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Biomedical subjects

T L Moore

Publications and source records attributed to T L Moore.

At least 19 recordsLinked to original sources

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

CCAAT box binding protein NF-Y facilitates in vivo recruitment of upstream DNA binding transcription factors.

NF-Y binds a CCAAT motif found in many eukaryotic polymerase II-dependent promoters. In the HLA-DRA promoter it has been demonstrated that stereo-specific alignment between this motif and the upstream elements X1 and X2 is required for activation. To study the underlying mechanism for this requirement, a panel of transfected cell lines that maintained integrated, wild-type and mutant promoters were analyzed by in vivo genomic footprinting. Cell lines harboring a mutated CCAAT element exhibited a loss of interactions at the CCAAT site, as expected, and no transcriptional activity. Most importantly, mutation of the CCAAT sequence nearly abolished in vivo binding at the X1 and X2 sites, while mutations of X1 and X2 had little effect on CCAAT box binding. However, X1 and X2 binding was interdependent. In vitro, X1 binding activities are known to be stabilized by NF-Y binding. Interaction between NF-Y and X box binding proteins was demonstrated by reciprocal co-immunoprecipitation in the absence of DNA and co-affinity purification in the presence of DNA. Collectively, these studies indicate that occupancy of the CCAAT element represents an early event affecting other protein-DNA interactions and suggest that NF-Y stabilizes and interacts with X box factors to mediate this function. These findings may represent a common theme among promoters containing a CCAAT element.

Antiporters

Thrombotic microangiographic hemolytic anemia in systemic lupus erythematosus.

Thrombotic microangiopathic hemolytic anemia (TMHA) is characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological symptoms, and kidney involvement. It presents as thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS). TMHA has been considered to occur only rarely in systemic lupus erythematosus (SLE). However, there has been an increase in the reporting of this association in recent years, and autopsy studies have suggested that TMHA may be underdiagnosed in SLE because of the similarity in symptoms. We report four patients with SLE-related TMHA and describe 24 more patients from a literature review. All patients were women, 50% had active SLE, 89% presented as TTP, and 11% presented as HUS. Those patients with active SLE had low complement levels. Antiphospholipid antibodies or lupus anticoagulant were positive in 5 of 8 cases. Patients treated with plasma infusions or plasmapheresis had a lower mortality rate at 25% compared with 57% mortality in patients who were not treated with plasma infusions or plasmapheresis. It is suggested that TMHA should be considered in any SLE patient presenting with neurological symptoms or renal failure associated with fever, hemolytic anemia, and thrombocytopenia. Early recognition and appropriate therapy with plasmapheresis may improve prognosis.

Adult

Cardioprotection with U-89232 is not reversible with glibenclamide: evidence of a novel anti-ischemic agent derived from cromakalim.

We have previously reported that cromakalim and U-89232 reduce infarct size in a rabbit model of myocardial ischemia. Because U-89232 appeared to lack activity in the vasculature, we tested its reversibility with glibenclamide. Twenty-eight ketamine-xylazine anesthetized open-chest, New Zealand White rabbits were instrumented for regional coronary occlusion and reperfusion. Study animals received either cromakalim, U-89232 or vehicle. In some animals, glibenclamide was administered. All animals were then subjected to ischemia (30 min) and reperfusion (120 min), and necrosis was determined using tetrazolium. With comparable hemodynamics and myocardium at risk, infarct size in control animals was 35.5 +/- 4.6% of risk region, and was not different from glibenclamide-treated animals (37.7 +/- 5.8%). Cromakalim alone has been shown to be protective, however when combined with glibenclamide necrosis amounted to 35.1 +/- 3.8% of the risk region (p = NS vs. control). In contrast, U-89232 was protective in the presence of glibenclamide (17.2 +/- 4.9% of the risk region). We conclude that U-89232 produces myoprotection independent of K-ATP channel inhibition, indicating that this compound possesses novel anti-ischemic characteristics.

Animals

Cytokine levels in serum and synovial fluid of patients with juvenile rheumatoid arthritis.

OBJECTIVE: Cytokines play an important role in mediating inflammation and in regulating the immune response of many rheumatological diseases. In patients with juvenile rheumatoid arthritis (JRA), levels of 6 cytokines, interleukin 1 alpha (IL-1 alpha), IL-1 beta (IL-1 beta), IL-2, IL-2 receptor (IL-2R), IL-6, and tumor necrosis factor alpha (TNF-alpha) were measured in serum and synovial fluid (SF) in an effort to evaluate their significance. METHODS: Serum concentrations of the 6 cytokines were measured in 62 patients with JRA including 22 pauciarticular onset, 26 polyarticular onset, and 14 systemic onset patients, and 29 disease and healthy controls using enzyme-linked immunoabsorbent assays (ELISA). Seventeen SF from patients with JRA were examined for cytokine levels. RESULTS: Elevated serum levels of IL-2R were found in patients with systemic onset and elevated IL-2 levels in pauciarticular and polyarticular onset JRA as compared to controls. Pauciarticular and polyarticular onset patients also had elevated IL-1 alpha and IL-6 levels. There were no statistical differences found between the groups for TNF-alpha and IL-1 beta. SF revealed elevated levels of IL-1 beta, IL-2R, and IL-6; however, correlation was noted between serum and SF levels only for IL-1 alpha, not for the other cytokines. Mean serum levels of IL-2R in all onset types with active disease and IL-6 levels in active polyarticular and pauciarticular onset were elevated when compared with mean inactive levels. CONCLUSION: Our studies indicate that (1) IL-1 alpha, IL-2, IL-2R, and IL-6 levels are increased in serum of patients with JRA with different onset types; (2) elevated levels of IL-1 beta, IL-2R, and IL-6 are found in their SF compared to serum levels; (3) a correlation exists between serum and SF levels only for IL-1 alpha; (4) mean IL-2R levels are elevated with active disease in all onset types and mean IL-6 levels with active polyarticular and pauciarticular onset disease are elevated compared to mean levels of inactive patients; and (5) cytokines may thus play a role as inflammatory mediators in JRA.

Adolescent

Clinical presentation and treatment of arthritis in the aged.

Arthritis is a common condition among older individuals; osteoarthritis is the most common. Other frequently encountered conditions are rheumatoid arthritis, polymyalgia rheumatica, gout, and pseudogout. The clinical presentation of these disorders may differ from those seen in younger patients. Therapeutic modalities, such as physical therapy, medications, and surgery should be modified sometimes to accommodate age-related changes in body mechanics and function.

Aged

Rheumatoid factors.

Rheumatoid factors (RFs) have been studied for over 50 years and are probably the most written about of any antibody. Nevertheless, the etiology of these RFs and the precise role they play in the pathogenesis of rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) remain a major interest. When RFs participate in the generation of inflammation in RA and JRA, they probably do so by forming immune complexes (IC) or are themselves able to bring about the inflammatory response. Their presence has been associated with more severe disease, vasculitis, and systemic symptoms. The present review summarises the literature over the last few years on new and interesting findings on RF. This review covers an update on RF assays, RF cross-reactivity, specificity studies, immune complex formation, RF lymphocyte studies, and RF binding.

Arthritis, Juvenile

Autoantibody studies in juvenile rheumatoid arthritis.

Early studies showed few immunologic abnormalities in juvenile rheumatoid arthritis (JRA) patients. There were no specific laboratory markers useful for diagnosis and assessment of the course of disease in JRA. Previous work showed an association of antinuclear antibodies (ANA) with early-onset pauciarticular disease and iridocyclitis. Similarly, the presence of 19S immunoglobulin (Ig) M rheumatoid factors (RF) was associated with late-onset polyarticular disease in girls. More recent studies have detected many unique autoantibodies. Newer assays show 19S IgM RF in up to 35% of JRA patients, although still mainly in girls with late-onset polyarticular disease. Hidden 19S IgM RF can be shown in up to 75% of JRA patients using different procedures, primarily in those with active polyarticular-or pauciarticular-onset disease. Immune complexes have been detected in JRA patients by means of different techniques; their presence usually correlates with active disease. Studies on a specific ANA in JRA have shown no common extractable nuclear antigen, but antihistone antibodies have been found in up to 75% of cases, again mainly in those with pauciarticular onset and iritis. Finally, a variety of unusual immunologic proteins have also been detected, including anti-ocular, anti-cellular, anti-cardiolipin, anti-perinuclear factor, and anti-collagen antibodies. This review evaluates the significance of these antibodies that can now be found in JRA.

Antibodies, Antinuclear

Limitation of infarct size in the rabbit by ischaemic preconditioning is reversible with glibenclamide.

OBJECTIVE: The aim was to determine whether ischaemic preconditioning occurs through the actions of ATP sensitive potassium (KATP) channels during ischaemia and whether pharmacological antagonism of these channels can reverse the protective effect of preconditioning. METHODS: 31 New Zealand White rabbits were instrumented for coronary occlusion and reperfusion. Control animals were subjected to ischaemia (30 min) and reperfusion (120 min) only. Study animals were divided into three experimental groups: (1) those receiving intravenous glibenclamide (0.3 mg.kg-1) prior to the 30 min ischaemia; (2) those receiving 5 min preconditioning ischaemia and 10 min reperfusion prior to the 30 min ischaemia; or (3) those receiving preconditioning in the presence of glibenclamide prior to the 30 min ischaemia. The resulting infarct and myocardium at risk were visualised with Indian ink and tetrazolium staining and quantified using computer assisted planimetry. RESULTS: Rabbits which were preconditioned showed a 63% reduction in infarct size [14.8(SEM 2.2)% of risk region] in comparison to non-preconditioned controls [39.8(2.1)%]. When rabbits were preconditioned in the presence of glibenclamide the protection was reversed [31.3(5.1)%] using a dose of glibenclamide which by itself did not alter necrosis [37.7(5.4)%]. CONCLUSIONS: Infarct size reduction in the rabbit via ischaemic preconditioning is reversible with the coadministration of glibenclamide.

Animals

Adult respiratory distress syndrome associated with antiphospholipid antibody syndrome.

Antiphospholipid antibody syndrome (APS) has been shown to be associated with arterial and venous thromboses, recurrent miscarriages, and thrombocytopenia. We describe 3 cases of adult respiratory distress syndrome (ARDS) in patients with primary APS. The autopsy in one patient revealed no evidence of vasculitis, but extensive small vessel thrombosis of multiple organs including the lungs was seen. No infectious process, connective tissue diseases, or pulmonary edema could be documented and there was no clinical or laboratory evidence of vasculitis in the other 2 patients. The 2 patients who survived responded dramatically to intravenous steroids.

Adult

Arthropathies of cystic fibrosis: case reports and review of the literature.

Patients with cystic fibrosis (CF) have demonstrated more arthritides with their longer life expectancy. The most common presentations have been that of an episodic arthritis or a hypertrophic osteoarthropathy. However, other arthropathies have been associated with CF. We now describe 3 new patients with CF and arthritis, and review the types of arthritis that may be found in patients with CF. This report is to increase awareness of the arthropathies that may be found in patients with CF so that proper evaluation, classification, and treatment may be facilitated.

Adult

The B cell-specific nuclear factor OTF-2 positively regulates transcription of the human class II transplantation gene, DRA.

The promoter of the major histocompatibility class II gene DRA contains an octamer element (ATTTGCAT) that is required for efficient DRA expression in B cells. Several DNA-binding proteins are known to bind this sequence. The best characterized are the B cell-specific OTF-2 and the ubiquitous OTF-1. This report directly demonstrates that OTF-2 but not OTF-1 regulates the DRA gene. In vitro transcription analysis using protein fractions enriched for the octamer-binding protein OTF-2 demonstrate a positive functional role for OTF-2 in DRA gene transcription. In contrast, OTF-1-enriched protein fractions did not affect DRA gene transcription although it functionally enhanced the transcription of another gene. Recombinant OTF-2 protein produced by in vitro transcription/translation could also enhance DRA gene transcription in vitro. In vivo transient transfection studies utilizing an OTF-2 expression vector resulted in similar findings: that OTF-2 protein enhanced DRA gene transcription, and that this effect requires an intact octamer element. Together these results constitute the first direct evidence of a positive role for the lymphoid-specific octamer-binding factor in DRA gene transcription.

Autoradiography

Antiperinuclear factor in juvenile rheumatoid arthritis.

The serological diagnosis of juvenile rheumatoid arthritis (JRA) is difficult, with only 7-10% of patients 19S IgM rheumatoid factor positive. About 60-70% of patients are positive for hidden 19S IgM rheumatoid factor, but this test requires serum separation and is not available in most laboratories. Antiperinuclear factor has been described in both seropositive and seronegative adult patients with rheumatoid arthritis, but has not been thoroughly evaluated in children with JRA. This study determined the diagnostic sensitivity and specificity of antiperinuclear factor in patients with JRA. Serum samples from 64 children with JRA, 24 with systemic lupus erythematosus (SLE), and 24 control subjects were tested for the presence of antiperinuclear factor. A total of 10 (83%) of seropositive, polyarticular onset and six (37%) of seronegative, polyarticular onset patients with JRA were positive for antiperinuclear factor. The occurrence of antiperinuclear factor in five (19%) with pauciarticular onset and one (10%) with systemic onset (JRA) as well as in four (17%) with SLE was not increased compared with the control subjects (1/24 (4%)). These data show an overall diagnostic sensitivity and specificity of 34 and 90% respectively in this group of patients. Although less sensitive than the hidden rheumatoid factor assay, the antiperinuclear factor assay is easier to perform and may contribute to the serological diagnosis of JRA.

Antibodies, Antinuclear