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1.
Avian Pathol ; 52(6): 401-411, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37605844

RESUMEN

Marek's disease (MD) is caused by oncogenic MD virus serotype 1 (MDV1) and is characterized by lymphoproliferative lesions resulting in high morbidity and mortality in chickens. Despite being ubiquitous on poultry farms, there is a dearth of information on its molecular characteristics in Nigeria. This study aimed at characterizing three virulence genes (Meq, pp38, and vIL-8) of MDV1 from chickens in Ogun state, Nigeria. Blood, feather quill, and tumour samples of chickens from different commercial poultry farms in Ogun State were pooled, spotted on 107 FTA cards, and screened for MDV1 by polymerase chain reaction (PCR). Phylogenetic analysis was carried out to compare Nigerian MDV1 Meq, pp38, and vIL-8 genes sequences with the published references. Thirteen samples were MDV1-positive and the Meq, as well as pp38, and vIL-8 genes from the different samples were 100% identical. The Meq genes contained 339 amino acids (aa) with three PPPP motifs in the transactivation domain and two interruptions of the PPPP motifs due to proline-to-arginine substitutions at positions 176 and 217 resulting in a 20.88% proline composition. Phylogenetic analysis revealed that the Meq gene clustered with strains from Egypt and very virulent ATE2539 strain from Hungary. Mutations were observed in the pp38 protein (at positions 107 and 109) and vIL-8 protein (at positions 4 and 31). Based on the molecular analysis of the three genes, the results indicate the presence of MDV1 with virulence signatures; therefore, further studies on in vivo pathotyping of Nigerian MDV1 from all states should be performed.RESEARCH HIGHLIGHTS Meq, pp38 and vIL-8 genes were 100% identical between Nigerian MDV strains.Proline content in Nigerian meq gene was 20.88% with two PPPP motifs interruptions.Meq, pp38 and vIL-8 genes of Nigerian MDV were similar to Egyptian and Indian strains.


Asunto(s)
Herpesvirus Gallináceo 2 , Enfermedad de Marek , Proteínas Oncogénicas Virales , Enfermedades de las Aves de Corral , Animales , Pollos , Filogenia , Nigeria/epidemiología , Herpesvirus Gallináceo 2/genética , Aves de Corral , Prolina/genética , Enfermedades de las Aves de Corral/epidemiología
2.
BMC Public Health ; 22(1): 2448, 2022 12 28.
Artículo en Inglés | MEDLINE | ID: mdl-36577991

RESUMEN

BACKGROUND: Income and housing are pervasive social determinants of health. Subsidized housing is a prominent affordability mechanism in Canada; however, waitlists are lengthy. Subsidized rents should provide greater access to residual income, which may theoretically improve health outcomes. However, little is known about the health of tenants who wait for and receive subsidized housing. This is especially problematic for New Brunswick, a Canadian province with low population density, whose inhabitants experience income inequality, social exclusion, and challenges with healthcare access.  METHODS: This study will use a longitudinal, prospective matched cohort design. All 4,750 households on New Brunswick's subsidized housing wait list will be approached to participate. The survey measures various demographic, social and health indicators at six-month intervals for up to 18 months as they wait for subsidized housing. Those who receive housing will join an intervention group and receive surveys for an additional 18 months post-move date. With consent, participants will have their data linked to a provincial administrative database of medical records.  DISCUSSION: Knowledge of housing and health is sparse in Canada. This study will provide stakeholders with a wealth of health information on a population that is historically under-researched and underserved.


Asunto(s)
Vivienda , Vivienda Popular , Humanos , Canadá , Salud Mental , Nuevo Brunswick , Estudios Prospectivos , Accesibilidad a los Servicios de Salud
3.
Epidemiol Infect ; 146(4): 508-514, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29429421

RESUMEN

To understand increasing rates of hepatitis C virus (HCV) infection in Tennessee, we conducted testing, risk factor analysis and a nested case-control study among persons who use drugs. During June-October 2016, HCV testing with risk factor assessment was conducted in sexually transmitted disease clinics, family planning clinics and an addiction treatment facility in eastern Tennessee; data were analysed by using multivariable logistic regression. A nested case-control study was conducted to assess drug-using risks and behaviours among persons who reported intranasal or injection drug use (IDU). Of 4753 persons tested, 397 (8.4%) were HCV-antibody positive. HCV infection was significantly associated with a history of both intranasal and IDU (adjusted odds ratio (aOR) 35.4, 95% confidence interval (CI) 24.1-51.9), IDU alone (aOR 52.7, CI 25.3-109.9), intranasal drug use alone (aOR 2.6, CI 1.8-3.9) and incarceration (aOR 2.7, CI 2.0-3.8). By 4 October 2016, 574 persons with a reported history of drug use; 63 (11%) were interviewed further. Of 31 persons who used both intranasal and injection drugs, 26 (84%) reported previous intranasal drug use, occurring 1-18 years (median 5.5 years) before their first IDU. Our findings provide evidence that reported IDU, intranasal drug use and incarceration are independent indicators of risk for past or present HCV infection in the study population.


Asunto(s)
Hepatitis C/epidemiología , Enfermedades de Transmisión Sexual/epidemiología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Demografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Tennessee/epidemiología
4.
Zoonoses Public Health ; 65(4): 425-430, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29430859

RESUMEN

The canine variant of the rabies virus has been eliminated in the United States. Among the public and many healthcare providers, however, dog bites are still associated with risk for rabies transmission. This study examined the risk of rabies in biting dogs and the use of rabies post-exposure prophylaxis (rPEP) for dog bite victims in Tennessee. The study included a retrospective analysis of laboratory testing requisitions for dogs from 2002 to 2016, collection of clinical data on confirmed rabies-positive dogs from 2008 to 2016 and analysis of hospital discharge data for rPEP from 2007 to 2014. Among dogs submitted for rabies testing, those having a recent history of biting were significantly less likely to test positive for rabies than dogs with no reported bite (OR = 0.01; 95% CI [0.003-0.04]). The most common clinical signs reported among rabies-positive dogs were anorexia, dysphagia, ataxia, limb paresis or paralysis, and lethargy; aggressiveness was uncommon. Among hospital patients with an animal-related injury who received rPEP, more than half (52%) presented with dog bites. These data show that laboratory submissions for rabies testing and prescriptions for rPEP do not reflect the epidemiology of rabies in Tennessee. Education and outreach targeting the public and healthcare providers should emphasize the animal species and situations associated with a greater risk for rabies transmission, such as bites from rabies reservoir species or animals exhibiting signs of neurologic disease.


Asunto(s)
Mordeduras y Picaduras/veterinaria , Reservorios de Enfermedades/veterinaria , Enfermedades de los Perros/transmisión , Profilaxis Posexposición/estadística & datos numéricos , Rabia/veterinaria , Animales , Mordeduras y Picaduras/epidemiología , Mordeduras y Picaduras/virología , Enfermedades de los Gatos/epidemiología , Enfermedades de los Gatos/transmisión , Enfermedades de los Gatos/virología , Gatos , Reservorios de Enfermedades/virología , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/virología , Perros , Personal de Salud/educación , Humanos , Salud Pública/economía , Salud Pública/educación , Rabia/epidemiología , Rabia/prevención & control , Rabia/transmisión , Vacunas Antirrábicas/administración & dosificación , Virus de la Rabia/aislamiento & purificación , Estudios Retrospectivos , Factores de Riesgo , Tennessee/epidemiología
5.
Poult Sci ; 96(7): 2074-2082, 2017 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-28160004

RESUMEN

Three experiments were conducted to evaluate the effect of in ovo administration of FloraMax®-B11 (FM) on Marek's disease (MD) herpesvirus of turkeys (HVT) vaccine protective efficacy, hatchability, microbiota composition, morphometric analysis, and Salmonella enteritidis (SE) infection in chickens. Experiment 1 consisted of 3 trials. In trials 1 and 2, d 18 White Leghorn 15I5x71 embryos were randomly distributed in 4 groups: 1) HVT vaccinated in ovo and no Marek's disease virus (MDV) challenge; 2), HVT + FM vaccinated in ovo and no MDV challenge; 3) HVT vaccinated in ovo and challenge with virulent MDV (vMDV; strain 583A); and 4), HVT + FM vaccinated in ovo and challenge with vMDV. Trial 3 was designed exactly the same as Experiment 1 but chicks were challenged with very virulent MDV (vvMDV; strains Md5 and 612). Birds were monitored until 8 wk of age, and tested for MD incidence. Experiment 2 consisted of 3 trials. In each trial, d 18 broiler embryos were injected in ovo with either saline or FM to measure hatchability and gastrointestinal bacterial composition. In Experiment 3, d 18 broiler embryos were injected in ovo with either saline or FM. All chickens that hatched were orally gavaged with SE at hatch and kept for 7 d to monitor post-hatch BW. No significant difference (P > 0.05) between MD percentage in birds vaccinated with HVT alone or HVT + FM were observed in Experiment 1. In Experiment 2, probiotic did not negatively affect hatchability, but did reduce lactose positive Gram-negative bacteria. Further, increase in BW was associated with higher villi surface area in the ileum in chickens that received the probiotic as well as a significant reduction in the SE incidence in Experiment 3. These results suggest that in ovo administration of FM does not negatively impact the ability of HVT to protect against MD or hatchability of chickens, but improves BW during the first 7 d of life and decreases SE recovery in chickens.


Asunto(s)
Pollos , Lactobacillales/química , Vacunas contra la Enfermedad de Marek/farmacología , Enfermedad de Marek/prevención & control , Enfermedades de las Aves de Corral/prevención & control , Probióticos/farmacología , Salmonelosis Animal/prevención & control , Animales , Embrión de Pollo , Herpesvirus Meleágrido 1/efectos de los fármacos , Enfermedad de Marek/virología , Vacunas contra la Enfermedad de Marek/administración & dosificación , Microbiota/efectos de los fármacos , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/virología , Probióticos/administración & dosificación , Reproducción , Salmonelosis Animal/microbiología , Salmonella enteritidis/efectos de los fármacos
6.
Avian Dis ; 60(1): 56-62, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26953944

RESUMEN

T-2 toxin, a very potent immunotoxic Type A trichothecene, is a secondary metabolite produced primarily by Fusarium spp., which grows on cereal grains and can lead to contaminated livestock feed. Repeated exposure to T-2 toxin has been shown to cause immunosuppression and decrease the resistance of exposed animals to a variety of infectious diseases; however, the effects of T-2 toxin on Marek's disease (MD) vaccinal immunity have not been reported. Four trials were conducted to determine the effects of T-2 toxin on vaccinal immunity against MD. Day-old, white leghorn chicks of Avian Disease and Oncology Laboratory line 15I5 × 71 were treated daily for 7 days via crop gavage with T-2 toxin at a sublethal dose of 1.25 mg/kg body weight. Treated and untreated chicks were also vaccinated with turkey herpesvirus (HVT) at hatch and were challenged with the JM strain of MD virus (MDV) at 8 days of age. Chickens were tested for HVT viremia at 1 wk postvaccination immediately before challenge, and for HVT and MDV viremia at 3 wk postchallenge. Chickens were observed for the development of MD lesions and mortality within 8 wk of age. T-2 toxin significantly reduced body weight and titers of HVT viremia within 7 days after hatch. T-2 toxin shortened the incubation period for the development of MD lesions and mortality, but only in unvaccinated chickens. The percent MD protection in T-2-toxin-treated, HVT-vaccinated chickens ranged from 82% to 96% and was comparable to that in HVT-vaccinated untreated control chickens (89%-100%). The data suggest that exposure of chickens to sublethal doses of T-2 toxin for 7 consecutive days after hatch may influence the development of 1) HVT viremia; and 2) MD lesions and mortality, but only in unvaccinated chickens.


Asunto(s)
Pollos , Herpesvirus Meleágrido 1/inmunología , Herpesvirus Gallináceo 2/inmunología , Enfermedad de Marek/inmunología , Enfermedades de las Aves de Corral/inmunología , Vacunas Virales/inmunología , Animales , Femenino , Masculino , Enfermedad de Marek/virología , Enfermedades de las Aves de Corral/virología , Toxina T-2 , Vacunación/veterinaria
8.
Zoonoses Public Health ; 58(7): 489-92, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21824352

RESUMEN

Brucellosis is a common zoonotic disease worldwide; however, few cases are reported in the US. Brucella melitensis infections are primarily acquired via consumption of high-risk foods or travel to endemic areas. We describe a case of B. melitensis infection in a Tennessee soldier following deployment in Iraq. Initial symptoms included knee and back pain. Culture of an aspirate of the left sacroiliac joint yielded B. melitensis. Genetic analysis indicated that this isolate came from the Middle East. Investigation of laboratory workers identified risky exposures and positive serology prompting post-exposure prophylaxis. Military personnel and other travellers should be advised to reduce risk regarding food consumption and animal contact in endemic areas. Additionally, medical providers should remain vigilant for non-endemic zoonoses among recent travellers.


Asunto(s)
Brucella melitensis , Brucelosis/epidemiología , Brucelosis/etiología , Guerra de Irak 2003-2011 , Personal Militar , Animales , Antibacterianos/uso terapéutico , Brucelosis/tratamiento farmacológico , Brucelosis/microbiología , Humanos , Masculino , Adulto Joven
9.
Vet Pathol ; 48(5): 993-8, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21239693

RESUMEN

Marek's disease (MD) is a disease of chickens that occurs worldwide and has serious economic consequences. MD can present as one of several forms, with the most commonly occurring forms being the lymphoproliferative diseases. Under experimental conditions, an early mortality syndrome has been recognized following infection by some but not all strains of MD virus (MDV). This is the first report of a confirmed case of mortality due to naturally occurring MDV infection in 1-week-old, nonvaccinated, chickens. Necrotizing lesions were observed in the bursa of Fabricius, lung, duodenum, jejunum, and proventriculus, and large intranuclear inclusion bodies were a striking feature in tissues with lesions in all birds. Immunohistochemical staining for the pp38 protein of MDV revealed abundant pp38 antigen in the affected tissues, confirming the presence of MDV within the lesions. PCR yielded an amplicon with 97% homology to the meq gene of MDV. No evidence of co-infection by either of the immunosuppressive agents chicken anemia virus and infectious bursal disease virus was detected.


Asunto(s)
Pollos , Herpesvirus Gallináceo 2/aislamiento & purificación , Enfermedad de Marek/virología , Animales , Antígenos Virales/análisis , ADN Viral/química , ADN Viral/genética , Herpesvirus Gallináceo 2/genética , Inmunohistoquímica/veterinaria , Enfermedad de Marek/mortalidad , Enfermedad de Marek/patología , Reacción en Cadena de la Polimerasa/veterinaria
10.
Poult Sci ; 89(10): 2083-91, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20852098

RESUMEN

Marek's disease (MD) is a T-cell lymphoma disease of domestic chickens induced by MD virus (MDV), a naturally oncogenic and highly contagious cell-associated α-herpesvirus. Earlier reports have shown that the MHC haplotype as well as non-MHC genes are responsible for genetic resistance to MD. The MHC was also shown to affect efficiency of vaccine response. Using specific-pathogen-free chickens from a series of 19 recombinant congenic strains and their 2 progenitor lines (lines 6(3) and 7(2)), vaccine challenge experiments were conducted to examine the effect of host genetic variation on vaccine efficacy. The 21 inbred lines of White Leghorns share the same B*2 MHC haplotype and the genome of each recombinant congenic strain differs by a random 1/8 sample of the susceptible donor line (7(2)) genome. Chickens from each of the lines were divided into 2 groups. One was vaccinated with turkey herpesvirus strain FC126 at the day of hatch and the other was treated as a nonvaccinated control. Chickens of both groups were inoculated with a very virulent plus strain of MDV on the fifth day posthatch. Analyses of the MD data showed that the genetic line significantly influenced MD incidence and days of survival post-MDV infection after vaccination of chickens (P<0.01). The protective indices against MD varied greatly among the lines with a range of 0 up to 84%. This is the first evidence that non-MHC host genetic variation significantly affects MD vaccine efficacy in chickens in a designed prospective study.


Asunto(s)
Pollos/genética , Pollos/inmunología , Variación Genética , Vacunas contra la Enfermedad de Marek/inmunología , Enfermedad de Marek/prevención & control , Animales , Enfermedad de Marek/inmunología , Organismos Libres de Patógenos Específicos
11.
J Med Entomol ; 47(3): 415-20, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20496589

RESUMEN

From April 2007 to September 2008, 1,793 adult and nymphal ixodid ticks were collected from 49 counties in Tennessee. Six species were identified, including Dermacentor variabilis (Say), Amblyomma americanum (L.), Ixodes texanus (Banks), Ixodes cookei Packard, Ixodes scapularis (Say), and Amblyomma maculatum Koch, from 13 medium- to large-sized mammalian hosts and dragging through vegetation. Raccoons were the most common vertebrate source (198 captures), accounting for 60% of ticks collected. Dermacentor variabilis was the predominant species from raccoons with a prevalence of 92% and mean intensity of 5.3. A. americanum was predominated in white-tailed deer and drags with respective mean intensities of 3.1 and 14.1 and prevalence values of 94%. All tick species were identified between April and August, coinciding with the majority of animal captures. Only A. americanum, I. texanus, and I. cookei were identified from 22 animal captures from November to March. I. texanus and I. cookei were more common in the eastern portions of the state, but this may be a result of higher raccoon captures in those areas. Only four specimens of I. scapularis were collected in this study, which may reflect the absence of small mammal or reptile captures. Two A. maculatum were collected, and we report new distribution records in Tennessee for this species. Despite unequal sampling among ecoregions, the large numbers of D. variabilis and A. americanum from multiple host species suggest their widespread distribution throughout the state. These species of ticks can transmit multiple pathogens, including spotted fever group rickettsiae and ehrlichiae.


Asunto(s)
Dermacentor/patogenicidad , Garrapatas/patogenicidad , Animales , Gatos/parasitología , Ciervos/parasitología , Ecosistema , Femenino , Zorros/parasitología , Ixodes , Larva , Masculino , Zarigüeyas/parasitología , Densidad de Población , Mapaches/parasitología , Estaciones del Año , Tennessee , Infestaciones por Garrapatas/epidemiología , Infestaciones por Garrapatas/veterinaria
12.
Poult Sci ; 88(7): 1373-80, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19531706

RESUMEN

The process of RNA interference (RNAi) has been exploited in cultured chicken cells and in chick embryos to assess the effect of specific gene inhibition on phenotypes related to development and disease. We previously demonstrated that avian leukosis virus-based retroviral vectors are capable of delivering effective RNAi against Marek's disease virus (MDV) in cell culture. In this study, similar RNAi vectors are shown to reduce the replication of MDV in live chickens. Retroviral vectors were introduced into d 0 chick embryos, followed by incubation until hatching. Chicks were challenged with 500 pfu of strain 648A MDV at day of hatch, followed by assays for viremia at 14 d postinfection. Birds were monitored for signs of Marek's disease for 8 wk. A stem-loop PCR assay was developed to measure siRNA expression levels in birds. Delivery of RNAi co-targeting the MDV gB glycoprotein gene and ICP4 transcriptional regulatory gene significantly reduced MDV viremia in vivo, although to lesser extents than were observed in cell culture. Concomitant reductions in disease incidence also were observed, and the extent of this effect depended on the potency of the MDV challenge virus inoculum. Successful modification of phenotypic traits in live birds with retroviral RNAi vectors opens up the possibility that such approaches could be used to alter the expression of candidate genes hypothesized to influence a variety of quantitative traits including disease susceptibility.


Asunto(s)
Mardivirus/fisiología , Interferencia de ARN , Animales , Secuencia de Bases , Línea Celular , Embrión de Pollo , Pollos , Regulación Viral de la Expresión Génica , Vectores Genéticos , Ensayo de Placa Viral , Proteínas Virales/metabolismo , Replicación Viral
13.
Avian Dis ; 51(3): 713-8, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17992931

RESUMEN

Marek's disease virus (MDV) is an oncogenic cell-associated herpesvirus that causes T-cell lymphoma in chickens. Lymphoproliferative neoplasms in Marek's disease (MD) occur in various organs and tissues, including the viscera, peripheral nerves, skin, gonads, and musculatures. MDV is restrictively produced in the feather follicle epithelial (FFE) cells, and it gains access to the external environment via infected cells or as infectious enveloped cell-free virus particles. The goals of the present study were to 1) determine whether the MDV-induced skin lesions are neoplastic in nature or inflammatory reactions to viral infection, 2) determine whether physical presence of feather follicles (FF) is necessary for skin tumor development, and 3) study the role of skin epithelial cells not associated with feathers or FF in the replication and dissemination of infectious virus particles. Scaleless chickens that produce only a few scattered feathers and no sculate scales along the anterior metatarsi were used as a unique model to study the pathogenesis of dermal lesions. Histologic and immunohistochemical analysis revealed that the cutaneous lesions were tumorous as was manifested by massive accumulation of lymphoblasts and extensive activation of meq oncoprotein, the hallmark of MDV oncogenesis, within the skin lesions. Neoplastic cutaneous lesions in the scaleless chickens indicate that feather follicles are not necessary for skin tumor development. Finally, our preliminary data indicate that inoculation with supernatant fluid from homogenized and sonicated skin samples of MDV-infected scaleless chickens induces MD in susceptible birds, suggesting that skin epithelial cells not associated with FF also harbor infectious viral particles.


Asunto(s)
Pollos/virología , Plumas , Enfermedad de Marek/patología , Neoplasias Cutáneas/veterinaria , Piel/patología , Piel/virología , Animales , Femenino , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/virología
14.
Neuropathol Appl Neurobiol ; 33(1): 77-85, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17239010

RESUMEN

The four GPI-anchored cell adhesion molecules that exemplify the IgLON family are most highly expressed in the nervous system and associate to form up to six different heterodimeric 'Diglons' that can modify cell adhesion and inhibit axon migration. Recently, two members, OPCML and LSAMP, were identified as putative tumour suppressor genes in ovarian and renal carcinomas respectively. In this study, we investigated OPCML expression in nonneoplastic brain tissue and 35 brain tumours (18 glioblastoma multiformes, five anaplastic gliomas, five meningiomas, six metastases and one medulloblastoma) and four glioma cell lines using quantitative reverse transcriptase polymerase chain reaction (RT-PCR). OPCML was highly expressed in cerebellum, less so in cerebral cortex, frontal lobe and meninges and was significantly reduced or absent in 83% of brain tumours and all cell lines compared with nonneoplastic whole brain. Two OPCML splice variants have been identified in humans, termed alpha1 and alpha2, but the latter has not been demonstrated in human neural tissues. Using PCR with specific primers, nonneoplastic brain and 3/6 of tested brain tumours expressed both splice variants, whereas the remaining brain tumours only expressed the alpha2 variant. Hypermethylation of the alpha1 OPCML promoter, associated with down-regulation of expression in ovarian tumours, did not correlate with expression levels in the subset of brain tumours tested, implying transcription of OPCML from an alternative promoter or a different mechanism of down-regulation. This study demonstrates that OPCML down-regulation occurs in the majority of brain tumours tested, warranting further investigation of OPCML and other IgLONs in the development and progression of brain tumours.


Asunto(s)
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Moléculas de Adhesión Celular/genética , Glioma/genética , Glioma/metabolismo , Empalme Alternativo/genética , Secuencia de Aminoácidos , Línea Celular Tumoral , ADN Complementario/biosíntesis , ADN Complementario/genética , Regulación hacia Abajo , Exones/genética , Proteínas Ligadas a GPI , Regulación Neoplásica de la Expresión Génica , Humanos , Metilación , Datos de Secuencia Molecular , Regiones Promotoras Genéticas/genética , ARN Neoplásico/biosíntesis , ARN Neoplásico/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
15.
Br J Cancer ; 94(8): 1186-93, 2006 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-16570050

RESUMEN

Angiogenesis and extracellular matrix degradation are key events in tumour progression, and factors regulating stromal-epithelial interactions and matrix composition are potential targets for the development of novel anti-invasive/antiangiogenic therapies. Here, we examine the expression of ADAMTS-8, a secreted protease with antiangiogenic properties, in brain tissues. Using quantitative RT-polymerase chain reaction (PCR), high, equivalent expression of ADAMTS-8 was found in normal whole brain, cerebral cortex, frontal lobe, cerebellum and meninges. ADAMTS-8 expression in 34 brain tumours (including 22 high-grade gliomas) and four glioma cell lines indicated at least two-fold reduction in mRNA compared to normal whole brain in all neoplastic tissues, and no detectable expression in 14 out of 34 (41%) tumours or four out of four (100%) cell lines. In contrast, differential expression of TSP1 and VEGF was seen in nine out of 15 (60%) and seven out of 13 (54%) tumours, with no relationship in the expression of these genes. Immunohistochemistry and Western analysis indicated downregulation of ADAMTS-8 protein in >77% tumours. Methylation-specific PCR analysis of ADAMTS-8 indicated promoter hypermethylation in one out of 24 brain tumours (a metastasis) and three out of four glioma cell lines suggesting an alternative mechanism of downregulation. These data suggest a role for ADAMTS-8 in brain tumorigenesis, warranting further investigation into its role in regulation of tumour angiogenesis and local invasion.


Asunto(s)
Proteínas ADAM/metabolismo , Inhibidores de la Angiogénesis/metabolismo , Neoplasias Encefálicas/metabolismo , Proteínas ADAM/genética , Proteínas ADAM/farmacología , Proteínas ADAMTS , Inhibidores de la Angiogénesis/genética , Inhibidores de la Angiogénesis/farmacología , Sitios de Unión , Western Blotting , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Regulación hacia Abajo , Perfilación de la Expresión Génica , Humanos , Metilación , Regiones Promotoras Genéticas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo
16.
Br J Cancer ; 91(6): 1149-54, 2004 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-15328519

RESUMEN

The antiangiogenic factor METH-2 (ADAMTS-8) was identified in a previous dual-channel cDNA microarray analysis to be at least two-fold under-represented in 85% (28 out of 33) of primary non-small-cell lung carcinomas (NSCLCs). This observation has been validated in an independent series of NSCLCs and adjacent normal tissues by comparative multiplex RT-PCR, and METH-2 mRNA expression was dramatically reduced in all 23 tumour samples analysed. Immunohistochemical analysis of the same sample set demonstrated that METH-2 was strongly expressed in 14 out of 19 normal epithelial sites examined but only one out of 20 NSCLCs. DNA methylation analysis of the proximal promoter region of this gene revealed abnormal hypermethylation in 67% of the adenocarcinomas and 50% of squamous cell carcinomas, indicating that epigenetic mechanisms are involved in silencing this gene in NSCLC. No homozygous deletions of METH-2 were found in lung cancer cell lines. Allelic imbalance in METH-2 was assessed by an intronic single nucleotide polymorphism (SNP) assay and observed in 44% of informative primary samples. In conclusion, the downregulation of METH-2 expression in primary NSCLC, often associated with promoter hypermethylation, is a frequent event, which may be related to the development of the disease.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Silenciador del Gen , Neoplasias Pulmonares/genética , Metaloendopeptidasas/genética , Regiones Promotoras Genéticas/genética , Proteínas ADAM , Proteínas ADAMTS , Adenocarcinoma/genética , Anciano , Carcinoma de Células Escamosas/genética , Metilación de ADN , ADN de Neoplasias/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Persona de Mediana Edad , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
17.
J Epidemiol Community Health ; 57(10): 792-7, 2003 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-14573584

RESUMEN

OBJECTIVE: To investigate relations between labour market income inequality and mortality in North American metropolitan areas. METHODS: An ecological cross sectional study of relations between income inequality and working age (25-64 years) mortality in 53 Canadian (1991) and 282 US (1990) metropolitan areas using four measures of income inequality. Two labour market income concepts were used: labour market income for households with non-trivial attachment to the labour market and labour market income for all households, including those with zero and negative incomes. Relations were assessed with weighted and unweighted bivariate and multiple regression analyses. RESULTS: US metropolitan areas were more unequal than their Canadian counterparts, across inequality measures and income concepts. The association between labour market income inequality and working age mortality was robust in the US to both the inequality measure and income concept, but the association was inconsistent in Canada. Three of four inequality measures were significantly related to mortality in Canada when households with zero and negative incomes were included. In North American models, increases in earnings inequality were associated with hypothetical increases in working age mortality rates of between 23 and 33 deaths per 100 000, even after adjustment for median metropolitan incomes. CONCLUSIONS: This analysis of labour market inequality provides more evidence regarding the robust nature of the relation between income inequality and mortality in the US. It also provides a more refined understanding of the nature of the relation in Canada, pointing to the role of unemployment in generating Canadian metropolitan level health inequalities.


Asunto(s)
Empleo/economía , Renta/estadística & datos numéricos , Mortalidad , Salud Urbana/estadística & datos numéricos , Adulto , Canadá/epidemiología , Estudios Transversales , Femenino , Humanos , Renta/tendencias , Masculino , Persona de Mediana Edad , Modelos Teóricos , Análisis de Regresión , Factores de Riesgo , Factores Socioeconómicos , Desempleo/estadística & datos numéricos , Estados Unidos/epidemiología
18.
Brain Res Bull ; 60(1-2): 43-52, 2003 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-12725891

RESUMEN

The effect of magnetic fields on interictal firing rates was investigated in three epileptic patients with depth electrode implantation in the hippocampus for pre-surgical evaluation. The protocol consisted of 10 min test periods, during which magnetic fields were cycled for 1 min on and 1 min off, and intervening 5 min rest periods. Only one patient revealed a 95% significant increase in the 10 s after the fields were switched on compared with the background estimate from the 10s before the fields were applied. This patient was also the only patient to show significant increases in firing rates during field-on compared with field-off periods, and during magnetic field test periods compared with intervening rest periods. This patient had a right hippocampal seizure onset. All patients showed increased firing rates during the 10 min periods of magnetic field testing compared to the 5 min rest periods between tests. This result was significant for the group at the 99% level. Two patients with right temporal lobe onset showed greater activity in the right hippocampus than the left. All patients exhibited a progressive increase in firing rates in rest periods between tests.


Asunto(s)
Campos Electromagnéticos , Epilepsia/fisiopatología , Electrodos Implantados , Electroencefalografía/métodos , Fenómenos Electromagnéticos , Potenciales Evocados/fisiología , Femenino , Hipocampo/anatomía & histología , Hipocampo/fisiopatología , Humanos , Masculino , Factores de Tiempo
19.
J Epidemiol Community Health ; 56(9): 671-81, 2002 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12177083

RESUMEN

STUDY OBJECTIVE: To investigate the relation between housing, socioeconomic status, and self reported general and mental health. This study is an empirical investigation of social and economic dimensions of housing, specifically, demand, control, and material (affordability, dwelling type) and meaningful (pride in dwelling, home as a refuge) dimensions of everyday life as they occur in the domestic environment. DESIGN: A cross sectional telephone survey was administered to a random sample of households. Survey items included measures of demand, control, and meaningfulness of the domestic environment, as well as standard measures of socioeconomic status and social support. Main outcome measures were self reported health (excellent, very good, good, fair, poor) and self reported frequency of feeling "downhearted and blue" in the two weeks before interview (from the Rand Mental Health Index). SETTING: Households (n=650) from 12 neighbourhood areas in the city of Vancouver, Canada. PARTICIPANTS: One randomly selected adult from each of 650 households completed the interview and constitute the sample for this study. MAIN RESULTS: In bivariate analyses, measures of housing demand, control and meaningfulness exhibited strong and significantly graded relations with self reported health and somewhat less strong relations with mental health. In logistic regression analyses housing demand and control variables made significant contributions to health both general and mental health. Respondents were more likely to report fair/poor health if they: reported that they couldn't stand to be at home sometimes (OR=2.29, p<0.05); rated their domestic housework as somewhat or quite a strain (OR=5.71, p<0.001); were somewhat or very dissatisfied with their social activities (OR=3.41, p<0.001); and reported that they were constantly under stress a good bit of the time or more (OR=3.56, p<0.05). In terms of mental health, respondents were more likely to report poorer mental health if they: lived longer in their neighbourhood (OR=1.05, p<0.05); reported their housework duties to be somewhat or quite a strain (OR=5.55, p<0.001); reported that they did not have somebody that could help them if they needed it (OR=9.28, p<0.001); and reported that they were constantly under stress a good bit of the time or more in the two weeks before the interview (OR=5.26, p<0.001). One of the main hypotheses investigated-that meaningful dimensions of housing are associated with health status-found support in bivariate analyses without controls, but did not contribute to multivariable models. CONCLUSIONS: The influence of housing demand and control variables superseded a well known correlate of health status, educational attainment, attesting to their importance. The findings of this paper lend support to the hypothesis that features of the domestic environment, especially as they pertain to the exercise of control and the experience of demand, are significant predictors of self reported general and mental health status. Housing is a concrete manifestation of socioeconomic status, which has an important part to play in the development of explanations of the social production of health inequalities.


Asunto(s)
Indicadores de Salud , Vivienda , Factores Socioeconómicos , Adolescente , Adulto , Anciano , Colombia Británica , Estudios Transversales , Femenino , Tareas del Hogar , Humanos , Renta , Modelos Logísticos , Masculino , Trastornos Mentales/etiología , Persona de Mediana Edad , Calidad de Vida , Características de la Residencia , Clase Social , Apoyo Social , Estrés Psicológico/etiología
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