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1.
Clin Case Rep ; 10(8): e6165, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35937017

RESUMO

It is important to increase the awareness and knowledge of head and neck surgeons about the recent surge of craniofacial mucormycosis in COVID-19 patients because early diagnosis and appropriate treatment are essential to improve the outcomes. Here, we describe clinical features, treatment protocols, and outcomes of treatment in eight patients with COVID-19-associated mucormycosis in the maxilla. Consistent with the findings of previous studies, our experience in the management of these eight patients shows that early administration of amphotericin B and prompt aggressive surgery are essential for optimal control of the disease.

2.
Mar Pollut Bull ; 181: 113913, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35810648

RESUMO

Pollution characteristics and associated ecological risks of PAHs in sediments from Brunei Bay, Brunei were investigated. The concentrations of ∑16 PAHs ranged from 826.7 to 2955.3 µg kg-1, indicating moderate to high level of pollution. Source apportionment of PAHs by molecular isomeric ratios and positive matrix factorization model indicated impact of potential anthropogenic PAH sources including combustion of biomass and fossil fuels. The data indicated relatively no significant ecotoxicological risk for most of PAH compounds. To estimate the individual c-PAH toxicity, the toxic equivalent quantity (c-TEQ) was calculated. Results of the TEQ analysis showed that BaP followed by DBA and BaA are the most carcinogenic of PAHs examined in the study area. The evaluation of human health risk of PAHs revealed that the cancer risk of PAHs for adults and children was higher than the USEPA threshold (<1E-06) and lower than 1E-3, implying low to moderate risk.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Baías , Brunei , Criança , China , Ecossistema , Monitoramento Ambiental , Sedimentos Geológicos , Humanos , Hidrocarbonetos Policíclicos Aromáticos/análise , Medição de Risco , Poluentes Químicos da Água/análise
3.
BMC Musculoskelet Disord ; 23(1): 593, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35725431

RESUMO

BACKGROUND: It was aimed to investigate the musculoskeletal status in individuals diagnosed with skeletal discrepancies. METHODS: This case-control study was performed on 35 patients with developmental skeletal discrepancies listed for orthognathic surgery as a case group and 33 patients who were nominated for wisdom tooth removal as a control group. All participants were aged 18-40 years and the research was carried out in the period between May 2018 and May 2019. Dual X-ray absorptiometry (DEXA) was used to assess bone mass density at three bone sites: total hip, femoral neck, and the spinal lumbar vertebrae (L1-L4). The appendicular muscle mass index (ASMI) was measured based on the four limbs from the DEXA scan. RESULTS: Our data showed that 45.7% (16) of the case group were osteopenic or osteoporotic while in the control group only 21.2% (7) were osteopenic in at least one region (total hip, femoral neck, or lumbar) (p-value = 0.03). Regarding muscle mass, there was significantly lower SMI in subjects with skeletal discrepancies (case group) compared with the control group (median (IQR) 5.9 (2.5) vs. 6.8 (2.9) (kg/m2), respectively, p = 0.04). CONCLUSIONS: There is an essential need for more studies to understand the exact interrelationship between musculoskeletal status and skeletal jaw discrepancies.


Assuntos
Densidade Óssea , Colo do Fêmur , Absorciometria de Fóton , Adulto , Densidade Óssea/fisiologia , Estudos de Casos e Controles , Colo do Fêmur/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagem , Músculos
4.
Trop Anim Health Prod ; 54(1): 54, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35028725

RESUMO

The aim of this study was to evaluate the effects of dietary vitamin C supplementation on blood parameters of pre-parturient (PP) dairy cows and growth performance and immune system of their newborn calves. Forty PP cows (at approximately 21 days before calving and an average weight 791 ± 50 kg) were allocated into two experimental treatments: (1) basal diet without vitamin C supplementation (CO) and (2) basal diet with 20 g of vitamin C supplementation from 21 days before calving to parturition (VC). After parturition, the experiment continued by grouping the calves into four dietary treatments with 8 calves in each treatment. The experimental treatments were (1) control calves with no vitamin C supplementation and from cows that received no vitamin C supplement (CON), (2) calves supplemented with 600 mg of vitamin C per day and from cows that received no vitamin C supplement (CVC), (3) calves supplemented with no vitamin C and from cows that received 20 g of vitamin C per day (MVC), and (4) calves supplemented with 600 mg of vitamin C per day and from cows that received 20 g of vitamin C per day (CMVC). Serum concentrations of glucose, HDL and LDL, cholesterol, triglycerides, total protein, and albumin of cows were not affected by vitamin C supplementation during pre-parturient period. However, cows that received VC diet had lower (P < 0.05) malondialdehyde (MDA) and aspartate aminotransferase (AST) concentrations, higher total antioxidant capacity (TAC), and vitamin C concentration in their blood compared to CO cows. Vitamin C supplementation had no effect on plasma iron, copper, and zinc concentrations of PP cows. Similarly, vitamin C supplementation had no effect on total feed intake and feed conversion ratio (FCR) of suckling calves. However, calves in the CMVC group had higher (P < 0.05) overall daily weight gain compared to the other groups. Calves in the CVC and CMVC groups had lower (P < 0.05) blood MDA concentration on days 7 and 21. The highest (P < 0.05) blood TAC level was recorded in CMVC calves. Control group calves had lower (P < 0.05) blood superoxide dismutase activity compared to the other calves. Blood levels of alanine aminotransferase on days 7 and 21 and aspartate aminotransferase on day 7 were higher (P < 0.05) for calves in the CON and MVC groups. Based on the results, vitamin C supplementation had positive health effects on the oxidative parameters of PP dairy cows and also improved the performance and health status of the calves.


Assuntos
Cobre , Zinco , Ração Animal/análise , Animais , Ácido Ascórbico , Bovinos , Dieta/veterinária , Suplementos Nutricionais , Feminino , Ferro
5.
Clin Case Rep ; 9(11): e05037, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34786193

RESUMO

We describe a novel modified intranasal approach to minimize the complications of the impacted mesiodens surgical extraction. Also, it can be performed under local anesthesia with proper preoperative workup.

6.
J Environ Health Sci Eng ; 19(1): 107-120, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34150222

RESUMO

Kermanshah Province as an agricultural hub exports food crops to neighboring countries. In this study, contamination status, bioavailability, spatial distribution, and ecological and human health risk of arsenic and heavy metals (HMs) in soil were investigate. For this purpose, 121 agricultural soil samples were collected and analyzed using ICP-MS. The data were studied by calculating some geochemical indices, and using geographical information system and statistical analysis. Results showed that Cd has the highest bioavailability, following by Cu and As. Also, Cu was severely associated with organic matter. Enrichment factor (EF) followed the order of As > Cu > Pb > Se > Cd > Zn > Ni > Cr, and the soil pollution index (SPI) ranged from 0.82 to 2.65. Low potential ecological risk was measured for most of the samples. However, Kermanshah County and Eastern parts of the Province showed the highest HMs enrichment and ecological risk. Moreover, high carcinogenic risk of Cr and Ni threatens the children. Cr showed also high non-carcinogenic hazard index (HI) for children. Principal component analysis (PCA) indicated the anthropogenic origins for As, Cd, Cu, Pb, Se and Zn, while Cr and Ni originated mainly from a geogenic source. Furthermore, Kruskal-Wallis H test revealed that As, Cd, Cr, Cu, Ni, Pb, Se and Zn concentrations were significantly different (p < 0.05) between 16 Counties of the Kermanshah Province. Overall, the management of urban and industrial contamination sources is required to minimize the concentration of bioavailable portion of HMs and preventing residents of the area from being exposed to contaminants.

7.
Environ Geochem Health ; 40(2): 721-735, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28856501

RESUMO

Surface sediment samples were collected from intertidal zone of Asaluyeh, Persian Gulf, to investigate distribution, sources and health risk of sixteen polycyclic aromatic hydrocarbons (PAHs). Total PAH concentrations ranged from 1.8 to 81.2 µg kg-1 dry weight, which can be categorized as low level of pollution. Qualitative and quantitative assessments showed that PAHs originated from both petrogenic and pyrogenic sources with slight pyrogenic dominance. Source apportionment using principal component analysis indicated that the main sources of PAHs were fossil fuel combustion (33.59%), traffic-related PAHs (32.77%), biomass and coal combustion (18.54%) and petrogenic PAHs (9.31%). According to the results from the sediment quality guidelines, mean effects range-median quotient (M-ERM-Q) and benzo[a]pyrene toxic equivalents (BaPeq), low negative ecological risks related to PAH compounds would occur in the intertidal zone of Asaluyeh. The total benzo[a]pyrene (BaP) toxic equivalent quotient (TEQcarc) for carcinogenic compounds ranged from 0.01 to 7 µg kg-1-BaPeq, indicating low carcinogenic risk. The human health risk assessment of PAH compounds via ingestion and dermal pathways suggests low and moderate potential risk to human health, respectively.


Assuntos
Sedimentos Geológicos/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Saúde da População , Poluentes Químicos da Água/análise , Biomassa , Humanos , Oceano Índico , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Análise de Componente Principal , Medição de Risco
8.
Arch Environ Contam Toxicol ; 73(3): 474-487, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28497299

RESUMO

The distribution, sources, and human health risk assessment of polycyclic aromatic hydrocarbons (PAHs) in surface sediment and the edible tissue of short-neck clam (Paphia undulata) from mudflat ecosystem in the west coast of Malaysia were investigated. The concentrations of ∑16 PAHs varied from 347.05 to 6207.5 and 179.32 to 1657.5 ng g-1 in sediment and short-neck clam samples, respectively. The calculations of mean PEL quotients (mean-PELQs) showed that the ecological risk of PAHs in the sediment samples was low to moderate-high level, whereas the total health risk through ingestion and dermal contact was considerably high. The PAHs biota sediment accumulation factors data for short-neck clam were obtained in this study, indicating a preferential accumulation of lower molecular weight PAHs. The source apportionment of PAHs in sediment using positive matrix factorization model indicated that the highest contribution to the PAHs was from diesel emissions (30.38%) followed by oil and oil derivate and incomplete coal combustion (23.06%), vehicular emissions (16.43%), wood combustion (15.93%), and natural gas combustion (14.2%). A preliminary evaluation of human health risk using chronic daily intake, hazard index, benzo[a]pyrene-equivalent (BaPeq) concentration, and the incremental lifetime cancer risk indicated that PAHs in short-neck clam would induce potential carcinogenic effects in the consumers.


Assuntos
Bivalves/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise , Animais , Benzo(a)pireno/análise , Ecotoxicologia , Humanos , Malásia , Poluição por Petróleo , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Medição de Risco , Poluentes Químicos da Água/toxicidade
9.
J Craniofac Surg ; 27(6): e562-3, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27428905

RESUMO

INTRODUCTION: The frequency of mandible fractures is relatively less in children compared with adults, but their treatment is significantly more challenging due to the concerns regarding mandible growth and the developing dentition. The authors have introduced a new way of closed reduction by using external nasal splints. METHODS: In 3 patients aged between 4 and 6-year old with parasymphyseal and body fractures of mandible, fractures were reduced under general anesthesia and thermoplastic nasal splints were directly formed and trimmed to fit the lingual surface of mandible.Splints were fixed to mandible with circummandibular wiring and were retained in place for 3 weeks. RESULTS: All fractures healed uneventfully and the occlusion in all patients was satisfactory. All patients gained good masticatory efficiency. There was no need to use the intermaxillary fixation in any of the patients. CONCLUSION: Using thermoplastic external nasal splint for fracture stabilization in children is an easy, rapid, nonexpensive, and conservative way to treat mandible fractures in pediatric patients.


Assuntos
Tratamento Conservador/métodos , Fraturas Mandibulares/terapia , Ácidos Polimetacrílicos , Contenções , Criança , Pré-Escolar , Oclusão Dentária , Desenho de Equipamento , Humanos , Fraturas Mandibulares/diagnóstico , Nariz , Radiografia Panorâmica
10.
EMBO J ; 32(9): 1225-37, 2013 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-23481255

RESUMO

Adenosine diphosphate (ADP)-ribosylation is a post-translational protein modification implicated in the regulation of a range of cellular processes. A family of proteins that catalyse ADP-ribosylation reactions are the poly(ADP-ribose) (PAR) polymerases (PARPs). PARPs covalently attach an ADP-ribose nucleotide to target proteins and some PARP family members can subsequently add additional ADP-ribose units to generate a PAR chain. The hydrolysis of PAR chains is catalysed by PAR glycohydrolase (PARG). PARG is unable to cleave the mono(ADP-ribose) unit directly linked to the protein and although the enzymatic activity that catalyses this reaction has been detected in mammalian cell extracts, the protein(s) responsible remain unknown. Here, we report the homozygous mutation of the c6orf130 gene in patients with severe neurodegeneration, and identify C6orf130 as a PARP-interacting protein that removes mono(ADP-ribosyl)ation on glutamate amino acid residues in PARP-modified proteins. X-ray structures and biochemical analysis of C6orf130 suggest a mechanism of catalytic reversal involving a transient C6orf130 lysyl-(ADP-ribose) intermediate. Furthermore, depletion of C6orf130 protein in cells leads to proliferation and DNA repair defects. Collectively, our data suggest that C6orf130 enzymatic activity has a role in the turnover and recycling of protein ADP-ribosylation, and we have implicated the importance of this protein in supporting normal cellular function in humans.


Assuntos
Glicosídeo Hidrolases/fisiologia , Doenças Neurodegenerativas/enzimologia , Poli Adenosina Difosfato Ribose/fisiologia , Tioléster Hidrolases/fisiologia , Sequência de Aminoácidos , Sequência de Bases , Células Cultivadas , Criança , Pré-Escolar , Família , Feminino , Glicosídeo Hidrolases/genética , Células HEK293 , Células HeLa , Humanos , Masculino , Modelos Moleculares , Dados de Sequência Molecular , Doenças Neurodegenerativas/genética , Linhagem , Poli Adenosina Difosfato Ribose/genética , Processamento de Proteína Pós-Traducional/genética , Homologia de Sequência de Aminoácidos , Tioléster Hidrolases/genética
11.
J Craniofac Surg ; 24(1): e33-6, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23348329

RESUMO

A 33-year-old lady was referred to the Department of Oral and Maxillofacial Surgery of Taleghani hospital in 2008. She complained of firm swelling on the left side of her face with toothache, lacrimation, and nasal stiffness. There was a large mass in the left maxillary sinus with extension to the orbital floor, nasal bone, ethmoid sinus, and infratemporal fossa. The incisional biopsy revealed a neurofibroma of the maxilla. She underwent hemimaxillectomy and simultaneous reconstruction with temporalis-coronoid flap for orbital floor reconstruction. After 2 months' follow-up with no complication, she complained of left globe upward movement during gum chewing. The orbital and visual examinations were otherwise normal. This unusual complication has continued for 4 years with no resolution, although the patient does not worry about it any more.


Assuntos
Neoplasias Maxilares/cirurgia , Neurofibroma/cirurgia , Órbita/fisiopatologia , Órbita/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Complicações Pós-Operatórias/fisiopatologia , Retalhos Cirúrgicos , Adulto , Biópsia , Feminino , Humanos , Neoplasias Maxilares/patologia , Neurofibroma/diagnóstico , Órbita/patologia
12.
Gen Dent ; 60(5): 403-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23032227

RESUMO

This article presents a case involving a 16-year-old boy who came to the Tripler Army Medical Center Oral and Maxillofacial Surgery with a central giant cell granuloma (CGCG) on the anterior mandible. Initial management consisted of surgical curettage and intralesional injection of corticosteroids. Upon completion of steroid therapy, there was clinical and radiographic evidence of remission; however, radiographic evidence of lesion recurrence was seen at a six-month follow-up visit. The CGCG was retreated with curettage and five months of systemic injections of calcitonin, both of which failed. The lesion was most likely an aggressive form of CGCG that progressed despite conservative therapy, with destruction of hard and soft tissues, root resorption, tooth displacement, and paraesthesia in the anterior mandible. The authors present a treatment algorithm with comprehensive management involving surgical resection, reconstruction, orthodontics, and orthognathic surgery with prosthodontic considerations.


Assuntos
Corticosteroides/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Calcitonina/uso terapêutico , Granuloma de Células Gigantes/cirurgia , Mandíbula/cirurgia , Doenças Mandibulares/cirurgia , Osteotomia Mandibular/métodos , Adolescente , Terapia Combinada , Curetagem , Granuloma de Células Gigantes/tratamento farmacológico , Granuloma de Células Gigantes/patologia , Humanos , Masculino , Mandíbula/diagnóstico por imagem , Mandíbula/patologia , Doenças Mandibulares/tratamento farmacológico , Doenças Mandibulares/patologia , Radiografia , Procedimentos de Cirurgia Plástica , Recidiva
13.
Artigo em Inglês | MEDLINE | ID: mdl-23367153

RESUMO

In prostate brachytherapy procedures, combining high-resolution endorectal coil (ERC)-MRI with Computed Tomography (CT) images has shown to improve the diagnostic specificity for malignant tumors. Despite such advantage, there exists a major complication in fusion of the two imaging modalities due to the deformation of the prostate shape in ERC-MRI. Conventionally, nonlinear deformable registration techniques have been utilized to account for such deformation. In this work, we present a model-based technique for accounting for the deformation of the prostate gland in ERC-MR imaging, in which a unique deformation vector is estimated for every point within the prostate gland. Modes of deformation for every point in the prostate are statistically identified using a set of MR-based training set (with and without ERC-MRI). Deformation of the prostate from a deformed (ERC-MRI) to a non-deformed state in a different modality (CT) is then realized by first calculating partial deformation information for a limited number of points (such as surface points or anatomical landmarks) and then utilizing the calculated deformation from a subset of the points to determine the coefficient values for the modes of deformations provided by the statistical deformation model. Using a leave-one-out cross-validation, our results demonstrated a mean estimation error of 1mm for a MR-to-MR registration.


Assuntos
Imageamento por Ressonância Magnética/métodos , Próstata/anormalidades , Neoplasias da Próstata/patologia , Humanos , Masculino , Reto
14.
J Vet Sci ; 10(4): 337-41, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19934600

RESUMO

The objective of this retrospective field study was to associate the type and smell of discharge, the size of the uterus, the ovarian and treatment status, and the time to diagnosis of animals with chronic clinical endometritis (CCE) with the incidence of ovarian cysts and with a marked loss in body condition in German Holstein Friesian cows. Two hundred and sixty-four cows diagnosed with CCE from day 14 to day 42 postpartum participated in this study. In addition, 100 days milk production and the parity of the animals were included in the analysis. With the use of logistic regression, a purulent vaginal discharge (>/= 50% pus), the decision not to treat the animals for CCE and a high 100 days milk production proved to be significant factors for the incidence of ovarian cysts. Additionally, the type of discharge showed interactions with the parity and the smell of the discharge, as more animals with fetid and purulent discharge and more animals in the first lactation with a purulent discharge developed ovarian cysts. A high milk production and the parity showed associations with an excessive body condition score loss. Additionally, more animals with a diagnosis of an oversized uterus in comparison to cows with an early involution experienced a considerable reduction in their nutritional condition.


Assuntos
Doenças dos Bovinos/patologia , Endometrite/veterinária , Cistos Ovarianos/veterinária , Animais , Bovinos , Doença Crônica , Endometrite/complicações , Endometrite/patologia , Feminino , Lactação , Modelos Biológicos , Cistos Ovarianos/complicações , Cistos Ovarianos/patologia , Paridade , Gravidez , Estudos Retrospectivos , Fatores de Risco
15.
BMC Musculoskelet Disord ; 9: 158, 2008 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-19036153

RESUMO

BACKGROUND: Congenital muscular torticollis is the third most common congenital musculoskeletal anomaly after dislocation of the hip and clubfoot. When diagnosed early, it is obvious that it can be managed with good or excellent results. The aim of this prospective study was to determine the efficacy of surgery in neglected adult cases. METHODS: From January 2003 to June 2007, 18 adult skeletally matured patients were surgically treated for neglected congenital muscular torticollis and prospectively followed (at least one year). Bipolar release was performed in all patients. Radiography and the modified Lee's scoring system which included function and cosmesis, were used to measure the surgical results. Complications were also recorded. RESULTS: Four cases were lost during follow-up. Of the remaining 14 patients, 10 cases were males and 4 females. The age at operation ranged from 18 to 32 (average 21.9) years. The mean follow-up period was 2.5 years (range 1-5 years). Excellent results were noted in 7 patients, good in 5, and poor in 2 patients. Significant improvement (>10 degrees) of the cervico-thoracic scoliosis was noted only in 3 of 10 patients. CONCLUSION: Patients with congenital muscular torticollis can benefit from surgical treatment even in adulthood. Surgical bipolar sectioning of the sternocleidomastoid muscle should be considered even in adults with irreversible facial and skeletal deformities. The surgery restores the range of neck motion and resolves the head tilt; therefore it can improve the quality of life. This procedure is an effective and relatively complication-free method.


Assuntos
Músculos do Pescoço/cirurgia , Procedimentos Neurocirúrgicos/métodos , Procedimentos Neurocirúrgicos/normas , Torcicolo/cirurgia , Adulto , Feminino , Movimentos da Cabeça/fisiologia , Humanos , Masculino , Músculos do Pescoço/patologia , Músculos do Pescoço/fisiopatologia , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Satisfação do Paciente/estatística & dados numéricos , Seleção de Pacientes , Estudos Prospectivos , Qualidade de Vida , Amplitude de Movimento Articular/fisiologia , Recuperação de Função Fisiológica/fisiologia , Torcicolo/congênito , Torcicolo/fisiopatologia , Resultado do Tratamento
16.
Mech Ageing Dev ; 126(8): 855-65, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15992610

RESUMO

Patients with X-linked lymphoproliferative syndrome (XLP) experience excessive T cell proliferation after primary Epstein-Barr virus (EBV) infection, due to mutations in the signalling lymphocyte activation molecule (SLAM) associated protein (SAP) molecule. We examined the impact of dysfunctional proliferative control on the extent of CD8+ T cell differentiation in XLP patients who recovered from primary EBV infection. Although these young patients have normal numbers of lytic and latent EBV-epitope-specific CD8+ T cells, they were extremely differentiated as defined by loss of CCR7 and CD27, low telomerase activity and very short telomeres. This was not a direct effect arising from the loss of SAP, but was due to excessive T cell stimulation due to this defect. Thus, transduction of XLP CD8+ T cells with the catalytic component of telomerase (hTERT), but not SAP, prevented telomere loss and considerably extended proliferative lifespan in vitro. These results indicate that excessive proliferation in CD8+ T cells in XLP patients may lead to end-stage differentiation and loss of functional EBV-specific CD8+ T cells through replicative senescence. This may contribute to the defective immunity found in XLP patients who survive acute EBV infection who develop EBV-related B cell lymphomas before the fourth decade of life.


Assuntos
Linfócitos T CD8-Positivos/citologia , Transtornos Linfoproliferativos/genética , Telômero/ultraestrutura , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Proteínas de Ligação a DNA/química , Epitopos/química , Citometria de Fluxo , Vetores Genéticos , Proteínas de Fluorescência Verde/metabolismo , Humanos , Memória Imunológica , Lentivirus/genética , Longevidade , Linfoma de Células B/imunologia , Mutação , Fenótipo , Retroviridae/genética , Linfócitos T/química , Linfócitos T/citologia , Linfócitos T/metabolismo , Telomerase/química , Telômero/química , Fatores de Tempo
17.
Blood ; 103(10): 3821-7, 2004 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-14726378

RESUMO

Cytotoxic T cells (CTLs) and natural killer cells play a major role in the immune response to Epstein-Barr virus (EBV) infection. In X-linked lymphoproliferative (XLP) disease, a severe immunodeficiency, immunodysregulatory phenomena are observed following EBV infection, suggesting that defects exist in these effector populations. The gene defective in XLP is SAP (signaling lymphocytic activation molecule [SLAM]-associated protein), an adaptor protein that mediates signals through SLAM and other immunoglobulin superfamily receptors including 2B4. We generated EBV-specific T-cell lines from controls and XLP patients and examined CTL function in response to different stimuli. We show that XLP patients can generate EBV-T-cell lines that are phenotypically similar to those from controls. XLP patient EBV-T-cell lines showed a significant decrease in interferon-gamma (IFN-gamma) production in response to 2B4 and autologous EBV-transformed lymphoblastoid cell line (LCL) stimulation but not in response to SLAM. Furthermore, XLP EBV-T-cell lines demonstrated markedly decreased cytotoxic activity against autologous LCLs. By retroviral gene transfer of the SAP gene into XLP EBV-T-cell lines, we show reconstitution of IFN-gamma production and of cytotoxic activity confirming SAP-dependent defects. These studies demonstrate that in XLP the lack of SAP affects specific signaling pathways resulting in severe disruption of CTL function.


Assuntos
Proteínas de Transporte/imunologia , Peptídeos e Proteínas de Sinalização Intracelular , Transtornos Linfoproliferativos/imunologia , Linfócitos T Citotóxicos/imunologia , Antígenos CD , Proteínas de Transporte/genética , Estudos de Casos e Controles , Células Cultivadas , Glicoproteínas/imunologia , Herpesvirus Humano 4/imunologia , Humanos , Imunoglobulinas/imunologia , Interferon gama/biossíntese , Transtornos Linfoproliferativos/etiologia , Receptores de Superfície Celular , Transdução de Sinais , Proteína Associada à Molécula de Sinalização da Ativação Linfocitária , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária , Transdução Genética
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