukaryotic expression vector pcDNA3.1. The pcDNA3.1-CD44st was transfected into MCF-7 cells using Lipofectamine. After transfection, the positive clones were obtained by G418 screening. The changes of the MMP-2 and MMP-9 genes and protein levels were detected by RT-PCR and gelatin zymography, respectively. The number of the cells penetrating through the artificial matrix membrane in each group (MCF-7, MCF-7+HA, MCF-7/neo, MCF-7/neo+HA, MCF-7/CD44st, MCF-7/CD44st+HA and MCF-7/CD44st+Anti-CD44+HA) was counted to compare the change of the invasion capability regulated by the CD44st. Erk and P-Erk were investigated by Western blotting to approach the molecular mechanisms of MMP-2 and MMP-9 expression regulated by the CD44st. Sensitive MCF-7, Lovo, K562 and HL-60 cells did not contain CD44st mRNA and CD44 protein. In contrast, the multidrug resistance MCF-7/Adr, Lovo/Adr, K562/Adr and HL-60/Adr cells expressed CD44st mRNA and CD44 protein. The CD44st m

  19. Curcumin induced nanoscale CD44 molecular redistribution and antigen-antibody interaction on HepG2 cell surface

    Wang Mu [Department of Chemistry, Jinan University, 601 Huangpu Road West, Tianhe District, Guangzhou 510632 (China); Ruan Yuxia [Department of Ophthalmology, The First Affiliated Hospital, Jinan University, 601 Huangpu Road West, Tianhe District, Guangzhou 510632 (China); Xing Xiaobo; Chen Qian; Peng, Yuan [Department of Chemistry, Jinan University, 601 Huangpu Road West, Tianhe District, Guangzhou 510632 (China); Cai Jiye, E-mail: tjycai@jnu.edu.cn [Department of Chemistry, Jinan University, 601 Huangpu Road West, Tianhe District, Guangzhou 510632 (China)

    2011-07-04

    Graphical abstract: Highlights: > In this study, we investigate the changes of CD44 expression and distribution on HepG2 cells after curcumin treatment. > We find curcumin is able to change the morphology and ultrastructure of HepG2 cells. > Curcumin can reduce the expression of CD44 molecules and induce the nanoscale molecular redistribution on cell surface. > The binding force between CD44-modified AFM tip and the HepG2 cell surface decreases after curcumin-treatment. - Abstract: The cell surface glycoprotein CD44 was implicated in the progression, metastasis and apoptosis of certain human tumors. In this study, we used atomic force microscope (AFM) to monitor the effect of curcumin on human hepatocellular carcinoma (HepG2) cell surface nanoscale structure. High-resolution imaging revealed that cell morphology and ultrastructure changed a lot after being treated with curcumin. The membrane average roughness increased (10.88 {+-} 4.62 nm to 129.70 {+-} 43.72 nm) and the expression of CD44 decreased (99.79 {+-} 0.16% to 75.14 {+-} 8.37%). Laser scanning confocal microscope (LSCM) imaging showed that CD44 molecules were located on the cell membrane. The florescence intensity in control group was weaker than that in curcumin treated cells. Most of the binding forces between CD44 antibodies and untreated HepG2 cell membrane were around 120-220 pN. After being incubated with curcumin, the major forces focused on 70-150 pN (10 {mu}M curcumin-treated) and 50-120 pN (20 {mu}M curcumin-treated). These results suggested that, as result of nanoscale molecular redistribution, changes of the cell surface were in response to external treatment of curcumin. The combination of AFM and LSCM could be a powerful method to detect the distribution of cell surface molecules and interactions between molecules and their ligands.

  20. Soluble CD44 concentration in the serum and peritoneal fluid samples of patients with different stages of endometriosis.

    Mashayekhi, Farhad; Aryaee, Hadis; Mirzajani, Ebrahim; Yasin, Ashraf Ale; Fathi, Abdolsatar

    2015-09-01

    Endometriosis is a gynecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity, most commonly implanted over visceral and peritoneal surface within the female pelvis. CD44 is a membrane protein expressed by human endometrial cells, and it has been shown to promote the adhesion of endometrial cells. The aim of this study was to determine the levels of soluble CD44 (sCD44) in the serum and peritoneal fluid (PF) samples of patients with different stages of endometriosis. 39 PF and serum samples from normal healthy and 130 samples from different stages of patients with endometriosis (33 cases of stage I, 38 stage II, 30 stage III and 29 stage IV) were included in this study. Total protein concentration (TPC) and the level of s-cMet in the serum were determined by Bio-Rad protein assay based on the Bradford dye procedure and enzyme-linked immunosorbent assay, respectively. No significant change in the TPC was seen in the serum of patients with endometriosis when compared to normal controls. Results obtained demonstrated that all serum and peritoneal fluid samples, presented sCD44 expression, whereas, starting from stages I to IV endometriosis, a significant increase of sCD44 expression was observed as compared to control group. The results of this study show that a high expression of sCD44 is correlated with advanced stages of endometriosis. It is also concluded that the detection of serum and/or peritoneal fluid sCD44 may be useful in classifying endometriosis.

  1. Li-Fraumeni syndrome with simultaneous osteosarcoma and liver cancer: Increased expression of a CD44 variant isoform after chemotherapy

    Yoshida, Go J; Kuroda, Tatsuo; Fuchimoto, Yasushi; Osumi, Tomoo; Shimada, Hiroyuki; Hosaka, Seiichi; Morioka, Hideo; Mukai, Makio; Masugi, Yohei; Sakamoto, Michiie

    2012-01-01

    Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome that is commonly associated with a germline mutation in the tumor suppressor gene p53. Loss of p53 results in increased expression of CD44, a cancer stem cell (CSC) marker, which is involved in the scavenging of reactive oxygen species (ROS). Here, we report a change in the expression of a CD44 variant isoform (CD44v8-10) in an 8-year-old female LFS patient with osteosarcoma and atypical liver cancer after chemotherapy. The patient visited a clinic with a chief complaint of chronic pain in a bruise on her right knee. Magnetic resonance imaging (MRI) raised the possibility of a bone malignancy. Biochemical testing also revealed significantly elevated levels of AFP, which strongly suggested the existence of a primary malignancy in the liver. MRI imaging showed the simultaneous development of osteosarcoma and liver cancer, both of which were confirmed upon biopsy. Combined therapy with surgical resection after chemotherapy was successful in this patient. Regardless of the absence of a familial history of hereditary cancer, a germline mutation in p53 was identified (a missense mutation defined as c.722 C>T, p.Ser241Phe). To better understand the cancer progression and response to treatment, immunohistochemical (IHC) analysis of biopsy specimens obtained before and after chemotherapy was performed using a specific antibody against CD44v8-10. This case demonstrates the ectopic up-regulation of CD44v8-10 in a biopsy sample obtained after cytotoxic chemotherapy, which confers high levels of oxidative stress on cancer cells. Because the alternative splicing of CD44 is tightly regulated epigenetically, it is possible that micro-environmental stress resulting from chemotherapy caused the ectopic induction of CD44v8-10 in vivo

  2. The CD44(high tumorigenic subsets in lung cancer biospecimens are enriched for low miR-34a expression.

    Saroj K Basak

    Full Text Available Cellular heterogeneity is an integral part of cancer development and progression. Progression can be associated with emergence of cells that exhibit high phenotypic plasticity (including "de-differentiation" to primitive developmental states, and aggressive behavioral properties (including high tumorigenic potentials. We observed that many biomarkers that are used to identify Cancer Stem Cells (CSC can label cell subsets in an advanced clinical stage of lung cancer (malignant pleural effusions, or MPE. Thus, CSC-biomarkers may be useful for live sorting functionally distinct cell subsets from individual tumors, which may enable investigators to hone in on the molecular basis for functional heterogeneity. We demonstrate that the CD44(hi (CD44-high cancer cell subsets display higher clonal, colony forming potential than CD44(lo cells (n=3 and are also tumorigenic (n=2/2 when transplanted in mouse xenograft model. The CD44(hi subsets express different levels of embryonal (de-differentiation markers or chromatin regulators. In archived lung cancer tissues, ALDH markers co-localize more with CD44 in squamous cell carcinoma (n=5/7 than Adeno Carcinoma (n=1/12. MPE cancer cells and a lung cancer cell line (NCI-H-2122 exhibit chromosomal abnormalities and 1p36 deletion (n=3/3. Since miR-34a maps to the 1p36 deletion site, low miR-34a expression levels were detected in these cells. The colony forming efficiency of CD44(hi cells, characteristic property of CSC, can be inhibited by mir-34a replacement in these samples. In addition the highly tumorigenic CD44(hi cells are enriched for cells in the G2 phase of cell cycle.

  3. Preventing occupational injury among police officers: does motivation matter?

    Chan, D K C; Webb, D; Ryan, R M; Tang, T C W; Yang, S X; Ntoumanis, N; Hagger, M S

    2017-08-01

    Injury prevention is an important issue for police officers, but the effectiveness of prevention initiatives is dependent on officers' motivation toward, and adherence to, recommended health and safety guidelines. To understand effects of police officers' motivation to prevent occupational injury on beliefs about safety and adherence to injury prevention behaviours. Full-time police officers completed a survey comprising validated psychometric scales to assess autonomous, controlled and amotivated forms of motivation (Treatment Self-Regulation Questionnaire), behavioural adherence (Self-reported Treatment Adherence Scale) and beliefs (Safety Attitude Questionnaire) with respect to injury prevention behaviours. There were 207 participants; response rate was 87%. Hierarchical multiple regression analyses demonstrated that autonomous motivation was positively related to behavioural adherence, commitment to safety and prioritizing injury prevention. Controlled motivation was a positive predictor of safety communication barriers. Amotivation was positively associated with fatalism regarding injury prevention, safety violation and worry. These findings are consistent with the tenets of self-determination theory in that autonomous motivation was a positive predictor of adaptive safety beliefs and adherence to injury prevention behaviours. © The Author 2017. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  4. Preventing Occupational Skin Disease: A Review of Training Programs.

    Zack, Bethany; Arrandale, Victoria H; Holness, D Linn

    Occupational contact dermatitis (OCD) is a common occupational disease that impacts a variety of worker groups. Skin protection and disease prevention training programs have shown promise for improving prevention practices and reducing the incidence of OCD. This review details the features of training programs for primary prevention of OCD and identifies gaps in the literature. Twelve studies were identified for in-depth review: many studies included wet workers employed in health care, hairdressing, cleaning, and food preparation; 1 program featured manufacturing workers. Few programs provided content on allergic contact dermatitis, and only 1 was evaluated for long-term effectiveness. Effective programs were similar in content, delivery method, and timing and were characterized by industry specificity, multimodal learning, participatory elements, skin care resource provision, repeated sessions, and management engagement. Long-term effectiveness, generalizability beyond OCD, workplace health and safety culture impact, and translation of programs in the North American context represent areas for future research.

  5. Enrichment of CD44 in basal-type breast cancer correlates with EMT, cancer stem cell gene profile, and prognosis

    Xu HX

    2016-01-01

    Full Text Available Hanxiao Xu,1 Yijun Tian,1 Xun Yuan,1 Yu Liu,2 Hua Wu,1 Qian Liu,1 Gen Sheng Wu,3,4 Kongming Wu1 1Department of Oncology, 2Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Oncology, 4Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA Abstract: Cluster of differentiation 44 (CD44 is a transmembrane glycoprotein that serves as the receptor for the extracellular matrix component hyaluronic acid. CD44 has been reported to play key roles in cell proliferation, motility, and survival, but its role in breast cancer remains controversial. In this study, we conducted a meta-analysis. A total of 23 published Gene Expression Omnibus databases were included to evaluate the association between CD44 mRNA expression and clinicopathological characteristics or prognosis of the patients with breast cancer. Our analysis revealed that CD44 expression was associated with clinicopathological features, including the histological grade, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor-2 status. Higher levels of CD44 expression were observed in the basal subtype of breast cancer both at the mRNA and protein levels (odds ratio [OR] =2.08, 95% confidence interval [CI]: 1.72–2.52; OR =2.11, 95% CI: 1.67–2.68. Patients with CD44 overexpression exhibited significantly worse overall survival (hazard ratio =1.27; 95% CI: 1.04–1.55. Whole gene profile analysis revealed that CD44 expression was enriched in basal-type breast cancer and correlated with epithelial–mesenchymal transition and cancer stem cell gene profiles. In summary, our analyses indicated that CD44 potentially might be a prognostic marker for breast cancer and thus can serve as a therapeutic target for basal-type breast cancer. Keywords: breast cancer, CD44, survival prediction, meta

  6. CCR2 and CD44 promote inflammatory cell recruitment during fatty liver formation in a lithogenic diet fed mouse model.

    Charlotte E Egan

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a common disease with a spectrum of presentations. The current study utilized a lithogenic diet model of NAFLD. The diet was fed to mice that are either resistant (AKR or susceptible (BALB/c and C57BL/6 to hepatitis followed by molecular and flow cytometric analysis. Following this, a similar approach was taken in congenic mice with specific mutations in immunological genes. The initial study identified a significant and profound increase in multiple ligands for the chemokine receptor CCR2 and an increase in CD44 expression in susceptible C57BL/6 (B6 but not resistant AKR mice. Ccr2(-/- mice were completely protected from hepatitis and Cd44(-/- mice were partially protected. Despite protection from inflammation, both strains displayed similar histological steatosis scores and significant increases in serum liver enzymes. CD45(+CD44(+ cells bound to hyaluronic acid (HA in diet fed B6 mice but not Cd44(-/- or Ccr2(-/- mice. Ccr2(-/- mice displayed a diminished HA binding phenotype most notably in monocytes, and CD8(+ T-cells. In conclusion, this study demonstrates that absence of CCR2 completely and CD44 partially reduces hepatic leukocyte recruitment. These data also provide evidence that there are multiple redundant CCR2 ligands produced during hepatic lipid accumulation and describes the induction of a strong HA binding phenotype in response to LD feeding in some subsets of leukocytes from susceptible strains.

  7. α6 Integrin and CD44 enrich for a primary keratinocyte population that displays resistance to UV-induced apoptosis.

    Helen Wray

    Full Text Available Epidermal human keratinocytes are exposed to a wide range of environmental genotoxic insults, including the UV component of solar radiation. Epidermal homeostasis in response to cellular or tissue damage is maintained by a population of keratinocyte stem cells (KSC that reside in the basal layer of the epithelium. Using cell sorting based on cell-surface markers, we have identified a novel α6 integrin(high+/CD44(+ sub-population of basal keratinocytes. These α6 integrin(high+/CD44(+ keratinocytes have both high proliferative potential, form colonies in culture that have characteristics of holoclones and have a unique pattern of resistance to apoptosis induced by UVB radiation or by agents that induce single- or double strand DNA breaks. Resistance to UVB induced apoptosis in the α6 integrin(high+/CD44(+ cells involved increased expression of TAp63 and was overcome by PI-3 kinase inhibition. In marked contrast, the α6 integrin(high+/CD44(+ cells were sensitive to apoptosis induced by the cross-linking agent cisplatin, and imatinib inhibition of c-Abl blocked the ability of cisplatin to kill α6 integrin(high+/CD44(+ cells. Our findings reveal a population of basal keratinocytes with long-term proliferative properties that display specific patterns of apoptotic resistance that is dependent upon the genotoxic stimulus, and provide insights into how these cells can be targeted with chemotherapeutic agents.

  8. Proactive prevention in occupational safety and health: how to identify tomorrow's prevention priorities and preventive measures.

    Hauke, Angelika; Flaspöler, Eva; Reinert, Dietmar

    2018-04-17

    Global trends such as digitalisation, globalisation and demographic change are changing workplaces, and accordingly occupational safety and health (OSH) needs. To better prepare for the future and to foster proactive prevention, the German Social Accident Insurance (DGUV) established an OSH risk observatory (RO OSH). The RO OSH relies on an online survey and calls upon the expertise of labour inspectors. 398 labour inspectors participated in the first RO OSH enquiry. They rated developments with regard to their sector-specific relevance for OSH in the near future. The RO OSH also provides ideas for preventive measures that can be implemented by the German Social Accident Insurance Institutions. Work intensity, demographic aspects, and digitalisation play a major role for most or all sectors. However, familiar OSH issues such as musculoskeletal strain and noise also continue to be of major importance and require further consideration and specific solutions in prevention. For the DGUV, training and consulting bear great potential for proactive prevention in the above priority areas, e.g. by fostering a prevention culture and supporting companies in (psychosocial) risk assessment (also for mobile work). For instance, concepts for increasing physical activity at sedentary workplaces, and data security require continued research.

  9. [Chronic migraine and work: occupational risks and prevention].

    Vicente-Herrero, M T; Ramírez Iñiguez de la Torre, M V; Capdevila García, L M; López-González, Á A; Terradillos García, M J

    2013-09-01

    Chronic migraine is a clinically difficult to manage primary headache which affects the quality of life of the patients. This impact is important in the occupational world, where along with the clinical aspects of the disease, the therapies used for the control of the symptoms or preventive aspects, must be assessed. The side effects of the drugs and the limitations associated with their symptoms are aspects to highlight in occupational health, especially in individual workplaces, where there is a high risk of work-related injuries. The medical officer must assess the occupational risks of particular importance in the progression of this disease, as well as preventive actions, within the ambit of the current Spanish legislation, that may be favorable for both the company and the worker. The coordinated medical intervention and knowledge of these occupational aspects can provide clinically relevant tools, andoccupational and social optimization in the use of available resources. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  10. Cooperativity of CD44 and CD49d in leukemia cell homing, migration, and survival offers a means for therapeutic attack.

    Singh, Vibuthi; Erb, Ulrike; Zöller, Margot

    2013-11-15

    A CD44 blockade drives leukemic cells into differentiation and apoptosis by dislodging from the osteogenic niche. Because anti-CD49d also supports hematopoietic stem cell mobilization, we sought to determine the therapeutic efficacy of a joint CD49d/CD44 blockade. To unravel the underlying mechanism, the CD49d(-) EL4 lymphoma was transfected with CD49d or point-mutated CD49d, prohibiting phosphorylation and FAK binding; additionally, a CD44(-) Jurkat subline was transfected with murine CD44, CD44 with a point mutation in the ezrin binding site, or with cytoplasmic tail-truncated CD44. Parental and transfected EL4 and Jurkat cells were evaluated for adhesion, migration, and apoptosis susceptibility in vitro and in vivo. Ligand-binding and Ab-blocking studies revealed CD44-CD49d cooperation in vitro and in vivo in adhesion, migration, and apoptosis resistance. The cooperation depends on ligand-induced proximity such that both CD44 and CD49d get access to src, FAK, and paxillin and via lck to the MAPK pathway, with the latter also supporting antiapoptotic molecule liberation. Accordingly, synergisms were only seen in leukemia cells expressing wild-type CD44 and CD49d. Anti-CD44 together with anti-CD49d efficiently dislodged EL4-CD49d/Jurkat-CD44 in bone marrow and spleen. Dislodging was accompanied by increased apoptosis susceptibility that strengthened low-dose chemotherapy, the combined treatment most strongly interfering with metastatic settlement and being partly curative. Ab treatment also promoted NK and Ab-dependent cellular cytotoxicity activation, which affected leukemia cells independent of CD44/CD49d tail mutations. Thus, mostly owing to a blockade of joint signaling, anti-CD44 and anti-CD49d hamper leukemic cell settlement and break apoptosis resistance, which strongly supports low-dose chemotherapy.

  11. 76 FR 28789 - Draft Alert Entitled “Preventing Occupational Respiratory Disease From Dampness in Office...

    2011-05-18

    ... NIOSH-238] Draft Alert Entitled ``Preventing Occupational Respiratory Disease From Dampness in Office... Institute for Occupational Safety and Health (NIOSH) of the Centers for Disease Control and Prevention (CDC), announces the availability of a draft Alert entitled ``Preventing Occupational Respiratory Disease from...

  12. Immunohistochemistry Analysis of CD44, EGFR, and p16 in Oral Cavity and Oropharyngeal Squamous Cell Carcinoma.

    Cohen, Erin R; Reis, Isildinha M; Gomez, Carmen; Pereira, Lutecia; Freiser, Monika E; Hoosien, Gia; Franzmann, Elizabeth J

    2017-08-01

    Objectives We analyze the relationship between CD44, epidermal growth factor receptor (EGFR), and p16 expression in oral cavity and oropharyngeal cancers in a diverse population. We also describe whether particular patterns of staining are associated with progression-free survival and overall survival. Study Design Prospective study, single-blind to pathologist and laboratory technologist. Setting Hospital based. Subjects and Methods Immunohistochemistry, comprising gross staining and cellular expression, was performed and interpreted in a blinded fashion on 24 lip/oral cavity and 40 oropharyngeal cancer specimens collected between 2007 and 2012 from participants of a larger study. Information on overall survival and progression-free survival was obtained from medical records. Results Nineteen cases were clinically p16 positive, 16 of which were oropharyngeal. Oral cavity lesions were more likely to exhibit strong CD44 membrane staining ( P = .0002). Strong CD44 membrane and strong EGFR membrane and/or cytoplasmic staining were more common in p16-negative cancers ( P = .006). Peripheral/mixed gross p16 staining pattern was associated with worse survival than the universal staining on univariate and multivariate analyses ( P = .006, P = .030). This held true when combining gross and cellular localization for p16. For CD44, universal gross staining demonstrated poorer overall survival compared with the peripheral/mixed group ( P = .039). CD44 peripheral/mixed group alone and when combined with universal p16 demonstrated the best survival on multivariate analysis ( P = .010). Conclusion In a diverse population, systematic analysis applying p16, CD44, and EGFR gross staining and cellular localization on immunohistochemistry demonstrates distinct patterns that may have prognostic potential exceeding current methods. Larger studies are warranted to investigate these findings further.

  13. Effectiveness of occupational injury prevention policies in Spain.

    Benavides, Fernando G; García, Ana M; Lopez-Ruiz, Maria; Gil, Josep; Boix, Pere; Martinez, José Miguel; Rodrigo, Fernando

    2009-01-01

    We examined the effectiveness of preventive interventions against occupational injuries (preferential action plans [PAPs]) developed by Spanish regional governments starting in 2000. We included 3,252,028 occupational injuries with sick leave due to mechanical causes occurring between 1994 and 2004 in manufacturing and private service companies. Time trends for occupational injury rates were estimated before and after implementation of PAPs in each region, with a control group defined for those regions in which no PAPs were implemented (e.g., Galicia, Madrid, and Cataluña). We determined annual change percentages and their 95% confidence intervals (CIs) through a negative binomial regression model. Regions were grouped into three categories according to formal quality of their PAPs. The regions with the best PAPs (Andalucia, Aragon, Valencia, and Murcia) showed annually increasing occupational injury rates (2.3%, 95% CI -2.5, 7.4) before implementation of PAPs. After PAPs were implemented, occupational injury rates decreased significantly to -7.4% (95% CI -10.2, -4.5). Similar results were also found for regions with PAPs of lower quality and even for regions that didn't implement a PAP (control group). These results did not vary substantially in stratified analysis by gender, age, type of contract, or length of sick leave. PAPs are not related to a general decline in occupational injury rates in Spain starting in 2000. Reinforcement of Spanish health and safety regulations and labor inspection activities since 2000, resulting from a social agreement between central government and social agents, remains an alternative hypothesis requiring additional research.

  14. Stable alterations of CD44 isoform expression in prostate cancer cells decrease invasion and growth and alter ligand binding and chemosensitivity

    Yang, Kui; Tang, Yaqiong; Habermehl, Gabriel K; Iczkowski, Kenneth A

    2010-01-01

    Dysregulated CD44 expression characterizes most human cancers, including prostate cancer (PCa). PCa loses expression of CD44 standard (CD44s) that is present in benign epithelium, and overexpresses the novel splice variant isoform, CD44v7-10. Using retroviral gene delivery to PC-3M PCa cells, we expressed luciferase-only, enforced CD44s re-expression as a fusion protein with luciferase at its C-terminus or as a protein separate from luciferase, or knocked down CD44v7-10 by RNAi. Invasion, migration, proliferation, soft agar colony formation, adhesion, Docetaxel sensitivity, and xenograft growth assays were carried out. Expression responses of merlin, a CD44 binding partner, and growth-permissive phospho-merlin, were assessed by western blot. Compared to luciferase-only PC-3M cells, all three treatments reduced invasion and migration. Growth and soft agar colony formation were reduced only by re-expression of CD44s as a separate or fusion protein but not CD44v7-10 RNAi. Hyaluronan and osteopontin binding were greatly strengthened by CD44s expression as a separate protein, but not a fusion protein. CD44v7-10 RNAi in PC-3M cells caused marked sensitization to Docetaxel; the two CD44s re-expression approaches caused minimal sensitization. In limited numbers of mouse subcutaneous xenografts, all three alterations produced only nonsignificant trends toward slower growth compared with luciferase-only controls. The expression of CD44s as a separate protein, but not a fusion protein, caused emergence of a strongly-expressed, hypophosphorylated species of phospho-merlin. Stable re-expression of CD44s reduces PCa growth and invasion in vitro, and possibly in vivo, suggesting CD44 alterations have potential as gene therapy. When the C-terminus of CD44s is fused to another protein, most phenotypic effects are lessened, particularly hyaluronan adhesion. Finally, CD44v7-10, although it was not functionally significant for growth, may be a target for chemosensitization

  15. Conformational and functional variants of CD44-targeted protein nanoparticles bio-produced in bacteria

    Pesarrodona, Mireia; Conchillo-Solé, Oscar; Unzueta, Ugutz; Xu, Zhikun; Ferrer-Miralles, Neus; Daura, Xavier; Vázquez, Esther; Villaverde, Antonio; Fernández, Yolanda; Foradada, Laia; Schwartz, Simó Jr; Abasolo, Ibane; Sánchez-Chardi, Alejandro; Roldán, Mónica; Villegas, Sandra; Rinas, Ursula

    2016-01-01

    Biofabrication is attracting interest as a means to produce nanostructured functional materials because of its operational versatility and full scalability. Materials based on proteins are especially appealing, as the structure and functionality of proteins can be adapted by genetic engineering. Furthermore, strategies and tools for protein production have been developed and refined steadily for more than 30 years. However, protein conformation and therefore activity might be sensitive to production conditions. Here, we have explored whether the downstream strategy influences the structure and biological activities, in vitro and in vivo, of a self-assembling, CD44-targeted protein-only nanoparticle produced in Escherichia coli. This has been performed through the comparative analysis of particles built from soluble protein species or protein versions obtained by in vitro protein extraction from inclusion bodies, through mild, non-denaturing procedures. These methods have been developed recently as a convenient alternative to the use of toxic chaotropic agents for protein resolubilization from protein aggregates. The results indicate that the resulting material shows substantial differences in its physicochemical properties and its biological performance at the systems level, and that its building blocks are sensitive to the particular protein source. (paper)

  16. Satellite Cells CD44 Positive Drive Muscle Regeneration in Osteoarthritis Patients

    Scimeca, Manuel; Bonanno, Elena; Piccirilli, Eleonora; Baldi, Jacopo; Mauriello, Alessandro; Orlandi, Augusto; Tancredi, Virginia; Gasbarra, Elena; Tarantino, Umberto

    2015-01-01

    Age-related bone diseases, such as osteoarthritis and osteoporosis, are strongly associated with sarcopenia and muscle fiber atrophy. In this study, we analyzed muscle biopsies in order to demonstrate that, in osteoarthritis patients, both osteophytes formation and regenerative properties of muscle stem cells are related to the same factors. In particular, thanks to immunohistochemistry, transmission electron microscopy, and immunogold labeling we investigated the role of BMP-2 in muscle stem cells activity. In patients with osteoarthritis both immunohistochemistry and transmission electron microscopy allowed us to note a higher number of CD44 positive satellite muscle cells forming syncytium. Moreover, the perinuclear and cytoplasmic expression of BMP-2 assessed by in situ molecular characterization of satellite cells syncytia suggest a very strict correlation between BMP-2 expression and muscle regeneration capability. Summing up, the higher BMP-2 expression in osteoarthritic patients could explain the increased bone mineral density as well as decreased muscle atrophy in osteoarthrosic patients. In conclusion, our results suggest that the control of physiological BMP-2 balance between bone and muscle tissues may be considered as a potential pharmacological target in bone-muscle related pathology. PMID:26101529

  17. Satellite Cells CD44 Positive Drive Muscle Regeneration in Osteoarthritis Patients

    Manuel Scimeca

    2015-01-01

    Full Text Available Age-related bone diseases, such as osteoarthritis and osteoporosis, are strongly associated with sarcopenia and muscle fiber atrophy. In this study, we analyzed muscle biopsies in order to demonstrate that, in osteoarthritis patients, both osteophytes formation and regenerative properties of muscle stem cells are related to the same factors. In particular, thanks to immunohistochemistry, transmission electron microscopy, and immunogold labeling we investigated the role of BMP-2 in muscle stem cells activity. In patients with osteoarthritis both immunohistochemistry and transmission electron microscopy allowed us to note a higher number of CD44 positive satellite muscle cells forming syncytium. Moreover, the perinuclear and cytoplasmic expression of BMP-2 assessed by in situ molecular characterization of satellite cells syncytia suggest a very strict correlation between BMP-2 expression and muscle regeneration capability. Summing up, the higher BMP-2 expression in osteoarthritic patients could explain the increased bone mineral density as well as decreased muscle atrophy in osteoarthrosic patients. In conclusion, our results suggest that the control of physiological BMP-2 balance between bone and muscle tissues may be considered as a potential pharmacological target in bone-muscle related pathology.

  18. CD147, CD44, and the epidermal growth factor receptor (EGFR) signaling pathway cooperate to regulate breast epithelial cell invasiveness.

    Grass, G Daniel; Tolliver, Lauren B; Bratoeva, Momka; Toole, Bryan P

    2013-09-06

    The immunoglobulin superfamily glycoprotein CD147 (emmprin; basigin) is associated with an invasive phenotype in various types of cancers, including malignant breast cancer. We showed recently that up-regulation of CD147 in non-transformed, non-invasive breast epithelial cells is sufficient to induce an invasive phenotype characterized by membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent invadopodia activity (Grass, G. D., Bratoeva, M., and Toole, B. P. (2012) Regulation of invadopodia formation and activity by CD147. J. Cell Sci. 125, 777-788). Here we found that CD147 induces breast epithelial cell invasiveness by promoting epidermal growth factor receptor (EGFR)-Ras-ERK signaling in a manner dependent on hyaluronan-CD44 interaction. Furthermore, CD147 promotes assembly of signaling complexes containing CD147, CD44, and EGFR in lipid raftlike domains. We also found that oncogenic Ras regulates CD147 expression, hyaluronan synthesis, and formation of CD147-CD44-EGFR complexes, thus forming a positive feedback loop that may amplify invasiveness. Last, we showed that malignant breast cancer cells are heterogeneous in their expression of surface-associated CD147 and that high levels of membrane CD147 correlate with cell surface EGFR and CD44 levels, activated EGFR and ERK1, and activated invadopodia. Future studies should evaluate CD147 as a potential therapeutic target and disease stratification marker in breast cancer.

  19. CD147, CD44, and the Epidermal Growth Factor Receptor (EGFR) Signaling Pathway Cooperate to Regulate Breast Epithelial Cell Invasiveness*

    Grass, G. Daniel; Tolliver, Lauren B.; Bratoeva, Momka; Toole, Bryan P.

    2013-01-01

    The immunoglobulin superfamily glycoprotein CD147 (emmprin; basigin) is associated with an invasive phenotype in various types of cancers, including malignant breast cancer. We showed recently that up-regulation of CD147 in non-transformed, non-invasive breast epithelial cells is sufficient to induce an invasive phenotype characterized by membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent invadopodia activity (Grass, G. D., Bratoeva, M., and Toole, B. P. (2012) Regulation of invadopodia formation and activity by CD147. J. Cell Sci. 125, 777–788). Here we found that CD147 induces breast epithelial cell invasiveness by promoting epidermal growth factor receptor (EGFR)-Ras-ERK signaling in a manner dependent on hyaluronan-CD44 interaction. Furthermore, CD147 promotes assembly of signaling complexes containing CD147, CD44, and EGFR in lipid raftlike domains. We also found that oncogenic Ras regulates CD147 expression, hyaluronan synthesis, and formation of CD147-CD44-EGFR complexes, thus forming a positive feedback loop that may amplify invasiveness. Last, we showed that malignant breast cancer cells are heterogeneous in their expression of surface-associated CD147 and that high levels of membrane CD147 correlate with cell surface EGFR and CD44 levels, activated EGFR and ERK1, and activated invadopodia. Future studies should evaluate CD147 as a potential therapeutic target and disease stratification marker in breast cancer. PMID:23888049

  20. Hyaluronan, CD44, and Emmprin Regulate Lactate Efflux and Membrane Localization of Monocarboxylate Transporters in Human Breast Carcinoma Cells

    Slomiany, Mark G.; Grass, G. Daniel; Robertson, Angela D.; Yang, Xiao Y.; Maria, Bernard L.; Beeson, Craig; Toole, Bryan P.

    2013-01-01

    Interactions of hyaluronan with CD44 in tumor cells play important cooperative roles in various aspects of malignancy and drug resistance. Emmprin (CD147; basigin)is a cell surface glycoprotein of the immunoglobulin superfamily that is highly up-regulated in malignant cancer cells and stimulates hyaluronan production, as well as several downstream signaling pathways. Emmprin also interacts with various monocarboxylate transporters (MCT). Malignant cancer cells use the glycolytic pathway and require MCTs to efflux lactate that results from glycolysis. Glycolysis and lactate secretion contribute to malignant cell behaviors and drug resistance in tumor cells. In the present study, we find that perturbation of endogenous hyaluronan, using small hyaluronan oligosaccharides, rapidly inhibits lactate efflux from breast carcinoma cells; down-regulation of emmprin, using emmprin small interfering RNA, also results in decreased efflux. In addition, we find that CD44 coimmunoprecipitates with MCT1, MCT4, and emmprin and colocalizes with these proteins at the plasma membrane. Moreover, after treatment of the cells with hyaluronan oligosaccharides, CD44, MCT1, and MCT4 become localized intracellularly whereas emmprin remains at the cell membrane. Together, these data indicate that constitutive interactions among hyaluronan, CD44, and emmprin contribute to regulation of MCT localization and function in the plasma membrane of breast carcinoma cells. PMID:19176383

  1. Hyaluronan-induced masking of ErbB2 and CD44-enhanced trastuzumab internalisation in trastuzumab resistant breast cancer.

    Pályi-Krekk, Zsuzsanna; Barok, Márk; Isola, Jorma; Tammi, Markku; Szöllosi, János; Nagy, Peter

    2007-11-01

    Although trastuzumab, a recombinant humanised anti-ErbB2 antibody, is widely used in the treatment of breast cancer, neither its mechanism of action, nor the factors leading to resistance are fully understood. We have previously shown that antibody-dependent cellular cytotoxicity is pivotal in the in vivo effect of trastuzumab against JIMT-1, a cell line showing in vitro resistance to the antibody, and suggested that masking of the trastuzumab-binding epitope by MUC-4, a cell surface mucin, took place. Here, we further explored the role of masking of ErbB2 in connection with CD44 expression and synthesis of its ligand, hyaluronan. We show that high expression of CD44 observed in JIMT-1 cells correlates with ErbB2 downregulation in vivo, while siRNA-mediated inhibition of CD44 expression leads to decreased rate of trastuzumab internalisation and low cell proliferation in vitro. An inhibitor of hyaluronan synthesis, 4-methylumbelliferon (4-MU) significantly reduced the hyaluronan level of JIMT-1 cells both in vivo and in vitro leading to enhanced binding of trastuzumab to ErbB2 and increased ErbB2 down-regulation. Furthermore, the inhibitory effect of trastuzumab on the growth of JIMT-1 xenografts was significantly increased by 4-MU treatment. Our results point to the importance of the CD44-hyaluronan pathway in the escape of tumour cells from receptor-oriented therapy.

  2. CD44 and Bak expression in IL-6 or TNF-alpha gene knockout mice after whole lung irradiation

    Sakai, Minako; Iwakawa, Mayumi; Ohta, Toshie; Tsujii, Hirohiko; Imai, Takashi; Iwakura, Yoichiro

    2008-01-01

    To understand the molecular mechanisms that underlie radiation pneumonitis, we examined whether knockout of the tumor necrosis factor (TNF) or the interleukin (IL)-6 gene could give mice an inherent resistance to radiation in the acute phase of alveolar damage after thoracic irradiation. The temporal expression of inflammation (CD44) and apoptosis (Bak) markers in lung after thoracic irradiation was measured to determine the degree of alveolar damage. At 4 weeks post-irradiation (10 Gy), small inflammatory foci were observed in all mice, but there were no obvious histological differences between control (C57BL/6JSlc), TNF-alpha knockout (TNF KO), and IL-6 knockout (IL-6 KO) mice. However, immunohistochemical analysis of CD44 and Bak expression over a time course of 2 weeks highlighted significant differences between the three groups. C57BL/6JSlc and TNF KO mice had increased numbers of both CD44-positive and Bak-positive cells after irradiation, while the IL-6 KO mice showed stable levels of CD44 and Bak. In conclusion, the radioresistant status of IL-6 KO mice in the acute phase of alveolar damage after irradiation suggested an important role for IL-6 in radiation pneumonitis. (author)

  3. CD44-deficiency attenuates the immunologic responses to LPS and delays the onset of endotoxic shock-induced renal inflammation and dysfunction.

    Elena Rampanelli

    Full Text Available Acute kidney injury (AKI is a common complication during systemic inflammatory response syndrome (SIRS, a potentially deadly clinical condition characterized by whole-body inflammatory state and organ dysfunction. CD44 is a ubiquitously expressed cell-surface transmembrane receptor with multiple functions in inflammatory processes, including sterile renal inflammation. The present study aimed to assess the role of CD44 in endotoxic shock-induced kidney inflammation and dysfunction by using CD44 KO and WT mice exposed intraperitoneally to LPS for 2, 4, and 24 hours . Upon LPS administration, CD44 expression in WT kidneys was augmented at all time-points. At 2 and 4 hours, CD44 KO animals showed a preserved renal function in comparison to WT mice. In absence of CD44, the pro-inflammatory cytokine levels in plasma and kidneys were lower, while renal expression of the anti-inflammatory cytokine IL-10 was higher. The cytokine levels were associated with decreased leukocyte influx and endothelial activation in CD44 KO kidneys. Furthermore, in vitro assays demonstrated a role of CD44 in enhancing macrophage cytokine responses to LPS and leukocyte migration. In conclusion, our study demonstrates that lack of CD44 impairs the early pro-inflammatory cytokine response to LPS, diminishes leukocyte migration/chemotaxis and endothelial activation, hence, delays endotoxic shock-induced AKI.

  4. A novel mechanism of regulating breast cancer cell migration via palmitoylation-dependent alterations in the lipid raft affiliation of CD44.

    Babina, Irina S; McSherry, Elaine A; Donatello, Simona; Hill, Arnold D K; Hopkins, Ann M

    2014-02-10

    Most breast cancer-related deaths result from metastasis, a process involving dynamic regulation of tumour cell adhesion and migration. The adhesion protein CD44, a key regulator of cell migration, is enriched in cholesterol-enriched membrane microdomains termed lipid rafts. We recently reported that raft affiliation of CD44 negatively regulates interactions with its migratory binding partner ezrin. Since raft affiliation is regulated by post-translational modifications including palmitoylation, we sought to establish the contribution of CD44 palmitoylation and lipid raft affiliation to cell migration. Recovery of CD44 and its binding partners from raft versus non-raft membrane microdomains was profiled in non-migrating and migrating breast cancer cell lines. Site-directed mutagenesis was used to introduce single or double point mutations into both CD44 palmitoylation sites (Cys286 and Cys295), whereupon the implications for lipid raft recovery, phenotype, ezrin co-precipitation and migratory behaviour was assessed. Finally CD44 palmitoylation status and lipid raft affiliation was assessed in primary cultures from a small panel of breast cancer patients. CD44 raft affiliation was increased during migration of non-invasive breast cell lines, but decreased during migration of highly-invasive breast cells. The latter was paralleled by increased CD44 recovery in non-raft fractions, and exclusive non-raft recovery of its binding partners. Point mutation of CD44 palmitoylation sites reduced CD44 raft affiliation in invasive MDA-MB-231 cells, increased CD44-ezrin co-precipitation and accordingly enhanced cell migration. Expression of palmitoylation-impaired (raft-excluded) CD44 mutants in non-invasive MCF-10a cells was sufficient to reversibly induce the phenotypic appearance of epithelial-to-mesenchymal transition and to increase cell motility. Interestingly, cell migration was associated with temporal reductions in CD44 palmitoylation in wild-type breast cells. Finally

  5. Curcumin induced nanoscale CD44 molecular redistribution and antigen-antibody interaction on HepG2 cell surface

    Wang Mu; Ruan Yuxia; Xing Xiaobo; Chen Qian; Peng, Yuan; Cai Jiye

    2011-01-01

    Graphical abstract: Highlights: → In this study, we investigate the changes of CD44 expression and distribution on HepG2 cells after curcumin treatment. → We find curcumin is able to change the morphology and ultrastructure of HepG2 cells. → Curcumin can reduce the expression of CD44 molecules and induce the nanoscale molecular redistribution on cell surface. → The binding force between CD44-modified AFM tip and the HepG2 cell surface decreases after curcumin-treatment. - Abstract: The cell surface glycoprotein CD44 was implicated in the progression, metastasis and apoptosis of certain human tumors. In this study, we used atomic force microscope (AFM) to monitor the effect of curcumin on human hepatocellular carcinoma (HepG2) cell surface nanoscale structure. High-resolution imaging revealed that cell morphology and ultrastructure changed a lot after being treated with curcumin. The membrane average roughness increased (10.88 ± 4.62 nm to 129.70 ± 43.72 nm) and the expression of CD44 decreased (99.79 ± 0.16% to 75.14 ± 8.37%). Laser scanning confocal microscope (LSCM) imaging showed that CD44 molecules were located on the cell membrane. The florescence intensity in control group was weaker than that in curcumin treated cells. Most of the binding forces between CD44 antibodies and untreated HepG2 cell membrane were around 120-220 pN. After being incubated with curcumin, the major forces focused on 70-150 pN (10 μM curcumin-treated) and 50-120 pN (20 μM curcumin-treated). These results suggested that, as result of nanoscale molecular redistribution, changes of the cell surface were in response to external treatment of curcumin. The combination of AFM and LSCM could be a powerful method to detect the distribution of cell surface molecules and interactions between molecules and their ligands.

  6. Immunohistochemical expression of CD44s in human neuroblastic tumors: Moroccan experience and highlights on current data

    2013-01-01

    Background Peripheral neuroblastic tumors (pNTs), including neuroblastoma (NB), ganglioneuroblastoma (GNB) and ganglioneuroma (GN), are extremely heterogeneous pediatric tumors responsible for 15 % of childhood cancer death. The aim of the study was to evaluate the expression of CD44s (‘s’: standard form) cell adhesion molecule by comparison with other specific prognostic markers. Methods An immunohistochemical profile of 32 formalin-fixed paraffin-embedded pNTs tissues, diagnosed between January 2007 and December 2010, was carried out. Results Our results have demonstrated the association of CD44s negative pNTs cells to lack of differentiation and tumour progression. A significant association between absence of CD44s expression and metastasis in human pNTs has been reported. We also found that expression of CD44s defines subgroups of patients without MYCN amplification as evidenced by its association with low INSS stages, absence of metastasis and favorable Shimada histology. Discussion These findings support the thesis of the role of CD44s glycoprotein in the invasive growth potential of neoplastic cells and suggest that its expression could be taken into consideration in the therapeutic approaches targeting metastases. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1034403150888863 Résumé Introduction les tumeurs neuroblastiques périphériques (TNPs), comprenant le neuroblastome (NB), le ganglioneuroblastome (GNB) et le ganglioneurome (GN), sont des tumeurs pédiatriques extrêmement hétérogènes responsables de 15% des décès par cancer chez les enfants. Le but de cette étude était d’évaluer l’expression de la molécule d’adhésion cellulaire CD44s (‘s’: pour standard) par rapport à d’autres facteurs pronostiques spécifiques. Méthodes Un profil immunohistochimique de 32 TNPs fixées au formol et incluses en paraffine, diagnostiquées entre Janvier 2007 et D

  7. Economic evaluation of occupational safety preventive measures in a hospital.

    Ramos, Delfina G; Arezes, Pedro M; Afonso, Paulo

    2015-01-01

    When an organization performs an integrated analysis of risks through its Occupational Health and Safety Management System, several steps are suggested to address the implications of the identified risks. Namely, the organization should make a detailed analysis of the monetary impact for the organization of each of the preventive measures considered. However, it is also important to perform an analysis of the impact of each measure on society (externalities). The aim of this paper is to present a case study related to the application of the proposed economic evaluation methodology. An analysis of the work accidents in a hospital has been made. Three of the major types of accidents have been selected: needle stings, falls and excessive strain. Following the risk assessment, some preventive measures have been designed. Subsequently, the Benefit/Cost ratio (B/C) of these measures has been calculated, both in financial terms (from the organization's perspective) and in economic terms (including the benefits for the worker and for the Society). While the financial ratio is only advantageous in some cases, when the externalities are taken into account, the B/C ratio increases significantly. It is important to consider external benefits to make decisions concerning the implementation of preventive measures in Occupational Health and Safety projects.

  8. Overexpression of CD44 accompanies acquired tamoxifen resistance in MCF7 cells and augments their sensitivity to the stromal factors, heregulin and hyaluronan

    Hiscox Stephen

    2012-10-01

    Full Text Available Abstract Background Acquired resistance to endocrine therapy in breast cancer is a significant problem with relapse being associated with local and/or regional recurrence and frequent distant metastases. Breast cancer cell models reveal that endocrine resistance is accompanied by a gain in aggressive behaviour driven in part through altered growth factor receptor signalling, particularly involving erbB family receptors. Recently we identified that CD44, a transmembrane cell adhesion receptor known to interact with growth factor receptors, is upregulated in tamoxifen-resistant (TamR MCF7 breast cancer cells. The purpose of this study was to explore the consequences of CD44 upregulation in an MCF7 cell model of acquired tamoxifen resistance, specifically with respect to the hypothesis that CD44 may influence erbB activity to promote an adverse phenotype. Methods CD44 expression in MCF7 and TamR cells was assessed by RT-PCR, Western blotting and immunocytochemistry. Immunofluorescence and immunoprecipitation studies revealed CD44-erbB associations. TamR cells (± siRNA-mediated CD44 suppression or MCF7 cells (± transfection with the CD44 gene were treated with the CD44 ligand, hyaluronon (HA, or heregulin and their in vitro growth (MTT, migration (Boyden chamber and wound healing and invasion (Matrigel transwell migration determined. erbB signalling was assessed using Western blotting. The effect of HA on erbB family dimerisation in TamR cells was determined by immunoprecipitation in the presence or absence of CD44 siRNA. Results TamR cells overexpressed CD44 where it was seen to associate with erbB2 at the cell surface. siRNA-mediated suppression of CD44 in TamR cells significantly attenuated their response to heregulin, inhibiting heregulin-induced cell migration and invasion. Furthermore, TamR cells exhibited enhanced sensitivity to HA, with HA treatment resulting in modulation of erbB dimerisation, ligand-independent activation of erbB2

  9. Suppression of human breast tumors in NOD/SCID mice by CD44 shRNA gene therapy combined with doxorubicin treatment

    Pham PV

    2012-05-01

    Full Text Available Phuc Van Pham1, Ngoc Bich Vu1, Thuy Thanh Duong1, Tam Thanh Nguyen1, Nhung Hai Truong1, Nhan Lu Chinh Phan1, Tue Gia Vuong1, Viet Quoc Pham1, Hoang Minh Nguyen1, Kha The Nguyen1, Nhung Thi Nguyen1, Khue Gia Nguyen1, Lam Tan Khat1, Dong Van Le2, Kiet Dinh Truong1, Ngoc Kim Phan11Laboratory of Stem Cell Research and Application, University of Science, Vietnam National University, HCM City, 2Military Medical University, Ha Noi, VietnamBackground: Breast cancer stem cells with a CD44+CD24- phenotype are the origin of breast tumors. Strong CD44 expression in this population indicates its important role in maintaining the stem cell phenotype. Previous studies show that CD44 down-regulation causes CD44+CD24- breast cancer stem cells to differentiate into non-stem cells that are sensitive to antitumor drugs and lose many characteristics of the original cells. In this study, we determined tumor suppression in non-obese severe combined immunodeficiency mice using CD44 shRNA therapy combined with doxorubicin treatment.Methods: Tumor-bearing non-obese severe combined immunodeficiency mice were established by injection of CD44+CD24- cells. To track CD44+CD24- cells, green fluorescence protein was stably transduced using a lentiviral vector prior to injection into mice. The amount of CD44 shRNA lentiviral vector used for transduction was based on CD44 down-regulation by in vitro CD44 shRNA transduction. Mice were treated with direct injection of CD44 shRNA lentiviral vector into tumors followed by doxorubicin administration after 48 hours. The effect was evaluated by changes in the size and weight of tumors compared with that of the control.Results: The combination of CD44 down-regulation and doxorubicin strongly suppressed tumor growth with significant differences in tumor sizes and weights compared with that of CD44 down-regulation or doxorubicin treatment alone. In the combination of CD44 down-regulation and doxorubicin group, the tumor weight was

  10. Overexpression of CD44 accompanies acquired tamoxifen resistance in MCF7 cells and augments their sensitivity to the stromal factors, heregulin and hyaluronan

    Hiscox, Stephen; Gee, Julia; Baruha, Bedanta; Smith, Chris; Bellerby, Rebecca; Goddard, Lindy; Jordan, Nicola; Poghosyan, Zaruhi; Nicholson, Robert I; Barrett-Lee, Peter

    2012-01-01

    Acquired resistance to endocrine therapy in breast cancer is a significant problem with relapse being associated with local and/or regional recurrence and frequent distant metastases. Breast cancer cell models reveal that endocrine resistance is accompanied by a gain in aggressive behaviour driven in part through altered growth factor receptor signalling, particularly involving erbB family receptors. Recently we identified that CD44, a transmembrane cell adhesion receptor known to interact with growth factor receptors, is upregulated in tamoxifen-resistant (TamR) MCF7 breast cancer cells. The purpose of this study was to explore the consequences of CD44 upregulation in an MCF7 cell model of acquired tamoxifen resistance, specifically with respect to the hypothesis that CD44 may influence erbB activity to promote an adverse phenotype. CD44 expression in MCF7 and TamR cells was assessed by RT-PCR, Western blotting and immunocytochemistry. Immunofluorescence and immunoprecipitation studies revealed CD44-erbB associations. TamR cells (± siRNA-mediated CD44 suppression) or MCF7 cells (± transfection with the CD44 gene) were treated with the CD44 ligand, hyaluronon (HA), or heregulin and their in vitro growth (MTT), migration (Boyden chamber and wound healing) and invasion (Matrigel transwell migration) determined. erbB signalling was assessed using Western blotting. The effect of HA on erbB family dimerisation in TamR cells was determined by immunoprecipitation in the presence or absence of CD44 siRNA. TamR cells overexpressed CD44 where it was seen to associate with erbB2 at the cell surface. siRNA-mediated suppression of CD44 in TamR cells significantly attenuated their response to heregulin, inhibiting heregulin-induced cell migration and invasion. Furthermore, TamR cells exhibited enhanced sensitivity to HA, with HA treatment resulting in modulation of erbB dimerisation, ligand-independent activation of erbB2 and EGFR and induction of cell migration

  11. Paternal occupation and birth defects: findings from the National Birth Defects Prevention Study.

    Desrosiers, T.A.; Herring, A.H.; Shapira, S.K.; Hooiveld, M.; Luben, T.J.; Herdt-Losavio, M.L.; Lin, S.; Olshan, A.F.

    2012-01-01

    Objectives: Several epidemiological studies have suggested that certain paternal occupations may be associated with an increased prevalence of birth defects in offspring. Using data from the National Birth Defects Prevention Study, the authors investigated the association between paternal occupation

  12. The interaction between aromatase, metalloproteinase 2,9 and cd44 in breast cancer A interação entre aromatase, metalloproteinase 2, 9 e cd44 no câncer de mama

    Fábio Bagnoli

    2010-01-01

    Full Text Available OBJECTIVE: This study intends to verify the expression levels and correlation of aromatase, matrix metalloproteinase 2 (MMP-2, matrix metalloproteinase 9 (MMP-9 and CD44 in ductal carcinoma in situ (DCIS and infiltrating ductal carcinoma (IDC when both are found in the same breast. METHODS: One hundred and ten cases were evaluated by tissue microarray (TMA and immunohistochemically screened with anti-aromatase polyclonal antibodies, anti-MMP-2 monoclonal antibodies, anti-MMP-9 policlonal antibodies and anti-CD44 monoclonal antibodies. RESULTS: Aromatase was expressed in IDC and DCIS in 63 (57.3% and 60 (67% of the cases respectively; MMP-2 was similarly expressed in IDC and DCIS in 15 (13.60% cases; MMP-9 was positively expressed in IDC and DCIS in 83 (75.50% and 82 (74.50% cases, respectively; CD44 was positively expressed in IDC and DCIS in 49 (44.50% and 48 (42.60% of the cases, respectively; all of them were highly correlated (pOBJETIVO: O objetivo desse estudo é verificar as expressões e correlações da aromatase, metalloproteinase 2 da matriz (MMP2, metalloproteinase 9 da matriz (MMP-9 e CD44 no carcinoma ductal in situ (CDIS e carcinoma ductal infiltrativo (CDI quando ambos estão presentes simultaneamente na mesma mama. MÉTODOS: Foram avaliados 110 casos pelo método de tissue microarray (TMA e através da utilização de anticorpos policlonais antiaromatase, anticorpos monoclonais anti-MMP-2, anticorpos policlonais anti-MMP-9 e anticorpos monoclonais anti-CD44. RESULTADOS: A aromatase estava expressa de forma positiva no CDI e CDIS em 63 (57,3% e 60 (67% casos, respectivamente. A expressão de MMP-2 estava expressa de forma positiva em 15 (13,6% casos tanto no CDI, quanto no CDIS. A expressão da MMP-9 estava expressa de forma positiva em 83 (75,5% e 82 (74,5% casos de CDI e CDIS, respectivamente. A expressão de CD44 estava expressa de forma positiva em 49 (44,5% e 48 (42,6% casos de CDI e CDIS, respectivamente. Todos eles

  13. Unveiling the role of PAK2 in CD44 mediated inhibition of proliferation, differentiation and apoptosis in AML cells

    Aldehaiman, Mansour M.

    2018-04-01

    Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the accumulation of immature nonfunctional highly proliferative hematopoietic cells in the blood, due to a blockage in myeloid differentiation at various stages. Since the success of the differentiation agent, All-trans retinoic acid (ATRA), in the treatment of acute promyelocytic leukemia (APL), much effort has gone into trying to find agents that are able to differentiate AML cells and specifically the leukemic stem cell (LSC). CD44 is a cell surface receptor that is over-expressed on AML cells. When bound to anti-CD44 monoclonal antibodies (mAbs), this differentiation block is relieved in AML cells and their proliferation is reduced. The molecular mechanisms that AML cells undergo to achieve this reversal of their apparent phenotype is not fully understood. To this end, we designed a study using quantitative phosphoproteomics approaches aimed at identifying differences in phosphorylation found on proteins involved in signaling pathways post-treatment with CD44-mAbs. The Rho family of GTPases emerged as one of the most transformed pathways following the treatment with CD44-mAbs. The P21 activated kinase 2(PAK2), a target of the Rho family of GTPases, was found to be differentially phosphorylated in AML cells post-treatment with CD44-mAbs. This protein has been found to possess a role similar to that of a switch that determines whether the cell survives or undergoes apoptosis. Beyond confirming these results by various biochemical approaches, our study aimed to determine the effect of knock down of PAK2 on AML cell proliferation and differentiation. In addition, over-expression of PAK2 mutants using plasmid cloning was also explored to fully understand how levels of PAK2 as well as the alteration of specific phospohorylation sites could alter AML cell responses to CD44-mAbs. Results from this study will be important in determining whether PAK2 could be used as a potential therapeutic target

  14. A novel CD44-binding peptide from the pro-matrix metalloproteinase-9 hemopexin domain impairs adhesion and migration of chronic lymphocytic leukemia (CLL) cells.

    Ugarte-Berzal, Estefanía; Bailón, Elvira; Amigo-Jiménez, Irene; Albar, Juan Pablo; García-Marco, José A; García-Pardo, Angeles

    2014-05-30

    (pro)MMP-9 binds to CLL cells through the PEX9 domain and contributes to CLL progression. To biochemically characterize this interaction and identify potential therapeutic targets, we prepared GST-PEX9 forms containing structural blades B1B2 or B3B4. We recently described a sequence in blade B4 (P3 sequence) that bound α4β1 integrin and partially impaired cell adhesion and migration. We have now studied the possible contribution of the B1B2 region to cell interaction with PEX9. CLL cells bound to GST-B1B2 and CD44 was the primary receptor. GST-B1B2 inhibited CLL cell migration as effectively as GST-B3B4. Overlapping synthetic peptides spanning the B1B2 region identified the sequence FDAIAEIGNQLYLFKDGKYW, present in B1 and contained in peptide P6, as the most effective site. P6 inhibited cell adhesion to PEX9 in a dose-dependent manner and with an IC50 value of 90 μM. P6 also inhibited cell adhesion to hyaluronan but had no effect on adhesion to VCAM-1 (α4β1 integrin ligand), confirming its specific interaction with CD44. Spatial localization analyses mapped P6 to the central cavity of PEX9, in close proximity to the previously identified P3 sequence. Both P6 and P3 equally impaired cell adhesion to (pro)MMP-9. Moreover, P6 synergistically cooperated with P3, resulting in complete inhibition of CLL cell binding to PEX9, chemotaxis, and transendothelial migration. Thus, P6 is a novel sequence in PEX9 involved in cell-PEX9/(pro)MMP-9 binding by interacting with CD44. Targeting both sites, P6 and P3, should efficiently prevent (pro)MMP-9 binding to CLL cells and its pathological consequences. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. 76 FR 30366 - Draft Alert Entitled “Preventing Occupational Respiratory Disease From Dampness in Office...

    2011-05-25

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention [Docket Number NIOSH-238] Draft Alert Entitled ``Preventing Occupational Respiratory Disease From Dampness in Office... Institute for Occupational Safety and Health, Centers for Disease Control and Prevention. [FR Doc. 2011...

  16. 75 FR 4406 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel: Occupational...

    2010-01-27

    ... recommendations to the Disease, Disability, and Injury Prevention and Control SEP: Occupational Safety and Health... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel: Occupational Safety and Health Training...

  17. Complete identification of E-selectin ligands on neutrophils reveals distinct functions of PSGL-1, ESL-1, and CD44.

    Hidalgo, Andrés; Peired, Anna J; Wild, Martin; Vestweber, Dietmar; Frenette, Paul S

    2007-04-01

    The selectins and their ligands are required for leukocyte extravasation during inflammation. Several glycoproteins have been suggested to bind to E-selectin in vitro, but the complete identification of its physiological ligands has remained elusive. Here, we showed that E-selectin ligand-1 (ESL-1), P-selectin glycoprotein ligand-1 (PSGL-1), and CD44 encompassed all endothelial-selectin ligand activity on neutrophils by using gene- and RNA-targeted loss of function. PSGL-1 played a major role in the initial leukocyte capture, whereas ESL-1 was critical for converting initial tethers into steady slow rolling. CD44 controlled rolling velocity and mediated E-selectin-dependent redistribution of PSGL-1 and L-selectin to a major pole on slowly rolling leukocytes through p38 signaling. These results suggest distinct and dynamic contributions of these three glycoproteins in selectin-mediated neutrophil adhesion and signaling.

  18. Experimental study on the expression of CD44 and CD54 in liver metastasis of colorectal carcinoma

    Ma Chen; Mao Dabeng; Wang Chengzhong; Guo Yu

    2004-01-01

    Objective: To study the significance of CD44 and CD54 expression in animal models with liver metastasis of colorectal cancer and try to find a stable biological marker for the early diagnosis of liver metastasis of colorectal cancer. Methods: Fourth two nude mice of 4-6 wks were adopted in the study. Thirty-six were used to establish animal models with liver metastasis of colorectal cancer, the rest 6 mice were used as the controls. 36 mice of the experimental group were divided into 6 subgroups, each containing 6 mice, in which low grade colorectal adenocarcinoma cells were injected in the subcapsule of the spleen. On the day 10th, 15th, 20th, 25th, 30th day and at the time of the brink of death, animas in each subgroup were sacrificed by eyeball removal and blood letting. Serum CD44, CD54 and CEA levels of the nude mice were measured by ELISA and the sizes and number of liver metastatic loci were observed and noted. the 6 mice for control were raised in the same cages and were killed on the 30th day, and were compared with that in the experimental group. Results: Through the measurement at different phrases, authors found with the development progression and metastasis of cancer, CD44 and CD54 levels in the animal serum tend to increase gradually and were correlated positively with the growth time, size, and extent metastasis of the cancer. Conclusion: CD44 and CD54 may be early tumor markers for liver metastasis of colorectal cancer

  19. Development and mechanistic insight into enhanced cytotoxic potential of hyaluronic acid conjugated nanoparticles in CD44 overexpressing cancer cells.

    Saneja, Ankit; Nayak, Debasis; Srinivas, M; Kumar, Amit; Khare, Vaibhav; Katoch, Archana; Goswami, Anindya; Vishwakarma, Ram A; Sawant, Sanghapal D; Gupta, Prem N

    2017-01-15

    The overexpression of CD44 in cancer cells reroutes number of oncogenic pathways including the central Pi3K/Akt/NF-kB pathway leading to cancer progression and malignancy. Herein, we developed hyaluronic acid-modified poly(dl-lactic-co-glycolic acid)-poly (ethylene glycol) nanoparticles (PLGA-PEG-HA NPs) for targeted delivery of TTQ (thio-tetrazolyl analog of a clinical candidate, IC87114) to CD44 overexpressing cancer cells. The PLGA-PEG co-polymer was synthesized and characterized by NMR and FTIR. The co-polymer based nanoparticles were prepared by solvent evaporation method and hyaluronic acid (HA) was conjugated on to the nanoparticle surface via EDC/NHS chemistry. The PLGA-PEG-HA NPs had a desirable particle size (AFM). In vitro cytotoxicity and cellular uptake studies demonstrated higher cytotoxicity and enhanced intracellular accumulation of PLGA-PEG-HA NPs compared to PLGA-PEG NPs in high CD44 expressing MiaPaca-2 cells compared to MDA-MB-231 and MCF7 cells. At the molecular level, the PLGA-PEG-HA NPs were found to be inducing premature senescence with increase in senescence associated β-galactosidase activity and senescence specific marker p21 expression through modulation of Pi3K/Akt/NF-kB signaling pathway in MiaPaca-2 cells. These findings collectively indicated that HA-modified nanoparticles might serve as a promising nanocarrier for site-specific drug delivery, and can be explored further to increase the therapeutic efficacy of anticancer drugs via targeting to CD44 over-expressing cancer cells. Copyright © 2016. Published by Elsevier B.V.

  20. Identification of the Molecular Mechanisms Responsible for the Inhibition of Homing of AML Cells Triggered by CD44-Ligation

    Al-Jifri, Ablah

    2011-08-03

    Acute Myeloid Leukemia (AML) is a cancerous disease that is defined by the inability to produce functional and mature blood cells, as well as the uncontrolled proliferation due to failure to undergo apoptosis of abnormal cells. The most common therapy for Leukemia, chemotherapy, has proven only to be partially efficient since it does not target the leukemic stem cells (LSCs) that have a high self-renewal and repopulation capacity and result in remission of the disease. Therefore targeting LSCs will provide more efficient therapy. One way to achieve this would be to inhibit their homing capability to the bone marrow. It has recently been shown that CD44, an adhesive molecule, plays a crucial role in cell trafficking and lodgement of both normal and leukemic stem cells. More importantly anti-CD44 monoclonal antibodies, along with its ability to induce differentiation of leukemic blasts, it inhibits specifically the homing capacity of LSCs to their micro-environmental niches. However, these molecular mechanisms that underlie the inhibition of homing have yet to be determined. To address these questions we conducted in vitro adhesion and blot-rolling assays to analyze the adherence and rolling capacity of these LSCs before and after treatment with anti-CD44 monoclonal antibody (mAb). Since glycosyltransferases play a crucial role in post translational carbohydrate decoration on adhesion molecules, we analyzed the expression (using quantitative PCR) of the different glycosyltransferases expressed in LSC\\'s before and after CD44 ligation (mAb treatment). Furthermore, we analyzed differentiation by flow cytometric analysis of treated and non-treated LSC\\'s. We anticipate that our results will set forth new insights into targeted therapies for AML.

  1. Proteoglycan from salmon nasal cartridge promotes in vitro wound healing of fibroblast monolayers via the CD44 receptor

    Ito, Gen; Kobayashi, Takeshi; Takeda, Yoshie; Sokabe, Masahiro

    2015-01-01

    Highlights: • Proteoglycan from salmon nasal cartridge (SNC-PG) promoted wound healing in fibroblast monolayers. • SNC-PG stimulated both cell proliferation and cell migration. • Interaction between chondroitin sulfate-units and CD44 is responsible for the effect. - Abstract: Proteoglycans (PGs) are involved in various cellular functions including cell growth, adhesion, and differentiation; however, their physiological roles are not fully understood. In this study, we examined the effect of PG purified from salmon nasal cartilage (SNC-PG) on wound closure using tissue-cultured cell monolayers, an in vitro wound-healing assay. The results indicated that SNC-PG significantly promoted wound closure in NIH/3T3 cell monolayers by stimulating both cell proliferation and cell migration. SNC-PG was effective in concentrations from 0.1 to 10 μg/ml, but showed much less effect at higher concentrations (100–1000 μg/ml). The effect of SNC-PG was abolished by chondroitinase ABC, indicating that chondroitin sulfates (CSs), a major component of glycosaminoglycans (GAGs) in SNC-PG, are crucial for the SNC-PG effect. Furthermore, chondroitin 6-sulfate (C-6-S), a major CS of SNC-PG GAGs, could partially reproduce the SNC-PG effect and partially inhibit the binding of SNC-PG to cells, suggesting that SNC-PG exerts its effect through an interaction between the GAGs in SNC-PG and the cell surface. Neutralization by anti-CD44 antibodies or CD44 knockdown abolished SNC-PG binding to the cells and the SNC-PG effect on wound closure. These results suggest that interactions between CS-rich GAG-chains of SNC-PG and CD44 on the cell surface are responsible for the SNC-PG effect on wound closure

  2. Proteoglycan from salmon nasal cartridge promotes in vitro wound healing of fibroblast monolayers via the CD44 receptor

    Ito, Gen; Kobayashi, Takeshi; Takeda, Yoshie [Department of Physiology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550 (Japan); Sokabe, Masahiro, E-mail: msokabe@med.nagoya-u.ac.jp [Department of Physiology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550 (Japan); Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550 (Japan); Mechanobiology Institute Singapore, National University of Singapore, Singapore 117411 (Singapore)

    2015-01-16

    Highlights: • Proteoglycan from salmon nasal cartridge (SNC-PG) promoted wound healing in fibroblast monolayers. • SNC-PG stimulated both cell proliferation and cell migration. • Interaction between chondroitin sulfate-units and CD44 is responsible for the effect. - Abstract: Proteoglycans (PGs) are involved in various cellular functions including cell growth, adhesion, and differentiation; however, their physiological roles are not fully understood. In this study, we examined the effect of PG purified from salmon nasal cartilage (SNC-PG) on wound closure using tissue-cultured cell monolayers, an in vitro wound-healing assay. The results indicated that SNC-PG significantly promoted wound closure in NIH/3T3 cell monolayers by stimulating both cell proliferation and cell migration. SNC-PG was effective in concentrations from 0.1 to 10 μg/ml, but showed much less effect at higher concentrations (100–1000 μg/ml). The effect of SNC-PG was abolished by chondroitinase ABC, indicating that chondroitin sulfates (CSs), a major component of glycosaminoglycans (GAGs) in SNC-PG, are crucial for the SNC-PG effect. Furthermore, chondroitin 6-sulfate (C-6-S), a major CS of SNC-PG GAGs, could partially reproduce the SNC-PG effect and partially inhibit the binding of SNC-PG to cells, suggesting that SNC-PG exerts its effect through an interaction between the GAGs in SNC-PG and the cell surface. Neutralization by anti-CD44 antibodies or CD44 knockdown abolished SNC-PG binding to the cells and the SNC-PG effect on wound closure. These results suggest that interactions between CS-rich GAG-chains of SNC-PG and CD44 on the cell surface are responsible for the SNC-PG effect on wound closure.

  3. CD44 and SSEA-4 positive cells in an oral cancer cell line HSC-4 possess cancer stem-like cell characteristics.

    Noto, Zenko; Yoshida, Toshiko; Okabe, Motonori; Koike, Chika; Fathy, Moustafa; Tsuno, Hiroaki; Tomihara, Kei; Arai, Naoya; Noguchi, Makoto; Nikaido, Toshio

    2013-08-01

    Cancer may be derived from cancer stem-like cells (CSCs), which are tumor-initiating cells that have properties similar to those of stem cells. Identification and isolation of CSCs needs to be improved further. CSCs markers were examined in human oral cancer cell lines by flow cytometry. The stem cell properties of subpopulations expressing different markers were assessed further by in vitro sphere formation assays, expression of stemness genes, drug resistance assays, and the ability to form tumors in nude mice. We demonstrated that CSCs could be isolated by the cell surface markers CD44 and stage-specific embryonic antigen-4 (SSEA-4). CD44+SSEA-4+ cells exhibited cancer stem-like properties, including extensive self-renewal into the bulk of cancer cells. In vivo xenograft experiments indicated that CD44+SSEA-4+ cells exhibit the highest tumorigenic capacity compared with the remaining subpopulations and parental cells. Double-positive cells for CD44 and SSEA-4 exhibited preferential expression of some stemness genes and were more resistant to the anticancer drugs, cisplatin and 5-fluorouracil (5-FU). In addition, cells expressing CD44 and SSEA-4 were detected in all tumor specimens analyzed, while coexpression of CD44 and SSEA-4 was not detectable in normal oral mucosa. Our findings suggest that CD44+SSEA-4+ cells exhibit the characteristics of CSCs in oral squamous cell carcinoma and provide a target for the development of more effective therapies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Challenging the roles of CD44 and lipolysis stimulated lipoprotein receptor in conveying Clostridium perfringens iota toxin cytotoxicity in breast cancer.

    Fagan-Solis, Katerina D; Reaves, Denise K; Rangel, M Cristina; Popoff, Michel R; Stiles, Bradley G; Fleming, Jodie M

    2014-07-02

    Translational exploration of bacterial toxins has come to the forefront of research given their potential as a chemotherapeutic tool. Studies in select tissues have demonstrated that Clostridium perfringens iota toxin binds to CD44 and lipolysis stimulated lipoprotein receptor (LSR) cell-surface proteins. We recently demonstrated that LSR expression correlates with estrogen receptor positive breast cancers and that LSR signaling directs aggressive, tumor-initiating cell behaviors. Herein, we identify the mechanisms of iota toxin cytotoxicity in a tissue-specific, breast cancer model with the ultimate goal of laying the foundation for using iota toxin as a targeted breast cancer therapy. In vitro model systems were used to determine the cytotoxic effect of iota toxin on breast cancer intrinsic subtypes. The use of overexpression and knockdown technologies confirmed the roles of LSR and CD44 in regulating iota toxin endocytosis and induction of cell death. Lastly, cytotoxicity assays were used to demonstrate the effect of iota toxin on a validated set of tamoxifen resistant breast cancer cell lines. Treatment of 14 breast cancer cell lines revealed that LSR+/CD44- lines were highly sensitive, LSR+/CD44+ lines were slightly sensitive, and LSR-/CD44+ lines were resistant to iota cytotoxicity. Reduction in LSR expression resulted in a significant decrease in toxin sensitivity; however, overexpression of CD44 conveyed toxin resistance. CD44 overexpression was correlated with decreased toxin-stimulated lysosome formation and decreased cytosolic levels of iota toxin. These findings indicated that expression of CD44 drives iota toxin resistance through inhibition of endocytosis in breast cancer cells, a role not previously defined for CD44. Moreover, tamoxifen-resistant breast cancer cells exhibited robust expression of LSR and were highly sensitive to iota-induced cytotoxicity. Collectively, these data are the first to show that iota toxin has the potential to be an

  5. In Vitro and In Vivo Prostate Cancer Metastasis and Chemoresistance Can Be Modulated by Expression of either CD44 or CD147

    Hao, Jingli; Madigan, Michele C.; Khatri, Aparajita; Power, Carl A.; Hung, Tzong-Tyng; Beretov, Julia; Chang, Lei; Xiao, Weiwei; Cozzi, Paul J.; Graham, Peter H.; Kearsley, John H.; Li, Yong

    2012-01-01

    CD44 and CD147 are associated with cancer metastasis and progression. Our purpose in the study was to investigate the effects of down-regulation of CD44 or CD147 on the metastatic ability of prostate cancer (CaP) cells, their docetaxel (DTX) responsiveness and potential mechanisms involved in vitro and in vivo. CD44 and CD147 were knocked down (KD) in PC-3M-luc CaP cells using short hairpin RNA (shRNA). Expression of CD44, CD147, MRP2 (multi-drug resistance protein-2) and MCT4 (monocarboxylate tranporter-4) was evaluated using immunofluorescence and Western blotting. The DTX dose-response and proliferation was measured by MTT and colony assays, respectively. The invasive potential was assessed using a matrigel chamber assay. Signal transduction proteins in PI3K/Akt and MAPK/Erk pathways were assessed by Western blotting. An in vivo subcutaneous (s.c.) xenograft model was established to assess CaP tumorigenecity, lymph node metastases and DTX response. Our results indicated that KD of CD44 or CD147 decreased MCT4 and MRP2 expression, reduced CaP proliferation and invasive potential and enhanced DTX sensitivity; and KD of CD44 or CD147 down-regulated p-Akt and p-Erk, the main signal modulators associated with cell growth and survival. In vivo, CD44 or CD147-KD PC-3M-luc xenografts displayed suppressed tumor growth with increased DTX responsiveness compared to control xenografts. Both CD44 and CD147 enhance metastatic capacity and chemoresistance of CaP cells, potentially mediated by activation of the PI3K and MAPK pathways. Selective targeting of CD44/CD147 alone or combined with DTX may limit CaP metastasis and increase chemosensitivity, with promise for future CaP treatment. PMID:22870202

  6. In vitro and in vivo prostate cancer metastasis and chemoresistance can be modulated by expression of either CD44 or CD147.

    Jingli Hao

    Full Text Available CD44 and CD147 are associated with cancer metastasis and progression. Our purpose in the study was to investigate the effects of down-regulation of CD44 or CD147 on the metastatic ability of prostate cancer (CaP cells, their docetaxel (DTX responsiveness and potential mechanisms involved in vitro and in vivo. CD44 and CD147 were knocked down (KD in PC-3M-luc CaP cells using short hairpin RNA (shRNA. Expression of CD44, CD147, MRP2 (multi-drug resistance protein-2 and MCT4 (monocarboxylate tranporter-4 was evaluated using immunofluorescence and Western blotting. The DTX dose-response and proliferation was measured by MTT and colony assays, respectively. The invasive potential was assessed using a matrigel chamber assay. Signal transduction proteins in PI3K/Akt and MAPK/Erk pathways were assessed by Western blotting. An in vivo subcutaneous (s.c. xenograft model was established to assess CaP tumorigenecity, lymph node metastases and DTX response. Our results indicated that KD of CD44 or CD147 decreased MCT4 and MRP2 expression, reduced CaP proliferation and invasive potential and enhanced DTX sensitivity; and KD of CD44 or CD147 down-regulated p-Akt and p-Erk, the main signal modulators associated with cell growth and survival. In vivo, CD44 or CD147-KD PC-3M-luc xenografts displayed suppressed tumor growth with increased DTX responsiveness compared to control xenografts. Both CD44 and CD147 enhance metastatic capacity and chemoresistance of CaP cells, potentially mediated by activation of the PI3K and MAPK pathways. Selective targeting of CD44/CD147 alone or combined with DTX may limit CaP metastasis and increase chemosensitivity, with promise for future CaP treatment.

  7. [Dectection of G3BP and CD44v6 in the tissues of laryngeal squamous cell carcinoma and their clinical significance].

    Luo, Dahu; Lou, Weihua

    2017-07-01

    Objective To study the expressions of RNA-binding Ras-GAP SH3 binding protein (G3BP) and tumor stem cell marker CD44v6 in laryngeal squamous cell carcinoma and their correlations with angiogenesis. Methods We collected the cancer tissues and corresponding paracancerous tissues from 56 patients with laryngeal squamous cell carcinoma. The expressions of G3BP and CD44v6 proteins were detected by Western blotting in cancer tissues and corresponding paracancerous tissues; the expressions of G3BP, CD44v6 and vascular endothelial growth factor A (VEGF-A) were tested by immunohistochemistry. Thereafter, we compared the positive expression rates of G3BP and CD44v6 between in cancer tissues and in normal tissues, analyzed the correlations between the expressions of G3BP, CD44v6 and the laryngeal squamous cell carcinoma features as well as their correlations with microvessel density (MVD) that was determined by FVIIIAg immunohistochemistry. Results Western blotting showed that the expressions of G3BP and CD44v6 proteins in the laryngeal squamous cell carcinoma were higher than those in the paracancerous tissues. Immunohistochemistry showed that compared with the paracancerous tissues, G3BP, CD44v6 and VEGF-A expressions (the positive rates are 58.9%, 53.6%, 46.4%, respectively) were higher in cancer tissues. The positive rates of G3BP and CD44v6 in cancer tissues were related with the clinical stage, recurrence or metastasis, and lymph node metastasis of laryngeal squamous cell carcinoma, but had nothing to do with patients' age and tumor size. Pearson correlation analysis showed the expressions of both G3BP and CD44v6 were positively correlated with VEGF-A (r=0.741, r=0.756). MVD values were significantly higher in the G3BP and CD44v6 positive cases than in paracancerous tissues, but there was no difference in MVD between those without G3BP and CD44v6 positive expressions and the paracancerous tissues. Conclusion The positive expression rates of G3BP and CD44v6 in laryngeal

  8. Evaluation of Occupational Therapy Workshops to Prevent Work-Related Injuries or Illnesses among Vocational Students

    Lecours, Alexandra; Therriault, Pierre-Yves

    2018-01-01

    The few studies aiming to evaluate prevention interventions provided by occupational therapists in health at work were conducted in work settings. However, to intervene in primary prevention, developing occupational therapy interventions with students learning a trade is relevant. The objective is to evaluate workshops designed and set up by…

  9. Novel Hyaluronic Acid Conjugates for Dual Nuclear Imaging and Therapy in CD44-Expressing Tumors in Mice In Vivo

    Dubey, Ravindra Dhar; Klippstein, Rebecca; Wang, Julie Tzu-Wen; Hodgins, Naomi; Mei, Kuo-Ching; Sosabowski, Jane; Hider, Robert C.; Abbate, Vincenzo; Gupta, Prem N.; Al-Jamal, Khuloud T.

    2017-01-01

    Hyaluronic acid, a natural CD44 receptor ligand, has attracted attention in the past years as a macromolecular delivery of anticancer agents to cancer. At the same time, the clinical applications of Gemcitabine (Gem) have been hindered by its short biological half-life, high dose and development of drug resistance. This work reports the synthesis of a hyaluronic acid (HA) conjugate for nuclear imaging, and in vivo Gem delivery to CD44-expressing solid tumors in mice. HA was individually conjugated, via amide coupling, to Gem (HA-Gem), 4'-(aminomethyl)fluorescein hydrochloride (HA-4'-AMF) or tris(hydroxypyridinone) amine (HA-THP) for cancer therapy, in vitro tracking or single photon emission computed tomography/computed tomography (SPECT/CT) imaging, respectively. Gem conjugation to HA was directly confirmed by nuclear magnetic resonance (1H NMR), gel permeation chromatography (GPC) and UV-visible spectrometry, or indirectly by a nucleoside transporter inhibition study. Gem conjugation to HA improved its plasma stability, reduced blood hemolysis and resulted in delayed cytotoxicity in vitro. Uptake inhibition studies in colon CT26 and pancreatic PANC-1 cells, by flow cytometry, revealed that uptake of fluorescent HA conjugate is CD44 receptor and macropinocytosis-dependent. Gamma scintigraphy and SPECT/CT imaging confirmed the relatively prolonged blood circulation profile and uptake in CT26 (1.5 % ID/gm) and PANC-1 (1 % ID/gm) subcutaneous tumors at 24 h after intravenous injection in mice. Four injections of HA-Gem at ~15 mg/kg, over a 28-day period, resulted in significant delay in CT26 tumor growth and prolonged mice survival compared to the free drug. This study reports for the first time dual nuclear imaging and drug delivery (Gem) of HA conjugates to solid tumors in mice. The conjugates show great potential in targeting, imaging and killing of CD44-over expressing cells in vivo. This work is likely to open new avenues for the application of HA

  10. A hyaluronic acid-based hydrogel enabling CD44-mediated chondrocyte binding and gapmer oligonucleotide release for modulation of gene expression in osteoarthritis

    Cai, Yunpeng; López-Ruiz, Elena; Wengel, Jesper

    2017-01-01

    Hyaluronic acid (HA) is an attractive biomaterial for osteoarthritis (OA) treatment due to inherent functional and compatibility properties as an endogenous knee joint component. In this work, we describe a HA-based hydrogel with the dual functionality of increased CD44-dependent chondrocyte......:3) for identifying designs displaying optimal engagement of OA patient-derived CD44-expressing chondrocytes. Correlation was found between cell binding and CD44 expression, with maximal binding exhibited at a HA/chitosan ratio of 7:3, that was 181% higher than CD44-negative MCF-7 cell control cells. Transfection...... agent-free uptake into OA chondrocytes of fluorescent 13-mer DNA oligonucleotides with a flanked locked nucleic acid (LNA) gapmer design, in contrast to naked siRNA, was demonstrated by confocal and flow cytometric analysis. A sustained and complete release over 5days was found with the 7:3 hydrogel...

  11. Menstrual endometrial cells from women with endometriosis demonstrate increased adherence to peritoneal cells and increased expression of CD44 splice variants.

    Griffith, Jason S; Liu, Ya-Guang; Tekmal, Rajeshwar R; Binkley, Peter A; Holden, Alan E C; Schenken, Robert S

    2010-04-01

    We previously demonstrated that adherence of endometrial epithelial (EECs) and stromal cells (ESCs) to peritoneal mesothelial cells (PMCs) is partly regulated by ESC/EEC CD44 interactions with PMC associated hyaluronan. CD44, a transmembrane glycoprotein and major ligand for hyaluronan, has numerous splice variants which may impact hyaluronan binding. Here, we assessed whether ESCs and EECs from women with endometriosis demonstrate increased adherence to PMCs and examined CD44 splice variants' potential role in this process. In vitro study. Academic medical center. Fertility patients with and without endometriosis. Menstrual endometrium was collected from women with and without endometriosis confirmed surgically. The adherence of ESC/EECs to PMCs was measured. The ESC/EEC CD44 splice variants were assessed using dot-blot analysis. The ESCs and EECs from women with endometriosis demonstrated increased adherence to PMCs. The predominant CD44 splice variants expressed by ESCs and EECs from women with and without endometriosis were v3, v6, v7, v8, v9, and v10. The ESCs and EECs from women with endometriosis were more likely to express v6, v7, v8, and v9. Increased eutopic endometrial-PMC adherence and CD44 splice variant expression may contribute to the histogenesis of endometriotic lesions. Elucidation of factors controlling this expression may lead to novel endometriosis therapies. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Evidence Based Prevention of Occupational Slips, Trips and Falls

    Jensen, Olaf Chresten

    2009-01-01

    It is estimated that about one third of the compensated occupational injuries and half of the most serious occupational injuries in merchant seafaring are related to slips, trips and falls (STF)-events. Among the elderly, STF is the risk factor that causes the largest number of inpatient days...

  13. Expression of Monocarboxylate Transporters 1, 2, and 4 in Human Tumours and Their Association with CD147 and CD44

    Céline Pinheiro

    2010-01-01

    Full Text Available Monocarboxylate transporters (MCTs are important cellular pH regulators in cancer cells; however, the value of MCT expression in cancer is still poorly understood. In the present study, we analysed MCT1, MCT2, and MCT4 protein expression in breast, colon, lung, and ovary neoplasms, as well as CD147 and CD44. MCT expression frequency was high and heterogeneous among the different tumours. Comparing with normal tissues, there was an increase in MCT1 and MCT4 expressions in breast carcinoma and a decrease in MCT4 plasma membrane expression in lung cancer. There were associations between CD147 and MCT1 expressions in ovarian cancer as well as between CD147 and MCT4 in both breast and lung cancers. CD44 was only associated with MCT1 plasma membrane expression in lung cancer. An important number of MCT1 positive cases are negative for both chaperones, suggesting that MCT plasma membrane expression in tumours may depend on a yet nonidentified regulatory protein.

  14. Comparison of DNA aneuploidy, chromosome 1 abnormalities, MYCN amplification and CD44 expression as prognostic factors in neuroblastoma.

    Christiansen, H; Sahin, K; Berthold, F; Hero, B; Terpe, H J; Lampert, F

    1995-01-01

    A comparison of the prognostic impact of five molecular variables in a large series was made, including tests of their nonrandom association and multivariate analysis. Molecular data were available for 377 patients and MYCN amplification, cytogenetic chromosome 1p deletion, loss of chromosome 1p heterozygosity, DNA ploidy and CD44 expression were investigated. Their interdependence and influence on event-free survival was tested uni- and multivariately using Pearson's chi 2-test, Kaplan-Meier estimates, log rank tests and the Cox's regression model. MYCN amplification was present in 18% (58/322) of cases and predicted poorer prognosis in localised (P < 0.001), metastatic (P = 0.002) and even 4S (P = 0.040) disease. CD44 expression was found in 86% (127/148) of cases, and was a marker for favourable outcome in patients with neuroblastoma stages 1-3 (P = 0.003) and 4 (P = 0.017). Chromosome 1p deletion was cytogenetically detected in 51% (28/55), and indicated reduced event-free survival in localised neuroblastoma (P = 0.020). DNA ploidy and loss of heterozygosity on chromosome 1p were of less prognostic value. Most factors of prognostic significance were associated with each other. By multivariate analysis, MYCN was selected as the only relevant factor. Risk estimation of high discriminating power is, therefore, possible for patients with localised and metastatic neuroblastoma using stage and MYCN.

  15. Activation of VCAM-1 and Its Associated Molecule CD44 Leads to Increased Malignant Potential of Breast Cancer Cells

    Pei-Chen Wang

    2014-02-01

    Full Text Available VCAM-1 (CD106, a transmembrane glycoprotein, was first reported to play an important role in leukocyte adhesion, leukocyte transendothelial migration and cell activation by binding to integrin VLA-1 (α4β1. In the present study, we observed that VCAM-1 expression can be induced in many breast cancer epithelial cells by cytokine stimulation in vitro and its up-regulation directly correlated with advanced clinical breast cancer stage. We found that VCAM-1 over-expression in the NMuMG breast epithelial cells controls the epithelial and mesenchymal transition (EMT program to increase cell motility rates and promote chemoresistance to doxorubicin and cisplatin in vitro. Conversely, in the established MDAMB231 metastatic breast cancer cell line, we confirmed that knockdown of endogenous VCAM-1 expression reduced cell proliferation and inhibited TGFβ1 or IL-6 mediated cell migration, and increased chemosensitivity. Furthermore, we demonstrated that knockdown of endogenous VCAM-1 expression in MDAMB231 cells reduced tumor formation in a SCID xenograft mouse model. Signaling studies showed that VCAM-1 physically associates with CD44 and enhances CD44 and ABCG2 expression. Our findings uncover the possible mechanism of VCAM-1 activation facilitating breast cancer progression, and suggest that targeting VCAM-1 is an attractive strategy for therapeutic intervention.

  16. Design and development of hyaluronan-functionalized polybenzofulvene nanoparticles as CD44 receptor mediated drug delivery system

    Licciardi, Mariano; Scialabba, Cinzia; Giammona, Gaetano; Paolino, Marco; Razzano, Vincenzo; Grisci, Giorgio; Giuliani, Germano; Makovec, Francesco; Cappelli, Andrea

    2017-06-01

    A tri-component polymer brush (TCPB ), composed of a polybenzofulvene copolymer bearing low molecular weight hyaluronic acid (HA) on the surface of its cylindrical brush-like backbone and oligo-PEG fractions, was employed in the preparation of 350 nm nanostructured drug delivery systems capable of delivering the anticancer drug doxorubicin. The obtained drug delivery systems were characterized on the basis of drug loading and release, dimensions and zeta potential, morphology and in vitro cell activity, and uptake on three different human cell lines, namely the bronchial epithelial 16HBE, the breast adenocarcinoma MCF-7, and the colon cancer HCT116 cells. Finally, the ability of doxorubicin-loaded TCPB nanoparticles (DOXO-TCPB) to be internalized into cancer cells by CD44 receptor mediated uptake was assessed by means of uptake studies in HCT cells. These data were supported by anti-CD44-FITC staining assay. The proposed TCPB nanostructured drug delivery systems have many potential applications in nanomedicine, including cancer targeted drug delivery.

  17. MET Signaling Mediates Intestinal Crypt-Villus Development, Regeneration, and Adenoma Formation and Is Promoted by Stem Cell CD44 Isoforms.

    Joosten, Sander P J; Zeilstra, Jurrit; van Andel, Harmen; Mijnals, R Clinton; Zaunbrecher, Joost; Duivenvoorden, Annet A M; van de Wetering, Marc; Clevers, Hans; Spaargaren, Marcel; Pals, Steven T

    2017-10-01

    Resistance of metastatic human colorectal cancer cells to drugs that block epidermal growth factor (EGF) receptor signaling could be caused by aberrant activity of other receptor tyrosine kinases, activating overlapping signaling pathways. One of these receptor tyrosine kinases could be MET, the receptor for hepatocyte growth factor (HGF). We investigated how MET signaling, and its interaction with CD44 (a putative MET coreceptor regulated by Wnt signaling and highly expressed by intestinal stem cells [ISCs] and adenomas) affects intestinal homeostasis, regeneration, and adenoma formation in mini-gut organoids and mice. We established organoid cultures from ISCs stimulated with HGF or EGF and assessed intestinal differentiation by immunohistochemistry. Mice with total epithelial disruption of MET (Ah Cre /Met fl/fl /LacZ) or ISC-specific disruption of MET (Lgr5 Creert2 /Met fl/fl /LacZ) and control mice (Ah Cre /Met +/+ /LacZ, Lgr5 Creert2 /Met +/+ /LacZ) were exposed to 10 Gy total body irradiation; intestinal tissues were collected, and homeostasis and regeneration were assessed by immunohistochemistry. We investigated adenoma organoid expansion stimulated by HGF or EGF using adenomas derived from Lgr5 Creert2 /Met fl/fl /Apc fl/fl and Lgr5 Creert2 /Met +/+ /Apc fl/fl mice. The same mice were evaluated for adenoma prevalence and size. We also quantified adenomas in Ah Cre /Met fl/fl /Apc fl/+ mice compared with Ah Cre /Met +/+ /Apc fl/+ control mice. We studied expansion of organoids generated from crypts and adenomas, stimulated by HGF or EGF, that were derived from mice expressing different CD44 splice variants (Cd44 +/+ , Cd44 -/- , Cd44 s/s , or Cd44 v4-10/v4-10 mice). Crypts incubated with EGF or HGF expanded into self-organizing mini-guts with similar levels of efficacy and contained all differentiated cell lineages. MET-deficient mice did not have defects in intestinal homeostasis. Total body irradiation reduced numbers of proliferating crypts in Ah Cre

  18. Process Evaluation of an Occupational Health Guideline Aimed at Preventing Weight Gain Among Employees

    Verweij, Lisanne M.; Proper, Karin I.; Hulshof, Carel T. J.; van Mechelen, Willem

    2011-01-01

    Objective: To evuate the process of an occupational health guideline aimed at preventing weight gain. Methods: Quantitative data on seven process items were assessed and linked to effects on employees' waist circumference and body weight at 6 months. Results: Occupational physicians (n = 7)

  19. Occupational skin diseases and prevention among sanitation workers in China.

    Yan, Yuehua; Wang, Xinggang; Wu, Jianbo; Xu, Li

    2015-09-01

    Little research has been focused on the health status or the occupational protection awareness of sanitation workers. The policy recommendations on the occupational safety and health of sanitation workers based on the scientific research are also insufficient in developing countries like China. To study the incidence of dermatoses and the relevance with occupational exposure, protection awareness and protective measures among sanitation workers for better management and protection of the sanitation workers. 273 sanitation workers and 113 administrative staff from 11 streets of Wuhan were recruited. Dermatological problems were evaluated and recorded by physical examination. Occupational exposure, protection awareness, the use of protective equipments and personal history of skin disease were assessed by questionnaires. Compared with administrative staff, sanitation workers had much more occupational dermatological problems and had a much higher rate of harmful ultraviolet ray exposure. Young sanitation workers were more aware of occupational self-protection and a relatively higher rate of them using protective equipments compared with old ones. Exposure to multiple health hazards and the poor use of protective equipments are related to skin diseases in sanitation workers. Prejob training of self-protection and the use of protective equipments are recommended.

  20. Overexpression of molecular chaperons GRP78 and GRP94 in CD44(hi)/CD24(lo) breast cancer stem cells.

    Nami, Babak; Ghasemi-Dizgah, Armin; Vaseghi, Akbar

    2016-01-01

    Breast cancer stem cell with CD44(hi)/CD24(lo) phonotype is described having stem cell properties and represented as the main driving factor in breast cancer initiation, growth, metastasis and low response to anti-cancer agents. Glucoseregulated proteins (GRPs) are heat shock protein family chaperons that are charged with regulation of protein machinery and modulation of endoplasmic reticulum homeostasis whose important roles in stem cell development and invasion of various cancers have been demonstrated. Here, we investigated the expression levels of GRP78 and GRP94 in CD44(hi)/CD24(lo) phenotype breast cancer stem cells (BCSCs). MCF7, T-47D and MDA-MB-231 breast cancer cell lines were used. CD44(hi)/CD24(lo) phenotype cell population were analyzed and sorted by fluorescence-activated cell sorting (FACS). Transcriptional and translational expression of GRP78 and GRP94 were investigated by western blotting and quantitative real time PCR. RESULTS showed different proportion of CD44(hi)/CD24(lo) phenotype cell population in their original bulk cells. The ranking of the cell lines in terms of CD44(hi)/CD24(lo) phenotype cell population was as MCF7hi)/CD24(lo) phenotype cells exhibited higher mRNA and protein expression level of GRP78 and GRP94 compared to their original bulk cells. Our results show a relationship between overexpression of GRP78 and GRP94 and exhibiting CD44hi/CD24lo phenotype in breast cancer cells. We conclude that upregulation of GRPs may be an important factor in the emergence of CD44hi/CD24lo phenotype BCSCs features.

  1. Absent/weak CD44 intensity and positive human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma indicates a very high survival

    Näsman, Anders; Nordfors, Cecilia; Grün, Nathalie; Munck-Wikland, Eva; Ramqvist, Torbjörn; Marklund, Linda; Lindquist, David; Dalianis, Tina

    2013-01-01

    Patients with human papillomavirus DNA positive (HPV DNA +) oropharyngeal squamous cell carcinoma (OSCC) have better clinical outcome than those with HPV DNA negative (HPV DNA −) OSCC upon intensive oncological treatment. All HPV DNA + OSCC patients may not require intensive treatment, however, but before potentially deintensifying treatment, additional predictive markers are needed. Here, we examined HPV, p16 INK4a , and CD44 in OSCC in correlation to clinical outcome. Pretreatment tumors from 290 OSCC patients, the majority not receiving chemotherapy, were analyzed for HPV DNA by Luminex and for p16 INK4a and CD44 by immunohistochemistry. 225/290 (78%) tumors were HPV DNA + and 211/290 (73%) overexpressed p16 INK4a , which correlated to presence of HPV (P < 0.0001). Presence of HPV DNA, absent/weak CD44 intensity staining correlated to favorable 3-year disease-free survival (DFS) and overall survival (OS) by univariate and multivariate analysis, and likewise for p16 INK4a by univariate analysis. Upon stratification for HPV, HPV DNA + OSCC with absent/weak CD44 intensity presented the significantly best 3-year DFS and OS, with >95% 3-year DFS and OS. Furthermore, in HPV DNA + OSCC, p16 INK4a + overexpression correlated to a favorable 3-year OS. In conclusion, patients with HPV DNA + and absent/weak CD44 intensity OSCC presented the best survival and this marker combination could possibly be used for selecting patients for tailored deintensified treatment in prospective clinical trials. Absence of/weak CD44 or presence of human papillomavirus (HPV) DNA was shown as a favorable prognostic factors in tonsillar and tongue base cancer. Moreover, patients with the combination of absence of/weak CD44 and presence of HPV DNA presented a very favorable outcome. Therefore, we suggest that this marker combination could potentially be used to single out patients with a high survival that could benefit from a de-escalated oncological treatment

  2. A mesenchymal-like phenotype and expression of CD44 predict lack of apoptotic response to sorafenib in liver tumor cells.

    Fernando, Joan; Malfettone, Andrea; Cepeda, Edgar B; Vilarrasa-Blasi, Roser; Bertran, Esther; Raimondi, Giulia; Fabra, Àngels; Alvarez-Barrientos, Alberto; Fernández-Salguero, Pedro; Fernández-Rodríguez, Conrado M; Giannelli, Gianluigi; Sancho, Patricia; Fabregat, Isabel

    2015-02-15

    The multikinase inhibitor sorafenib is the only effective drug in advanced cases of hepatocellular carcinoma (HCC). However, response differs among patients and effectiveness only implies a delay. We have recently described that sorafenib sensitizes HCC cells to apoptosis. In this work, we have explored the response to this drug of six different liver tumor cell lines to define a phenotypic signature that may predict lack of response in HCC patients. Results have indicated that liver tumor cells that show a mesenchymal-like phenotype, resistance to the suppressor effects of transforming growth factor beta (TGF-β) and high expression of the stem cell marker CD44 were refractory to sorafenib-induced cell death in in vitro studies, which correlated with lack of response to sorafenib in nude mice xenograft models of human HCC. In contrast, epithelial-like cells expressing the stem-related proteins EpCAM or CD133 were sensitive to sorafenib-induced apoptosis both in vitro and in vivo. A cross-talk between the TGF-β pathway and the acquisition of a mesenchymal-like phenotype with up-regulation of CD44 expression was found in the HCC cell lines. Targeted CD44 knock-down in the mesenchymal-like cells indicated that CD44 plays an active role in protecting HCC cells from sorafenib-induced apoptosis. However, CD44 effect requires a TGF-β-induced mesenchymal background, since the only overexpression of CD44 in epithelial-like HCC cells is not sufficient to impair sorafenib-induced cell death. In conclusion, a mesenchymal profile and expression of CD44, linked to activation of the TGF-β pathway, may predict lack of response to sorafenib in HCC patients. © 2014 UICC.

  3. Impact of Expression of CD44, a Cancer Stem Cell Marker, on the Treatment Outcomes of Intensity Modulated Radiation Therapy in Patients With Oropharyngeal Squamous Cell Carcinoma

    Motegi, Atsushi, E-mail: amotegi@east.ncc.go.jp [Division of Radiation Oncology, National Cancer Center Hospital East, Kashiwa, Chiba (Japan); Fujii, Satoshi [Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba (Japan); Zenda, Sadamoto; Arahira, Satoko [Division of Radiation Oncology, National Cancer Center Hospital East, Kashiwa, Chiba (Japan); Tahara, Makoto [Division of Head and Neck Oncology, National Cancer Center Hospital East, Kashiwa, Chiba (Japan); Hayashi, Ryuichi [Division of Head and Neck Surgery, National Cancer Center Hospital East, Kashiwa, Chiba (Japan); Akimoto, Tetsuo [Division of Radiation Oncology, National Cancer Center Hospital East, Kashiwa, Chiba (Japan)

    2016-03-01

    Purpose: To investigate the significance of CD44 protein expression on the treatment outcomes of radiation therapy in patients with oropharyngeal squamous cell carcinoma (OPSCC) with or without p16 protein expression in the tumor tissue. Methods and Materials: We reviewed the medical records of 58 OPSCC patients who had undergone radiation therapy and examined the tumor tissue expressions of CD44 and p16 protein by immunohistochemical staining. The correlations between the expressions of these proteins and the patients' treatment outcomes were analyzed. Results: The data of 58 consecutive OPSCC patients who had undergone definitive intensity modulated radiation therapy were analyzed. The male/female ratio was 55:3, and the median age was 64 years. The clinical stage of the disease was stage II in 7 patients, stage III in 5 patients, stage IVA in 35 patients, and stage IVB in 11 patients. Of the patients, 79% received additional induction and/or concurrent chemotherapy. The median follow-up duration was 34 months. The 3-year overall survival, progression-free survival (PFS) and locoregional control (LRC) rates of all the patients, regardless of the results of immunohistochemistry, were 73%, 64% and 76%, respectively. The PFS and LRC rates in the CD44{sup −} patients (86% and 93%, respectively) were significantly higher than those in the CD44{sup +} patients (57% and 70%, respectively). The PFS and LRC rates in the p16{sup +} patients (83% and 90%, respectively) were significantly higher than those in the p16{sup −} patients (45% and 61%, respectively). Patients who were CD44{sup −}/p16{sup +} showed the best LRC rates, and those who were CD44{sup +}/p16{sup −} showed the worst PFS and LRC rates among all the groups. Conclusions: Profiling of CD44 and p16 protein expressions by immunohistochemical staining is useful for predicting the treatment outcomes in patients with OPSCC undergoing definitive intensity modulated radiation therapy.

  4. Selective regain of egfr gene copies in CD44+/CD24-/low breast cancer cellular model MDA-MB-468

    Agelopoulos, Konstantin; Buerger, Horst; Brandt, Burkhard; Greve, Burkhard; Schmidt, Hartmut; Pospisil, Heike; Kurtz, Stefan; Bartkowiak, Kai; Andreas, Antje; Wieczorek, Marek; Korsching, Eberhard

    2010-01-01

    Increased transcription of oncogenes like the epidermal growth factor receptor (EGFR) is frequently caused by amplification of the whole gene or at least of regulatory sequences. Aim of this study was to pinpoint mechanistic parameters occurring during egfr copy number gains leading to a stable EGFR overexpression and high sensitivity to extracellular signalling. A deeper understanding of those marker events might improve early diagnosis of cancer in suspect lesions, early detection of cancer progression and the prediction of egfr targeted therapies. The basal-like/stemness type breast cancer cell line subpopulation MDA-MB-468 CD44 high /CD24 -/low , carrying high egfr amplifications, was chosen as a model system in this study. Subclones of the heterogeneous cell line expressing low and high EGF receptor densities were isolated by cell sorting. Genomic profiling was carried out for these by means of SNP array profiling, qPCR and FISH. Cell cycle analysis was performed using the BrdU quenching technique. Low and high EGFR expressing MDA-MB-468 CD44 + /CD24 -/low subpopulations separated by cell sorting showed intermediate and high copy numbers of egfr, respectively. However, during cell culture an increase solely for egfr gene copy numbers in the intermediate subpopulation occurred. This shift was based on the formation of new cells which regained egfr gene copies. By two parametric cell cycle analysis clonal effects mediated through growth advantage of cells bearing higher egfr gene copy numbers could most likely be excluded for being the driving force. Subsequently, the detection of a fragile site distal to the egfr gene, sustaining uncapped telomere-less chromosomal ends, the ladder-like structure of the intrachromosomal egfr amplification and a broader range of egfr copy numbers support the assumption that dynamic chromosomal rearrangements, like breakage-fusion-bridge-cycles other than proliferation drive the gain of egfr copies. Progressive genome modulation

  5. Interventions to prevent occupational noise-induced hearing loss.

    Tikka, Christina; Verbeek, Jos H; Kateman, Erik; Morata, Thais C; Dreschler, Wouter A; Ferrite, Silvia

    2017-07-07

    This is the second update of a Cochrane Review originally published in 2009. Millions of workers worldwide are exposed to noise levels that increase their risk of hearing disorders. There is uncertainty about the effectiveness of hearing loss prevention interventions. To assess the effectiveness of non-pharmaceutical interventions for preventing occupational noise exposure or occupational hearing loss compared to no intervention or alternative interventions. We searched the CENTRAL; PubMed; Embase; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; and OSH UPDATE to 3 October 2016. We included randomised controlled trials (RCT), controlled before-after studies (CBA) and interrupted time-series (ITS) of non-clinical interventions under field conditions among workers to prevent or reduce noise exposure and hearing loss. We also collected uncontrolled case studies of engineering controls about the effect on noise exposure. Two authors independently assessed study eligibility and risk of bias and extracted data. We categorised interventions as engineering controls, administrative controls, personal hearing protection devices, and hearing surveillance. We included 29 studies. One study evaluated legislation to reduce noise exposure in a 12-year time-series analysis but there were no controlled studies on engineering controls for noise exposure. Eleven studies with 3725 participants evaluated effects of personal hearing protection devices and 17 studies with 84,028 participants evaluated effects of hearing loss prevention programmes (HLPPs). Effects on noise exposure Engineering interventions following legislationOne ITS study found that new legislation in the mining industry reduced the median personal noise exposure dose in underground coal mining by 27.7 percentage points (95% confidence interval (CI) -36.1 to -19.3 percentage points) immediately after the implementation of stricter legislation. This roughly translates to a 4.5 dB(A) decrease in

  6. Hyaluronic Acid Immobilized Polyacrylamide Nanoparticle Sensors for CD44 Receptor Targeting and pH Measurement in Cells

    Sun, Honghao; Benjaminsen, Rikke Vicki; Almdal, Kristoffer

    2012-01-01

    Our ability to design receptor-targeted nanocarriers aimed at drug release after endocytosis is limited by the current knowledge of intracellular nanoparticle (NP) trafficking. It is not clear if NP size, surface chemistry, and/or targeting of cell surface receptors changes the intracellular fate...... of NPs; i.e., will all NPs enter acidic compartments and eventually end up in lysosomes or are there escape mechanisms or receptor-specific signaling that can be induced to change the cellular processing of an internalized NP? To give new insight into the intracellular trafficking of NPs that target...... nanosensors indicates that the intracellular trafficking is aimed at lysosomes regardless of whether CD44 receptor-specific or unspecific uptake is induced....

  7. Revealing the mechanisms of protein disorder and N-glycosylation in CD44-hyaluronan binding using molecular simulation

    Olgun eGuvench

    2015-06-01

    Full Text Available The extracellular N-terminal hyaluronan binding domain (HABD of CD44 is a small globular domain that confers hyaluronan (HA binding functionality to this large transmembrane glycoprotein. When recombinantly expressed by itself, HABD exists as a globular water-soluble protein that retains the capacity to bind HA. This has enabled atomic-resolution structural biology experiments that have revealed the structure of HABD and its binding mode with oligomeric HA. Such experiments have also pointed to an order-to-disorder transition in HABD that is associated with HA binding. However, it had remained unclear how this structural transition was involved in binding since it occurs in a region of HABD distant from the HA-binding site. Furthermore, HABD is known to be N-glycosylated, and such glycosylation can diminish HA binding when the associated N-glycans are capped with sialic acid residues. The intrinsic flexibility of disordered proteins and of N-glycans makes it difficult to apply experimental structural biology approaches to probe the molecular mechanisms of how the order-to-disorder transition and N-glycosylation can modulate HA binding by HABD. We review recent results from molecular dynamics simulations that provide atomic-resolution mechanistic understanding of such modulation to help bridge gaps between existing experimental binding and structural biology data. Findings from these simulations include: Tyr42 may function as a molecular switch that converts the HA binding site from a low affinity to a high affinity state; in the partially-disordered form of HABD, basic amino acids in the C-terminal region can gain sufficient mobility to form direct contacts with bound HA to further stabilize binding; and terminal sialic acids on covalently-attached N-glycans can form charge-paired hydrogen bonding interactions with basic amino acids that could otherwise bind to HA, thereby blocking HA binding to glycosylated CD44 HABD.

  8. Role of the Phosphorylation of mTOR in the Differentiation of AML Cells Triggered with CD44 Antigen

    Darwish, Manar M

    2013-05-01

    Acute myeloid leukemia (AML) is a hematological disorder characterized by blockage of differentiation of myeloblasts. To date, the main therapy for AML is chemotherapy. Yet, studies are seeking a better treatment to enhance the survival rate of patients and minimize the relapsing of the disease. Since the major problem in these cells is that they are arrested in cellular differentiation, drugs that could induce their differentiation have proven to be efficient and of major interest for AML therapy. CD44 triggering appeared as a promising target for AML therapy as it has been shown that specific monoclonal antibodies, such as A3D8 and H90, reversed the blockage of differentiation, inhibited the proliferation of all AML subtypes, and in some cases, induced cell apoptosis. Studies conducted in our laboratory have added strength to these antibodies as potential treatment for AML. Indeed, our laboratory found that treating HL60 cells with A3D8 shows a decrease in the phosphorylation of the mammalian target of Rapamycin (mTOR) kinase correlated with the inhibition of proliferation/induction of differentiation of AML cells.The relationship between the induction of differentiation and the inhibition of proliferation and the decrease of mTOR phosphorylation remains to be clarified. To study the importance of the de-phosphorylation of mTOR and the observed effect of CD44 triggering on differentiation and/or proliferation, we sought to prepare phospho-mimic mutants of the mTOR kinase that will code for a constitutively phosphorylated form of mTOR and used two main methods to express this mutant in HL60 cells: lentiviral and simple transfection (cationic-liposomal transfection).

  9. Glycoprotein CD44 expression in normal, hyperplasic and neoplastic endometrium. An immunohistochemical study including correlations with p53, steroid receptor status and proliferative indices (PCNA, MIB1).

    Zagorianakou, N; Ioachim, E; Mitselou, A; Kitsou, E; Zagorianakou, P; Stefanaki, S; Makrydimas, G; Agnantis, N J

    2003-01-01

    We have studied by immunohistochemistry the presence and localization of CD44, estrogen and progesterone receptors, p53 and proliferative associated indices (MIB1, PCNA) in archival endometrial tissue, in order to determine their diagnostic and prognostic value as well as the possible correlations between them. We examined 186 samples of endometrial tissue (100 endometrial carcinomas of endometrioid type, 40 cases of hyperplasia and 46 of normal endometrium). Patient records were examined for FIGO stage, grade, and depth of myometrial invasion, histology, and lympho-vascular space invasion. Strong membranous immunostaining (> 10% of neoplastic cells) was observed in 45% of the carcinomas. A statistically significant correlation was found in the expression of protein in stromal cells, when compared with epithelial cells (p failed to show any statistical correlation with tumor grade or with vessel invasion. The expression of the protein was lower in FIGO Stage II compared with Stage I (p = 0.03). A positive relation of CD44 expression with progesterone receptor status (p = 0.02) was detected. CD44 expression was also positively associated with the proliferation associated with the proliferative index MIB1 (p = 0.001). CD44 is closely related to the secretory phase of the normal menstrual cycle and its expression is decreased in hyperplasia (simple or complex with or without atypia) and in cancer cases. These observations suggest that decreased CD44 expression might be functionally involved in the multiple mechanisms of the development and progression of endometrial lesions.

  10. An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells

    Ali, Amal J.

    2017-05-03

    Selectins guide the traffic of activated T-cells through the blood stream by mediating their tethering and rolling onto inflamed endothelium, in this way acting as beacons to help navigate them to sites of inflammation. Here, we present a comprehensive analysis of E-selectin ligands expressed on activated human T-cells. We identified several novel glycoproteins that function as E-selectin ligands. Specifically, we compared the role of P-selectin glycoprotein ligand-1 (PSGL-1) and CD43, known E-selectin ligands, to CD44, a ligand that has not previously been characterized as an E-selectin ligand on activated human T-cells. We showed that CD44 acts as a functional E-selectin ligand when expressed on both CD4+ and CD8+ T-cells. Moreover, the CD44 protein carries a binding epitope identifying it as hematopoietic cell E- and/or L-selectin ligand (HCELL). Furthermore, by knocking down these ligands individually or together in primary activated human T-cells, we demonstrated that CD44/HCELL, and not CD43, cooperates with PSGL-1 as a major E-selectin ligand. Additionally, we demonstrated the relevance of our findings to chronic autoimmune disease, by showing that CD44/HCELL and PSGL-1, but not CD43, from T-cells isolated from psoriasis patients, bind E-selectin.

  11. Targeted delivery of CD44s-siRNA by ScFv overcomes de novo resistance to cetuximab in triple negative breast cancer.

    Fu, Wenyan; Sun, Hefen; Zhao, Yang; Chen, Mengting; Yang, Lipeng; Yang, Xueli; Jin, Wei

    2018-05-16

    The overexpression of EGFR often occurs in TNBC, and the anti-EGFR receptor antibody cetuximab is used widely to treat metastatic cancer in the clinic. However, EGFR-targeted therapies have been developed for TNBC without clinical success. In this study, we show that impaired EGFR degradation is crucial for resistance to cetuximab, which depends on the cell surface molecule CD44. To further investigate the role of CD44 in EGFR signaling and its treatment potential, we developed a targeting fusion protein composed of an anti-EGFR scFv generated from cetuximab and truncated protamine, called Ce-tP. CD44 siRNA can be specifically delivered into EGFR-positive TNBC cells by Ce-tP. Efficient knockdown of CD44 and suppression of both EGFR and downstream signaling by the Ce-tP/siRNA complex were observed in EGFR-positive TNBC cells. More importantly, our results also showed that targeted delivery of siRNA specific for CD44 can efficiently overcome resistance to EGFR targeting in TNBC cells both in vitro and in vivo. Overall, our results establish a new principle to achieve EGFR inhibition in TNBC and limit drug resistance. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Review of bus drivers' occupational stress and stress prevention

    Kompier, M.A.J.; Di Martino, V.

    1995-01-01

    Although heterogeneous in methodology and content, 32 studies from 13 countries on bus drivers' work and health are similar in their conclusions. Bus-driving–characterized by high demands, low control and low support – can be regarded as a classic example of high-strain occupation, with high risks

  13. Interventions to prevent occupational noise-induced hearing loss

    Verbeek, Jos H.; Kateman, Erik; Morata, Thais C.; Dreschler, Wouter A.; Mischke, Christina

    2012-01-01

    Background Millions of workers worldwide are exposed to noise levels that increase their risk of hearing impairment. Little is known about the effectiveness of hearing loss prevention interventions. Objectives To assess the effectiveness of non-pharmaceutical interventions for preventing

  14. Interventions to prevent occupational noise induced hearing loss

    Verbeek, Jos H.; Kateman, Erik; Morata, Thais C.; Dreschler, Wout; Sorgdrager, Bas

    2009-01-01

    BACKGROUND: Millions of workers worldwide are exposed to noise levels that increase their risk of hearing impairment. Little is known about the effectiveness of hearing loss prevention interventions. OBJECTIVES: To assess the effectiveness of non-pharmaceutical interventions for preventing

  15. Targeting Tumor Cells with Anti-CD44 Antibody Triggers Macrophage-Mediated Immune Modulatory Effects in a Cancer Xenograft Model.

    Maisel, Daniela; Birzele, Fabian; Voss, Edgar; Nopora, Adam; Bader, Sabine; Friess, Thomas; Goller, Bernhard; Laifenfeld, Daphna; Weigand, Stefan; Runza, Valeria

    2016-01-01

    CD44, a transmembrane receptor reported to be involved in various cellular functions, is overexpressed in several cancer types and supposed to be involved in the initiation, progression and prognosis of these cancers. Since the sequence of events following the blockage of the CD44-HA interaction has not yet been studied in detail, we profiled xenograft tumors by RNA Sequencing to elucidate the mode of action of the anti-CD44 antibody RG7356. Analysis of tumor and host gene-expression profiles led us to the hypothesis that treatment with RG7356 antibody leads to an activation of the immune system. Using cytokine measurements we further show that this activation involves the secretion of chemo-attractants necessary for the recruitment of immune cells (i.e. macrophages) to the tumor site. We finally provide evidence for antibody-dependent cellular phagocytosis (ADCP) of the malignant cells by macrophages.

  16. Targeting Tumor Cells with Anti-CD44 Antibody Triggers Macrophage-Mediated Immune Modulatory Effects in a Cancer Xenograft Model.

    Daniela Maisel

    Full Text Available CD44, a transmembrane receptor reported to be involved in various cellular functions, is overexpressed in several cancer types and supposed to be involved in the initiation, progression and prognosis of these cancers. Since the sequence of events following the blockage of the CD44-HA interaction has not yet been studied in detail, we profiled xenograft tumors by RNA Sequencing to elucidate the mode of action of the anti-CD44 antibody RG7356. Analysis of tumor and host gene-expression profiles led us to the hypothesis that treatment with RG7356 antibody leads to an activation of the immune system. Using cytokine measurements we further show that this activation involves the secretion of chemo-attractants necessary for the recruitment of immune cells (i.e. macrophages to the tumor site. We finally provide evidence for antibody-dependent cellular phagocytosis (ADCP of the malignant cells by macrophages.

  17. Unintentional injury prevention and the role of occupational therapy in the Solomon Islands: an integrative review.

    Daufanamae, Barbara U; Franklin, Richard C; Eagers, Jackie

    2016-01-01

    Unintentional injuries (injuries for which there is no evidence of a predetermined intent) are one of the leading causes of death worldwide, particularly in low- and middle-income countries (LMICs). Although evidence demonstrates unintentional injuries are preventable it is a public health challenge for many LMICs such as the Solomon Islands. Occupational therapists are well placed to contribute to injury prevention, as they have specialised skills to analyse the accessibility and safety of the environments within which people conduct their daily occupations. While the role of occupational therapy in unintentional injury prevention is well known in high-income countries, it is unfamiliar in LMICs, especially in the Solomon Islands. This integrative review aimed to explore the incidence of common unintentional injuries, and the burden in the Solomon Islands; and explore the potential role of occupational therapy in unintentional injury prevention in the Solomon Islands, based on current activities in LMICs. Articles were reviewed from six databases (Medline, CINAHL, OTDBase, OT Seeker, Scopus and PsychInfo). Five articles met the inclusion criteria for the first objective and 15 articles met the inclusion criteria for the second objective. These articles were thematically analysed where themes and codes associated with the research objectives were extracted and analysed. Unintentional injuries in the Solomon Islands reported in the literature included ocular trauma, falls from fruit trees and coconut palms, and road traffic crashes. Burden of injury reported was mostly associated with loss of productivity. Occupational therapists undertook rehabilitative, biomechanical, neurodevelopmental and educational roles in LMIC, focusing on tertiary and secondary injury prevention. This integrative review suggests that there is limited information regarding injury in the Solomon Islands. However, evidence is available in LMICs to suggest that occupational therapy services can

  18. Environmental and occupational interventions for primary prevention of cancer: a cross-sectorial policy framework.

    Espina, Carolina; Porta, Miquel; Schüz, Joachim; Aguado, Ildefonso Hernández; Percival, Robert V; Dora, Carlos; Slevin, Terry; Guzman, Julietta Rodriguez; Meredith, Tim; Landrigan, Philip J; Neira, Maria

    2013-04-01

    Nearly 13 million new cancer cases and 7.6 million cancer deaths occur worldwide each year; 63% of cancer deaths occur in low- and middle-income countries. A substantial proportion of all cancers are attributable to carcinogenic exposures in the environment and the workplace. We aimed to develop an evidence-based global vision and strategy for the primary prevention of environmental and occupational cancer. We identified relevant studies through PubMed by using combinations of the search terms "environmental," "occupational," "exposure," "cancer," "primary prevention," and "interventions." To supplement the literature review, we convened an international conference titled "Environmental and Occupational Determinants of Cancer: Interventions for Primary Prevention" under the auspices of the World Health Organization, in Asturias, Spain, on 17-18 March 2011. Many cancers of environmental and occupational origin could be prevented. Prevention is most effectively achieved through primary prevention policies that reduce or eliminate involuntary exposures to proven and probable carcinogens. Such strategies can be implemented in a straightforward and cost-effective way based on current knowledge, and they have the added benefit of synergistically reducing risks for other noncommunicable diseases by reducing exposures to shared risk factors. Opportunities exist to revitalize comprehensive global cancer control policies by incorporating primary interventions against environmental and occupational carcinogens.

  19. Promoting prevention with economic arguments – The case of Finnish occupational health services

    Suhonen Aki

    2008-04-01

    Full Text Available Abstract Background Both social and ethical arguments have been used to support preventive occupational health services (OHS. During the 1990s it became more common to support political argumentation for occupational health and safety by converting the consequences of ill health at work into monetary units. In addition, OHS has been promoted as a profitable investment for companies, and this aspect has been used by OHS providers in their marketing. Our intention was to study whether preventive occupational health services positively influence a company's economic performance. Methods We combined the financial statements provided by Statistics Finland and employers' reimbursement applications for occupational health services (OHS costs to the Social Insurance Institution. The data covered the years 1997, 1999 and 2001 and over 6000 companies. We applied linear regression analysis to assess whether preventive OHS had had a positive influence on the companies' economic performance after two or four years. Results Resources invested in preventive OHS were not positively related to a company's economic performance. In fact, the total cost of preventive OHS per turnover was negatively correlated to economic performance. Conclusion Even if OHS has no effect on the economic performance of companies, it may have other effects more specific to OHS. Therefore, we recommend that the evaluation of prevention in OHS should move towards outcome measures, such as sickness absence, disability pension and productivity, when applicable, both in occupational health service research and in practice at workplaces.

  20. 76 FR 4911 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel: Occupational...

    2011-01-27

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel: Occupational Safety and Health...)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and...

  1. A review of the literature on preventive occupational health and safety activities in small enterprises

    Hasle, Peter; Limborg, Hans Jørgen

    2006-01-01

    The scientific literature regarding preventive occupational health and safety activities in small enterprises has been reviewed in order to identify effective preventive approaches and to develop a future research strategy. During the last couple of years, there has been a significant increase...

  2. [Prevention of occupational accidents with biological material as per Green and Kreuter Model].

    Manetti, Marcela Luisa; da Costa, João Carlos Souza; Marziale, Maria Helena Palucci; Trovó, Marli Elisa

    2006-03-01

    This study aimed at diagnosing the occurrence of occupational accidents deriving from exposition to biological substance among workers of a hospital from São Paulo, Brazil, analyzing the adopted safety measures and elaborating a flowchart of preventive actions according to the Health Promotion Model by Green and Kreuter. It is an exploratory study with data collected electronically from the website REPAT - Electronic Network for the Prevention of Occupational Accidents with biological substances. The strategy used by the hospital did not reduce the injures. Results were used to elaborate a flowchart of preventive actions in order to improve the workers' quality of life.

  3. Lockout and tagout procedures to prevent occupational injury and fatality.

    Chalupka, Stephanie

    2011-07-01

    Hazardous energy control programs that include lockout and tagout procedures as well as worker training can prevent serious injury and death during machine maintenance. Copyright 2011, SLACK Incorporated.

  4. Systematic Review of Interventions Supported by ICT for the Prevention Treatment of Occupational Stress.

    Narváez, Santiago; Tobar, Angela M; López, Diego M

    2014-01-01

    Stress-related disorders have become one of the main problems of public health in many countries and of worldwide organizations, and they are expected to become more common in the forthcoming decades. This article aims at providing a systematic review and a descriptive evaluation of the interventions supported by ICT for the prevention and treatment of occupational stress. A systematic review of five databases (EBSCO, The Cochrane Library, PubMed, ScienceDirect and IEEEXplorer) was carried out. This article provides a quantitative and qualitative description of 21 studies about occupational stress interventions supported by ICT. The following factors were considered for the analysis: impact of the intervention, design of the study, type of intervention, purpose of the intervention, type of instrument for the measurement of occupational stress, and type of ICT used. The systematic review demonstrated that interventions supported by ICT for the prevention and treatment of occupational stress are scarce but effective.

  5. Evidence based guidelines for the prevention, identification, and management of occupational asthma.

    Nicholson, P J; Cullinan, P; Taylor, A J Newman; Burge, P S; Boyle, C

    2005-05-01

    Occupational asthma is the most frequently reported work related respiratory disease in many countries. This work was commissioned by the British Occupational Health Research Foundation to assist the Health and Safety Executive in achieving its target of reducing the incidence of occupational asthma in Great Britain by 30% by 2010. The guidelines aim to improve the prevention, identification, and management of occupational asthma by providing evidence based recommendations on which future practice can be based. The literature was searched systematically using Medline and Embase for articles published in all languages up to the end of June 2004. Evidence based statements and recommendations were graded according to the Royal College of General Practitioner's star system and the revised Scottish Intercollegiate Guidelines Network grading system. A total of 474 original studies were selected for appraisal from over 2500 abstracts. The systematic review produced 52 graded evidence statements and 22 recommendations based on 223 studies. Evidence based guidelines have become benchmarks for practice in healthcare and the process used to prepare them is well established. This evidence review and its recommendations focus on interventions and outcomes to provide a robust approach to the prevention, identification, and management of occupational asthma, based on and using the best available medical evidence. The most important action to prevent cases of occupational asthma is to reduce exposure at source. Thereafter surveillance should be performed for the early identification of symptoms, including occupational rhinitis, with additional functional and immunological tests where appropriate. Effective management of workers suspected to have occupational asthma involves the identification and investigation of symptoms suggestive of asthma immediately they occur. Those workers who are confirmed to have occupational asthma should be advised to avoid further exposure completely

  6. Prevention of occupational injuries: Evidence for effective good practices in foundries.

    Porru, Stefano; Calza, Stefano; Arici, Cecilia

    2017-02-01

    Occupational injuries are a relevant research and practical issue. However, intervention studies evaluating the effectiveness of workplace injury prevention programs are seldom performed. The effectiveness of a multifaceted intervention aimed at reducing occupational injury rates (incidence/employment-based=IR, frequency/hours-based=FR, severity=SR) was evaluated between 2008 and 2013 in 29 Italian foundries (22 ferrous; 7 non-ferrous; 3,460 male blue collar workers/year) of varying sizes. Each foundry established an internal multidisciplinary prevention team for risk assessment, monitoring and prevention of occupational injuries, involving employers, occupational physicians, safety personnel, workers' representatives, supervisors. Targets of intervention were workers, equipment, organization, workplace, job tasks. An interrupted time series (ITS) design was applied. 4,604 occupational injuries and 83,156 lost workdays were registered between 2003 and 2013. Statistical analysis showed, after intervention, a reduction of all injury rates (-26% IR, -15% FR, -18% SR) in ferrous foundries and of SR (-4%) in non-ferrous foundries. A significant (p=0.021) 'step-effect' was shown for IR in ferrous foundries, independent of secular trends (pgood external validity; promotion of effective good practices. Main limitations were the non-randomized nature and a medium length post-intervention period. In conclusion, a multifaceted, pragmatic and accountable intervention is effective in reducing the burden of occupational injuries in small-, medium- and large-sized foundries. Practical Applications: The study poses the basis for feasible good practice guidelines to be implemented to prevent occupational injuries, by means of sector-specific numerical benchmarks, with potentially relevant impacts on workers, companies, occupational health professionals and society at large. Copyright © 2016 National Safety Council and Elsevier Ltd. All rights reserved.

  7. Occupational contact urticaria: lessons from the French National Network for Occupational Disease Vigilance and Prevention (RNV3P).

    Bensefa-Colas, L; Telle-Lamberton, M; Faye, S; Bourrain, J-L; Crépy, M-N; Lasfargues, G; Choudat, D; Momas, I

    2015-12-01

    Occupational contact urticaria (OCU) is an occupational contact dermatitis that can cause serious health consequences and disability at work. To describe OCU and its temporal trends by the main causal agents and activity sectors in a nationwide scheme in France. Using data from the French National Network for Occupational Disease Vigilance and Prevention (RNV3P), we described OCU reported during the period 2001-10 and analysed the temporal trends of OCU and OCU attributed to the most frequent agents over the study period. Trends analyses were supported by reporting odds ratios using a logistic regression model with reference to 2001, or with time as a continuous variable. During the study period, 251 cases of OCU were reported in RNV3P, half of which were due to natural rubber latex, in particular in the health and social work activity sector (HSW). The number of these cases declined significantly over the study period (19% per year), and particularly after 2006. Conversely, the other causes of OCU did not decrease. Using surveillance data from a French national network, this study has found that there was a significant decline in OCU due to natural rubber latex, particularly in the HSW, when powdered latex gloves were banned from French hospitals. Our results show the effectiveness of this preventive measure, and suggest that this practice should be extended to other sectors. © 2015 British Association of Dermatologists.

  8. The Union Health Center: a working model of clinical care linked to preventive occupational health services.

    Herbert, R; Plattus, B; Kellogg, L; Luo, J; Marcus, M; Mascolo, A; Landrigan, P J

    1997-03-01

    As health care provision in the United States shifts to primary care settings, it is vital that new models of occupational health services be developed that link clinical care to prevention. The model program described in this paper was developed at the Union Health Center (UHC), a comprehensive health care center supported by the International Ladies Garment Workers Union (now the Union of Needletrades, Industrial and Textile Employees) serving a population of approximately 50,000 primarily minority, female garment workers in New York City. The objective of this paper is to describe a model occupational medicine program in a union-based comprehensive health center linking accessible clinical care with primary and secondary disease prevention efforts. To assess the presence of symptoms suggestive of occupational disease, a health status questionnaire was administered to female workers attending the UHC for routine health maintenance. Based on the results of this survey, an occupational medicine clinic was developed that integrated direct clinical care with worker and employer education and workplace hazard abatement. To assess the success of this new approach, selected cases of sentinel health events were tracked and a chart review was conducted after 3 years of clinic operation. Prior to initiation of the occupational medicine clinic, 64% (648) of the workers surveyed reported symptoms indicative of occupational illnesses. However, only 42 (4%) reported having been told by a physician that they had an occupational illness and only 4 (.4%) reported having field a workers' compensation claim for an occupational disease. In the occupational medicine clinic established at the UHC, a health and safety specialist acts as a case manager, coordinating worker and employer education as well as workplace hazard abatement focused on disease prevention, ensuring that every case of occupational disease is treated as a potential sentinel health event. As examples of the success

  9. Relationship of PCNA, C-erbB2 and CD44s expression with tumor grade and stage in urothelial carcinomas of the bladder

    Yıldırım, Ayhan; Kösem, Mustafa; Sayar, İlyas; Gelincik, İbrahim; Yavuz, Alparslan; Bozkurt, Aliseydi; Erkorkmaz, Ünal; Bayram, İrfan

    2014-01-01

    In the present study, the intention was to reveal the relationship of histological grade and stage with c-erbB2, CD44s, and PCNA immunoreactivity in bladder urothelial carcinomas (UC). In our study, we evaluated 46 items of transurethral resection material of patients submitted by YYU Faculty of Medicine, Main Department of Pathology, with a mass revealed in their bladder after clinical and radiological studies at our laboratories and who were diagnosed with urothelial carcinomas. PCNA, c-erbB2, and CD44s were applied in an immunohistochemical manner comprised from nine low-malignant potential papillary urothelial neoplasia, 23 low-grade papillary urothelial carcinoma, and 14 high-grade papillary urothelial carcinoma. Immunostaining was scored according to the percentage of positive cells. The immunohistochemical study demonstrated that the c-erbB2 and PCNA staining ratio increased when an increase occurred in stage and grade. The CD44s staining ratio decreased. C-erbB2, PCNA, and CD44s appear to be a useful marker in the assessment of the prognosis and treatment options in urothelial carcinomas. PMID:25035774

  10. Delayed wound healing in aged skin rat models after thermal injury is associated with an increased MMP-9, K6 and CD44 expression.

    Simonetti, Oriana; Oriana, Simonetti; Lucarini, Guendalina; Guendalina, Lucarini; Cirioni, Oscar; Oscar, Cirioni; Zizzi, Antonio; Antonio, Zizzi; Orlando, Fiorenza; Fiorenza, Orlando; Provinciali, Mauro; Mauro, Provinciali; Di Primio, Roberto; Roberto, Di Primio; Giacometti, Andrea; Andrea, Giacometti; Offidani, Annamaria; Annamaria, Offidani

    2013-06-01

    Age-related differences in wound healing have been documented but little is known about the wound healing mechanism after burns. Our aim was to compare histological features and immunohistochemical expression of matrix metalloproteinase-9 (MMP-9), collagen IV, K6 and CD44 in the burn wound healing process in aged and young rats. Following burns the appearance of the wound bed in aged rats had progressed but slowly, resulting in a delayed healing process compared to the young rats. At 21 days after injury, epithelial K6, MMP-9 and CD44 expression was significantly increased in aged rats with respect to young rats; moreover, in the aged rat group we observed a not fully reconstituted basement membrane. K6, MMP-9 and CD44 expression was significantly increased in wounded skin compared to unwounded skin both in young and aged rats. We hypothesise that delayed burn skin wound healing process in the aged rats may represent an age dependent response to injury where K6, MMP-9 and CD44 play a key role. It is therefore possible to suggest that these factors contribute to the delayed wound healing in aged skin and that modulation could lead to a better and faster recovery of skin damage in elderly. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  11. Dual-targeting hybrid nanoparticles for the delivery of SN38 to Her2 and CD44 overexpressed human gastric cancer

    Yang, Zhe; Luo, Huiyan; Cao, Zhong; Chen, Ya; Gao, Jinbiao; Li, Yingqin; Jiang, Qing; Xu, Ruihua; Liu, Jie

    2016-06-01

    Gastric cancer (GC), particularly of the type with high expression of both human epidermal growth factor receptor 2 (Her2) and cluster determinant 44 (CD44), is one of the most malignant human tumors which causes a high mortality rate due to rapid tumor growth and metastasis. To develop effective therapeutic treatments, a dual-targeting hybrid nanoparticle (NP) system was designed and constructed to deliver the SN38 agent specifically to human solid gastric tumors bearing excessive Her2 and CD44. The hybrid NPs consist of a particle core made of the biodegradable polymer PLGA and a lipoid shell prepared by conjugating the AHNP peptides and n-hexadecylamine (HDA) to the carboxyl groups of hyaluronic acid (HA). Upon encapsulation of the SN38 agent in the NPs, the AHNP peptides and HA on the NP surface allow preferential delivery of the drug to gastric cancer cells (e.g., HGC27 cells) by targeting Her2 and CD44. Cellular uptake and in vivo biodistribution experiments verified the active targeting and prolonged in vivo circulation properties of the dual-targeting hybrid NPs, leading to enhanced accumulation of the drug in tumors. Furthermore, the anti-proliferation mechanism studies revealed that the inhibition of the growth and invasive activity of HGC27 cells was not only attributed to the enhanced cellular uptake of dual-targeting NPs, but also benefited from the suppression of CD44 and Her2 expression by HA and AHNP moieties. Finally, intravenous administration of the SN38-loaded dual-targeting hybrid NPs induced significant growth inhibition of HGC27 tumor xenografted in nude mice compared with a clinical antitumor agent, Irinotecan (CPT-11), and the other NP formulations. These results demonstrate that the designed dual-targeting hybrid NPs are promising for targeted anti-cancer drug delivery to treat human gastric tumors over-expressing Her2 and CD44.Gastric cancer (GC), particularly of the type with high expression of both human epidermal growth factor receptor

  12. [Prevention of Occupational Injuries Related to Hands: Calculation of Subsequent Injury Costs for the Austrian Social Occupational Insurance Institution (AUVA)].

    Rauner, M S; Mayer, B; Schaffhauser-Linzatti, M M

    2015-08-01

    Occupational injuries cause short-term, direct costs as well as long-term follow-up costs over the lifetime of the casualties. Due to shrinking budgets accident insurance companies focus on cost reduction programmes and prevention measures. For this reason, a decision support system for consequential cost calculation of occupational injuries was developed for the main Austrian social occupational insurance institution (AUVA) during three projects. This so-called cost calculation tool combines the traditional instruments of accounting with quantitative methods such as micro-simulation. The cost data are derived from AUVA-internal as well as external economic data sources. Based on direct and indirect costs, the subsequent occupational accident costs from the time of an accident and, if applicable, beyond the death of the individual casualty are predicted for the AUVA, the companies in which the casualties are working, and the other economic sectors. By using this cost calculation tool, the AUVA classifies risk groups and derives related prevention campaigns. In the past, the AUVA concentrated on falling, accidents at construction sites and in agriculture/forestry, as well as commuting accidents. Currently, among others, a focus on hand injuries is given and first prevention programmes have been initiated. Hand injuries represent about 38% of all casualties with average costs of about 7,851 Euro/case. Main causes of these accidents are cutting injuries in production, agriculture, and forestry. Beside a low, but costly, number of amputations with average costs of more than 100,000 Euro/case, bone fractures and strains burden the AUVA-budget with about 17,500 and 10,500 € per case, respectively. Decision support systems such as this cost calculation tool represent necessary instruments to identify risk groups and their injured body parts, causes of accidents, and economic activities, which highly burden the budget of an injury company, and help derive

  13. Nudging for Prevention in Occupational Health and Safety in South Africa Using Fiscal Policies.

    de Jager, Pieter; Rees, David; Kisting, Sophia; Kgalamono, Spo; Ndaba, Mpume; Stacey, Nicolas; Tugendhaft, Aviva; Hofman, Karen

    2017-08-01

    Currently, in some countries occupational health and safety policy and practice have a bias toward secondary prevention and workers' compensation rather than primary prevention. Particularly, in emerging economies, research has not adequately contributed to effective interventions and improvements in workers' health. This article, using South Africa as a case study, describes a methodology for identifying candidate fiscal policy interventions and describes the policy interventions selected for occupational health and safety. It is argued that fiscal policies are well placed to deal with complex intersectoral health problems and to focus efforts on primary prevention. A major challenge is the lack of empirical evidence to support the effectiveness of fiscal policies in improving workers' health. A second challenge is the underprioritization of occupational health and safety partly due to the relatively small burden of disease attributed to occupational exposures. Both challenges can and should be overcome by (i) conducting policy-relevant research to fill the empirical gaps and (ii) reconceptualizing, both for policy and research purposes, the role of work as a determinant of population health. Fiscal policies to prevent exposure to hazards at work have face validity and are thus appealing, not as a replacement for other efforts to improve health, but as part of a comprehensive effort toward prevention.

  14. Climate change and occupational allergies: an overview on biological pollution, exposure and prevention.

    D'Ovidio, Maria Concetta; Annesi-Maesano, Isabella; D'Amato, Gennaro; Cecchi, Lorenzo

    2016-01-01

    Climate change, air pollution, temperature increase and other environmental variables are modifying air quality, contributing to the increase of prevalence of allergic respiratory diseases. Allergies are complex diseases characterized by multilevel interactions between individual susceptibility, response to immune modulation and environmental exposures to physical, chemical and biological agents. Occupational allergies introduce a further complexity to these relationships by adding occupational exposure to both the indoor and outdoor ones in the living environment. The aim of this paper is to overview climate-related allergy affecting environmental and occupational health, as literature data are scanty in this regard, and to suggest a management model of this risk based on a multidisciplinary approach, taking the case of biological pollution, with details on exposure and prevention. The management of climate-related occupational allergy should take into account preventive health strategies, environmental, public and occupational interventions, as well as to develop, implement, evaluate, and improve guidelines and standards protecting workers health under changing climatic conditions; new tools and strategies based on local conditions will have to be developed. Experimental studies and acquisition of environmental and personal data have to be matched to derive useful information for the scope of occupational health and safety.

  15. [Knowledge and practices by adolescents in preventing occupational injuries: a qualitative study].

    Nagai, Roberta; Lefèvre, Ana Maria C; Lefèvre, Fernando; Steluti, Josiane; Teixeira, Liliane R; Zinn, Lílian C S; Soares, Nilson S; Fischer, Frida M

    2007-06-01

    To describe knowledge and practices adopted by high school students to prevent occupational injuries. The study was carried out in a public school located in São Paulo, in 2003. Fifty-three evening students aged 14 to 21 years old participated the study, they were divided into two groups with and without job experience (32 and 21 students, respectively). The students answered two questions: "Why do occupational injuries occur?" and "How do you avoid occupational injuries?" Analyses were performed using the software "Quali-quanti" to structure collective discourses. ANALYSIS OF DISCOURSES: Adolescents with work experience reported that occupational injuries occur due to carelessness of the employee, bad luck of the employee, employer's negligence, lack of training, and unsafe workplace. Adolescents without work experience reported that the main causes of work injuries were carelessness of the employee and employer's negligence. Regarding the ways to protect themselves against occupational injuries, both groups reported that: they pay attention (would pay attention) and wear safety equipment (would wear) safety equipment. Adolescents from both groups showed limited knowledge about occupational injuries and prevention methods. Students "blamed the victim" to explain the injuries and considered "paying attention to work" as the best way to protect themselves. These facts showed that the culture of blaming the victim is present since adolescence and probably it is an outcome of a learning process of the society.

  16. Training Needs Assessment in Occupational Risk Prevention into Schools

    Burgos-Garcia, Antonio; Alonso-Morillejo, Enrique; Pozo-Munoz, Carmen

    2011-01-01

    The assessment of needs plays a relevant role in the training for preventing of risks at work into school, as it is a scientific procedure to identify and prioritise problems existing within an educative context. This type of assessment is the starting point for a subsequent planning of the educative interventions that will enable pupils and…

  17. Interventions to prevent occupational noise-induced hearing loss

    Tikka, Christina; Verbeek, Jos H.; Kateman, Erik; Morata, Thais C.; Dreschler, Wouter A.; Ferrite, Silvia

    2017-01-01

    This is the second update of a Cochrane Review originally published in 2009. Millions of workers worldwide are exposed to noise levels that increase their risk of hearing disorders. There is uncertainty about the effectiveness of hearing loss prevention interventions. To assess the effectiveness of

  18. Fostering functioning of workers: A new challenge for prevention in occupational health.

    van Amelsvoort, Ludovic G P M; de Brouwer, Carin P M; Heerkens, Yvonne F; Widdershoven, Guy A M; Kant, IJmert

    2017-01-01

    Given large changes in working conditions and society, occupational health care has to prioritize its efforts towards fostering health and functioning of workers and as such promote work participation. This requires that more emphasis is given on the application of biopsychological models in the care of workers. Although a biopsychological approach is often mentioned as essential part of occupational health care, it's application is often hampered in practice, by practical barriers and lack of practical knowledge. This is illustrated by a study that uncovered facilitating and hindering factors in the implementation process of a preventive strategy, proven effective in reducing the risk of long term sickness absence. To facilitate the use of biopsychological models in occupational health care, it is shown that setting up a training curriculum is possible, based on the International Classification of Functioning, Disability and Health (ICF) grafted on available training in evidence based practice skills is possible. Furthermore, there is a need for elaboration of the personal factors relevant for workers and the relevant work-related environmental factors to support practical application of ICF in occupational health care. A paradigm shift in occupational health care can facilitate widespread implementation of the biopsychosocial approach in occupational health and may stimulate occupational health professionals to further integrate this approach in their daily practice.

  19. Occupational Skin Disease Prevention: An Educational Intervention for Hairdresser Cosmetology Students.

    Haughtigan, Kara; Main, Eve; Bragg-Underwood, Tonya; Watkins, Cecilia

    2017-11-01

    Cosmetologists frequently develop occupational skin disease related to workplace exposures. The purpose of this study was to evaluate an educational intervention to increase cosmetology students' occupational skin disease knowledge and use of preventive practices. A quasi-experimental design was used to evaluate students' knowledge, behaviors, intentions, expectancies, and expectations. A 20-minute verbal presentation and printed two-page educational handout were provided for participants. Statistically significant increases in knowledge, frequency of glove use, and frequency of moisturizer use were found, but the frequency of handwashing did not increase. In addition, the Behavioral Strategies subscale, the Intention subscale, and the Expectancies subscale showed statistically significant improvements. The results of this study suggest an educational intervention can increase cosmetology students' knowledge of occupational skin diseases and their use of preventive strategies.

  20. Creating a Culture of Prevention in Occupational Safety and Health Practice.

    Kim, Yangho; Park, Jungsun; Park, Mijin

    2016-06-01

    The incidence of occupational injuries and diseases associated with industrialization has declined markedly following developments in science and technology, such as engineering controls, protective equipment, safer machinery and processes, and greater adherence to regulations and labor inspections. Although the introduction of health and safety management systems has further decreased the incidence of occupational injuries and diseases, these systems are not effective unless accompanied by a positive safety culture in the workplace. The characteristics of work in the 21(st) century have given rise to new issues related to workers' health, such as new types of work-related disorders, noncommunicable diseases, and inequality in the availability of occupational health services. Overcoming these new and emerging issues requires a culture of prevention at the national level. The present paper addresses: (1) how to change safety cultures in both theory and practice at the level of the workplace; and (2) the role of prevention culture at the national level.

  1. Creating a Culture of Prevention in Occupational Safety and Health Practice

    Yangho Kim

    2016-06-01

    Full Text Available The incidence of occupational injuries and diseases associated with industrialization has declined markedly following developments in science and technology, such as engineering controls, protective equipment, safer machinery and processes, and greater adherence to regulations and labor inspections. Although the introduction of health and safety management systems has further decreased the incidence of occupational injuries and diseases, these systems are not effective unless accompanied by a positive safety culture in the workplace. The characteristics of work in the 21st century have given rise to new issues related to workers' health, such as new types of work-related disorders, noncommunicable diseases, and inequality in the availability of occupational health services. Overcoming these new and emerging issues requires a culture of prevention at the national level. The present paper addresses: (1 how to change safety cultures in both theory and practice at the level of the workplace; and (2 the role of prevention culture at the national level.

  2. Interventions to prevent occupational noise-induced hearing loss: a Cochrane systematic review

    Verbeek, Jos H.; Kateman, Erik; Morata, Thais C.; Dreschler, Wouter A.; Mischke, Christina

    2014-01-01

    To assess the effectiveness of interventions for preventing occupational noise exposure or hearing loss compared to no intervention or alternative interventions. We searched biomedical databases up to 25 January 2012 for randomized controlled trials (RCT), controlled before-after studies and

  3. Do workers' health surveillance examinations fulfill their occupational preventive objective? Analysis of the medical practice of occupational physicians in Catalonia, Spain.

    Rodríguez-Jareño, Mari Cruz; Molinero, Emilia; de Montserrat, Jaume; Vallès, Antoni; Aymerich, Marta

    2017-10-06

    Although routine workers' health examinations are extensively performed worldwide with important resource allocation, few studies have analyzed their quality. The objective of this study has been to analyze the medical practice of workers' health examinations in Catalonia (Spain) in terms of its occupational preventive aim. A cross-sectional study was carried out by means of an online survey addressed to occupational physicians who were members of the Catalan Society of Safety and Occupational Medicine. The questionnaire included factual questions on how they performed health examinations in their usual practice. The bivariate analysis of the answers was performed by type of occupational health service (external/internal). The response rate was 57.9% (N = 168), representing 40.3% of the reference population. A high percentage of occupational physicians had important limitations in their current medical practice, including availability of clinical and exposure information, job-specificity of tests, and early detection and appropriate management of suspected occupational diseases. The situation in external occupational health services - that covered the great majority of Catalan employees - was worse remarkably in regard to knowledge of occupational and nonoccupational sickness absence data, participation in the investigation of occupational injuries and diseases, and accessibility for workers to the occupational health service. This study raises serious concerns about the occupational preventive usefulness of these health examinations, and subsequently about our health surveillance system, based primarily on them. Professionals alongside health and safety institutions and stakeholders should promote the rationalization of this system, following the technical criteria of need, relevance, scientific validity and effectiveness, whilst ensuring that its ultimate goal of improving the health and safety of workers in relation to work is fulfilled. Other countries with

  4. Do workers’ health surveillance examinations fulfill their occupational preventive objective? Analysis of the medical practice of occupational physicians in Catalonia, Spain

    Mari Cruz Rodríguez-Jareño

    2017-10-01

    Full Text Available Objectives: Although routine workers’ health examinations are extensively performed worldwide with important resource allocation, few studies have analyzed their quality. The objective of this study has been to analyze the medical practice of workers’ health examinations in Catalonia (Spain in terms of its occupational preventive aim. Material and Methods: A cross-sectional study was carried out by means of an online survey addressed to occupational physicians who were members of the Catalan Society of Safety and Occupational Medicine. The questionnaire included factual questions on how they performed health examinations in their usual practice. The bivariate analysis of the answers was performed by type of occupational health service (external/internal. Results: The response rate was 57.9% (N = 168, representing 40.3% of the reference population. A high percentage of occupational physicians had important limitations in their current medical practice, including availability of clinical and exposure information, job-specificity of tests, and early detection and appropriate management of suspected occupational diseases. The situation in external occupational health services – that covered the great majority of Catalan employees – was worse remarkably in regard to knowledge of occupational and nonoccupational sickness absence data, participation in the investigation of occupational injuries and diseases, and accessibility for workers to the occupational health service. Conclusions: This study raises serious concerns about the occupational preventive usefulness of these health examinations, and subsequently about our health surveillance system, based primarily on them. Professionals alongside health and safety institutions and stakeholders should promote the rationalization of this system, following the technical criteria of need, relevance, scientific validity and effectiveness, whilst ensuring that its ultimate goal of improving the health

  5. [Occupational physician's role in the prevention of the accidents in construction industry].

    Mosconi, G; Riva, M M; Apostoli, P

    2008-01-01

    The aim of this work is to discuss about the role of the occupational physician in the prevention of the accidents in construction industry. Using the experience of 12 years of surveillance of workers in Bergamo province, the authors analyse the "human factors" which may influence the risk to have an accident, and the role of the physicians not only for the early diagnosis of work-related diseases, but also for the formulation of correct fitness to work, which consider accidents' prevention. Health conditions, psychological elements, fatigue and life style are some of the most important "human factors" which can amplify the accident phenomenon in construction industry. Our experience demonstrates that the occupational physicians can operate in preventive way on these factors, formulating correct fitness to work, giving their collaboration in the risk evaluation and management, suggesting runs of rehabilitation and recovery for the workers who need it, promoting information meetings related to the correct life habits.

  6. [Preventing addictive practices in the workplace thanks to occupational health services].

    Dano, Corinne

    2017-06-01

    The workplace can be concerned by all types and all levels of addictive practices: consumption of alcohol or psychoactive substances, work addiction, internet addiction and technology addiction. Addictions can be related to multiple factors, both within and outside the workplace. With the employer, responsible for occupational health and safety, the multidisciplinary team of the inter-company occupational health service must today implement a collective and global prevention policy with regard to addictions, in addition to the traditional follow-up. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Complete identification of E-selectin ligand activity on neutrophils reveals a dynamic interplay and distinct functions of PSGL-1, ESL-1 and CD44

    Wild, Martin; Vestweber, Dietmar; Frenette, Paul S.

    2014-01-01

    SUMMARY The selectins and their ligands are required for leukocyte extravasation during inflammation. Several glycoproteins have been suggested to bind to E-selectin in vitro but the complete identification of its physiological ligands has remained elusive. Here, we show using gene- and RNA-targeted loss-of-function that E-selectin ligand-1 (ESL-1), PSGL-1 and CD44 encompass all endothelial selectin ligand activity on neutrophils. PSGL-1 plays a major role in the initial leukocyte capture, while ESL-1 is critical to convert initial tethers into steady slow rolling. CD44 controls rolling velocity and mediates E-selectin-dependent redistribution of PSGL-1 and L-selectin to a major pole on slowly rolling leukocytes through p38 signaling. These results suggest distinct and dynamic contributions of these three glycoproteins in selectin-mediated neutrophil adhesion and signaling. PMID:17442598

  8. A cell surface chondroitin sulfate proteoglycan, immunologically related to CD44, is involved in type I collagen-mediated melanoma cell motility and invasion

    Faassen, A E; Schrager, J A; Klein, D J

    1992-01-01

    The metastatic spread of tumor cells occurs through a complex series of events, one of which involves the adhesion of tumor cells to extracellular matrix (ECM) components. Multiple interactions between cell surface receptors of an adherent tumor cell and the surrounding ECM contribute to cell...... collagen could also be inhibited by removing cell surface chondroitin sulfate with chondroitinase. In contrast, type I collagen-mediated melanoma cell adhesion and spreading were not affected by either beta-D-xyloside or chondroitinase treatments. These results suggest that mouse melanoma CSPG...... was shown to be mediated, at least in part, by chondroitin sulfate. Additionally we have determined that mouse melanoma CSPG is composed of a 110-kD core protein that is recognized by anti-CD44 antibodies on Western blots. Collectively, our data suggests that interactions between a cell surface CD44-related...

  9. Occupational disease disclosed by preventive follow-up of former uranium ore miners

    Pacina, V.; Vich, Z.; Elterlein, E.

    1982-01-01

    The aim of preventive follow-up examinations of former employees of the concern Czechoslovak Uranium Mines is to determine possible health damage of chronically exposed workers in an area that can become manifest even following a long time after leaving the high-risk working environment. In a group of 1,139 persons that had undergone preventive follow-up examinations in the years 1977 to 1980 there were 63 cases of newly detected affections that were reported as occupational diseases, and other serious affections. The system of preventive follow-up examinations represents a significant contribution to the improvement of health care of the workers. (author)

  10. Contribution of immunocytochemical stainings for galectin-3, CD44, and HBME1 to fine-needle aspiration cytology diagnosis of papillary thyroid carcinoma.

    Das, Dilip K; Al-Waheeb, Salah K M; George, Sara S; Haji, Bahiyah I; Mallik, Mrinmay K

    2014-06-01

    In cytology practice some papillary thyroid carcinoma (PTC) cases have indeterminate diagnoses and overlapping cytological features with benign lesions. This study was undertaken to find out if immunocytochemistry using Galectin-3, CD-44 and HBME-1 could be of help in such situations. Forty-six cases consisting of 22 malignancy (PTC) cases, 7 suspicious of (S/O) PTC, 1 follicular neoplasm, 5 follicular lesion of undetermined significance (FLUS), and 11 benign (colloid goiter) cases diagnosed by FNA were included in this study. Staining reactions were graded in a sliding scale of -, 1+, 2+, 3+, and 4+. In an assessment of 100 cells, each cell with weak, and moderate to strong positive reaction were assigned a score of 1 and 4, respectively. Staining reaction of ≥+2 and scores >100 were considered positive. Frequency of cases with ≥+2 reaction, and scores >100 for each of Galectin-3, CD-44, and HBME-1 were significantly higher in PTC or combined PTC and S/O PTC cases as compared with FLUS and benign cases taken together (P = 0.01744 to 0.00000). When the cases were compared according to histological malignant and benign diagnoses, the difference was also significant in respect of ≥+2 reaction, and scores >100 for Galectin-3 and CD44 (P = 0.04923 to 0.00947); however, there was no significant difference, when these parameters for HBME1 were compared. Galectin 3, CD 44, and to some extent HBME 1 are useful immunocytochemical parameters with potential to support FNAC diagnosis of PTC, especially in situations with difficult differential diagnoses. Copyright © 2013 Wiley Periodicals, Inc.

  11. Spatial distribution of osteopontin, CD44v6 and podoplanin in the lining epithelium of odontogenic keratocyst, and their biological relevance.

    Kechik, Khamisah Awang; Siar, Chong Huat

    2018-02-01

    The odontogenic keratocyst (OKC) remains the most challenging jaw cyst to treat because of its locally-aggressive behaviour and high recurrence potential. Emerging evidence suggests that osteopontin, its receptors CD44v6 and integrin α v , and podoplanin, have a role in the local invasiveness of this cyst. However the spatial distribution characteristics of these pro-invasive markers in the lining epithelium of OKC, and their association with the clinicopathologic parameters of OKC are largely unexplored. This study sought to address these issues in comparison with dentigerous cysts (DCs) and radicular cysts (RCs) and to evaluate their biological relevance. A sample consisting of 20 OKC cases, 10 DCs and 10 RCs was subjected to immunohistochemical staining for osteopontin, CD44v6 and integrin α v , and podoplanin, and semiquantitative analysis was performed. All factors (except integrin α v ) were detected heterogeneously in the constitutive layers of the lining epithelium in all three cyst types. Key observations were significant upregulation of CD44v6 and podoplanin in OKC compared to DCs and RCs, suggesting that these protein molecules may play crucial roles in promoting local invasiveness in OKC (P<0.05). Osteopontin underexpression and distribution patterns were indistinctive among all three cysts indicating its limited role as pro-invasive factor. Clinical parameters showed no significant correlations with all protein factors investigated. Present findings suggest that an osteopontin low CD44v6 high and podoplanin high immunoprofile most probably represent epithelial signatures of OKC and are markers of local invasiveness in this cyst. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Prognostic value of E-cadherin, beta-catenin, CD44v6, and HER2/neu in metastatic cutaneous adenocarcinoma.

    Pozdnyakova, Olga; Hoang, Mai M P; Dresser, Karen A; Mahalingam, Meera

    2009-08-01

    Our recent experience with a patient developing cutaneous metastases within 3 months of diagnosis of esophageal adenocarcinoma suggests that altered expression of the cellular adhesion molecules, E-cadherin and CD44v6, may have had a role to play in the rapid onset of metastases. To corroborate these findings, we designed a cross-sectional study to investigate the expression of select molecules involved in the metastatic cascade. E-cadherin, beta-catenin, CD44v6, and HER2/neu immunohistochemical stains were performed on archival materials of metastatic adenocarcinoma to the skin from 27 patients and the available corresponding primary tumors in 10 patients. The primary sites included breast (n = 10; 37%), gastrointestinal tract (n = 10; 37%), ovary (n = 1; 4%), thyroid (n = 2; 7%), lung (n = 1; 4%), and unknown primary (n = 3; 11%). Expression of all markers was noted with the most significant increases observed in beta-catenin (26 of 27 cases; 96%), followed by CD44v6 (24 of 27 cases; 89%), E-cadherin (22 of 27 cases; 82%), and HER2/neu (11 of 27 cases; 41%). Contrasting expression of these molecules in the primary versus the metastatic tumors, enhanced expression of CD44v6 was observed in the cutaneous metastases relative to the primary in 6 of 10 (60%) cases. Of interest, 2 of these 6 cases (33%) also showed reduction in E-cadherin--a member of the cadherin family functioning as an invasion suppressor molecule. These findings reinforce the complexities of the metastatic cascade and imply that the variation in adhesive properties of tumor cells is, perhaps, a consequence of the difference in density of the molecules mediating this process.

  13. A smart pH-responsive nano-carrier as a drug delivery system for the targeted delivery of ursolic acid: suppresses cancer growth and metastasis by modulating P53/MMP-9/PTEN/CD44 mediated multiple signaling pathways.

    Jiang, Kai; Chi, Ting; Li, Tao; Zheng, Guirong; Fan, Lulu; Liu, Yajun; Chen, Xiufen; Chen, Sijia; Jia, Lee; Shao, Jingwei

    2017-07-13

    Ursolic acid (UA) has been recently used as a promising anti-tumor and cancer metastatic chemo-preventive agent due to its low toxicity and liver-protecting property. However, the low bioavailability and nonspecific tumor targeting restrict its further clinical application. To address the problem, a silica-based mesoporous nanosphere (MSN) controlled-release drug delivery system (denoted UA@M-CS-FA) was designed and successfully synthesized, and was functionalized with folic acid (FA) and pH-sensitive chitosan (CS) for the targeted delivery of UA to folate receptor (FR) positive tumor cells. UA@M-CS-FA were spherical with mean diameter below 150 nm, and showed about -20 mV potential. Meanwhile, UA@M-CS-FA exhibited a pH-sensitive release manner and high cellular uptake in FR over-expressing HeLa cancer cells. Also, in vitro cellular assays suggested that UA@M-CS-FA inhibited cancer cell growth, invasion and migration. Mechanistically, UA@M-CS-FA induced cancer cell apoptosis and inhibited migration via cell cycle arrest in the G0/G1 stage, regulating the PARP/Bcl-2/MMP-9/CD44/PTEN/P53. Importantly, in vivo experiments further confirmed that UA@M-CS-FA significantly suppressed the tumor progression and lung metastasis in tumor-bearing nude mice. Immunohistochemical analysis revealed that UA@M-CS-FA treatment regulated CD44, a biomarker of cancer metastasis. Overall, our data demonstrated that a CS and FA modified MSN controlled-release drug delivery system could help broaden the usage of UA and reflect the great application potential of the UA as an anticancer or cancer metastatic chemopreventive agent.

  14. Expression of COX-2, CD44v6 and CD147 and relationship with invasion and lymph node metastasis in hypopharyngeal squamous cell carcinoma.

    Qing Yang

    Full Text Available To assess the expression of COX-2,CD44v6 and CD147 in hypopharyngeal squamous cell carcinomas and the three biomarkers correlation with tumor invasion and lymph node metastasis of Chinese people. 101 cases of surgically excised primary tumor were included in this study, and 40 tissues of epithelium adjacent to carcinoma were used as controls. We characterized the immunohistochemical expression of COX-2, CD44v6, and CD147 in 141 formalin-fixed, paraffin-embedded tissues, and measured the mean optical density (OD of the positive area to identify the expression of the three bio-markers and relationship with tumor invasion and lymph node metastasis. Our study demonstrates that the expression of the COX-2 and CD147 were significantly increased in carcinoma tissues compared to the epithelium adjacent to carcinoma. We also observed that the expression of COX-2, CD44v6, and CD147 were significantly associated with T classification, lymph node metastasis and clinical stage. There was strong significant correlation among the three biomarkers as well. Additionally, we indicated that recurrence and ≥ P50 level of COX-2 expression had an independent prognostic effect on prognosis. In conclusion, the three biomarkers play important roles in tumor invasion and lymph node metastases and might be valuable indicators of tumor metastasis in hypopharyngeal squamous cell carcinoma.

  15. Manualization of Occupational Therapy Interventions: Illustrations from the Pressure Ulcer Prevention Research Program

    Blanche, Erna Imperatore; Fogelberg, Donald; Diaz, Jesus; Carlson, Mike; Clark, Florence

    2011-01-01

    The manualization of a complex occupational therapy intervention is a crucial step in ensuring treatment fidelity for both clinical application and research purposes. Towards this latter end, intervention manuals are essential for assuring trustworthiness and replicability of randomized controlled trials (RCT’s) that aim to provide evidence of the effectiveness of occupational therapy. In this paper, literature on the process of intervention manualization is reviewed. The prescribed steps are then illustrated through our experience in implementing the University of Southern California/Rancho Los Amigos National Rehabilitation Center’s collaborative Pressure Ulcer Prevention Project (PUPP). In this research program, qualitative research provided the initial foundation for manualization of a multifaceted occupational therapy intervention designed to reduce incidence of medically serious pressure ulcers in people with SCI. PMID:22214116

  16. Let us prevent occupational cancers - Paris, 18-20 November 2009

    Delepine, A.; Falcy, M.; Hery, M.

    2010-01-01

    This document first presents and comments the proposals for action made by the colloquium scientific committee: improvement of the policy of information on risks, identification, suppression and substitution of carcinogenic products, improved action towards very small and medium-sized enterprises, and a better consideration of activities related to production (maintenance, cleaning and so on). The next part proposes large abstracts of contributions on various themes: current status (changes of institutions and practices of prevention, the CMR national plan, experience and action of a CHSCT of the oil industry sector), present issues (occupational cancers, detection of emerging pathologies in occupational environment), assessment of the number of occupational cancers, exposure characterization and assessment, mobilization and substitution, exposure tracing, information, training and awareness raising

  17. Hyaluronic acid–nimesulide conjugates as anticancer drugs against CD44-overexpressing HT-29 colorectal cancer in vitro and in vivo

    Jian YS

    2017-03-01

    Full Text Available You-Sin Jian,1 Ching-Wen Chen,1 Chih-An Lin,2 Hsiu-Ping Yu,1 Hua-Yang Lin,3 Ming-Yuan Liao,1 Shu-Huan Wu,1 Yan-Fu Lin,1 Ping-Shan Lai1,2,4,5 1Department of Chemistry, 2PhD Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung, 3Preclinical Development Research Department, Holy Stone Healthcare Co., Ltd., Taipei, 4Research Center for Sustainable Energy and Nanotechnology, 5Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan Abstract: Carrier-mediated drug delivery systems are promising therapeutics for targeted delivery and improved efficacy and safety of potent cytotoxic drugs. Nimesulide is a multifactorial cyclooxygenase 2 nonsteroidal anti-inflammatory drug with analgesic, antipyretic and potent anticancer properties; however, the low solubility of nimesulide limits its applications. Drugs conjugated with hyaluronic acid (HA are innovative carrier-mediated drug delivery systems characterized by CD44-mediated endocytosis of HA and intracellular drug release. In this study, hydrophobic nimesulide was conjugated to HA of two different molecular weights (360 kDa as HA with high molecular weight [HAH] and 43kDa as HA with low molecular weight [HAL] to improve its tumor-targeting ability and hydrophilicity. Our results showed that hydrogenated nimesulide (N-[4-amino-2-phenoxyphenyl]methanesulfonamide was successfully conjugated with both HA types by carbodiimide coupling and the degree of substitution of nimesulide was 1%, which was characterized by 1H nuclear magnetic resonance 400 MHz and total correlation spectroscopy. Both Alexa Fluor® 647 labeled HAH and HAL could selectively accumulate in CD44-overexpressing HT-29 colorectal tumor area in vivo, as observed by in vivo imaging system. In the in vitro cytotoxic test, HA–nimesulide conjugate displayed >46% cell killing ability at a nimesulide concentration of 400 µM in HT-29 cells, whereas

  18. HAb18G/CD147 Promotes pSTAT3-Mediated Pancreatic Cancer Development via CD44s †, ‡

    Li, Ling; Tang, Wenhua; Wu, Xiaoqing; Karnak, David; Meng, Xiaojie; Thompson, Rachel; Hao, Xinbao; Li, Yongmin; Qiao, Xiaotan T.; Lin, Jiayuh; Fuchs, James; Simeone, Diane M.; Chen, Zhi-Nan; Lawrence, Theodore S.; Xu, Liang

    2013-01-01

    Purpose STAT3 plays a critical role in initiation and progression of pancreatic cancer. However, therapeutically targeting STAT3 is failure in clinic. We previously identified HAb18G/CD147 as an effective target for cancer treatment. In this study, we aimed to investigate potential role of HAb18G/CD147 in STAT3-involved pancreatic tumorigenesis in vitro and in vivo. Experimental Design The expression of HAb18G/CD147, pSTAT3 and CD44s were determined in tissue microarrays. The tumorigenic function and molecular signaling mechanism of HAb18G/CD147 was assessed by in vitro cellular and clonogenic growth, reporter assay, immunoblot, immunofluorescence staining, immunoprecipitation, and in vivo tumor formationusing loss or gain-of-function strategies. Results Highly expressed HAb18G/CD147 promoted cellular and clonogenic growth in vitro and tumorigenicity in vivo. CyPA, a ligand of CD147, stimulated STAT3 phosphorylation and its downstream genes cyclin D1/survivin through HAb18G/CD147 dependent mechanisms. HAb18G/CD147 was associated and co-localized with cancer stem cell marker CD44s in lipid rafts. The inhibitors of STAT3 and survivin, as well as CD44s neutralizing antibodies suppressed the HAb18G/CD147-induced cell growth. High HAb18G/CD147 expression in pancreatic cancer was significantly correlated with the poor tumor differentiation, and the high co-expression of HAb18G/CD147-CD44s-STAT3 associated with poor survival of patients with pancreatic cancer. Conclusions We identified HAb18G/CD147 as a novel upstream activator of STAT3 via interacts with CD44s and plays a critical role in the development of pancreatic cancer. The data suggest HAb18G/CD147 could be a promising therapeutic target for highly aggressive pancreatic cancer and a surrogate marker in the STAT3-targeted molecular therapies. PMID:24132924

  19. [Field investigation of occupational disease diagnosis in Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment from 2009 to 2014: an analysis of 136 cases].

    Fan, C Y; Li, X D; Wen, W; Wang, Y Y; Zhang, Y; Lang, L

    2016-04-20

    To investigate the characteristics of 136 patients with occupational diseases, to summarize key techniques used in field investigation, and to provide a scientific basis for the development of standard operating procedures for field investigation of occupational disease diagnosis. Field investigation and routine data analysis were performed to analyze the cases diagnosed by Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment from January 2009 to December 2014. A total of 136 cases of occupational diseases were diagnosed by Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment from 2009 to 2014, and there were 66 cases of leukemia, 18 cases of suspected occupational benzene poisoning, 12 cases of suspected occupational handarm vibration disease, and 11 cases of suspected pneumoconiosis. Of all these patients, 41.91% were engaged in at least three types of work, 70.59% were exposed to at least three types of chemicals, 25.74% experienced changes in technical processes and chemicals, and 47.06% had disputes on the chemicals they were exposed to during verification by both parties. Occupational hazard factors were detected. Most samples (358)were used to measure benzene concentration in workplace air, among which 11.7% had a benzene concentration of >6.00 mg/m(3)(exceeding standard), 13.41% had a benzene concentration of 3.26~6.00 mg/m(3), 75.42% had a benzene concentration ofoccupational hand-arm vibration disease, suspected pneumoconiosis, and suspected occupational noiseinduced hearing loss had high overstandard rates (100%, 93.8%, and 83.3%, respectively). Field investigation of occupational disease diagnosis reveals large numbers of cases of leukemia, suspected occupational benzene poisoning, suspected occupational hand-arm vibration disease, and suspected pneumoconiosis. The key aspects of field investigation include confirmation of the history of occupational exposure, identification of occupational hazard

  20. [Theories of behavior change through preventive and health promotion interventions in occupational therapy].

    Filiatrault, Johanne; Richard, Lucie

    2005-02-01

    Community occupational therapy practice challenges therapists in their health educator role and incites them to implement preventive strategies with their clients. Working in the community also provides an interesting context for the implementation of strategies targeting health promotion at the community level. This article describes some of the theories that are used in the public health and health promotion fields to explain health-related behaviour change. It also highlights their potential for community practice in occupational therapy. The theories presented in this paper are the health belief model, social cognitive theory, theory of reasoned action and theory of planned behavior. They are among the most widely used for health-related behaviour analysis and intervention. Since these theories emphasize a set of factors that influence health behaviours, reviewing these theories could contribute to enhance the effectiveness of educational interventions with regards to clients'adherence to their prevention and health promotion recommendations.

  1. Prevention of risks in relation with occupational exposure to ionizing radiation

    2005-01-01

    After remind the base notions in the field of ionizing radiation, this file evaluates the situation on the natural and occupational exposures: modes, sources, and exposure level, risk for health. It presents the principles of prevention allowing in a professional area (out of nuclear industry) to reduce and control these exposures. Some practical cases illustrate the radiation protection approach. references are given: regulatory benchmarks, useful links, books to consult. (N.C.)

  2. Experiences of occupational physicians with the implementation of indicated prevention for long term sickness absence.

    de Brouwer, Carin P M; Verdonk, Petra; van Amelsvoort, Ludovic G P M; Jansen, Nicole W H; Kant, IJmert; Widdershoven, Guy A M

    2017-01-01

    Functioning including work participation, is an emerging challenge in occupational health. The prevention of long term sickness absence (LTSA) through a strategy involving screening and structured early consultation (preventive strategy) was proven effective and can address participation issues. Implementation of this strategy has proven difficult. The aim of this study is to investigate the experiences of occupational physicians (OPs) delivering a structured early consultation to office workers, in order to enhance implementation of the strategy. In this case study, a mixed method design was used. Interviews and surveys were conducted to obtain an in-depth picture of OPs experiences. Factors hindering implementation in relation to the OPs were difficulties in communicating the risk of future sick leave, prioritization of other tasks, maintaining a reactive approach due to work pressure, preference for prevention on the level of the work environment, privacy issues related to labeling workers to have mental or psychosocial issues, and the biomedical model being the mental model in use. Implementation of the preventive strategy seems to require a more profound focus on the biopsychosocial approach. Training of relevant skills is important to achieve a focus on prevention and fostering health over the lifespan.

  3. [Use of hypertext as information and training tools in the prevention of occupational risk].

    Franco, G

    1998-01-01

    Modern medical education is based on a variety of teaching techniques, by means of which individuals learn most effectively. The availability of the new technologies together with the diffusion of personal computers is favouring the spreading of the use of hypertexts through the World Wide Web. This contribution describes 2 hypertexts ("Human Activities and Health Risk"; "Occupation, Risk and Disease. A Problem-Oriented Hypertext-Tool to Learn Occupational Medicine") and the prototype "Virtual Hospital". Assuming that prevention of health risks is based upon their knowledge, they have been created with the aim of providing users with problem-oriented tools, whose retorical aspects (content, information organization, user interface) are analysed. The "Human Activities and Health Risk" deals with the description of working activities and allows user to recognize health risks. The "Occupation, Risk and Disease. A Problem-Oriented Hypertext-Tool to Learn Occupational Medicine" embodies a case report containing the clustered information about the patient and the library including educational material (risk factors, symptoms and signs, organ system diseases, jobs, occupational risk factors, environment related diseases. The "Virtual Hospital" has been conceived assuming that an appropriate information can change workers' behaviour in hospital, where health risks can be often underevaluated. It consists of a variety of structured and unstructured information, which can be browsed by users, allowing the discovery of links and providing the awareness of the semantic relationship between related information elements (including environment, instruments, drugs, job analysis, situations at risk for health, preventive means). The "Virtual Hospital" aims making the understanding of the working situations at risk easier and more interesting, stimulating the awareness of the relationship between jobs and risks.

  4. AN EFFECTIVE RISK-PREVENTIVE MODEL PROPOSAL FOR OCCUPATIONAL ACCIDENTS AT SHIPYARDS

    Ozge Acuner

    2016-03-01

    Full Text Available According to the statistics of occupational accidents, it is observed that the number of accidents occurred in shipbuilding industry is high and the rate of deaths and serious injuries among these accidents is higher than in other industries. However, the number of the studies to prevent these accidents in both industrial and scientific practices is considerably low. Therefore, the objective of this study is to develop an efficient risk preventive model in accordance with occupational health and safety regulations for industrial organizations. The approach proposed in this study differs from those described in the literature, because it is based on fuzzy set theory in order to cope with uncertainties on probability and severity definitions in terms of occupational health and safety. Furthermore, in this paper, risk severity is considered in terms of harm to worker, harm to environment, and harm to hardware, whereas in the literature, risk severity is generally considered solely in terms of only harm to worker. Then, risk magnitude is obtained by utilizing fuzzy inference system. The proposed approach is applied to a shipyard located in the Marmara Region in order to illustrate the applicability of the model.

  5. Clinically relevant morphological structures in breast cancer represent transcriptionally distinct tumor cell populations with varied degrees of epithelial-mesenchymal transition and CD44+CD24- stemness.

    Denisov, Evgeny V; Skryabin, Nikolay A; Gerashchenko, Tatiana S; Tashireva, Lubov A; Wilhelm, Jochen; Buldakov, Mikhail A; Sleptcov, Aleksei A; Lebedev, Igor N; Vtorushin, Sergey V; Zavyalova, Marina V; Cherdyntseva, Nadezhda V; Perelmuter, Vladimir M

    2017-09-22

    Intratumor morphological heterogeneity in breast cancer is represented by different morphological structures (tubular, alveolar, solid, trabecular, and discrete) and contributes to poor prognosis; however, the mechanisms involved remain unclear. In this study, we performed 3D imaging, laser microdissection-assisted array comparative genomic hybridization and gene expression microarray analysis of different morphological structures and examined their association with the standard immunohistochemistry scorings and CD44 + CD24 - cancer stem cells. We found that the intratumor morphological heterogeneity is not associated with chromosomal aberrations. By contrast, morphological structures were characterized by specific gene expression profiles and signaling pathways and significantly differed in progesterone receptor and Ki-67 expression. Most importantly, we observed significant differences between structures in the number of expressed genes of the epithelial and mesenchymal phenotypes and the association with cancer invasion pathways. Tubular (tube-shaped) and alveolar (spheroid-shaped) structures were transcriptionally similar and demonstrated co-expression of epithelial and mesenchymal markers. Solid (large shapeless) structures retained epithelial features but demonstrated an increase in mesenchymal traits and collective cell migration hallmarks. Mesenchymal genes and cancer invasion pathways, as well as Ki-67 expression, were enriched in trabecular (one/two rows of tumor cells) and discrete groups (single cells and/or arrangements of 2-5 cells). Surprisingly, the number of CD44 + CD24 - cells was found to be the lowest in discrete groups and the highest in alveolar and solid structures. Overall, our findings indicate the association of intratumor morphological heterogeneity in breast cancer with the epithelial-mesenchymal transition and CD44 + CD24 - stemness and the appeal of this heterogeneity as a model for the study of cancer invasion.

  6. Organotypic culture of normal, dysplastic and squamous cell carcinoma-derived oral cell lines reveals loss of spatial regulation of CD44 and p75 NTR in malignancy.

    Dalley, Andrew J; AbdulMajeed, Ahmad A; Upton, Zee; Farah, Camile S

    2013-01-01

    Oral squamous cell carcinomas (OSCC) often arise from dysplastic lesions. The role of cancer stem cells in tumour initiation is widely accepted, yet the potential existence of pre-cancerous stem cells in dysplastic tissue has received little attention. Cell lines from oral diseases ranging in severity from dysplasia to malignancy provide opportunity to investigate the involvement of stem cells in malignant progression from dysplasia. Stem cells are functionally defined by their ability to generate hierarchical tissue structures in consortium with spatial regulation. Organotypic cultures readily display tissue hierarchy in vitro; hence, in this study, we compared hierarchical expression of stem cell-associated markers in dermis-based organotypic cultures of oral epithelial cells from normal tissue (OKF6-TERT2), mild dysplasia (DOK), severe dysplasia (POE-9n) and OSCC (PE/CA P J15). Expression of CD44, p75(NTR), CD24 and ALDH was studied in monolayers by flow cytometry and in organotypic cultures by immunohistochemistry. Spatial regulation of CD44 and p75(NTR) was evident for organotypic cultures of normal (OKF6-TERT2) and dysplasia (DOK and POE-9n) but was lacking for OSCC (PE/CA PJ15)-derived cells. Spatial regulation of CD24 was not evident. All monolayer cultures exhibited CD44, p75(NTR), CD24 antigens and ALDH activity (ALDEFLUOR(®) assay), with a trend towards loss of population heterogeneity that mirrored disease severity. In monolayer, increased FOXA1 and decreased FOXA2 expression correlated with disease severity, but OCT3/4, Sox2 and NANOG did not. We conclude that dermis-based organotypic cultures give opportunity to investigate the mechanisms that underlie loss of spatial regulation of stem cell markers seen with OSCC-derived cells. © 2012 John Wiley & Sons A/S.

  7. CD44+/CD24- breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide RADA16 nanofiber scaffold

    Mi K

    2015-04-01

    Full Text Available Kun Mi,1 Zhihua Xing2 1Department of Biochemistry and Molecular Biology, Sichuan Cancer Hospital and Institute, 2Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Background: Self-assembling peptide nanofiber scaffolds have been shown to be a ­permissive biological material for tissue repair, cell proliferation, differentiation, etc. Recently, a subpopulation (CD44+/CD24- of breast cancer cells has been reported to have stem/progenitor cell properties. The aim of this study was to investigate whether this subpopulation of cancer cells have different phenotypes in self-assembling COCH3-RADARADARADARADA-CONH2 (RADA16 peptide nanofiber scaffold compared with Matrigel® (BD Biosciences, Two Oak Park, Bedford, MA, USA and collagen I.Methods: CD44 and CD24 expression was determined by flow cytometry. Cell proliferation was measured by 5-bromo-2'-deoxyuridine assay and DNA content measurement. Immunostaining was used to indicate the morphologies of cells in three-dimensional (3D cultures of different scaffolds and the localization of β-catenin in the colonies. Western blot was used to determine the expression of signaling proteins. In vitro migration assay and inoculation into nude mice were used to evaluate invasion and tumorigenesis in vivo.Results: The breast cancer cell line MDA-MB-435S contained a high percentage (>99% of CD44+/CD24- cells, which exhibited phenotypic reversion in 3D RADA16 nanofiber scaffold compared with collagen I and Matrigel. The newly formed reverted acini-like colonies reassembled a basement membrane and reorganized their cytoskeletons. At the same time, cells cultured and embedded in RADA16 peptide scaffold exhibited growth arrest. Also, they exhibited different migration potential, which links their migration ability with their cellular morphology. Consistent with studies in vitro, the in vivo tumor

  8. Amelioration of murine passive immune thrombocytopenia by IVIg and a therapeutic monoclonal CD44 antibody does not require the Myd88 signaling pathway.

    Andrew R Crow

    Full Text Available Immune thrombocytopenia (ITP is an autoimmune bleeding disorder characterized by a low platelet count and the production of anti-platelet antibodies. The majority of ITP patients have antibodies to platelet integrin α(IIbβ₃ (GPIIbIIIa which can direct platelet phagocytosis by macrophages. One effective treatment for patients with ITP is intravenous immunoglobulin (IVIg which rapidly reverses thrombocytopenia. The exact mechanism of IVIg action in human patients is unclear, although in mouse models of passive ITP, IVIg can rapidly increase platelet counts in the absence of adaptive immunity. Another antibody therapeutic that can similarly increase platelet counts independent of adaptive immunity are CD44 antibodies. Toll-like receptors (TLRs are pattern recognition receptors which play a central role in helping direct the innate immune system. Dendritic cells, which are notable for their expression of TLRs, have been directly implicated in IVIg function as an initiator cell, while CD44 can associate with TLR2 and TLR4. We therefore questioned whether IVIg, or the therapeutic CD44 antibody KM114, mediate their ameliorative effects in a manner dependent upon normal TLR function. Here, we demonstrate that the TLR4 agonist LPS does not inhibit IVIg or KM114 amelioration of antibody-induced thrombocytopenia, and that these therapeutics do not ameliorate LPS-induced thrombocytopenia. IVIg was able to significantly ameliorate murine ITP in C3H/HeJ mice which have defective TLR4. All known murine TLRs except TLR3 utilize the Myd88 adapter protein to drive TLR signaling. Employing Myd88 deficient mice, we found that both IVIg and KM114 ameliorate murine ITP in Myd88 deficient mice to the same extent as normal mice. Thus both IVIg and anti-CD44 antibody can mediate their ameliorative effects in murine passive ITP independent of the Myd88 signaling pathway. These data help shed light on the mechanism of action of IVIg and KM114 in the amelioration of

  9. Genetic Variants in CD44 and MAT1A Confer Susceptibility to Acute Skin Reaction in Breast Cancer Patients Undergoing Radiation Therapy

    Mumbrekar, Kamalesh Dattaram; Bola Sadashiva, Satish Rao [Department of Radiation Biology and Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka (India); Kabekkodu, Shama Prasada [Department of Biotechnology, School of Life Sciences, Manipal University, Manipal, Karnataka (India); Fernandes, Donald Jerard [Department of Radiotherapy and Oncology, Shirdi Saibaba Cancer Hospital and Research Centre, Kasturba Hospital, Manipal, Karnataka (India); Vadhiraja, Bejadi Manjunath [Department of Radiation Oncology, Manipal Hospital, Bengaluru, Karnataka (India); Suga, Tomo; Shoji, Yoshimi; Nakayama, Fumiaki; Imai, Takashi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Satyamoorthy, Kapaettu, E-mail: ksatyamoorthy@yahoo.com [Department of Biotechnology, School of Life Sciences, Manipal University, Manipal, Karnataka (India)

    2017-01-01

    Purpose: Heterogeneity in radiation therapy (RT)-induced normal tissue toxicity is observed in 10% of cancer patients, limiting the therapeutic outcomes. In addition to treatment-related factors, normal tissue adverse reactions also manifest from genetic alterations in distinct pathways majorly involving DNA damage–repair genes, inflammatory cytokine genes, cell cycle regulation, and antioxidant response. Therefore, the common sequence variants in these radioresponsive genes might modify the severity of normal tissue toxicity, and the identification of the same could have clinical relevance as a predictive biomarker. Methods and Materials: The present study was conducted in a cohort of patients with breast cancer to evaluate the possible associations between genetic variants in radioresponsive genes described previously and the risk of developing RT-induced acute skin adverse reactions. We tested 22 genetic variants reported in 18 genes (ie, NFE2L2, OGG1, NEIL3, RAD17, PTTG1, REV3L, ALAD, CD44, RAD9A, TGFβR3, MAD2L2, MAP3K7, MAT1A, RPS6KB2, ZNF830, SH3GL1, BAX, and XRCC1) using TaqMan assay-based real-time polymerase chain reaction. At the end of RT, the severity of skin damage was scored, and the subjects were dichotomized as nonoverresponders (Radiation Therapy Oncology Group grade <2) and overresponders (Radiation Therapy Oncology Group grade ≥2) for analysis. Results: Of the 22 single nucleotide polymorphisms studied, the rs8193 polymorphism lying in the micro-RNA binding site of 3′-UTR of CD44 was significantly (P=.0270) associated with RT-induced adverse skin reactions. Generalized multifactor dimensionality reduction analysis showed significant (P=.0107) gene–gene interactions between MAT1A and CD44. Furthermore, an increase in the total number of risk alleles was associated with increasing occurrence of overresponses (P=.0302). Conclusions: The genetic polymorphisms in radioresponsive genes act as genetic modifiers of acute normal tissue toxicity

  10. INTERDISCIPLINARY MODULE IN PREVENTION AND HEALTH PROMOTION IN POPULATION HEALTH FOR OCCUPATIONAL THERAPY AND PHYSIOTHERAPY STUDENTS

    Brandt, Jørgen

    -operate towards appropriate solutions. The groups suggest and present preventive and health promotion solutions and strategies especially designed for this particular situation. The groups are supervised by an interdisciplinary team of occupational therapy and physiotherapy lecturers. In addition......PURPOSE: The purpose is to provide physiotherapy and occupational therapy students at the University College Cvu vita in Holstebro, Denmark, the opportunity to develop competences for interdisciplinary working situations concerning promotion of population health. RELEVANCE: The Danish Ministry...... of the Interior and Health participates in co-operation within the European Union on health areas, which focuses on efforts with respect to public health (Article 152 of the Treaty on EU). The curricula for both educations underline the importance of preparing the students for interdisciplinary co...

  11. Organisational factors of occupational accidents with movement disturbance (OAMD) and prevention.

    Leclercq, Sylvie

    2014-01-01

    Workplace design and upkeep, or human factors, are frequently advanced for explaining so-called Occupational Slip, Trip and Fall Accidents (OSTFAs). Despite scientific progress, these accidents, and more broadly Occupational Accidents with Movement Disturbance (OAMDs), are also commonly considered to be "simple". This paper aims to stimulate changes in such perceptions by focusing on organisational factors that often combine with other accident factors to cause movement disturbance and injury in work situations. These factors frequently lead to arbitration between production and safety, which involves implementation of controls by workers. These controls can lead to greater worker exposure to OAMD risk. We propose a model that focuses on such controls to account specifically for the need to confront production and safety logics within a company and to enhance the potential for appropriate prevention action. These are then integrated into the set of controls highlighted by work organisation model developed by the NIOSH.

  12. Managing preventive occupational health and safety activities in Danish enterprises during a period of financial crisis

    Andersen, Hans H. K.; Bach, Elsa

    2017-01-01

    The onset of the financial crisis in 2008 has put pressure on enterprises that in turn have downsized and reorganized. Research has shown that economic recession has an effect on psychological and behavioral health that is attributed to working environment problems. The objective of this study is...... focus on the management of preventive workplace health and safety activities in enterprises during a period of economic recession....... is to unravel whether the onset of a general economic recession has had an impact on companies’ and public institutions’ preventive occupational health and safety activities. Hypotheses of the role of pro-cyclical and countercyclical effects are presented. This study is based on a survey of enterprise...... preventive occupational health safety activities. The baseline for the survey was established, in 2006 before the onset of the recession, with a follow up in 2011. Findings are discussed that support both the pro-cyclical and the countercyclical hypotheses. It is concluded that there is a need for a special...

  13. A single molecule assay to probe monovalent and multivalent bonds between hyaluronan and its key leukocyte receptor CD44 under force

    Bano, Fouzia; Banerji, Suneale; Howarth, Mark; Jackson, David G.; Richter, Ralf P.

    2016-09-01

    Glycosaminoglycans (GAGs), a category of linear, anionic polysaccharides, are ubiquitous in the extracellular space, and important extrinsic regulators of cell function. Despite the recognized significance of mechanical stimuli in cellular communication, however, only few single molecule methods are currently available to study how monovalent and multivalent GAG·protein bonds respond to directed mechanical forces. Here, we have devised such a method, by combining purpose-designed surfaces that afford immobilization of GAGs and receptors at controlled nanoscale organizations with single molecule force spectroscopy (SMFS). We apply the method to study the interaction of the GAG polymer hyaluronan (HA) with CD44, its receptor in vascular endothelium. Individual bonds between HA and CD44 are remarkably resistant to rupture under force in comparison to their low binding affinity. Multiple bonds along a single HA chain rupture sequentially and independently under load. We also demonstrate how strong non-covalent bonds, which are versatile for controlled protein and GAG immobilization, can be effectively used as molecular anchors in SMFS. We thus establish a versatile method for analyzing the nanomechanics of GAG·protein interactions at the level of single GAG chains, which provides new molecular-level insight into the role of mechanical forces in the assembly and function of GAG-rich extracellular matrices.

  14. MDR1 siRNA loaded hyaluronic acid-based CD44 targeted nanoparticle systems circumvent paclitaxel resistance in ovarian cancer

    Yang, Xiaoqian; Lyer, Arun K.; Singh, Amit; Choy, Edwin; Hornicek, Francis J.; Amiji, Mansoor M.; Duan, Zhenfeng

    2015-02-01

    Development of multidrug resistance (MDR) is an almost universal phenomenon in patients with ovarian cancer, and this severely limits the ultimate success of chemotherapy in the clinic. Overexpression of the MDR1 gene and corresponding P-glycoprotein (Pgp) is one of the best known MDR mechanisms. MDR1 siRNA based strategies were proposed to circumvent MDR, however, systemic, safe, and effective targeted delivery is still a major challenge. Cluster of differentiation 44 (CD44) targeted hyaluronic acid (HA) based nanoparticle has been shown to successfully deliver chemotherapy agents or siRNAs into tumor cells. The goal of this study is to evaluate the ability of HA-PEI/HA-PEG to deliver MDR1 siRNA and the efficacy of the combination of HA-PEI/HA-PEG/MDR1 siRNA with paclitaxel to suppress growth of ovarian cancer. We observed that HA-PEI/HA-PEG nanoparticles can efficiently deliver MDR1 siRNA into MDR ovarian cancer cells, resulting in down-regulation of MDR1 and Pgp expression. Administration of HA-PEI/HA-PEG/MDR1 siRNA nanoparticles followed by paclitaxel treatment induced a significant inhibitory effect on the tumor growth, decreased Pgp expression and increased apoptosis in MDR ovarian cancer mice model. Our findings suggest that CD44 targeted HA-PEI/HA-PEG/MDR1 siRNA nanoparticles can serve as a therapeutic tool with great potentials to circumvent MDR in ovarian cancer.

  15. The implementation of knowledge dissemination in the prevention of occupational skin diseases.

    Wilke, A; Bollmann, U; Cazzaniga, S; Hübner, A; John, S M; Karadzinska-Bislimovska, J; Mijakoski, D; Šimić, D; Simon, D; Sonsmann, F; Stoleski, S; Weinert, P; Wulfhorst, B

    2018-03-01

    Occupational skin diseases (OSD) have a high medical, social, economic and political impact. Knowledge dissemination from research activities to key stakeholders involved in health care is a prerequisite to make prevention effective. To study and prioritize different activity fields and stakeholders that are involved in the prevention of OSD, to reflect on their inter-relationships, to develop a strategic approach for knowledge dissemination and to develop a hands-on tool for OSD prevention projects METHODS: Seven different activity fields that are relevant in the prevention of OSD have been stepwise identified. This was followed by an impact analysis. Fifty-five international OSD experts rated the impact and the influence of the activity fields for the prevention of OSD with a standardized questionnaire. Activity fields identified to have a high impact in OSD prevention are the political system, mass media and industry. The political system has a strong but more indirect effect on the general population via the educational system, local public health services or the industry. The educational system, mass media, industry and local public health services have a strong direct impact on the OSD 'at risk' worker. Finally, a hands-on tool for future OSD prevention projects has been developed that addresses knowledge dissemination and different stakeholder needs. Systematic knowledge dissemination is important to make OSD prevention more effective and to close the gap between research and practice. This study provides guidance to identify stakeholders, strategies and dissemination channels for systematic knowledge dissemination which need to be adapted to country-specific structures, for example the social security system and healthcare systems. A key for successful knowledge dissemination is building linkages among different stakeholders, building strategic partnerships and gaining their support right from the inception phase of a project. © 2017 European Academy of

  16. Occupational therapists lead a national injury prevention strategy to help older drivers.

    Craik, Janet M

    2011-04-01

    As older adults are the fastest growing segment of the driving population, the Canadian Association of Occupational Therapists (CAOT) has taken older driver safety as a key priority. The purpose of this paper is to present the National Blueprint for Injury Prevention in Older Drivers (Blueprint) and its related activities. Since 2006, CAOT has been working on initiatives relating to the National Blueprint for Injury Prevention in Older Drivers. The most recent activities include the launch of informational brochures and a website. The Blueprint and its related activities were developed with the intent to prolong safe driving among older adults in Canada, and to propose future actions to be addressed by all stakeholders interested in older driver safety.

  17. 41 CFR 102-74.360 - What are the specific accident and fire prevention responsibilities of occupant agencies?

    2010-07-01

    ... other hanging materials that are made of non-combustible or flame-resistant fabric; (f) Use only... resistant; (g) Cooperate with GSA to develop and maintain fire prevention programs that provide the maximum... accident and fire prevention responsibilities of occupant agencies? 102-74.360 Section 102-74.360 Public...

  18. Occupational injuries and illnesses in rubber factory: Profile, Potential Hazards and possible prevention

    Tri Hari Irfani

    2015-12-01

    Full Text Available Rubber is one of the important commodities in the world. Globally, workers are facing so many problems of hazards that produce by rubber process. In Indonesia, there are several data of occupational problems such as respiratory diseases, muscle and skeletal diseases, gastrointestinal diseases, diseases of the teeth and oral cavity, skin diseases and skin tissue. In Iranian rubber factory, Iran, workers had suffered from some kind of musculoskeletal symptoms. Stomach and liver cancers in workers are having in Shanghai tire factory. In addition, Germany has cancer problem of their workers who work in rubber factory. Most of the rubber process in the factory can cause some hazards of the workers. In unloading area and area that operator is taking the dirt manually, workers are facing ergonomic problems. The possible control is reduce weight of load, team lift the object with two or more workers and Use mechanical assist. Machine safeguarding is essential for protecting from Cutting process that can make workers amputation organs such as hands, and fingers. In bale process, the workers need to cut raw rubber into bale in bale cutting. Furthermore, workers are facing with amputation problem. To manage that, It must be designed as a standard which has interlocking guards to prevent access to the cutting area. When wrapped using plastic, workers use a heated iron and sticked in plastic so that it blends neatly. The risks are fingers can cut accidently and then the workers also get contamination from polyvinyl chloride (PVC. The possible preventions are use an automatic plastic wrapping machine with palletized product sitting on a turntable and respirator. Another problem is contact dermatitis that has been reported frequently among rubber workers. The prevention for that problem is using Gloves. The aim of researcher is to provide the profile of occupational injuries and illnesses, potential hazards in rubber factory to prevent the workers.

  19. Promoter- and cell-specific epigenetic regulation of CD44, Cyclin D2, GLIPR1 and PTEN by Methyl-CpG binding proteins and histone modifications

    Schwarzenbach Heidi

    2010-06-01

    Full Text Available Abstract Background The aim of the current study was to analyze the involvement of methyl-CpG binding proteins (MBDs and histone modifications on the regulation of CD44, Cyclin D2, GLIPR1 and PTEN in different cellular contexts such as the prostate cancer cells DU145 and LNCaP, and the breast cancer cells MCF-7. Since global chromatin changes have been shown to occur in tumours and regions of tumour-associated genes are affected by epigenetic modifications, these may constitute important regulatory mechanisms for the pathogenesis of malignant transformation. Methods In DU145, LNCaP and MCF-7 cells mRNA expression levels of CD44, Cyclin D2, GLIPR1 and PTEN were determined by quantitative RT-PCR at the basal status as well as after treatment with demethylating agent 5-aza-2'-deoxycytidine and/or histone deacetylase inhibitor Trichostatin A. Furthermore, genomic DNA was bisulfite-converted and sequenced. Chromatin immunoprecipitation was performed with the stimulated and unstimulated cells using antibodies for MBD1, MBD2 and MeCP2 as well as 17 different histone antibodies. Results Comparison of the different promoters showed that MeCP2 and MBD2a repressed promoter-specifically Cyclin D2 in all cell lines, whereas in MCF-7 cells MeCP2 repressed cell-specifically all methylated promoters. Chromatin immunoprecipitation showed that all methylated promoters associated with at least one MBD. Treatment of the cells by the demethylating agent 5-aza-2'-deoxycytidine (5-aza-CdR caused dissociation of the MBDs from the promoters. Only MBD1v1 bound and repressed methylation-independently all promoters. Real-time amplification of DNA immunoprecipitated by 17 different antibodies showed a preferential enrichment for methylated lysine of histone H3 (H3K4me1, H3K4me2 and H3K4me3 at the particular promoters. Notably, the silent promoters were associated with unmodified histones which were acetylated following treatment by 5-aza-CdR. Conclusions This study is one

  20. Promoter- and cell-specific epigenetic regulation of CD44, Cyclin D2, GLIPR1 and PTEN by Methyl-CpG binding proteins and histone modifications

    Müller, Imke; Wischnewski, Frank; Pantel, Klaus; Schwarzenbach, Heidi

    2010-01-01

    The aim of the current study was to analyze the involvement of methyl-CpG binding proteins (MBDs) and histone modifications on the regulation of CD44, Cyclin D2, GLIPR1 and PTEN in different cellular contexts such as the prostate cancer cells DU145 and LNCaP, and the breast cancer cells MCF-7. Since global chromatin changes have been shown to occur in tumours and regions of tumour-associated genes are affected by epigenetic modifications, these may constitute important regulatory mechanisms for the pathogenesis of malignant transformation. In DU145, LNCaP and MCF-7 cells mRNA expression levels of CD44, Cyclin D2, GLIPR1 and PTEN were determined by quantitative RT-PCR at the basal status as well as after treatment with demethylating agent 5-aza-2'-deoxycytidine and/or histone deacetylase inhibitor Trichostatin A. Furthermore, genomic DNA was bisulfite-converted and sequenced. Chromatin immunoprecipitation was performed with the stimulated and unstimulated cells using antibodies for MBD1, MBD2 and MeCP2 as well as 17 different histone antibodies. Comparison of the different promoters showed that MeCP2 and MBD2a repressed promoter-specifically Cyclin D2 in all cell lines, whereas in MCF-7 cells MeCP2 repressed cell-specifically all methylated promoters. Chromatin immunoprecipitation showed that all methylated promoters associated with at least one MBD. Treatment of the cells by the demethylating agent 5-aza-2'-deoxycytidine (5-aza-CdR) caused dissociation of the MBDs from the promoters. Only MBD1v1 bound and repressed methylation-independently all promoters. Real-time amplification of DNA immunoprecipitated by 17 different antibodies showed a preferential enrichment for methylated lysine of histone H3 (H3K4me1, H3K4me2 and H3K4me3) at the particular promoters. Notably, the silent promoters were associated with unmodified histones which were acetylated following treatment by 5-aza-CdR. This study is one of the first to reveal the histone code and MBD profile

  1. Molecular imaging of EGFR and CD44v6 for prediction and response monitoring of HSP90 inhibition in an in vivo squamous cell carcinoma model

    Spiegelberg, Diana; Mortensen, Anja C.; Stenerloew, Bo [Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala (Sweden); Selvaraju, Ram K.; Eriksson, Olof [Uppsala University, Preclinical PET Platform, Uppsala (Sweden); Nestor, Marika [Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala (Sweden); Uppsala University, Unit of Otolaryngology and Head and Neck Surgery, Department of Surgical Sciences, Uppsala (Sweden)

    2016-05-15

    Heat shock protein 90 (HSP90) is essential for the activation and stabilization of numerous oncogenic client proteins. AT13387 is a novel HSP90 inhibitor promoting degradation of oncogenic proteins upon binding, and may also act as a radiosensitizer. For optimal treatment there is, however, the need for identification of biomarkers for patient stratification and therapeutic response monitoring, and to find suitable targets for combination treatments. The aim of this study was to assess the response of surface antigens commonly expressed in squamous cell carcinoma to AT13387 treatment, and to find suitable biomarkers for molecular imaging and radioimmunotherapy in combination with HSP90 inhibition. Cancer cell proliferation and radioimmunoassays were used to evaluate the effect of AT13387 on target antigen expression in vitro. Inhibitor effects were then assessed in vivo in mice-xenografts. Animals were treated with AT13387 (5 x 50 mg/kg), and were imaged with PET using either {sup 18}F-FDG or {sup 124}I-labelled tracers for EGFR and CD44v6, and this was followed by ex-vivo biodistribution analysis and immunohistochemical staining. AT13387 exposure resulted in high cytotoxicity and possible radiosensitization with IC{sub 50} values below 4 nM. Both in vitro and in vivo AT13387 effectively downregulated HSP90 client proteins. PET imaging with {sup 124}I-cetuximab showed a significant decrease of EGFR in AT13387-treated animals compared with untreated animals. In contrast, the squamous cell carcinoma-associated biomarker CD44v6, visualized with {sup 124}I-AbD19384 as well as {sup 18}F-FDG uptake, were not significantly altered by AT13387 treatment. We conclude that AT13387 downregulates HSP90 client proteins, and that molecular imaging of these proteins may be a suitable approach for assessing treatment response. Furthermore, radioimmunotherapy targeting CD44v6 in combination with AT13387 may potentiate the radioimmunotherapy outcome due to radiosensitizing effects of

  2. CD133(+)/CD44(+)/Oct4(+)/Nestin(+) stem-like cells isolated from Panc-1 cell line may contribute to multi-resistance and metastasis of pancreatic cancer.

    Wang, Dongqing; Zhu, Haitao; Zhu, Ying; Liu, Yanfang; Shen, Huiling; Yin, Ruigen; Zhang, Zhijian; Su, Zhaoliang

    2013-05-01

    Pancreatic cancer is an aggressive malignant disease. Owing to the lack of early symptoms, accompanied by extensive metastasis and high resistance to chemotherapy, pancreatic adenocarcinoma becomes the fourth leading cause of cancer-related deaths. In this study, we identified a subpopulation of cells isolated from the Panc-1 cell line and named pancreatic cancer stem-like cells. These Panc-1 stem-like cells expressed high levels of CD133/CD44/Oct4/Nestin. Compared to Panc-1 cells, Panc-1 stem-like cells were resistant to gemcitabine and expressed high levels of MDR1; furthermore, Panc-1 stem-like cells have high anti-apoptotic, but weak proliferative potential. These results indicated that Panc-1 stem-like cells, as a novel group, may be a potential major cause of pancreatic cancer multidrug resistance and extensive metastasis. Copyright © 2012 Elsevier GmbH. All rights reserved.

  3. [Role of specialized care services of the national health service in the framework for the prevention of occupational risks (II)].

    Gallo-Fernández, M

    Since 1986, the Government of Navarra has taken over the functions of security and health as part of the health 'area', with a broad conception of health, avoiding separating the citizen from the worker. In 1993, the Instituto Navarro de Salud Laboral created, under the direction of the departments of Health and Labor, combined diverse functions and resources, integrating preexisting structures into a technical department to be responsible for the overall health care of workers. The structure is based on two coordinated pillars, security and hygiene at work and occupational health. As more specifically to do with health, we describe the systems of epidemiological information and vigilance and programs for occupational disabilities, health activities in industry and investigation of diseases. The Unidades de Salud Laboral link the workplace with the public health service. The occupational health plan of Navarra will set out future strategies. It is necessary to involve neurologists in occupational health. Occupational risks and injury are everyone's problem. The neurologist's role in accidents is usually of health care; detection of illness is more difficult when an occupational relationship is not considered. Data from work should be included in the clinical history. The official figures for occupational neurological diseases are ridiculous and more cases should be detected. There should be a fluid relationship between neurologists, occupational doctors and experts in prevention.

  4. Biomarker screening of oral cancer cell lines revealed sub-populations of CD133-, CD44-, CD24- and ALDH1- positive cancer stem cells

    Kendall K

    2013-05-01

    Full Text Available Head and neck squamous cell carcinoma (HNSCC ranks sixth worldwide for cancer-related mortality. For the past several decades the mainstay of treatment for HNSCC has been surgery and external beam radiation, although more recent trials combining chemotherapy and radiation have demonstrated improvements. However, cancer recurrence and treatment failures continue to occur in a significant percentage of patients. Recent advances in tumor biology have led to the discovery that many cancers, including HNSCC, may contain subpopulations of cells with stem cell-like properties that may explain relapse and recurrence. The objective of this study was to screen existing oral cancer cell lines for biomarkers specific for cells with stem cell-like properties. RNA was isolated for RT-PCR screening using primers for specific mRNA of the biomarkers: CD44, CD24, CD133, NANOG, Nestin, ALDH1, and ABCG2 in CAL27, SCC25 and SCC15 cells. This analysis revealed that some oral cancer cell lines (CAL27 and SCC25 may contain small subpopulations of adhesion- and contact-independent cells (AiDC that also express tumor stem cell markers, including CD44, CD133, and CD24. In addition, CAL27 cells also expressed the intracellular tumor stem cell markers, ALDH1 and ABCG2. Isolation and culture of the adhesion- and contact-independent cells from CAL27 and SCC25 populations revealed differential proliferation rates and more robust inhibition by the MEK inhibitor PD98059, as well as the chemotherapeutic agents Cisplatin and Paclitaxel, within the AiDC CAL27 cells. At least one oral cancer cell line (CAL27 contained subpopulations of cells that express specific biomarkers associated with tumor stem cells which were morphologically and phenotypically distinct from other cells within this cell line.

  5. Who will use claims data for the prevention of occupational trauma?

    Larsson, Tore J

    2003-01-01

    If claims data from the public fund workers' compensation system is merged with the relevant census data, the relative distribution of occupational injury risk in the system can be calculated. A reconstituted occupational code, made from combining the present occupational and industrial codes, can be used to differentiate occupations in relation to hazards. A four-part injury severity index, generated in the claims settling process, can be used to further differentiate occupations, tasks and ...

  6. Interventions to prevent occupational noise-induced hearing loss: A Cochrane systematic review

    Verbeek, Jos H.; Kateman, Erik; Morata, Thais C.; Dreschler, Wouter A.; Mischke, Christina

    2015-01-01

    Objective To assess the effectiveness of interventions for preventing occupational noise exposure or hearing loss compared to no intervention or alternative interventions. Design We searched biomedical databases up to 25 January 2012 for randomized controlled trials (RCT), controlled before-after studies and interrupted time-series of hearing loss prevention among workers exposed to noise. Study sample We included 19 studies with 82 794 participants evaluating effects of hearing loss prevention programs (HLPP). The overall quality of studies was low to very low, as rated using the GRADE approach. Results One study of stricter legislation showed a favorable effect on noise levels. Three studies, of which two RCTs, did not find an effect of a HLPP. Four studies showed that better use of hearing protection devices in HLPPs decreased the risk of hearing loss. In four other studies, workers in a HLPP still had a 0.5 dB greater hearing loss at 4 kHz (95% CI – 0.5 to 1.7) than non-exposed workers. In two similar studies there was a substantial risk of hearing loss in spite of a HLPP. Conclusions Stricter enforcement of legislation and better implementation of HLPPs can reduce noise levels in workplaces. Better evaluations of technical interventions and long-term effects are needed. PMID:24564697

  7. Interventions to prevent occupational noise-induced hearing loss: a Cochrane systematic review.

    Verbeek, Jos H; Kateman, Erik; Morata, Thais C; Dreschler, Wouter A; Mischke, Christina

    2014-03-01

    To assess the effectiveness of interventions for preventing occupational noise exposure or hearing loss compared to no intervention or alternative interventions. We searched biomedical databases up to 25 January 2012 for randomized controlled trials (RCT), controlled before-after studies and interrupted time-series of hearing loss prevention among workers exposed to noise. We included 19 studies with 82 794 participants evaluating effects of hearing loss prevention programs (HLPP). The overall quality of studies was low to very low, as rated using the GRADE approach. One study of stricter legislation showed a favorable effect on noise levels. Three studies, of which two RCTs, did not find an effect of a HLPP. Four studies showed that better use of hearing protection devices in HLPPs decreased the risk of hearing loss. In four other studies, workers in a HLPP still had a 0.5 dB greater hearing loss at 4 kHz (95% CI - 0.5 to 1.7) than non-exposed workers. In two similar studies there was a substantial risk of hearing loss in spite of a HLPP. Stricter enforcement of legislation and better implementation of HLPPs can reduce noise levels in workplaces. Better evaluations of technical interventions and long-term effects are needed.

  8. A comparative analysis of occupational health and safety risk prevention practices in Sweden and Spain.

    Morillas, Rosa María; Rubio-Romero, Juan Carlos; Fuertes, Alba

    2013-12-01

    Scandinavian countries such as Sweden implemented the occupational health and safety (OHS) measures in the European Directive 89/391/EEC earlier than other European counties, including Spain. In fact, statistics on workplace accident rates reveal that between 2004 and 2009, there were considerably fewer accidents in Sweden than in Spain. The objective of the research described in this paper was to reduce workplace accidents and to improve OHS management in Spain by exploring the OHS practices in Sweden. For this purpose, an exploratory comparative study was conducted, which focused on the effectiveness of the EU directive in both countries. The study included a cross-sectional analysis of workplace accident rates and other contextual indicators in both national contexts. A case study of 14 Swedish and Spanish companies identified 14 differences in the preventive practices implemented. These differences were then assessed with a Delphi study to evaluate their contribution to the reduction of workplace accidents and their potential for improving health and safety management in Spain. The results showed that there was agreement concerning 12 of the 14 practices. Finally, we discuss opportunities of improvement in Spanish companies so that they can make their risk management practices more effective. The findings of this comparative study on the implementation of the European Directive 89/391/EEC in both Sweden and Spain have revealed health and safety managerial practices which, if properly implemented, could contribute to improved work conditions and accident statistics of Spanish companies. In particular, the results suggest that Spanish employers, safety managers, external prevention services, safety deputies and Labour Inspectorates should consider implementing streamlined internal preventive management, promoting the integration of prevention responsibilities to the chain of command, and preventing health and safety management from becoming a mere exchange of

  9. Occupational cancer

    Alderson, M.

    1986-01-01

    This book aims to review the occurrence and causes of occupational cancer and is aimed at assisting medical and safety staff, management and health and safety representatives. It is presented in the following chapters: 1) Epidemiological method 2) Agents causing occupationally induced cancer, including radiation 3) Occupations associated with risk of cancer 4) Aetiology of cancer 5) Control of occupationally induced cancer, research, prevention, legislation, national and international bodies, control of specific occupational carcinogens, including irradiation. (U.K.)

  10. Hazard Prevention Regarding Occupational Accidents Involving Blue-Collar Foreign Workers: A Perspective of Taiwanese Manpower Agencies.

    Chang, Huan-Cheng; Wang, Mei-Chin; Liao, Hung-Chang; Cheng, Shu-Fang; Wang, Ya-Huei

    2016-07-13

    Since 1989, blue-collar foreign workers have been permitted to work in Taiwanese industries. Most blue-collar foreign workers apply for jobs in Taiwan through blue-collar foreign workers' agencies. Because blue-collar foreign workers are not familiar with the language and culture in Taiwan, in occupational accident education and hazard prevention, the agencies play an important role in the coordination and translation between employees and blue-collar foreign workers. The purpose of this study is to establish the agencies' role in the occupational accidents education and hazard prevention for blue-collar foreign workers in Taiwan. This study uses a qualitative method-grounded theory-to collect, code, and analyze the data in order to understand the agencies' role in occupational accident education and hazard prevention for blue-collar foreign workers in Taiwan. The results show that the duty of agencies in occupational accident education and hazard prevention includes selecting appropriate blue-collar foreign workers, communicating between employees and blue-collar foreign workers, collecting occupational safety and health information, assisting in the training of occupational safety and health, and helping blue-collar foreign workers adapt to their lives in Taiwan. Finally, this study suggests seven important points and discusses the implementation process necessary to improve governmental policies. The government and employees should pay attention to the education/training of occupational safety and health for blue-collar foreign workers to eliminate unsafe behavior in order to protect the lives of blue-collar foreign workers.

  11. Hazard Prevention Regarding Occupational Accidents Involving Blue-Collar Foreign Workers: A Perspective of Taiwanese Manpower Agencies

    Huan-Cheng Chang

    2016-07-01

    Full Text Available Since 1989, blue-collar foreign workers have been permitted to work in Taiwanese industries. Most blue-collar foreign workers apply for jobs in Taiwan through blue-collar foreign workers’ agencies. Because blue-collar foreign workers are not familiar with the language and culture in Taiwan, in occupational accident education and hazard prevention, the agencies play an important role in the coordination and translation between employees and blue-collar foreign workers. The purpose of this study is to establish the agencies’ role in the occupational accidents education and hazard prevention for blue-collar foreign workers in Taiwan. This study uses a qualitative method—grounded theory—to collect, code, and analyze the data in order to understand the agencies’ role in occupational accident education and hazard prevention for blue-collar foreign workers in Taiwan. The results show that the duty of agencies in occupational accident education and hazard prevention includes selecting appropriate blue-collar foreign workers, communicating between employees and blue-collar foreign workers, collecting occupational safety and health information, assisting in the training of occupational safety and health, and helping blue-collar foreign workers adapt to their lives in Taiwan. Finally, this study suggests seven important points and discusses the implementation process necessary to improve governmental policies. The government and employees should pay attention to the education/training of occupational safety and health for blue-collar foreign workers to eliminate unsafe behavior in order to protect the lives of blue-collar foreign workers.

  12. Occupational risk perception, safety training, and injury prevention: testing a model in the Italian printing industry.

    Leiter, Michael P; Zanaletti, William; Argentero, Piergiorgio

    2009-01-01

    This study examined occupational risk perception in relation to safety training and injuries. In a printing industry, 350 workers from 6 departments completed a survey. Data analysis showed significant differences in risk perceptions among departments. Differences in risk perception reflected the type of work and the injury incidents in the departments. A structural equation analysis confirmed a model of risk perception on the basis of employees' evaluation of the prevalence and lethalness of hazards as well as the control over hazards they gain from training. The number of injuries sustained was positively related to the perception of risk exposure and negatively related to evaluations about the safety training. The results highlight the importance of training interventions in increasing workers' adoption of safety procedures and prevention of injuries.

  13. Neuropeptide Y stimulation as primary target for preventive measures of maladaptative cardiovascular reactions in occupational chronic stress exposure.

    Ciumaşu-Rîmbu, Mălina; Popa, Livia; Vulpoi, Carmen

    2012-01-01

    Chronic stress may produce a decrease in central NPY expression and subjects exposed to it may prove hypersensitivity to a novel stressor with dysfunctions in the NPY system and cardiovascular maladaptation to stress, even hypertension. Upregulation of NPY expression may contribute to successful behavioral adaptation to stress by reducing cardiovascular tone and suppressing anxious behaviors. Adaptogens, a new class of metabolic regulators stimulate NPY expression and release. The aim of this study is to increase tolerance and adaptation to stress of hypersensitive to novel stressor, occupational chronic stress exposed subjects with cardiovascular maladaptation to mild new stressor using adaptogens as part of prevention protocol. 40 military personnel with known cardiostressor reactional mode and occupational chronic stress exposure were exposed to mild novel stressor: occupational medicine routine evaluation and clinically assessed for maladaptative cardiovascular response prior and before application of 30 day prevention protocol. Employees were randomly split in two groups, one receiving standard prevention protocol (lifestyle counseling) plus adaptogens in multiple dose administration, twice daily and the other receiving only standard prevention protocol. We found significant statistic differences in all cardiovascular parameters in adaptogen group and only in diastolic blood pressure in control group. Adaptogens could be an important factor in successful prevention protocols of chronic occupational stress dysfunctions involving NPY systems.

  14. Gender specific analysis of occupational diseases of the low back caused by carrying, lifting or extreme trunk flexion—use of a prevention index to identify occupations with high prevention needs

    Thiede, Markus; Liebers, Falk; Seidler, Andreas; Gravemeyer, Stefan; Latza, Ute

    2014-01-01

    Background Gender specific analysis of the occupational disease of the lumbar spine caused by carrying, lifting, or extreme trunk flexion in Germany (OD No.2108) with the aim to identify areas of focus for prevention and research with a prevention index (PI). Methods Data from the German Statutory Accident Insurance stratified by gender are shown. Results From 2002 until 2009 there were 2,877 confirmed cases of an OD No. 2108 (40.1% male and 59.1% female). The PI indicated the highest prevention need for female nursing/midwifery associate professionals and male building frame and related trades workers. Patient transfer and working in extremely bent posture were the most frequent exposures. Conclusions The identified occupations with high need for prevention among men come from nearly all major occupational groups whereas women cluster in occupational groups from the health and care sectors. Am. J. Ind. Med. 57:233–244, 2014. © 2013 The Authors. American Journal of Industrial Medicine Published by Wiley Periodicals, Inc. PMID:24243091

  15. Supporting our military families: a case for a larger role for occupational therapy in prevention and mental health care.

    Cogan, Alison M

    2014-01-01

    More than 2 million U.S. military servicemembers have deployed to Afghanistan or Iraq since September 11, 2001. Unlike during prior conflicts, many servicemembers leave spouses and children behind. Long, multiple deployments cause strain on family at home, with new challenges arising when servicemembers return from combat and reintegrate into family and civilian life. In World Wars I and II, occupational therapy practitioners played a significant role in supporting servicemember reintegration. However, their presence in program delivery in this practice area is limited. Occupational therapy researchers and practitioners can make a valuable contribution by helping families tailor daily activities and routines to address challenges and optimize health and wellness. However, barriers such as reimbursement for services, workforce availability, and access to military families have limited the profession's full engagement. Advocacy is needed to help establish occupational therapy as a key component of the mental and preventive health care teams serving military servicemembers. Copyright © 2014 by the American Occupational Therapy Association, Inc.

  16. In vivo characterization of the novel CD44v6-targeting Fab fragment AbD15179 for molecular imaging of squamous cell carcinoma: a dual-isotope study

    2014-01-01

    Background Patients with squamous cell carcinoma in the head and neck region (HNSCC) offer a diagnostic challenge due to difficulties to detect small tumours and metastases. Imaging methods available are not sufficient, and radio-immunodiagnostics could increase specificity and sensitivity of diagnostics. The objective of this study was to evaluate, for the first time, the in vivo properties of the radiolabelled CD44v6-targeting fragment AbD15179 and to assess its utility as a targeting agent for radio-immunodiagnostics of CD44v6-expressing tumours. Methods The fully human CD44v6-targeting Fab fragment AbD15179 was labelled with 111In or 125I, as models for radionuclides suitable for imaging with SPECT or PET. Species specificity, antigen specificity and internalization properties were first assessed in vitro. In vivo specificity and biodistribution were then evaluated in tumour-bearing mice using a dual-tumour and dual-isotope setup. Results Both species-specific and antigen-specific binding of the conjugates were demonstrated in vitro, with no detectable internalization. The in vivo studies demonstrated specific tumour binding and favourable tumour targeting properties for both conjugates, albeit with higher tumour uptake, slower tumour dissociation, higher tumour-to-blood ratio and higher CD44v6 sensitivity for the 111In-labelled fragment. In contrast, the 125I-Fab demonstrated more favourable tumour-to-organ ratios for liver, spleen and kidneys. Conclusions We conclude that AbD15179 efficiently targets CD44v6-expressing squamous cell carcinoma xenografts, and particularly, the 111In-Fab displayed high and specific tumour uptake. CD44v6 emerges as a suitable target for radio-immunodiagnostics, and a fully human antibody fragment such as AbD15179 can enable further clinical imaging studies. PMID:24598405

  17. [Surveillance groups and occupational phisicians for prevention and security in work environment: legal aspects].

    Aceto, A

    2006-01-01

    Italian jurisdiction, since the setting up of the Republic in 1948, has experienced a real and proper Copernican revolution, not only in the field of prevention of accidents and safety at work, which has meant that at the centre of the system there is no longer a State-finality but the individual person, in the form of inviolable rights that the Democratic Republic-vehicle recognises and guarantees in every place, including all places of occupation. To this end the entrepreneur/employer has become the guarantor of the health of his employees through a complex series of laws and regulations that imposes the adoption of safety measures on an individual, general and organizational level in the company. This guarantee has been reinforced by bringing in penalties for all those evasions or violations of these obligations of the entrepreneur/employer. The centralizing of the culture of prevention has meant that all the controls converge on the judicial police, with the head of the surveillance bodies having the status of officer of the judicial police, and with the adoption of regulations that follow the code of criminal procedures, which, while being binding for the same surveillance bodies is also a guarantee in respecting the right to be defended of the entrepreneur/employer.

  18. STUDY ON STUDENTS’ AWARENESS CONCERNING ENVIRONMENTAL AND OCCUPATIONAL HAZARDOUS AGENTS OF CANCER RISK AND PREVENTION METHODS

    Antonina Cebulska-Wasilewska

    2010-09-01

    Full Text Available Background. The aim of our study was to assess the level of awareness and knowledge on environmental and occupational risk of cancer and its prevention among Polish students. We were interested also in their sources of knowledge. Methods. Survey, using the questionnaire, was conducted among 1080 respondents, who are or probably will be in their future work, exposed to harmful agents, due to study profile. Results. Students rated their knowledge on environmental and occupational cancer agents and cancer prevention mostly as limited (over 77%. Participation in “Safety Work and Environment” courses did not differentiate their level of cancer risk awareness. 901 students (84% responded to question about specific substances, which may cause cancer. Almost 2% of students indicated none from 10 given agents as carcinogenic. About 34% of respondents pointed all given agents, 39% pointed on 8–9 of them, 5–7 agents 13.2% of surveyed and 9% of them indicated on 1–4 agents. Students were aware of carcinogenic features of radiation, asbestos, cigarettes smoking (93.2–93.8%, benzene, benzo[?]pirene and pesticides (79,2 –83,6%. Less of them declared carcinogenic features of PAHs (75.4%, heavy metals (73.9%, electromagnetic field (64.8% and infections (60.8%. Only 48% of respondents specified possible lowering of the cancer by risk intervention practices. Medical and engineering profile, as well as attendance in courses covering the issues of health safety at work or environment (SWE significantly decreased percentage of respondents who didn’t specified any procedure (but it was still high: 48–62%. Conclusion. Our results demonstrate that most students, only to some extent, are aware of the most well known cancer-causing substances occurrence. Their knowledge is mostly limited and they do not know prevention procedures and ways to lower or eliminate the risk. Therefore the modernization of educational programs and development of more efficient

  19. 乳腺癌外周血微转移hSBEM mRNA和CD44V6 mRNA的检测%The detection of micrometastases in the peripheral blood of patients with breast cancer for hSBEM mRNA and CD44V6 mRNA

    2008-01-01

    Objective:Successful treatment of breast cancer greatly depends on the early detection of its metastasis, therefore a sensitive and specific biomarker for detecting dissemination of the cancer cells will help to achieve this goal. This study was to evaluate the prognostic significance of human small breast epithelial mucin (hSBEM) and CD44V6 in breast cancer. Methods: The expressions of hSBEM mRNA and CD44V6 mRNA were detected with nested reverse transcription polymerase chain reaction (nested RT-PCR) in 67 samples of breast cancer and adjacent normal breast tissue, 16 samples of breast benign lesions tissue, and 67 specimens of peripheral blood from patients with breast cancer, 16 specimens of benign breast lesions, 20 specimens of healthy volunteers, and 25 (each five cases) other carcinomas tissue samples, including those of gastric carcinoma, colorectal carcinoma, esophageal carcinoma, lung carcinoma, and ovary carcinoma, were analyzed for hSBEM mRNA expression by nested RT-PCR. Results: hSBEM mRNA expression was observed in 62/67 (92.54%)of breast cancer, 14/16 (87.50%) of breast benign lesions and 59/67 (88.05%) of normal breast tissue, with no significant differences between them (P>0.05). None of the samples from other cancer tissues were positive. In peripheral blood the expression of hSBEM mRNA was detected in 34/67 (50.75%) from patients with breast cancer, with significant increasing (P< 0.05) in the cases of metastatic disease (stage Ⅳ) and those with lymph node metastasis compared with localized disease (stage Ⅰ, Ⅱ and Ⅲ) and without lymph node metastasis, but its expression was not found in peripheral blood of patients with benign breast lesions or healthy volunteers. Although CD44V6 mRNA was significantly higher in breast cancer than in benign breast lesions tissue and normal breast tissue, its expression in peripheral blood show no significant difference (P>0.05) in the patients with breast cancer (82.09%), benign breast lesion (75

  20. Interventions to reduce risky sexual behaviour for preventing HIV infection in workers in occupational settings.

    Ojo, Olumuyiwa; Verbeek, Jos H; Rasanen, Kimmo; Heikkinen, Jarmo; Isotalo, Leena K; Mngoma, Nomusa; Ruotsalainen, Eija

    2011-12-07

    The workplace provides an important avenue to prevent HIV. To evaluate the effect of behavioral interventions for reducing HIV on high risk sexual behavior when delivered in an occupational setting. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and PsycINFO up until March 2011 and CINAHL, LILACS, DARE, OSH Update, and EPPI database up until October 2010. Randomised control trials (RCTs) in occupational settings or among workers at high risk for HIV that measured HIV, sexual transmitted diseases (STD), Voluntary Counseling and Testing (VCT), or risky sexual behaviour. Two reviewers independently selected studies for inclusion, extracted data and assessed risk of bias. We pooled studies that were similar. We found 8 RCTs with 11,164 participants but one study did not provide enough data. Studies compared VCT to no VCT and education to no intervention and to alternative education.VCT uptake increased to 51% when provided at the workplace compared to a voucher for VCT (RR=14.0 (95% CI 11.8 to16.7)). After VCT, self-reported STD decreased (RR = 0.10 (95% CI 0.01 to 0.73)) but HIV incidence (RR=1.4 (95% CI 0.7 to 2.7)) and unprotected sex (RR=0.71 (0.48 to 1.06)) did not decrease significantly. .Education reduced STDs (RR = 0.68 (95%CI 0.48 to 0.96)), unprotected sex (Standardised Mean Difference (SMD)= -0.17 (95% CI -0.29 to -0.05), sex with a commercial sex worker (RR = 0.88 (95% CI 0.81 to 0.96) but not multiple sexual partners (Mean Difference (MD) = -0.22 (95% CI -0.52 to 0.08) nor use of alcohol before sex (MD = -0.01 (95% CI of -0.11 to 0.08). Workplace interventions to prevent HIV are feasible. There is moderate quality evidence that VCT offered at the work site increases the uptake of testing. Even though this did no lower HIV-incidence, there was a decrease in self-reported sexual transmitted diseases and a decrease in risky sexual behaviour. There is low quality evidence that educational interventions decrease sexually

  1. Dual pH/redox responsive and CD44 receptor targeting hybrid nano-chrysalis based on new oligosaccharides of hyaluronan conjugates.

    Chen, Daquan; Dong, Xue; Qi, Mengjiao; Song, Xiaoyan; Sun, Jingfang

    2017-02-10

    A smart hybrid microenvironment-mediated dual pH/redox-responsive polymeric nanoparticles combined with inorganic calcium phosphate (CaP) was fabricated, which we term as armored nano-chrysalis inspired by butterfly pupa. The nano-chrysalis has an inner core composed of specially designed oligosaccharides of hyaluronan (oHA) targeting CD44 receptor. The inner core has two functions, i.e., the dual pH/redox responsive polymeric conjugate and the fluorescent curcumin-prodrug function. The prepared nano-chrysalis possessed a smaller size (102.5±4.6nm) than the unarmored nano-chrysalis (122.5±6.6nm). Interestingly, while the nano-chrysalis were stable under pH 7.4, when incubated under the tumor acidic conditions (pH 6.5) the outer CaP armor would dissolve in a pH-dependent, sustained manner. Moreover, nano-chrysalis was demonstrated to present the most effective antitumor efficacy than other formulations. This study provides a promising smart nano-carrier platform to enhance the stability, decrease the side effects, and improve the therapeutic efficacy of anticancer drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Vascular wall-resident CD44+ multipotent stem cells give rise to pericytes and smooth muscle cells and contribute to new vessel maturation.

    Diana Klein

    Full Text Available Here, we identify CD44(+CD90(+CD73(+CD34(-CD45(- cells within the adult human arterial adventitia with properties of multipotency which were named vascular wall-resident multipotent stem cells (VW-MPSCs. VW-MPSCs exhibit typical mesenchymal stem cell characteristics including cell surface markers in immunostaining and flow cytometric analyses, and differentiation into adipocytes, chondrocytes and osteocytes under culture conditions. Particularly, TGFß1 stimulation up-regulates smooth muscle cell markers in VW-MPSCs. Using fluorescent cell labelling and co-localisation studies we show that VW-MPSCs differentiate to pericytes/smooth muscle cells which cover the wall of newly formed endothelial capillary-like structures in vitro. Co-implantation of EGFP-labelled VW-MPSCs and human umbilical vein endothelial cells into SCID mice subcutaneously via Matrigel results in new vessels formation which were covered by pericyte- or smooth muscle-like cells generated from implanted VW-MPSCs. Our results suggest that VW-MPSCs are of relevance for vascular morphogenesis, repair and self-renewal of vascular wall cells and for local capacity of neovascularization in disease processes.

  3. Preventing passenger vehicle occupant injuries by vehicle design--a historical perspective from IIHS.

    O'Neill, Brian

    2009-04-01

    and chest injury measures recorded on driver and front-seat test dummies. NHTSA later added side crash tests and rollover ratings to the U.S. NCAP. Consumer crash testing spread worldwide in the 1990s. In 1995, the Insurance Institute for Highway Safety (IIHS) began using frontal offset crash tests to rate and compare frontal crashworthiness and later added side and rear crash assessments. Shortly after, Europe launched EuroNCAP to assesses new car performance including front, side, and front-end pedestrian tests. The influence of these consumer-oriented crash test programs on vehicle designs has been major. From the beginning, U.S. NCAP results prompted manufacturers to improve seat belt performance. Frontal offset tests from IIHS and EuroNCAP resulted in greatly improved front-end crumple zones and occupant compartments. Side impact tests have similarly resulted in improved side structures and accelerated the introduction of side impact airbags, especially those designed to protect occupant's heads. Vehicle safety designs, initially driven by regulations and later by consumer demand because of crash testing, have proven to be very successful public health measures. Since they were first introduced in the late 1960s, vehicle safety designs have saved hundreds of thousands of lives and prevented countless injuries worldwide. The designs that improved vehicle crashworthiness have been particularly effective. Some newer crash avoidance designs also have the potential to be effective-e.g., electronic stability control is already saving many lives in single-vehicle crashes. However, determining the actual effectiveness of these new technologies is a slow process and needs real-world crash experience because there are no assessment equivalent of crash tests for crash avoidance designs.

  4. Tertiary individual prevention improves mental health in patients with severe occupational hand eczema.

    Breuer, K; John, S M; Finkeldey, F; Boehm, D; Skudlik, C; Wulfhorst, B; Dwinger, C; Werfel, T; Diepgen, T L; Schmid-Ott, G

    2015-09-01

    Occupational hand eczema (OHE) is associated with impaired health-related quality of life (QoL) and mental distress. Interdisciplinary inpatient rehabilitation measures in the framework of tertiary individual prevention (TIP) offered by the German employers' liability insurance associations include dermatological treatment, education and psychological interventions. To investigate the effects of interdisciplinary inpatient rehabilitation in the framework of TIP on mental health in patients with severe OHE and the relationships between recovery of OHE and improvement of mental health and QoL. A total of 122 patients participated in the study. A test battery consisting of the German versions of the Hospital Anxiety and Depression Scale (HADS-D), the Dermatology Life Quality Index (DLQI), the Short Form Health Survey-36 (SF-36) and the Trier Inventory for the Assessment of Chronic Stress (TICS) was applied at the time of admission (T1) and 3 weeks after dismissal (T2). Severity of hand eczema was assessed with the Osnabrueck Hand Eczema Severity Index (OHSI). All parameters improved significantly from T1 to T2. A relationship was established between the improvement of QoL and recovery of OHE, while there was no such relationship between the improvement of mental distress and improvement of OHE. Nonresponders had significantly more cumulative days of sickness at T1. Our data underscore the importance of psychological interventions in addition to dermatological treatment in the framework of prevention measures for OHE. These measures should be applied at an early stage of OHE prior to the occurrence of sick leave. © 2015 European Academy of Dermatology and Venereology.

  5. Indicators to assess the quality of programs to prevent occupational risk for tuberculosis: are they feasible?

    Santos, Talita Raquel Dos; Padoveze, Maria Clara; Nichiata, Lúcia Yasuko Izumi; Takahashi, Renata Ferreira; Ciosak, Suely Itsuko; Gryschek, Anna Luiza de Fátima Pinho Lins

    2016-06-07

    to analyze the feasibility of quality indicators for evaluation of hospital programs for preventing occupational tuberculosis. a descriptive cross-sectional study. We tested indicators for evaluating occupational tuberculosis prevention programs in six hospitals. The criterion to define feasibility was the time spent to calculate the indicators. time spent to evaluate the indicators ranged from 2h 52min to 15h11min 24sec. The indicator for structure evaluation required less time; the longest time was spent on process indicators, including the observation of healthcare workers' practices in relation to the use of N95 masks. There was an hindrance to test one of the indicators for tuberculosis outcomes in five situations, due to the lack of use of tuberculin skin test in these facilities. The time requires to calculate indicators in regarding to the outcomes for occupational tuberculosis largely depends upon the level of organizational administrative structure for gathering data. indicators to evaluate the structure for occupational tuberculosis prevention are highly feasible. Nevertheless, the feasibility of indicators for process and outcome is limited due to relevant variations in administrative issues at healthcare facilities. analisar a viabilidade de indicadores de qualidade para avaliação de programas hospitalares de prevenção de tuberculose ocupacional. estudo descritivo transversal. Testaram-se indicadores de avaliação de programas de prevenção de tuberculose ocupacional em seis hospitais. O critério para definir a viabilidade foi o tempo necessário para aplicar os indicadores. o tempo necessário para avaliar os indicadores variou de 02'52'' até 15h11'24''. O indicador para a avaliação da estrutura demandou menor tempo; o maior tempo foi utilizado com os indicadores de processo, incluindo a observação das práticas dos trabalhadores de saúde em relação ao uso de máscaras N95. Um dos indicadores de resultados de tuberculose deixou de ser

  6. Prevention of risks in relation with occupational exposure to ionizing radiation; Prevention des risques lies a l'exposition professionnelle aux rayonnements ionisants

    NONE

    2005-07-01

    After remind the base notions in the field of ionizing radiation, this file evaluates the situation on the natural and occupational exposures: modes, sources, and exposure level, risk for health. It presents the principles of prevention allowing in a professional area (out of nuclear industry) to reduce and control these exposures. Some practical cases illustrate the radiation protection approach. references are given: regulatory benchmarks, useful links, books to consult. (N.C.)

  7. Occupational Health Update: Focus on Preventing the Acquisition of Infections with Pre-exposure Prophylaxis and Postexposure Prophylaxis.

    Weber, David J; Rutala, William A

    2016-09-01

    Health care personnel are commonly exposed to infectious agents via sharp injuries (eg, human immunodeficiency virus, hepatitis B virus, and hepatitis C virus), direct patient care (eg, pertussis and meningococcus), and the contaminated environment (eg, Clostridium difficile). An effective occupational program is a key aspect of preventing acquisition of an infection by offering the following: (1) education of health care personnel regarding proper handling of sharps, early identification and isolation of potentially infectious patients, and hand hygiene; (2) assuring immunity to vaccine-preventable diseases; and, (3) immediate availability of a medical evaluation after a nonprotected exposure to an infectious disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Hyaluronan-CD44v3 Interaction with Oct4-Sox2-Nanog Promotes miR-302 Expression Leading to Self-renewal, Clonal Formation, and Cisplatin Resistance in Cancer Stem Cells from Head and Neck Squamous Cell Carcinoma*

    Bourguignon, Lilly Y. W.; Wong, Gabriel; Earle, Christine; Chen, Liqun

    2012-01-01

    Human head and neck squamous cell carcinoma (HNSCC) is a highly malignant cancer associated with major morbidity and mortality. In this study, we determined that human HNSCC-derived HSC-3 cells contain a subpopulation of cancer stem cells (CSCs) characterized by high levels of CD44v3 and aldehyde dehydrogenase-1 (ALDH1) expression. These tumor cells also express several stem cell markers (the transcription factors Oct4, Sox2, and Nanog) and display the hallmark CSC properties of self-renewal/clonal formation and the ability to generate heterogeneous cell populations. Importantly, hyaluronan (HA) stimulates the CD44v3 (an HA receptor) interaction with Oct4-Sox2-Nanog leading to both a complex formation and the nuclear translocation of three CSC transcription factors. Further analysis reveals that microRNA-302 (miR-302) is controlled by an upstream promoter containing Oct4-Sox2-Nanog-binding sites, whereas chromatin immunoprecipitation (ChIP) assays demonstrate that stimulation of miR-302 expression by HA-CD44 is Oct4-Sox2-Nanog-dependent in HNSCC-specific CSCs. This process results in suppression of several epigenetic regulators (AOF1/AOF2 and DNMT1) and the up-regulation of several survival proteins (cIAP-1, cIAP-2, and XIAP) leading to self-renewal, clonal formation, and cisplatin resistance. These CSCs were transfected with a specific anti-miR-302 inhibitor to silence miR-302 expression and block its target functions. Our results demonstrate that the anti-miR-302 inhibitor not only enhances the expression of AOF1/AOF2 and DNMT1 but also abrogates the production of cIAP-1, cIAP-2, and XIAP and HA-CD44v3-mediated cancer stem cell functions. Taken together, these findings strongly support the contention that the HA-induced CD44v3 interaction with Oct4-Sox2-Nanog signaling plays a pivotal role in miR-302 production leading to AOF1/AOF2/DNMT1 down-regulation and survival of protein activation. All of these events are critically important for the acquisition of cancer

  9. Hyaluronan-CD44v3 interaction with Oct4-Sox2-Nanog promotes miR-302 expression leading to self-renewal, clonal formation, and cisplatin resistance in cancer stem cells from head and neck squamous cell carcinoma.

    Bourguignon, Lilly Y W; Wong, Gabriel; Earle, Christine; Chen, Liqun

    2012-09-21

    Human head and neck squamous cell carcinoma (HNSCC) is a highly malignant cancer associated with major morbidity and mortality. In this study, we determined that human HNSCC-derived HSC-3 cells contain a subpopulation of cancer stem cells (CSCs) characterized by high levels of CD44v3 and aldehyde dehydrogenase-1 (ALDH1) expression. These tumor cells also express several stem cell markers (the transcription factors Oct4, Sox2, and Nanog) and display the hallmark CSC properties of self-renewal/clonal formation and the ability to generate heterogeneous cell populations. Importantly, hyaluronan (HA) stimulates the CD44v3 (an HA receptor) interaction with Oct4-Sox2-Nanog leading to both a complex formation and the nuclear translocation of three CSC transcription factors. Further analysis reveals that microRNA-302 (miR-302) is controlled by an upstream promoter containing Oct4-Sox2-Nanog-binding sites, whereas chromatin immunoprecipitation (ChIP) assays demonstrate that stimulation of miR-302 expression by HA-CD44 is Oct4-Sox2-Nanog-dependent in HNSCC-specific CSCs. This process results in suppression of several epigenetic regulators (AOF1/AOF2 and DNMT1) and the up-regulation of several survival proteins (cIAP-1, cIAP-2, and XIAP) leading to self-renewal, clonal formation, and cisplatin resistance. These CSCs were transfected with a specific anti-miR-302 inhibitor to silence miR-302 expression and block its target functions. Our results demonstrate that the anti-miR-302 inhibitor not only enhances the expression of AOF1/AOF2 and DNMT1 but also abrogates the production of cIAP-1, cIAP-2, and XIAP and HA-CD44v3-mediated cancer stem cell functions. Taken together, these findings strongly support the contention that the HA-induced CD44v3 interaction with Oct4-Sox2-Nanog signaling plays a pivotal role in miR-302 production leading to AOF1/AOF2/DNMT1 down-regulation and survival of protein activation. All of these events are critically important for the acquisition of cancer

  10. Contribution of job-exposure matrices for exposure assessment in occupational safety and health monitoring systems: application from the French national occupational disease surveillance and prevention network.

    Florentin, Arnaud; Zmirou-Navier, Denis; Paris, Christophe

    2017-08-01

    To detect new hazards ("signals"), occupational health monitoring systems mostly rest on the description of exposures in the jobs held and on reports by medical doctors; these are subject to declarative bias. Our study aims to assess whether job-exposure matrices (JEMs) could be useful tools for signal detection by improving exposure reporting. Using the French national occupational disease surveillance and prevention network (RNV3P) data from 2001 to 2011, we explored the associations between disease and exposure prevalence for 3 well-known pathology/exposure couples and for one debatable couple. We compared the associations measured when using physicians' reports or applying the JEMs, respectively, for these selected diseases and across non-selected RNV3P population or for cases with musculoskeletal disorders, used as two reference groups; the ratio of exposure prevalences according to the two sources of information were computed for each disease category. Our population contained 58,188 subjects referred with pathologies related to work. Mean age at diagnosis was 45.8 years (95% CI 45.7; 45.9), and 57.2% were men. For experts, exposure ratios increase with knowledge on exposure causality. As expected, JEMs retrieved more exposed cases than experts (exposure ratios between 12 and 194), except for the couple silica/silicosis, but not for the MSD control group (ratio between 0.2 and 0.8). JEMs enhanced the number of exposures possibly linked with some conditions, compared to experts' assessment, relative to the whole database or to a reference group; they are less likely to suffer from declarative bias than reports by occupational health professionals.

  11. Design of the Balance@Work project: systematic development, evaluation and implementation of an occupational health guideline aimed at the prevention of weight gain among employees

    Verweij, Lisanne M.; Proper, Karin I.; Weel, Andre N. H.; Hulshof, Carel T. J.; van Mechelen, Willem

    2009-01-01

    Occupational health professionals may play an important role in preventive health promotion activities for employees. However, due to a lack of knowledge and evidence- and practice based methods and strategies, interventions are hardly being implemented by occupational physicians to date. The aim of

  12. Design of the Balance@Work project: systematic development, evaluation and implementation of an occupational health guideline aimed at the prevention of weight gain among employees

    Verweij, L.M.; Proper, K.I.; Weel, A.N.H.; Hulshof, C.T.J.; van Mechelen, W.

    2009-01-01

    Background: Occupational health professionals may play an important role in preventive health promotion activities for employees. However, due to a lack of knowledge and evidence-and practice based methods and strategies, interventions are hardly being implemented by occupational physicians to date.

  13. MRSA colonization and infection among persons with occupational livestock exposure in Europe: Prevalence, preventive options and evidence.

    Goerge, Tobias; Lorenz, Marthe Barbara; van Alen, Sarah; Hübner, Nils-Olaf; Becker, Karsten; Köck, Robin

    2017-02-01

    Colonization with livestock-associated Methicillin-resistant Staphylococcusaureus (LA-MRSA) among persons occupationally exposed to pigs, cattle or poultry is very frequent. In Europe, LA-MRSA mostly belong to the clonal lineage CC398. Since colonized persons have an increased risk of developing MRSA infections, defining the burden of work-related infection caused by LA-MRSA CC398 is of interest to exposed personnel, insurance companies and infection control staff. This review summarizes data on the types of occupation-related infections caused by LA-MRSA CC398, the incidence of such infections as well as potential preventive strategies. We identified twelve case reports on infections among livestock-exposed persons. Overall, there is a lack of data describing the incidence of occupation-related infections due to MRSA CC398. Currently, no specific guidance towards the prevention of LA-MRSA CC398 colonization of persons with routine exposure exists. In vitro, MRSA CC398 strains are susceptible (>95%) to mupirocin. Single reports have described effective decolonization of persons carrying LA-MRSA CC398, but long-term success rates are low in case of continuous livestock contact. Overall, the occupational health risk due to LA-MRSA CC398 is not well understood. Currently, prevention of human LA-MRSA CC398 infection is mostly based on the recommendation to perform screening and decolonization therapies prior to elective medical interventions in order to avoid nosocomial infections, but there is no conclusive evidence to perform specific measures aiming to forestall community-acquired infections. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Creating a Culture of Prevention in Occupational Safety and Health Practice

    Kim, Yangho; Park, Jungsun; Park, Mijin

    2016-01-01

    The incidence of occupational injuries and diseases associated with industrialization has declined markedly following developments in science and technology, such as engineering controls, protective equipment, safer machinery and processes, and greater adherence to regulations and labor inspections. Although the introduction of health and safety management systems has further decreased the incidence of occupational injuries and diseases, these systems are not effective unless accompanied by a...

  15. Strategy for Coordinated EPA/Occupational Safety and Health Administration (OSHA) Implementation of the Chemical Accident Prevention Requirements of the Clean Air Act Amendments of 1990

    EPA and the Occupational Safety and Health Administration (OSHA) share responsibility for prevention: OSHA has the Process Safety Management Standard to protect workers, and EPA the Risk Management Program to protect the general public and environment.

  16. Cleaning and disinfecting environmental surfaces in health care: Toward an integrated framework for infection and occupational illness prevention.

    Quinn, Margaret M; Henneberger, Paul K; Braun, Barbara; Delclos, George L; Fagan, Kathleen; Huang, Vanthida; Knaack, Jennifer L S; Kusek, Linda; Lee, Soo-Jeong; Le Moual, Nicole; Maher, Kathryn A E; McCrone, Susan H; Mitchell, Amber Hogan; Pechter, Elise; Rosenman, Kenneth; Sehulster, Lynne; Stephens, Alicia C; Wilburn, Susan; Zock, Jan-Paul

    2015-05-01

    The Cleaning and Disinfecting in Healthcare Working Group of the National Institute for Occupational Safety and Health, National Occupational Research Agenda, is a collaboration of infection prevention and occupational health researchers and practitioners with the objective of providing a more integrated approach to effective environmental surface cleaning and disinfection (C&D) while protecting the respiratory health of health care personnel. The Working Group, comprised of >40 members from 4 countries, reviewed current knowledge and identified knowledge gaps and future needs for research and practice. An integrated framework was developed to guide more comprehensive efforts to minimize harmful C&D exposures without reducing the effectiveness of infection prevention. Gaps in basic knowledge and practice that are barriers to an integrated approach were grouped in 2 broad areas related to the need for improved understanding of the (1) effectiveness of environmental surface C&D to reduce the incidence of infectious diseases and colonization in health care workers and patients and (2) adverse health impacts of C&D on health care workers and patients. Specific needs identified within each area relate to basic knowledge, improved selection and use of products and practices, effective hazard communication and training, and safer alternatives. A more integrated approach can support multidisciplinary teams with the capacity to maximize effective and safe C&D in health care. Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

  17. [Effect of Biejiajian Pills on Wnt signal pathway molecules β-catenin and GSK-3β and the target genes CD44v6 and VEGF in hepatocellular carcinoma cells].

    Sun, Haitao; He, Songqi; Wen, Bin; Jia, Wenyan; Fan, Eryan; Zheng, Yan

    2014-10-01

    To investigate the effect of Biejiajian Pills on the expressions of the signal molecules and target genes of Wnt signal pathway in HepG2 cells and explore the mechanisms by which Biejiajian pills suppress the invasiveness of hepatocellular carcinoma. HepG2 cells were cultured for 48 h in the presence of serum collected from rats fed with Biejiajian Pills. The expressions of β-catenin, GSK-3β and P-GSK-3β in the cultured cells were assessed by Western blotting and the expressions of CD44v6 and VEGF were detected using immunohistochemistry. HepG2 cells cultured with the serum of rats fed with Biejiajian Pills showed lowered expressions of β-catenin protein both in the cytoplasm and the nuclei with also inhibition of phosphorylation of GSK-3β and reduced expression of CD44v6 and VEGF. Biejiajian Pills can significantly reduce the expression of β-catenin by decreasing the phosphorylation of GSK-3β and blocking the Wnt/β-catenin signaling pathway to cause down-regulation of the target genes CD44v6 and VEGF, which may be one of the molecular mechanisms by which Biejiajian Pills suppress the proliferation and invasiveness of hepatocellular carcinoma.

  18. Effects of an injury and illness prevention program on occupational safety behaviors among rice farmers in Nakhon Nayok Province, Thailand

    Santaweesuk S

    2014-03-01

    Full Text Available Sapsatree Santaweesuk,1,2 Robert S Chapman,1 Wattasit Siriwong1,3 1College of Public Health Sciences, Chulalongkorn University, Bangkok, Thailand; 2Srinakarinwirot University Ongkharak Campus, Nakhon Nayok, Thailand; 3Thai Fogarty ITREOH Center, Chulalongkorn University, Bangkok, Thailand Abstract: The objective of this study was to determine the effects of an Injury and Illness Prevention (IIP program intervention on occupational safety behavior among rice farmers in Nakhon Nayok province, Thailand. This was a quasi-experimental study in an intervention group and a control group. It was carried out in two rice farming communities, in which most people are rice farmers with similar socio-demographic characteristics. Multistage sampling was employed, selecting one person per rice farming household. The intervention group was 62 randomly selected rice farmers living in a rural area; another 55 rice farmers served as the control group. A structured face-to-face interview questionnaire was administered to participants to evaluate their safety behaviors in four areas: equipment use, pesticide use, ergonomics, and working conditions. The 2-week intervention program consisted of four elements: 1 health education, 2 safety inspection, 3 safety communication, and 4 health surveillance. Data were collected at baseline and 4 months after the intervention (follow-up. We used a general linear model repeated-measures analysis of variance to assess the mean difference between baseline and follow-up occupational safety behavior points between the intervention and control groups. Pesticide safety behaviors significantly increased in the intervention group compared with the control group. Ergonomics and working conditions points also increased in the intervention group, but not significantly so. The equipment use score decreased in the intervention group. It is necessary to identify and develop further measures to improve occupational safety behaviors. Some

  19. Social representations of biosecurity in nursing: occupational health and preventive care.

    Sousa, Álvaro Francisco Lopes de; Queiroz, Artur Acelino Francisco Luz Nunes; Oliveira, Layze Braz de; Moura, Maria Eliete Batista; Batista, Odinéa Maria Amorim; Andrade, Denise de

    2016-01-01

    to understand the biosecurity social representations by primary care nursing professionals and analyze how they articulate with quality of care. exploratory and qualitative research based on social representation theory. The study participants were 36 nursing workers from primary health care in a state capital in the Northeast region of Brazil. The data were analyzed by descending hierarchical classification. five classes were obtained: occupational accidents suffered by professionals; occupational exposure to biological agents; biosecurity management in primary health care; the importance of personal protective equipment; and infection control and biosecurity. the different positions taken by the professionals seem to be based on a field of social representations related to the concept of biosecurity, namely exposure to accidents and risks to which they are exposed. However, occupational accidents are reported as inherent to the practice.

  20. Occupational Health

    Occupational health problems occur at work or because of the kind of work you do. These problems can include ... by exposure to radiation Exposure to germs in health care settings Good job safety and prevention practices ...

  1. Occupational rhinitis.

    Petrick, Maria M; Slavin, Raymond G

    2003-05-01

    This article aims to define occupational rhinitis, classify its various causes, review the steps in its diagnosis, and describe its nonpharmacologic and pharmacologic principles of management. Occupational rhinitis frequently coexists with asthma but also occurs alone. Although it does not have the same impact as occupational asthma, occupational rhinitis causes distress, discomfort, and work inefficiency. By concentrating on the patient's workplace, the clinician has an opportunity to practice preventive medicine: to recognize substances in the patient's micro- and macroenvironment that are causing the problems and then to intervene by altering the environment or removing the patient from the environment.

  2. [Informatics support for risk assessment and identification of preventive measures in small and micro-enterprises: occupational hazard datasheets].

    de Merich, D; Forte, Giulia

    2011-01-01

    Risk assessment is the fundamental process of an enterprise's prevention system and is the principal mandatory provision contained in the Health and Safety Law (Legislative Decree 81/2008) amended by Legislative Decree 106/2009. In order to properly comply with this obligation also in small-sized enterprises, the appropriate regulatory bodies should provide the enterprises with standardized tools and methods for identifying, assessing and managing risks. To assist in particular small and micro-enterprises (SMEs) with risk assessment, by providing a flexible tool that can also be standardized in the form of a datasheet, that can be updated with more detailed information on the various work contexts in Italy. Official efforts to provide Italian SMEs with information may initially make use of the findings of research conducted by ISPESL over the past 20 years, thanks in part to cooperation with other institutions (Regions, INAIL-National Insurance Institute for Occupational Accidents and Diseases), which have led to the creation of an information system on prevention consisting of numerous databases, both statistical and documental ("National System of Surveillance on fatal and serious accidents", "National System of Surveillance on work-related diseases", "Sector hazard profiles" database, "Solutions and Best Practices" database, "Technical Guidelines" database, "Training packages for prevention professionals in enterprises" database). With regard to evaluation criteria applicable within the enterprise, the possibility of combining traditional and uniform areas of assessment (by sector or by risk factor) with assessments by job/occupation has become possible thanks to the cooperation agreement made in 2009 by ISPESL, the ILO (International Labour Organisation) of Geneva and IIOSH (Israel Institute for Occupational Health and Hygiene) regarding the creation of an international Database (HDODB) based on risk datasheets per occupation. The project sets out to assist in

  3. Occupational mental health promotion: a prevention agenda based on education and treatment. The American Psychological Association/National Institute for Occupational Safety and Health, Health Promotion Panel, 1990 Work and Well-Being Conference.

    1992-01-01

    PURPOSE OF THE REVIEW. Psychological disorders are one of the 10 leading work-related diseases and injuries in the United States according to the National Institute for Occupational Safety and Health. This article addresses occupational metal health and preventive stress management in the workplace. The individual and organizational costs are briefly considered with concern for reducing the burden of suffering associated with these problems. SEARCH METHOD. As an American Psychological Association interdisciplinary panel, we searched the psychological, medical, public health, and organizational literature. We selected articles relevant to the problem of psychological disorders in the workplace and to enhancing occupational mental health and preventive stress management. IMPORTANT FINDINGS. The panel proposed a national agenda of education and treatment, combined with a program of evaluation research, for addressing these issues. Target populations are identified, and the need for collaboration among a variety of national constituencies is considered. Advancing occupational mental health and promoting skills in preventive stress management is considered in the context of comprehensive health promotion. MAJOR CONCLUSIONS. The panel concluded that there is a pressing need to: 1) set a 'gold' standard concerning the current state of knowledge in the domains of occupational mental health and stress management; 2) identify Diagnostically Related Groups (DRGs) which are stress-related; 3) establish assessment standards for stress and mental health; 4) set guidelines for reasonable interventions; and 5) establish acceptable post-outcome criteria.

  4. Design of the Balance@Work project: systematic development, evaluation and implementation of an occupational health guideline aimed at the prevention of weight gain among employees

    Weel Andre NH

    2009-12-01

    Full Text Available Abstract Background Occupational health professionals may play an important role in preventive health promotion activities for employees. However, due to a lack of knowledge and evidence- and practice based methods and strategies, interventions are hardly being implemented by occupational physicians to date. The aim of the Balance@Work project is to develop, evaluate, and implement an occupational health guideline aimed at the prevention of weight gain among employees. Methods Following the guideline development protocol of the Netherlands Society of Occupational Medicine and the Intervention Mapping protocol, the guideline was developed based on literature, interviews with relevant stakeholders, and consensus among an expert group. The guideline consists of an individual and an environmental component. The individual component includes recommendations for occupational physicians on how to promote physical activity and healthy dietary behavior based on principles of motivational interviewing. The environmental component contains an obesogenic environment assessment tool. The guideline is evaluated in a randomised controlled trial among 20 occupational physicians. Occupational physicians in the intervention group apply the guideline to eligible workers during 6 months. Occupational physicians in the control group provide care as usual. Measurements take place at baseline and 6, 12, and 18 months thereafter. Primary outcome measures include waist circumference, daily physical activity and dietary behavior. Secondary outcome measures include sedentary behavior, determinants of behavior change, body weight and body mass index, cardiovascular disease risk profile, and quality of life. Additionally, productivity, absenteeism, and cost-effectiveness are assessed. Discussion Improving workers' daily physical activity and dietary behavior may prevent weight gain and subsequently improve workers' health, increase productivity, and reduce absenteeism

  5. Design of the Balance@Work project: systematic development, evaluation and implementation of an occupational health guideline aimed at the prevention of weight gain among employees.

    Verweij, Lisanne M; Proper, Karin I; Weel, Andre N H; Hulshof, Carel T J; van Mechelen, Willem

    2009-12-14

    Occupational health professionals may play an important role in preventive health promotion activities for employees. However, due to a lack of knowledge and evidence- and practice based methods and strategies, interventions are hardly being implemented by occupational physicians to date. The aim of the Balance@Work project is to develop, evaluate, and implement an occupational health guideline aimed at the prevention of weight gain among employees. Following the guideline development protocol of the Netherlands Society of Occupational Medicine and the Intervention Mapping protocol, the guideline was developed based on literature, interviews with relevant stakeholders, and consensus among an expert group. The guideline consists of an individual and an environmental component. The individual component includes recommendations for occupational physicians on how to promote physical activity and healthy dietary behavior based on principles of motivational interviewing. The environmental component contains an obesogenic environment assessment tool. The guideline is evaluated in a randomised controlled trial among 20 occupational physicians. Occupational physicians in the intervention group apply the guideline to eligible workers during 6 months. Occupational physicians in the control group provide care as usual. Measurements take place at baseline and 6, 12, and 18 months thereafter. Primary outcome measures include waist circumference, daily physical activity and dietary behavior. Secondary outcome measures include sedentary behavior, determinants of behavior change, body weight and body mass index, cardiovascular disease risk profile, and quality of life. Additionally, productivity, absenteeism, and cost-effectiveness are assessed. Improving workers' daily physical activity and dietary behavior may prevent weight gain and subsequently improve workers' health, increase productivity, and reduce absenteeism. After an effect- and process evaluation the guideline will be

  6. Expression profiles of cancer stem cell markers: CD133, CD44, Musashi-1 and EpCAM in the cardiac mucosa-Barrett's esophagus-early esophageal adenocarcinoma-advanced esophageal adenocarcinoma sequence.

    Mokrowiecka, Anna; Veits, Lothar; Falkeis, Christina; Musial, Jacek; Kordek, Radzislaw; Lochowski, Mariusz; Kozak, Jozef; Wierzchniewska-Lawska, Agnieszka; Vieth, Michael; Malecka-Panas, Ewa

    2017-03-01

    Barrett's esophagus (BE), which develops as a result of gastroesophageal reflux disease, is a preneoplastic condition for esophageal adenocarcinoma (EAC). A new hypothesis suggests that cancer is a disease of stem cells, however, their expression and pathways in BE - EAC sequence are not fully elucidated yet. We used a panel of putative cancer stem cells markers to identify stem cells in consecutive steps of BE-related cancer progression. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded blocks from 58 patients with normal cardiac mucosa (n=5), BE (n=14), early EAC (pT1) from mucosal resection (n=17) and advanced EAC (pT1-T4) from postoperative specimens (n=22). Expression of the CD133, CD44, Musashi-1 and EpCAM was analyzed using respective monoclonal antibodies. All markers showed a heterogeneous expression pattern, mainly at the base of the crypts of Barrett's epithelium and EAC, with positive stromal cells in metaplastic and dysplastic lesions. Immuno-expression of EpCAM, CD44 and CD133 in cardiac mucosa was significantly lower (mean immunoreactivity score (IRS)=1.2; 0.0; 0.4; respectively) compared to their expression in Barrett's metaplasia (mean IRS=4.3; 0.14; 0.7; respectively), in early adenocarcinoma (mean IRS=4.4; 0.29; 1.3; respectively) and in advanced adenocarcinoma (mean IRS=6.6; 0.7; 2.7; respectively) (p<0.05). On the contrary, Musashi-1 expression was higher in BE and early ADC compared to GM and advanced ADC (NS). Our results suggest that the stem cells could be present in premalignant lesions. EpCAM, CD44 and CD133 expression could be candidate markers for BE progression, whereas Musashi-1 may be a marker of the small intestinal features of Barrett's mucosa. Copyright © 2016 Elsevier GmbH. All rights reserved.

  7. A bibliometric analysis in the fields of preventive medicine, occupational and environmental medicine, epidemiology, and public health

    Soteriades Elpidoforos S

    2006-12-01

    Full Text Available Abstract Background Research in the fields of Preventive Medicine, Occupational/Environmental Medicine, Epidemiology and Public Health play an important role in the advancement of knowledge. In order to map the research production around the world we performed a bibliometric analysis in the above fields. Methods All articles published by different world regions in the above mentioned scientific fields and cited in the Journal Citation Reports (JCR database of the Institute for Scientific Information (ISI during the period 1995 and 2003, were evaluated. The research production of different world regions was adjusted for: a the gross domestic product in 1995 US dollars, and b the population size of each region. Results A total of 48,861 articles were retrieved and categorized. The USA led the research production in all three subcategories. The percentage of articles published by USA researchers was 43%, 44% and 61% in the Preventive Medicine, Epidemiology, and Public Health subcategories, respectively. Canada and Western Europe shared the second position in the first two subcategories, while Oceania researchers ranked second in the field of Public Health. Conclusion USA researchers maintain a leadership position in the production of scientific articles in the fields of Preventive Medicine, Occupational/Environmental Medicine and Epidemiology, at a level similar to other scientific disciplines, while USA contribution to science in the field of Public Health is by all means outstanding. Less developed regions would need to support their researchers in the above fields in order to improve scientific production and advancement of knowledge in their countries.

  8. [Individual prevention of occupational contact dermatitis: protective gloves and skin protection recommendations as part of the patient management scheme by the public statutory employers' liability insurance].

    Wilke, A; Skudlik, C; Sonsmann, F K

    2018-05-02

    The dermatologist's procedure is a pivotal tool for early recognition of occupational contact dermatitis (OCD), for reporting OCD cases to the statutory accident insurance and for treating the diseases. The employer is in charge of implementing skin protection measures at the workplace. However, in terms of an individual prevention approach it may be necessary to propose targeted skin protection recommendations in specific patient cases. The patient's own skin protection behavior significantly contributes to regenerating and maintaining healthy skin. This behavior includes the use of occupational skin products, and in particular the correct use of appropriately selected protective gloves. Protective gloves are the most important personal protective measure in the prevention of OCD. Prevention services, occupational health and safety specialists, occupational physicians and centers specialized in occupational dermatology can support the identification of suitable protective measures. Nowadays, suitable protective gloves exist for (almost) every occupational activity and exposure. However, improper use in practice can become a risk factor by itself for the skin (e. g., incorrectly used gloves). Therefore, it is of utmost importance to identify application errors, to educate patients in terms of skin protection and to motivate them to perform an appropriate skin protection behavior. With particular focus on protective gloves, this article gives an overview of various types, materials and potentially glove-related allergens, presents strategies for reducing occlusion effects and discusses some typical application errors and solutions.

  9. Tartrate-resistant acid phosphatase (TRAP/ACP5) promotes metastasis-related properties via TGFβ2/TβR and CD44 in MDA-MB-231 breast cancer cells.

    Reithmeier, Anja; Panizza, Elena; Krumpel, Michael; Orre, Lukas M; Branca, Rui M M; Lehtiö, Janne; Ek-Rylander, Barbro; Andersson, Göran

    2017-09-15

    Tartrate-resistant acid phosphatase (TRAP/ACP5), a metalloenzyme that is characteristic for its expression in activated osteoclasts and in macrophages, has recently gained considerable focus as a driver of metastasis and was associated with clinically relevant parameters of cancer progression and cancer aggressiveness. MDA-MB-231 breast cancer cells with different TRAP expression levels (overexpression and knockdown) were generated and characterized for protein expression and activity levels. Functional cell experiments, such as proliferation, migration and invasion assays were performed as well as global phosphoproteomic and proteomic analysis was conducted to connect molecular perturbations to the phenotypic changes. We identified an association between metastasis-related properties of TRAP-overexpressing MDA-MB-231 breast cancer cells and a TRAP-dependent regulation of Transforming growth factor (TGFβ) pathway proteins and Cluster of differentiation 44 (CD44). Overexpression of TRAP increased anchorage-independent and anchorage-dependent cell growth and proliferation, induced a more elongated cellular morphology and promoted cell migration and invasion. Migration was increased in the presence of the extracellular matrix (ECM) proteins osteopontin and fibronectin and the basement membrane proteins collagen IV and laminin I. TRAP-induced properties were reverted upon shRNA-mediated knockdown of TRAP or treatment with the small molecule TRAP inhibitor 5-PNA. Global phosphoproteomics and proteomics analyses identified possible substrates of TRAP phosphatase activity or signaling intermediates and outlined a TRAP-dependent regulation of proteins involved in cell adhesion and ECM organization. Upregulation of TGFβ isoform 2 (TGFβ2), TGFβ receptor type 1 (TβR1) and Mothers against decapentaplegic homolog 2 (SMAD2), as well as increased intracellular phosphorylation of CD44 were identified upon TRAP perturbation. Functional antibody-mediated blocking and chemical

  10. Extracellular matrix components expression in human pluripotent stem cell-derived retinal organoids recapitulates retinogenesis in vivo and reveals an important role for IMPG1 and CD44 in the development of photoreceptors and interphotoreceptor matrix.

    Felemban, Majed; Dorgau, Birthe; Hunt, Nicola Claire; Hallam, Dean; Zerti, Darin; Bauer, Roman; Ding, Yuchun; Collin, Joseph; Steel, David; Krasnogor, Natalio; Al-Aama, Jumana; Lindsay, Susan; Mellough, Carla; Lako, Majlinda

    2018-05-17

    The extracellular matrix (ECM) plays an important role in numerous processes including cellular proliferation, differentiation, migration, maturation, adhesion guidance and axonal growth. To date, there has been no detailed analysis of the ECM distribution during retinal ontogenesis in humans and the functional importance of many ECM components is poorly understood. In this study, the expression of key ECM components in adult mouse and monkey retina, developing and adult human retina and retinal organoids derived from human pluripotent stem cells was studied. Our data indicate that basement membrane ECMs (Fibronectin and Collagen IV) were expressed in Bruch's membrane and the inner limiting membrane of the developing human retina, whilst the hyalectins (Versican and Brevican), cluster of differentiation 44 (CD44), photoreceptor-specific ECMs Interphotoreceptor Matrix Proteoglycan 1 (IMPG1) and Interphotoreceptor Matrix Proteoglycan 2 (IMPG2) were detected in the developing interphotoreceptor matrix (IPM). The expression of IMPG1, Versican and Brevican in the developing IPM was conserved between human developing retina and human pluripotent stem cell-derived retinal organoids. Blocking the action of CD44 and IMPG1 in pluripotent stem cell derived retinal organoids affected the development of photoreceptors, their inner/outer segments and connecting cilia and disrupted IPM formation, with IMPG1 having an earlier and more significant impact. Together, our data suggest an important role for IMPG1 and CD44 in the development of photoreceptors and IPM formation during human retinogenesis. The expression and the role of many extracellular matrix (ECM) components during human retinal development is not fully understood. In this study, expression of key ECM components (Collagen IV, Fibronectin, Brevican, Versican, IMPG1 and IMPG2) was investigated during human retinal ontogenesis. Collagen IV and Fibronectin were expressed in Bruch's membrane; whereas Brevican, Versican

  11. Metrics to assess injury prevention programs for young workers in high-risk occupations: a scoping review of the literature

    Jennifer Smith

    2018-05-01

    Full Text Available Introduction: Despite legal protections for young workers in Canada, youth aged 15–24 are at high risk of traumatic occupational injury. While many injury prevention initiatives targeting young workers exist, the challenge faced by youth advocates and employers is deciding what aspect(s of prevention will be the most effective focus for their efforts. A review of the academic and grey literatures was undertaken to compile the metrics—both the indicators being evaluated and the methods of measurement—commonly used to assess injury prevention programs for young workers. Metrics are standards of measurement through which efficiency, performance, progress, or quality of a plan, process, or product can be assessed. Methods: A PICO framework was used to develop search terms. Medline, PubMed, OVID, EMBASE, CCOHS, PsychINFO, CINAHL, NIOSHTIC, Google Scholar and the grey literature were searched for articles in English, published between 1975-2015. Two independent reviewers screened the resulting list and categorized the metrics in three domains of injury prevention: Education, Environment and Enforcement. Results: Of 174 acquired articles meeting the inclusion criteria, 21 both described and assessed an intervention. Half were educational in nature (N=11. Commonly assessed metrics included: knowledge, perceptions, self-reported behaviours or intentions, hazardous exposures, injury claims, and injury counts. One study outlined a method for developing metrics to predict injury rates. Conclusion: Metrics specific to the evaluation of young worker injury prevention programs are needed, as current metrics are insufficient to predict reduced injuries following program implementation. One study, which the review brought to light, could be an appropriate model for future research to develop valid leading metrics specific to young workers, and then apply these metrics to injury prevention programs for youth.

  12. Effectiveness of protocols for preventing occupational exposure to blood and body fluids in Dutch hospitals

    van Gemert-Pijnen, Julia E.W.C.; Hendrix, M.G.R.; van der Palen, Jacobus Adrianus Maria; Schellens, P.J.

    2006-01-01

    Compliance of different healthcare workers (HCWs) (nurses, physicians, laboratory technicians and cleaners) with protocols to prevent exposure to blood and body fluids (BBF) was studied. Questionnaires were used to assess perception of risks, familiarity with protocols, motivation and actual

  13. Tool for evaluation compliance standards and expectations in occupational risk prevention by collaborating companies

    Duran Perez, A.; Gomez Pardo, M. A.; Cao Tejero, R.; Millan Verdejo, J. A.; Blas Perez, P.

    2013-01-01

    Within the framework of a single security in ANAV, in our Action Plan on prevention, we consider it essential to include workers from ECCE working for and by ANAV in compliance with standards and expectations both in the accounts of the incidents. With this system is intended to standardize a set of observed deviations report and a tool for measuring the degree of compliance, allowing to monitor the evolution of each company and the effectiveness of prevention plan.

  14. Occupational Hepatitis B Exposure: A Peek into Indian Dental Students’ Knowledge, Opinion, and Preventive Practices

    Sandeep Kumar

    2015-01-01

    Full Text Available Objective. To determine the level of knowledge, opinions, and preventive practices followed by dental students against Hepatitis B. The study also explored if any correlation existed between knowledge, opinion, and preventive practices score. Materials and Methods. A cross-sectional study was conducted in a dental teaching institution. The subjects comprised 216 dental students. The study was conducted using a pretested, self-administered questionnaire. The questionnaire was prepared to assess knowledge, opinion, and preventive practices against Hepatitis B. Kruskal-Wallis and Kendall Tau test were performed. Results. The study found that only 44.4% of the students were vaccinated with Hepatitis B vaccine. 59.3% of the students reported washing their hands after contact with patient’s body fluids. 63.9% used personal protective measures like facemask, aprons, head cap, eye shields, and so forth, while treating patients. Median knowledge, opinion, and practice scores were found to be 5.00, 3.00, and 3.00, respectively. Significant correlation was obtained between knowledge and preventive practices score (r=0.385, p value <0.0001. Conclusion. Effective measures need to be taken to improve preventive practices of the students to prevent them from risk of Hepatitis transmission. Mandatory vaccination against Hepatitis B needs to be implemented.

  15. How much do workers' health examinations add to health and safety at the workplace? Occupational preventive usefulness of routine health examinations.

    Rodríguez-Jareño, Maria Cruz; Molinero, Emilia; de Montserrat, Jaume; Vallès, Antoni; Aymerich, Marta

    2015-01-01

    Despite no evidence in favour, routine workers' health examinations, mostly pre-employment and periodic, are extensively performed worldwide with important allocation of resources. In Spain they are performed within a theoretical job-specific health surveillance system. Our objective was to ascertain their occupational preventive usefulness from the perspective of occupational health professionals. Cross sectional study. Online survey addressed to all physicians and nurses members of the Catalan Society of Safety and Occupational Medicine (n=539) in 2011. Univariate and bivariate analyses of prevalence and prevalence differences of answers. Response rate 53% (n=285). According to more than 70% of respondents the health surveillance system isn't cost-effective, doesn't meet the goal of early detection of health damage related to work, and doesn't contribute to improve the occupational risk prevention system. Further deficiencies were identified regarding specificity and scientific basis for health examinations, quality of collective health surveillance and referral of suspected cases to mutual insurance companies for diagnosis and treatment. Bivariate analysis showed a significantly more negative opinion for several items amongst physicians (versus nurses) and amongst professionals working in external prevention services (versus internal services). This study raises serious concerns about how health examinations are performed within our workers' health surveillance system, which should be reviewed to ensure the fulfilment of its occupational preventive objective. Our results might encourage other countries with similar practices to assess them in order to assure their fitness for purpose. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  16. Occupational health

    Coosemans, R.

    1997-01-01

    Health at work and healthy work environments are among the most valuable assets of individuals, communities and countries. Nowadays, new broader approach is promoted, recognizing the fact that occupational health is a key, but not a unique element of workers’ health. Workers health is a public health approach to resolving the health problems of working populations including all determinants of health recognized as targets of risk management. It focuses on primary prevention of occupational an...

  17. Occupational physical activity assessment for chronic disease prevention and management: A review of methods for both occupational health practitioners and researchers.

    Scott, Kenneth A; Browning, Raymond C

    2016-01-01

    Occupational physical activity (OPA) is an occupational exposure that impacts worker health. OPA is amenable to measurement and modification through the hierarchy of controls. Occupational exposure scientists have roles in addressing inadequate physical activity, as well as excessive or harmful physical activity. Occupational health researchers can contribute to the development of novel OPA exposure assessment techniques and to epidemiologic studies examining the health impacts of physical activity at work. Occupational health practitioners stand to benefit from understanding the strengths and limitations of physical activity measurement approaches, such as accelerometers in smartphones, which are already ubiquitous in many workplaces and in some worksite health programs. This comprehensive review of the literature provides an overview of physical activity monitoring for occupational exposure scientists. This article summarizes data on the public health implications of physical activity at work, highlighting complex relationships with common chronic diseases. This article includes descriptions of several techniques that have been used to measure physical activity at work and elsewhere, focusing in detail on pedometers, accelerometers, and Global Positioning System technology. Additional subjective and objective measurement strategies are described as well.

  18. Analysis of occupational accidents: prevention through the use of additional technical safety measures for machinery

    Dźwiarek, Marek; Latała, Agata

    2016-01-01

    This article presents an analysis of results of 1035 serious and 341 minor accidents recorded by Poland's National Labour Inspectorate (PIP) in 2005–2011, in view of their prevention by means of additional safety measures applied by machinery users. Since the analysis aimed at formulating principles for the application of technical safety measures, the analysed accidents should bear additional attributes: the type of machine operation, technical safety measures and the type of events causing injuries. The analysis proved that the executed tasks and injury-causing events were closely connected and there was a relation between casualty events and technical safety measures. In the case of tasks consisting of manual feeding and collecting materials, the injuries usually occur because of the rotating motion of tools or crushing due to a closing motion. Numerous accidents also happened in the course of supporting actions, like removing pollutants, correcting material position, cleaning, etc. PMID:26652689

  19. Analysis of occupational accidents: prevention through the use of additional technical safety measures for machinery.

    Dźwiarek, Marek; Latała, Agata

    2016-01-01

    This article presents an analysis of results of 1035 serious and 341 minor accidents recorded by Poland's National Labour Inspectorate (PIP) in 2005-2011, in view of their prevention by means of additional safety measures applied by machinery users. Since the analysis aimed at formulating principles for the application of technical safety measures, the analysed accidents should bear additional attributes: the type of machine operation, technical safety measures and the type of events causing injuries. The analysis proved that the executed tasks and injury-causing events were closely connected and there was a relation between casualty events and technical safety measures. In the case of tasks consisting of manual feeding and collecting materials, the injuries usually occur because of the rotating motion of tools or crushing due to a closing motion. Numerous accidents also happened in the course of supporting actions, like removing pollutants, correcting material position, cleaning, etc.

  20. Innovation in the occupational health physician profession requires the development of a work collective to improve the efficiency of MSD prevention.

    Caroly, S; Landry, A; Cholez, C; Davezies, P; Bellemare, M; Poussin, N

    2012-01-01

    Given the ageing population of occupational health physicians and the deteriorating situation of employee health, reforms targeting the multi-disciplinary nature of occupational health are currently being drawn up. These are of great concern to doctors in terms of the future of occupational health, notably with regard to changing medical practices. The objective of this study is to explore the actual practices of occupational health physicians within the framework of MSD prevention in France. By analysing the activity of occupational health physicians, we could gain a better understanding of the coordination between those involved in OHS with the ultimate goal being to improve prevention. Based on an analysis of peer activity, this method made it possible to push beyond pre-constructed discourse. According to activity theories, it is through others that the history and controversies of a profession can be grasped and skills developed. The results produced by these collective discussions on activity analysis contributed to establish a collective point of view about the important aspects of their profession that need defending and the variations in professional genre in relation to the current reforms, notably.

  1. Direct demonstration of the infiltration of murine central nervous system by Pgp-1/CD44high CD45RB(low) CD4+ T cells that induce experimental allergic encephalomyelitis

    Zeine, R; Owens, T

    1992-01-01

    -labelled CD4+ cells isolated from the CNS were responsive to MBP in vitro, whereas PKH2+ CD4+ cells from lymph nodes showed almost undetectable responses. In control experiments in which ovalbumin (OVA)-reactive T cells were transferred, a small number of fluorescent-labelled CD4+ T cells were also......In experimental allergic encephalomyelitis (EAE), autoimmune T cells infiltrate the central nervous system (CNS) and initiate demyelinating pathology. We have used flow cytometry to directly analyse the migration to the CNS of MBP-reactive CD4+ T cells labelled with a lipophilic fluorescent dye...... (PKH2), in SJL/J mice with passively transferred EAE. Labelled cells constituted about 45% of the CNS CD4+ population at the time of EAE onset. Almost all (greater than 90%) of the PKH2-labelled CD4+ T cells from EAE CNS were blasts and were alpha/beta T cell receptor (TCR)+, CD44(Pgp-1)high...

  2. Intranasal administration of vitamin D attenuates blood-brain barrier disruption through endogenous upregulation of osteopontin and activation of CD44/P-gp glycosylation signaling after subarachnoid hemorrhage in rats.

    Enkhjargal, Budbazar; McBride, Devin W; Manaenko, Anatol; Reis, Cesar; Sakai, Yasushi; Tang, Jiping; Zhang, John H

    2017-07-01

    In this study, we investigated the role of vitamin D3 (VitD3) on endogenous osteopontin (OPN), a neuroprotective glycoprotein, after subarachnoid hemorrhage (SAH). The endovascular perforation SAH model in Sprague-Dawley rats was used to study the effect of intranasal VitD3 (30 ng/kg) before (Pre-SAH + VitD3) and after (Post-SAH + VitD3) subarachnoid hemorrhage. Vitamin D3 (30, 60, 120 ng/kg/day) increased more than one fold endogenous OPN expression in astrocytes and endothelial cells of rat brain. Vitamin D3 significantly decreased brain edema and Evans blue extravasation. In addition, neurobehavioral scores were significantly higher in Pre-SAH + VitD3, but partly higher in Post-SAH + VitD3, group compared with SAH group. These protective effects of vitamin D3 were completely attenuated by intracerebroventricular injection of transcription inhibitor Actinomycin D and significantly inhibited by small interfering ribonucleic acid (siRNA) for vitamin D receptor and OPN in Pre-SAH + VitD3 rats. OPN expression was significantly higher in Pre-SAH + VitD3 rats, specifically A and C, but not B, isomers were upregulated in the astrocytes, leading to CD44 splicing, and P-gp glycosylation in brain endothelial cells. The results show that intranasal vitamin D3 attenuates blood-brain barrier (BBB) disruption through endogenous upregulation of OPN and subsequent CD44 and P-gp glycosylation signals in brain endothelial cells. Furthermore, this study identifies a novel strategy for the cost-effective management of subarachnoid hemorrhage.

  3. Two Domains of Vimentin Are Expressed on the Surface of Lymph Node, Bone and Brain Metastatic Prostate Cancer Lines along with the Putative Stem Cell Marker Proteins CD44 and CD133

    Steinmetz, Nicole F. [Case Western Reserve University, Department of Biomedical Engineering, 10900 Euclid Ave, Cleveland, OH 44106 (United States); Maurer, Jochen [Sanford-Burnham, Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037 (United States); Sheng, Huiming [Torrey Pines Institute for Molecular Studies, Division of Immune Regulation, 3550 General Atomics Court, San Diego, CA 92121 (United States); Bensussan, Armand [INSERM U976, Hôpital Saint Louis, F-75475 Paris (France); Department of Immunology, Dermatology and Oncology, Univ Paris Diderot, Sorbonne Paris Cité, UMRS976 F-75475 Paris (France); Maricic, Igor; Kumar, Vipin [Torrey Pines Institute for Molecular Studies, Laboratory of Autoimmunity, 3550 General Atomics Court, San Diego, CA 92121 (United States); Braciak, Todd A., E-mail: tbraciak@tpims.org [Torrey Pines Institute for Molecular Studies, Division of Immune Regulation, 3550 General Atomics Court, San Diego, CA 92121 (United States)

    2011-07-13

    Vimentin was originally identified as an intermediate filament protein present only as an intracellular component in many cell types. However, this protein has now been detected on the surface of a number of different cancer cell types in a punctate distribution pattern. Increased vimentin expression has been indicated as an important step in epithelial-mesenchymal transition (EMT) required for the metastasis of prostate cancer. Here, using two vimentin-specific monoclonal antibodies (SC5 and V9 directed against the coil one rod domain and the C-terminus of the vimentin protein, respectively), we examined whether either of these domains would be displayed on the surface of three commonly studied prostate cancer cell lines isolated from different sites of metastases. Confocal analysis of LNCaP, PC3 and DU145 prostate cancer cell lines (derived from lymph node, bone or brain prostate metastases, respectively) demonstrated that both domains of vimentin are present on the surface of these metastatic cancer cell types. In addition, flow cytometric analysis revealed that vimentin expression was readily detected along with CD44 expression but only a small subpopulation of prostate cancer cells expressed vimentin and the putative stem cell marker CD133 along with CD44. Finally, Cowpea mosaic virus (CPMV) nanoparticles that target vimentin could bind and internalize into tested prostate cancer cell lines. These results demonstrate that at least two domains of vimentin are present on the surface of metastatic prostate cancer cells and suggest that vimentin could provide a useful target for nanoparticle- or antibody- cancer therapeutic agents directed against highly invasive cancer and/or stem cells.

  4. [An analysis of status of personnel in occupational disease prevention and treatment institutions in Hunan Province, China, from 1996 to 2015].

    Liu, X L; Xiao, Y L; Tang, H Q; Chen, B L; Yang, L H; Xiao, Y L; Lv, S J

    2018-01-20

    Objective: To analyze the status of personnel in occupational disease prevention and treatment institutions in Hunan Province, China, from 1996 to 2015, to predict staff composition using grey model (GM) (1, 1) , and to provide a scientific basis and reference for optimizing human resource planning of occupational disease prevention and treatment in other provinces and regions and promoting the service capacity of the institutions. Methods: The data of the staff in occupational disease prevention and treatment institutions in Hunan Province, China, from 1996 to 2015 were obtained from the established basic information management system. The descriptive analysis method was used to analyze the dynamic changes in number and composition of the staff and the GM (1, 1) was used to predict the staff composition. Results: The numbers of the staff members in 1996 and 2015 in occupational disease prevention and treatment institutions in Hunan Province, China were 1591 and 1429, respectively. In the twenty years, the main education level of the staff transformed from "technical secondary school education and non-academic qualifications" to "bachelor degree or above and college degree"; the main major of the staff transformed from "other majors" to "public health and clinical medicine"; the proportion of the staff members without professional titles changed from >1/3 to 5%; and the proportions of the staff members with senior, intermediate, and junior professional titles were steadily rising. GM prediction showed that the proportions of highly educated staff members in 2018 and 2020 would be up to 41.00% and 45.61%, respectively; and the proportions of the staff members with a major in public health in 2018 and 2020 would be up to 44.15% and 46.60%, respectively. Conclusion: The staff in occupational disease prevention and treatment institutions in Hunan Province, China, in the twenty years have slight changes in staff size and great improvement in staff quality, which is

  5. [An analysis of appeals against the ruling of the occupational physician's lodged to the Department of Prevention and Safety in the Working Environment--Health Prevention and Occupational Epidemiology Operative Unit within the A.S.P. Palermo (Palermo Health Authority), years 2008-2010].

    Marsala, M G L; Morici, M; Lacca, G; Curcurù, L; Eduardo, E Costagliola; Ilardo, S; Trapani, E; Caracausi, R; Firenze, A

    2012-01-01

    The purpose of this study is to analyze the appeals against a "suitability judgment for work" lodged to the U.O.S. "Health Prevention and Occupational Epidemiology Operative Unit" of Department of Prevention and Safety in the Working Environment within the ASP Palermo (U.O.S.), from 2008 to 2010. Studying the appeals gives an indirect view on the occupational physician activity and allows to monitor their actions, analysis aims at highlighting those issues around which any planning and implementation of coordination activities should be focused.

  6. [Mutual aid societies for industrial accidents and occupational diseases in the social security service within the framework of the Prevention of Occupational Risk Act].

    Albalá-Ortiz, M

    The passing of the Prevention of Industrial Risks Act, in force from 9 February 1996 has altered previous ideas on the subject, which is currently considered to be of utmost importance for national and community legislation. In this article we describe the preventive functions of the Mutual Aid Societies for Industrial Accidents and professional diseases of the National Health Service. We have analysed the current legislation so as to clarify the activities of the Mutual Aid Societies in the field of the prevention of industrial accidents, and have defined the actions which may be taken in this field according to the present laws. Two different types of preventive activities are considered: (1) Those which depend on contributions, included in the professional risks cover, and which are obliged to prepare an annual plan of the measures taken to prevent industrial accidents and professional illness, following the guidelines established by the Ministry of Labor and Social Services and according to certain priorities. (2) The functions corresponding to the services for third-party prevention exclusively for their associated companies when the Mutual Aid Society is approved as a service for third party cover. This requires a voluntary or professional contract and the financial cost is borne by the company which requests it. The objective of the current legislation is, amongst other things, to introduce the new preventive approach established by the Prevention of Industrial Risks Act in the workplace and through the Mutual Aid Societies as well as to foment a new culture of prevention.

  7. Identification the intangibles arising from investments in prevention of occupational risks and their perception in SMEs. Implications in the service sector and the servitization

    Máximo Cortés

    2014-04-01

    Full Text Available Purpose: Based on the concept of Intellectual Capital and the analysis of component elements, the study aims to identify potential intangibles arising from investments in prevention of occupational risks, analyzing if adequate preventive management helps to increase the value of the company, and establishing a comparative analysis of the industrial and service companies in order to observe specifications for each case. Besides the impact and implications arising thereon due to increased outsourcing and servitization processes in business are determined. Design/methodology: Analysis of the concept and components of Intellectual Capital, intangible generated on preventive action and indicators. Study of the relevant factors servitización and outsourcing, and implications with prevention. Empirical study: Initial study and further study. A comparative analysis considers their impact on the industrial sector relative to the service sector. Analysis of results and conclusions. Findings: This article determines if adequate preventive management helps to improve the image and increase the value of the company. The possible application of the components of Intellectual Capital with respect to intangibles generated in the prevention of occupational hazards is established, outlining the indicators to measure the generation of intangibles in preventive activities.Using both the initial and then further studies, the opinions and evaluation of entrepreneurs in Madrid can be assessed. A comparative analysis considers their impact on the industrial sector relative to the service sector, their particular characteristics, and the observed trend in the awareness of the benefits of prevention, in addition to establishing implications for the progressive increase servitization and outsourcing activities. Originality / Value: The paper provides information and interpretations which confirmed the importance of risk prevention as an intangible asset and a profitable

  8. Novel CD44 receptor targeting multifunctional “nano-eggs” based on double pH-sensitive nanoparticles for co-delivery of curcumin and paclitaxel to cancer cells and cancer stem cells

    Chen, Daquan; Wang, Guohua; Song, Weiguo; Zhang, Qiang

    2015-01-01

    Most anticancer drugs cannot kill cancer stem cells (CSCs) effectively, which lead to the failure of anticancer chemotherapy, such as relapse and metastasis. In this study, we prepared a multifunctional oligosaccharides of hyaluronan (oHA) conjugates, oHA-histidine-menthone 1,2-glycerol ketal (oHM). The oHM conjugates possess pH-sensitive menthone 1,2-glycerol ketal (MGK) as hydrophobic moieties and oHA as the target of CD44 receptor. Anticancer drugs, curcumin(Cur) and paclitaxel(PTX), were loaded into oHM micelles via self-assembly. Then, oHM micelles were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method to fabricate the “nano-eggs.” The formed nano-eggs had a smaller size (120.6 ± 4.5 nm) than oHM micelles (158.6 ± 6.4 nm), indicating that mineralization made the appearance of compact nanoparticles. Interestingly, when the nano-eggs were put into the acidic conditions (pH 6.5), their outer shell(inorganic minerals) will be destroyed with the larger size, while the “nano-eggs” were stable under pH 7.4. For both nano-eggs and oHM micelles, the Cur and PTX were released in a sustained manner depending on the pH of the solution. However, the nano-eggs showed much lower released than the oHM micelles due to the dissolution of the inorganic minerals and pH-sensitive ketal at mildly acidic environments (pH 6.5). In vivo study, the nano-eggs could get to the tumor site more effectively than oHM micelles. CSCs were sorted by a side population assay from MDA-MB-231 breast cancer cell lines over-expressing CD44 receptors. Antitumor activity was also evaluated on MDA-MB-231 xenografts in nude mice. The antitumor efficacy indicated that nano-eggs with co-delivery of Cur and PTX produced the strongest antitumor efficacy, and nano-eggs showed strong activity against cancer stem cells. These double pH-sensitive nano-eggs may provide a promising strategy for drug

  9. Novel CD44 receptor targeting multifunctional “nano-eggs” based on double pH-sensitive nanoparticles for co-delivery of curcumin and paclitaxel to cancer cells and cancer stem cells

    Chen, Daquan, E-mail: cdq1981@126.com [Peking University, School of Pharmaceutical Sciences, Health Science Center (China); Wang, Guohua [China Academy of Chinese Medical Sciences, Institute of Chinese Materia Madica (China); Song, Weiguo [Shouguang Fukang Pharmceutial Co., Ltd. (China); Zhang, Qiang, E-mail: zqdodo@bjmu.edu.cn [Peking University, School of Pharmaceutical Sciences, Health Science Center (China)

    2015-10-15

    Most anticancer drugs cannot kill cancer stem cells (CSCs) effectively, which lead to the failure of anticancer chemotherapy, such as relapse and metastasis. In this study, we prepared a multifunctional oligosaccharides of hyaluronan (oHA) conjugates, oHA-histidine-menthone 1,2-glycerol ketal (oHM). The oHM conjugates possess pH-sensitive menthone 1,2-glycerol ketal (MGK) as hydrophobic moieties and oHA as the target of CD44 receptor. Anticancer drugs, curcumin(Cur) and paclitaxel(PTX), were loaded into oHM micelles via self-assembly. Then, oHM micelles were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method to fabricate the “nano-eggs.” The formed nano-eggs had a smaller size (120.6 ± 4.5 nm) than oHM micelles (158.6 ± 6.4 nm), indicating that mineralization made the appearance of compact nanoparticles. Interestingly, when the nano-eggs were put into the acidic conditions (pH 6.5), their outer shell(inorganic minerals) will be destroyed with the larger size, while the “nano-eggs” were stable under pH 7.4. For both nano-eggs and oHM micelles, the Cur and PTX were released in a sustained manner depending on the pH of the solution. However, the nano-eggs showed much lower released than the oHM micelles due to the dissolution of the inorganic minerals and pH-sensitive ketal at mildly acidic environments (pH 6.5). In vivo study, the nano-eggs could get to the tumor site more effectively than oHM micelles. CSCs were sorted by a side population assay from MDA-MB-231 breast cancer cell lines over-expressing CD44 receptors. Antitumor activity was also evaluated on MDA-MB-231 xenografts in nude mice. The antitumor efficacy indicated that nano-eggs with co-delivery of Cur and PTX produced the strongest antitumor efficacy, and nano-eggs showed strong activity against cancer stem cells. These double pH-sensitive nano-eggs may provide a promising strategy for drug

  10. Occupational Clusters.

    Pottawattamie County School System, Council Bluffs, IA.

    The 15 occupational clusters (transportation, fine arts and humanities, communications and media, personal service occupations, construction, hospitality and recreation, health occupations, marine science occupations, consumer and homemaking-related occupations, agribusiness and natural resources, environment, public service, business and office…

  11. Role of CD44 in Tumor Progression

    Underhill, Charles

    1999-01-01

    ...) that we isolated from cartilage by affinity chromatography. We found that the HAbc was able to block the growth of tumors cells in mice as well as in the chorioallantoic membrane (CAM) of chicken embryos...

  12. Quantitative Characterization of E-selectin Interaction with Native CD44 and P-selectin Glycoprotein Ligand-1 (PSGL-1) Using a Real Time Immunoprecipitation-based Binding Assay

    Abu Samra, Dina Bashir Kamil; Al Kilani, Alia; Hamdan, Samir; Sakashita, Kosuke; Gadhoum, Samah Z.; Merzaban, Jasmeen

    2015-01-01

    Selectins (E-, P-, and L-selectins) interact with glycoprotein ligands to mediate the essential tethering/rolling step in cell transport and delivery that captures migrating cells from the circulating flow. In this work, we developed a real time immunoprecipitation assay on a surface plasmon resonance chip that captures native glycoforms of two well known E-selectin ligands (CD44/hematopoietic cell E-/L-selectin ligand and P-selectin glycoprotein ligand-1) from hematopoietic cell extracts. Here we present a comprehensive characterization of their binding to E-selectin. We show that both ligands bind recombinant monomeric E-selectin transiently with fast on- and fast off-rates, whereas they bind dimeric E-selectin with remarkably slow onand off-rates. This binding requires the sialyl Lewis x sugar moiety to be placed on both O- and N-glycans, and its association, but not dissociation, is sensitive to the salt concentration. Our results suggest a mechanism through which monomeric selectins mediate initial fast on and fast off kinetics to help capture cells out of the circulating shear flow; subsequently, tight binding by dimeric/oligomeric selectins is enabled to significantly slow rolling. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Quantitative Characterization of E-selectin Interaction with Native CD44 and P-selectin Glycoprotein Ligand-1 (PSGL-1) Using a Real Time Immunoprecipitation-based Binding Assay

    Abu Samra, Dina Bashir Kamil

    2015-06-29

    Selectins (E-, P-, and L-selectins) interact with glycoprotein ligands to mediate the essential tethering/rolling step in cell transport and delivery that captures migrating cells from the circulating flow. In this work, we developed a real time immunoprecipitation assay on a surface plasmon resonance chip that captures native glycoforms of two well known E-selectin ligands (CD44/hematopoietic cell E-/L-selectin ligand and P-selectin glycoprotein ligand-1) from hematopoietic cell extracts. Here we present a comprehensive characterization of their binding to E-selectin. We show that both ligands bind recombinant monomeric E-selectin transiently with fast on- and fast off-rates, whereas they bind dimeric E-selectin with remarkably slow onand off-rates. This binding requires the sialyl Lewis x sugar moiety to be placed on both O- and N-glycans, and its association, but not dissociation, is sensitive to the salt concentration. Our results suggest a mechanism through which monomeric selectins mediate initial fast on and fast off kinetics to help capture cells out of the circulating shear flow; subsequently, tight binding by dimeric/oligomeric selectins is enabled to significantly slow rolling. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Human immunodeficiency virus and hepatitis B virus infection prevention following occupational exposure among staff at a regional referral hospital in Western Kenya

    Barbara Kabai Burmen

    2018-01-01

    Full Text Available Background: Postexposure prophylaxis (PEP with antiretroviral therapy (ART and vaccination against hepatitis B virus (HBV aides in preventing human immunodeficiency virus (HIV infection and HBV, respectively, from accidental or occupational exposure. We assessed compliance to guidelines for HIV and HBV prevention after occupational exposure among hospital staff at a referral Kenyan hospital. Methods: We reviewed PEP registers for hospital staff reporting an occupational injury at a referral hospital in Western Kenya between January 2011 and December 2012. Proportions were used to summarize number of participants receiving the recommended services, Kaplan–Meier curves were used to describe time to ART initiation, and Chi-square statistics was used to describe the association between participant characteristics and PEP completion rates. P < 0.05 was considered statistically significant. Results: Majority of documented hospital staff (n = 52 were health workers (63% and students (27% and had high HIV risk exposures (97%. All had timely PEP initiation with 50% completing PEP. Completion rates did not vary by gender (P = 0.78, exposure type (P = 1.0, or department of exposure (P = 0.75. Retesting for HIV and negativity rates at months 1.5, 3, and 6 were 96%, 25%, and 17% and 100%, 100%, and 100%, respectively. At the time of exposure, 17% (9 of staff were HBV vaccinated and HBV status of sources was unknown; no intervention was provided for HBV prevention. Conclusions: Low rates of completion and follow-up negate intended benefits of PEP. Efforts should be directed to enforce universal precaution practices and completion of PEP. Low rates of HBV testing and vaccination illustrate the need for support for the implementation of HBV prevention guidelines.

  15. Occupational health problems, prevention and safety in solid recovered fuel facilities; Tyoeympaeristoen vaarojen arviointi ja torjunta toimenpiteet kiinteaen jaetteen kaesittelylaitoksilla

    Wilen, C.; Ajanko, S.; Rautalin, A. [VTT Processes, Espoo (Finland); Liesivuori, J.; Kallunki, H. [Finnish Institute of Occupational Health, Kuopio (Finland)

    2003-07-01

    New directives and laws will increase the utilization of wastes in the near future. At the same time the number of people employed in waste handling will increase. The aim of this study is to compare manual sorting in demolition waste handling facility to automatic sorting system in commercial and industrial waste facility. Many studies have shown, for example Danish, Dutch and German researches, that waste handling workers have problems especially in occupational health issues. Symptoms like headache, tiredness, joint pain, chest tightens, fever, diarrhea have been reported. Diseases reported are respiratory (asthma, ODTS), muscular, gastroinsteal diseases. Accident risk among waste workers is six times more common that among occupations usually. Finnish Institute of Occupational health carried out the occupational measurements together with VTT Processes. The EU direcitive accepted in 1999 requires for new waste handling facilities a work space and equipment hazardous classification until 2003 and based on it, an explosion protection document. An example for required actions and documents has been prepared in this project, which can be used as a tool and model in waste management companies and REF production facilities. A dust explosion risks analyse, a work space and equipment classifications and explosion protection document have been done for the Lohja REF-production facility. (orig.)

  16. Preparing Occupational Therapy Students to Address Mental Health Promotion, Prevention, and Intervention in School-Based Practice

    Blackwell, Cindy DeRuiter; Bilics, Andrea

    2018-01-01

    Directors of entry-level occupational therapy (OT) programs were surveyed regarding how their programs prepare students to become mental health practitioners in schools. Analysis of quantitative data included descriptive statistics to examine participants' ratings of their program's ability to prepare students for mental health practice. We found…

  17. Occupational health problems, prevention and safety in solid recovered fuel facilities; Tyoeympaeristoen vaarojen arviointi kiinteiden jaetteiden kaesittelylaitoksilla

    Wilen, C. [VTT Processes, Espoo (Finland)

    2005-07-01

    New directives and laws will increase the utilization of wastes in the near future. At the same time the number of people employed in waste handling will increase. The aim of this study is to compare manual sorting in demolition waste handling facility to automatic sorting system in commercial and industrial waste facility. Many studies have shown, for example Danish, Dutch and German investigations that waste handling workers have problems especially in occupational health issues. Symptoms like headache, tiredness, joint pain, chest tightens, fever, diarrhea have been reported. Diseases reported are respiratory (asthma, ODTS), muscular, gastroinsteal diseases. Accident risk among waste workers is six times more common that among occupations usually. Finnish Institute of Occupational health carried out the occupational measurements together with VTT Processes. The EU directive accepted in 1999 requires for new waste handling facilities a work space and equipment hazardous classification until 2003 and based on it, an explosion protection document. An example for required actions and documents has been prepared in this project, which can be used as a tool and model in waste management companies and REF production facilities. A dust explosion risks analyse, a work space and equipment classifications and explosion protection document have been done for the Lohja REF-production facility. (orig.)

  18. [Occupational skin cancer : Prevention and recommendations for UV protection as part of the treatment approved by the public statutory employers' liability insurance].

    Rocholl, M; Ludewig, M; Skudlik, C; Wilke, A

    2018-04-27

    In Germany, approximately 2 to 3 million employees work in outdoor professions. They are exceptionally exposed to solar ultraviolet (UV) radiation for a large part of their daily working time. Cumulative UV exposure is associated with a significantly increased risk of skin cancer for outdoor workers from various occupational groups (e. g. landscape and horticulture, agriculture and forestry, fisheries and seafaring, construction and trade, as well as sports teachers, lifeguards and mountain guides). Since 1 January 2015, squamous cell carcinoma and multiple actinic keratosis due to natural UV radiation can be recognised as occupational disease No. 5103 by the German statutory social accident insurance. Reducing cumulative UV exposure is the main prevention aspect of this type of skin damage. Therefore, technical, organisational and personal UV protection measures should be implemented in the professional and private environment. Moreover, they have to be regularly used in an appropriate way. In addition to guideline-oriented therapy, training and counselling of patients with already existing actinic skin damage or a recognised occupational disease No. 5103 is therefore of particular importance. The focus should be on improving the individual UV protection behaviour. This article gives an overview of current recommendations for UV protection in the professional environment. It outlines possible solutions for patient counselling in terms of UV protection in everyday practice.

  19. Health hazards from fine asbestos dusts. An analysis of 70,656 occupational preventive medical investigations from 1973 to the end of 1986.

    Raithel, H J; Weltle, D; Bohlig, H; Valentin, H

    1989-01-01

    For the period from 1973 to the end of 1986, 70,656 data sets on occupational preventive medical examinations in employees exposed occupationally to asbestos dust (G 1.2) were made available to us by the Central Registry for Employees Exposed to Asbestos Dust (ZAS). On the basis of this data, an analysis of asbestosis risk was to be made in relation to specific areas of work, taking into consideration the beginning and duration of exposure. Proceedings for declaratory appraisal in accordance with occupational disease no. 4103 were instituted in 1760 cases in the report period. In accordance with the character of the available data, the X-ray findings in the lungs were available from the persons investigated as parameters of possible asbestosis risk on the basis of coding consistent with the International Pneumoconiosis Classification (ILO U/C 1971 and/or ILO 1980 West Germany). The major result of the statistical analyses on the mainframe macrocomputer of the University of Erlangen-Nuremberg was that the relatively highest risk of asbestosis was present in persons whose exposure began before 1955. On the other hand, with increasing duration of exposure, an unequivocal rise of the asbestosis risk could not be detected on the basis of the overall population. In relation to the individual fields of work, the relatively highest risk of asbestosis was shown to be in the asbestos textile and paper industry, as well as in the asbestos cement industry. No detectable risk of asbestosis was present in the fields of mining, traffic and health service and for women in the industrial sectors of building material, gas and water, catering trade, building, commerce as well as banking and insurance. Accordingly, it can be assumed that certain fields of work are or were exposed to such a small extent or not at all that a risk of asbestosis which is relevant in terms of occupational medicine is no longer to be assumed or was not to be assumed. This applies above all to certain work

  20. Typical occupational accidents with employees of a university hospital in the south of Brazil: epidemiology and prevention.

    Sêcco, Iara Aparecida de Oliveira; Robazzi, Maria Lúcia do Carmo Cruz; Shimizu, Denise Sayuri; Rúbio, Márcia Maria da Silva

    2008-01-01

    Descriptive epidemiologic study that aimed to analyze the typical occupational accidents notified by employees of a university hospital in the South of Brazil from 1997 to 2002, and to estimate their risk indicators. A total of 717 accidents were registered; 86% of them (616) were typical and presented an annual average risk coefficient of 6.0 per 100 employees. The groups that presented more risks for accidents were cooks, woodworkers and nursing auxiliaries, while hands were the most affected area. Regarding the accidents nature, the greatest risks involved biological material. Hence, it is necessary to orient personnel about the legal aspects of occupational accidents and review work processes, especially those related to employees who perform activities at greater risk of transmissible diseases like AIDS and hepatitis B and C.

  1. Developing Occupation-Based Preventive Programs for Late-Middle-Aged Latino Patients in Safety-Net Health Systems.

    Schepens Niemiec, Stacey L; Carlson, Mike; Martínez, Jenny; Guzmán, Laura; Mahajan, Anish; Clark, Florence

    2015-01-01

    Latino adults between ages 50 and 60 yr are at high risk for developing chronic conditions that can lead to early disability. We conducted a qualitative pilot study with 11 Latinos in this demographic group to develop a foundational schema for the design of health promotion programs that could be implemented by occupational therapy practitioners in primary care settings for this population. One-on-one interviews addressing routines and activities, health management, and health care utilization were conducted, audiotaped, and transcribed. Results of a content analysis of the qualitative data revealed the following six domains of most concern: Weight Management; Disease Management; Mental Health and Well-Being; Personal Finances; Family, Friends, and Community; and Stress Management. A typology of perceived health-actualizing strategies was derived for each domain. This schema can be used by occupational therapy practitioners to inform the development of health-promotion lifestyle interventions designed specifically for late-middle-aged Latinos. Copyright © 2015 by the American Occupational Therapy Association, Inc.

  2. A police education programme to integrate occupational safety and HIV prevention: protocol for a modified stepped-wedge study design with parallel prospective cohorts to assess behavioural outcomes

    Strathdee, Steffanie A; Arredondo, Jaime; Rocha, Teresita; Abramovitz, Daniela; Rolon, Maria Luisa; Patiño Mandujano, Efrain; Rangel, Maria Gudelia; Olivarria, Horcasitas Omar; Gaines, Tommi; Patterson, Thomas L; Beletsky, Leo

    2015-01-01

    Introduction Policing practices are key drivers of HIV among people who inject drugs (PWID). This paper describes the protocol for the first study to prospectively examine the impact of a police education programme (PEP) to align law enforcement and HIV prevention. PEPs incorporating HIV prevention (including harm reduction programmes like syringe exchange) have been successfully piloted in several countries but were limited to brief pre–post assessments; the impact of PEPs on policing behaviours and occupational safety is unknown. Objectives Proyecto ESCUDO (SHIELD) aims to evaluate the efficacy of the PEP on uptake of occupational safety procedures, as assessed through the incidence of needle stick injuries (NSIs) (primary outcome) and changes in knowledge of transmission, prevention and treatment of HIV and viral hepatitis; attitudes towards PWID, adverse behaviours that interfere with HIV prevention and protective behaviours (secondary outcomes). Methods/analysis ESCUDO is a hybrid type I design that simultaneously tests an intervention and an implementation strategy. Using a modified stepped-wedge design involving all active duty street-level police officers in Tijuana (N=∼1200), we will administer one 3 h PEP course to groups of 20–50 officers until the entire force is trained. NSI incidence and geocoded arrest data will be assessed from department-wide de-identified data. Of the consenting police officers, a subcohort (N=500) will be randomly sampled from each class to undergo pre-PEP and post-PEP surveys with a semiannual follow-up for 2 years to assess self-reported NSIs, attitudes and behaviour changes. The impact on PWIDs will be externally validated through a parallel cohort of Tijuana PWIDs. Ethics/dissemination Research ethics approval was obtained from the USA and Mexico. Findings will be disseminated through open access to protocol materials through the Law Enforcement and HIV Network. Trial registration number NCT02444403. PMID:26260350

  3. Data linkage between the National Birth Defects Prevention Study and the Occupational Information Network (O*NET) to assess workplace physical activity, sedentary behaviors, and emotional stressors during pregnancy.

    Lee, Laura J; Symanski, Elaine; Lupo, Philip J; Tinker, Sarah C; Razzaghi, Hilda; Pompeii, Lisa A; Hoyt, Adrienne T; Canfield, Mark A; Chan, Wenyaw

    2016-02-01

    Knowledge of the prevalence of work-related physical activities, sedentary behaviors, and emotional stressors among pregnant women is limited, and the extent to which these exposures vary by maternal characteristics remains unclear. Data on mothers of 6,817 infants without major birth defects, with estimated delivery during 1997 through 2009 who worked during pregnancy were obtained from the National Birth Defects Prevention Study. Information on multiple domains of occupational exposures was gathered by linking mother's primary job to the Occupational Information Network Version 9.0. The most frequent estimated physical activity associated with jobs during pregnancy was standing. Of 6,337 mothers, 31.0% reported jobs associated with standing for ≥75% of their time. There was significant variability in estimated occupational exposures by maternal age, race/ethnicity, and educational level. Our findings augment existing literature on occupational physical activities, sedentary behaviors, emotional stressors, and occupational health disparities during pregnancy. © 2015 Wiley Periodicals, Inc.

  4. Occupational exposure prevention program to oil and gas industry; Antecipacao, reconhecimento, avaliacao e controle dos riscos ambientais em uma planta de petroleo e gas

    Moraes, Paulo Sergio de [TRANSPETRO - PETROBRAS Transporte S.A., Rio de Janeiro, RJ (Brazil); Palierini, Renato Martins [TWA Brasil, Sao Caetano do Sul, SP (Brazil)

    2005-07-01

    PETROBRAS/TRANSPETRO Pipelines and Terminals have 500 regular employees and 5.064 out sourced workers in its Southeast Division. The out sourced employees work under 125 contracts involving a wide range of activities such as maintenance, pipeline operation, pipeline launching, engineering, administrative and auxiliary services. Among these workers, 1.200 peoples are subjected to occupational exposure, which may be present in the industrial process or in the products transported in our pipelines, e.g. industrial noise, sulfidric gas, toluene, xylene and benzene (recognized as a carcinogen according to ACGIH and Brazilian Ministry of Labour). Our PPRA (acronym in Portuguese for Occupational Exposure Prevention Program) involves the workforce and fosters health by anticipation, recognition, evaluation and control of the situations that may result in injuries. Further actions include the procurement of equipment for detection of these agents not only in the air but also diluted in liquids and the introduction of state-of the- art technologies for a better process control. The priority is the acquisition of equipment for collective protection not forgetting the individual protection equipment (IPE) and the required training. Implementation of this program counted on the effective involvement of the managers, contract supervisors and HSE professionals whose main task was to advise all involved parts on the use the Risk Analysis Methods tailored for Occupational Hygiene. Furthermore, these information will be used in a info system called SD-2000 that will gather and compare Health, Hygiene e Human Resources data in order to support the professional in the management and decision making process. (author)

  5. The impact of occupational health and safety regulations on prevention through design in construction projects: Perspectives from Spain and the United Kingdom.

    Martínez-Aires, María Dolores; Rubio Gámez, María Carmen; Gibb, Alistair

    2015-01-01

    Since the mid-1990 s, Prevention through Design (PtD) has become increasingly prevalent in the built environment. The acceptance of PtD has largely been due to the removal or reduction of risks during the execution phase of construction projects. European States have had the added impetus of national legislation. This paper analyzes the influence of European Union Directive 92/57/EEC on occupational safety and health injury prevention in the project design phase. Qualitative methods comprised individual semi-structured interviews and focus groups with a panel of experts. Sixty individuals from construction and related professions (architects, engineers, constructors, developers, and other construction experts) answered 17 key questions to establish national perceptions of the effectiveness of Directive 92/57/EEC in Spain and the United Kingdom (UK). The implementation of PtD in the project design phase in the UK is clearer since the regulations explicitly state the obligations of project designers as well as those of the coordinator. Interviews with Spanish experts show that, in Spain, the prevention culture is less frequently realized. The most significant differences between the European Directive and national regulations which influence PtD are linked to the Health and Safety Coordinator, and Health and Safety documents.

  6. OCCUPATIONAL EXPOSURE AND COPD

    Würtz, Else Toft

    Chronic Obstructive Pulmonary Disease (COPD) is a common disease. The main risk factor is smoking although 15% of the COPD cases are expected to be preventable if the occupational exposures from vapour, gas, dust, and fume were eliminated; the population attributable fraction (PAF). The thesis...... addresses the association between occupational exposure and COPD in a population-based cohort of Danes aged 45-84-years. 4717 participants were included at baseline and 2624 at the four year follow-up. COPD was defined by spirometry and the occupational exposure was based on specialist defined jobs...... and questionnaires. The main occupational exposure was organic dust and 49% reported no lifetime occupational exposure. The results suggest occupational exposures to be associated to COPD also in never smokers and women. We found an exposure-response relation in the cross sectional analyses. The results...

  7. The Occupational Disease Prevention and Control Act of the People's Republic of China: an awareness assessment among workers at foreign-invested enterprises.

    Yongming, Shou; Rongzhu, Lu; Jie, Lin; Yan, Xu; Zhu, Yiliang; Schweigert, Michael

    2011-01-01

    The Occupational Disease Prevention and Control Act (ODPC-Act) of the People's Republic of China came into effect on May 1, 2002. Given the scope of foreign-invested enterprises (FIEs) in China and an unabated increasing trend of foreign investment, compliance with the ODPC-Act among FIEs is of particular interest, yet little is known. The extent to which an employer educates its workforce to understand the ODPC-Act may be a measure of an employer's compliance. Based on a 25-item questionnaire survey, we found that among 166 workers from three FIEs in Wuxi, Jiangsu Province, the majority had little knowledge regarding the ODPC-Act; many were unaware of their rights granted under the ODPC-Act. They were also unable to recognize employers' potential violations of the ODPC-Act. Improving FIE workers' awareness of the ODPC-Act is desirable.

  8. [Good practices and techniques for prevention of accidents at work and occupational diseases. New database of Inail].

    Bindi, L; Ossicini, A

    2007-01-01

    The project "The publication of good practices and good techniques for prevention" is one the priorities of nail. This computerized system for the collection of good practices and standards of Good Technology is aimed to health and safety of workers. The basic objective of the database is to provide a valuable tool, usable, dynamic and implemented, in order to facilitate and direct the access to BP and BT it by people responsible for SSL. At the same time constitutes a tool strategically important for enterprises (especially SMEs) in terms of technological innovation and competitiveness, related to the prevention, safety and health of workers. The realization of this project has involved many of the professionals (chemists, engineers, doctors, biologists, geologists, etc.), and everyone gives his intake of qualified professional competence.

  9. [Examination of the Prevention of Severe Hand Trauma Injury Cases due to Occupational Accidents--An Expert Opinion Gathering Meeting].

    Zenke, Yukichi; Kajiki, Shigeyuki; Yoshikawa, Toru; Nakao, Toyoki; Yoshikawa, Etsuko; Shoji, Takurou; Fukumoto, Keizo; Sakai, Akinori

    2015-12-01

    We gathered seven specialists from various fields who are interested in worker injury prevention programs, based on cases of patients who had suffered refractory injuries requiring hand surgery because of industrial accidents. The patients were asked to write their thoughts and ideas on the theme, "Measures that must be implemented to prevent arm injuries." The content obtained was classified into different categories, using the KJ method, and was scripted to sort out the items. As a result, the following eleven points were identified as measures to prevent serious hand surgery-related injuries: 1. Purchase safe machinery, 2. Create a list of machines that require caution, 3. Enclose a machine's various rotating parts, 4. Carry out periodic maintenance work on the machines, 5. Indicate dangerous areas by putting up signs that attract attention, 6. Illuminate the rotating parts more brightly and avoid placing objects around them, 7. Systematically carry out safety education that creates a strong impact, 8. Encourage workers to look after their own health, 9. Announce policies on health and safety, 10. Re-examine the operational procedures, and 11. Be prepared in case an accident occurs. A perspective based on the results of this research is deemed important in creating a workplace improvement manual in the future.

  10. Occupational hand injuries: a current review of the prevalence and proposed prevention strategies for physical therapists and similar healthcare professionals.

    Gyer, Giles; Michael, Jimmy; Inklebarger, James

    2018-03-01

    Hand injury is the second most common work-related musculoskeletal injury among physical therapists (PTs) and other manual therapy professionals such as osteopaths, physiotherapists, chiropractors, acupuncturists and massage therapists. However, the nature and extent of this problem have not been fully explored yet. Therefore, the objective of this study was to review the existing literature published on the prevalence, risk factors, consequences, and prevention of hand injuries among PTs and similar healthcare professionals. The lifetime prevalence of hand injuries was about 15%-46%, and the annual prevalence was reported as 5%-30%. Thumb injuries were found to be the most prevalent of all injuries, accounting more than 50% of all hand-related problems. The most significant risk factors for job-related hand injuries were performing manual therapy techniques, repetitive workloads, treating many patients per day, continued work while injured or hurt, weakness of the thumb muscles, thumb hypermobility, and instability at the thumb joints. PTs reported modifying treatment technique, taking time off on sick leave, seeking intervention, shifting the specialty area, and decreasing patient contact hours as the major consequences of these injuries. The authors recommend that PTs should develop specific preventive strategies and put more emphasis on the use of aids and equipment to reduce the risk of an unnecessary injury. Copyright © 2018 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

  11. Occupational exposure to benzene: a prevention program for employees and contractors; PPEOB - Programa de Prevencao a Exposicao Ocupacional ao Benzeno para Empregados Proprios e Contratados

    Moraes, Paulo Sergio de; Silva, Edson Ferreira da; Patto, Claudio Monteiro [TRANSPETRO, Rio de Janeiro, RJ (Brazil)

    2004-07-01

    PETROBRAS/TRANSPETRO Pipelines and Terminals has 500 regular employees and 5.064 out sourced workers in its Southeast Division. The out sourced employees work through 125 contracts involving a wide range of activities such as maintenance, operational, pipeline launching , engineering, administrative and auxiliary services. Among these workers, 200 people are subjected to benzene occupational exposure, which might be present in the products we transport in our pipelines. Benzene is recognized as a carcinogen according to ACGIH and Brazilian Ministry of Labour regulation NR- 15. Exposure to benzene in an uncontrolled way, be it chronic or sharp, may affect the worker's health such as: hematological alterations, neoplasys, neurobehavior alterations. Our program PPEOB (acronym in Portuguese for benzene occupational exposure prevention program) involved the work force and fosters health by anticipation, recognition, evaluation and control of the situations that may result in injuries. Further actions include the acquisition of equipment for benzene detection in the air or diluted in liquids and the introduction of new technologies for process control. The priority is the acquisition of equipment for collective protection not forgetting the individual protection equipment (IPE) and the required training. Implementation of this program counted with the effective participation of managers, contract supervisors and HSE professionals whose main task was to advise all involved parts. Furthermore, an auto-evaluation was released in order to assess the adherence of the PPEOB related to the facility reality. Since a suitable level of adherence is reached, the PPEOB can be used as a standard in the whole TRANSPETRO. (author)

  12. Managing Occupational Irritant Contact Dermatitis Using a Two-Step Skincare Regimen Designed to Prevent Skin Damage and Support Skin Recovery.

    von Grote, Erika C; Palaniswarmy, Kiruthi; Meckfessel, Matthew H

    2016-12-01

    Occupational irritant contact dermatitis (ICD) affecting the hands is a common and difficult-to-manage condition. Occupations that necessitate contact with harsh chemicals, use of alcohol-based disinfectants, and frequent hand washing elevate the risk of ICD. Management strategies that do not adequately prevent accumulated damage and repair skin, can develop into chronic dermatoses which negatively impact work productivity and quality of life. A 2-step skin-care regimen (Excipial Daily Protection Hand Cream (EP) and Excipial Rapid Repair Hand Cream (ER), Galderma Laboratories, L.P.) has been developed as a daily-use management strategy to protect and repair vulnerable hands. The protective barrier cream is formulated with aluminum chlorohydrate and designed for pre-exposure application to enhance the skin's natural protective barrier and minimize excessive moisture while wearing protective gloves. The repair cream, a lipid-rich formulation, is intended for post-exposure application to rehydrate and facilitate the skin's natural healing process. The results of 3 clinical studies highlighted in this review demonstrate how the use of a 2-step skin-care regimen offers a greater protective effect against ICD than the use of barrier cream alone, and also how the formulation of the barrier cream used in these studies helps minimize the occlusion effect caused by gloves and does not interfere with the antibacterial efficacy of an alcohol-based hand sanitizer. This 2-step skin-care regimen is effectively designed to manage and minimize the risk of ICD development in a variety of patients and provides clinicians an additional tool for helping patients manage ICD. J Drugs Dermatol. 2016;15(12):1504-1510.

  13. Effectiveness of skin protection creams in the prevention of occupational dermatitis: results of a randomized, controlled trial.

    Winker, Robert; Salameh, Bayda; Stolkovich, Sabine; Nikl, Michael; Barth, Alfred; Ponocny, Elisabeth; Drexler, Hans; Tappeiner, Gerhard

    2009-04-01

    The aim of the trial was to investigate whether the publicized effects of skin protection creams can be replicated in a real occupational setting during activities that expose the skin. A prospective, randomized, four-tailed controlled pilot trial was performed to compare the effect of skin protection and skin care alone or in combination with cleansing against a control group (only cleansing). Two branches were selected for the investigation: the building industry and the timber industry. A total of 1,006 workers from these two branches were recruited, and out of these 485 workers were examined longitudinally for at least three time points over 1 year (lost for follow-up: 430 workers, exclusion: 91 workers). At each time point, as a primary outcome measure, we assessed the condition of the skin at both hands in a blinded manner and the individual was assigned to one of the following categories: no eczema, mild, moderate and severe eczema. As a secondary outcome measure, the worker's transepidermal water loss (TEWL) was measured under standardized conditions at the back of both hands. In addition, the workers were asked to evaluate their skin condition during the study. With regard to differences in the occurrence of eczemas, we found only in workers in building industry without application of skin protection or skin care creams a statistical significant increase in the incidence between the first and the second visit and a statistical significant decrease in the incidence between the second and third visit. When evaluating the secondary outcome-measurement changes in the TEWL values, an improvement was found for the group skin protection and skin care in combination and by skin care alone. Females in the timber industry started with better TEWL values than males, which may be due to better overall skin care. In this group we found an improvement for the group skin protection and skin care in combination and by skin protection alone. For skin protection alone, we

  14. Occupational skin diseases

    Mahler, V; Aalto-Korte, K; Alfonso, J H

    2017-01-01

    BACKGROUND: Work-related skin diseases (WSD) are caused or worsened by a professional activity. Occupational skin diseases (OSD) need to fulfil additional legal criteria which differ from country to country. OSD range amongst the five most frequently notified occupational diseases (musculoskeletal...... diseases, neurologic diseases, lung diseases, diseases of the sensory organs, skin diseases) in Europe. OBJECTIVE: To retrieve information and compare the current state of national frameworks and pathways to manage patients with occupational skin disease with regard to prevention, diagnosis, treatment...... in Science and Technology (COST) Action TD 1206 (StanDerm) (www.standerm.eu). RESULTS: Besides a national health service or a statutory health insurance, most European member states implemented a second insurance scheme specifically geared at occupational diseases [insurance against occupational risks...

  15. Occupational medicine and toxicology

    Fischer Axel

    2006-02-01

    Full Text Available Abstract This editorial is to announce the Journal of Occupational Medicine and Toxicology, a new Open Access, peer-reviewed, online journal published by BioMed Central. Occupational medicine and toxicology belong to the most wide ranging disciplines of all medical specialties. The field is devoted to the diagnosis, prevention, management and scientific analysis of diseases from the fields of occupational and environmental medicine and toxicology. It also covers the promotion of occupational and environmental health. The complexity of modern industrial processes has dramatically changed over the past years and today's areas include effects of atmospheric pollution, carcinogenesis, biological monitoring, ergonomics, epidemiology, product safety and health promotion. We hope that the launch of the Journal of Occupational Medicine and Toxicology will aid in the advance of these important areas of research bringing together multi-disciplinary research findings.

  16. Can a new behaviorally oriented training process to improve lifting technique prevent occupationally related back injuries due to lifting?

    Lavender, Steven A; Lorenz, Eric P; Andersson, Gunnar B J

    2007-02-15

    A prospective randomized control trial. To determine the degree to which a new behavior-based lift training program (LiftTrainer; Ascension Technology, Burlington, VT) could reduce the incidence of low back disorder in distribution center jobs that require repetitive lifting. Most studies show programs aimed at training lifting techniques to be ineffective in preventing low back disorders, which may be due to their conceptual rather than behavioral learning approach. A total of 2144 employees in 19 distribution centers were randomized into either the LiftTrainer program or a video control group. In the LiftTrainer program, participants were individually trained in up to 5, 30-minute sessions while instrumented with motion capture sensors to quantify the L5/S1 moments. Twelve months following the initial training, injury data were obtained from company records. Survival analyses (Kaplan-Meier) indicated that there was no difference in injury rates between the 2 training groups. Likewise, there was no difference in the turnover rates. However, those with a low (<30 Nm) average twisting moment at the end of the first session experienced a significantly (P < 0.005) lower rate of low back disorder than controls. While overall the LiftTrainer program was not effective, those with twisting moments below 30 Nm reported fewer injuries, suggesting a shift in focus for "safe" lifting programs.

  17. Occupational activity and cognitive reserve: implications in terms of prevention of cognitive aging and Alzheimer’s disease

    Adam S

    2013-04-01

    Full Text Available Stéphane Adam1, Eric Bonsang2, Catherine Grotz1, Sergio Perelman3 1Unité de Psychologie de la Sénescence, University of Liège, Belgium; 2Research Centre for Education and the Labour Market, Maastricht University, The Netherlands; 3Center of Research in Public Economics and Population Economics, University of Liège, Belgium Abstract: This paper investigates the relationship between the concept of activity (including both professional and nonprofessional and cognitive functioning among older European individuals. In this research, we used data collected during the first wave of SHARE (Survey on Health, Ageing and Retirement in Europe, and a measurement approach known as stochastic frontier analysis, derived from the economic literature. SHARE includes a large population (n > 25,000 geographically distributed across Europe, and analyzes several dimensions simultaneously, including physical and mental health activity. The main advantages of stochastic frontier analysis are that it allows estimation of parametric function relating cognitive scores and driving factors at the boundary and disentangles frontier noise and distance to frontier components, as well as testing the effect of potential factors on these distances simultaneously. The analysis reveals that all activities are positively related to cognitive functioning in elderly people. Our results are discussed in terms of prevention of cognitive aging and Alzheimer’s disease, and regarding the potential impact that some retirement programs might have on cognitive functioning in individuals across Europe. Keywords: cognitive aging, cognitive reserve, retirement, Alzheimer’s disease

  18. Evaluation of the results of the prevention program “Protect your voice” implemented by The Greater Poland Center of Occupational Medicine of Poznań

    Magdalena Jałowska

    2017-10-01

    Full Text Available Background: The aim of the study was to evaluate the rationale for training in voice emission and voice prophylaxis among teachers and to assess the effects of voice disorders rehabilitation in the selected group of teachers participating in the program “Protect your voice.” Material and Methods: An anonymous survey was conducted among 463 teachers participating in the training part of the program. The effectivness of rehabilitation of teachers with occupational voice disorders was evaluated among 51 subjects (average age: 43 years taking part in diagnostic and rehabilitation part of the program. Phonation voice exercises with speech therapist and physiotherapy (iontophoresis, inhalations and elektrostimulation were administered. Evaluation of rehabilitation was based on phoniatric examination, including videostroboscopy and statistical calculations. Results: The survey showed that among teachers there is high demand (98% for training in proper voice emission, hygiene and prevention of voice. The effectiveness of rehabilitation has been confirmed by the observed improvements in phonatory activities of larynx, proper breathing during phonation (p = 0.0000, the voice quality (p = 0.0022, prolonged phonation time (an average of 1.39 s, increased number of people who correctly activated resonators (p = 0.0000 and increased number of people with phonation without excesive muscle tension of the neck. Conclusions: The results indicate that among all the professionally active teachers, there is a need for regular training of proper voice emission and vocal hygiene and then conduct individually phonation and breathing exercises, supported by the physiotherapy. This should be an effective method of voice disorders prevention in teachers. Med Pr 2017;68(5:593–603

  19. [Evaluation of the results of the prevention program "Protect your voice" implemented by The Greater Poland Center of Occupational Medicine of Poznan].

    Jałowska, Magdalena; Wośkowiak, Grażyna; Wiskirska-Woźnica, Bożena

    2017-07-26

    The aim of the study was to evaluate the rationale for training in voice emission and voice prophylaxis among teachers and to assess the effects of voice disorders rehabilitation in the selected group of teachers participating in the program "Protect your voice." An anonymous survey was conducted among 463 teachers participating in the training part of the program. The effectivness of rehabilitation of teachers with occupational voice disorders was evaluated among 51 subjects (average age: 43 years) taking part in diagnostic and rehabilitation part of the program. Phonation voice exercises with speech therapist and physiotherapy (iontophoresis, inhalations and elektrostimulation) were administered. Evaluation of rehabilitation was based on phoniatric examination, including videostroboscopy and statistical calculations. The survey showed that among teachers there is high demand (98%) for training in proper voice emission, hygiene and prevention of voice. The effectiveness of rehabilitation has been confirmed by the observed improvements in phonatory activities of larynx, proper breathing during phonation (p = 0.0000), the voice quality (p = 0.0022), prolonged phonation time (an average of 1.39 s), increased number of people who correctly activated resonators (p = 0.0000) and increased number of people with phonation without excesive muscle tension of the neck. The results indicate that among all the professionally active teachers, there is a need for regular training of proper voice emission and vocal hygiene and then conduct individually phonation and breathing exercises, supported by the physiotherapy. This should be an effective method of voice disorders prevention in teachers. Med Pr 2017;68(5):593-603. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  20. Knowledge of preventive measures against occupational risks and spread of healthcare-associated infections among nursing students. An epidemiological prevalence study from Ferrara, Italy.

    Bergamini, M; Cucchi, A; Stefanati, A; Cavallaro, A; Gabutti, G

    2009-06-01

    Exposure to biological agents is the most common occupational risk for nursing staff. This study verified changes in attitudes and knowledge occurred in the nursing students after the first year of degree. The survey was conducted in academic year 2006/07 among the students of the Professional Nursing Course at University of Ferrara (Italy) using a structured questionnaire. Students were 85 at the beginning and 80 at the end of the courses. The rate of subjects using gloves for intramuscular injections and fingertip puncture was unsatisfactory. A high percentage of students performed recap of needles. The use of gloves in case of washing of surgical instruments was high. The compliance in the use of gloves in handling test tubes remained low. Only 2/3 of the students washes their hands coming in ward. Incorrect attitudes have been observed in changing or wearing gloves. The students considered vaccination against hepatitis-B necessary, vaccination against flu unnecessary. A high percentage of students had not performed any prophylaxis for tuberculosis. Students intend the use of gloves mainly to perform self-protection. The concept of self-protection is contradicted by the large percentage of students that recap used needles. A significant percentage of students have not yet gained the critical thinking necessary to consider the importance of universal precautions as a means not only of self-protection but also of prevention of hospital infections. Students consider the basic standard measures for the control of infectious diseases only like self-protection and not to prevent hospital infections.

  1. [Good practice in occupational health services--Certification of stroke as an accident at work. Need for secondary prevention in people returning to work after acute cerebrovascular events].

    Marcinkiewicz, Andrzej; Walusiak-Skorupa, Jolanta

    2015-01-01

    The classification of an acute vascular episode, both heart infarct and stroke, as an accident at work poses difficulties not only for post accidental teams, but also to occupational health professionals, experts and judges at labor and social insurance courts. This article presents the case of a 41-year-old office worker, whose job involved client services. While attending a very aggressive customer she developed solid stress that resulted in symptoms of the central nervous system (headache, speech disturbances). During her hospitalisation at the neurological unit ischemic stroke with transient mixed type aphasia was diagnosed. Magnetic resonance imaging (MRI) scan of the head revealed subacute ischemia. After an analysis of the accident circumstances, the employer's post accidental team decided that ischemic stroke had been an accident at work, because it was a sudden incident due to an external cause inducing work-related traumatic stroke. As a primary cause tough stress and emotional strain due to the situation developed while attending the customer were acknowledged. During control medical check up after 5 months the patient was found to be fit for work, so she could return to work. However, it should be noted that such a check up examination of subjects returning to work after stroke must be holistic, including the evaluation of job predispositions and health education aimed at secondary prevention of heart and vascular diseases with special reference to their risk factors. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  2. Good practice in occupational health services – Certification of stroke as an accident at work. Need for secondary prevention in people returning to work after acute cerebrovascular events

    Andrzej Marcinkiewicz

    2015-08-01

    Full Text Available The classification of an acute vascular episode, both heart infarct and stroke, as an accident at work poses difficulties not only for post accidental teams, but also to occupational health professionals, experts and judges at labor and social insurance courts. This article presents the case of a 41-year-old office worker, whose job involved client services. While attending a very aggressive customer she developed solid stress that resulted in symptoms of the central nervous system (headache, speech disturbances. During her hospitalisation at the neurological unit ischemic stroke with transient mixed type aphasia was diagnosed. Magnetic resonance imaging (MRI scan of the head revealed subacute ischemia. After an analysis of the accident circumstances, the employer’s post accidental team decided that ischemic stroke had been an accident at work, because it was a sudden incident due to an external cause inducing work-related traumatic stroke. As a primary cause tough stress and emotional strain due to the situation developed while attending the customer were acknowledged. During control medical check up after 5 months the patient was found to be fit for work, so she could return to work. However, it should be noted that such a check up examination of subjects returning to work after stroke must be holistic, including the evaluation of job predispositions and health education aimed at secondary prevention of heart and vascular diseases with special reference to their risk factors. Med Pr 2015;66(4:595–599

  3. Prevention

    Halken, S; Høst, A

    2001-01-01

    , breastfeeding should be encouraged for 4-6 months. In high-risk infants a documented extensively hydrolysed formula is recommended if exclusive breastfeeding is not possible for the first 4 months of life. There is no evidence for preventive dietary intervention neither during pregnancy nor lactation...... populations. These theories remain to be documented in proper, controlled and prospective studies. Breastfeeding and the late introduction of solid foods (>4 months) is associated with a reduced risk of food allergy, atopic dermatitis, and recurrent wheezing and asthma in early childhood. In all infants....... Preventive dietary restrictions after the age of 4-6 months are not scientifically documented....

  4. Occupational Mental Health, Labor Accidents and Occupational Diseases

    Naveillan, F. Pedro

    1973-01-01

    The article discusses the relationship between mental health and labor accidents as it pertains to accident prevention, treatment of accident victims, and their rehabilitation. It also comments briefly on mental health and occupational diseases and the scope of the field of occupational mental health from a Chilean perspective. (AG)

  5. Occupational skin cancers

    Gawkrodger, D.J. [Royal Hallamshire Hospital, Sheffield (United Kingdom). Dept. of Dermatology

    2004-10-01

    Skin cancer due to occupation is more common than is generally recognized, although it is difficult to obtain an accurate estimate of its prevalence. Over the past two centuries, occupational skin cancers have particularly been due to industrial exposure of men (it seems more so than women) to chemical carcinogens such as polycyclic hydrocarbons (e.g. from coal tar products) or to arsenic. Industrial processes have improved in most Western countries to limit this type of exposure, but those with outdoor occupations are still exposed to solar ultraviolet irradiation without this being widely recognized as an industrial hazard. Ionizing radiation such as X-rays can also cause skin cancer. Occupational skin cancers often resemble skin tumours found in non-occupational subjects, e.g. basal cell carcinoma, squamous cell carcinoma and malignant melanoma, but some pre-malignant lesions can be more specific and point to an occupational origin, e.g. tar keratoses or arsenical keratoses. An uncommon but well-recognized cause of occupational skin cancer is that which results from scar formation following an industrial burn. In the future it will be necessary to focus on preventative measures, e.g. for outdoor workers, the need to cover up in the sun and use sun protective creams and a campaign for earlier recognition of skin cancers, which are usually curable if treated in their early stages.

  6. [News on occupational contact dermatitis].

    Crépy, Marie-Noëlle; Bensefa-Colas, Lynda

    2014-03-01

    Contact dermatitis--irritant contact dermatitis, allergic contact dermatitis and protein contact dermatitis--are the most common occupational skin diseases, most often localized to the hands. Contact urticaria is rarer The main occupational irritants are wet work, detergents and disinfectants, cutting oils, and solvents. The main occupational allergens are rubber additives, metals (chromium, nickel, cobalt), plastics (epoxy resins, acrylic), biocides and plants. Diagnosis is based on clinical examination, medical history and allergy testing. For a number of irritating or sensitizing agents, irritant or allergic dermatitis can be notified as occupational diseases. The two main prevention measures are reducing skin contact with irritants and complete avoidance of skin contact with offending allergens.

  7. A comprehensive overview of the frequency and the severity of injuries sustained by car occupants and subsequent implications in terms of injury prevention.

    Page, Yves; Cuny, Sophie; Hermitte, Thierry; Labrousse, Maxime

    2012-01-01

    The objective of the paper is to give an overview of the road injuries issues in France in the 2010's by determining the frequency and the severity of injuries sustained by car occupants, and to infer the implications in terms of vehicule safety. Three types of analysis are conducted. First, we present a time series analysis at a macro statistical level showing a dramatic decrease of injured and fatally injured occupants in passenger cars compared to other modes of road transport. Secondly, we propose a descriptive statistical analysis of the injuries (frequency and severity) sustained by car occupants, by body regions, using the AIS. Finally we propose some insights into the effectiveness of some safety features. French National crash census (BAAC) is used for a general overview of injury frequencies and raw severity scores (fatal, hospitalized, slighty injured) in car crashes. In-depth crash investigations data are used to specify the body regions and the severity of the injuries sustained by car occupants. Data show that car occupants mortality and morbidity decreased more over the last decade than other road modes: -58 % fatalities and -64 % hospitalized (compared to -39% and -55% for pedestrians, and -21% and -44% for motorcyclists for example). In crashes for which at least one person has been injured, 19 % of occupants are uninjured, 49 % of occupants sustain MAIS 1 injuries, 15 % MAIS2, 8% MAIS 3, and 9 % MAIS 4+. Regardless of seat belt use, the body regions most often injured are head, upper and lower extremities and thorax. However, at least two third up to 92% of involved persons sustain no injury at each of these body regions. The frequency of severe injuries is low, often less than 10 % and concern head and thorax mainly. Finally, the frequency and severity of injuries decrease for belted occupants in newer cars compared to older cars, whatever body regions. The frequency of severe injuries decreased by almost 50 % in these newer cars.

  8. Zoonoses as occupational diseases

    Giorgio Battelli

    2008-12-01

    Full Text Available Zoonoses are discussed as occupational diseases, with special reference to animal husbandry and related activities. After quoting some historical references, occupational zoonoses are examined in relation to the evolution of the concept of occupational zoonosis, the involvement of the World Health Organization in this field, their socio-economic significance, the principal working activities, zoonoses of greatest importance (with special reference to the Mediterranean region, the evaluation of damage and risks. An outline is made of the transmission of zoonoses from farm workers to animals and the biological hazards from the environment. The present situation of occupational zoonoses and related risks in industrialised and traditional farming activities are presented and the importance of some emerging and re-emerging zoonoses for the health of workers is highlighted. The author concludes by stressing that the prevention of occupational zoonoses must be implemented jointly by both veterinary and medical services through preventive measures and epidemiological surveillance of human and animal health, risk evaluation, diagnosis of infections and prompt reporting. It is hoped that the future will offer better inter-disciplinary collaboration and that legislation will be timely and better tailored to safeguard working health and safety.

  9. An interdisciplinary approach to occupational respiratory disorders

    van Rooy, G.B.G.J.

    2010-01-01

    The World Health Organization estimates that worldwide about 50 million new cases of occupational respiratory diseases emerge every year. Without preventative action, the burden of occupational diseases is expected to increase. In this thesis an alternative approach to deliver occupational health

  10. Zagazig Journal of Occupational Health and Safety

    Zagazig Journal of Occupational Health and Safety is aimed at physicians and researchers in the wide-ranging discipline of occupational and environmental health and safety. The field is devoted to the diagnosis, prevention, management and scientific analysis of occupational , environmental and safety health problems; ...

  11. [Concept of occupational pathology service development in Kazakhstan].

    Amanbekova, A U; Sakiev, K Z; Dzhakupbekova, G M; Ibrayeva, L K

    2015-01-01

    Improvement of occupational medical care management is aimed to preserve workers' health through better prevention, early diagnosis and rehabilitation of occupational diseases. Strategic directions of occupational pathology service development are improvement of legislation base on occupational diseases, modernization of occupational pathology service, development of personnel resources system, advancement of research activity in medical ecology, industrial hygiene and occupational pathology and increased efficiency of intra-sectoral and inter-agency interactions about workers' health preservation.

  12. Occupational injuries in Bahrain.

    al-Arrayed, A; Hamza, A

    1995-10-01

    A study was conducted to show the problem of occupational injuries in Bahrain and try to highlight some solutions that may help to prevent or reduce workplace hazards. The data for occupational injuries between 1988 to 1991 from the social insurance records were reviewed and analysed. The data were summarized, grouped and tabulated according to age, sex, nationality, work place, type of injuries, cause and site of injury. Data were analysed statistically, frequencies were computed and results represented graphically. The study shows that there was a decline in the number of injuries in 1990 and 1991 due to a slow-down of economic activities in general in the Arabian Gulf region during the Gulf War. It also shows that Asian workers are at a high risk of occupational injuries.

  13. [Role of the occupational health nurse].

    Rauch, Nadine

    2018-02-01

    The missions of occupational health nurses are exclusively preventive, except in the event of emergency situations. They are involved in the prevention of occupational stress, the assessment of psychosocial risks and the improvement of quality of life at work. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Preventive occupational health interventions in the meat processing industry in upper-middle and high-income countries: a systematic review on their effectiveness

    van Holland, B.J.; Soer, R.; de Boer, M.R.; Reneman, M.F.; Brouwer, S.

    2015-01-01

    Objective: To investigate the effectiveness of occupational health interventions in the meat processing industry on work and health-related outcomes. Methods: A systematic literature review was performed. PubMed, Embase, and The Cochrane Library were searched. Studies were included when they

  15. Preventive occupational health interventions in the meat processing industry in upper-middle and high-income countries : a systematic review on their effectiveness

    van Holland, Berry J.; Soer, Remko; de Boer, Michiel R.; Reneman, Michiel F.; Brouwer, Sandra

    2015-01-01

    OBJECTIVE: To investigate the effectiveness of occupational health interventions in the meat processing industry on work and health-related outcomes. METHODS: A systematic literature review was performed. PubMed, Embase, and The Cochrane Library were searched. Studies were included when they

  16. Occupational cancer

    Choril, A.C.; McCracken, W.J.; Dowd, E.C.; Stewart, Charles; Burton, D.F.; Dyer, D.W.

    1981-01-01

    This paper reviews the experience of the Workmen's Compensation Board of Ontario in identifying cases of cancer that could be attributed to occupational hazards. Workers' claims for compensation are allowed if there is reasonable medical evidence that their cancer was caused by exposure to risk factors associated with their occupation. Details of the types of cancers associated with specific carcinogens or fields of employment are discussed. About 50% of the cases were related to exposure in particular industrial operations that functioned for relatively brief periods. The number of deaths from cancer identified as being caused by occupational factors is compared with the total for cancer from all causes in Ontario during the period 1971 through 1975. Although all workers eligible for compensation may not have been identified, the data suggest that less than 1% is presently caused by occupational factors

  17. Occupational Cancer

    ... November 3, 2015 Content source: National Institute for Occupational Safety and Health Division of Surveillance, Hazard Evaluations, and Field Studies ... Fear Act OIG 1600 Clifton Road Atlanta , GA 30329-4027 ...

  18. Occupational health

    Fingret, Dr Ann

    2013-01-01

    Offers a comprehensive view of health and safety issues at work. An invaluable resource for managers, personnel professionals and occupational health practitioners. Recommended by the Institute of Personnel Management.

  19. Occupational cancer

    Nelson, N.

    1987-01-01

    Cancer resulting from occupational exposure is now receiving major attention, focusing on identification, regulation, and control of cancer-causing agents. Such cancer can result from exposure to chemicals and ionizing and nonionizing radiation. Extended exposure (often years) and an extended latent period of perhaps decades may intervene before tumor appearance. Although the actual extent of occupational cancer is in debate, estimates have ranged from 4 to 15 per cent of all cancer

  20. Occupational health in Brazil.

    Bedrikow, B; Algranti, E; Buschinelli, J T; Morrone, L C

    1997-01-01

    Brazil is a recently industrialised country with marked contrasts in social and economic development. The availability of public/private services in its different regions also varies. Health indicators follow these trends. Occupational health is a vast new field, as in other developing countries. Occupational medicine is a required subject in graduation courses for physicians. Specialisation courses for university graduated professionals have more than 700 hours of lectures and train occupational health physicians, safety engineers and nursing staff. At the technical level, there are courses with up to 1300 hours for the training of safety inspectors. Until 1986 about 19,000 occupational health physicians, 18,000 safety engineers and 51,000 safety inspectors had been officially registered. Although in its infancy, postgraduation has attracted professionals at university level, through residence programmes as well as masters and doctors degrees, whereby at least a hundred good-quality research studies have been produced so far. Occupational health activities are controlled by law. Undertakings with higher risks and larger number of employees are required to hire specialised technical staff. In 1995 the Ministry of Labour demanded programmes of medical control of occupational health (PCMSO) for every worker as well as a programme of prevention of environmental hazards (PPRA). This was considered as a positive measure for the improvement of working conditions and health at work. Physicians specialising in occupational medicine are the professionals more often hired by the enterprises. Reference centres (CRSTs) for workers' health are connected to the State or City Health Secretariat primary health care units. They exist in more populated areas and are accepted by workers as the best way to accomplish the diagnosis of occupational diseases. There is important participation by the trade unions in the management of these reference centres. For 30 years now employers

  1. Koenimbin, a natural dietary compound of Murraya koenigii (L Spreng: inhibition of MCF7 breast cancer cells and targeting of derived MCF7 breast cancer stem cells (CD44+/CD24-/low: an in vitro study

    Ahmadipour F

    2015-02-01

    Full Text Available Fatemeh Ahmadipour,1 Mohamed Ibrahim Noordin,1 Syam Mohan,2 Aditya Arya,1 Mohammadjavad Paydar,3 Chung Yeng Looi,3 Yeap Swee Keong,4 Ebrahimi Nigjeh Siyamak,4 Somayeh Fani,1 Maryam Firoozi,5 Chung Lip Yong,1 Mohamed Aspollah Sukari,6 Behnam Kamalidehghan1 1Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Medical Research Center, Jazan University, Jazan, Kingdom of Saudi Arabia; 3Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 4UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Malaysia; 5Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran; 6Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang, Malaysia Background: Inhibition of breast cancer stem cells has been shown to be an effective therapeutic strategy for cancer prevention. The aims of this work were to evaluate the efficacy of koenimbin, isolated from Murraya koenigii (L Spreng, in the inhibition of MCF7 breast cancer cells and to target MCF7 breast cancer stem cells through apoptosis in vitro. Methods: Koenimbin-induced cell viability was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Nuclear condensation, cell permeability, mitochondrial membrane potential, and cytochrome c release were observed using high-content screening. Cell cycle arrest was examined using flow cytometry, while human apoptosis proteome profiler assays were used to investigate the mechanism of apoptosis. Protein expression levels of Bax, Bcl2, and heat shock protein 70 were confirmed using Western blotting. Caspase-7, caspase-8, and caspase-9 levels were measured, and nuclear factor kappa B (NF-κB activity was assessed using a high-content screening assay. Aldefluor™ and mammosphere formation assays were used to evaluate the effect of koenimbin on MCF7

  2. Occupational skin cancer and precancer

    Fifinela Raissa

    2016-12-01

    Full Text Available Occupational skin cancer and precancerous lesions are skin disorders caused by exposure to chemical carcinogens such as polycyclic hydrocarbons and arsenic, or radiation, such as ultraviolet light and ionizing light in the workplace. Annual increase in skin cancer incidence is believed to be related to various factors such as frequent intense sunlight exposure (i.e. at work, recreational activities, and sun-tanning habit, ozone depletion, an increase in number of geriatric population, and an increase of public awareness in skin cancer. The most common occupational skin cancers are basal cell carcinoma, squamous cell carcinoma, and melanoma. Examples of occupational precancerous lesion of the skin are actinic keratosis and Bowen’s disease. Particular diagnostic criteria to diagnose occupational diseases has been developed. Early detection of occupational skin cancer and precancerous lesion is necessary. An effective prevention program consists of primary prevention such as prevention of hazardous material exposure, secondary prevention such as early detection of disease for early intervention, and tertiary prevention such as minimizing long-term impact of the disease.

  3. Noise-Induced Hearing Loss - A Preventable Disease? Results of a 10-Year Longitudinal Study of Workers Exposed to Occupational Noise.

    Frederiksen, Thomas W; Ramlau-Hansen, Cecilia H; Stokholm, Zara A; Grynderup, Matias B; Hansen, Åse M; Kristiansen, Jesper; Vestergaard, Jesper M; Bonde, Jens P; Kolstad, Henrik A

    2017-01-01

    To survey current, Danish industrial noise levels and the use of hearing protection devices (HPD) over a 10-year period and to characterise the association between occupational noise and hearing threshold shift in the same period. Furthermore, the risk of hearing loss among the baseline and the follow-up populations according to first year of occupational noise exposure is evaluated. In 2001-2003, we conducted a baseline survey of noise- and hearing-related disorders in 11 industries with suspected high noise levels. In 2009-2010, we were able to follow up on 271 out of the 554 baseline workers (49%). Mean noise levels per industry and self-reported HPD use are described at baseline and follow-up. The association between cumulative occupational noise exposure and hearing threshold shift over the 10-year period was assessed using linear regression, and the risk of hearing loss according to year of first occupational noise exposure was evaluated with logistic regression. Over the 10-year period, mean noise levels declined from 83.9 dB(A) to 82.8 dB(A), and for workers exposed >85 dB(A), the use of HPD increased from 70.1 to 76.1%. We found a weak, statistically insignificant, inverse association between higher ambient cumulative noise exposure and poorer hearing (-0.10 dB hearing threshold shift per dB-year (95% confidence interval (CI): -0.36; 0.16)). The risk of hearing loss seemed to increase with earlier first year of noise exposure, but odds ratios were only statistically significant among baseline participants with first exposure before the 1980s (odds ratio: 1.90, 95% CI: 1.11; 3.22). We observed declining industrial noise levels, increased use of HPD and no significant impact on hearing thresholds from current ambient industrial noise levels, which indicated a successful implementation of Danish hearing conservation programs.

  4. Enhanced antitumor activity of cabazitaxel targeting CD44+ receptor ...

    (DOAJ), African Journal Online, Bioline International, Open-J-Gate and Pharmacy Abstracts ... due to poor survival rates, new drugs have been ... cycle arrest, leading to cell death [10,11]. ..... in therapy against triple negative breast cancer.

  5. Atomistic fingerprint of hyaluronan-CD44 binding

    Vuorio, J.; Vattulainen, I.; Martinez-Seara, Hector

    2017-01-01

    Roč. 13, č. 7 (2017), č. článku e1005663. ISSN 1553-734X R&D Projects: GA ČR(CZ) GBP208/12/G016 Institutional support: RVO:61388963 Keywords : molecular simulations * protein interaction * N-glycosylation Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 4.542, year: 2016 http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005663

  6. Future challenges for occupational health services can be prevented by proactive collaboration with the companies using the services: a participatory and reflection project

    Lydell, Marie; Hildingh, Cathrine; Söderbom, Arne; Ziegert, Kristina

    2017-01-01

    Background There is clearly a need for research in the field of occupational health service (OHS) for applying new perspectives. Proactive collaboration is needed between the OHSs and the companies. The customers of the companies using the services should be able to safeguard themselves from the health problems caused by the work environment through proactive collaboration with the OHSs. Objective The main purpose of this interdisciplinary study was to explore how the stakeholders reflected to create and agree on core values for future challenges in OHS, as seen from the perspectives of OHS professionals and customer companies. Methodology An action research process was conducted. This study was divided into three phases. In phase I, the data were collected from interviews and diaries of interdisciplinary occupational health professionals (n=12). A focus group that sampled the eight managers of the customer companies was also included. In phase II, a questionnaire was developed with 24 questions focusing on examining the future challenges for OHS. The questionnaire was sent to customer companies (n=116). In phase III, a scoping review was undertaken. Results Three categories emerged from the analysis: “Balancing complex situations” clarified the complexity regarding senior employees; “Working with a proactive approach” indicated the need for working with a new proactive approach supporting sustainable health; and “Collaborate internally and externally” showed good relationships between the customer and the OHS, which is a mutual responsibility to both the partners. Conclusion The results outlined that it is necessary to take action to apply new proactive health promotions, with a focus on workplace health promotion. The results also indicated that interventions for senior employees are of importance. This study was done in collaboration with the stakeholders from the occupational health care service center and the managers from the customer companies

  7. Future challenges for occupational health services can be prevented by proactive collaboration with the companies using the services: a participatory and reflection project.

    Lydell, Marie; Hildingh, Cathrine; Söderbom, Arne; Ziegert, Kristina

    2017-01-01

    There is clearly a need for research in the field of occupational health service (OHS) for applying new perspectives. Proactive collaboration is needed between the OHSs and the companies. The customers of the companies using the services should be able to safeguard themselves from the health problems caused by the work environment through proactive collaboration with the OHSs. The main purpose of this interdisciplinary study was to explore how the stakeholders reflected to create and agree on core values for future challenges in OHS, as seen from the perspectives of OHS professionals and customer companies. An action research process was conducted. This study was divided into three phases. In phase I, the data were collected from interviews and diaries of interdisciplinary occupational health professionals (n=12). A focus group that sampled the eight managers of the customer companies was also included. In phase II, a questionnaire was developed with 24 questions focusing on examining the future challenges for OHS. The questionnaire was sent to customer companies (n=116). In phase III, a scoping review was undertaken. Three categories emerged from the analysis: "Balancing complex situations" clarified the complexity regarding senior employees; "Working with a proactive approach" indicated the need for working with a new proactive approach supporting sustainable health; and "Collaborate internally and externally" showed good relationships between the customer and the OHS, which is a mutual responsibility to both the partners. The results outlined that it is necessary to take action to apply new proactive health promotions, with a focus on workplace health promotion. The results also indicated that interventions for senior employees are of importance. This study was done in collaboration with the stakeholders from the occupational health care service center and the managers from the customer companies. The use of a participatory research design, including close

  8. Noise-Induced Hearing Loss – A Preventable Disease? Results of a 10-Year Longitudinal Study of Workers Exposed to Occupational Noise

    Frederiksen, Thomas W.; Ramlau-Hansen, Cecilia H.; Stokholm, Zara A.; Grynderup, Matias B.; Hansen, Åse M.; Kristiansen, Jesper; Vestergaard, Jesper M.; Bonde, Jens P.; Kolstad, Henrik A.

    2017-01-01

    Aims: To survey current, Danish industrial noise levels and the use of hearing protection devices (HPD) over a 10-year period and to characterise the association between occupational noise and hearing threshold shift in the same period. Furthermore, the risk of hearing loss among the baseline and the follow-up populations according to first year of occupational noise exposure is evaluated. Materials and Methods: In 2001–2003, we conducted a baseline survey of noise- and hearing-related disorders in 11 industries with suspected high noise levels. In 2009–2010, we were able to follow up on 271 out of the 554 baseline workers (49%). Mean noise levels per industry and self-reported HPD use are described at baseline and follow-up. The association between cumulative occupational noise exposure and hearing threshold shift over the 10-year period was assessed using linear regression, and the risk of hearing loss according to year of first occupational noise exposure was evaluated with logistic regression. Results: Over the 10-year period, mean noise levels declined from 83.9 dB(A) to 82.8 dB(A), and for workers exposed >85 dB(A), the use of HPD increased from 70.1 to 76.1%. We found a weak, statistically insignificant, inverse association between higher ambient cumulative noise exposure and poorer hearing (−0.10 dB hearing threshold shift per dB-year (95% confidence interval (CI): −0.36; 0.16)). The risk of hearing loss seemed to increase with earlier first year of noise exposure, but odds ratios were only statistically significant among baseline participants with first exposure before the 1980s (odds ratio: 1.90, 95% CI: 1.11; 3.22). Conclusions: We observed declining industrial noise levels, increased use of HPD and no significant impact on hearing thresholds from current ambient industrial noise levels, which indicated a successful implementation of Danish hearing conservation programs. PMID:29192620

  9. Noise-Induced Hearing Loss – A Preventable Disease? Results of a 10-Year Longitudinal Study of Workers Exposed to Occupational Noise

    Thomas W Frederiksen

    2017-01-01

    Full Text Available Aims: To survey current, Danish industrial noise levels and the use of hearing protection devices (HPD over a 10-year period and to characterise the association between occupational noise and hearing threshold shift in the same period. Furthermore, the risk of hearing loss among the baseline and the follow-up populations according to first year of occupational noise exposure is evaluated. Materials and Methods: In 2001–2003, we conducted a baseline survey of noise- and hearing-related disorders in 11 industries with suspected high noise levels. In 2009–2010, we were able to follow up on 271 out of the 554 baseline workers (49%. Mean noise levels per industry and self-reported HPD use are described at baseline and follow-up. The association between cumulative occupational noise exposure and hearing threshold shift over the 10-year period was assessed using linear regression, and the risk of hearing loss according to year of first occupational noise exposure was evaluated with logistic regression. Results: Over the 10-year period, mean noise levels declined from 83.9 dB(A to 82.8 dB(A, and for workers exposed >85 dB(A, the use of HPD increased from 70.1 to 76.1%. We found a weak, statistically insignificant, inverse association between higher ambient cumulative noise exposure and poorer hearing (−0.10 dB hearing threshold shift per dB-year (95% confidence interval (CI: −0.36; 0.16. The risk of hearing loss seemed to increase with earlier first year of noise exposure, but odds ratios were only statistically significant among baseline participants with first exposure before the 1980s (odds ratio: 1.90, 95% CI: 1.11; 3.22. Conclusions: We observed declining industrial noise levels, increased use of HPD and no significant impact on hearing thresholds from current ambient industrial noise levels, which indicated a successful implementation of Danish hearing conservation programs.

  10. Conhecimentos e práticas de adolescentes na prevenção de acidentes de trabalho: estudo qualitativo Knowledge and practices by adolescents in preventing occupational injuries: a qualitative study

    Roberta Nagai

    2007-06-01

    Full Text Available OBJETIVO: Descrever conhecimentos e práticas adotados por estudantes do ensino médio na prevenção de acidentes de trabalho. DELINEAMENTO DO ESTUDO: O estudo foi realizado em uma escola pública, localizada no Município de São Paulo, em 2003. Participaram 53 estudantes do período noturno, com idades entre 14 e 21 anos, divididos em dois grupos: com e sem experiência de trabalho (32 e 21 adolescentes, respectivamente. Eles responderam a duas questões: "Por quê os acidentes de trabalho ocorrem?" e "O que você faz para evitar que ocorram acidentes de trabalho?". As análises dos dados foram feitas no programa Quali-quanti, para a elaboração do discurso de sujeito coletivo. ANÁLISE DOS DISCURSOS: Para os adolescentes com experiência de trabalho, acidentes ocorrem devido ao descuido ou má sorte do funcionário, irresponsabilidade do patrão, falta de treinamento no trabalho e ambiente de trabalho inseguro. Os adolescentes sem experiência relataram que acidentes de trabalho ocorrem devido ao descuido do funcionário e irresponsabilidade do patrão. Sobre as formas de proteção dos acidentes de trabalho os adolescentes de ambos grupos relataram que: prestam (prestariam atenção no trabalho e usam (usariam equipamentos de segurança. CONCLUSÕES: Os adolescentes dos dois grupos mostraram conhecimento limitado sobre acidentes de trabalho e formas de prevenção. Os adolescentes apontaram como "culpa da vítima" as ocorrências dos acidentes de trabalho e a melhor forma de proteção "prestar atenção no trabalho". A cultura de culpar a vítima está presente desde a adolescência e provavelmente é resultado de um processo de aprendizado na sociedade.OBJECTIVE: To describe knowledge and practices adopted by high school students to prevent occupational injuries. STUDY DESIGN: The study was carried out in a public school located in São Paulo, in 2003. Fifty-three evening students aged 14 to 21 years old participated the study, they were

  11. Future challenges for occupational health services can be prevented by proactive collaboration with the companies using the services: a participatory and reflection project

    Lydell M

    2017-05-01

    Full Text Available Marie Lydell,1 Cathrine Hildingh,1 Arne Söderbom,2 Kristina Ziegert1 1Center of Research on Welfare, Health and Sport (CVHI, School of Social and Health Sciences, 2Center for Innovation, Entrepreneurship and Learning Research (CIEL, School of Economics, Technology and Science, Halmstad University, Halmstad, Sweden Background: There is clearly a need for research in the field of occupational health service (OHS for applying new perspectives. Proactive collaboration is needed between the OHSs and the companies. The customers of the companies using the services should be able to safeguard themselves from the health problems caused by the work environment through proactive collaboration with the OHSs. Objective: The main purpose of this interdisciplinary study was to explore how the stakeholders reflected to create and agree on core values for future challenges in OHS, as seen from the perspectives of OHS professionals and customer companies. Methodology: An action research process was conducted. This study was divided into three phases. In phase I, the data were collected from interviews and diaries of interdisciplinary occupational health professionals (n=12. A focus group that sampled the eight managers of the customer companies was also included. In phase II, a questionnaire was developed with 24 questions focusing on examining the future challenges for OHS. The questionnaire was sent to customer companies (n=116. In phase III, a scoping review was undertaken. Results: Three categories emerged from the analysis: “Balancing complex situations” clarified the complexity regarding senior employees; “Working with a proactive approach” indicated the need for working with a new proactive approach supporting sustainable health; and “Collaborate internally and externally” showed good relationships between the customer and the OHS, which is a mutual responsibility to both the partners. Conclusion: The results outlined that it is necessary to

  12. Occupational Animal Allergy.

    Stave, Gregg M

    2018-02-16

    This review explores animal allergen exposure in research laboratories and other work settings, focusing on causes and prevention. (1) Consistent with the hygiene hypothesis, there is new evidence that early childhood exposure to pets produces changes in the gut microbiome that likely lead to a lower risk of allergy. (2) Anaphylaxis from laboratory animal bites occurs more frequently than suggested by prior literature. (3) Animal allergens represent an occupational hazard in a wide variety of work settings ranging from fields that work with animals to public settings like schools and public transportation where allergens are brought into or are present in the workplace. Exposure to animal allergens can result in allergy, asthma, and anaphylaxis. Animal allergy has been most studied in the research laboratory setting, where exposure reduction can prevent the development of allergy. Similar prevention approaches need to be considered for other animal work environments and in all settings where animal allergens are present.

  13. Occupational hazards

    Paz-Fuchs, Amir; Ronen, Yaël

    2012-01-01

    This article provides an analysis and a critique of the law governing the employment relationship between Israeli employers and Palestinian employees in industries operating in the West Bank. \\ud \\ud Through an analysis of Israeli jurisprudence it highlights the intersection among different areas of law: choice of law, public international law (in particular the law of occupation), and labor law. The article explores the tensions that this intersection creates: first, between the importance t...

  14. Occupational Health and the Arts.

    Hinkamp, David L; McCann, Michael; Babin, Angela

    2017-09-01

    Work in the visual arts, performing arts, and writing can involve exposures to occupational hazards, including hazardous materials, equipment, and conditions, but few art workplaces have strong occupational health resources. Literature searches were conducted for articles that illustrate these concerns. Medical databases were searched for art-related health articles. Other sources were also reviewed, including, unindexed art-health publications, and popular press articles. Information was located that described some exposed populations, art-related hazards, and resulting disorders. Anecdotal reports were used when more complete data were not available. Health hazards in the arts are significant. Occupational health professionals are familiar with most of these concerns and understand their treatment and prevention. The occupational health approach can reduce the health hazards encountered by at-risk art workers. Additional research would benefit these efforts. Resources for further information are available.

  15. Occupational accidents aboard merchant ships

    Hansen, H.L.; Nielsen, D.; Frydenberg, Morten

    2002-01-01

    Objectives: To investigate the frequency, circumstances, and causes of occupational accidents aboard merchant ships in international trade, and to identify risk factors for the occurrence of occupational accidents as well as dangerous working situations where possible preventive measures may...... be initiated. Methods: The study is a historical follow up on occupational accidents among crew aboard Danish merchant ships in the period 1993–7. Data were extracted from the Danish Maritime Authority and insurance data. Exact data on time at risk were available. Results: A total of 1993 accidents were...... aboard. Relative risks for notified accidents and accidents causing permanent disability of 5% or more were calculated in a multivariate analysis including ship type, occupation, age, time on board, change of ship since last employment period, and nationality. Foreigners had a considerably lower recorded...

  16. 77 FR 40622 - Mine Safety and Health Research Advisory Committee, National Institute for Occupational Safety...

    2012-07-10

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Mine Safety and Health Research Advisory Committee, National Institute for Occupational Safety and Health (MSHRAC, NIOSH..., oxygen supply partnership, safety culture, occupational health and safety management systems, preventing...

  17. Occupation: nurse; occupational hazard: radiation

    Nickson, K.

    1984-01-01

    The work of the occupational health nurses at the Pickering Generating Station is described. A staff of two nurses teach first aid and safety, practice an emergency plan, and monitor personnel for minimum health standards for radiation workers. Special attention is paid to problems which might be aggravated by radiation, such as skin complaints, respiratory diseases, emotional stability, or phobias regarding heights, plastic suits, or radiation itself. Procedures used in treating contaminated personnel are outlined

  18. Occupation: nurse; occupational hazard: radiation

    Nickson, K

    1984-03-01

    The work of the occupational health nurses at the Pickering Generating Station is described. A staff of two nurses teach first aid and safety, practice an emergency plan, and monitor personnel for minimum health standards for radiation workers. Special attention is paid to problems which might be aggravated by radiation, such as skin complaints, respiratory diseases, emotional stability, or phobias regarding heights, plastic suits, or radiation itself. Procedures used in treating contaminated personnel are outlined.

  19. Occupational health and safety services

    Kwantes, J.H.; Hooftman, W.; Michiel, F.

    2014-01-01

    The position, role and aim of the protective and preventive services (article 7 of the Framework directive (89/391/EEC within the legal OSH-system will be the focus point of this article. Article 13 of the EU Treaty gives the EU the possibility to draft a legal framework on occupational safety and

  20. Transitioning to HIV Pre-Exposure Prophylaxis (PrEP) from Non-Occupational Post-Exposure Prophylaxis (nPEP) in a Comprehensive HIV Prevention Clinic: A Prospective Cohort Study.

    Siemieniuk, Reed A C; Sivachandran, Nirojini; Murphy, Pauline; Sharp, Andrea; Walach, Christine; Placido, Tania; Bogoch, Isaac I

    2015-08-01

    The uptake of pre-exposure prophylaxis (PrEP) for HIV prevention remains low. We hypothesized that a high proportion of patients presenting for HIV non-occupational post-exposure prophylaxis (nPEP) would be candidates for PrEP based on current CDC guidelines. Outcomes from a comprehensive HIV Prevention Clinic are described. We evaluated all patients who attended the HIV Prevention Clinic for nPEP between January 1, 2013 and September 30, 2014. Each patient was evaluated for PrEP candidacy based on current CDC-guidelines and subjectively based on physician opinion. Patients were then evaluated for initiation of PrEP if they met guideline suggestions. Demographic, social, and behavioral factors were then analyzed with logistic regression for associations with PrEP candidacy and initiation. 99 individuals who attended the nPEP clinic were evaluated for PrEP. The average age was 32 years (range, 18-62), 83 (84%) were male, of whom 46 (55%) men who had have sex with men (MSM). 31 (31%) met CDC guidelines for PrEP initiation, which had very good agreement with physician recommendation (kappa=0.88, 0.78-0.98). Factors associated with PrEP candidacy included sexual exposure to HIV, prior nPEP use, and lack of drug insurance (p<0.05 for all comparisons). Combining nPEP and PrEP services in a dedicated clinic can lead to identification of PrEP candidates and may facilitate PrEP uptake. Strategies to ensure equitable access of PrEP should be explored such that those without drug coverage may also benefit from this effective HIV prevention modality.

  1. Occupational physiology

    Toomingas, Allan; Tornqvist, Ewa Wigaeus

    2011-01-01

    In a clear and accessible presentation, Occupational Physiology focuses on important issues in the modern working world. Exploring major public health problems-such as musculoskeletal disorders and stress-this book explains connections between work, well-being, and health based on up-to-date research in the field. It provides useful methods for risk assessment and guidelines on arranging a good working life from the perspective of the working individual, the company, and society as a whole.The book focuses on common, stressful situations in different professions. Reviewing bodily demands and r

  2. Salud laboral y género: Apuntes para la incorporación de la perspectiva de género en el ámbito de la prevención de riesgos laborales Occupational health and gender: Notes to incorporate the gender mainstreaming in the occupational risks prevention field

    Mª Fernanda González Gómez

    2011-01-01

    Full Text Available En el ámbito nacional e internacional existe un amplio marco normativo y programático que vincula las acciones de entidades públicas y privadas con la igualdad de oportunidades para mujeres y hombres; sin embargo, las condiciones en que se desenvuelven unas y otros siguen siendo extremadamente diferentes y desiguales. En el contexto de la salud laboral, como en otros, se añade a esto la incapacidad de las instituciones para conocer la situación real de las y los trabajadores y por tanto, la imposibilidad de emprender acciones que promuevan adecuadamente la salud de hombres y mujeres en dicho medio. La incorporación de la perspectiva de género en el actuar de los servicios de prevención contribuye a detectar y corregir los sesgos de género en las actividades preventivas y de vigilancia de la salud. El presente documento pretende apuntar algunas acciones específicas que sirvan de herramientas prácticas para la incorporación de la perspectiva de género en las actividades que se realizan desde los servicios de Salud Laboral.At national and international level, there is a wide legal frame enlacing public and private entities´ actions with the equal opportunities for men and women; nevertheless, the conditions in which they work are extremely different. In the occupational health context, like in others, the entities´ incapacity to know the real situation of men and women and the impossibility, as a result, to develop actions to improve accurately men and women´s health, are summed to the actual inequity. The gender mainstreaming in the occupational risks prevention world contribute to detect and correct the gender slant in the preventive activities and in the health surveillance. This paper aims to provide some simple tools to facilitate the incorporation of gender perspective in the activities developed by the Occupational Health Services.

  3. Occupational safety in the petroleum industry

    Elsner, W

    1987-03-01

    The original technique-oriented accident prevention today has grown to a comprehensive occupational workers protection system. Modern occupational safety requires latest strategies. Side by side with technical and organizational measures we see duties for all superiors directed to plant related occupational safety. These new principles of leadership on the basis of occupational safety policies from top management require equivalent tactics to cause change in behaviour of the employees. Such a not only formulated but also accepted safety strategy is extremely clear by its positive results in the petroleum industry.

  4. Occupational skin cancer: Systematic review

    Jéssica Suellen Sena

    2016-06-01

    Full Text Available SUMMARY Objective: To analyze the epidemiological profile, risk factors in the workplace environment and prevention methods for professionals at risk of skin cancer. Method: A systematic review of articles on occupational skin cancer, published in the Lilacs, Scielo, Medline and Cochrane Library from January 1st, 2008, to December 31st, 2013, was performed. The search included the following terms: “neoplasias cutâneas” (DeCS, “exposição ocupacional” (DeCS, “epidemiologia” (DeCS as well as the keyword “prevenção”, and their equivalents in English. Results: After analyzing the titles and summaries of articles, the search strategy resulted in 83 references, of which 22 articles met the eligibility criteria. Discussion: We found that sun exposure is the main occupational risk factor for skin cancer, causing outdoor workers to be the most vulnerable to developing occupational skin cancer. Professionals with low levels of education and European descent are at increased risk of developing this cancer. Conclusion: Outdoor workers are more vulnerable to developing occupational skin cancer, estimating that professionals with low level of education and European descent are at increased risk of developing this cancer. Therefore, companies need to invest more in the health of workers by providing protective equipment and thus preventing occupational skin cancer.

  5. THE DETERMINATION AND APPRECIATION OF OCCUPATIONAL TOXICITY AT WORK

    Oana CHIVU; Claudiu BABIS; Andrei DIMITRESCU

    2017-01-01

    The occupational toxins are those chemicals that workers come into contact with during the exercise of the profession and which under certain conditions have harmful effects on the body. The paper aims to address the determination and assessment of occupational toxicities in a workplace with the aim of ensuring an adequate working enviro nment as well as preventing occupational diseases, accidents and chronic fatigue.

  6. Civilian law: from occupational medicine to occupational event.

    Mpotos, N; Watelet, J B

    Civilian law:from occupational medicine to occupational event. Despite the growing importance of objective measurements, the health effects of many occupational risk factors are currently not fully quantified. Occupational noise, as a widespread risk factor, is illustrative in this regard; there is a strong body of evidence linking it to an important health outcome (hearing loss), but it is less decisively associated with others (such as psychological disorders). It is also distinct from environmental noise, and therefore falls under the responsibility of employers as well as individuals. Noise-induced hearing loss (NIHL) is, at present, incurable and irreversible. However, it is preventable, if effective and global hearing conservation programmes can be implemented. These programmes should not be isolated efforts, but should be integrated into the overall hazard prevention and control programme of the workplace. Belgian law encompasses a set of provisions for prevention and the protection of the health and safety of workers within the workplace, including aspects pertaining to the hygiene of the workplace and psychosocial aspects at work (stress, violence, bullying and sexual harassment, among others). In principle, combating environmental noise is fully addressed in this country. However, other levels of policy-making also play an important role in this regard. For example, the federal government is in charge of product standards, and therefore also of noise emission standards for products. The interpretation and enforcement of Belgian legislation on well-being at work converts European directives and international agreements on well-being at work into Belgian law.

  7. Occupational injuries in workers from different ethnicities.

    Mekkodathil, Ahammed; El-Menyar, Ayman; Al-Thani, Hassan

    2016-01-01

    Occupational injuries remain an important unresolved issue in many of the developing and developed countries. We aimed to outline the causes, characteristics, measures and impact of occupational injuries among different ethnicities. We reviewed the literatures using PUBMED, MEDLINE, Google Scholar and EMBASE search engine using words: "Occupational injuries" and "workplace" between 1984 and 2014. Incidence of fatal occupational injuries decreased over time in many countries. However, it increased in the migrant, foreign born and ethnic minority workers in certain high risk industries. Disproportionate representations of those groups in different industries resulted in wide range of fatality rates. Overrepresentation of migrant workers, foreign born and ethnic minorities in high risk and unskilled occupations warrants effective safety training programs and enforcement of laws to assure safe workplaces. The burden of occupational injuries at the individual and community levels urges the development and implementation of effective preventive programs.

  8. Effectiveness of three interventions for secondary prevention of low back pain in the occupational health setting - a randomised controlled trial with a natural course control.

    Rantonen, J; Karppinen, J; Vehtari, A; Luoto, S; Viikari-Juntura, E; Hupli, M; Malmivaara, A; Taimela, S

    2018-05-08

    We assessed the effectiveness of three interventions that were aimed to reduce non-acute low back pain (LBP) related symptoms in the occupational health setting. Based on a survey (n = 2480; response rate 71%) on LBP, we selected a cohort of 193 employees who reported moderate LBP (Visual Analogue Scale VAS > 34 mm) and fulfilled at least one of the following criteria during the past 12 months: sciatica, recurrence of LBP ≥ 2 times, LBP ≥ 2 weeks, or previous sickness absence. A random sample was extracted from the cohort as a control group (Control, n = 50), representing the natural course of LBP. The remaining 143 employees were invited to participate in a randomised controlled trial (RCT) of three 1:1:1 allocated parallel intervention arms: multidisciplinary rehabilitation (Rehab, n = 43); progressive exercises (Physio, n = 43) and self-care advice (Advice, n = 40). Seventeen employees declined participation in the intervention. The primary outcome measures were physical impairment (PHI), LBP intensity (Visual Analogue Scale), health related quality of life (QoL), and accumulated sickness absence days. We imputed missing values with multiple imputation procedure. We assessed all comparisons between the intervention groups and the Control group by analysing questionnaire outcomes at 2 years with ANOVA and sickness absence at 4 years by using negative binomial model with a logarithmic link function. Mean differences between the Rehab and Control groups were - 3 [95% CI -5 to - 1] for PHI, - 13 [- 24 to - 1] for pain intensity, and 0.06 [0.00 to 0.12] for QoL. Mean differences between the Physio and Control groups were - 3 [95% CI -5 to - 1] for PHI, - 13 [- 29 to 2] for pain intensity, and 0.07 [0.01 to 0.13] for QoL. The main effects sizes were from 0.4 to 0.6. The interventions were not effective in reducing sickness absence. Rehab and Physio interventions improved health related quality of life, decreased

  9. Occupational Disease Registries-Characteristics and Experiences.

    Davoodi, Somayeh; Haghighi, Khosro Sadeghniat; Kalhori, Sharareh Rostam Niakan; Hosseini, Narges Shams; Mohammadzadeh, Zeinab; Safdari, Reza

    2017-06-01

    Due to growth of occupational diseases and also increase of public awareness about their consequences, attention to various aspects of diseases and improve occupational health and safety has found great importance. Therefore, there is the need for appropriate information management tools such as registries in order to recognitions of diseases patterns and then making decision about prevention, early detection and treatment of them. These registries have different characteristics in various countries according to their occupational health priorities. Aim of this study is evaluate dimensions of occupational diseases registries including objectives, data sources, responsible institutions, minimum data set, classification systems and process of registration in different countries. In this study, the papers were searched using the MEDLINE (PubMed) Google scholar, Scopus, ProQuest and Google. The search was done based on keyword in English for all motor engines including "occupational disease", "work related disease", "surveillance", "reporting", "registration system" and "registry" combined with name of the countries including all subheadings. After categorizing search findings in tables, results were compared with each other. Important aspects of the registries studied in ten countries including Finland, France, United Kingdom, Australia, Czech Republic, Malaysia, United States, Singapore, Russia and Turkey. The results show that surveyed countries have statistical, treatment and prevention objectives. Data sources in almost the rest of registries were physicians and employers. The minimum data sets in most of them consist of information about patient, disease, occupation and employer. Some of countries have special occupational related classification systems for themselves and some of them apply international classification systems such as ICD-10. Finally, the process of registration system was different in countries. Because occupational diseases are often

  10. Cancer risks and prevention

    Vessey, M.P.; Gray, M.

    1985-01-01

    A series of essays in honour of Sir Richard Doll is presented. Chapters cover the preventability of cancer, geography, smoking, diet, occupation, radiation, infections and immune impairment, exogenous and endogenous hormones, other drugs, prevention through legislation and by education and cancer risks and prevention in the Third World. The chapter on radiation has been indexed separately. (UK)

  11. An overview of occupational voice disorders in Poland

    Ewa Niebudek-Bogusz

    2013-10-01

    Full Text Available Occupational voice disorders make the most frequently certified category of occupational diseases in Poland, making up approximately 20% of all cases. This study presents the current knowledge of the etiopathogenesis of occupational voice disorders. It stresses the importance of the evaluation of vocal loading by means of objective measurements. Furthermore, this study discusses the medico-legal aspects of the procedure of certifying occupational voice disorders in Poland. The paper also describes the preventive programs addressed particularly to teachers, including multidisciplinary and holistic management of occupational dysphonia. Their role in the improvement of occupational safety and health (OSH arrangement for vocally demanding professions is emphasized.

  12. Individual and occupational factors related to fatal occupational injuries: a case-control study.

    Villanueva, Vicent; Garcia, Ana M

    2011-01-01

    This study has been designed in order to identify factors increasing the risk of a fatal outcome when occupational accidents occur. The aim is to provide further evidence for the design and implementation of preventive measures in occupational settings. The Spanish Ministry of Labour registry of occupational injuries causing absence from work includes information on individual and occupational characteristics of injured workers and events. Registered fatal occupational injuries in 2001 (n=539) were compared to a sample of non-fatal injuries in the same year (n=3493). Risks for a fatal result of occupational injuries, adjusted by individual and occupational factors significantly associated, were obtained through logistic regression models. Compared to non-fatal injuries, fatal occupational injuries were mostly produced by trapping or by natural causes, mostly related to elevation and transport devices and power generators, and injured parts of body more frequently affected were head, multiple parts or internal organs. Adjusted analyses showed increased risk of fatality after an occupational injury for males (adjusted odds ratio aOR=10.92; 95%CI 4.80-24.84) and temporary workers (aOR=5.18; 95%CI 2.63-10.18), and the risk increased with age and with advancing hour of the work shift (p for trends accidents in agricultural or construction companies. These data can help to select and define priorities for programmes aimed to prevent fatal consequences of occupational injuries. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. 78 FR 64504 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

    2013-10-29

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety and Health (NIOSH or..., Number 177, Pages 56235-56236. Contact Person for More Information: Price Connor, Ph.D., NIOSH Health...

  14. Evaluation of Occupational Closed Globe Eye Injuries

    Berna Akova-Budak

    2016-01-01

    Full Text Available Aim: To evaluate closed glob injuries related to occupational accidents of patients who had official occupational accident records. Material and Method: The medical records of patients with ocular injuries who referred to Department of Ophthalmology or emergency of Uludag University, School of Medicine between January 2010 and December 2013 with official occupational accident report were retrospectively reviewed. The patients with closed globe injuries following trauma were included. Age, sex, the injured eye, the cause of the trauma, whether the precautions were taken or not by the patient, the damage due to trauma were recorded. Results: According to the official records, 108 patients referred to our clinic with closed globe injury related to occupational accident. One hundred twenty eyes of 108 patients ( 2 females, 106 males were evaluated. The mean age of the patients was 33±8.6 years. The most frequent cause of injury was foreign bodies on the ocular surface followed by blunt trauma. The mean age of the patients injured with foreign bodies was found to be significantly lower than the patients injured with blunt objects (p=0.039. Thirteen patients reported that they had used preventive equipment. Discussion: It is of utmost importance that the awareness of the workers should be raised and they should be educated about the use of preventive equipment to prevent the occupational eye injuries. The education of particularly the younger patients about the occupational injuries when they begin to work may decrease the rate of occupational accident related eye injuries.

  15. Occupational diseases in Poland, 2012

    Urszula Wilczyńska

    2013-06-01

    Full Text Available Background: The aim of the paper was to present basic statistical data on occupational diseases diagnosed in 2012. Material and Methods: The work was based on the data from "Occupational Disease Reporting Forms" received by the Central Register of Occupational Diseases in 2012. The data comprised information on nosologic units, gender and age of patients, duration of occupational exposure, sections of the national economy and voivodeships. The incidence was specified in terms of the number of cases in relation to paid employees or to employed people. Results: The number of occupational diseases accounted for 2402 cases. The incidence rate was 23 cases per 100 000 paid employees. In spite of the general decline in the number of cases, the incidence of infectious and parasitic diseases increased by 8.6%. The highest incidence was noted for infectious and parasitic diseases (6.8/100 000, pneumoconioses (5.5/100 000, hearing loss (2.1/100 000, diseases of: the peripheral nervous system (2/100 000, voice disorders (1.9/100 000 and the musculo-skeletal system pathologies (1.1/100 000. The pathologies specified above accounted in total for 84% of all occupational diseases. The industrial sectors of the national economy characterized by the highest incidence included mining and quarrying (288.3/100 000 and manufacturing (27.8/100 000. The highest incidence was recorded in the Silesian (46.2/100 000 and the lowest in the Opolskie (4.2/100 000 voivodeships. Conclusions: The downward trend in the incidence of occupational diseases continues. Different incidence of voice disorders among teachers in individual provinces suggests that uniform preventive, diagnostic and certification standards are missing. Med Pr 2013;64(3:317–326

  16. Occupational hazards to health of port workers.

    Wang, Yukun; Zhan, Shuifen; Liu, Yan; Li, Yan

    2017-12-01

    The aim of this article is to reduce the risk of occupational hazards and improve safety conditions by enhancing hazard knowledge and identification as well as improving safety behavior for freight port enterprises. In the article, occupational hazards to health and their prevention measures of freight port enterprises have been summarized through a lot of occupational health evaluation work, experience and understanding. Workers of freight port enterprises confront an equally wide variety of chemical, physical and psychological hazards in production technology, production environment and the course of labor. Such health hazards have been identified, the risks evaluated, the dangers to health notified and effective prevention measures which should be put in place to ensure the health of the port workers summarized. There is still a long way to go for the freight port enterprises to prevent and control the occupational hazards. Except for occupational hazards and their prevention measures, other factors that influence the health of port workers should also be paid attention to, such as age, work history, gender, contraindication and even the occurrence and development rules of occupational hazards in current production conditions.

  17. Human Asymptomatic Epitopes Identified from the Herpes Simplex Virus Tegument Protein VP13/14 (UL47) Preferentially Recall Polyfunctional Effector Memory CD44high CD62Llow CD8+ TEM Cells and Protect Humanized HLA-A*02:01 Transgenic Mice against Ocular Herpesvirus Infection.

    Srivastava, Ruchi; Khan, Arif A; Garg, Sumit; Syed, Sabrina A; Furness, Julie N; Vahed, Hawa; Pham, Tiffany; Yu, Howard T; Nesburn, Anthony B; BenMohamed, Lbachir

    2017-01-15

    Herpes simplex virus 1 (HSV-1) infection is widespread among humans. The HSV-1 virion protein 13/14 (VP13/14), also known as UL47, is a tegument antigen targeted by CD8 + T cells from HSV-seropositive individuals. However, whether VP13/14-specific CD8 + T cells play a role in the natural protection seen in asymptomatic (ASYMP) individuals (individuals who have never had a clinical herpetic disease) has not been elucidated. Using predictive computer-assisted algorithms, we identified 10 potential HLA-A*02:01-restricted CD8 + T-cell epitopes from the 693-amino-acid sequence of the VP13/14 protein. Three out of 10 epitopes exhibited a high to moderate affinity of binding to soluble HLA-A*02:01 molecules. The phenotype and function of CD8 + T cells specific for each epitope were compared in HLA-A*02:01-positive ASYMP individuals and symptomatic (SYMP) individuals (individuals who have frequent clinical herpetic diseases) using determination of a combination of tetramer frequency and the levels of granzyme B, granzyme K, perforin, gamma interferon, tumor necrosis factor alpha, and interleukin-2 production and CD107 a/b cytotoxic degranulation. High frequencies of multifunctional CD8 + T cells directed against three epitopes, VP13/14 from amino acids 286 to 294 (VP13/14 286-294 ), VP13/14 from amino acids 504 to 512 (VP13/14 504-512 ), and VP13/14 from amino acids 544 to 552 (VP13/14 544-552 ), were detected in ASYMP individuals, while only low frequencies were detected in SYMP individuals. The three epitopes also predominantly recalled more CD45RA low CD44 high CCR7 low CD62L low CD8 + effector memory T cells (T EM cells) in ASYMP individuals than SYMP individuals. Moreover, immunization of HLA-A*02:01 transgenic mice with the three CD8 + T EM -cell epitopes from ASYMP individuals induced robust and polyfunctional HSV-specific CD8 + T EM cells associated with strong protective immunity against ocular herpesvirus infection and disease. Our findings outline the phenotypic

  18. Occupational risk factors and voice disorders.

    Vilkman, E

    1996-01-01

    From the point of view of occupational health, the field of voice disorders is very poorly developed as compared, for instance, to the prevention and diagnostics of occupational hearing disorders. In fact, voice disorders have not even been recognized in the field of occupational medicine. Hence, it is obviously very rare in most countries that the voice disorder of a professional voice user, e.g. a teacher, a singer or an actor, is accepted as an occupational disease by insurance companies. However, occupational voice problems do not lack significance from the point of view of the patient. We also know from questionnaires and clinical studies that voice complaints are very common. Another example of job-related health problems, which has proved more successful in terms of its occupational health status, is the repetition strain injury of the elbow, i.e. the "tennis elbow". Its textbook definition could be used as such to describe an occupational voice disorder ("dysphonia professional is"). In the present paper the effects of such risk factors as vocal loading itself, background noise and room acoustics and low relative humidity of the air are discussed. Due to individual factors underlying the development of professional voice disorders, recommendations rather than regulations are called for. There are many simple and even relatively low-cost methods available for the prevention of vocal problems as well as for supporting rehabilitation.

  19. Occupational skin diseases and prevention among sanitation ...

    in body defense, and is predisposed to disease when subjected to ... sanitation workers in Wuhan (China) for better manage- ment and ... Symptoms of facial skin photo .... ronment, diet nutrition and working environment were also poor.

  20. Prevention of occupational risks in animal experimentation

    Martinez Palacio, J.

    2007-01-01

    This work focuses on the main specific risks for those working with laboratory animals in a Research Center such as CIEMAT. First we present the general biological risks, their laws and rules. Next, we development the specific risks associated with the laboratory animals, zoonotic diseases and allergies. then we deal with the risks that can be consequence of working with laboratory animals, ionizing radiations, chemical products, genetically modified organisms, liquid nitrogen management, bio containment and human samples management. As they are subjects of interest, we also include the workers health assesment for those exposed to biological agents, including recommendations about hygiene and disinfections. (Author)

  1. Occupational injury among migrant workers in China: a systematic review

    Fitzgerald, Simon; Chen, Xin; Qu, Hui; Sheff, Mira Grice

    2017-01-01

    Objectives This review considers the state of occupational injury surveillance and prevention among migrant workers in China and suggests areas of focus for future research on the topic. Methods Bibliographic databases were searched for qualitative and quantitative studies on surveillance of and interventions to prevent occupational injury among migrant workers in mainland China. Additional abstracts were identified from the citations of relevant articles from the database search. Studies fitting the inclusion criteria were evaluated, and findings were extracted and summarised. Results The search uncovered 726 studies in the English-language databases searched, and 3109 in the Chinese database. This article analyses a total of 19 research articles that fit the inclusion criteria with qualitative or quantitative data on occupational injury surveillance and prevention of migrant workers in China. Despite evidence of the vulnerability of migrant workers in the workplace, there is little systematic surveillance of occupational injury and few evaluated interventions. Conclusions Migrant workers account for a disproportionate burden of occupational injury morbidity and mortality in China. However, data are inconsistent and inadequate to detail injury incidence or to evaluate interventions. The following are suggestions to decrease injury incidence among migrants: strengthen the national system of occupational injury surveillance; focus surveillance and interventions on high-risk occupations employing migrants such as construction, manufacturing and small mining operations; improve occupational safety training and access to appropriate safety equipment; evaluate recent changes in occupational health and safety and evaluate outcome of multi-party interventions to reduce occupational injury among migrant workers. PMID:23710065

  2. [Fatal occupational accidents in Lombardy].

    Pianosi, G

    1995-01-01

    All fatal occupational accidents compensated in Lombardy from 1984 to 1989 were analyzed (1259 cases): significant differences between geographical distribution of fatal occupational accidents and workers were observed. Males accounted for about 95% of fatalities; an excess of cases was shown in both young and elderly workers. Death was the consequence of injuries involving most frequently the head, thorax and spinal cord. An excess of fatalities was observed in agriculture and, at a lower level, in manufacturing industries; small enterprises were involved in approximately 25% of fatalities occurring in the manufacturing industries and services. Employers were the victims of fatal accidents in 50% of cases in agriculture and in 70% of cases in craft industries. Construction, agriculture and transport accounted for about 50% of all fatalities. About 50% of fatal occupational accidents were related to vehicle use: the victim was the driver in the majority of cases, sometimes the victim was run over by a vehicle or fell from a vehicle. The results agree with some previous observations (e.g.: sex and age distribution; construction, agriculture and transport as working activities at high accident risk); but some original observations have emerged, in particular about the frequency of employers as victims and the role of vehicles in the genesis of fatal occupational accidents. If further studies confirm these latter observations, important developments could follow in preventive action design and implementation.

  3. Occupational hearing loss

    ... this page: //medlineplus.gov/ency/article/001048.htm Occupational hearing loss To use the sharing features on this page, please enable JavaScript. Occupational hearing loss is damage to the inner ear from noise ...

  4. Current and new challenges in occupational lung diseases

    Sara De Matteis

    2017-11-01

    Full Text Available Occupational lung diseases are an important public health issue and are avoidable through preventive interventions in the workplace. Up-to-date knowledge about changes in exposure to occupational hazards as a result of technological and industrial developments is essential to the design and implementation of efficient and effective workplace preventive measures. New occupational agents with unknown respiratory health effects are constantly introduced to the market and require periodic health surveillance among exposed workers to detect early signs of adverse respiratory effects. In addition, the ageing workforce, many of whom have pre-existing respiratory conditions, poses new challenges in terms of the diagnosis and management of occupational lung diseases. Primary preventive interventions aimed to reduce exposure levels in the workplace remain pivotal for elimination of the occupational lung disease burden. To achieve this goal there is still a clear need for setting standard occupational exposure limits based on transparent evidence-based methodology, in particular for carcinogens and sensitising agents that expose large working populations to risk. The present overview, focused on the occupational lung disease burden in Europe, proposes directions for all parties involved in the prevention of occupational lung disease, from researchers and occupational and respiratory health professionals to workers and employers.

  5. Aggregate Exposure and Cumulative Risk Assessment--Integrating Occupational and Non-occupational Risk Factors.

    Lentz, T J; Dotson, G S; Williams, P R D; Maier, A; Gadagbui, B; Pandalai, S P; Lamba, A; Hearl, F; Mumtaz, M

    2015-01-01

    Occupational exposure limits have traditionally focused on preventing morbidity and mortality arising from inhalation exposures to individual chemical stressors in the workplace. While central to occupational risk assessment, occupational exposure limits have limited application as a refined disease prevention tool because they do not account for all of the complexities of the work and non-occupational environments and are based on varying health endpoints. To be of greater utility, occupational exposure limits and other risk management tools could integrate broader consideration of risks from multiple exposure pathways and routes (aggregate risk) as well as the combined risk from exposure to both chemical and non-chemical stressors, within and beyond the workplace, including the possibility that such exposures may cause interactions or modify the toxic effects observed (cumulative risk). Although still at a rudimentary stage in many cases, a variety of methods and tools have been developed or are being used in allied risk assessment fields to incorporate such considerations in the risk assessment process. These approaches, which are collectively referred to as cumulative risk assessment, have potential to be adapted or modified for occupational scenarios and provide a tangible path forward for occupational risk assessment. Accounting for complex exposures in the workplace and the broader risks faced by the individual also requires a more complete consideration of the composite effects of occupational and non-occupational risk factors to fully assess and manage worker health problems. Barriers to integrating these different factors remain, but new and ongoing community-based and worker health-related initiatives may provide mechanisms for identifying and integrating risk from aggregate exposures and cumulative risks from all relevant sources, be they occupational or non-occupational.

  6. One thousand cases of severe occupational contact dermatitis

    Schwensen, Jakob Ferløv; Friis, Ulrik Fischer; Menné, Torkil

    2013-01-01

    Background. Occupational contact dermatitis is frequent, and further understanding of the epidemiology will improve the basis of its prevention. Objectives. To identify occupations at risk for severe occupational contact dermatitis. Methods. The last 1000 cases of severe occupational contact...... dermatitis seen at our department were identified. Results. The study population comprised 618 females and 382 males. The mean age at onset of irritant contact dermatitis was significantly lower than the mean age at onset of allergic contact dermatitis for both sexes, irrespective of the presence of atopic....... Occupational contact dermatitis remains frequent, even if only severe cases are considered. It is a concern that no effective, systematic interventions and prevention schemes have been launched in Europe, despite documentation of a significant problem overmany years, and knowledge of risk occupations and risk...

  7. Relationship of occupational and non-occupational stress with smoking in automotive industry workers.

    Hassani, Somayeh; Yazdanparast, Taraneh; Seyedmehdi, Seyed Mohammad; Ghaffari, Mostafa; Attarchi, Mirsaeed; Bahadori, Baharak

    2014-01-01

    Tobacco use is the second cause of death and first cause of preventable mortality worldwide. Smoking in the workplace is particularly concerning. Smoking-free workplaces decrease the risk of exposure of non-smoking personnel to cigarette smoke. Recent studies have mostly focused on the effect of daily or non-occupational stressors (in comparison with occupational stress) on prevalence of smoking. Occupational stress is often evaluated in workplaces for smoking cessation or control programs, but the role of non-occupational stressors is often disregarded in this respect. This cross-sectional study was conducted in an automobile manufacturing company. The response of automotive industry workers to parts of the validated, reliable, Farsi version of Musculoskeletal Intervention Center (MUSIC)-Norrtalje questionnaire was evaluated. A total of 3,536 factory workers participated in this study. Data were analyzed using SPSS and P<0.05 was considered statistically significant. The correlation of smoking with demographic factors, occupational stressors and life events was evaluated. The results of logistic regression analysis showed that even after adjusting for the confounding factors, cigarette smoking was significantly correlated with age, sex, level of education, job control and life events (P<0.05). The results showed that of occupational and non-occupational stressors, only job control was correlated with cigarette smoking. Non-occupational stressors had greater effect on cigarette smoking. Consideration of both non-occupational and occupational stressors can enhance the success of smoking control programs. On the other hand, a combination of smoking control and stress (occupational and non-occupational) control programs can be more effective than smoking cessation interventions alone.

  8. Occupational injuries due to violence.

    Hales, T; Seligman, P J; Newman, S C; Timbrook, C L

    1988-06-01

    Each year in the United States, an estimated 800 to 1,400 people are murdered at work, and an unknown number of nonfatal injuries due to workplace violence occur. Based on Ohio's workers' compensation claims from 1983 through 1985, police officers, gasoline service station employees, employees of the real estate industry, and hotel/motel employees were found to be at the highest risk for occupational violent crime (OVC) injury and death. Grocery store employees, specifically those working in convenience food stores, and employees of the real estate industry had the most reported rapes. Four previously unidentified industries at increased risk of employee victimization were described. Identification of industries and occupations at high risk for crime victimization provides the opportunity to focus preventive strategies to promote employee safety and security in the workplace.

  9. THE DETERMINATION AND APPRECIATION OF OCCUPATIONAL TOXICITY AT WORK

    Oana CHIVU

    2017-05-01

    Full Text Available The occupational toxins are those chemicals that workers come into contact with during the exercise of the profession and which under certain conditions have harmful effects on the body. The paper aims to address the determination and assessment of occupational toxicities in a workplace with the aim of ensuring an adequate working enviro nment as well as preventing occupational diseases, accidents and chronic fatigue.

  10. Occupational Health: Meeting the Challenges of the Next 20 Years

    Harrison, John; Dawson, Leonie

    2015-01-01

    Background: The industrial revolution that took place in the United Kingdom (UK) between 1760 and 1830 led to profound social change. Occupational medicine was concerned with the diagnosis, treatment, and prevention of occupational diseases, that is, diseases directly caused by exposure to workplace hazards. A similar pattern of development has occurred globally. Methods: A review of relevant literature. Results: The international conceptualization and development of occupational health...

  11. Occupational Disease Registries–Characteristics and Experiences

    Davoodi, Somayeh; Haghighi, Khosro Sadeghniat; Kalhori, Sharareh Rostam Niakan; Hosseini, Narges Shams; Mohammadzadeh, Zeinab; Safdari, Reza

    2017-01-01

    Introduction: Due to growth of occupational diseases and also increase of public awareness about their consequences, attention to various aspects of diseases and improve occupational health and safety has found great importance. Therefore, there is the need for appropriate information management tools such as registries in order to recognitions of diseases patterns and then making decision about prevention, early detection and treatment of them. These registries have different characteristics in various countries according to their occupational health priorities. Aim: Aim of this study is evaluate dimensions of occupational diseases registries including objectives, data sources, responsible institutions, minimum data set, classification systems and process of registration in different countries. Material and Methods: In this study, the papers were searched using the MEDLINE (PubMed) Google scholar, Scopus, ProQuest and Google. The search was done based on keyword in English for all motor engines including “occupational disease”, “work related disease”, “surveillance”, “reporting”, “registration system” and “registry” combined with name of the countries including all subheadings. After categorizing search findings in tables, results were compared with each other. Results: Important aspects of the registries studied in ten countries including Finland, France, United Kingdom, Australia, Czech Republic, Malaysia, United States, Singapore, Russia and Turkey. The results show that surveyed countries have statistical, treatment and prevention objectives. Data sources in almost the rest of registries were physicians and employers. The minimum data sets in most of them consist of information about patient, disease, occupation and employer. Some of countries have special occupational related classification systems for themselves and some of them apply international classification systems such as ICD-10. Finally, the process of registration system was

  12. [Occupational injury, a public health priority].

    Benavides, Fernando G; Delclos, Jordi; Benach, Joan; Serra, Consol

    2006-01-01

    The aim of this review is to stimulate new ideas and actions for the prevention of this important public health problem. In 2002 and 2003, respectively, the number of non-fatal occupational injuries was 971,406 and 906,638. Thus, every day in Spain there are more than 2500 non-fatal and between 2 and 3 fatal occupational injuries. Although the profile of the at-risk worker population has changed greatly over the past decade, both quantitatively and qualitatively, the risk of occupational injury still centers on blue collar workers, whether qualified or nonqualified, in the primary and secondary sectors of economic activity. The most common mechanisms of occupational injuries are overexertion for non-fatal injuries and traffic-related for fatal events. The adverse health consequences of new types of employment, which emphasize flexibility and deregulation of the labour market, are exemplified by the association between temporary employment and increased risk of occupational injury. New injury prevention programs have emerged in the last decade, but they appear to have had limited impact. Preventive activities should focus both on working conditions at the company level (micro) as well as on employment and industrial public policies (macro). Greater evaluation is needed of these latter policies.

  13. Dermatitis, an approach from occupational medicine

    Felipe Martínez Lomakin

    2013-04-01

    Full Text Available Occupational dermatitis is one of the most common occupational diseases in clinical practice. Prevalence varies according to the job activities and types of exposure, with figures of up to 37% reported in the literature. Its origin may be irritant or allergic. Atopy and frequent hand washing or exposure to wetness or humidity is described has been described as risk factors, while evidence for gender and tobacco consumption, among others, is controversial. Diagnosis is based on physical examination, etiological patch testing and certification of occupational origin using standardized criteria. The condition has been associated with reduced productivity, absenteeism and occupational changes, as well as significant decreases in the quality of life of patients. Prevention is based primarily on education and restriction of exposure. These strategies are coupled with the treatment, which include the use of drugs such as topical steroids and calcineurin inhibitors.(X Close Abstract

  14. Mexico, maquiladoras, and occupational medicine training.

    Cordes, D H; Rea, D F; Schwartz, I; Rea, J

    1989-01-01

    Industrialization and its concomitant social and environmental effects in developing countries are considered in this paper. Mexico offers one example of economic progress achieved through the promotion of industrial growth. Recognising the need for trained experts with global experience in occupational health, the University of Arizona (UA) has begun a programme to train occupational and preventive medicine residents in international aspects of occupational health in the nearby industrialized border regions of Mexico. By using the maquiladora (assembly plant) industries and the resources of the Instituto Mexicano del Seguro Social with the State of Sonora, residents observe existing problems in occupational safety and health in addition to adding to their understanding of the need for worldwide cooperation for research and reform in this field.

  15. Occupational risk involving students of health

    Éder Oliveira Rocha

    2014-01-01

    Full Text Available Objective: To analyze the social representations of occupational risks involving students in the area of health. Method: Exploratory research with 160 students from nursing, medicine and dentistry, through interviews. The data were processed in ALCESTE 4.8 and lexical analysis done by descending hierarchical classification. Results: In four semantic classes, namely: occupational risks involving students in the area of health, the work environment and occupational risks, exposure to accidents with sharps and adoption of standard precautions as biosecurity measures. Conclusion: Students healthcare represent occupational risks, such as a concern for the prevention of cross infection in the workplace, should both professionals and students of health, adopt standard precautions and biosecurity measures in the environment work.

  16. Building an evidence base for occupational health interventions

    Verbeek, Jos; Husman, Kaj; van Dijk, Frank; Jauhiainen, Merja; Pasternack, Iris; Vainio, Harri

    2004-01-01

    This article summarizes arguments for building an evidence base for occupational health. Evidence is needed on the most effective ways of eliminating health hazards in the workplace and at work, enhancing healthy behavior or the empowerment of workers, and preventing and treating occupational

  17. International survey of occupational health nurses' roles in multidisciplinary teamwork in occupational health services.

    Rogers, Bonnie; Kono, Keiko; Marziale, Maria Helena Palucci; Peurala, Marjatta; Radford, Jennifer; Staun, Julie

    2014-07-01

    Access to occupational health services for primary prevention and control of work-related injuries and illnesses by the global workforce is limited (World Health Organization [WHO], 2013). From the WHO survey of 121 (61%) participating countries, only one-third of the responding countries provided occupational health services to more than 30% of their workers (2013). How services are provided in these countries is dependent on legal requirements and regulations, population, workforce characteristics, and culture, as well as an understanding of the impact of workplace hazards and worker health needs. Around the world, many occupational health services are provided by occupational health nurses independently or in collaboration with other disciplines' professionals. These services may be health protection, health promotion, or both, and are designed to reduce health risks, support productivity, improve workers' quality of life, and be cost-effective. Rantanen (2004) stated that basic occupational health services must increase rather than decline, especially as work becomes more complex; workforces become more dynamic and mobile, creating new models of work-places; and jobs become more precarious and temporary. To better understand occupational health services provided by occupational health nurses globally and how decisions are made to provide these services, this study examined the scope of services provided by a sample of participating occupational health nurses from various countries. Copyright 2014, SLACK Incorporated.

  18. Prevention of hand eczema

    Fisker, Maja H; Ebbehøj, Niels E; Vejlstrup, Søren Grove

    2018-01-01

    Objective Occupational hand eczema has adverse health and socioeconomic impacts for the afflicted individuals and society. Prevention and treatment strategies are needed. This study aimed to assess the effectiveness of an educational intervention on sickness absence, quality of life and severity...... of hand eczema. Methods PREVEX (PreVention of EXema) is an individually randomized, parallel-group superiority trial investigating the pros and cons of one-time, 2-hour, group-based education in skin-protective behavior versus treatment as usual among patients with newly notified occupational hand eczema...

  19. Value of Gerontology for Occupational Social Work.

    Safford, Florence

    1988-01-01

    As aging affects society increasingly, occupational social workers can benefit from gerontological research and practice in developing programs to help older employees counteract ageism, prepare for retirement, cope with health challenges, and reduce stress in family relations. The workplace is a convenient site for preventive and therapeutic…

  20. The status of occupational safety among health service providers in ...

    identify and bring under control at workplaces all health risks; provide ... on the status of occupational safety among hospital workers in Tanzania. ..... The assistance from the IPC/IS. National ... tions of the Healthcare Infection Prevention.

  1. [Current status of occupational health and related countermeasures in Guangzhou, China].

    Zeng, W F; Wu, S H; Wang, Z; Liu, Y M

    2016-02-20

    To investigate the current status of occupational health and related countermeasures in Guangzhou, China. Related data were collected from occupational poisoning accident investigation, diagnosis and identification of occupational diseases, and the occupational disease hazard reporting system, and the statistical data of occupational health in Guangzhou were analyzed retrospectively. The number of enterprises reporting for occupational disease hazards in Guangzhou was 20 890, and the total number of workers was 1 457 583. The number of workers exposed to occupational hazards was 284 233, and the cumulative number of workers with occupational diseases was 1 502. There were many risk factors for occupational diseases in enterprises, and there were a large number of workers with occupational diseases, as well as newly diagnosed cases. From 2001 to 2014, the total number of cases of occupational diseases was 958. The situation for the prevention and control of occupational diseases is grim in Guangzhou. Occupational health supervision and law enforcement should be enhanced, the three-level supervision system should be established and perfected, and the occupational health supervision system with a combination of "prevention, treatment, and protection" should be established and promoted, so as to gradually establish a technical service support system for occupational health.

  2. Using Narrative Text and Coded Data to Develop Hazard Scenarios for Occupational Injury Interventions

    Lincoln, A

    2004-01-01

    Objective: To determine whether narrative text in safety reports contains sufficient information regarding contributing factors and precipitating mechanisms to prioritize occupational back injury prevention strategies...

  3. Inference for occupancy and occupancy dynamics

    O'Connell, Allan F.; Bailey, Larissa L.; O'Connell, Allan F.; Nichols, James D.; Karanth, K. Ullas

    2011-01-01

    This chapter deals with the estimation of occupancy as a state variable to assess the status of, and track changes in, species distributions when sampling with camera traps. Much of the recent interest in occupancy estimation and modeling originated from the models developed by MacKenzie et al. (2002, 2003), although similar methods were developed independently (Azuma et al. 1990; Bayley and Petersen 2001; Nichols and Karanth, 2002; Tyre et al. 2003), all of which deal with species occurrence information and imperfect detection. Less than a decade after these publications, the modeling and estimation of species occurrence and occupancy dynamics have increased significantly. Special features of scientific journals have explored innovative uses of detection–nondetection data with occupancy models (Vojta 2005), and an entire volume has synthesized the use and application of occupancy estimation methods (MacKenzie et al. 2006). Reviews of the topical concepts, philosophical considerations, and various sampling designs that can be used for occupancy estimation are now readily available for a range of audiences (MacKenzie and Royle 2005; MacKenzie et al. 2006; Bailey et al. 2007; Royle and Dorazio 2008; Conroy and Carroll 2009; Kendall and White 2009; Hines et al. 2010; Link and Barker 2010). As a result, it would be pointless here to recast all that these publications have so eloquently articulated, but that said, a review of any scientific topic requires sufficient context and relevant background information, especially when relatively new methodologies and techniques such as occupancy estimation and camera traps are involved. This is especially critical in a digital age where new information is published at warp speed, making it increasingly difficult to stay abreast of theoretical advances and research developments.

  4. [Need for occupational and environmental allergology in occupational health - the 45th Japanese society of Occupational and Environmental Allergy Annual Meeting 2014 in Fukuoka].

    Kishikawa, Reiko; Oshikawa, Chie

    2014-12-01

    The 45th Japanese Society of Occupational and Environmental Allergy (OEA) Annual Meeting 2014 was held in Fukuoka city in conjunction with a technical course for occupational health physicians to learn occupational and environmental diseases more deeply. Allergic reaction due to low concentrations of chemical and biological materials is important in toxicological diseases due to highly concentrated chemical materials in the field of occupational and environmental medicine. In this paper we describe the activities of the OEA, which was established in 1970 and has completely cured patients with severe occupational asthma, such as the regional Konjac asthma in Gunma prefecture and Sea Squirt asthma in Hiroshima prefecture. Regard for the occupational environment will prevent the onset and/or exacerbation of allergic occupational disease in individual employees with allergy. Occupational cancer of the bile duct and asbestosis are also current, serious issues that should be resolved as soon as possible. It is desirable for the occupational health physician to have a large stock of knowledge about toxicological and allergic diseases in various occupational settings to maintain the health and safety of workers.

  5. Occupational hearing loss in Korea.

    Kim, Kyoo Sang

    2010-12-01

    In this article, current status of noise exposure in workplaces, trend of workers with noise-induced hearing loss (NIHL), and prevalence of NIHL in workers by industry and job category in Korea were reviewed. In addition, trends of research on the audiological effects such as hearing loss from noise and occupational hearing loss from non-noise in Korea were addressed through reports in industrial audiology. Though noise exposure level has improved, noise still shows the highest rate of cases exceeding exposure limit among workplace hazards. NIHL is the most common occupational disease except work-related disease such as musculoskeletal disorders and cerebrovascular diseases, and NIHL prevalence is thought to be much higher than reported in official publications. Noise affecting hearing comes from various sources such as workplaces, military settings, areas with exposure to high noise, and specific noise sources. There is also occupational hearing loss by non-noise including chemicals such as organic solvents and heavy metals, barotrauma, and trauma due to welding spark. Noise affects daily life through audiological effects such as hearing loss and tinnitus, non-audiological physical effects (e.g., cardiovascular), and psychosocial and behavioral effects. Development of systematic and comprehensive hearing conservation programs for lowering the noise level in workplaces and preventing the NIHL, and preparation of technological, administrative system for its settlement at workplace are urgently needed.

  6. [Occupational risks in grocery stores].

    Graziosi, Francesca; Bonfiglioli, Roberta; Violante, Francesco S

    2014-01-01

    This work provides an overview of the spectrum of possible occupational risk factors in the retail grocery store/supermarket workplace. Literature on this theme, obtained consulting PubMed database and Google Scholar, was checked. We also exjlore results from the National bInstitute for Occupational Safety and Health (NIOSH) and the Occupational Safety and Health Administration (OSHA). RESULTs: Contacts with objects, use of dangerous equipment (cutter, food slicer) and falls to the same level (slips, trips and falls) are the mainly described workplace hazards. Exposure to chemical (flour dust, components of detergents or disinfectants, volatile organic compounds and contact with nickel) and physical agents (cold exposure, nonionizing radiation and whole bpdy vibration) are reported by many authors. Relations between biomechanical and ergonomic risk factors and musculoskeletal disorders represent the main subjects of study. Few studies are found about biological agents (particularly among butchers). Data regarding psychosocial risks factors in this setting are still limited. Musculoskeletal disorders continue to be the most recurrent health problem between the grocery store workers (particularly low back pain and carpal tunnel syndrome among cashiers). Many technical documents and international Srecommendations are present to prevent these kinds of disorders. Psychosocial risk factors and risk of workplace violence should deserve further investigation.

  7. The Future of Occupational Health Nursing in a Changing Health Care System.

    McCauley, Linda; Peterman, Katherine

    2017-04-01

    Repealing the Affordable Care Act (ACA) has significant implications for the future of occupational health nursing practice. As changes are proposed and implemented, occupational health nurses must continue to prioritize preventive care, chronic disease management, healthy communities, environmental health, and sustainability. In particular, immigrant workers are a vulnerable population needing attention by occupational health nurses.

  8. 78 FR 11651 - Board of Scientific Counselors, National Institute for Occupational Safety and Health (BSC, NIOSH)

    2013-02-19

    ... Scientific Counselors, National Institute for Occupational Safety and Health (BSC, NIOSH) In accordance with..., research, experiments, and demonstrations relating to occupational safety and health and to mine health... Occupational Safety and Health on research and prevention programs. Specifically, the Board shall provide...

  9. 77 FR 47850 - Board of Scientific Counselors, National Institute for Occupational Safety and Health (BSC, NIOSH)

    2012-08-10

    ... Scientific Counselors, National Institute for Occupational Safety and Health (BSC, NIOSH) In accordance with..., research, experiments, and demonstrations relating to occupational safety and health and to mine health... Occupational Safety and Health on research and prevention programs. Specifically, the Board shall provide...

  10. Role of radiology in occupational medicine

    Vehmas, T.

    2004-01-01

    This review discusses the contribution of radiology to occupational medicine as well as work-related problems in radiology dept.s. Research issues are emphasized. Radiology has been used especially when diagnosing occupational respiratory and locomotive system problems and solvent-induced encephalo- and hepatopathy. The aim of research in these areas is usually to characterize occupational dise