RESUMEN
MicroRNAs are short non-coding RNAs that regulate gene expression by binding to, and suppressing the expression of genes. Research show that microRNAs have potential to be used as biomarkers for diagnosis, treatment response and can be used for therapeutic interventions. Furthermore, microRNA expression has effects on immune cell functions, which may lead to disease. Considering the important protective role of neutrophils and B-cells during M.tb infection, we evaluated the expression of microRNAs, known to alter function of these cells, in the context of human TB. We utilised real-time PCR to evaluate the levels of microRNA transcripts in the peripheral blood of TB cases and healthy controls. We found that neutrophil-associated miR-197-3p, miR-99b-5p and miR-191-5p transcript levels were significantly lower in TB cases. Additionally, B-cell-associated miR-320a, miR-204-5p, miR331-3p and other transcript levels were higher in TB cases. The miRNAs differentially expressed in neutrophils are predominantly implicated in signalling pathways leading to cytokine productions. Here, the decreased expression in TB cases may imply a lack of suppression on signalling pathways, which may lead to increased production of pro-inflammatory cytokines such as interferon-gamma. Furthermore, the miRNAs differentially expressed in B-cells are mostly involved in the induction/suppression of apoptosis. Further functional studies are however required to elucidate the significance and functional effects of changes in the expression of these microRNAs.
Asunto(s)
Linfocitos B/metabolismo , MicroARNs/genética , Neutrófilos/metabolismo , Tuberculosis/genética , Tuberculosis/inmunología , Linfocitos B/patología , Estudios de Casos y Controles , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Humanos , Masculino , Análisis por Micromatrices , Neutrófilos/patología , Tuberculosis/patologíaRESUMEN
Mycobacterium bovis infection, the cause of bovine tuberculosis (BTB), is endemic in wildlife in the Kruger National Park (KNP), South Africa. In lions, a high infection prevalence and BTB mortalities have been documented in the KNP; however, the ecological consequences of this disease are currently unknown. Sensitive assays for the detection of this infection in this species are therefore required. Blood from M. bovis-exposed, M. bovis-unexposed, M. tuberculosis-exposed and M. bovis-infected lions was incubated in QuantiFERON® -TB Gold (QFT) tubes containing either saline or ESAT-6/CFP-10 peptides. Using qPCR, selected reference genes were evaluated for expression stability in these samples and selected target genes were evaluated as markers of antigen-dependent immune activation. The abundance of monokine induced by gamma interferon (MIG/CXCL9) mRNA, measured in relation to that of YWHAZ, was used as a marker of ESAT-6/CFP-10 sensitization. The gene expression assay results were compared between lion groups, and lenient and stringent diagnostic cut-off values were calculated. This CXCL9 gene expression assay combines a highly specific stimulation platform with a sensitive diagnostic marker that allows for discrimination between M. bovis-infected and M. bovis-uninfected lions.
Asunto(s)
Leones/microbiología , Mycobacterium bovis/genética , Tuberculosis/veterinaria , Animales , Mycobacterium bovis/aislamiento & purificación , Prevalencia , Sudáfrica/epidemiología , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Tuberculosis/microbiologíaRESUMEN
New diagnostics and vaccines for tuberculosis (TB) are urgently needed, but require an understanding of the requirements for protection from/susceptibility to TB. Previous studies have used unbiased approaches to determine gene signatures in single-site populations. The present study utilized a targeted approach, reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA), to validate these genes in a multisite study. We analysed ex vivo whole blood RNA from a total of 523 participants across four sub-Saharan countries (Ethiopia, Malawi, South Africa, and The Gambia) with differences in TB and human immunodeficiency virus (HIV) status. We found a number of genes that were expressed at significantly lower levels in participants with active disease than in those with latent TB infection (LTBI), with restoration following successful TB treatment. The most consistent classifier of active disease was FCGR1A (high-affinity IgG Fc receptor 1 (CD64)), which was the only marker expressed at significantly higher levels in participants with active TB than in those with LTBI before treatment regardless of HIV status or genetic background. This is the first study to identify a biomarker for TB that is not affected by HIV status or geo-genetic differences. These data provide valuable clues for understanding TB pathogenesis, and also provide a proof-of-concept for the use of RT-MLPA in rapid and inexpensive validation of unbiased gene expression findings.
Asunto(s)
Biomarcadores/sangre , Expresión Génica , Receptores de IgG/sangre , Tuberculosis/diagnóstico , Adolescente , Adulto , África del Sur del Sahara , Sangre , Etnicidad , Femenino , Perfilación de la Expresión Génica , Infecciones por VIH/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
HIV-1 is a major health problem in South Africa with an average prevalence rate of 29.1% in pregnant women and between 4.9 and 6.1 million people infected. Using env gp120 V3 serotyping and genotyping techniques 410 patient samples were investigated. Most of the samples were obtained from different clinics in the greater Cape Town area of the Western Cape Province in South Africa. These included an academic hospital, state and private clinics, an informal settlement, sex worker cohorts, and the blood transfusion services. RNA was extracted from plasma samples followed by RT-PCR and sequencing of the env gp120 V3 region. Sequence fragments were assembled using Sequencher V4.7 and subsequently codon aligned. Distance calculation, tree construction methods, and bootstrap analysis were implemented using MEGA version 4.0. Viral load measurements indicated that HIV-1 RNA levels from 74 samples were below the assay detection limit. Three hundred thirty-six samples were used for env PCR and sequencing and 320 were assigned to subtypes. The majority of the sequences were subtyped as C (n = 285, 89.0%). Other subtypes detected were subtype A (n = 10, 3.1%); subtype B (n = 22, 6.8%); one each of subtypes F1, G, U, and a CH recombinant. Whether this diversity will have major implications for HIV-1 evolution and vaccine development in this region remains undetermined.
Asunto(s)
Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/aislamiento & purificación , Polimorfismo Genético , Adolescente , Adulto , Anciano , Niño , Preescolar , Análisis por Conglomerados , Femenino , Genotipo , Proteína gp120 de Envoltorio del VIH/genética , Proteína gp120 de Envoltorio del VIH/inmunología , VIH-1/genética , Humanos , Lactante , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Datos de Secuencia Molecular , Filogenia , Recombinación Genética , Análisis de Secuencia de ADN , Homología de Secuencia , Serotipificación , Sudáfrica , Carga Viral , Adulto JovenRESUMEN
The value of magnetic resonance imaging (MRI) in the early diagnosis of avascular necrosis (AVN) of the hip in SLE was investigated. Twenty females with severe SLE were studied prospectively. Each underwent 6-monthly X-rays, technetium -99m (Tc-99m) pyrophosphate bone scans and MRI of the hips over a 3-yr period. AVN was diagnosed in five hips of three patients (15%) during the study period. It was confirmed histologically in three hips of two patients who underwent core decompression. Radiological evidence of AVN was present in two patients at diagnosis. One patient developed progressive radiological changes despite core decompression. Bone scintigraphy was abnormal at some stage in all three patients with AVN however failed to detect the early ischaemic stage of AVN. MRI was the most reliable investigation and was able to detect asymptomatic AVN prior to the appearance of radiological or scintigraphic abnormalities.
Asunto(s)
Articulación de la Cadera , Lupus Eritematoso Sistémico/complicaciones , Imagen por Resonancia Magnética , Osteonecrosis/diagnóstico , Osteonecrosis/etiología , Adolescente , Adulto , Femenino , Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/patología , Articulación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/patología , Humanos , Osteonecrosis/diagnóstico por imagen , Estudios Prospectivos , Pirofosfato de Tecnecio Tc 99m , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
A prospective study was undertaken to compare the morphology of the pituitary gland by computed tomography (CT) and magnetic resonance imaging (MRI) in 27 consecutive patients. CT is an accepted imaging modality but this study suggested that MRI has certain advantages. MRI is proposed as the imaging modality of choice for lesions of the pituitary gland.
Asunto(s)
Imagen por Resonancia Magnética , Hipófisis/patología , Tomografía Computarizada por Rayos X , Femenino , Humanos , Masculino , Estudios ProspectivosRESUMEN
Pharmacokinetic drug interaction between methotrexate (MTX) and nonsteroidal anti-inflammatory drugs (NSAID) has been implicated in several case reports of MTX related toxicity. We therefore studied the kinetics of low dose (15 mg) oral MTX with and without concomitant NSAID therapy after preliminary determination of the systemic bioavailability of commercial tablets. Fourteen patients with rheumatoid arthritis, age range 44-77 years, participated in paired kinetic studies performed 1-4 weeks apart. The Abbott TDx fluorescence polarization immunoassay was used to measure serum levels and urinary excretion of MTX over 72 h after a single dose. The mean systemic bioavailability was 73% for the 15 mg oral dose. Area under the serum concentration versus time curve for a 50 mg oral dose was 1.1-2.7 times that of the 15 mg oral dose indicating dose dependent absorption. Mean kinetic variables after oral MTX did not differ significantly with and without NSAID therapy despite apparent interactions in individual patients. Renal clearance of MTX correlated with creatinine clearance (r = 0.8, p less than 0.01).
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Reumatoide/metabolismo , Metotrexato/farmacocinética , Adulto , Anciano , Artritis Reumatoide/tratamiento farmacológico , Disponibilidad Biológica , Creatinina/orina , Interacciones Farmacológicas , Quimioterapia Combinada , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Metotrexato/administración & dosificación , Metotrexato/metabolismo , Persona de Mediana EdadRESUMEN
Facilities for magnetic resonance imaging (MRI) have been available in South Africa since November 1985. This article summarizes our experience with this new imaging modality, illustrates normal anatomical features and pathological conditions in sagittal, coronal and axial planes, and compares MRI with computed tomography scans of the same regions.
Asunto(s)
Encefalopatías/diagnóstico , Espectroscopía de Resonancia Magnética , Encéfalo/anatomía & histología , Humanos , Enfermedades de la Médula Espinal/diagnóstico , Tomografía Computarizada por Rayos XRESUMEN
A case of calcified hydatid cyst of the pancreatic tail is presented. The ultrasonographic and computed tomographic features of the lesion suggested the presence of a cystadenoma or a calcified hydatid cyst. Computed tomography proved the most useful investigation and accurately localized the lesion. A distal pancreatectomy and splenectomy were performed because on the basis of the results of pre-operative investigations and macroscopic operative findings, carcinoma of the pancreatic tail could not be ruled out with certainty. The patient made an uneventful recovery.
Asunto(s)
Equinococosis/cirugía , Quiste Pancreático/cirugía , Anciano , Calcinosis , Equinococosis/diagnóstico por imagen , Femenino , Humanos , Quiste Pancreático/diagnóstico por imagen , Radiografía , UltrasonografíaRESUMEN
A case of intrathoracic lipoma in a child is presented. The diagnosis was made before operation by means of computer-assisted tomography, a non-interventional procedure.
Asunto(s)
Lipoma/diagnóstico por imagen , Neoplasias Torácicas/diagnóstico por imagen , Preescolar , Femenino , Humanos , Tomografía Computarizada por Rayos XRESUMEN
A right-sided rectus sheath haematoma developed during heparin therapy for deep vein thrombosis. Computed tomography of the abdomen provided accurate pre-operative images of the size and extent of the haematoma, and surgical evacuation thereof resulted in uneventful recovery.
Asunto(s)
Músculos Abdominales , Hematoma/inducido químicamente , Heparina/efectos adversos , Músculos Abdominales/efectos de los fármacos , Anciano , Femenino , HumanosRESUMEN
The 2 cases reported here indicate that on ultrasound examination uninfected simple and echinococcal cysts can sometimes show a pseudosolid internal consistency like that of a neoplasm, probably owing to floating crystals or particles. This has important implications as far as further diagnostic and therapeutic measures are concerned. The presence of a regular and well-defined rim remains an important clue to the possibly cystic nature of such lesions.
Asunto(s)
Quistes/diagnóstico , Equinococosis Hepática/diagnóstico , Enfermedades del Bazo/diagnóstico , Ultrasonografía , Adulto , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Oral cholecystography and ultrasonography of the gallbladder were performed in 190 patients with the aim of diagnosing gallstones. At surgery gallstones were found in 23 patients and a roundworm in 1 patient. The results obtained with the two methods are comparable. Since neither radiation nor contrast agents are employed in ultrasonography, it is suggested that this be regarded as the primary special examination in the diagnosis of gallstones.
Asunto(s)
Colecistografía , Colelitiasis/diagnóstico , Ultrasonografía , Colelitiasis/diagnóstico por imagen , HumanosRESUMEN
In a prospective 6 month study, sonographic diagnosis of biliary ascariasis was made in 12 patients: In five, the diagnosis was confirmed by other means, mainly intravenous cholangiography. In three, such confirmation was not sought, but all had proven intestinal infestation. One possible and three definite false-positive diagnoses were made. There were no established false-negative diagnoses. The echogenic, nonshadowing images of the worms were seen in the main bile duct and/or gallbladder as single strips (on one occasion with its digestive tract seen as an anechoic "inner tube"), as multiple strips giving a spaghettilike appearance, as coils, or as more amorphous fragments. Follow-up sonograms were obtained in six patients and showed expulsion of the worms by medical treatment.
Asunto(s)
Ascariasis/diagnóstico , Enfermedades de las Vías Biliares/diagnóstico , Ultrasonografía , Adolescente , Niño , Preescolar , Reacciones Falso Positivas , Humanos , Masculino , Estudios ProspectivosAsunto(s)
Encefalopatías/diagnóstico , Meningitis , Efusión Subdural , Ultrasonografía , Humanos , Lactante , MétodosRESUMEN
Carcinoid tumours are not common, but have been found along the digestive tract and at other sites in the body. The carcinoid syndrome is associated with some of these tumours. A case of gastric carcinoid, without the syndrome, is discussed, and a review of the biochemistry involved and the treatment is given.