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2.
Epidemiol Infect ; 146(4): 430-436, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29307318

RESUMO

A salmonellosis outbreak occurred at a California prison in April and May 2016. In a cohort study of 371 inmates, persons who consumed dishes from the prison kitchen made from ground meat had a higher attack rate (15%) than those who did not (4%) (risk ratio 3.4, 95% CI 1.1-10.6). The ground meat product was composed exclusively of beef, mechanically separated chicken (MSC) and textured vegetable protein; eight of eight lots of the product collected from the prison and processing facility were contaminated with Salmonella enterica of eight serotypes and 17 distinct PFGE patterns, including multidrug-resistant S. Infantis. Either the MSC or the beef could have been the source of the particular strains of S. enterica isolated from patients or the product. The microbiological evidence is most consistent with MSC as the source of the high levels of S. enterica in the epidemiologically linked meat product. Our findings contribute to the growing body of evidence about the hazard posed by the use of products containing raw mechanically separated poultry in kitchens in institutions.


Assuntos
Surtos de Doenças , Proteínas de Vegetais Comestíveis , Aves Domésticas/microbiologia , Prisões , Carne Vermelha/microbiologia , Intoxicação Alimentar por Salmonella/epidemiologia , Intoxicação Alimentar por Salmonella/microbiologia , Salmonella enterica/isolamento & purificação , Animais , California/epidemiologia , Farmacorresistência Bacteriana Múltipla , Microbiologia de Alimentos , Humanos , Testes de Sensibilidade Microbiana , Sorogrupo
3.
Epidemiol Infect ; 146(3): 297-302, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29386076

RESUMO

A large outbreak of Legionnaires' disease occurred at a California state prison in August 2015. We conducted environmental and epidemiological investigations to identify the most likely source of exposure and characterise morbidity. Sixty-four inmates had probable Legionnaires' disease; 14 had laboratory-confirmed legionellosis. Thirteen (17%) inmates were hospitalised; there were no deaths. Ill inmates were more likely to be ⩾65 years old (P < 0.01), have the chronic obstructive pulmonary disease (P < 0.01), diabetes mellitus (P = 0.02), hepatitis C infection (P < 0.01), or end-stage liver disease (P < 0.01). The case-patients were in ten housing units throughout the prison grounds. All either resided in or were near the central clinical building (for appointments or yard time) during their incubation periods. Legionella pneumophila serogroup 1 was cultured from three cooling towers on top of the central medical clinic (range, 880-1200 cfu/ml). An inadequate water management program, dense biofilm within the cooling towers, and high ambient temperatures preceding the outbreak created an ideal environment for Legionella sp. proliferation. All state prisons were directed to develop local operating procedures for maintaining their cooling towers and the state health department added a review of the maintenance plans to their environmental inspection protocol.


Assuntos
Surtos de Doenças , Legionella pneumophila/isolamento & purificação , Doença dos Legionários/epidemiologia , Prisões , Microbiologia da Água , Adulto , Idoso , Idoso de 80 Anos ou mais , California/epidemiologia , Humanos , Legionella/classificação , Legionella/isolamento & purificação , Legionella pneumophila/classificação , Legionelose/epidemiologia , Legionelose/microbiologia , Doença dos Legionários/microbiologia , Pessoa de Meia-Idade , Fatores de Risco , Abastecimento de Água
5.
Proc Natl Acad Sci U S A ; 111(44): E4779-88, 2014 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-25331903

RESUMO

Despite the critical role of the presynaptic dopamine (DA) transporter (DAT, SLC6A3) in DA clearance and psychostimulant responses, evidence that DAT dysfunction supports risk for mental illness is indirect. Recently, we identified a rare, nonsynonymous Slc6a3 variant that produces the DAT substitution Ala559Val in two male siblings who share a diagnosis of attention-deficit hyperactivity disorder (ADHD), with other studies identifying the variant in subjects with bipolar disorder (BPD) and autism spectrum disorder (ASD). Previously, using transfected cell studies, we observed that although DAT Val559 displays normal total and surface DAT protein levels, and normal DA recognition and uptake, the variant transporter exhibits anomalous DA efflux (ADE) and lacks capacity for amphetamine (AMPH)-stimulated DA release. To pursue the significance of these findings in vivo, we engineered DAT Val559 knock-in mice, and here we demonstrate in this model the presence of elevated extracellular DA levels, altered somatodendritic and presynaptic D2 DA receptor (D2R) function, a blunted ability of DA terminals to support depolarization and AMPH-evoked DA release, and disruptions in basal and psychostimulant-evoked locomotor behavior. Together, our studies demonstrate an in vivo functional impact of the DAT Val559 variant, providing support for the ability of DAT dysfunction to impact risk for mental illness.


Assuntos
Anfetamina/farmacologia , Comportamento Animal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Transtornos Mentais/metabolismo , Mutação de Sentido Incorreto , Substituição de Aminoácidos , Animais , Dopamina/genética , Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Neurônios Dopaminérgicos/patologia , Feminino , Humanos , Masculino , Transtornos Mentais/genética , Transtornos Mentais/patologia , Camundongos , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo
6.
Epidemiol Infect ; 144(1): 123-37, 2016 01.
Artigo em Inglês | MEDLINE | ID: mdl-26062721

RESUMO

In this study, we evaluated the association between high-risk human papillomavirus (hrHPV) and the vaginal microbiome. Participants were recruited in Nigeria between April and August 2012. Vaginal bacterial composition was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V4) on Illumina MiSeq and HPV was identified using the Roche Linear Array® HPV genotyping test. We used exact logistic regression models to evaluate the association between community state types (CSTs) of vaginal microbiota and hrHPV infection, weighted UniFrac distances to compare the vaginal microbiota of individuals with prevalent hrHPV to those without prevalent hrHPV infection, and the Linear Discriminant Analysis effect size (LEfSe) algorithm to characterize bacteria associated with prevalent hrHPV infection. We observed four CSTs: CST IV-B with a low relative abundance of Lactobacillus spp. in 50% of participants; CST III (dominated by L. iners) in 39·2%; CST I (dominated by L. crispatus) in 7·9%; and CST VI (dominated by proteobacteria) in 2·9% of participants. LEfSe analysis suggested an association between prevalent hrHPV infection and a decreased abundance of Lactobacillus sp. with increased abundance of anaerobes particularly of the genera Prevotella and Leptotrichia in HIV-negative women (P < 0·05). These results are hypothesis generating and further studies are required.


Assuntos
Microbiota , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Vagina/microbiologia , Adolescente , Adulto , Idoso , DNA Bacteriano/genética , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Nigéria/epidemiologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Prevalência , RNA Ribossômico 16S/genética , Vagina/virologia , Adulto Jovem
9.
S Afr Med J ; 114(3b): e1367, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-39041443

RESUMO

BACKGROUND: In the paediatric liver transplant programme in Johannesburg, South Africa (SA), tacrolimus is the calcineurin inhibitor of choice, comprising an essential component of the immunosuppression regimen. It is characterised by a narrow therapeutic index and wide interpatient variability, necessitating therapeutic drug monitoring of whole-blood concentrations. Pharmacogenetic research, although not representative of SA population groups, suggests that single-nucleotide polymorphisms within the cytochrome P450 3A5 (CYP3A5) gene contribute to the variability in tacrolimus dosing requirements. The rs776746 polymorphism, CYP3A5*3, results in a splice defect and a non-functional enzyme. Clinically, to reach the same tacrolimus concentration-to-dose ratio (CDR), expressors (CYP3A5*1/*1 and *1/*3) require a higher tacrolimus dose than non-expressors (*3/*3). OBJECTIVES: To compare the pharmacokinetics of tacrolimus in paediatric liver transplant recipients with their donors' CYP3A5 genotypes, considering both donor and recipient characteristics. METHODS: Blood samples from 46 living liver donors were collected, their genomic DNA was extracted, and their CYP3A5 genotype was established (polymerase chain reaction and restriction fragment length polymorphism analysis, validated by Sanger sequencing). The relationship of donor and recipient characteristics with the mean tacrolimus CDR was analysed using a general linear model. Non- confounding significant variables were included in a multiple regression model. RESULTS: The study showed that all expressor donors genotyped as CYP3A5*1/*1 were of black African self-reported race and ethnicity. During the first 15 days post-transplant, we found that children who received grafts from donor CYP3A5 expressors (CYP3A5*1/*1 and *1/*3) had significantly lower mean tacrolimus CDRs compared with those who received grafts from donor CYP3A5 non-expressors (*3/*3); the recipients of CYP3A5 expressor grafts therefore require higher doses of oral tacrolimus to achieve the same therapeutic target range. In addition, graft-to-recipient weight ratio and the CYP3A5 donor genotypes were independent factors that significantly (p<0.05) affected mean tacrolimus CDRs in recipients. CONCLUSION: In this study, we showed that all CYP3A5*1 homozygote donors were of black African self-reported race and ethnicity, and tacrolimus CDRs in paediatric living-donor liver transplant recipients were significantly affected by donor graft size and donor CYP3A5 genotypes. Information from this study may inform the development of an Afrocentric tacrolimus precision-medicine algorithm to optimise recipient safety and graft outcomes.


Assuntos
Citocromo P-450 CYP3A , Genótipo , Imunossupressores , Transplante de Fígado , Polimorfismo de Nucleotídeo Único , Tacrolimo , Humanos , Tacrolimo/farmacocinética , Tacrolimo/administração & dosagem , Tacrolimo/uso terapêutico , Citocromo P-450 CYP3A/genética , África do Sul , Criança , Imunossupressores/farmacocinética , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Masculino , Feminino , Pré-Escolar , Adolescente , Doadores Vivos , Lactente
10.
Nat Genet ; 6(2): 157-62, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8162070

RESUMO

Cervical carcinoma is now known to be associated with human papillomaviruses (HPV), but the evidence for a link with specific HLA loci is controversial. The role of genetic variation at the HLA class II loci and among HPV types in cervical carcinoma was investigated by PCR DNA amplification and oligonucleotide probe typing of paraffin-embedded invasive cervical cancer tissue from Hispanic patients and of cervical swabs from Hispanic controls. Certain HLA class II haplotypes (such as DRB1*1501-DQB1*0602) were associated significantly, while DR13 haplotypes were negatively associated with cervical carcinoma. These associations are HPV16-type specific. These results suggest that specific HLA class II haplotypes may influence the immune response to specific HPV-encoded epitopes and affect the risk of cervical neoplasia.


Assuntos
Adenocarcinoma/imunologia , Carcinoma de Células Escamosas/imunologia , Antígenos HLA-DQ/análise , Antígenos HLA-DR/análise , Papillomaviridae/fisiologia , Neoplasias do Colo do Útero/imunologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/virologia , Carcinoma de Células Escamosas/virologia , Estudos de Casos e Controles , Suscetibilidade a Doenças , Feminino , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Haplótipos , Hispânico ou Latino , Teste de Histocompatibilidade , Humanos , Razão de Chances , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Sudoeste dos Estados Unidos , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologia , Neoplasias do Colo do Útero/virologia
11.
Front Radiol ; 3: 1305390, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38249159

RESUMO

Alzheimer's Disease (AD) is a leading cause of morbidity. Management of AD has traditionally been aimed at symptom relief rather than disease modification. Recently, AD research has begun to shift focus towards disease-modifying therapies that can alter the progression of AD. In this context, a class of immunotherapy agents known as monoclonal antibodies target diverse cerebral amyloid-beta (Aß) epitopes to inhibit disease progression. Aducanumab was authorized by the US Food and Drug Administration (FDA) to treat AD on June 7, 2021. Aducanumab has shown promising clinical and biomarker efficacy but is associated with amyloid-related imaging abnormalities (ARIA). Neuroradiologists play a critical role in diagnosing ARIA, necessitating familiarity with this condition. This pictorial review will appraise the radiologic presentation of ARIA in patients on aducanumab.

12.
Int J Cancer ; 131(1): 106-16, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-21858807

RESUMO

In the Phase III PATRICIA study (NCT00122681), the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix(®), GlaxoSmithKline Biologicals) was highly efficacious against HPV-16/18 infections and precancerous lesions in women HPV-16/18 deoxyribose nucleic acid (DNA) negative and seronegative at baseline. We present further data on vaccine efficacy (VE) against HPV-16/18 in the total vaccinated cohort including women who may have been exposed to HPV-16/18 infection before vaccination. In women with no evidence of current or previous HPV-16/18 infection (DNA negative and seronegative), VE was 90.3% (96.1% confidence interval: 87.3-92.6) against 6-month persistent infection (PI), 91.9% (84.6-96.2) against cervical intraepithelial neoplasia (CIN)1+ and 94.6% (86.3-98.4) against CIN2+ [97.7% (91.1-99.8) when using the HPV type assignment algorithm (TAA)]. In women HPV-16/18 DNA negative but with serological evidence of previous HPV-16/18 infection (seropositive), VE was 72.3% (53.0-84.5) against 6-month PI, 67.2% (10.9-89.9) against CIN1+, and 68.8% (-28.3-95.0) against CIN2+ [88.5% (10.8-99.8) when using TAA]. In women with no evidence of current HPV-16/18 infection (DNA negative), regardless of their baseline HPV-16/18 serological status, VE was 88.7% (85.7-91.1) against 6-month PI, 89.1% (81.6-94.0) against CIN1+ and 92.4% (84.0-97.0) against CIN2+ [97.0% (90.6-99.5) when using TAA]. In women who were DNA positive for one vaccine type, the vaccine was efficacious against the other vaccine type. The vaccine did not impact the outcome of HPV-16/18 infections present at the time of vaccination. Vaccination was generally well tolerated regardless of the woman's HPV-16/18 DNA or serological status at entry.


Assuntos
Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Adjuvantes Imunológicos , Adolescente , Adulto , Anticorpos Antivirais/sangue , Estudos de Coortes , DNA Viral/sangue , Feminino , Humanos , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/efeitos adversos , Resultado do Tratamento , Vacinação , Adulto Jovem , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/prevenção & controle
13.
Am J Transplant ; 11(5): 1058-63, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21449943

RESUMO

Patients who undergo Epstein-Barr virus (EBV) seromismatch (D+/R-) transplants have a higher risk for the development of post-transplant lymphoproliferative disorder (PTLD). Adult renal transplant recipients at a single institution were prospectively monitored for EBV during the first year post-transplant. Over a 2-year period, 34 patients (7.78%) were identified as being EBV D+/R-recipients. Patients who developed symptoms or had persistent viremia were pre-emptively administered rituximab. Six recipients were discharged without monitoring on the protocol. Of those six, three (50%) developed PTLD and all three lost their grafts. Twenty (60.6%) of the 34 recipients developed viremia during the first year post-transplant. Of the recipients who became viremic, six (30%) received rituximab. None of the six who received rituximab-developed PTLD. We found that recipients who were not monitored on the protocol were more likely to have PTLD and graft loss compared to those who were (p = 0.008). Post-transplant monitoring of adults who undergo EBV D+/R-kidney transplants for viremia and symptoms associated with EBV infection may prompt intervention which reduces the incidence of PTLD within the first year. Use of rituximab in preventing PTLD among patients with primary EBV infection requires further prospective study to determine its overall safety and efficacy.


Assuntos
Infecções por Vírus Epstein-Barr/metabolismo , Herpesvirus Humano 4/metabolismo , Transplante de Rim/métodos , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Murinos/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/virologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Rituximab , Carga Viral
14.
Lancet ; 374(9706): 1975-85, 2009 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-19962185

RESUMO

BACKGROUND: Prophylactic human papillomavirus (HPV) vaccines have to provide sustained protection. We assessed efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. METHODS: Women aged 15-25 years, with normal cervical cytology, who were HPV-16/18 seronegative and oncogenic HPV DNA-negative (14 types) at screening participated in a double-blind, randomised, placebo-controlled initial study (n=1113; 560 vaccine group vs 553 placebo group) and follow-up study (n=776; 393 vs 383). 27 sites in three countries participated in the follow-up study. Cervical samples were tested every 6 months for HPV DNA. Management of abnormal cytologies was prespecified, and HPV-16/18 antibody titres were assessed. The primary objective was to assess long-term vaccine efficacy in the prevention of incident cervical infection with HPV 16 or HPV 18, or both. We report the analyses up to 6.4 years of this follow-up study and combined with the initial study. For the primary endpoint, the efficacy analysis was done in the according-to-protocol (ATP) cohort; the analysis of cervical intraepithelial neoplasia grade 2 and above (CIN2+) was done in the total vaccinated cohort (TVC). The study is registered with ClinicalTrials.gov, number NCT00120848. FINDINGS: For the combined analysis of the initial and follow-up studies, the ATP efficacy cohort included 465 women in the vaccine group and 454 in the placebo group; the TVC included 560 women in the vaccine group and 553 in the placebo group. Vaccine efficacy against incident infection with HPV 16/18 was 95.3% (95% CI 87.4-98.7) and against 12-month persistent infection was 100% (81.8-100). Vaccine efficacy against CIN2+ was 100% (51.3-100) for lesions associated with HPV-16/18 and 71.9% (20.6-91.9) for lesions independent of HPV DNA. Antibody concentrations by ELISA remained 12-fold or more higher than after natural infection (both antigens). Safety outcomes were similar between groups: during the follow-up study, 30 (8%) participants reported a serious adverse event in the vaccine group versus 37 (10%) in the placebo group. None was judged related or possibly related to vaccination, and no deaths occurred. INTERPRETATION: Our findings show excellent long-term efficacy, high and sustained immunogenicity, and favourable safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. FUNDING: GlaxoSmithKline Biologicals (Belgium).


Assuntos
Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Placebos , Resultado do Tratamento , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/virologia , Adulto Jovem
15.
Lancet ; 374(9686): 301-14, 2009 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-19586656

RESUMO

BACKGROUND: The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic, generally well tolerated, and effective against HPV-16 or HPV-18 infections, and associated precancerous lesions in an event-triggered interim analysis of the phase III randomised, double-blind, controlled PApilloma TRIal against Cancer In young Adults (PATRICIA). We now assess the vaccine efficacy in the final event-driven analysis. METHODS: Women (15-25 years) were vaccinated at months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for efficacy (ATP-E; vaccine, n=8093; control, n=8069), total vaccinated cohort (TVC, included all women receiving at least one vaccine dose, regardless of their baseline HPV status; represents the general population, including those who are sexually active; vaccine, n=9319; control, n=9325), and TVC-naive (no evidence of oncogenic HPV infection at baseline; represents women before sexual debut; vaccine, n=5822; control, n=5819). The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2+ (CIN2+) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline, and DNA negative at baseline and month 6 for the corresponding type (ATP-E). This trial is registered with ClinicalTrials.gov, number NCT00122681. FINDINGS: Mean follow-up was 34.9 months (SD 6.4) after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92.9% (96.1% CI 79.9-98.3) in the primary analysis and 98.1% (88.4-100) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types (ATP-E cohort). Vaccine efficacy against CIN2+ irrespective of HPV DNA in lesions was 30.4% (16.4-42.1) in the TVC and 70.2% (54.7-80.9) in the TVC-naive. Corresponding values against CIN3+ were 33.4% (9.1-51.5) in the TVC and 87.0% (54.9-97.7) in the TVC-naive. Vaccine efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54.0% (34.0-68.4; ATP-E). Individual cross-protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45 was seen in the TVC. INTERPRETATION: The HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2+ associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes. FUNDING: GlaxoSmithKline Biologicals.


Assuntos
Papillomavirus Humano 16 , Papillomavirus Humano 18 , Infecções por Papillomavirus , Vacinas contra Papillomavirus/imunologia , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Adolescente , Adulto , Método Duplo-Cego , Feminino , Humanos , Vacinação em Massa , Estadiamento de Neoplasias , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Lesões Pré-Cancerosas/prevenção & controle , Lesões Pré-Cancerosas/virologia , Segurança , Comportamento Sexual , Resultado do Tratamento , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Adulto Jovem , Displasia do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/virologia
16.
Epidemiol Infect ; 138(4): 507-11, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19845993

RESUMO

Coccidioidomycosis results from inhaling spores of the fungus Coccidioides spp. in soil or airborne dust in endemic areas. We investigated an outbreak of coccidioidomycosis in a 12-person civilian construction crew that excavated soil during an underground pipe installation on Camp Roberts Military Base, California in October 2007. Ten (83.3%) workers developed symptoms of coccidioidomycosis; eight (66.7%) had serologically confirmed disease, seven had abnormal chest radiographs, and one developed disseminated infection; none used respiratory protection. A diagnosis of coccidioidomycosis in an eleventh worker followed his exposure to the outbreak site in 2008. Although episodic clusters of infections have occurred at Camp Roberts, the general area is not associated with the high disease rates found in California's San Joaquin Valley. Measures to minimize exposure to airborne spores during soil-disrupting activities should be taken before work begins in any coccidioides-endemic area, including regions with only historic evidence of disease activity.


Assuntos
Coccidioides/isolamento & purificação , Coccidioidomicose/epidemiologia , Surtos de Doenças , Adulto , Anticorpos Antifúngicos/sangue , California/epidemiologia , Coccidioidomicose/diagnóstico , Coccidioidomicose/patologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Radiografia Torácica , Adulto Jovem
17.
Osteoarthritis Cartilage ; 17(7): 944-52, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19250984

RESUMO

OBJECTIVE: To determine changes in chondrocyte transcription of a range of anabolic, catabolic and signaling genes following simultaneous treatment of cartilage with Insulin-like growth factor-1 (IGF-1) and ramp-and-hold mechanical compression, and compare with effects on biosynthesis. METHODS: Explant disks of bovine calf cartilage were slowly compressed (unconfined) over 3-min to their 1mm cut-thickness (0%-compression) or to 50%-compression with or without 300 ng/ml IGF-1. Expression of 24 genes involved in cartilage homeostasis was measured using qPCR at 2, 8, 24, 32, 48 h after compression +/-IGF-1. Clustering analysis was used to identify groups of co-expressed genes to further elucidate mechanistic pathways. RESULTS: IGF-1 alone stimulated gene expression of aggrecan and collagen II, but simultaneous 24h compression suppressed this effect. Compression alone up-regulated expression of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5 and transforming growth factor (TGF)-beta, an effect not reversed by simultaneous IGF-1 treatment. Temporal changes in expression following IGF-1 treatment were generally slower than that following compression. Clustering analysis revealed five distinct groups within which the pairings, tissue inhibitor of metalloproteinase (TIMP)-3 and ADAMTS-5, MMP-1 and IGF-2, and IGF-1 and Collagen II, were all robustly co-expressed, suggesting inherent regulation and feedback in chondrocyte gene expression. While aggrecan synthesis was transcriptionally regulated by IGF-1, inhibition of aggrecan synthesis by sustained compression appeared post-transcriptionally regulated. CONCLUSION: Sustained compression markedly altered the effects of IGF-1 on expression of genes involved in cartilage homeostasis, while IGF-1 was largely unable to moderate the transcriptional effects of compression alone. The demonstrated co-expressed gene pairings suggest a balance of anabolic and catabolic activity following simultaneous mechanical and growth factor stimuli.


Assuntos
Condrócitos/fisiologia , Expressão Gênica/efeitos dos fármacos , Homeostase/genética , Fator de Crescimento Insulin-Like I/farmacologia , Estresse Mecânico , Transcrição Gênica/fisiologia , Animais , Cartilagem Articular/fisiologia , Bovinos , Expressão Gênica/fisiologia
18.
J Cell Biol ; 51(21): 384-95, 1971 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-4939526

RESUMO

The purpose of this investigation was to study the formation and origin of basal lamina and anchoring fibrils in adult human skin. Epidermis and dermis were separated by "cold trypsinization." Viable epidermis and viable, inverted dermis were recombined and grafted to the chorioallantoic membrane of embryonated chicken eggs for varying periods up to 10 days. Basal lamina and anchoring fibrils were absent from the freshly trypsinized epidermis before grafting although hemidesmosomes and tonofilaments of the basal cells remained intact. Basal lamina and anchoring fibrils were absent from freshly cut, inverted surface of the dermis. Beginning 3 days after grafting, basal lamina was noted to form immediately subjacent to hemidesmosomes of epidermal basal cells at the epidermal-dermal interface. From the fifth to the seventh day after grafting, basal lamina became progressively more dense and extended to become continuous in many areas at the epidermal-dermal interface. Anchoring fibrils appeared first in grafts consisting of epidermis and viable dermis at five day cultivation and became progressively more numerous thereafter. In order to determine the epidermal versus dermal origin of basal lamina and anchoring fibrils, dermis was rendered nonviable by repeated freezing and thawing 10 times followed by recombination with viable epidermis. Formation of basal lamina occurred as readily in these recombinants of epidermis with freeze-thawed, nonviable dermis as with viable dermis, indicating that dermal viability was not essential for synthesis of basal lamina. This observation supports the concept of epidermal origin for basal lamina. Anchoring fibrils did not form in recombinants containing freeze-thawed dermis, indicating that dermal viability was required for anchoring fibrils formation. This observation supports the concept of dermal origin of anchoring fibrils.


Assuntos
Membrana Basal , Organoides , Pele/citologia , Animais , Membrana Celular , Embrião de Galinha , Técnicas de Cultura , Desmossomos , Membranas Extraembrionárias , Congelamento , Humanos , Junções Intercelulares , Métodos , Microscopia Eletrônica , Modelos Biológicos , Morfogênese , Pele/embriologia , Pele/crescimento & desenvolvimento , Transplante de Pele , Fatores de Tempo , Tripsina
19.
Neuron ; 17(3): 451-60, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8816708

RESUMO

Hereditary demyelinating peripheral neuropathies consist of a heterogeneous group of genetic disorders that includes hereditary neuropathy with liability to pressure palsies (HNPP), Charcot-Marie-Tooth disease (CMT), Dejerine-Sottas syndrome (DSS), and congenital hypomyelination (CH). The clinical classification of these neuropathies into discrete categories can sometimes be difficult because there can be both clinical and pathologic variation and overlap between these disorders. We have identified five novel mutations in the myelin protein zero (MPZ) gene, encoding the major structural protein (P0) of peripheral nerve myelin, in patients with either CMT1B, DSS, or CH. This finding suggests that these disorders may not be distinct pathophysiologic entities, but rather represent a spectrum of related "myelinopathies" due to an underlying defect in myelination. Furthermore, we hypothesize the differences in clinical severity seen with mutations in MPZ are related to the type of mutation and its subsequent effect on protein function (i.e., loss of function versus dominant negative).


Assuntos
Doença de Charcot-Marie-Tooth/genética , Doenças Desmielinizantes/genética , Neuropatia Hereditária Motora e Sensorial/genética , Proteína P0 da Mielina/genética , Adulto , Doença de Charcot-Marie-Tooth/diagnóstico , Clonagem Molecular , Estudos de Coortes , Cristalografia , Análise Mutacional de DNA , Doenças Desmielinizantes/congênito , Doenças Desmielinizantes/diagnóstico , Feminino , Genótipo , Neuropatia Hereditária Motora e Sensorial/diagnóstico , Humanos , Masculino , Microscopia Eletrônica , Proteína P0 da Mielina/química , Fenótipo , Mutação Puntual/fisiologia , Conformação Proteica , Nervo Sural/ultraestrutura
20.
Ecol Appl ; 17(7): 1911-28, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17974331

RESUMO

The proliferation of woody plants in grasslands over the past 100+ years can alter carbon, nitrogen, and water cycles and influence land surface-atmosphere interactions. Although the majority of organic carbon in these ecosystems resides belowground, there is no consensus on how this change in land cover has affected soil organic carbon (SOC) and total nitrogen (TN) pools. The degree to which duration of woody plant occupation, climate, and edaphic conditions have mediated SOC and TN responses to changes in life-form composition are poorly understood. We addressed these issues at a desert grassland site in Arizona, USA, where the leguminous shrub velvet mesquite (Prosopis velutina) has proliferated along an elevation/precipitation/temperature gradient and on contrasting soil morphologic surfaces. On sandy loam complexes of mid-Holocene origin, mean SOC and TN of soils in the grassland matrix increased approximately 68% and approximately 45%, respectively, with increasing elevation. Soil organic carbon pools were comparable and TN pools were approximately 23% higher in Pleistocene-aged clay loam complexes co-occurring with Holocene-aged soils at the upper elevation/climatic zone. Across the site, belowground resources associated with large Prosopis plants were 21-154% (SOC) and 18-127% (TN) higher than those in the grassy matrix. The variance in SOC and TN pools accounted for by Prosopis stem size (a rough surrogate for time of site occupation) was highest at the low- and mid-elevation sites (69-74%) and lowest at the upper elevation site (32-38%). Soil delta15N values ranged from 5.5 per thousand to 6.7 per thousand across the soil/elevation zones but were comparable in herbaceous and shrub-impacted soils and exhibited a weak relationship with Prosopis basal stem diameter (r2 < 0.1) and TN (r2 < 0.08). The SOC delta13C values decreased linearly with increasing Prosopis basal diameter, suggesting that size and isotopic composition of the SOC pool is a function of time of Prosopis site occupation. Isotopic mixture models indicate that encroachment of C3 woody plants has also promoted SOC additions from C4 plant sources, indicative of long-term herbaceous facilitation. Grassy sites in contrasting soil/elevation combinations, initially highly distinctive in their SOC pool size and delta13C, appear to be converging on similar values following approximately 100 years of woody plant proliferation.


Assuntos
Carbono/análise , Nitrogênio/análise , Poaceae , Prosopis , Solo/análise , Isótopos de Carbono/análise , Clima , Clima Desértico , Chuva , Temperatura
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