RESUMEN
Previous studies have associated activating Killer cell Immunoglobulin-like Receptor (KIR) genes with protection from cytomegalovirus (CMV) replication after organ transplantation. Whether KIR-associated protection is operating in the context of primary infection, re-activation, or both, remains unknown. Here we correlated KIR genotype and CMV serostatus at the time of transplantation with rates of CMV viremia in 517 heart (n=57), kidney (n=223), liver (n=165) or lung (n=72) allograft recipients reported to the Swiss Transplant Cohort Study. Across the entire cohort we found B haplotypes-which in contrast to A haplotypes may contain multiple activating KIR genes-to be protective in the most immunosuppressed patients (receiving anti-thymocyte globulin induction and intensive maintenance immunosuppression) (hazard ratio after adjustment for covariates 0.46, 95% confidence interval 0.29-0.75, P=0.002). Notably, a significant protection was detected only in recipients who were CMV-seropositive at the time of transplantation (HR 0.45, 95% CI 0.26-0.77, P=0.004), but not in CMV seronegative recipients (HR 0.59, 95% CI 0.22-1.53, P=0.28). These data indicate a prominent role for KIR-and presumably natural killer (NK) cells-in the control of CMV replication in CMV seropositive organ transplant recipients treated with intense immunosuppression.
Asunto(s)
Infecciones por Citomegalovirus/genética , Trasplante de Órganos , Receptores KIR/genética , Adolescente , Adulto , Anciano , Niño , Citomegalovirus/fisiología , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/inmunología , Femenino , Haplotipos , Humanos , Inmunidad Innata , Huésped Inmunocomprometido , Lactante , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Viremia/etiología , Viremia/genética , Viremia/inmunología , Replicación ViralRESUMEN
The pathophysiology of drug allergy is complex and relies on the interaction between the drug and the immune system in combination with environmental factors, in particular viruses. Genetic predisposition plays an important role in drug allergy. Recent publications have shown the importance of HLA genes, particularly in the delayed hypersensitivity reactions. In fact, particular HLA alleles were identified as risk factors in the development of severe allergic reactions to certain drugs, identifying people at risk of hypersensitivity before initiation of specific treatment. In the future, identification of other alleles in HLA genes will improve patients care by preventing hypersensitivity reactions associated with significant morbidity and mortality.
Asunto(s)
Hipersensibilidad a las Drogas/genética , Antígenos HLA/genética , Hipersensibilidad Tardía/inducido químicamente , Alelos , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/inmunología , Predisposición Genética a la Enfermedad , Humanos , Hipersensibilidad Tardía/genética , Hipersensibilidad Tardía/inmunología , Factores de RiesgoRESUMEN
Long-term insulin independence after islets of Langerhans transplantation is rarely achieved. The aims of this study were to identify the histological and immunological features of islets transplanted in a type 1 diabetic patient who died of a cerebral hemorrhage after >13 years insulin independence. Islets were pooled from two donors with respectively one and five HLA mismatches. Insulin-positive islets were found throughout the right and left liver, and absent in the pancreas. Two- and three-dimensional analysis showed that islets lost their initial rounded and compact morphology, had a mean diameter of 136 µm and were constituted of an unfolded epithelial band of 39.1 µm. Leukocyte phenotyping showed no evidence of a tolerogenic environment in the islet-containing portal spaces. Finally, HLA typing of microdissected islets showed HLA from the best matched donor in all 23 microdissection samples, compared to 1/23 for the least matched donor. This case report demonstrates that allogeneic islets can survive over 13 years while maintaining insulin independence. Allogeneic islets had unique morphologic features and implanted in the liver regardless of their size. Finally, our results suggest that, in this case, rejection had been prevalent over autoimmunity, although this hypothesis warrants further investigation.
Asunto(s)
Diabetes Mellitus Tipo 1/terapia , Insulina/uso terapéutico , Trasplante de Islotes Pancreáticos/métodos , Adulto , Autoinmunidad , Femenino , Antígenos HLA/química , Cadenas HLA-DRB1/genética , Humanos , Sistema Inmunológico , Células Secretoras de Insulina/citología , Trasplante de Riñón/métodos , Leucocitos/citología , Hígado/patología , Microscopía Fluorescente , Páncreas/patología , Fenotipo , Reacción en Cadena de la Polimerasa , Resultado del TratamientoRESUMEN
This paper describes the development of a polyimide-based MEMS strain-sensing device. Finite element analysis was used to investigate an artificial knee implant and assist on device design and to optimize sensing characteristics. The sensing element of the device was fabricated using polyimide micromachining with embedded thin-metallic wires and placed into a knee prosthesis. The device was evaluated experimentally in a mechanical knee simulator using static and dynamic axial load conditions similar to those encountered in vivo. Results indicates the sensor is capable of measuring the strain associated to the total axial forces in the range of approximately 4 times body weight with a good sensitivity and accuracy for events happening within 1 s time window.
Asunto(s)
Prótesis de la Rodilla , Sistemas Microelectromecánicos/instrumentación , Prótesis e Implantes , Artroplastia de Reemplazo de Rodilla/métodos , Diseño de Equipo , Análisis de Elementos Finitos , Humanos , Sistemas Microelectromecánicos/métodos , MicrotecnologíaRESUMEN
Pre-formed and de novo anti-human leukocyte antigen (HLA) antibodies induce antibody-mediated rejection and are also involved in mechanisms leading to chronic graft nephropathy. The detection of anti-HLA antibodies by solid-phase assay (SPA) has revolutionized the management of immunized patients before and after kidney transplantation. Characterized by high sensitivity and specificity, the clinical relevance of anti-HLA antibodies by SPA has to be clarified. The presence of donor-specific antibody at the epitope level, their titer, and the use of different crossmatch technologies could help to determine which of the anti-HLA antibodies are friends and which are foes in kidney transplantation. In this review, we summarize the current state of the art on this debated topic, and give clinical guidelines for the management of antibody detection pre- and post-transplantation, based on these evidences and our own clinical expertise.
Asunto(s)
Antígenos HLA/inmunología , Isoanticuerpos/análisis , Trasplante de Riñón/inmunología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/inmunología , Humanos , Inmunoensayo , Isoanticuerpos/biosíntesis , Isoanticuerpos/inmunología , Guías de Práctica Clínica como Asunto , Sensibilidad y EspecificidadRESUMEN
Cytomegalovirus (CMV) infection is a common complication after organ transplantation. Previous studies have demonstrated that activating killer-cell immunoglobulin-like receptors (KIR) may reduce the rate of CMV infection. KIR genes can be divided into haplotype A (containing a fixed set of inhibitory receptors) and haplotype B (carrying additional activating KIR genes). The KIR locus is divided into a centromeric and a telomeric portion, both of which may carry A or B haplotype motifs. We studied a cohort of 339 kidney transplant recipients to elucidate which KIR genes protect from CMV infection. CMV infection occurred in 139 patients (41%). Possession of telomeric (hazard ratio 0.64, 95% confidence interval 0.44-0.94, p = 0.02) but not centromeric (HR 0.86, 95% CI 0.60-1.23, p = 0.41) B motifs was associated with statistically significant protection from CMV infection. Due to linkage disequilibrium, we were not able to identify a single protective gene within the telomeric B complex (which may contain the KIR2DS1, KIR3DS1, KIR2DL5A and KIR2DS5 genes). The presence of known or putative ligands to activating KIR did not significantly modify the influence of telomeric B group genes. We confirm that B haplotypes protect from CMV infection after kidney transplantation and show that this arises from telomeric B haplotype genes.
Asunto(s)
Centrómero , Infecciones por Citomegalovirus/prevención & control , Trasplante de Riñón/efectos adversos , Receptores KIR/genética , Telómero , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
In solid organ transplanted patients, annual influenza immunization is strongly recommended because of morbidity and mortality of influenza infections. In 2009, the rapid spread of a novel H1N1 influenza A virus led to the accelerated development of novel pandemic influenza vaccines. In Switzerland, the recipients received one dose of seasonal influenza and two doses of AS03-adjuvanted H1N1 vaccines. This situation provided a unique opportunity to analyze the influence of novel adjuvanted influenza vaccines on the production of de novo anti-HLA antibodies. We prospectively followed two independent cohorts including 92 and 59 kidney-transplanted patients, assessing their anti-HLA antibodies before, 6 weeks and 6 months after vaccination. Sixteen of 92 (17.3%) and 7 of 59 (11.9%) patients developed anti-HLA antibodies. These antibodies, detected using the single antigen beads technology, were mostly at low levels and included both donor-specific and non-donor-specific antibodies. In 2 of the 20 patients who were followed at 6 months, clinical events possibly related to de novo anti-HLA antibodies were observed. In conclusion, multiple doses of influenza vaccine may lead to the production of anti-HLA antibodies in a significant proportion of kidney transplant recipients. The long-term clinical significance of these results remains to be addressed.
Asunto(s)
Autoanticuerpos/inmunología , Antígenos HLA/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/administración & dosificación , Trasplante de Riñón , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Vacunas contra la Influenza/inmunología , Masculino , Persona de Mediana Edad , Estaciones del AñoRESUMEN
Renal thrombotic microangiopathy (TMA) is a severe complication of systemic lupus erythematosus (SLE), which is associated with the presence of antiphospholipid (aPL) antibodies. In its most fulminant form, TMA leads to a rapid and irreversible end-stage renal failure. Eculizumab, an anti-C5 monoclonal antibody, is a novel therapy of choice for patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome. Here, we report the case of a 27-year-old woman, known for SLE and end-stage renal disease due to fulminant TMA. Both aPL antibodies and antinucleosome antibodies were positive. The patient underwent a living-related kidney transplantation with immediate production of urine. Although serum creatinine was remaining high, a graft biopsy, performed on day 6, demonstrated a TMA recurrence. Despite a treatment with plasma exchange, the situation got worse and dialysis was started. Eculizumab treatment was subsequently administered and renal function improved rapidly. Three months after transplantation, serum creatinine was at 100 µmol/L, without proteinuria. This case illustrates the benefit of eculizumab therapy in a fulminant recurrence of TMA after kidney transplantation, resistant to classical therapy.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Trasplante de Riñón/efectos adversos , Microangiopatías Trombóticas/tratamiento farmacológico , Anticuerpos Antifosfolípidos/sangre , Femenino , Humanos , Fallo Renal Crónico/etiología , Lupus Eritematoso Sistémico/complicaciones , RecurrenciaRESUMEN
Results of islet of Langerhans transplantation have markedly improved in recent years, but most patients still lose insulin independence in the long-term. We report herein the longest (over 11 years) case of insulin independence after allogeneic islet transplantation. The subject had a 27-year history of type 1 diabetes and received a single islet-after-kidney graft of 8800 islet equivalents (IEQ)/kg, pooled from 2 donors. Insulin was discontinued by 3 months posttransplant and the patient has remained off insulin ever since. Yearly follow-up studies have revealed normal metabolic control, including normal oral glucose tolerance test (OGTT). Reasons for success may involve choice of immunosuppression, low metabolic demand and low immune responsiveness as suggested by an excellent HLA matching and a high count of circulating regulatory T cells. This observation is so far an exceptional case, but clearly demonstrates the validity of the concept that long-term insulin independence after allogeneic islet transplantation is an achievable target.
Asunto(s)
Diabetes Mellitus Tipo 1/cirugía , Hipoglucemiantes/sangre , Insulina/sangre , Trasplante de Islotes Pancreáticos , Adulto , Glucemia/metabolismo , Femenino , Supervivencia de Injerto , Humanos , Terapia de Inmunosupresión , Periodo Posoperatorio , Factores de Tiempo , Trasplante Homólogo , Resultado del TratamientoRESUMEN
We report here the sequence of a new human leucocyte antigen-A2 allele, A*9251, identified in a volunteer haematopoietic stem cell donor of the international registry. A*9251 differs from A*02010101 by two nucleotides at codons 113-114, resulting in a single His>Asp substitution at codon 114.
Asunto(s)
Alelos , Antígeno HLA-A2/genética , Células Madre Hematopoyéticas , Sistema de Registros , Donantes de Tejidos , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Asparagina/metabolismo , Secuencia de Bases , Codón , Cartilla de ADN/química , Cartilla de ADN/genética , Exones , Humanos , Microesferas , Datos de Secuencia Molecular , Análisis de Secuencia por Matrices de Oligonucleótidos , Análisis de Secuencia de ADN , Terminología como AsuntoRESUMEN
Cytomegalovirus (CMV) infection is the most common viral complication after solid organ transplantation (SOT). Whilst current immunosuppression is known to impair antiviral-specific T-cell immunity in SOT, a potential role for natural killer (NK) cells not affected by immunosuppressive therapy remains to be determined. To address this, we compared the genotype of the NK immunoglobulin-like receptor (KIR) genes and their HLA cognate ligands to the rate of CMV infection in 196 kidney transplant recipients. We have shown that the absence of the HLA-C ligand for inhibitory KIR and the presence of activating KIR genes in the recipients were both associated with a lower rate of CMV infection after transplantation. In a cohort of 17 recipients with acute CMV infection, NK cells were phenotyped over a period of time after diagnosis by their expression profile of C-type lectin receptors and capacity to secrete IFN-gamma. The increased expression of the activating C-type lectin receptors NKG2C and NKG2D was paralleled by the decreased IFN-gamma secretion during the early phase of CMV infection. In conclusion, our findings suggest that KIR/HLA genotype and expression of NKG2C and NKG2D might play a significant role in regulating NK cell function and anti-CMV immunity after kidney transplantation.
Asunto(s)
Infecciones por Citomegalovirus/epidemiología , Trasplante de Riñón , Lectinas Tipo C/metabolismo , Complicaciones Posoperatorias , Receptores de Células Asesinas Naturales/metabolismo , Adulto , Citomegalovirus/inmunología , Infecciones por Citomegalovirus/inmunología , Femenino , Genotipo , Antígenos HLA-C/genética , Antígenos HLA-C/metabolismo , Humanos , Interferón gamma/metabolismo , Trasplante de Riñón/inmunología , Células Asesinas Naturales/fisiología , Lectinas Tipo C/genética , Ligandos , Masculino , Persona de Mediana Edad , Subfamília C de Receptores Similares a Lectina de Células NK/genética , Subfamília C de Receptores Similares a Lectina de Células NK/metabolismo , Subfamilia K de Receptores Similares a Lectina de Células NK/genética , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Receptores KIR/genética , Receptores KIR/metabolismo , Receptores de Células Asesinas Naturales/genética , Estudios Retrospectivos , Factores de RiesgoRESUMEN
We report here a new DR4 allele, DRB1*0474, identified in a volunteer hematopoietic stem cell donor of the Swiss National Registry. DRB1*0474 differs from DRB1*040701 by two nucleotide residues resulting in a single Thr --> Asn substitution at codon 77.
Asunto(s)
Exones/genética , Antígeno HLA-DR4/genética , Alelos , Sustitución de Aminoácidos , Secuencia de Bases , Humanos , Datos de Secuencia Molecular , Alineación de SecuenciaRESUMEN
Major histocompatibility complex class II (MHCII) molecules play a pivotal role in the immune system because they direct the development and activation of CD4(+) T cells. There are three human MHCII isotypes, HLA-DR, HLA-DQ, and HLA-DP. Key transcription factors controlling MHCII genes have been identified by virtue of the fact that they are mutated in a hereditary immunodeficiency resulting from a lack of MHCII expression. RFXAP-one of the factors affected in this disease-is a subunit of RFX, a DNA-binding complex that recognizes the X box present in all MHCII promoters. To facilitate identification of conserved regions in RFXAP, we isolated the mouse gene. We then delimited conserved domains required to restore endogenous MHCII expression in cell lines lacking a functional RFXAP gene. Surprisingly, we found that 80% of RFXAP is dispensable for the reactivation of DR expression. Only a short C-terminal segment of the protein is essential for this isotype. In contrast, optimal expression of DQ and DP requires a larger C-terminal segment. These results define an RFXAP domain with an MHCII isotype-specific function. Expression of the three MHCII isotypes exhibits a differential requirement for this domain. We show that this is due to a differential dependence on this domain for promoter occupation and recruitment of the coactivator CIITA in vivo.
Asunto(s)
Antígenos HLA-DP/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Proteínas Nucleares , Factores de Transcripción/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Mapeo Cromosómico , ADN Complementario , Expresión Génica , Glutamina , Humanos , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Señales de Localización Nuclear , Regiones Promotoras Genéticas , Transactivadores/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/fisiología , Activación TranscripcionalRESUMEN
Major histocompatibility complex class II (MHC-II) molecules occupy a pivotal position in the adaptive immune system, and correct regulation of their expression is therefore of critical importance for the control of the immune response. Several regulatory factors essential for the transcription of MHC-II genes have been identified by elucidation of the molecular defects responsible for MHC-II deficiency, a hereditary immunodeficiency disease characterized by regulatory defects abrogating MHC-II expression. Three of these factors, RFX5, RFXAP, and RFXANK, combine to form the RFX complex, a regulatory protein that binds to the X box DNA sequence present in all MHC-II promoters. In this study we have undertaken a dissection of the structure and function of RFX5, the largest subunit of the RFX complex. The results define two distinct domains serving two different essential functions. A highly conserved N-terminal region of RFX5 is required for its association with RFXANK and RFXAP, for assembly of the RFX complex in vivo and in vitro, and for binding of this complex to its X box target site in the MHC-II promoter. This N-terminal region is, however, not sufficient for activation of MHC-II expression. This requires an additional domain within the C-terminal region of RFX5. This C-terminal domain mediates cooperative binding between the RFX complex and NF-Y, a transcription factor binding to the Y box sequence of MHC-II promoters. This provides direct evidence that RFX5-mediated cooperative binding between RFX and NF-Y plays an essential role in the transcriptional activation of MHC-II genes.
Asunto(s)
Proteínas de Unión al ADN/metabolismo , Antígenos de Histocompatibilidad Clase II/genética , Complejo Mayor de Histocompatibilidad/genética , Regiones Promotoras Genéticas , Factores de Transcripción/metabolismo , Secuencia de Aminoácidos , Animales , Linfocitos B , Proteínas Potenciadoras de Unión a CCAAT , Secuencia Conservada , Proteínas de Unión al ADN/genética , Prueba de Complementación Genética , Humanos , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Unión Proteica , Estructura Terciaria de Proteína , Factores de Transcripción del Factor Regulador X , Homología de Secuencia de Aminoácido , Activación TranscripcionalRESUMEN
AIM: The endoluminal stent-grafting represents an alternative to surgery in the treatment of lesions of the descending thoracic aorta. The purpose of the present study was to evaluate the mid-term results of the Talent stent-graft in the different indications of aortic disease and the use of magnetic resonance angiography (MRA) in the diagnosis of complications. METHODS: Over a 3-year period, 23 patients with a high surgical risk and presenting a localized lesion of the descending thoracic aorta had an implantation of a Talent stent-graft. Indications were degenerative aneurysm (n=13), false aneurysm (n=7) and penetrating atherosclerotic ulcer (n=3). The feasibility of the endovascular treatment and sizing of the aorta and stent-grafts were determined pre-operatively by MRA and intraoperative angiography. Immediate and mid-term technical and clinical success were assessed by clinical and MRA follow-up. RESULTS: Endovascular treatment was completed successfully in all patients with no conversion to open repair. There was no intraoperative mortality. The mean operative time was 38+/-7 min. Primary success rate was 100%. We didn't have perioperative mortality. The mean follow-up period was 15+/-5 months. The survival rate was 97% (n=22). Regression of the aneurysmal size was observed in 70% (n=16). MRA diagnosed 3 over 4 postoperative endoleaks that were not diagnosed with the CT-scan, and did not interfere with the nitinol structure of the stent-graft. CONCLUSIONS: Endovascular treatment of the various localized diseases of the descending thoracic aorta is a promising, feasible, alternative technique to open surgery in well selected patients. MRA is well adapted to diagnose postoperative endoleaks.
Asunto(s)
Aneurisma Falso , Aneurisma de la Aorta Torácica , Aterosclerosis , Implantación de Prótesis Vascular/métodos , Angiografía por Resonancia Magnética , Stents , Úlcera , Anciano , Anciano de 80 o más Años , Aneurisma Falso/diagnóstico , Aneurisma Falso/epidemiología , Aneurisma Falso/cirugía , Aorta Torácica/patología , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/diagnóstico , Aneurisma de la Aorta Torácica/epidemiología , Aneurisma de la Aorta Torácica/cirugía , Aterosclerosis/complicaciones , Aterosclerosis/diagnóstico , Aterosclerosis/cirugía , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tasa de Supervivencia/tendencias , Factores de Tiempo , Resultado del Tratamiento , Úlcera/diagnóstico , Úlcera/etiología , Úlcera/cirugíaRESUMEN
In kidney transplantation, hyperacute rejection is mediated by anti-HLA antibody which are also responsible for antibody-mediated acute rejection. In addition anti-HLA antibody are also implicated in the physiopathological mechanism of chronic rejection. The gold standard methodology to detect anti-HLA antibody is based on the complement-dependant-cytotoxicity. This technic is neither specific nor sensitive. New powerful technologies, which are specific and very sensitive, have been developed like Elisa and flow cytometer with fluorescent micro-beads to detect anti-HLA antibody. In this article, we review the importance of anti-HLA antibody in humoral rejection. We also discussed the clinical relevance of the detection of anti-HLA antibody by these new approaches.
Asunto(s)
Anticuerpos/análisis , Rechazo de Injerto/inmunología , Antígenos HLA/inmunología , Trasplante de Riñón/inmunología , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , HumanosRESUMEN
A total of 3 novel human leukocyte antigen-B (HLA-B) alleles were detected by next generation sequencing and confirmed by monoallelic sequencing.
Asunto(s)
Alelos , Exones , Antígenos HLA/genética , Antígeno HLA-B18/genética , Antígeno HLA-B8/genética , Polimorfismo de Nucleótido Simple , Sustitución de Aminoácidos , Expresión Génica , Genotipo , Antígenos HLA/inmunología , Antígeno HLA-B18/inmunología , Antígeno HLA-B8/inmunología , Trasplante de Células Madre Hematopoyéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Prueba de Histocompatibilidad , Humanos , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Receptores de TrasplantesRESUMEN
We used the standard M27-T technique to study organic and aqueous leaf extracts of two Moroccan Cistus L. species: Cistus villosus L. and Cistus monspeliensis L. (Cistaceae L.) used in traditional medicine, for their antimicrobial properties against microorganisms, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Candida krusei, Candida glabrata and Aspergillus fumigatus. The broth dilution method M27-T, standardized by the National Committee for Clinical Laboratory Standards (NCCLS) allowed to determine the minimum inhibitory concentrations (MICs) of different extracts. Results showed that the different extracts differed clearly in their antimicrobial activities. Cistus villosus extracts exhibited more interesting activity than Cistus monspeliensis extracts when used on Staphylococcus aureus (MIC=0.78 mg/ml) and Candida glabrata (MIC=0.19 mg/ml), which are the most susceptible microorganisms. On the other hand, Candida krusei and Aspergillus fumigatus were the least susceptible microorganisms to all Cistus extracts. Comparison results were carried out using chloramphenicol, amoxicillin and amphotericin B as standard antibiotics.
Asunto(s)
Antiinfecciosos/farmacología , Cistus , Pruebas de Sensibilidad Microbiana , Antiinfecciosos/aislamiento & purificación , Aspergillus fumigatus/efectos de los fármacos , Aspergillus fumigatus/aislamiento & purificación , Candida albicans/efectos de los fármacos , Candida albicans/aislamiento & purificación , Marruecos , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Hojas de la PlantaRESUMEN
A series of 11 cloned cell lines derived from a primary, nickel-induced rat rhabdomyosarcoma was evaluated for their metastatic capacity (number of lung colonies following i.v. injection) and attachment kinetics to confluent pig endothelial cell monolayers grown in vitro. The morphology of the adhering cells was also studied by optical and scanning electron microscopy. Cells from all lines tested began to attach to the endothelial monolayers within 15 min of incubation at 37 degrees C, with 64% to 93% of the cells adhering after 2 h. Attachment rates at 30 min ranged from 29 to 48% for four lines classed as "weakly adhesive" (attachment, less than 50%) and from 53 to 78% for seven lines classed as "highly adhesive" (attachment, greater than 50%). Four clones of five displaying low lung-colonizing capacities also showed low attachment rates to endothelial monolayers in vitro. All of six highly colonizing lines studied had high attachment rates. A degree of positive correlation was observed between the amount of cell surface fibronectin as evaluated by immunofluorescence and the early phase attachment rates (and lung-colonizing capabilities) of the different cloned cell lines. Early (15 min) attachment of tumor cells to isolated extracellular matrix preparations proceeded at higher rates than to endothelial monolayers, and previously detected differences between high- and low-colonizing clones were less evident with these matrix substrates. Our results suggest possible interrelationships between specific cell adhesion properties and the metastatic potential of blood-borne tumor cells.
Asunto(s)
Rabdomiosarcoma/patología , Animales , Adhesión Celular , Células Clonales , Endotelio/citología , Fibronectinas/metabolismo , Pulmón/patología , Neoplasias Pulmonares/secundario , Metástasis de la Neoplasia , Ratas , Factores de TiempoRESUMEN
The monitoring of the immune response is not very sensitive. In addition, assays that could allow the quantification of the immune response are missing or not performed by most of routine laboratory. Coming from the research, new approaches and new technologies have revolutionized the monitoring of the immune response. Several of these new approaches are part of the routine to monitor the immune response. Some others, still in development, will also be part of the new assays propose by the laboratories to increase the specificity and the quantification of the immune function.