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1.
Georgian Med News ; (264): 139-143, 2017 Mar.
Artículo en Ruso | MEDLINE | ID: mdl-28480867

RESUMEN

The aim of research was to assess the impact of the introduction of information system 1C: Enterprise on the work of medical staff. It was evaluated staff satisfaction in terms of quality and speed of their duties, as well as sociological changes after the introduction in the work the information system 1C: Enterprise from 2010. The research involved 138 employees of the hospital, including 48 doctors and 90 nurses with experience of at least 5 years. The average age of respondents was 45 years. The study was conducted through questionnaires, including questions relating to life expectancy, changing the speed and quality of execution of tasks, also attended to questions about the change in the frequency of conflict situations and wages. Separately, it was included open-ended question about the change in the level of motivation before and after the implementation of the information system. Respondents gave the evaluation and describe the specific changes they have noticed. Objective assessment of the effectiveness was evaluated according to the official statistics on the number of people served, the time spent on one patient, the level of qualification of medical personnel. 76% of employees have noted positive changes in the work after the implementation of the information system 1C: Enterprise in the work, there is a change of diagnosis rate, the quality of treatment, 72.3% of physicians and 48% of nurses have noted a decrease in time spent on paperwork. 13.6% of physicians and 23.0% of nurses did not notice any difference. Other members expressed dissatisfaction, because of the necessity of learning of a computer program. After the number of the served population program of work increased by 6.8%, decreased the number of days of hospitalization by 12%. The use of modern information systems increases the level of health services and health workers, increasing productivity.


Asunto(s)
Sistemas de Información en Hospital/organización & administración , Programas Informáticos , Eficiencia Organizacional , Personal de Hospital
2.
J Physiol ; 594(4): 1037-49, 2016 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-26537335

RESUMEN

KEY POINTS: Position sense at the human forearm can be measured in blindfolded subjects by matching positions of the arms or by a subject pointing to the perceived position of an unseen arm. Effects on position sense tested were: elbow muscle conditioning with a voluntary contraction, muscle vibration, loading the arm and elbow skin stretch. Conditioning contractions and vibration produced errors in a matching task, consistent with the action of muscle spindles as position sensors. Position errors in a pointing task were not consistent with the action of muscle spindles. Loading the arm or skin stretch had no effect in either matching or pointing tasks. It is proposed that there are two kinds of position sense: (i) indicating positions of different body parts relative to one another, using signals from muscle spindles; and (ii) indicating position of the body in extrapersonal space, using signals from exteroceptors, vision, touch and hearing. ABSTRACT: Human limb position sense can be measured in two ways: in a blindfolded matching task, position of one limb is indicated with the other limb. Alternatively, position of a limb, hidden from view, is indicated with a pointer, moved by pressing a lever. These experiments examined the sensory basis of position sense measured in these two ways. Position errors were measured in 14 subjects after elbow flexors or extensors had been conditioned with a half-maximum voluntary contraction. In agreement with previous studies, in the matching trials, position errors were distributed according to a pattern consistent with the action of muscle spindles as the position sensors. In the pointing trials, all errors lay in the direction of extension of the true position of the hidden arm and their distribution was inconsistent with influences arising in muscle spindles. Vibration of elbow muscles produced an illusion of muscle lengthening during a matching task, while during the pointing task no illusion was present. Finally, the matching-pointing error difference was preserved, even when one arm was loaded with a weight or skin over the elbow was stretched. It is proposed that there are two kinds of position sense. One is signalled by muscle spindles, indicating position of one part of the body relative to another. A second provides information about the position of the body in extrapersonal space and here we hypothesise that exteroceptors, including vision, touch and hearing, acting via a central map of the body, provide the spatial information.


Asunto(s)
Imagen Corporal , Sensación , Femenino , Antebrazo/inervación , Antebrazo/fisiología , Humanos , Masculino , Movimiento , Contracción Muscular , Músculo Esquelético/inervación , Músculo Esquelético/fisiología , Espacio Personal , Desempeño Psicomotor , Adulto Joven
3.
Exp Brain Res ; 233(9): 2635-43, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26048159

RESUMEN

These experiments were designed to test the idea that, in a forearm position-matching task, it is the difference in afferent signals coming from the antagonist muscles of the forearm that determines the perceived position of the arm. In one experiment, flexor and then extensor muscles of the reference arm were conditioned by isometric voluntary contractions while the arm was held at the test angle, approximately 45° from the horizontal. At the same time, indicator arm flexor muscles were contracted while the arm was flexed, or extensors were contracted while it was extended. After an indicator flexor contraction, during matching, subjects made large errors in the direction of flexion, by 9.3° relative to the reference arm and after an indicator extensor contraction by 7.4° in the direction of extension. In the second experiment, with reference muscles conditioned as before, slack was introduced in indicator muscles by a combination of muscle contraction and stretch. This was expected to lower levels of afferent activity in indicator muscles. The subsequent matching experiment yielded much smaller errors than before, 1.4° in the direction of flexion. In both experiments, signal levels coming from the reference arm remained the same and what changed was the level of indicator signal. The fact that matching errors were small when slack was introduced in indicator muscles supported the view that the signal coming from reference muscles was also small. It was concluded that the brain is concerned with the signal difference from the antagonist pair of each arm and with the total signal difference between the two arms.


Asunto(s)
Codo/inervación , Potenciales Evocados Motores/fisiología , Antebrazo/fisiología , Contracción Isométrica/fisiología , Músculo Esquelético/fisiología , Propiocepción/fisiología , Adulto , Análisis de Varianza , Electromiografía , Femenino , Humanos , Masculino , Potenciometría , Adulto Joven
4.
J Physiol ; 592(12): 2679-94, 2014 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-24665096

RESUMEN

These experiments on the human forearm are based on the hypothesis that drift in the perceived position of a limb over time can be explained by receptor adaptation. Limb position sense was measured in 39 blindfolded subjects using a forearm-matching task. A property of muscle, its thixotropy, a contraction history-dependent passive stiffness, was exploited to place muscle receptors of elbow muscles in a defined state. After the arm had been held flexed and elbow flexors contracted, we observed time-dependent changes in the perceived position of the reference arm by an average of 2.8° in the direction of elbow flexion over 30 s (Experiment 1). The direction of the drift reversed after the arm had been extended and elbow extensors contracted, with a mean shift of 3.5° over 30 s in the direction of elbow extension (Experiment 2). The time-dependent changes could be abolished by conditioning elbow flexors and extensors in the reference arm at the test angle, although this led to large position errors during matching (±10°), depending on how the indicator arm had been conditioned (Experiments 3 and 4). When slack was introduced in the elbow muscles of both arms, by shortening muscles after the conditioning contraction, matching errors became small and there was no drift in position sense (Experiments 5 and 6). These experiments argue for a receptor-based mechanism for proprioceptive drift and suggest that to align the two forearms, the brain monitors the difference between the afferent signals from the two arms.


Asunto(s)
Articulación del Codo/fisiología , Músculo Esquelético/fisiología , Propiocepción/fisiología , Adulto , Brazo , Femenino , Humanos , Masculino , Contracción Muscular , Adulto Joven
5.
Tech Coloproctol ; 18(5): 467-72, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24197901

RESUMEN

BACKGROUND: Various conditions lead to the development of colonic fistulas. Contemporary surgical data is scarce and it is unclear whether advances in surgical care have impacted outcome. The aim of the present study was to review the short- and long-term outcome of patients treated surgically for colonic fistula over an 8-year period at a tertiary institution. METHODS: A retrospective review was performed, focusing on the type of operative interventions, short- and long-term complications, length of hospital stay, readmission rate, mortality rate, and fistula recurrence. RESULTS: Forty-five patients were treated for colonic fistula. The most common etiology was diverticulitis (74%). Fistula type was colovesical (58%), colocutaneous (18%) and colovaginal (15%). Laparoscopic resection was performed in 42% of cases. An intraoperative complication occurred in 4%. A primary anastomosis was performed in 96% of patients and 10 (23%) had a temporary stoma. Median length of hospital stay was 6 days. Postoperative complications were common (47%) and wound infection was noted in 20% of patients. The readmission rate was 29% and the 90-day mortality was 4%. All patients healed their fistula with no recurrences noted during a median follow-up of 37 months. CONCLUSIONS: Surgical intervention healed the majority of patients with colonic fistula. However postoperative complications were common and readmission occurred in one-third of the cases. Laparoscopic excision was feasible in nearly half of the patients.


Asunto(s)
Enfermedades del Colon/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Fístula Intestinal/cirugía , Adulto , Anciano , Anciano de 80 o más Años , California , Enfermedades del Colon/mortalidad , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Procedimientos Quirúrgicos del Sistema Digestivo/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Fístula Intestinal/mortalidad , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Recurrencia , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento
6.
Allergy ; 67(2): 235-41, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22092159

RESUMEN

BACKGROUND: Allergen measurements are widely used for environmental exposure assessments and for determining the potency of allergen vaccines, yet few purified allergen standards have been developed. The aim of the study was to develop a single standard containing multiple purified allergens that could be used in enzyme immunoassays and in multiplex arrays for the standardization of allergen measurements. METHODS: Eight purified allergens were formulated into a single multi-allergen, or 'universal', standard based on amino acid analysis. Dose-response curves were compared with previous individual ELISA standards and allergen measurements of house dust extracts to obtain correction factors. Measured allergen concentrations were also modeled using linear regression, and the predictive accuracy was determined. RESULTS: Parallel dose-response curves were obtained between the universal allergen standard and the individual ELISA standards, with close agreement between curves for 5/8 allergens. Quantitative differences of greater than twofold were observed for Fel d 1, Can f 1, and Der f 1, which were confirmed by the analysis of house dust extracts. Correction factors were developed that allowed ELISA data to be expressed in terms of the universal standard. Linear regression data confirmed the predictive accuracy of the universal standard. CONCLUSION: This study shows that a single standard of eight purified allergens can be used to compare allergen measurements by immunoassay. This approach will improve the continuity of environmental exposure assessments and provide improved standardization of allergy diagnostics and vaccines used for immunotherapy.


Asunto(s)
Alérgenos/análisis , Inmunoensayo/normas , Alérgenos/inmunología , Calibración , Relación Dosis-Respuesta Inmunológica , Exposición a Riesgos Ambientales , Ensayo de Inmunoadsorción Enzimática , Humanos , Estándares de Referencia
7.
Allergy ; 63(3): 310-26, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18269676

RESUMEN

Allergen extracts have been used for diagnosis and treatment of allergy for around 100 years. During the second half of 20th century, the notion increasingly gained foothold that accurate standardization of such extracts is of great importance for improvement of their quality. As a consequence, manufacturers have implemented extensive protocols for standardization and quality control. These protocols have overall IgE-binding potencies as their focus. Unfortunately, each company is using their own in-house reference materials and their own unique units to express potencies. This does not facilitate comparison of different products. During the last decades, most major allergens of relevant allergen sources have been identified and it has been established that effective immunotherapy requires certain minimum quantities of these allergens to be present in the administered maintenance dose. Therefore, the idea developed to introduce major allergens measurements into standardization protocols. Such protocols based on mass units of major allergen, quantify the active ingredients of the treatment and will at the same time allow comparison of competitor products. In 2001, an EU funded project, the CREATE project, was started to support introduction of major allergen based standardization. The aim of the project was to evaluate the use of recombinant allergens as reference materials and of ELISA assays for major allergen measurements. This paper gives an overview of the achievements of the CREATE project.


Asunto(s)
Alérgenos/clasificación , Guías como Asunto , Hipersensibilidad/diagnóstico , Proteínas Recombinantes , Estudios de Validación como Asunto , Cromatografía Líquida de Alta Presión/normas , Desensibilización Inmunológica/normas , Ensayo de Inmunoadsorción Enzimática/normas , Europa (Continente) , Femenino , Humanos , Masculino , Espectrometría de Masas/normas , Proteínas Recombinantes/normas , Estándares de Referencia , Valores de Referencia , Sensibilidad y Especificidad , Análisis Espectral/normas , Organización Mundial de la Salud
8.
Neurosci Biobehav Rev ; 52: 221-32, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25783221

RESUMEN

There is growing evidence that chronic pain conditions can have an associated central pathology, involving both cortical reorganisation and an incongruence between expected and actual sensory-motor feedback. While such findings are primarily driven by the recent proliferation of neuroimaging studies, the psychophysical tasks that complement those investigations have received little attention. In this review, we discuss the literature that involves the subjective appraisal of body representation in patients with chronic pain. We do so by examining three broad sensory systems that form the foundations of the sense of physical self in patients with common chronic pain disorders: (i) reweighting of proprioceptive information; (ii) altered sensitivity to exteroceptive stimuli; and, (iii) disturbed interoceptive awareness of the state of the body. Such findings present compelling evidence for a multisensory and multimodal approach to therapies for chronic pain disorders.


Asunto(s)
Concienciación , Imagen Corporal , Dolor Crónico/fisiopatología , Sensación/fisiología , Sistema Nervioso Autónomo/fisiopatología , Discriminación en Psicología , Humanos , Equilibrio Postural/fisiología , Postura , Psicofísica
9.
J Bone Miner Res ; 18(9): 1584-92, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12968667

RESUMEN

UNLABELLED: TNF-alpha is a major inflammatory factor that is induced in response to injury, and it contributes to the normal regulatory processes of bone resorption. The role of TNF-alpha during fracture healing was examined in wild-type and TNF-alpha receptor (p55(-/-)/p75(-/-))-deficient mice. The results show that TNF-alpha plays an important regulatory role in postnatal endochondral bone formation. INTRODUCTION: TNF-alpha is a major inflammatory factor that is induced as part of the innate immune response to injury, and it contributes to the normal regulatory processes of bone resorption. METHODS: The role of TNF-alpha was examined in a model of simple closed fracture repair in wild-type and TNF-alpha receptor (p55(-/-)/p75(-/-))-deficient mice. Histomorphometric measurements of the cartilage and bone and apoptotic cell counts in hypertrophic cartilage were carried out at multiple time points over 28 days of fracture healing (n = 5 animals per time point). The expression of multiple mRNAs for various cellular functions including extracellular matrix formation, bone resorption, and apoptosis were assessed (triplicate polls of mRNAs). RESULTS AND CONCLUSIONS: In the absence of TNF-alpha signaling, chondrogenic differentiation was delayed by 2-4 days but subsequently proceeded at an elevated rate. Endochondral tissue resorption was delayed 2-3 weeks in the TNF-alpha receptor (p55(-/-)/p75(-/-))-deficient mice compared with the wild-type animals. Functional studies of the mechanisms underlying the delay in endochondral resorption indicated that TNF-alpha mediated both chondrocyte apoptosis and the expression of proresorptive cytokines that control endochondral tissue remodeling by osteoclasts. While the TNF-alpha receptor ablated animals show no overt developmental alterations of their skeletons, the results illustrate the primary roles that TNF-alpha function contributes to in promoting postnatal fracture repair as well as suggest that processes of skeletal tissue development and postnatal repair are controlled in part by differing mechanisms. In summary, these results show that TNF-alpha participates at several functional levels, including the recruitment of mesenchymal stem, apoptosis of hypertrophic chondrocytes, and the recruitment of osteoclasts function during the postnatal endochondral repair of fracture healing.


Asunto(s)
Cartílago/fisiología , Curación de Fractura/fisiología , Factor de Necrosis Tumoral alfa/fisiología , Animales , Antígenos CD/genética , Antígenos CD/fisiología , Apoptosis , Secuencia de Bases , Resorción Ósea/genética , Resorción Ósea/patología , Resorción Ósea/fisiopatología , Cartílago/fisiopatología , Condrocitos/patología , Condrocitos/fisiología , Masculino , Ratones , Ratones Noqueados , Ratones Transgénicos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores del Factor de Necrosis Tumoral/deficiencia , Receptores del Factor de Necrosis Tumoral/genética , Receptores del Factor de Necrosis Tumoral/fisiología , Receptores Tipo I de Factores de Necrosis Tumoral , Receptores Tipo II del Factor de Necrosis Tumoral , Transducción de Señal , Factor de Necrosis Tumoral alfa/deficiencia , Factor de Necrosis Tumoral alfa/genética
10.
Endocrinology ; 139(10): 4353-63, 1998 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9751519

RESUMEN

Chemokines, including interleukin-8 (IL-8), function as key mediators in diverse inflammatory disorders via promoting the recruitment, proliferation, and activation of vascular and immune cells. IL-8 levels are elevated in inflammatory diseases, such as rheumatoid arthritis, osteoarthritis, osteomyelitis, and periodontal disease, that also exhibit progressive bone loss. Therefore, it is possible that IL-8 contributes to the osteopenia associated with these pathological conditions. Although macrophages, neutrophils, and endothelial cells are considered the primary sources of inflammation-induced IL-8 increases, we report here for the first time that human bone marrow-derived osteoclast-like cells (hOCL) as well as authentic bone-resorbing human osteoclasts (hOC) isolated from osteoporotic femoral heads express messenger RNA (mRNA) for IL-8 and secrete high levels of IL-8 during culture. Basal IL-8 release by cultured hOC or hOCL was orders of magnitude greater than the release of the proinflammatory cytokines IL-1beta, IL-6, and tumor necrosis factor-alpha. At a cellular level, in situ hybridization analysis revealed that IL-8 mRNA was expressed in resorbing hOC of rheumatoid arthritic pannus and was substantially greater than that expressed in hOC of noninflammatory giant cell tumor of bone tissue. Therefore, the potential inflammation-mediated induction of IL-8 was directly assessed using cultured hOCL. IL-8 release was stimulated by proinflammatory signals (IL-1alpha, tumor necrosis factor-alpha, lipopolysaccharide, or phorbol 12-myristate 13-acetate), unaffected by various other osteotropic modulators (transforming growth factor-beta1 and -beta3, IL-6, 17beta-estradiol, or calcitonin) and was decreased by interferon-gamma, vitamin D3, and the antiinflammatory glucocorticoid dexamethasone. Changes in IL-8 secretion were paralleled by corresponding changes in IL-8 mRNA steady state levels. We conclude that hOC and hOCL synthesize and secrete high constitutive and inflammation-stimulated levels of the chemokine IL-8. Consequently, hOC-derived IL-8 could act as an important regulatory signal for bone, vascular, and immune cell recruitment and activation during normal and pathological bone remodeling.


Asunto(s)
Artritis Reumatoide/metabolismo , Interleucina-8/biosíntesis , Osteoclastos/metabolismo , Calcitriol/farmacología , Células Cultivadas , Dexametasona/farmacología , Humanos , Interleucina-8/genética , ARN Mensajero/análisis
11.
Clin Exp Allergy ; 32(11): 1596-601, 2002 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12569980

RESUMEN

BACKGROUND: International guidelines recommend allergen avoidance for asthma management, but do not include making assessments of allergen exposure. Mite allergen exposure cannot be assumed, especially in geographical regions where climatic conditions vary. OBJECTIVE: To develop a rapid test that would enable consumers to detect mite allergen in the home. METHODS: A lateral flow test using gold labelled antibody for mite group 2 allergen was developed as part of a detection kit incorporating the MITEST dust sampling device. Dust samples were assayed by ELISA for group 1 and group 2 allergens and by using the rapid test. The tests were compared as indices of mite allergen exposure. RESULTS: There was a good correlation between group 1 and group 2 levels by ELISA (n = 349, r = 0.60, P < 0.001). In a multi-centre study of 65 homes (263 dust samples) in five countries, there was a strong correlation between ELISA and the rapid test. Most samples with high scores in the test (43/48, 90%) contained > 1 microg/m2 group 2 allergen, whereas most low samples contained < 1 microg/m2 (50/64, 78%). Differences between mean group 2 levels of samples that scored low (0.28 microg/m2), medium (1.68 microg/m2) or high (3.18 microg/m2) on the test were highly significant (P 0.007 to < 0.001). CONCLUSIONS: A simple rapid test has been developed that detects mite allergen in the home within 10 min. The mite screening test should educate consumers about allergen exposure and encourage compliance with allergen-avoidance procedures. This technology has applications for the detection of other common environmental allergens.


Asunto(s)
Alérgenos/análisis , Monitoreo del Ambiente/instrumentación , Vivienda , Ácaros/inmunología , Animales , Polvo , Monitoreo del Ambiente/métodos , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Reproducibilidad de los Resultados , Manejo de Especímenes/instrumentación , Manejo de Especímenes/métodos
12.
Exp Dermatol ; 4(3): 146-54, 1995 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7551562

RESUMEN

We examined the effects of daily topical application of 0.05% tretinoin cream on photodamaged Caucasian facial skin by electron microscopy. Specimens obtained pretreatment, after 6 and 12 months of tretinoin therapy (20 patients), and after 6 months of vehicle treatment (5 patients) were compared in a blinded fashion, with special attention to the dermoepidermal junction and papillary dermis. Baseline specimens disclosed various degrees of damage including reduplication of basal lamina, smudging and sparsity of collagen fibers, and nodular arrangement of degenerated microfibrils in the papillary dermis. No significant changes were observed at 6 months in the papillary dermis of either tretinoin-treated or vehicle-treated patients. After 12 months of tretinoin treatment, however, disorganized collagen fibers, which were conspicuous in 11 patients at baseline, were replaced by new well-organized collagen fibers in a wavy pattern in 6 patients. In addition, the amount of nodularly degenerated microfibrillar material decreased in 15 of 18 patients with this finding at baseline. In contrast, no significant change was noted in the number of anchoring fibrils per unit length of the lamina densa. These observations provide further evidence that topical treatment with 0.05% tretinoin produces papillary dermal reconstruction, for which more than 6 months of application were required.


Asunto(s)
Epidermis/ultraestructura , Proteínas de la Matriz Extracelular , Queratolíticos/farmacología , Envejecimiento de la Piel/efectos de los fármacos , Tretinoina/farmacología , Administración Tópica , Adulto , Colágeno/metabolismo , Proteínas Contráctiles/metabolismo , Método Doble Ciego , Tejido Elástico/efectos de los fármacos , Tejido Elástico/metabolismo , Epidermis/metabolismo , Epidermis/patología , Cara , Femenino , Humanos , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Factores de Empalme de ARN , Factores de Tiempo , Tretinoina/administración & dosificación
13.
Am J Dermatopathol ; 14(3): 224-30, 1992 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-1510219

RESUMEN

We used clinical criteria to study skin biopsy specimens with mild to moderate photoaging taken from the face and dorsal forearms of 74 Caucasian volunteers between the ages of 30 and 50. Facial skin had a greater number of granular cell layers, a higher degree of keratinocytic atypia, and more often showed a compact stratum corneum than arm skin. Furthermore, the dermis of facial skin had a more extensive perivascular and perifollicular lymphocytic infiltrate, more perifollicular fibrosis, a greater number of mast cells and melanophages, and thinner vascular walls than forearm skin. This study demonstrated that the photoaging process is different for face and arm skin. Appreciation of these differences should permit more refined studies of photoaging and the development of more efficient therapies.


Asunto(s)
Brazo , Cara , Envejecimiento de la Piel/patología , Adulto , Tejido Elástico/patología , Epidermis/patología , Femenino , Fibrosis , Foliculitis/patología , Histiocitos/patología , Humanos , Queratinocitos/patología , Masculino , Mastocitos/patología , Melaninas , Melanocitos/patología , Persona de Mediana Edad , Mucinas , Piel/patología
14.
Arthritis Rheum ; 43(2): 250-8, 2000 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10693863

RESUMEN

OBJECTIVE: Osteoclast differentiation factor (ODF; also known as osteoprotegerin ligand, receptor activator of nuclear factor kappaB ligand, and tumor necrosis factor-related activation-induced cytokine) is a recently described cytokine known to be critical in inducing the differentiation of cells of the monocyte/macrophage lineage into osteoclasts. The role of osteoclasts in bone erosion in rheumatoid arthritis (RA) has been demonstrated, but the exact mechanisms involved in the formation and activation of osteoclasts in RA are not known. These studies address the potential role of ODF and the bone and marrow microenvironment in the pathogenesis of osteoclast-mediated bone erosion in RA. METHODS: Tissue sections from the bone-pannus interface at sites of bone erosion were examined for the presence of osteoclast precursors by the colocalization of messenger RNA (mRNA) for tartrate-resistant acid phosphatase (TRAP) and cathepsin K in mononuclear cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to identify mRNA for ODF in synovial tissues, adherent synovial fibroblasts, and activated T lymphocytes derived from patients with RA. RESULTS: Multinucleated cells expressing both TRAP and cathepsin K mRNA were identified in bone resorption lacunae in areas of pannus invasion into bone in RA patients. In addition, mononuclear cells expressing both TRAP and cathepsin K mRNA (preosteoclasts) were identified in bone marrow in and adjacent to areas of pannus invasion in RA erosions. ODF mRNA was detected by RT-PCR in whole synovial tissues from patients with RA but not in normal synovial tissues. In addition, ODF mRNA was detected in cultured adherent synovial fibroblasts and in activated T lymphocytes derived from RA synovial tissue, which were expanded by exposure to anti-CD3. CONCLUSION: TRAP-positive, cathepsin K-positive osteoclast precursor cells are identified in areas of pannus invasion into bone in RA. ODF is expressed by both synovial fibroblasts and by activated T lymphocytes derived from synovial tissues from patients with RA. These synovial cells may contribute directly to the expansion of osteoclast precursors and to the formation and activation of osteoclasts at sites of bone erosion in RA.


Asunto(s)
Artritis Reumatoide/metabolismo , Proteínas Portadoras/biosíntesis , Glicoproteínas de Membrana/biosíntesis , Membrana Sinovial/química , Células de la Médula Ósea/metabolismo , Neoplasias Óseas/química , Neoplasias Óseas/metabolismo , Resorción Ósea/metabolismo , Catepsina K , Catepsinas/genética , Expresión Génica , Tumor Óseo de Células Gigantes/química , Tumor Óseo de Células Gigantes/metabolismo , Humanos , Osteoclastos/fisiología , Ligando RANK , Receptor Activador del Factor Nuclear kappa-B , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
15.
Ann Rheum Dis ; 62(2): 100-7, 2003 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-12525377

RESUMEN

OBJECTIVES: To examine the potential role of the angiogenic growth factor angiopoietin-1 (Ang-1) in inflammatory arthritis. METHODS: Eighteen synovial tissue samples were obtained from 17 patients with a clinical diagnosis of rheumatoid arthritis (RA) and compared with six synovial tissue samples from six patients with osteoarthritis (OA). Ang-1 expression in synovial tissues was determined by immunohistochemistry and in situ hybridisation. Ang-1 mRNA and protein expression were also examined by northern blot analysis and enzyme linked immunosorbent assay (ELISA) in cultured synovial fibroblasts and human umbilical vein endothelial cells (HUVECs) before and after treatment with tumour necrosis factor (TNF)alpha. RESULTS: Ang-1 protein expression was detected by immunohistochemistry in 16/18 RA synovial tissue samples. Ang-1 protein was frequently observed in the synovial lining layer and in cells within the sublining synovial tissue, in both perivascular areas and in areas remote from vessels. In contrast, Ang-1 was only weakly detected in these sites in OA samples. Ang-1 mRNA and protein were also expressed in cultured synovial fibroblasts derived from patients with RA. In addition, induction of Ang-1 mRNA and protein was observed by northern blot analysis and ELISA after stimulation of RA synovial fibroblasts, but not HUVECs, with the proinflammatory cytokine TNF alpha. CONCLUSIONS: Ang-1 mRNA and protein are expressed in the synovium of patients with RA, and are up regulated in synovial fibroblasts by TNF alpha. Ang-1 may therefore be an important regulator of angiogenesis in inflammatory arthritis.


Asunto(s)
Inductores de la Angiogénesis/metabolismo , Artritis Reumatoide/metabolismo , Glicoproteínas de Membrana/metabolismo , Membrana Sinovial/metabolismo , Inductores de la Angiogénesis/genética , Angiopoyetina 1 , Angiopoyetina 2 , Artritis Reumatoide/patología , Northern Blotting/métodos , Técnicas de Cultivo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Técnicas para Inmunoenzimas , Hibridación in Situ , Interleucina-1/farmacología , Glicoproteínas de Membrana/genética , Osteoartritis/metabolismo , ARN Mensajero/genética , Membrana Sinovial/irrigación sanguínea , Factor de Necrosis Tumoral alfa/farmacología
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