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T L Moore

Publications and source records attributed to T L Moore.

At least 37 records · Page 2Linked to original sources

Effect of methotrexate on the temporomandibular joint and facial morphology in juvenile rheumatoid arthritis patients.

Juvenile rheumatoid arthritis is a disease characterized by chronic inflammation in one or more joints; it affects children and adolescents up to 18 years of age. This disease may cause significant skeletal joint destruction, and the temporomandibular joint, like other joints, may become severely affected resulting in aberrant mandibular growth, abnormal dentofacial development, and/or altered orofacial muscle function. Methotrexate is the most common remittive agent used in juvenile rheumatoid arthritis to modify the course of inflammatory destruction of peripheral joints. The purpose of this study was: (1) to evaluate the effect of methotrexate therapy on the prevalence of temporomandibular joint lesions and aberration in craniofacial development in children afflicted with juvenile rheumatoid arthritis; (2) to further examine the relationship between the temporomandibular joint/cephalometric findings and rheumatologic data (ie, age at onset, duration of disease); and (3) to evaluate further pauciarticular- and polyarticular-onset disease in juvenile rheumatoid arthritis and the prevalence of temporomandibular joint lesions and facial dysmorphology. The following information was obtained from 45 patients with juvenile rheumatoid arthritis: (1) routine rheumatologic clinical examination data; (2) anamnestic temporomandibular joint evaluation data; (3) clinical temporomandibular joint examination data; (4) lateral cephalometric measurement data; (5) posteroanterior cephalometric measurement data; and (6) individually corrected axial tomographic data. The results demonstrated the following: (1) radiographic evidence of condylar degeneration was apparent in 63% of all patients with juvenile rheumatoid arthritis with pauciarticular patients showing less temporomandibular involvement than polyarticular patients; (2) polyarticular juvenile rheumatoid arthritis patients receiving methotrexate showed less severe temporomandibular joint involvement than the polyarticular patients not receiving methotrexate; (3) the craniofacial structure was affected to a greater extent in the polyarticular form of the disease; (4) the craniomandibular index scores were significantly greater in the polyarticular group; (5) vertical height asymmetry and chin deviation were noted in more than 50% of the patients; and (6) there was a correlation between the severity of condylar lesions and cephalometric findings (ie, mandibular retroposition, posterior rotation, smaller ramus and mandibular dimensions) and the onset and duration of the disease. In conclusion, under the conditions of this study, methotrexate therapy was effective in minimizing temporomandibular joint destruction and craniofacial dysmorphology in juvenile rheumatoid arthritis patients with the polyarticular form of the disease.

Adolescent↗

Juvenile spondyloarthropathies.

This paper reviews the recent literature on the juvenile spondyloarthropathies. Several case reports emphasized clinical characteristics of the spondyloarthropathies including reactive arthritis. MR imaging seemed to enhance the detection of sacroiliitis in children with spondyloarthropathies. The presence of different cytokines in various forms of juvenile arthritis including the juvenile spondyloarthropathies was investigated and suggested a role for the anti-inflammatory cytokines in milder disease. Evidence for the association of low-molecular-weight polypeptide gene polymorphism with susceptibility to acute anterior uveitis was found in a Mexican population of patients with spondyloarthropathies, including 80 with juvenile spondyloarthropathy. A review of therapeutic use of sulfasalazine in children with chronic arthritis, including those with juvenile spondyloarthropathy, concluded that it was safe and effective. Last, a study assessed aerobic fitness and physical activity in patients with juvenile spondyloarthropathy in remission and suggested a decline in physical fitness in older patients.

Adolescent↗

Parvovirus-associated arthritis.

Human parvovirus B19 is the cause of several distinct clinical syndromes. The most common is erythema infectiosum (fifth disease), a febrile exanthem occurring primarily in children. Recent studies have shown that parvovirus B19 can cause acute arthritis and occasionally a chronic arthropathy, both in children and adults. Parvovirus B19 DNA has been detected in studies in the synovial tissue of patients with rheumatoid arthritis, but other studies have varied in their findings. Recent studies also indicate a possible connective tissue disease-like syndrome with parvoviral infections. The common features of this syndrome are malar eruption, arthralgias, arthritis, and laboratory abnormalities including antinuclear antibody and rheumatoid factor positivity. However, the data indicate it is unlikely that B19 infection causes rheumatoid arthritis or systemic lupus erythematosus. Continued studies of the pathogenesis of acute and chronic parvoviral B19 infections and arthropathy may provide insights into virus-host interactions and mechanisms of joint disease and connective tissue disease.

Adult↗

Estrogen and progesterone regulation of human fibroblast-like synoviocyte function in vitro: implications in rheumatoid arthritis.

OBJECTIVE: Despite increasing evidence regarding the significance of sex hormones in rheumatoid arthritis (RA), their etiopathological role and potential longterm effect on joint destruction remain unclear. We hypothesized that estrogen receptors (ER-alpha) are present in fibroblast-like synoviocytes, and 17beta-estradiol can modulate the production and activity of matrix degrading enzymes produced by these cells. Thus, depending on the endocrine balance, fibroblast-like synoviocyte activity can be suppressed or enhanced, leading to amelioration or exacerbation of the disease process, respectively. METHODS: By utilizing an in vitro cartilage invasion model, in combination with the molecular analyses of hormone receptors, matrix metalloproteinases (MMP) and their respective inhibitors, we investigated the effect of hormones (i.e., estrogen and progesterone) on fibroblast-like synoviocyte phenotypic changes, with particular emphasis on their functional interactions with cartilage. RESULTS: Our studies reveal the presence of functional ER-alpha in fibroblast-like synoviocytes. The findings indicate that estrogen exerts a stimulatory effect, while progesterone has an inhibitory effect on the expression of MMP, their tissue inhibitors (TIMP), and enzymatic activity of MMP produced by these cells. Furthermore, transfection of fibroblast-like synoviocytes with the ER-alpha gene resulted in the increased degradation and invasion of cartilage. CONCLUSION: We identified the presence of functional ER-alpha in fibroblast-like synoviocytes. This renders fibroblast-like synoviocytes as target cells for hormonal regulation. The regulatory effect of estrogen is partly targeted to the MMP and their respective inhibitors associated with fibroblast-like synoviocytes. Such studies provide a link between hormonal status and disease activity in RA and open new venues for future therapeutic intervention to combat this debilitating disease.

Adolescent↗

C1q-containing immune complexes purified from sera of juvenile rheumatoid arthritis patients mediate IL-8 production by human synoviocytes: role of C1q receptors.

Immune complexes that vary in size and composition are present in the sera and synovial fluid of juvenile rheumatoid arthritis (JRA) patients. They are believed to be potent inducers of the ongoing inflammatory process in JRA. However, the precise composition and role of these complexes in the pathophysiology of JRA remain unclear. We hypothesized that circulating ICs have the potential to interact with resident joint synovial fibroblasts (synoviocytes) and induce the expression of inflammatory cytokines. To test this hypothesis, cultures of synoviocytes from healthy individuals were treated with ICs isolated from the sera of JRA patients. Studies reported in this work demonstrate that IgM affinity-purified ICs from the sera of JRA patients contain IgM, C1q, IgG, and C3 to a variable extent. These ICs induce IL-8 mRNA and protein production in normal synoviocytes. Our data indicate that C1q in these ICs mediates, in part, IL-8 induction in synoviocytes. This is based on our findings of C1q-binding proteins for collagen stalks (cC1qR) and globular heads (gC1q-binding protein) of C1q in synoviocytes. In addition, collagen stalk and to some extent globular head fragments of C1q inhibit IC-mediated IL-8 induction in synoviocytes. Together, these findings provide evidence for a novel mechanism of IL-8 production by synoviocytes, which could play a key role in inflammation by recruiting leukocytes to synovial tissue and fluid-and subsequently contributing to joint disease.

Adolescent↗

Parvovirus infection mimicking systemic lupus erythematosus in a pediatric population.

OBJECTIVES: To assess the striking similarities of presentation in a pediatric population between human parvovirus B19 (HPV-B19) infection and systemic lupus erythematous (SLE). METHODS: Medical records of seven patients (ages 6 to 15) with HPV-B19 infection were reviewed retrospectively. RESULTS: Six of seven cases presented with a history of malar rash, and all seven had prolonged arthralgias and fatigue. Six of seven had a positive antinuclear antibody (ANA) titer ranging from 1:40 to greater than 1:640, with two patients having antibodies to Scl-70 and others to Sm, RNP, SS-A (Ro), or SS-B (La). The erythrocyte sedimentation rate (ESR) varied from 2 to 68 mm/h. Two patients presented with elevated rheumatoid factor (RF) titers of 24 and 271 IU/mL, respectively. All had elevated IgM antibody levels to parvovirus at the onset, and markedly elevated IgG levels when evaluated throughout their disease course. Over the course of 2 to 3 months, three improved, but the other four continued to have symptomatology for 14, 40, 78, and 120 weeks, respectively. Treatment was symptomatic, and no one developed classic SLE. CONCLUSIONS: HPV-B19 infection in a pediatric patient group may present with SLE-like symptomatology and positive serology suggestive of SLE. The course of the disease is usually self-limited, though it may be prolonged in some for up to 120 weeks.

Adolescent↗

Immunopathogenesis of juvenile rheumatoid arthritis.

The immunopathogenic mechanisms of juvenile rheumatoid arthritis (JRA) have been debated. A possible cellular-mediated hypothesis versus a possible B cell hyperreactivity have been entertained. This review will focus on some recent cellular work in JRA and also further evaluation of cytokine levels and their role in inflammation in JRA. Recent studies have evaluated the interrelationship of Th1/Th2 immune responses in the immunopathogenesis of JRA, and their effect on cytokine release. Studies have indicated a pro-inflammatory response in systemic-onset JRA manifested by increased secretion of interleukin-6, whereas an anti-inflammatory response has been noted by increases of IL-4 mRNA and IL-10 mRNA in pauciarticular-onset JRA. The continued finding of elevated levels of tumor necrosis factor-alpha (TNF-alpha) and its receptors in association with inflammatory activity has been seen. The recent use of a TNF fusion protein to block TNF-alpha activity in JRA has further contributed to this finding. Further studies on specific cytokines will be helpful in the future in trying to determine the different roles cytokines play in JRA subtypes and would contribute to the development of better therapeutic regimens.

Adolescent↗

Expression of macrophage markers by a population of T cells obtained from synovial fluid of a subgroup of patients with juvenile rheumatoid arthritis.

OBJECTIVE: To characterize distinctive lymphoid cell populations in the synovial fluid (SF) of patients with juvenile rheumatoid arthritis (JRA) that have the specific ability to display monocytic markers when cultured in vitro. METHODS: Mononuclear cells obtained from SF of patients with JRA and depleted of adherent macrophages were cultured in vitro in RPMI 1640 medium supplemented with only fetal calf serum (FCS). Phenotypic evaluation of these cells was by flow cytometry and immunohistochemical analysis was by specific fluorochrome labeled antibodies. RESULTS: T cells from a JRA subgroup displayed some typical macrophage attributes, i.e., abundant cytoplasm, adherence to plastic, and phagocytosis of latex beads when cultured in vitro. These cells have the ability to survive in culture for several weeks in RPMI 1640 medium containing only 10% FCS. The macrophage-like T cells rosetted with sheep red blood cells and proliferated when stimulated with phytohemagglutinin or anti-CD3, indicating functional T cell responses. CONCLUSION: Our data indicate that a population of T cells obtained from the SF of a subgroup of patients with JRA exhibited characteristics of macrophages, yet retained their CD3 and T cell receptor expression. Whether this promiscuous behavior is caused by malignant transformation of lymphoid precursor cells or is induced by the concerted effect of a myriad of cytokines and growth factors present in the SF remains unknown. The presence of these cells in the SF of 2 patients with JRA with different onset types raises the question of their function and significance in an autoimmune disorder such as JRA.

Adolescent↗

Mycoplasma infection and rheumatoid arthritis: analysis of their relationship using immunoblotting and an ultrasensitive polymerase chain reaction detection method.

OBJECTIVE: To examine the relationship between infection with Mycoplasma and the development of rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA). METHODS: Immunoblotting of patient synovial fluid and sera on detergent-phase membrane protein extracts of various Mycoplasma species was carried out to learn whether patients exhibited serologic evidence of previous exposure to mycoplasmas. Moreover, an ultrasensitive polymerase chain reaction (PCR) method was developed for assessing whether Mycoplasma DNA could be detected in synovial fluid from patients and controls. RESULTS: Immunoblotting provided serologic evidence of previous Mycoplasma exposure in patients and controls. The genus-specific PCR detected known human Mycoplasma species and could reliably detect <5 copies of Mycoplasma hominis, Mycoplasma fermentans, or a molecular mimic control in synovial fluid. Repeat testing revealed no evidence of Mycoplasma DNA in patient synovial samples. CONCLUSION: This study provided serologic evidence suggesting that, while previous exposure to Mycoplasma was common, there was no detectable persistence of Mycoplasma DNA in the synovial fluid or tissue of patients with RA or JRA.

Adult↗

Induction of invasive and degradative phenotype in normal synovial fibroblasts exposed to synovial fluid from patients with juvenile rheumatoid arthritis: role of mononuclear cell population.

OBJECTIVE: To investigate the effect of synovial fluid (SF) from patients with juvenile rheumatoid arthritis (JRA) on proliferation and induction of degradative and invasive phenotype in normal synovial fibroblasts, and to elucidate the contribution of SF cells to this activity. METHODS: SF and/or conditioned medium (CM) from SF cells were evaluated for their ability to (1) stimulate a proliferative response, (2) induce the "activated phenotype" capable of invading cartilage matrix, and (3) promote the release of key matrix metalloproteinases (MMP) in normal synovial fibroblasts. RESULTS: Proliferation of normal synovial fibroblasts exposed to SF or CM from SF cells of patients with JRA was up to 3 times greater than untreated controls. Concomitant with induction of an activated phenotype in the treated synovial fibroblasts, the activated form exhibited up to 250% invasiveness of cartilage matrix compared to untreated synovial fibroblasts (100%), in addition to releasing increased MMP activity, not normally associated with these quiescent cells. This induction was not solely due to tumor necrosis factor-alpha, transforming growth factor-beta, interleukin 1beta (IL-1beta), and IL-6, as SF and/or CM depleted of these cytokines sustained about 40% of their invasive and inducing ability. We observed that the mononuclear cell (MNC) population that infiltrated into the joint cavity secretes this "inducing activity," which can be maintained in culture up to several weeks. CONCLUSION: Our data suggest that the cellular component of SF releases soluble factor(s) that directly or indirectly contribute to (a) proliferation of synovial fibroblasts, and (b) production and release of extracellular MMP by synovial fibroblasts, thereby inducing a degradative and invasive phenotype culminating in cartilage and bone destruction.

Antibodies↗

Effects of systemic onset juvenile rheumatoid arthritis on facial morphology and temporomandibular joint form and function.

OBJECTIVE: Twenty-four patients with systemic onset juvenile rheumatoid arthritis (JRA) were evaluated to determine its effects on facial morphology and temporomandibular joint (TMJ) form and function. METHODS: Patients were evaluated with medical and dental histories, facial photographs, intraoral examination, TMJ examination, lateral tomograms or panoramic radiographs, cephalograms, and impressions for study models. The craniomandibular index (CMI) was used to quantitate mandibular movement, tenderness, and TMJ noise. Symptoms were measured by symptom severity index (SSI). CMI data from the patients with JRA were compared to a group of 24 children without JRA with similar mean age and sex distribution. RESULTS: Our study indicates the facial morphology of patients with systemic onset JRA is similar to that of healthy children except for a mild convex facial profile and backward rotation of the mandible. Changes in facial form were associated with radiographic condylar abnormalities. CMI scores and SSI scores of systemic onset patients were significantly greater than controls, and radiographic condylar changes were noted in 29.2% of the patients with systemic onset JRA. CONCLUSION: Our study suggests that systemic onset JRA significantly affects TMJ form and function. Facial form was only affected in the few patients with significant radiographic condylar changes.

Adolescent↗

Effects of polyarticular and pauciarticular onset juvenile rheumatoid arthritis on facial and mandibular growth.

OBJECTIVE: To characterize the functional and morphologic effects of polyarticular and pauciarticular onset juvenile rheumatoid arthritis (JRA) on the temporomandibular joint (TMJ). METHODS: Medical and dental histories, intraoral, lateral cephalometric, and panoramic radiographs, facial photographs, and dental study models were obtained for each of 30 patients with JRA (17 pauciarticular and 13 polyarticular onset). Measures of TMJ dysfunction were gathered during the clinical examination, and an index of condylar morphology was inferred from the panoramic radiographs. The lateral cephalograms were traced, and data from 34 linear and angular measures used to compare the facial morphology of the 2 JRA onset types, both to normative standards and to each other (Student's t test). The Kruskal-Wallis test was used to evaluate the significance of between-group differences for the various ordinal indices. RESULTS: As indicated by the higher TMJ dysfunction and condylar index scores, polyarticular onset JRA affects the form and function of the TMJ more frequently and severely than does pauciarticular onset. Moreover, compared to normative cephalometric standards, the patients with polyarticular onset had small, short faces with underdeveloped mandibles. CONCLUSION: Both polyarticular and pauciarticular onset JRA have a negative effect on the form, function, and esthetics of the face and mandible; however, the effects are more pronounced with polyarticular JRA than pauciarticular onset.

Adolescent↗

Major histocompatibility complex class II-associated invariant chain gene expression is up-regulated by cooperative interactions of Sp1 and NF-Y.

Expression of the major histocompatibility complex (MHC) class II-associated invariant chain (Ii) is required for efficient and complete presentation of antigens by MHC class II molecules and a normal immune response. The Ii gene is generally co-regulated with the MHC class II molecules at the level of transcription and a shared SXY promoter element has been described. This report defines the proximal promoter region of Ii which may regulate Ii transcription distinct from MHC class II. In vivo genomic footprinting identified an occupied, imperfect CCAAT box and an adjacent GC box in the proximal region. These sites are bound in Ii-ositive cell lines and upon interferon-gamma induction of Ii transcription. In contrast, both sites are unoccupied in Ii-egative cell lines and in inducible cell lines prior to interferon-gamma treatment. Together these two sites synergize to stimulate transcription. Independently, the transcription factor NF-Y binds poorly to the imperfect CCAAT box with a rapid off rate, while Sp1 binds to the GC box. Stabilization of NF-Y binding occurs upon Sp1 binding to DNA. In addition, the half-life of Sp1 binding also increased in the presence of NF-Y binding. These findings suggest a mechanism for the complete functional synergy of the GC and CCAAT elements observed in Ii transcription. Furthermore, this report defines a CCAAT box of imperfect sequence which binds NF-Y and activates transcription only when stabilized by an adjacent factor, Sp1.

Animals↗

Parvovirus infection mimicking systemic lupus erythematosus.

There are striking similarities between human parvovirus B19 (HPV-B19) infection and systemic lupus erythematosus (SLE): both may present with malar rash, fever, arthropathy, myalgia, cytopenia, hypocomplementemia, anti-DNA, and antinuclear antibodies (ANA). Therefore, it is difficult at times to differentiate HPV-B19 infection from SLE presentation or exacerbation. We report 4 cases of HPV-B19 infection mimicking SLE and review 10 other reported cases, all of whom were women. The similarity to a typical SLE presentation was indeed striking: most patients presented with rash, arthropathy, myalgia, fever, and positive ANA. In some cases, HPV-B19 infection seemed to exacerbate SLE rather then resemble it, and differentiation was difficult. Nearly all patients improved within several weeks. However, a few patients had symptoms and laboratory abnormalities lasting more than 6 months. The possibility of HPV-B19 infection should be entertained in patients presenting with SLE-like features.

Adult↗