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[PMID]: 26431065
[Au] Autor:Rageh AA; Ferrington DA; Roehrich H; Yuan C; Terluk MR; Nelson EF; Montezuma SR
[Ad] Address:a Department of Ophthalmology and Visual Neurosciences....
[Ti] Title:Lactoferrin Expression in Human and Murine Ocular Tissue.
[So] Source:Curr Eye Res;41(7):883-9, 2016 Jul.
[Is] ISSN:1460-2202
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:PURPOSE: Lactoferrin (LF) is a multifunctional protein known to provide innate defense due to its antimicrobial and anti-inflammatory properties. In the eye, LF has been identified in the tears and vitreous humor. Its presence in other ocular tissues has not been determined. Our aim is to assess the presence of LF in the cornea, iris, retina and retinal pigment epithelium (RPE) of humans and mice. METHODS: To test for the endogenous production of LF, reverse transcription polymerase chain reaction was performed in cultured human cells from the cornea and RPE and in murine tissues. To confirm LF localization in specific ocular tissue, immunohistochemistry was performed on flat mounts of cornea, retina and RPE in human donor eyes. The presence of LF was assessed by western blotting in human and mouse ocular tissue and human culture cells (cornea and RPE). To verify antibody specificity, purified human LF and transferrin (TF) were used on 1D and 2D western blots. RESULTS: LF gene expression was confirmed in the cornea and RPE cell cultures from humans, suggesting that LF is an endogenously produced protein. PCR results from mouse ocular tissue showed LF expression in cornea, iris, RPE, but not in retina. These results were also consistent with immunohistochemical localization of LF in human donor tissue. Antibody reaction for human LF was specific and western blotting showed its presence in the cornea, iris and RPE tissues. A faint reaction for the retina was observed but was likely due to contamination from other ocular tissues. Multiple commercially available antibodies for murine LF cross-reacted with TF, so no reliable results were obtained for murine western blot. CONCLUSION: LF is expressed in multiple eye tissues of humans and mice. This widespread expression and multifunctional activity of LF suggests that it may play an important role in protecting eye tissues from inflammation-associated diseases.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1607
[Cu] Class update date: 160702
[Lr] Last revision date:160702
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.3109/02713683.2015.1075220

  2 / 267266 MEDLINE  
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[PMID]: 26968737
[Au] Autor:Chen L; Martino V; Dombkowski A; Williams T; West-Mays J; Gage PJ
[Ad] Address:Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States....
[Ti] Title:AP-2ß Is a Downstream Effector of PITX2 Required to Specify Endothelium and Establish Angiogenic Privilege During Corneal Development.
[So] Source:Invest Ophthalmol Vis Sci;57(3):1072-81, 2016 Mar.
[Is] ISSN:1552-5783
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:PURPOSE: The homeodomain transcription factor, PITX2, is at the apex of a genetic pathway required for corneal development, but the critical effector genes regulated by the PITX2 remain unknown. The purpose of this study was to discover and validate PITX2-dependent mechanisms required for specifying cell lineages and establishing angiogenic privilege within the developing cornea. METHODS: Microarrays were used to compare gene expression in corneas isolated from temporal Pitx2 knockout embryos and control littermates. Quantitative RT-PCR and immunohistochemistry was used to further validate Tfap2b expression differences in Pitx2 knockout versus control corneas. In situ hybridization and protein immunohistochemistry were used to assay eyes of a Tfap2b allelic series of embryos to identify differentiated cellular lineages in the cornea, blood vessel endothelium, or lymphatic vessel endothelium. RESULTS: We show that PITX2 is required for the expression of Tfap2b, encoding the AP-2ß transcription factor, in the neural crest during corneal development. Markers of differentiated corneal epithelium and stroma are expressed in the absence of AP-2ß. In contrast, markers of differentiated corneal endothelium are not expressed in the absence of AP-2ß. Endomucin+ blood vessels are present throughout the developing corneal stroma in the absence of AP-2ß, whereas LYVE1+ lymphatic vessels are not found. CONCLUSIONS: The AP-2ß transcription factor is an important effector of PITX2 function during corneal development, required for differentiation of corneal endothelium and establishment of angiogenic privilege. Unlike PITX2, AP-2ß is not required for the early expression of available lineage specific markers for the corneal epithelium and stroma during embryogenesis, nor establishment of lymphangiogenic privilege. Therefore, additional PITX2-dependent factors likely regulate these latter processes during embryonic development. These results extend our understanding of the genetic mechanisms regulating cornea development.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1603
[Cu] Class update date: 160603
[Lr] Last revision date:160603
[Js] Journal subset:IM
[St] Status:In-Process
[do] DOI:10.1167/iovs.15-18103

  3 / 267266 MEDLINE  
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[PMID]: 26943151
[Au] Autor:Kobayashi M; Iwase T; Yamamoto K; Ra E; Murotani K; Matsui S; Terasaki H
[Ad] Address:Department of Ophthalmology Nagoya University Graduate School of Medicine, Nagoya, Japan....
[Ti] Title:Association Between Photoreceptor Regeneration and Visual Acuity Following Surgery for Rhegmatogenous Retinal Detachment.
[So] Source:Invest Ophthalmol Vis Sci;57(3):889-98, 2016 Mar.
[Is] ISSN:1552-5783
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:PURPOSE: The purpose of this study was to evaluate foveal regeneration and the association between retinal restoration and visual acuity following reattachment surgery for rhegmatogenous retinal detachment (RRD). METHODS: Twenty-nine eyes of 29 patients with successfully reattached macula-off RRD were retrospectively analyzed. We used spectral-domain optical coherence tomography to image macular regions and measure retinal thickness and Snellen chart visual acuity (VA) to evaluate best-corrected VA (BCVA) at 1, 2, 3, 6, 9, and 12 months after vitrectomy. Best-corrected visual acuity data were converted to the logarithm of the minimum angle of resolution scale. Opposite eyes were used as controls. RESULTS: The thicknesses of the external limiting membrane (ELM)-ellipsoid zone (EZ) and EZ-retinal pigment epithelium (RPE) were significantly thinner in involved eyes than in corresponding unaffected eyes at 1 month after surgery (P < 0.001 for both), and the thickness increased over time (P < 0.001 for both). Best-corrected visual acuity significantly improved over time (P < 0.001), and the improvement correlated with EZ-RPE thickness (r = -0.45, P = 0.021). Multiple regression analysis demonstrated the presence of a foveal bulge as the independent predictor of final BCVA (P < 0.001). Eyes with a foveal bulge had significantly better BCVA and greater EZ-RPE thickness than those without throughout the follow-up period. Significant restoration of the integrity of EZ and cone interdigitation zone (CIZ) was observed over time (P < 0.001 for both) in eyes with a foveal bulge. CONCLUSIONS: The thickness of EZ-RPE and cone density increased during foveal regeneration, as demonstrated by the continuous improvements in CIZ integrity over time, leading to the formation of foveal bulge and good vision following successful reattachment of macula-off RRD.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1603
[Js] Journal subset:IM
[St] Status:In-Process
[do] DOI:10.1167/iovs.15-18403

  4 / 267266 MEDLINE  
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[PMID]: 26780117
[Au] Autor:Kidder GM; Cyr DG
[Ad] Address:Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario N6A 5C1, Canada. Electronic address: gmk@uwo.ca.
[Ti] Title:Roles of connexins in testis development and spermatogenesis.
[So] Source:Semin Cell Dev Biol;50:22-30, 2016 Feb.
[Is] ISSN:1096-3634
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The development and differentiation of cells involved in spermatogenesis requires highly regulated and coordinated interactions between cells. Intercellular communication, particularly via connexin43 (Cx43) gap junctions, plays a critical role in the development of germ cells during fetal development and during spermatogenesis in the adult. Loss of Cx43 in the fetus results in a decreased number of germ cells, while the loss of Cx43 in the adult Sertoli cells results in complete inhibition of spermatogenesis. Connexins 26, 32, 33, 36, 45, 46 and 50 have also been localized to specific compartments of the testis in various mammals. Loss of Cx46 is associated with an increase in germ cell apoptosis and loss of the integrity of the blood-testis barrier, while loss of other connexins appears to have more subtle effects within the seminiferous tubule. Outside the seminiferous tubule, the interstitial Leydig cells express connexins 36 and 45 along with Cx43; deletion of the latter connexin did not reveal it to be crucial for steroidogenesis or for the development and differentiation of Leydig cells. In contrast, loss of Cx43 from Sertoli cells results in Leydig cell hyperplasia, suggesting important cross-talk between Sertoli and Leydig cells. In the epididymis connexins 26, 30.3, Cx31.1, 32, and 43 have been identified and differentiation of the epithelium is associated with dramatic changes in their expression. Decreased expression of Cx43 results in decreased sperm motility, a function acquired by spermatozoa during epididymal transit. Clearly, intercellular gap junctional communication within the testis and epididymis represents a critical aspect of male reproductive function and fertility. The implications of this mode of intercellular communication for male fertility remains a poorly understood but important facet of male reproduction.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1603
[Js] Journal subset:IM
[St] Status:In-Process

  5 / 267266 MEDLINE  
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[PMID]: 26849947
[Au] Autor:Beaumont M; Andriamihaja M; Lan A; Khodorova N; Audebert M; Blouin JM; Grauso M; Lancha L; Benetti PH; Benamouzig R; Tomé D; Bouillaud F; Davila AM; Blachier F
[Ad] Address:UMR PNCA, AgroParisTech, INRA, Université Paris-Saclay, Paris, France....
[Ti] Title:Detrimental effects for colonocytes of an increased exposure to luminal hydrogen sulfide: The adaptive response.
[So] Source:Free Radic Biol Med;93:155-64, 2016 Apr.
[Is] ISSN:1873-4596
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Protein fermentation by the gut microbiota releases in the large intestine lumen various amino-acid derived metabolites. Among them, hydrogen sulfide (H2S) in excess has been suspected to be detrimental for colonic epithelium energy metabolism and DNA integrity. The first objective of this study was to evaluate in rats the epithelial response to an increased exposure to H2S. Experiments from colonocyte incubation and intra-colonic instillation indicate that low millimolar concentrations of the sulfide donor NaHS reversibly inhibited colonocyte mitochondrial oxygen consumption and increased gene expression of hypoxia inducible factor 1α (Hif-1α) together with inflammation-related genes namely inducible nitric oxide synthase (iNos) and interleukin-6 (Il-6). Additionally, rat colonocyte H2S detoxification capacity was severely impaired in the presence of nitric oxide. Based on the γH2AX ICW technique, NaHS did not induce DNA damage in colonocytes. Since H2S is notably produced by the gut microbiota from sulfur containing amino acids, the second objective of the study was to investigate the effects of a high protein diet (HPD) on large intestine luminal sulfide content and on the expression of genes involved in H2S detoxification in colonocytes. We found that HPD markedly increased H2S content in the large intestine but the concomitant increase of the content mass maintained the luminal sulfide concentration. HPD also provoked an increase of sulfide quinone reductase (Sqr) gene expression in colonocytes, indicating an adaptive response to increased H2S bacterial production. In conclusion, low millimolar NaHS concentration severely affects colonocyte respiration in association with increased expression of genes associated with intestinal inflammation. Although HPD increases the sulfide content of the large intestine, the colonic adaptive responses to this modification limit the epithelial exposure to this deleterious bacterial metabolite.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1603
[Js] Journal subset:IM
[St] Status:In-Process

  6 / 267266 MEDLINE  
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[PMID]: 26845617
[Au] Autor:Cheng X; He S; Yuan J; Miao S; Gao H; Zhang J; Li Y; Peng W; Wu P
[Ad] Address:Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China....
[Ti] Title:Lipoxin A4 attenuates LPS-induced mouse acute lung injury via Nrf2-mediated E-cadherin expression in airway epithelial cells.
[So] Source:Free Radic Biol Med;93:52-66, 2016 Apr.
[Is] ISSN:1873-4596
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:A fundamental element of acute lung injury (ALI) is the inflammation that is part of the body's immune response to a variety of local or systemic stimuli. Lipoxins (LXs) are important endogenous lipids that mediate resolution of inflammation. Previously, we demonstrated that LXA4 reduced the LPS inhalation-induced pulmonary edema, neutrophil infiltration and TNF-α production in mice. With the same model, the current investigation focused on the role of the airway epithelium, a first-line barrier and a prime target of inhaled toxicants. We report that LXA4 strongly inhibited LPS-induced ALI in mice, in part by protecting the airway epithelium and preserving the E-cadherin expression and airway permeability. Using a cryo-imaging assay and fluorescence detection, LXA4 was shown to block LPS-induced ROS generation and preserve mitochondrial redox status both in vivo and in vitro. To further assess whether and how NF-E2-related factor 2 (Nrf2) was involved in the protective effect of LXA4, fluorescence resonance energy transfer (FRET) analysis was employed in human epithelial cell line (16HBE), to determine the relative distance between Nrf2 and its negative regulator or cytosolic inhibitor, Kelch-like ECH-associated protein 1 (Keap1). It provided us the evidence that LXA4 further promoted the dissociation of Nrf2 and Keap1 in LPS-treated 16HBE cells. The results also showed that LXA4 activates Nrf2 by phosphorylating it on Ser40 and triggering its nuclear translocation. Moreover, when the plasmid expression dominant negative mutation of Nrf2 was transfected as an inhibitor of wild-type Nrf2, the protective effect of LXA4 on E-cadherin expression was almost completely blocked. These results provide a new mechanism by which LXA4 inhibits LPS-induced ALI through Nrf2-mediated E-cadherin expression.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1603
[Js] Journal subset:IM
[St] Status:In-Process

  7 / 267266 MEDLINE  
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[PMID]: 26899845
[Au] Autor:Lapii GA; Bakarev MA; Nepomnyashchikh GI; Kapustina VI; Nepomnyashchikh DL; Vinogradova EV; Postnikova OA
[Ad] Address:Institute of Molecular Pathology and Pathomorphology, Novosibirsk, Russia. pathol@inbox.ru....
[Ti] Title:Structural Characteristics of Gastric Cell Populations in Chronic Gastritis and Chronic Hepatitis under Conditions of Helicobacter pylori Persistence.
[So] Source:Bull Exp Biol Med;160(4):514-8, 2016 Feb.
[Is] ISSN:1573-8221
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Helicobacter pylori persistence in patients with chronic gastritis is associated with a complex of nonspecific structural reactions, the type of these reactions correlates with the severity of infection: catarrhal fibrotic changes in the gastric mucosa predominate in cases with manifest colonization, while the absence of H. pylori is associated with predominance of fibrotic process. Analysis of the incidence of some pathomorphological phenomena (degeneration, atrophy, metaplasia, and dysplasia of the surface epithelium) shows no relationship between the presence of H. pylori and colonization intensity. In all patients with chronic hepatitis, the gastric mucosa is involved in the pathological process; fibrosis (gastropathy) was the most common process. No appreciable correlations between the structural changes and hepatitis activity and the presence of H. pylori were detected.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1603
[Js] Journal subset:IM
[St] Status:In-Process
[do] DOI:10.1007/s10517-016-3210-z

  8 / 267266 MEDLINE  
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[PMID]: 26883689
[Au] Autor:Al-Saqi SH; Jonasson AF; Naessén T; Uvnäs-Moberg K
[Ad] Address:Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden shahla.alsaqi@gmail.com....
[Ti] Title:Oxytocin improves cytological and histological profiles of vaginal atrophy in postmenopausal women.
[So] Source:Post Reprod Health;22(1):25-33, 2016 Mar.
[Is] ISSN:2053-3705
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE: To investigate if topical oxytocin can reverse vaginal atrophy, as assessed by cytological and histological examination of the vaginal mucosal epithelium, in postmenopausal women after 12 weeks of treatment as compared to placebo. STUDY DESIGN: Sixty-eight postmenopausal women diagnosed with vaginal atrophy were randomized for this multicenter, double-blinded, placebo-controlled trial. Thirty-three women received 600 IU vagitocin, an oxytocin containing gel, and 35 women received a placebo gel intravaginally. The dose was 600 IU daily for the first two weeks and thereafter 600 IU twice a week for 10 weeks. All participant women underwent four visits and a subgroup of 20 women had a further fifth visit. Vaginal smears for cytological evaluation were collected at all visits. Vaginal biopsies were taken in 20 women before and after 12 weeks of treatment for histological analysis. In these women a vaginal smear was also collected after 14 weeks. RESULTS: The increase in the percentage of superficial cells between 0 and 2 weeks was significantly greater after treatment with vagitocin in comparison with placebo (p = 0.04). The difference in the maturation value between 0 and 12 weeks was significantly higher in the vagitocin than in the placebo group (p = 0.01). The reduction in the scores of atrophy was according to the histological investigation significantly greater in the vagitocin group than in the placebo group at 12 weeks (p < 0.04). CONCLUSION: Daily intravaginal treatment with vagitocin 600 IU improves expressions of vaginal atrophy as recorded by cytological investigation of vaginal smears and histological analysis of vaginal biopsies. Treatment twice weekly seems to be less effective regarding the increase in superficial cells.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1603
[Js] Journal subset:IM
[St] Status:In-Process
[do] DOI:10.1177/2053369116629042

  9 / 267266 MEDLINE  
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[PMID]: 26981790
[Au] Autor:Abdelwhab el-SM; Veits J; Breithaupt A; Gohrbandt S; Ziller M; Teifke JP; Stech J; Mettenleiter TC
[Ad] Address:a Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health , Greifswald , Germany....
[Ti] Title:Prevalence of the C-terminal truncations of NS1 in avian influenza A viruses and effect on virulence and replication of a highly pathogenic H7N1 virus in chickens.
[So] Source:Virulence;7(5):546-57, 2016 Jul 3.
[Is] ISSN:2150-5608
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Highly pathogenic (HP) avian influenza viruses (AIV) evolve from low pathogenic (LP) precursors after circulation in poultry by reassortment and/or single mutations in different gene segments including that encoding NS1. The carboxyl terminal end (CTE) of NS1 exhibits deletions between amino acid 202 and 230 with still unknown impact on virulence of AIV in chickens. In this study, NS1 protein sequences of all AIV subtypes in birds from 1902 to 2015 were analyzed to study the prevalence and distribution of CTE truncation (ΔCTE). Thirteen different ΔCTE forms were observed in NS1 proteins from 11 HA and 8 NA subtypes with high prevalences in H9, H7, H6 and H10 and N9, N2, N6 and N1 subtypes particularly in chickens and minor poultry species. With 88% NS217 lacking amino acids 218-230 was the most common ΔCTE form followed by NS224 (3.6%). NS217 was found in 10 and 8 different HA and NA subtypes, respectively, whereas NS224 was detected exclusively in the Italian HPAIV H7N1 suggesting relevance for virulence. To test this assumption, 3 recombinant HPAIV H7N1 were constructed carrying wild-type HP NS1 (Hp-NS224), NS1 with extended CTE (Hp-NS230) or NS1 from LPAIV H7N1 (Hp-NSLp), and tested in-vitro and in-vivo. Extension of CTE in Hp NS1 significantly decreased virus replication in chicken embryo kidney cells. Truncation in the NS1 decreased the tropism of Hp-NS224 to the endothelium, central nervous system and respiratory tract epithelium without significant difference in virulence in chickens. This study described the variable forms of ΔCTE in NS1 and indicated that CTE is not an essential virulence determinant particularly for the Italian HPAIV H7N1 but may be a host-adaptation marker required for efficient virus replication.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1607
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1080/21505594.2016.1159367

  10 / 267266 MEDLINE  
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[PMID]: 26215873
[Au] Autor:Gallhoefer NS; Spiess BM; Guscetti F; Hilbe M; Hartnack S; Hafezi F; Pot SA
[Ad] Address:Augen Vet, Lindenthalguertel 83, 50935, Cologne, Germany....
[Ti] Title:Penetration depth of corneal cross-linking with riboflavin and UV-A (CXL) in horses and rabbits.
[So] Source:Vet Ophthalmol;19(4):275-84, 2016 Jul.
[Is] ISSN:1463-5224
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:OBJECTIVE: CXL penetration depth is an important variable influencing clinical treatment effect and safety. The purposes of this study were to determine the penetration depth of CXL in rabbit and equine corneas in epithelium-on and epithelium-off procedures and to assess an ex vivo fluorescent biomarker staining assay for objective assessment of CXL penetration depth. PROCEDURES: CXL treatment was performed according to a standardized protocol on 21 and 17 rabbit eyes and on 12 and 10 equine eyes with and without debridement, respectively. Control corneas were treated similarly, but not exposed to CXL. Hemicorneas were stained with either phalloidin and DAPI to visualize intracellular F-actin and nuclei, or with hematoxylin and eosin. Loss of actin staining was measured and compared between groups. RESULTS: Epithelium-off CXL caused a median actin cytoskeleton loss with a demarcation at 274 µm in rabbits and 173 µm in horses. In non-CXL-treated controls, we observed a median actin cytoskeleton loss with a demarcation at 134 µm in rabbits and 149 µm in horses. No effect was detected in the epithelium-on procedure. CONCLUSIONS: CXL penetration depth, as determined by a novel ex vivo fluorescent assay, shows clear differences between species. A distinct effect was observed following epithelium-off CXL treatment in the anterior stroma of rabbits, but no different effect was observed in horses in comparison with nontreated controls. Different protocols need to be established to effectively treat equine patients with infectious corneal disease.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1607
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1111/vop.12301


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