RESUMEN
The ability to adapt to dynamic environments requires tracking multiple signals with variable sensory salience and fluctuating behavioral relevance. This complex process requires integrative crosstalk between sensory and cognitive brain circuits. Functional interactions between cortical and thalamic regions are now considered essential for both sensory perception and cognition but a clear account of the functional link between sensory and cognitive circuits is currently lacking. This review aims to document how thalamic nuclei may effectively act as a bridge allowing to fuse perceptual and cognitive events into meaningful experiences. After highlighting key aspects of thalamocortical circuits such as the classic first-order/higher-order dichotomy, we consider the role of the thalamic reticular nucleus from directed attention to cognition. We next summarize research relying on Pavlovian learning paradigms, showing that both first-order and higher-order thalamic nuclei contribute to associative learning. Finally, we propose that modulator inputs reaching all thalamic nuclei may be critical for integrative purposes when environmental signals are computed. Altogether, the thalamus appears as the bridge linking perception, cognition and possibly affect.
Asunto(s)
Cognición , Tálamo , Humanos , Aprendizaje , Vías Nerviosas , PercepciónRESUMEN
Various tumours can be resected even for cure with complete removal. Surgical excision with a wide margin to ensure complete removal has therefore been suggested as the primary treatment for such lesions. The histological examination of the three-dimensional (3D) excision margins (3D histology) constitutes an important part of the quality control mechanisms in tumour surgery. Understanding histologically relevant properties of the constituents of the microenvironment in tumours and the circumferential portion of non-lesional tissue is therefore critical. Accompanied by the increasing availability of high performance computers in recent decades, there has been a strong movement aiming at the development of mathematical models whose implementations allow in silico simulations of biological reaction networks. Due to its relevance in numerous biological and pathological processes, there have been various attempts to model biased migration of single cells. The model introduced in this paper plays a prominent role insofar as it covers the under-represented 3D case. Moreover, it is uniformly formulated for both two and three dimensions. The velocity of each cell is characterised by a generalised Langevin equation, a stochastic differential equation, where chemotaxis as well as contact guidance are considered to simulate selected aspects of interactions between carcinoma cell groups and fibroblast-like cells. Algorithmic and numeric aspects of the developed equations are detailed in this paper and the results of the simulations are illustrated in different manners to emphasise specific features. A simple test scenario as well as a geometry based on segmentation data of a real histological slide has served for verification of the software. The resulting morphologies closely resemble that of desmoplastic stromal reaction readily identifiable in histological slides of infiltrating carcinoma, and the images can be interpreted in the context of 3D histology.
Asunto(s)
Movimiento Celular/fisiología , Matriz Extracelular/patología , Fibroblastos/patología , Modelos Biológicos , Neoplasias/patología , Humanos , Análisis Numérico Asistido por Computador , Procesos EstocásticosRESUMEN
Virtual tissue can be generated by employing various methods. First steps en route to virtual tissue may encompass the generation of virtual cells. One such approach termed Quaoaring was applied to produce artificial erythrocytes and these were both discocyte and echinocyte in shape. The results were subsequently compared with data gleaned from scanning electron microscopy and atomic force microscopy. Quaoaring has, however, proved to be unsuccessful in creating convincing objects, particularly those which should be echinocytic in appearance.
Asunto(s)
Eritrocitos/patología , Microscopía de Fuerza Atómica , Microscopía Electrónica de Rastreo , Interfaz Usuario-Computador , Animales , Simulación por Computador , Humanos , Modelos Teóricos , Control de CalidadRESUMEN
In the present study, a semi-automatic segmentation and classification algorithm is proposed for the analysis of histological and cytological images. In view of the fact that histological and cytological images usually exhibit poor contrast and blurred outlines, classical segmentation algorithms often fail to detect relevant structures. A new algorithm for texture segmentation based on signal processing methods in combination with machine learning techniques was therefore developed.
Asunto(s)
Algoritmos , Inteligencia Artificial , Técnicas Citológicas , Técnicas Histológicas , Procesamiento de Imagen Asistido por Computador , Modelos Teóricos , Simulación por Computador , Tejido Conectivo/patología , Vasos Coronarios/patología , Humanos , Aumento de la Imagen , Imagenología Tridimensional , Reconocimiento de Normas Patrones Automatizadas , Túnica Íntima/patología , Túnica Media/patologíaRESUMEN
A mathematical model of collagen fiber mesh formation was created to evaluate the possible role of chemotaxis and haptotaxis in the histomorphology of a desmoplastic stromal reaction (DSR). Fibroblasts were mathematicaly interpreted as mobile discrete objects, characterized by their velocity and position, both dependent on time. This resulted in cell migration paths, commonly termed "trajectories" which are modulated as stochastic process. The implementation of chemotactic effects requires knowledge of the concentration and distribution of the appropriate chemical substance in the scenario. A simplistic model assumption allows the calculation of a numerical solution of the resulting diffusion equation. Adding haptotaxis necessitates the simulation of the extracellular matrix (ECM). The fiber distribution is modeled as a vector field which contains information on both, fiber density and direction. The production of new fibers is based on ordinary differential equations coupled with the migratory behavior of the cells. Filters help smooth the trajectories. Appropriate visualization allows a direct comparison of the simulation results with histomorphology. Matches between computed data and their real counterparts indicate that the development of mathematical models is appropriate to describe and forecast the course of DSR. This makes systems biology a stepping stone to improving biomedical research.
Asunto(s)
Carcinoma de Células Escamosas/patología , Movimiento Celular/fisiología , Quimiotaxis/fisiología , Colágeno/metabolismo , Simulación por Computador , Matriz Extracelular/patología , Fibroblastos/patología , Microfibrillas/patología , Modelos Teóricos , Células del Estroma/patología , Biología de Sistemas/métodos , Gráficos por Computador , Difusión , Neoplasias Faciales/patología , Neoplasias Faciales/cirugía , Humanos , Procesamiento de Imagen Asistido por Computador , Neoplasias Maxilomandibulares/patología , Neoplasias Maxilomandibulares/cirugía , Neoplasias de la Boca/patología , Neoplasias de la Boca/cirugíaRESUMEN
There are rare cases in which inhibitors of the angiotensin-converting enzyme can cause an angioneurotic edema of the upper aerodigestive tract. The pathomechanism of this side effect depends on an interaction of the drug with hormones regulating vascular permeability, such as the kallikrein kinin system and the prostaglandin system. Angioedema is characterized by subcutaneous or submucosal swellings, which usually affect the lips, soft palate, tongue and larynx. Pathomechanisms, differential diagnosis and treatment of ACE-inhibitor-induced edema of the upper aerodigestive tract are described in three case reports.
Asunto(s)
Angioedema/inducido químicamente , Angioedema/fisiopatología , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Angioedema/diagnóstico , Angioedema/terapia , Diagnóstico Diferencial , Enfermedades del Sistema Digestivo/inducido químicamente , Enfermedades del Sistema Digestivo/diagnóstico , Enfermedades del Sistema Digestivo/fisiopatología , Enfermedades del Sistema Digestivo/terapia , Epiglotis , Humanos , Labio , Masculino , Persona de Mediana Edad , Faringe , Enfermedades Respiratorias/inducido químicamente , Enfermedades Respiratorias/diagnóstico , Enfermedades Respiratorias/fisiopatología , Enfermedades Respiratorias/terapia , LenguaRESUMEN
Maternal and cord blood samples of 290 pregnant women in the eastern part of Germany with a mean age of 28 years (16-41 years) were analyzed for antibodies to vaccine-preventable diseases. Both mothers and infants had detectable levels of antibodies to mumps in 96% and to tetanus in 93% of cases. Detectable levels to poliomyelitis, diphtheria, measles and rubella varied from 55% to 91%. Cord blood samples had a significantly higher prevalence of antibodies to pertussis (61%) and diphtheria (81%) in comparison to maternal samples (pertussis 37%, diphtheria 70%) as well as significantly enhanced antibody concentrations to diphtheria. In conclusion, the prevalence of antibodies to pertussis (61%), diphtheria (81 %), poliomyelitis (55-59%) and measles (85%) is suggested to be insufficient in newborn infants to protect them against these infectious diseases.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Anticuerpos Antivirales/sangre , Sangre Fetal/inmunología , Embarazo/inmunología , Adolescente , Adulto , Femenino , Alemania , Edad Gestacional , Humanos , Recién Nacido , Sarampión/inmunología , Paperas/inmunología , Rubéola (Sarampión Alemán)/inmunología , Estudios Seroepidemiológicos , Tétanos/inmunología , VacunaciónRESUMEN
Possible genotoxic effects exerted by three widely used pesticides, permethrin, N,N-diethyl-m-toluamide (DEET) and diazinon, in primary human nasal mucosal cells were investigated. Primary nasal mucosa cells were prepared from tissue biopsies taken from 21 patients who underwent nasal surgery. Cells were exposed to 0.5-1.0 mM concentrations of permethrin, DEET and diazinon for 60 min. Genotoxic effects were detected by the alkaline microgel electrophoresis assay ("comet assay"). Within the concentration range, no significant cytotoxic effects were observed, but all three tested pesticides showed a significant genotoxic response that was concentration dependent. More pronounced genotoxic effects were observed in mucosal cells from the middle turbinate than in the inferior turbinate. The results provide some evidence for the potential carcinogenicity of these agents to human nasal mucosal cells. This should be further investigated.
Asunto(s)
DEET/metabolismo , DEET/toxicidad , Diazinón/metabolismo , Diazinón/toxicidad , Repelentes de Insectos/metabolismo , Repelentes de Insectos/toxicidad , Insecticidas/metabolismo , Insecticidas/toxicidad , Mucosa Nasal/efectos de los fármacos , Permetrina/metabolismo , Permetrina/toxicidad , Adulto , Células Cultivadas , Aductos de ADN/metabolismo , Aductos de ADN/toxicidad , Femenino , Humanos , Masculino , Mutágenos/metabolismo , Mutágenos/toxicidadRESUMEN
Clinical studies have suggested a causal or contributory role of Chlamydia pneumoniae infection in asthma and atherosclerosis. The activation of synthetic functions of smooth muscle cells (SMC) including the production of cytokines and growth factors plays a major role in the formation of fibrous atherosclerotic plaques as well as in structural remodelling of the airway wall in chronic asthma. In this study we demonstrated that C. pneumoniae induced the production of low levels of interferon (IFN)-beta in bronchial and vascular SMC when infected cells were treated with tumour necrosis factor-alpha (TNF-alpha). IFN-beta production was analysed by reverse transcription-PCR and enzyme-linked immunosorbent assay. The upregulation of IFN-beta was paralleled by an increase in mRNA levels of interferon regulatory factor-1 and interferon-stimulated gene factor 3gamma, two transcription factors activating the expression of the IFN-beta gene. In addition, C. pneumoniae infection enhanced the mRNA level of indoleamine 2,3-dioxygenase, an IFN-inducible factor mediating the restriction of intracellular chlamydial growth, in TNF-alpha-stimulated SMC. C. pneumoniae-induced IFN-beta production by SMC may modulate inflammation and tissue remodelling during respiratory and vascular infection.
Asunto(s)
Infecciones por Chlamydia/microbiología , Chlamydophila pneumoniae/inmunología , Interferón beta/biosíntesis , Músculo Liso/microbiología , Bronquios/citología , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica , Humanos , Factor 1 Regulador del Interferón , Factor 3 de Genes Estimulados por el Interferón , Subunidad gamma del Factor 3 de Genes Estimulados por el Interferón , Interferón beta/genética , Músculo Liso/inmunología , Músculo Liso Vascular/citología , Fosfoproteínas/metabolismo , Factores de Transcripción/metabolismoRESUMEN
OBJECTIVE: Reactive arthritis (ReA) triggered by Chlamydia trachomatis or enteric bacteria such as yersinia, salmonella, Campylobacter jejuni, or shigella is an important differential diagnosis in patients presenting with the clinical picture of an undifferentiated oligoarthritis (UOA). This study was undertaken to evaluate the best diagnostic approach. PATIENTS AND METHODS: 52 patients with ReA, defined by arthritis and a symptomatic preceding infection of the gut or the urogenital tract, and 74 patients with possible ReA, defined by oligoarthritis without a preceding symptomatic infection and after exclusion of other diagnoses (UOA), were studied. The following diagnostic tests were applied for the identification of the triggering bacterium: for yersinia induced ReA-stool culture, enzyme immunoassay (EIA), and Widal's agglutination test for detection of antibodies to yersinia; for salmonella or campylobacter induced ReA-stool culture, EIA for the detection of antibodies to salmonella and Campylobacter jejuni; for infections with shigella-stool culture; for infections with Chlamydia trachomatis-culture of the urogenital tract, microimmunofluorescence and immunoperoxidase assay for the detection of antibodies to Chlamydia trachomatis. RESULTS: A causative pathogen was identified in 29/52 (56%) of all patients with ReA. In 17 (52%) of the patients with enteric ReA one of the enteric bacteria was identified: salmonella in 11/33 (33%) and yersinia in 6/33 (18%). Chlamydia trachomatis was the causative pathogen in 12/19 (63%) of the patients with urogenic ReA. In patients with the clinical picture of UOA a specific triggering bacterium was also identified in 35/74 (47%) patients: yersinia in 14/74 (19%), salmonella in 9/74 (12%), and Chlamydia trachomatis in 12/74 (16%). CONCLUSIONS: Chlamydia trachomatis, yersinia, and salmonella can be identified as the causative pathogen in about 50% of patients with probable or possible ReA if the appropriate tests are used.
Asunto(s)
Artritis Reactiva/diagnóstico , Infecciones por Campylobacter/diagnóstico , Infecciones por Chlamydia/diagnóstico , Disentería Bacilar/diagnóstico , Infecciones por Salmonella/diagnóstico , Yersiniosis/diagnóstico , Adolescente , Adulto , Anciano , Pruebas de Aglutinación , Artritis Reactiva/microbiología , Campylobacter jejuni/aislamiento & purificación , Chlamydia trachomatis/aislamiento & purificación , Enteritis/diagnóstico , Enteritis/microbiología , Ensayo de Inmunoadsorción Enzimática , Heces/microbiología , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prohibitinas , Sensibilidad y Especificidad , Uretritis/diagnóstico , Uretritis/microbiología , Cervicitis Uterina/diagnóstico , Cervicitis Uterina/microbiologíaRESUMEN
The effects of two oral contraceptive combinations, dienogest 2.0 mg plus ethinyl estradiol 0.03 mg (Valette) and desogestrel 0.15 mg plus ethinyl estradiol 0.02 mg (Lovelle), on the human immune system were compared over one treatment cycle of 31 patients (n = 15 and n = 16, respectively). Lovelle but not Valette significantly increased the numbers of lymphocytes, monocytes and granulocytes. Valette decreased CD4 lymphocytes after 10 days' treatment; Lovelle had the opposite effect. Lovelle increased CD19 and CD23 after 21 days' treatment. Phagocytic activity was unaffected by either treatment. After 10 days' treatment, both contraceptives reduced serum IgA, IgG and IgM, which remained lowered at day 21 with Lovelle but returned to baseline with Valette. Secretory IgA was unaffected by either contraceptive. Neither treatment affected levels of interleukins, except for a significant difference between the treatment groups for interleukin-6 after 10 days' treatment that disappeared after 21 days' treatment. Levels of non-immunoglobulin serum components fluctuated; macroglobulin was increased with Valette. However, total protein and albumin levels were reduced more with Lovelle than with Valette. Complement factors also fluctuated. There was no evidence for any sustained immunosuppression with either Valette or Lovelle.
Asunto(s)
Anticonceptivos Orales/efectos adversos , Desogestrel/efectos adversos , Inmunidad/efectos de los fármacos , Nandrolona/análogos & derivados , Adolescente , Adulto , Recuento de Linfocito CD4 , Desogestrel/administración & dosificación , Femenino , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Interleucina-6/sangre , Recuento de Leucocitos , Ciclo Menstrual , Nandrolona/administración & dosificación , Nandrolona/efectos adversosRESUMEN
Chlamydia pneumoniae infection has been associated with asthma and atherosclerosis. Smooth muscle cells represent host cells for chlamydiae during chronic infection. In this study we demonstrated that C. pneumoniae infection of human smooth muscle cells in vitro increased production of interleukin 6 (IL-6) and basic fibroblast growth factor (bFGF) as shown by reverse transcription-PCR, immunoblotting, and enzyme-linked immunosorbent assay. In contrast, levels of platelet-derived growth factor A-chain mRNA were not affected after infection. The stimulation of bFGF and IL-6 production was most effective when viable chlamydiae were used as inoculum. Furthermore, inhibition of bacterial protein synthesis with chloramphenicol prevented up-regulation of IL-6 and bFGF in infected cells. Addition of IL-6 antibody to infected cultures diminished bFGF expression, indicating involvement of produced IL-6. These findings suggest that chlamydial infection of smooth muscle cells elicits a cytokine response that may contribute to structural remodeling of the airway wall in chronic asthma and to fibrous plaque formation in atherosclerosis.
Asunto(s)
Chlamydophila pneumoniae/inmunología , Factor 2 de Crecimiento de Fibroblastos/biosíntesis , Interleucina-6/biosíntesis , Músculo Liso/microbiología , Arteriosclerosis/etiología , Asma/etiología , Bronquios/citología , Chlamydia trachomatis/inmunología , Inmunoensayo , Factor de Crecimiento Derivado de Plaquetas/biosíntesis , Especificidad de la EspecieRESUMEN
Besides group A (GAS), Lancefield group C beta-haemolytic streptococci (GCS) have been implicated as a causative agent in outbreaks of purulent pharyngitis. In this study we have investigated a class CI M protein of a Streptococcus dysgalactiae1:256, revealed that 26% of these sera showed serological cross-reactivity between a 68-kDa cartilage protein and the N-terminal part of MC. Only 8% of the sera of healthy patients showed this property. In additional, MC also cross-reacted with antibodies recognising epidermal keratins. The cross-reacting 68-kDa protein from cartilage was different from human serum albumin, but was recognised with anti-vimentin immune serum. The MC was cloned and the gene sequenced. By using PCR, recombinant gene fragments encoding characteristic peptide fragments of MC were expressed in Escherichia coli. The peptides were used to map the binding sites for plasma proteins and to locate the cross-reacting epitopes on the MC molecule. In consequence, sequence alignments revealed that MC shared homologous regions with vimentin and different keratins. Our data, obtained with MC, suggest that not only infections with GAS but also infections with GCS and possibly GGS (the latter species can also produce class CI M-like proteins) may be responsible for the formation of streptococcal-associated sequel diseases.
Asunto(s)
Antígenos Bacterianos , Proteínas de la Membrana Bacteriana Externa , Proteínas Bacterianas/metabolismo , Proteínas Sanguíneas/metabolismo , Proteínas Portadoras/metabolismo , Cartílago/metabolismo , Queratinas/metabolismo , Streptococcus/química , Heridas y Lesiones/microbiología , Secuencia de Aminoácidos , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/inmunología , Western Blotting , Proteínas Portadoras/genética , Proteínas Portadoras/inmunología , Cartílago/química , Cartílago/inmunología , Embrión de Pollo , Reacciones Cruzadas , Electroforesis en Gel de Poliacrilamida , Epítopos/inmunología , Epítopos/metabolismo , Humanos , Sueros Inmunes/inmunología , Sueros Inmunes/farmacología , Queratinas/química , Queratinas/inmunología , Datos de Secuencia Molecular , Fagocitosis , Unión Proteica , Conejos , Homología de Secuencia de Aminoácido , Infecciones Estreptocócicas/microbiología , Streptococcus/aislamiento & purificación , Streptococcus/patogenicidad , Virulencia/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate the effect of long-term antibiotic treatment in patients with reactive arthritis (ReA) and undifferentiated oligoarthritis. METHODS: One hundred twenty-six patients were treated with ciprofloxacin (500 mg twice a day) or placebo for 3 months, in a double-blind, randomized study. Of these patients, 104 (48 treated with ciprofloxacin and 56 treated with placebo) were valid for clinical evaluation: 55 were diagnosed as having ReA with a preceding symptomatic urogenic or enteric infection and 49 as having undifferentiated oligoarthritis. These 2 groups were randomized separately. The triggering bacterium was sought by serology and/or culture. The percentage of patients in remission after 3 months of treatment was chosen as the primary efficacy parameter. RESULTS: A triggering bacterium could be identified in 52 patients (50%): Chlamydia trachomatis in 13, Yersinia in 14, and Salmonella in 25. No patient was positive for Campylobacter jejuni or for Shigella. No difference in outcome was found between treatment with ciprofloxacin or placebo in the whole group or in subgroups of patients with ReA or undifferentiated oligoarthritis. No difference was seen in patients with a disease duration <3 months. Ciprofloxacin was not effective in Yersinia- or Salmonella-induced arthritis but seemed to be better than placebo in Chlamydia-induced arthritis. This difference was not significant, however, which might be due to the small sample size. CONCLUSION: Long-term treatment of ReA with ciprofloxacin is not effective; however, it might be useful in the subgroup of patients who have Chlamydia-induced arthritis. This has to be proven in a bigger study focusing on patients with Chlamydia-induced arthritis.
Asunto(s)
Antiinfecciosos/uso terapéutico , Artritis Reactiva/tratamiento farmacológico , Infecciones por Chlamydia/tratamiento farmacológico , Ciprofloxacina/uso terapéutico , Adulto , Anciano , Antiinfecciosos/farmacocinética , Chlamydia trachomatis , Ciprofloxacina/efectos adversos , Ciprofloxacina/farmacocinética , Método Doble Ciego , Humanos , Persona de Mediana Edad , Placebos , Prohibitinas , Infecciones por Salmonella/tratamiento farmacológico , Equivalencia Terapéutica , Factores de Tiempo , Yersiniosis/tratamiento farmacológicoRESUMEN
Synovial fibroblasts probably represent host cells for Chlamydia trachomatis during initial intra-articular infection in reactive arthritis. In vitro synovial cells produce interferon-beta (IFN-beta) in response to chlamydial infection. IFN-beta expression can be activated by interferon regulatory factor-1 (IRF-1) and interferon-stimulated gene factor 3gamma (ISGF3gamma). In this study, we demonstrate that infection of synovial fibroblasts with C. trachomatis serotype D induced the expression of IRF-1 mRNA as shown by reverse transcription-PCR. Tumor necrosis factor-alpha (TNF-alpha) stimulation enhanced IRF-1 mRNA levels in infected cells and was required to detect IRF-1 protein by immunoblotting. The level of constitutively expressed IRF-2 was not significantly affected after infection. C. trachomatis was found to cause an up-regulation of ISGF3gamma protein in synovial cells. Induction of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) is an important mechanism of the host cell response to control intracellular infection by chlamydiae. It has been described that IRF-1 can induce IDO gene expression. Infection of synovial fibroblasts alone in the absence of exogenous cytokine induced the expression of IDO mRNA which was enhanced by TNF-alpha treatment. The stimulation of IRF-1, ISGF3gamma, and IDO expression was most effective when viable chlamydiae were used as inoculum. Neutralization of IFN-beta in the culture medium of infected cells diminished but did not abrogate expression of IRF-1, ISGF3gamma, and IDO. The increased production of IRF-1 and ISGF3gamma in C. trachomatis-infected synovial fibroblasts may contribute to induction of IFN-beta and IDO.
Asunto(s)
Chlamydia trachomatis/crecimiento & desarrollo , Proteínas de Unión al ADN/biosíntesis , Fibroblastos/microbiología , Fosfoproteínas/biosíntesis , Membrana Sinovial/citología , Triptófano Oxigenasa/biosíntesis , Anticuerpos/inmunología , Proteínas Bacterianas/biosíntesis , Células Cultivadas , Chlamydia trachomatis/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Immunoblotting , Indolamina-Pirrol 2,3,-Dioxigenasa , Factor 1 Regulador del Interferón , Interferón beta/inmunología , Interferón beta/fisiología , Fagocitosis , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Triptófano/farmacología , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
OBJECTIVE: The correlation between human papillomavirus (HPV) and Chlamydia, trachomatis infections was evaluated in 144 patients with normal cytology or with atypical squamous cells of undetermined significance (ASCUS). METHODS: Cervical samples were analysed using polymerase chain reaction (PCR) and non-radioactive Southern blot analysis. Specificity and sensitivity of two C. trachomatis PCR systems: major outer membrane protein (MOMP)-PCR and plasmid-PCR were determined. Southern blot hybridization of the PCR amplicons was done using 5' and 3' biotinylated oligonucleotide probes. RESULTS: All cervical samples were tested by the plasmid-PCR due to a 10 times higher sensitivity compared to the MOMP-PCR. To determine the specificity of our C. trachomatis primer sets different bacteria and viruses which can cause urogenital infections were analysed. Comparison of the probes revealed an increased sensitivity of the 5' and 3' double-biotinylated probe vs. the 5' biotinylated probe. The infection rate of C. trachomatis in cervical samples of HPV-positive patients was 10.3% (three out of 29) vs. 1.7% (two out of 115; P< or =0.05) in HPV-negative patients. In patients HPV-X (unsequenced HPV-types) positive the rate was 14.3% (one out of seven) vs. 2.9% (four out of 137: P = 0.2) in HPV-X negative patients. In high risk (HR) HPV-positive cervical samples the infection rate was 9.1% (two out of 22) vs. 2.5% (three out of 122; P = 0.14) in HR HPV-negative samples. Chlamydia trachomatis frequency of patients with cytological changes (ASCUS) was 27.3% (three out of 11) vs. 1.5% (two out of 1 33) in patients with normal cytology (P = 0.003). The highest prevalence rate of C. trachomatis-positive cervical samples (50%; one out of two) was found in HR HPV-positive patients with cytological changes (ASCUS) vs. 5% (one out of 20) in HR HPV-positive patients with normal cytology (P = 0.17). Patients negative for HPV and positive for ASCIIS have a C. trachomatis rate of 22.2% (two out of nine) vs. HPV-negative patients with normal cytology (none out of 106; P = 0.006) and vs. HR HPV-negative patients with normal cytology (0.9%; one out of 113; P = 0.014). CONCLUSIONS: There appears to be a correlation between cervical HPV and cervical C. trachomatis infections. The prevalence rate of C. trachomatis was significantly higher in patients with abnormal cytology (ASCUS) vs. normal cytology.
Asunto(s)
Cuello del Útero/microbiología , Cuello del Útero/virología , Chlamydia trachomatis/aislamiento & purificación , ADN Bacteriano/aislamiento & purificación , Southern Blotting , Infecciones por Chlamydia/complicaciones , Infecciones por Chlamydia/diagnóstico , Sondas de ADN , ADN Viral/aislamiento & purificación , Electroforesis en Gel de Agar , Femenino , Humanos , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Infecciones Tumorales por Virus/genética , Frotis Vaginal/métodosRESUMEN
OBJECTIVE: Since Chlamydia-induced reactive arthritis is associated with the presence of viable chlamydiae in the synovial membrane, we studied the ability of Chlamydia trachomatis to stimulate a cytokine response by fibroblast-like synoviocytes in culture. METHODS: Fibroblast-like cells derived from biopsies of the synovial membrane were infected with Chlamydia trachomatis serotype E. Interleukin-6 (IL-6), transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) were determined using bio-assays. Granulocyte macrophage colony stimulating factor (GMCSF) was quantified by ELISA. RESULTS: Fibroblast-like synovial cells were capable of supporting chlamydial growth in vitro. Chlamydia trachomatis stimulated synoviocytes to produce IL-6, TGF-beta, and GMCSF. IL-1beta increased the production of IL-6 and GMCSF by mock-infected and infected cells. Treatment of synoviocytes with interferon-gamma resulted in the release of TNF-alpha in response to chlamydial infection. CONCLUSION: Chlamydia-induced cytokine release from synovial fibroblasts may contribute to alterations in the synovial membrane promoting the development of joint inflammation.
Asunto(s)
Infecciones por Chlamydia/metabolismo , Infecciones por Chlamydia/patología , Chlamydia trachomatis , Citocinas/metabolismo , Membrana Sinovial/metabolismo , Membrana Sinovial/patología , Bacterias , Bioensayo , Células Cultivadas , Chlamydia trachomatis/crecimiento & desarrollo , Ensayo de Inmunoadsorción Enzimática , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/microbiología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Humanos , Interferón gamma/farmacología , Interleucina-6/metabolismo , Membrana Sinovial/efectos de los fármacos , Membrana Sinovial/microbiología , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Infection of fibroblast-like synovial cells with Chlamydia trachomatis (serotype D strain IC Cal 8) in culture induced the secretion of beta interferon (IFN-beta). Chlamydial infection inhibited IFN-gamma-induced expression of HLA-DR antigen in the cells. Addition of IFN-beta antibody directly to infected cultures mitigated HLA-DR inhibition, suggesting involvement of produced IFN-beta.
Asunto(s)
Chlamydia trachomatis/fisiología , Fibroblastos/metabolismo , Antígenos HLA-DR/biosíntesis , Interferón beta/metabolismo , Interferón gamma/fisiología , Células Cultivadas , Fibroblastos/microbiología , Humanos , Interferón gamma/antagonistas & inhibidores , Membrana Sinovial/citologíaRESUMEN
BACKGROUND: Chlamydia trachomatis is associated with Reiter's syndrome and reactive arthritis but the form in which the organism survives in synovial cells is unclear. AIM: To compare in situ hybridisation with direct fluorescence in the detection of inapparent chlamydial infection in synovial tissue. METHODS: Synovial tissue from four patients with reactive arthritis patients was examined using biotin labelled probes for chlamydial DNA and fluorescein isothiocyanate (FITC) labelled monoclonal antibodies against the major outer membrane protein. RESULTS: In two of the four patients, evidence of chlamydial infections was detected by in situ hybridisation in parallel sections but not with FITC labelled monoclonal antibodies. CONCLUSIONS: Detection of chlamydial DNA by in situ DNA hybridisation may be a better way to identify chlamydial infection in synovial tissue than phenotype targeting with FITC conjugated antibodies, which is used as a standard procedure for screening clinical specimens for chlamydia.