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BACKGROUND: Implant removal in orthopaedics after fracture consolidation is a very common procedure but is still associated with a high rate of surgical site infection (SSI). Antibiotic prophylaxis is not recommended but advocated by some. AIM: To assess the efficacy of antibiotic prophylaxis in the prevention of early SSI following orthopaedic implant removal. METHODS: A monocentric retrospective cohort study was conducted. Patients who underwent orthopaedic implant removal procedures performed from 2016 to 2021 were included. A 1:1 propensity score matching function was used to create a cohort with matched baseline characteristics and associated risk factors for SSI. Inter-cohort comparison of the occurrence of SSI (superficial or deep) and revision surgery for SSI, after propensity score matching, was performed using the odds ratio to determine the effect of preoperative antibiotic prophylaxis. FINDINGS: In total, 965 distinct surgical procedures were included. Of these, 69 (7.15%) had an SSI, 24 (35.7%) of which required surgical revision; 214 procedures (22.18%) were performed under preoperative antibiotic prophylaxis. The propensity-matched cohort consisted of 396 procedures (198 with and without antibiotic prophylaxis). The SSI rates were 11.11% and 3.03%, respectively, in the control and antibiotic prophylaxis groups (odds ratio: 0.25; 95% confidence interval: 0.099; 0.63; P = 0.011). No difference was found for revision surgery. CONCLUSION: Preoperative administration of antibiotic prophylaxis considerably reduces the risk of SSI during the removal of an orthopaedic implant without increasing the risk of side-effects.
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Antibacterianos , Ortopedia , Humanos , Antibacterianos/uso terapéutico , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/etiología , Estudios de Cohortes , Estudios Retrospectivos , Profilaxis Antibiótica/métodosRESUMEN
This study aimed to analyze upper-extremity combat-related injuries (CRIs) and non-combat-related injuries (NCRIs) treated in the French Forward Surgical Team currently deployed in Gao, Mali. A retrospective study was conducted using the French Military Health Service OpEX surgical database from February 2013 to March 2020. All patients operated on for upper-extremity injury were included: 224 patients, with a mean age of 28.15 years, for 249 upper-extremity injuries. Seventy-six (33.9%) sustained CRIs and 148 (66.1%) NCRIs. Multiple upper-extremity injuries and associated injuries were significantly more common in the CRI group. The majority of NCRIs involved the hand. Debridement and wound care was the most common procedure in both groups. External fixation and fasciotomy were significantly more frequent in the CRI group, and internal fracture fixation in the NCRI group. The overall number of procedures was significantly higher in the CRI group. Due to the high frequency of upper-extremity injury in current theaters of operations, deployed orthopedic surgeons should be trained in basic hand surgery so as to optimally manage both CRIs and NCRIs.
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Traumatismos del Brazo , Guerra , Adulto , Traumatismos del Brazo/cirugía , Humanos , Malí/epidemiología , Estudios Retrospectivos , Extremidad Superior/lesiones , Extremidad Superior/cirugíaRESUMEN
INTRODUCTION: The objective was to report on the experience of the French Army Health Service in the management of blast injury of the hands related to warfare explosive devices. METHODS: A retrospective study was conducted in the Percy Military Hospital (role 4 medical treatment facility) among French soldiers who presented with a combat-related blast injury of the hand between 2002 and 2018. The functional result was assessed by the disabilities of the arm, shoulder and hand (DASH) and the Orthotics and Prosthetics User Survey (OPUS, upper extremity functional status) scores. Proximal amputations (PAs) and distal amputations (DAs) were distinguished for the analysis. RESULTS: Fifteen patients with a mean age of 31±8 years were included. They totalised 20 blasted hands. There were 16 traumatic amputations: 8 in each of the PA and DA groups. Twelve patients had additional injuries, four of which were polytraumatic. Skin closure time and flap use were higher in the DA group. Only one thumb reconstruction was performed. At a mean follow-up of 6.5±4 years, the number of amputees wearing a prosthesis was higher in the PA group. The mean DASH and OPUS scores were 35.5%±24.0% and 64.0%±19.0%, respectively, with no difference between the two groups. CONCLUSION: The severity of hand blasts related to warfare explosive devices requires the systematic application of damage control surgery. PAs are frequent and secondary reconstruction options are limited. The functional result is poor and similar between proximal and distal amputees.
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Traumatismos por Explosión , Sustancias Explosivas , Servicios de Salud Militares , Adulto , Traumatismos por Explosión/epidemiología , Humanos , Estudios Retrospectivos , Guerra , Adulto JovenRESUMEN
Microsurgery is an unusual procedure in the theatres of military operations. We sought to analyze the state of microsurgical practices in the French medical treatment facilities (MTFs) deployed around the world in the 21st century. A retrospective study was conducted among all patients who were operated on in French forward surgical facilities between 2003 and 2015. Those who underwent microsurgical procedures for nerve injury, vascular injury, or extremity reconstruction were included. Only early vascular results were assessed. Among the 2589 patients operated on for an extremity injury during the study period, 56 (2.1%) were included, with the group composed of 29 patients with isolated nerve injuries, 28 patients with nerve and arterial injuries, and two patients with isolated arterial injuries, mostly at the hand level. Nerve procedures predominantly consisted of direct suturing, although autografting and nerve transfers were also performed. Thirteen microvascular repairs were carried out, including nine cases of proximal or digital revascularization; revascularization was successful in six of the nine cases. These procedures were completed by orthopedic surgeons trained in microsurgery, mostly under loupes magnification. Routine nerve repair in the field seems to be specific to French MTFs. Salvage of amputated or devascularized fingers in the combat zone had never been reported before. Such emphasizes the need to train deployed orthopedic surgeons to perform microsurgical procedures and to equip all MTFs with basic microsurgical sets and magnification means.
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Extremidades/cirugía , Microcirugia/estadística & datos numéricos , Servicios de Salud Militares , Procedimientos Neuroquirúrgicos/estadística & datos numéricos , Procedimientos Ortopédicos/estadística & datos numéricos , Adulto , Arterias/lesiones , Arterias/cirugía , Extremidades/lesiones , Femenino , Fracturas Óseas/cirugía , Francia , Hospitales Militares , Humanos , Masculino , Unidades Móviles de Salud , Cirujanos Ortopédicos/estadística & datos numéricos , Traumatismos de los Nervios Periféricos/cirugía , Reimplantación , Estudios RetrospectivosRESUMEN
Mycetoma is a disease that occurs in the mycetoma belt, between latitudes 15Ì south and 30Ì north. It affects disadvantaged regions with limited access to medical and health facilities. Its general principles of care have changed little and are poorly known. We analyzed the management of mycetoma in Chad by French military surgeons deployed within the Epervier and Barkhane operations. This retrospective descriptive study was conducted among the cohort of Chadian patients managed by the N'Djamena forward surgical team from 2007 to 2018 as part of the medical support to the population. It includes 132 patients who had surgery for mycetoma. Surgical parameters of primary treatment and revisions procedures were analyzed. Postoperative follow-up was at least six months. Amputation was performed in 87/132 (66%) patients. Overall 11 (8.3%) required revision surgery, including 7 (5%) with eumycetoma recurrence. All recurrences occurred in the lower limb. The recurrence rate after excision was 10.2% (5/49) versus 2.3% after amputation (2/87). In the absence of effective and accessible medical treatment, surgery remains the basic treatment for mycetoma. Salvage surgery with local excision should always be considered. However, amputation is the only reliable treatment in cases with late presentation. It should not be proposed too early as limb function is preserved for a long time.
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Micetoma/cirugía , Adolescente , Adulto , Anciano , Chad , Femenino , Francia , Cirugía General , Humanos , Cooperación Internacional , Masculino , Persona de Mediana Edad , Medicina Militar , Recurrencia , Estudios Retrospectivos , Adulto JovenRESUMEN
Gunshot wounds to the hand often produce complex injuries and large segmental bone defects. Bone reconstruction remains a challenge in this context. The induced membrane technique is a simple and effective procedure for reconstruction of segmental bone defects. The technique is straightforward but must be performed rigorously. Usually polymethylmethacrylate (PMMA) cement is required for the first stage of the surgery. We describe four cases of metacarpal bone reconstruction after gunshot wounds in a limited-resource setting. Two patients were treated using the induced membrane technique with a polypropylene syringe body instead of PMMA cement, which was unavailable in this situation. A thick membrane was observed 6 weeks after spacer implantation. Bone union was achieved in all cases.
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Cuerpos Extraños , Reacción a Cuerpo Extraño/etiología , Regeneración Tisular Dirigida/métodos , Huesos del Metacarpo/cirugía , Heridas por Arma de Fuego/cirugía , Adulto , Antibacterianos/uso terapéutico , Hueso Esponjoso/trasplante , Hueso Cortical/trasplante , Curación de Fractura , Fracturas Abiertas/cirugía , Humanos , Ilion/trasplante , Masculino , Huesos del Metacarpo/lesiones , Polipropilenos , Colgajos Quirúrgicos , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/terapia , Tibia/trasplanteRESUMEN
In developing countries, road traffic accidents result in many cases of open trauma, especially fractures, with the tibia area at particular risk in motorcycle crashes. Despite a high prevalence of severe leg trauma with multi-tissue injuries, few studies have focused on the challenge of their reconstruction in these limited-resource settings. The first part of this review presents the surgical strategy. Limitations and principles of initial limb salvage are detailed. Orthopedic procedures for early damage control, based on debridement and temporary bone stabilization, are often required. The priority is to shorten the time to initial surgical management to avoid infection, which jeopardizes reconstruction.
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Fracturas Abiertas/cirugía , Recuperación del Miembro/métodos , Recuperación del Miembro/normas , Fracturas de la Tibia/cirugía , Fracturas Abiertas/clasificación , Recursos en Salud , Humanos , Procedimientos Ortopédicos , Fracturas de la Tibia/clasificaciónRESUMEN
PURPOSE: Nerve transfers to restore elbow flexion have been described for traumatic brachial plexus palsy in adults. Indications are less frequent in infants and the results are less published. METHODS: Ten patients with obstetrical brachial plexus palsy were operated on for lack of flexion against gravity with ulnar or median nerve transfer to biceps motor branch. The primary endpoint was improvement in elbow flexion and supination. RESULTS: Mean age at surgery was 12.5 months and mean follow-up was 2.6 years. The Active Movement Scale (AMS) was used to evaluate elbow flexion and forearm supination. At the last follow-up, the average AMS score improved from 0.3 to 5.7 for elbow flexion and from 0.6 to 5.8 for forearm supination. There was no statistical correlation between the age at surgery and the AMS score 18 months post-operatively. CONCLUSIONS: Nerve transfer to the biceps motor branch can improve elbow flexion and forearm supination in selected patients with upper lesions and can be safely performed until the age of two years.
RESUMEN
Although the development of multitissue limb reconstruction has reduced the role of post-traumatic primary amputation of the leg, some patients should nonetheless undergo emergency amputations. In developing countries, the socioeconomic context associated with the limited health care supply compromises still further the prognosis of preservation efforts. The decision criteria for surgery are thus different in these settings. The choice of emergency leg amputation or attempted preservation in developing countries depends on the epidemiology of severe leg trauma, the local and general prognosis, and the practice conditions. Three factors must be combined before limb preservation can be attempted: adequate local and general adequate wound elements, an available, experienced surgeon with a competent care structure, and a favorable social context.
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Amputación Quirúrgica , Tratamiento de Urgencia , Traumatismos de la Pierna/cirugía , Árboles de Decisión , Países en Desarrollo , Recursos en Salud , Humanos , Puntaje de Gravedad del Traumatismo , PobrezaRESUMEN
Silencing genes essential for replication and division using siRNA has potential as a therapeutic strategy for cancer treatment. In order to identify the most potent siRNA, target sequence and siRNA design must be considered together, as tolerance for structural changes can be sequence-dependent. Here we have used growth inhibition assays to investigate the effects of silencing of RRM1, RRM2, and PLK1 with standard siRNAs, Stealth() duplexes, and Dicer substrate siRNAs. The growth inhibitory effect of RRM1, RRM2, or PLK1 knockdown in A549 cells varied with mRNA target site and the format of the siRNA, with longer modified siRNAs generally more effective than standard siRNAs specific for the same target site. Standard siRNAs of varying activity became more potent inhibitors of growth when converted to Stealth() duplexes, and the increase in activity was due to a combination of chemical modification and length. In each case, the effect on activity of changing the siRNA format depended on the siRNA sequence. Taken together these results suggest that, in vitro, longer siRNAs with chemical modifications are in general more active than standard siRNAs targeting the same site, and that structure, chemical modification, and target site must be considered together to identify the most active siRNAs.
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Interferencia de ARN , ARN Interferente Pequeño/química , ARN Interferente Pequeño/genética , Secuencia de Bases , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/genética , Línea Celular , Proliferación Celular , Cartilla de ADN/genética , Ingeniería Genética , Humanos , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/genética , ARN sin Sentido/química , ARN sin Sentido/genética , Ribonucleósido Difosfato Reductasa/antagonistas & inhibidores , Ribonucleósido Difosfato Reductasa/genética , Transfección , Proteínas Supresoras de Tumor/antagonistas & inhibidores , Proteínas Supresoras de Tumor/genética , Quinasa Tipo Polo 1RESUMEN
The p53 tumor suppressor plays a major role in preventing tumor development by transactivating genes to remove or repair potentially tumorigenic cells. Here we show that the Y-box-binding protein, YB1, acts as a negative regulator of p53. Using reporter assays we show that YB1 represses transcription of the p53 promoter in a sequence-specific manner. We also show that YB1 reduces endogenous levels of p53, which in turn reduces p53 activity. Conversely, inhibiting YB1 in a variety of tumor cell lines induces p53 activity, resulting in significant apoptosis via a p53-dependent pathway. These data suggest that YB1 may, in some situations, protect cells from p53-mediated apoptosis, indicating that YB1 may be a good target for the development of new therapeutics.
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Apoptosis/fisiología , Proteínas Potenciadoras de Unión a CCAAT/fisiología , Proteínas de Unión al ADN/genética , Regulación de la Expresión Génica/fisiología , Genes p53/genética , Proteínas Represoras/genética , Factores de Transcripción/genética , Animales , Apoptosis/genética , Clonación Molecular , Proteínas de Unión al ADN/fisiología , Humanos , Factores de Transcripción NFI , Proteínas Nucleares , Regiones Promotoras Genéticas , Ratas , Proteínas Recombinantes/metabolismo , Proteínas Represoras/fisiología , Factores de Transcripción/fisiología , Transcripción Genética , Transfección , Células Tumorales Cultivadas , Proteína 1 de Unión a la Caja YRESUMEN
The epidermis is a stratified, continually renewing epithelium dependent on a balance among cell proliferation, differentiation, and death for homeostasis. In normal epidermis, a mitotically active basal layer gives rise to terminally differentiating keratinocytes that migrate outward and are ultimately sloughed from the skin surface as enucleated squames. Although many proteins are known to function in maintaining epidermal homeostasis, the molecular coordination of these events is poorly understood. RIP4 is a novel RIP (receptor-interacting protein) family kinase with ankyrin repeats cloned from a keratinocyte cDNA library. RIP4 deficiency in mice results in perinatal lethality associated with abnormal epidermal differentiation. The phenotype of RIP4(-/-) mice in part resembles that of mice lacking IKKalpha, a component of a complex that regulates NF-kappaB. Despite the similar keratinocyte defects in RIP4- and IKKalpha-deficient mice, these kinases function in distinct pathways. RIP4 functions cell autonomously within the keratinocyte lineage. Unlike IKKalpha, RIP4-deficient skin fails to fully differentiate when grafted onto a normal host. Instead, abnormal hair follicle development and epidermal dysplasia, indicative of progression into a more pathologic state, are observed. Thus, RIP4 is a critical component of a novel pathway that controls keratinocyte differentiation.
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Diferenciación Celular/fisiología , Queratinocitos/fisiología , Proteínas Quinasas/metabolismo , Proteínas/metabolismo , Animales , Células Epidérmicas , Epidermis/crecimiento & desarrollo , Epidermis/patología , Epidermis/fisiología , Femenino , Homeostasis , Queratinas/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Membrana Mucosa/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Proteínas Quinasas/genética , Proteínas Serina-Treonina Quinasas , Proteínas/genética , Proteína Serina-Treonina Quinasas de Interacción con ReceptoresRESUMEN
A novel fibroblast growth factor receptor (FGFR), designated FGFR5, was identified from an EST database of a murine lymph node stromal cell cDNA library. The EST has approximately 32% identity to the extracellular domain of FGFR1-4. Library screening with this EST identified two full-length alternative transcripts which we designated as FGFR5 beta and FGFR5 gamma. The main difference between these transcripts is that FGFR5 beta contains three extracellular Ig domains whereas FGFR5 gamma contains only two. A unique feature of FGFR5 is that it does not contain an intracellular tyrosine kinase domain. Predictive structural modelling of the extracellular domain of FGFR5 gamma suggested that it was a member of the I-set subgroup of the Ig-superfamily, consistent with the known FGFRs. Northern analysis of mouse and human FGFR5 showed detectable mRNA in a broad range of tissues, including kidney, brain and lung. Genomic sequencing identified four introns but identified no alternative transcripts containing a tyrosine kinase domain. Extracellular regions of FGFR5 beta and 5 gamma were cloned in-frame with the Fc fragment of human IgG(1) to generate recombinant non-membrane bound protein. Recombinant FGFR5 beta Fc and R5 gamma Fc demonstrated specific binding to the ligand FGF-2, but not FGF-7 or EGF. However, biological data suggest that FGF-2 binding to these proteins is with lower affinity than its cognate receptor FGFR2C. The above data indicate that this receptor should be considered as the fifth member of the FGFR family.
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Receptores de Factores de Crecimiento de Fibroblastos/genética , Células 3T3 , Empalme Alternativo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Unión Competitiva , Northern Blotting , ADN/química , ADN/genética , ADN Complementario/química , ADN Complementario/genética , ADN Complementario/aislamiento & purificación , Exones , Femenino , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Expresión Génica , Genes/genética , Humanos , Intrones , Ratones , Datos de Secuencia Molecular , Estructura Terciaria de Proteína , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptor Tipo 5 de Factor de Crecimiento de Fibroblastos , Receptores de Factores de Crecimiento de Fibroblastos/química , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Distribución TisularRESUMEN
High throughput sequencing of a mouse keratinocyte library was used to identify an expressed sequence tag with homology to the epidermal growth factor (EGF) family of growth factors. We have named the protein encoded by this expressed sequence tag Epigen, for epithelial mitogen. Epigen encodes a protein of 152 amino acids that contains features characteristic of the EGF superfamily. Two hydrophobic regions, corresponding to a putative signal sequence and transmembrane domain, flank a core of amino acids encompassing six cysteine residues and two putative N-linked glycosylation sites. Epigen shows 24-37% identity to members of the EGF superfamily including EGF, transforming growth factor alpha, and Epiregulin. Northern blotting of several adult mouse tissues indicated that Epigen was present in testis, heart, and liver. Recombinant Epigen was synthesized in Escherichia coli and refolded, and its biological activity was compared with that of EGF and transforming growth factor alpha in several assays. In epithelial cells, Epigen stimulated the phosphorylation of c-erbB-1 and mitogen-activated protein kinases and also activated a reporter gene containing enhancer sequences present in the c-fos promoter. Epigen also stimulated the proliferation of HaCaT cells, and this proliferation was blocked by an antibody to the extracellular domain of the receptor tyrosine kinase c-erbB-1. Thus, Epigen is the newest member of the EGF superfamily and, with its ability to promote the growth of epithelial cells, may constitute a novel molecular target for wound-healing therapy.
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Factor de Crecimiento Epidérmico/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Clonación Molecular , Factor de Crecimiento Epidérmico/metabolismo , Epigen , Escherichia coli , Queratinocitos , Ratones , Datos de Secuencia Molecular , Alineación de Secuencia , Análisis de SecuenciaRESUMEN
Dermal papilla (DEPA) cells are resident at the base of hair follicles and are fundamental to hair growth and development. Cultured DEPA cells, in contrast to normal fibroblast cells, are capable of inducing de novo hair follicle growth in vivo. By differential screening of a DEPA cDNA library, we have demonstrated that dermal papilla cells are different from fibroblasts at the molecular level. We further studied these cells by random sequencing of 5130 clones from the DEPA cDNA library. Fifty percent had a BLASTX E value < or =1 x 10(-25). Twenty-one percent had similarity to proteins involved in cell structure/motility with 4 of the top 10 most abundant clones encoding extracellular matrix proteins. Clones encoding growth factor molecules were also abundant. The remaining 50.7% of clones had low similarity scores, demonstrating many novel molecules. For example, we identified a new CTGF family member, the rat homologue of Elm1.
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Etiquetas de Secuencia Expresada , Folículo Piloso/citología , Folículo Piloso/fisiología , Proteínas Oncogénicas , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Proteínas CCN de Señalización Intercelular , Células Cultivadas , ADN Complementario , Fibroblastos , Regulación de la Expresión Génica , Biblioteca de Genes , Datos de Secuencia Molecular , Especificidad de Órganos , Proteínas Proto-Oncogénicas , Ratas , Ratas Endogámicas , Proteínas Represoras/genéticaRESUMEN
Phospho-glycoproteins are members of the ABC transporter family encoded by the multidrug-resistant genes. These proteins are highly expressed in many tumor cells derived from patients undergoing treatment with anti-cancer drugs. Phospho-glycoproteins are large 12 transmembrane spanning molecules of 170 kDa, involved in adenosine-5'-triphosphate-dependent efflux of molecules out of the cell, known currently as multidrug-resistant pumps. Expression analysis of phospho-glycoproteins in mice and humans indicates widespread distribution in a number of organs, such as brain and testis. We have analyzed skin, and more particularly keratinocytes, to determine whether they express phospho-glycoproteins and express the multidrug-resistant phenotype. Immunofluorescent staining of skin showed that keratinocytes located in the basal layer of the epidermis preferentially expressed phospho-glycoproteins, as did the outer root sheath cells of hair follicles. Phospho-glycoprotein expression on the basal cells was restricted to the cell surface. Polymerase chain reaction analysis of first strand cDNA from keratinocytes identified the phospho-glycoproteins to be mdr1b. Using beta1 integrin expression and density gradient centrifugation we were able to enrich and identify the basal cell compartment by flow cytometric analysis and assay this subset of cells for phospho-glycoprotein activity. Basal cells loaded with rhodamine 123, a substrate for multidrug-resistant pumps, effluxed the molecule from the cells in a time-dependent manner. This study shows that basal layer keratinocytes express functional phospho-glycoproteins. We speculate that phospho-glycoproteins may play a role in regulating the level of environmental toxins and differentiation factors, as has been suggested for other progenitor cell compartments.
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Resistencia a Múltiples Medicamentos/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/inmunología , Animales , Anticuerpos/análisis , Secuencia de Bases , Genes MDR , Inmunohistoquímica , Integrina beta1/biosíntesis , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Rodamina 123/metabolismo , Piel/citología , Piel/metabolismoRESUMEN
A novel alpha-chemokine, designated KS1, was identified from an EST database of a murine immature keratinocyte cDNA library. The EST has 94% similarity to a recently cloned human gene, BRAK, that has no demonstrated function. Northern analysis of mouse and human genes showed detectable mRNA in brain, intestine, muscle and kidney. Tumour panel blots showed that BRAK was down-regulated in cervical adenocarcinoma and uterine leiomyoma, but was up-regulated in breast invasive ductal carcinoma. KS1 bound specifically to B cells and macrophages, as well as two B cell lines, CESS and A20, and a monocyte line, THP-1. KS1 showed no binding to naive or activated T cells. In addition, KS1 stimulated the chemotaxis of CESS and THP-1 cells but not T cells. The s.c. injection of KS1 creates a mixed inflammatory response in Nude and C3H/HeJ mice. The above data indicates that KS1 and its human homologue represents a novel non-ELR alpha-chemokine that may have important roles in trafficking of B cells and monocytes. We propose the name B cell- and monocyte-activating chemokine (BMAC) for this molecule to reflect the described biological functions.
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Linfocitos B/inmunología , Quimiocinas CXC/genética , Monocitos/inmunología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Northern Blotting , Línea Celular , Quimiocinas CXC/análisis , Quimiocinas CXC/metabolismo , Quimiocinas CXC/farmacología , Quimiotaxis/efectos de los fármacos , Citometría de Flujo , Biblioteca de Genes , Humanos , Queratinocitos/inmunología , Ratones , Ratones Endogámicos C3H , Ratones Desnudos , Datos de Secuencia Molecular , Quistes Odontogénicos/inmunología , ARN Mensajero/análisis , Piel/efectos de los fármacos , Piel/inmunologíaRESUMEN
The cytokine production profile, focusing on interleukin-4 (IL-4), interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) of human CD4+, CD8+ and CD4- CD8- alpha beta T cells cloned from the peripheral blood of healthy individuals was compared. Solid-phase anti-CD3 stimulation of CD4- CD8- alpha beta T cell clones from one individual revealed a significantly increased frequency of IL-4-producing clones (81%), compared to CD4+ T cells (24%) or CD8+ (28%). All five CD4- CD8- alpha beta T-cell clones from two other individuals also produced IL-4. Clones that produced IFN-gamma with undetectable IL-4 production, thus being of the 'classical' Th1 phenotype, were infrequent in CD4- CD8- alpha beta T-cell clones (19%) compared to CD4+ (71%), and CD8+ clones (72%) cloned in OKT3, and CD4+ cells cloned in phytohaemaglutinin A (77%). Unlike previously reported studies with gamma delta cells, the alpha beta CD4- CD8- T cells produced IL-10 at appreciable frequency (38%) in PHA generated clones. The supernatants from anti-CD3 stimulated CD4- CD8- alpha beta T-cell clones contained sufficient IL-4 to activate B cells, enhancing CD23 and surface immunoglobulin M (IgM) expression and co-stimulating B-cell proliferation. These findings suggest that the function of CD4- CD8- alpha beta T cells is distinct from that of most CD4+ or CD8+ T cells.
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Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Interferón gamma/biosíntesis , Interleucinas/biosíntesis , Receptores de Antígenos de Linfocitos T alfa-beta/análisis , Linfocitos B/inmunología , Células Cultivadas , Células Clonales/inmunología , Humanos , Interleucina-10/biosíntesis , Interleucina-4/biosíntesis , Activación de LinfocitosRESUMEN
We have studied the nature of human CD4-CD8- (double negative) alpha beta T cells to determine whether they possess unique characteristics which could further differentiate them from conventional CD4+ or CD8+ (single positive) T cells. We observed that double negative TCR alpha beta+ T cells differ from single positive T cells in the following respects: (i) their T cell receptor (TCR) repertoire is different, as revealed by the analysis of 47 clones derived from three individuals and by analysis of peripheral blood lymphocytes (PBL) prior to in vitro manipulation; (ii) their in vivo CD3:TCR expression is lower before in vitro manipulation and expansion; (iii) their direct proliferative response to IL-3, which is not mediated by secondary release of other T cell growth factors. These characteristics have also been recently ascribed to murine double negative alpha beta T cells, which develop extrathymically and are considered to be a distinct T cell lineage. Our data suggest that, like their murine counterparts, human double negative alpha beta T cells may represent a distinct T cell lineage which might develop extrathymically.