RESUMO
We describe a lupus flare in a 59-year-old woman who presented with pancytopenia, nephritis, severe renal dysfunction and marked hyperferritinemia. The course of the disease was further complicated by an iron-laden, intraspinal ancient schwannoma that compressed the cervical cord mimicking a lupus-related myelopathy and was removed surgically. Treatment with mycophenolate mofetil (MMF) and prednisone induced a gradual decline in levels of serum ferritin with a concomitant improvement in renal function and reduction of proteinuria. Serum ferritin may be a useful marker of the response to treatment with MMF in renal lupus.
Assuntos
Ferritinas/sangue , Nefrite Lúpica/complicações , Neurilemoma/complicações , Neurilemoma/patologia , Neoplasias da Medula Espinal/complicações , Neoplasias da Medula Espinal/patologia , Antirreumáticos/uso terapêutico , Vértebras Cervicais , Feminino , Humanos , Nefrite Lúpica/sangue , Nefrite Lúpica/tratamento farmacológico , Pessoa de Meia-Idade , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Prednisona/uso terapêuticoRESUMO
The protein encoded by the protooncogene c-jun, included in the activator protein-1 (AP-1) complex, is probably the critical trans-acting factor controlling transcription of the procollagenase gene which is rate limiting for subsequent synthesis of procollagenase. Therefore, to elucidate possible mechanisms whereby IL-1 stimulates procollagenase synthesis, we measured levels of c-jun and procollagenase mRNA in human serum-starved dermal fibroblasts in response to human recombinant IL-1 beta (hrIL-1 beta). hrIL-1 beta or serum induced rapid increases in c-jun mRNA levels; mRNA levels declined rapidly after hrIL-1 beta and more slowly after exposure to serum. The increases in levels of c-jun mRNA preceded the increases in procollagenase mRNA. Whereas the increases in levels of procollagenase mRNA were blunted by cycloheximide, those of c-jun mRNA were enhanced. We interpret these results as follows: IL-1 or serum induce transcription of c-jun by mechanisms independent of new protein synthesis; c-JUN, the protein product of c-jun in the AP-1 complex, is an essential mediator of the effects of IL-1 or serum in the subsequent induction of expression of the procollagenase gene.
Assuntos
Fenômenos Fisiológicos Sanguíneos , Colagenases , Proteínas de Ligação a DNA/biossíntese , Precursores Enzimáticos/biossíntese , Fibroblastos/metabolismo , Interleucina-1/farmacologia , Colagenase Microbiana/biossíntese , Proteínas Proto-Oncogênicas/biossíntese , RNA Mensageiro/biossíntese , Fatores de Transcrição/biossíntese , Células Cultivadas , Meios de Cultura , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Humanos , Proteínas Proto-Oncogênicas c-jun , RNA Mensageiro/efeitos dos fármacos , Proteínas Recombinantes/farmacologiaRESUMO
The response of human T lymphocytes to various stimuli includes the expression of the matrix metalloproteinase (MMP) genes stromelysin 2, gelatinase A and gelatinase B. The proteins encoded by these genes could confer the capacity to degrade macromolecular components of the extracellular matrix (ECM), and to shed transmembrane proteins such as tumor necrosis factor (TNF), TNF receptor, Interleukin-6 receptor and Fas ligand. To identify further MMP genes transcribed in T lymphocytes exposed to phorbol 12-myristate 13-acetate and a calcium ionophore, we combined reverse transcription and polymerase chain reaction using primers specific for conserved domains and detected collagenase 3 transcripts, first described in a human breast cancer. However, when the sequence of the complementary DNA was compared, additional 23 nucleotides were found in the 5' nontranslated region of the lymphocyte messenger RNA (mRNA). Northern blot analysis revealed 2 major inducible mRNA species of 1.9 and 2.8 kilobases, whose levels were lower than those of stromelysin 2. The observation that activated T lymphocytes transcribe several MMP genes, including a collagenase, indicates that the effector functions of these cells include enzymatic activities towards most constituents of the ECM, as well as some transmembrane proteins relevant to inflammation and apoptosis.
Assuntos
Colagenases/genética , Metaloproteinase 3 da Matriz/genética , Linfócitos T/enzimologia , Northern Blotting , Neoplasias da Mama/enzimologia , Clonagem Molecular , Colagenases/biossíntese , Colagenases/fisiologia , DNA Complementar/biossíntese , DNA Complementar/genética , Feminino , Humanos , Análise de Sequência de DNARESUMO
In the inflammatory synovium production of collagenase is probably responsible for the degradation of collagen in the extracellular matrix and distortion of the architecture and function of the joints. Major collagenase-producing cells are mesenchymal cells such as fibroblasts and chondrocytes, which synthesize and secrete the enzyme influenced by the action of cytokines produced by adjacent mononuclear cells. The cytokines act primarily through cell-surface receptors, whose signal is probably then mediated by complexes of nuclear oncoproteins, to activate transcription of the procollagenase gene. The increased production of collagenase ultimately is the result of a cascade of cellular effects involving complex interactions of different ligands in a system characterized by amplification and feedback loops.
Assuntos
Artrite Reumatoide/enzimologia , Matriz Extracelular/ultraestrutura , Colagenase Microbiana/metabolismo , Artrite Reumatoide/patologia , Células Cultivadas , Humanos , Cinética , Colagenase Microbiana/genética , Modelos Biológicos , Membrana Sinovial/enzimologia , Membrana Sinovial/patologiaRESUMO
The effect of adenosine-5'-N-ethylcarboxamide, (NECA), a long-lasting adenosine derivative with pronounced vasoactivity was investigated on glucagon and insulin release from the in situ isolated blood perfused pancreas in the anesthetized dog: NECA (10(-9) to 10(-5) mol/l) led to a dose-dependent glucagon release. Insulin release was inhibited by NECA at low concentrations, but significantly increased at higher concentrations of the adenosine analogue. Similar effects were observed with infusion of adenosine at 10(-7) and 10(-6) mol/l. Aminophylline (10(-4) mol/l) produced a 10-fold attenuation of the actions of NECA. The preponderance of glucagon release at low concentrations of NECA and adenosine in contrast to that of insulin release at high concentrations may represent a local pancreatic regulatory mechanism of adenosine in glucose homeostasis.
Assuntos
Adenosina/análogos & derivados , Adenosina/farmacologia , Glucagon/metabolismo , Insulina/metabolismo , Pâncreas/metabolismo , Adenosina-5'-(N-etilcarboxamida) , Aminofilina/farmacologia , Anestesia , Animais , Glicemia/metabolismo , CãesRESUMO
The effect of beta-adrenoceptor antagonists on the intravenous glucose tolerance test was investigated in conscious dogs. dl-Celiprolol (cardioselective with ISA = intrinsic sympathomimetic activity) 200 and 1000 microgram/kg i.v., dl-metoprolol (cardio-selective without ISA) 200 and 1000 microgram/kg i.v., dl-pindolol (non-selective with ISA) 5 and 25 microgram i.v. and l-bupranolol (non-selective without ISA) 10 and 50 microgram/kg i.v. were used in the study. The influence of beta-adrenoceptor antagonists on the plasma glucose and immunoreactive insulin following intravenous glucose tolerance test were evaluated by calculating the respective areas under the plasma curve. The present investigation clearly demonstrates the marked difference between the various beta-adrenoceptor antagonists on heart rate and, especially on metabolic parameters. dl-Metoprolol, a beta-adrenoceptor antagonist with cardioselectivity and without ISA can be assumed not to alter plasma insulin level and glucose assimilation. l-Bupranolol, a non-selective beta-adrenoceptor antagonist without ISA reduces plasma insulin level and probably enhances peripheral glucose uptake, resulting in an "unchanged" glucose tolerance. dl-Celiprolol or dl-pindolol, beta-adrenoceptor antagonists with ISA, but cardioselective or non-selective enhance both, basal insulin level and insulin level after glucose stimulation but must be assumed to decrease peripheral glucose uptake since here too glucose tolerance was unchanged.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Glucose/farmacologia , Insulina/sangue , Animais , Glicemia/metabolismo , Cães , Ácidos Graxos não Esterificados/sangue , Glucagon/sangue , Teste de Tolerância a Glucose , Meia-Vida , Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacosRESUMO
The relevance of the steric configuration to the effects of two non-selective beta-adrenoceptor antagonists without intrinsic sympathomimetic activity (+)- and (--)-bupranolol (10 and 50 micrograms/kg i.v.) and (4)- and (--)-propranolol (100 and 500 micrograms/kg i.v.) on the i.v. glucose tolerance test (IVGTT) were investigated in conscious, normoglycemic dogs. The effects of the beta-adrenoceptor antagonists on plasma glucose, and insulin levels and insulin-glucagon ratio following IVGTT were evaluated by calculating the respective areas under the curve (AUC). The AUC values for plasma glucose were significantly increased by the (--)-configuration of both beta-adrenoceptor increased by the (--)-configuration of both beta-adrenoceptor antagonists. In the (+)-configuration only propranolol (500 micrograms/kg i.v.) increased the AUC value for plasma glucose significantly. The AUC values for plasma insulin and also for the plasma insulin-glucagon ratio were significantly increased by (--)-propranolol (500 micrograms/kg i.v.) and by (--)-bupranolol (10 and 50 micrograms/kg i.v.). Thus the impairment of glucose tolerance, due to suppression of the plasma insulin level, depends mainly on the beta-adrenoceptor antagonistic activity of the (--)-configuration.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Glicemia/análise , Insulina/sangue , Animais , Bupranolol/farmacologia , Cães , Glucagon/sangue , Teste de Tolerância a Glucose , Propranolol/farmacologia , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Matrix metalloproteinases (MMP) are a family of structurally related endopeptidases that resorb macromolecules of the extracellular matrix (ECM). They are involved in normal tissue remodeling and wound repair as well as in pathological processes such as the irreversible destruction of joints observed in rheumatoid arthritis (RA). In addition, MMP catalyze the cleavage of the transmembrane form of tumor necrosis factor (TNF). Since cells of the monocyte lineage are major producers of TNF in the rheumatoid synovium we analysed the expression of MMP genes in these cells. To examine the transcriptional activity of MMP genes in undifferentiated monocytic cell lines (MonoMac6, U937) and in nature human monocytes isolated from peripheral blood, we developed an assay that is based on reverse transcription (RT) followed by a polymerase chain reaction (PCR). This screening procedure demonstrates that several MMP genes are transcriptionally active in the cells tested after exposure to a variety of stimuli such as phorbol ester, lipopolysaccharide (LPS) and staphylococcal enterotoxin B (SEB). The data were confirmed by quantitative Northern blot analysis. In conclusion, cells of the monocyte lineage produce high mRNA levels of at least six members of the MMP gene family that could participate in joint destruction by resorption of the ECM and secretion of TNF.
Assuntos
Regulação Enzimológica da Expressão Gênica , Metaloendopeptidases/biossíntese , Monócitos/enzimologia , Diferenciação Celular , Células Cultivadas , Humanos , Metaloendopeptidases/genética , Monócitos/citologiaRESUMO
Blood flow was measured both in the circumflex and descending branch of the left coronary artery of anaesthetized dogs. Venous blood was sampled from the areas supplied by these vessels and arterial blood from the aorta for determination of oxygen-saturation, haemoglobin content, pCO2, glucose, lactate, and free fatty acids (FFA). The coronary blood flow in both branches, heart rate, aortic blood pressure, LVEDP and LVdp/dtmax were registered continuously. After taking control values, resting blood flow in the circumflex branch was mechanically reduced by 40% and the changes in haemodynamics and myocardial metabolism were measured 30 min thereafter. Heart rate, blood flow in the descending branch and LVEDP rose, whilst arterial blood pressure and LVdp/dt were not significantly changed. The partially ischaemic myocardium showed a decrease in lactate, FFA and oxygen uptake and CO2 release. The simultaneously determined metabolic parameters for the non-ischaemic region showed significant increases in lactate and oxygen uptake and CO2 and H-ion release. The overall balance (partially ischaemic and normal regions) showed a significant decrease in lactate and FFA uptake, which was, however, of very small magnitude. These results show that the antianginal action of drugs should not be assessed by determination of arterio-coronary venous balances for the whole heart, but for partially ischaemic and normal regions separately, as is possible in the presented experimental model. Moreover, sympathetic or direct stimulation can be used to stimulate increased effort of the heart such as occurs in angina pectoris.
Assuntos
Circulação Coronária/efeitos dos fármacos , Doença das Coronárias/fisiopatologia , Coração/efeitos dos fármacos , Animais , Cães , Modelos BiológicosRESUMO
Churg-Strauss Syndrome (CSS) is rare in children. It consists of a small- and medium-sized vessel vasculitis, with skin and peripheral nerve involvement. It is characterized by eosinophilia, extravascular necrotizing granuloma, and eosinophilic infiltration of multiple organs particularly the lungs, but may also involve the gastrointestinal tract, the heart, and the kidneys. The condition is usually associated with a preceding history of asthma or allergic sinusitis. It has rarely been reported in children, where most of the cases had pre-existing asthma, allergic rhinitis, or atopic disease. We report a 10-year-old Arab girl proven to have CSS, with no history of asthma or allergic rhinitis, who presented with tender cutaneous nodules of lower extremities, foot drop, and peripheral eosinophilia, without any clinical respiratory symptoms or signs.
Assuntos
Carteolol/uso terapêutico , Doença das Coronárias/tratamento farmacológico , Eletrocardiografia , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Propanolaminas/uso terapêutico , Carteolol/farmacologia , Humanos , Sistema Nervoso Simpático/efeitos dos fármacosRESUMO
The matrix metalloproteinases, i.e. collagenases, gelatinases and stromelysins, are members of a gene family. They are capable of degrading every component of the extracellular matrix. Tissue destruction observed in inflammatory joint disease is largely accounted for by the action of these enzymes. Among the most potent inducers of metalloproteinase expression are the inflammatory cytokines IL-1 and TNF-alpha. Studies of mechanisms of induction by these mediators at the transcriptional level have improved our understanding of the biological controls of metalloproteinase synthesis. Cytokine inhibitors might serve to inhibit or postpone the crippling consequences of metalloproteinase action.
Assuntos
Artrite/fisiopatologia , Metaloendopeptidases/fisiologia , Matriz Extracelular/enzimologia , Expressão Gênica , Humanos , Família MultigênicaRESUMO
OBJECTIVE: T lymphocytes are known to interact with cellular and structural components of the extracellular matrix. We investigated whether T lymphocytes could also contribute to matrix breakdown by expression of a matrix metalloproteinase (MMP) gene. METHODS: Complementary DNA (cDNA) was synthesized from messenger RNA extracted from cultured peripheral blood T lymphocytes after exposure to phorbol myristate acetate and calcium ionophore A23187 and amplified by the polymerase chain reaction with primers derived from two conserved domains in MMP genes. RESULTS: An amplification product of 402 basepairs was generated and cloned; sequence analysis revealed identity to human stromelysin-2 cDNA. Using the amplified stromelysin-2 cDNA as a probe for Northern analyses, we detected a 1.8-kilobase transcript in stimulated T lymphocytes. CONCLUSION: T lymphocytes are a potential source of stromelysin-2 transcripts and may have a role in the degradation of extracellular matrix constituents.
Assuntos
Metaloendopeptidases/genética , Linfócitos T/enzimologia , Sequência de Bases , Humanos , Metaloproteinase 10 da Matriz , Metaloendopeptidases/isolamento & purificação , Dados de Sequência Molecular , RNA Mensageiro/isolamento & purificação , Análise de Sequência de DNARESUMO
A 42-year-old man had a 4 year history of sarcoidosis stage II (lung). In biopsied specimens of the antrum we found epithelioid granulomas caused by gastric involvement in sarcoidosis. Coincidentally we found a gastric ulcer which was later the source of gastric bleeding. The granulomas were located around this ulcer and also under intact mucosa. Therefore, in our opinion it was not the case that granulomatous gastritis caused the ulceration in a direct way. We saw a connection between hypercalcemia--often found in patients with sarcoidosis, as in our patient--and the gastric ulcer. Therapy was thus aimed at lowering the blood calcium concentration. Steroids were avoided at this time. The ulceration healed, although granulomatous gastritis continued.
Assuntos
Gastrite/patologia , Sarcoidose/patologia , Biópsia , Feminino , Mucosa Gástrica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Antro Pilórico/patologia , Úlcera Gástrica/patologiaRESUMO
Keratinocyte growth factor (KGF) has been implicated in wound re-epithelialization and branching morphogenesis of several organs. To determine whether KGF induces these effects via induction of matrix metalloproteinase expression we have analysed the effect of KGF on the expression of stromelysin-2 in cultured HaCaT keratinocytes. Here we show a strong induction of stromelysin-2 mRNA within 5-8 h of stimulation of these cells with KGF. The degree of induction was similar to that achieved by treatment with epidermal growth factor or tumour necrosis factor alpha, whereas the stimulatory effect of transforming growth factor beta 1 was even stronger. To determine whether the induction of stromelysin-2 expression by growth factors and cytokines might be important for wound healing, we analysed the expression of this gene during the healing process of full-thickness excisional wounds in mice. Whereas stromelysin-2 mRNA could hardly be detected in unwounded skin, a biphasic induction was seen after injury and highest levels were found at days 1 and 5 after wounding. Hybridization in situ revealed the presence of stromelysin-2 mRNA in basal keratinocytes at the wound edge but not in the underlying mesenchymal tissue. During impaired wound healing as seen in glucocorticoid-treated mice, stromelysin-2 expression was significantly increased compared with untreated control mice. Taken together, these results suggest that correct regulation of this broad-spectrum metalloproteinase might be important for normal repair.
Assuntos
Fatores de Crescimento de Fibroblastos , Regulação Enzimológica da Expressão Gênica , Substâncias de Crescimento/farmacologia , Queratinócitos/enzimologia , Metaloendopeptidases/biossíntese , Cicatrização , Ferimentos e Lesões/fisiopatologia , Animais , Células Cultivadas , Feminino , Fator 10 de Crescimento de Fibroblastos , Fator 7 de Crescimento de Fibroblastos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/farmacologia , Humanos , Hibridização In Situ , Queratinócitos/fisiologia , Metaloproteinase 10 da Matriz , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase , RNA Mensageiro/biossíntese , Pele/enzimologia , Transcrição Gênica/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/enzimologiaRESUMO
We describe a patient wit posttraumatic reflex sympathetic dystrophy involving the right hand who subsequently developed inverse psoriatic skin lesions and psoriatic arthritis in the injured hand as well as in other joints.
Assuntos
Artrite Psoriásica/etiologia , Traumatismos da Mão/complicações , Psoríase/etiologia , Distrofia Simpática Reflexa/etiologia , Adulto , Mãos/diagnóstico por imagem , Mãos/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , CintilografiaRESUMO
In this study, we investigated the expression patterns of 15 matrix metalloproteinases (MMPs) and three tissue inhibitors of metalloproteinase in gliomas, medulloblastomas, and normal brain tissue. By Northern blot analysis we found increased levels of mRNAs encoding for gelatinase A, gelatinase B, two membrane-type MMPs (mt1- and mt2-MMP), and tissue inhibitors of metalloproteinase-1 in glioblastomas and medulloblastomas. We observed a significant increase of mt1-MMP, gelatinase A, gelatinase B, and tissue inhibitors of metalloproteinase-1 in glioblastomas as compared with low-grade astrocytomas, anaplastic astrocytomas, and normal brain. In medulloblastomas, the expression of mt1-MMP, mt2-MMP, and gelatinase A were also increased, but to a lesser extent than that observed in glioblastomas. These data were confirmed at the protein level by immunostaining analysis. Moreover, substrate gel electrophoresis showed that the activated forms of gelatinases A and B were present in glioblastomas and medulloblastomas. These results suggest that increased expression of mt1-MMP/gelatinase A is closely related to the malignant progression observed in gliomas. Furthermore, the present study demonstrates, to our knowledge for the first time, that medulloblastomas express high levels of MMP.
Assuntos
Neoplasias Encefálicas/enzimologia , Metaloendopeptidases/biossíntese , Inibidores Teciduais de Metaloproteinases/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Northern Blotting , Neoplasias Encefálicas/metabolismo , Criança , Colagenases/metabolismo , Feminino , Gelatinases/metabolismo , Glioma/enzimologia , Glioma/metabolismo , Humanos , Técnicas Imunoenzimáticas , Masculino , Metaloproteinase 15 da Matriz , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Metaloproteinases da Matriz Associadas à Membrana , Metaloendopeptidases/genética , Metaloendopeptidases/metabolismo , Pessoa de Meia-Idade , Tumores Neuroectodérmicos Primitivos/enzimologia , Tumores Neuroectodérmicos Primitivos/metabolismo , Reação em Cadeia da Polimerase , Inibidores de Proteases/metabolismo , RNA/análise , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Inibidores Teciduais de Metaloproteinases/genéticaRESUMO
The aim of the present study was to test simple reaction sequences which describe calcium-independent plus calcium-dependent phosphorylation of sarcoplasmic reticulum transport. ATPase by orthophosphate including the function of magnesium in phosphoenzyme formation. The reaction schemes considered were based on the reaction sequence for calcium-independent phosphorylation proposed previously; namely that the transport enzyme (E) forms a ternary complex (Mg . E . Pi), by random binding of free magnesium and free orthophosphate, which is in equilibrium with the magnesium-phosphoenzyme (Mg . E-P). Phosphorylation, performed at pH 7.0 20 degrees C and a constant free orthophosphate concentration using sarcoplasmic reticulum vesicles either unloaded or loaded passively with calcium in the presence of 5 mM or 40 mM CaCl2, resulted in a gradual decrease in the apparent magnesium half-saturation constant and an increase in maximum phosphoprotein formation with increasing calcium loads. When phosphorylation of sarcoplasmic reticulum vesicles preloaded in the presence of 5 mM CaCl2 was performed at a constant free magnesium concentration, a decrease in the apparent orthophosphate half-saturation constant and an increase in maximum phosphoprotein formation was observed as compared with vesicles from which calcium inside has been removed by ionophore X-537A plus EGTA treatment; however, both parameters remained unchanged by increasing free magnesium from 20 mM to 30 mM. When phosphorylation of sarcoplasmic reticulum vesicles passively loaded with calcium in the presence of 40 mM CaCl2, at which the saturation of the low-affinity calcium binding sites of the ATPase is presumably near maximum, was performed at increasing concentrations of free orthophosphate, there was a parallel shift of phosphoprotein formation as a function of free magnesium and vice versa, with no change in the maximum phosphoenzyme formation. Comparison of the experimental data with the pattern of phosphoprotein formation predicted from model equations for various theoretical possible reaction sequences suggests that phosphoenzyme formation from orthophosphate possesses the following features. Firstly, calcium present at the inside of the sarcoplasmic reticulum membrane binds to the free enzyme and in sequential order to E . Mg . Pi or Mg . E-P or to both, but neither to E. Mg nor to E . Pi. Secondly, calcium-independent and calcium-dependent phosphoproteins are magnesium-phosphoenzymes. Calcium-dependent phosphoenzyme is a magnesium-calcium-enzyme phosphate complex with 1 magnesium, 2 calciums and 1 orthophosphate (the last covalently) bound to the enzyme [Mg . E-P . (Cai)2], and not a 'calcium-phosphoprotein' without bound magnesium.
Assuntos
Adenosina Trifosfatases/metabolismo , Cálcio/farmacologia , Magnésio/farmacologia , Retículo Sarcoplasmático/metabolismo , Animais , Cinética , Matemática , Modelos Biológicos , Músculos/enzimologia , Fosfatos/farmacologia , Fosforilação , CoelhosRESUMO
PURPOSE: To assess the accuracy of different MR sequences for the detection of articular cartilage abnormalities in rheumatoid arthritis. DESIGN AND PATIENTS: Ten metacarpophalangeal joints and 10 metatarsophalangeal joints (specimens from arthritis patients undergoing ablative joint surgery) were examined with a fat-suppressed (FS) 3D FLASH, a FS 3D FISP, a FS 2D fast spin-echo T2-weighted, and a 2D FS spin-echo T1-weighted sequence. Each cartilage lesion and each cortical lesion was graded from 0 to 4 (modified Outerbridge staging system). Subsequently, the results of each sequence were compared with the macroscopic findings and statistically tested against each other. RESULTS: The study shows that 3D gradient-echo sequences with fat suppression were best for imaging and grading of cartilage lesions in arthritis of the small joints of the hands and feet. Using 3D techniques, all grade 2, grade 3, and grade 4 lesions of cartilage or cortical bone were detected. CONCLUSION: FS 3D gradient-echo techniques were best for the detection and grading of hyaline cartilage and subchondral bone lesions in rheumatoid arthritis. MRI has a great potential as an objective method of evaluating cartilage damage and bone erosions in rheumatoid arthritis.
Assuntos
Artrite Reumatoide/patologia , Cartilagem Articular/patologia , Imageamento por Ressonância Magnética/métodos , Articulação Metacarpofalângica/patologia , Articulação Metatarsofalângica/patologia , Tecido Adiposo , Idoso , Artrite Reumatoide/classificação , Artroplastia , Artroplastia de Substituição , Medula Óssea/patologia , Humanos , Hialina , Processamento de Imagem Assistida por Computador/métodos , Articulação Metacarpofalângica/cirurgia , Articulação Metatarsofalângica/cirurgia , Pessoa de Meia-Idade , Projetos Piloto , Sensibilidade e EspecificidadeRESUMO
Substitution of glycine for arginine at position 127 of the mature human interleukin 1 beta protein generates a mutant IL-1 beta protein (IL-1 beta R----G) which binds cellular IL-1 receptors with high affinity but fails to elicit significant proliferation of T-helper cells (Gehrke, L., Jobling, S. A., Paik, L. S. K., McDonald, B., Rosenwasser, L. J., and Auron, P. E. (1990) J. Biol. Chem. 265, 5922-5925). Although both IL-1 beta and the IL-1 beta R----G mutein stimulate transcription of fibroblast immediate early (fos and jun) and early (IL-1 beta and IL-6) genes, the IL-1 beta R----G mutein, in contrast to the wild-type IL-1 beta protein, induces minimal or no transcription of late genes such as procollagenase and prostromelysin. The effect of the naturally occurring IL-1 receptor antagonist protein (IL-1ra) on fibroblast transcription is distinct from that of the IL-1 beta R----G mutein, for the IL-1ra fails to stimulate not only late (procollagenase and prostromelysin) but also immediate early (fos and jun) gene expression. These data suggest that the IL-I beta R----G mutein triggers an incomplete or defective signal transduction cascade and demonstrate that fibroblast fos and jun expression is not necessarily accompanied by increased transcription of genes containing the AP-1 binding site. These data also suggest that at least two events are required for IL-1-mediated late gene induction in fibroblasts.