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Biomedical subjects

A M Reed

Publications and source records attributed to A M Reed.

At least 19 recordsLinked to original sources
PubMed2000

Autoantibodies to DEK oncoprotein in human inflammatory disease.

OBJECTIVE: To evaluate the specificity of anti-DEK antibodies for juvenile rheumatoid arthritis (JRA). METHODS: Anti-DEK autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA) using affinity-purified his6-DEK fusion protein. Sera from 639 subjects (417 patients with systemic autoimmune disease, 13 with sarcoidosis, 44 with pulmonary tuberculosis, 125 with uveitis, and 6 with scleritis, and 34 healthy control subjects) were screened. Reactivity was verified by immunoblotting and immunoprecipitation studies using baculovirus-expressed human DEK. RESULTS: Anti-DEK activity was found at the following frequencies: JRA 39.4% (n = 71), systemic lupus erythematosus (SLE) 25.1% (n = 216), sarcoidosis 46.2% (n = 13), rheumatoid arthritis 15.5% (n = 71), systemic sclerosis 36.0% (n = 22), polymyositis 6.2% (n = 16), and adult Still's disease 0% (n = 21). Autoantibodies also were detected in 9.1% of tuberculosis sera (n = 44), but were undetectable in sera from the 34 healthy controls. Western blot and immunoprecipitation assay results correlated well with the ELISA findings. In general, levels of anti-DEK autoantibodies were higher in SLE than in other patient subsets, including JRA. CONCLUSION: Anti-DEK autoantibodies are less specific for JRA than previously believed. They are produced in association with a variety of inflammatory conditions, many of which are associated with granuloma formation and/or predominant Thl cytokine production. Anti-DEK antibodies may be a marker for a subset of autoimmunity associated with interferon-gamma production rather than a particular disease subset.

Adolescent↗
PubMed2000

Immunogenetic associations in childhood dermatomyositis.

Childhood dermatomyositis is a multisystem autoimmune disease characterized by acute and chronic inflammatory infiltrate and vasculitis seen primarily in skin and muscle. The disease occurs in genetically susceptible individuals with a yet undescribed environmental trigger. Genetic associations in this disease demonstrate disease susceptibility as well as chronicity and severity and likely play a role in disease pathogenesis. The majority of the associations to date have been seen with the HLA alleles, with additional immune responsive and influential genes being increasingly investigated.

Child↗
PubMed1999

Development of validated disease activity and damage indices for the juvenile idiopathic inflammatory myopathies. II. The Childhood Myositis Assessment Scale (CMAS): a quantitative tool for the evaluation of muscle function. The Juvenile Dermatomyositis Disease Activity Collaborative Study Group.

OBJECTIVE: To develop, validate, and determine the measurement characteristics of a quantitative tool for assessing the severity of muscle involvement in children with idiopathic inflammatory myopathies. METHODS: The Childhood Myositis Assessment Scale (CMAS) was developed from 2 existing observational functional assessment tools to assess muscle function in the areas of strength and endurance across a wide range of ability and ages. The 14 ordinal items included were chosen to assess primarily axial and proximal muscle groups and are ranked with standard performance and scoring methods. Following the development of the CMAS, a training video and written instructions were developed and reviewed by the physicians participating in this study. Subsequently, utilizing a randomized block design, 12 physicians independently scored 10 children (9 with dermatomyositis, 1 with polymyositis; ages 4-15 years) twice in one day (morning and afternoon) on the CMAS. A pediatric physical therapist performed quantitative manual muscle strength testing (MMT) twice on each child (morning and afternoon), including the neck, trunk, and proximal and distal extremity muscle groups. RESULTS: The CMAS has a potential range of 0-51, with higher scores indicating greater muscle strength and endurance. The observed mean for the 10 patients was 36.4 (median 44, SD 14.1, observed range 5-51). The total score for the CMAS correlated with the physician's global assessment (by visual analog scale) of disease activity, the MMT score, serum creatine kinase level, and the Juvenile Arthritis Functional Assessment Report score. The score on the CMAS was not correlated with patient age. Interrater reliability (Kendall's coefficient of concordance) ranged from 0.77 to 1.0 for individual items (all P < 0.001), and overall, it was 0.95 (P < 0.001). Intrarater reliability for the individual physicians was measured by correlation of the CMAS scores for each patient on 2 separate evaluations and ranged from 0.97 to 0.99, with an overall correlation for all physicians of 0.98 (all P < 0.001). CONCLUSION: The CMAS demonstrated an acceptable range of observed scores, excellent convergent validity, and excellent inter- and intrarater reliability. The CMAS is validated to quantitatively assess muscle function in the areas of strength and endurance in children with idiopathic inflammatory myopathies. It can be used in routine clinical care as well as therapeutic trials.

Adolescent↗
PubMed1999

Prevention of leg length discrepancy in young children with pauciarticular juvenile rheumatoid arthritis by treatment with intraarticular steroids.

OBJECTIVE: To determine if intraarticular (i.a.) injection of triamcinolone hexacetonide (steroids) used early in the course of pauciarticular juvenile rheumatoid arthritis (pauci JRA) is associated with less leg length discrepancy (LLD) or thigh circumference discrepancy (TCD). METHODS: Children with pauci JRA who had asymmetric lower-extremity arthritis diagnosed before age 7 years in Seattle, Washington (WA; n = 16) and in Chapel Hill and Durham, North Carolina (NC; n = 14) were retrospectively identified. WA children were given i.a. steroids within 2 months of diagnosis; the injections were repeated if synovitis recurred in the same joint or in a different joint. These children were compared with NC children who were not treated with i.a. steroids. Thigh circumference was measured at 10 cm above the patella, and leg length was measured from the anterior superior iliac spine to the mid-medial malleolus, by a single observer. LLD and TCD are reported as the percentage of difference between leg measurements in each subject. RESULTS: The WA and NC subjects had comparable disease severity and duration of followup (in months). Twelve WA children had subsequent i.a. steroid injections (mean 3.25 injections per child over mean +/- SD 42 +/- 11 months). The WA subjects had significantly less LLD (P = 0.005, by Student's 2-sided t-test) and prescriptions for shoe lifts (P = 0.002, by Fisher's 2-sided exact test). There was not a significant difference in TCD between the 2 groups (P = 0.139, by Student's 2-sided t-test). Similar findings were obtained when the analysis was limited to children with monarticular knee arthritis. CONCLUSION: Early and continued use of i.a. steroids may be associated with less LLD in young children with pauci JRA. This may indicate decreased duration of synovitis.

Adolescent↗
PubMed1999

Analysis of HLA-DM polymorphism in juvenile dermatomyositis (JDM) patients.

Annually approximately 1:200,000 young children and adolescents are affected by juvenile dermatomyositis (JDM). Genetic factors are thought to contribute to the etiology. Since the discovery of the human leukocyte antigen class II associated DM molecule much has been learned about its role in the normal processing of HLA-class II molecules with a limited number of polymorphisms being found. Blood samples were collected from 30 patients who were seen in the clinic and 40 healthy volunteers. Exon 3 of the HLA-DM A and B genes were amplified and specific polymorphisms were identified given allele designations. The DMA*0103 allele was found in 43% of patient alleles versus 8% in the control group, this difference reached significance at a p value of 0.0004. The DMB*0102 allele was found in 20% of patients compared with 3% of the controls with a calculated p value of 0.037. Relative risk (RR) ratios with CI were as follows: DMA*0103 vs control RR = 5.7 and DMB*0102 vs control RR = 8. In conclusion, we feel that the polymorphisms represented in the DMA*0103 and the DMB*0102 alleles are increased in frequency in our JDM patients.

Child↗
PubMed1999

Familial dermatomyositis.

Susceptibility, response to therapy, prognosis, and natural history of connective tissue diseases are variably linked to histocompatibility antigens (HLA), although the precise role that such genes play is still not clear. In juvenile dermatomyositis (JDMS) there are few reports of both concordance and discordance in identical twins and occurrence in more than one family member. To further document the familial occurrence of JDMS, we describe 2 sisters, one with classical JDMS and the other with amyopathic dermatomyositis. The 2 patients were shown to share the HLA-DQA1*0501 allele, known to be associated with susceptibility to JDMS.

Child↗
PubMed1998

Immunogenetic studies in families of children with juvenile dermatomyositis.

OBJECTIVE: We reported an association between juvenile dermatomyositis (JDMS) and the HLA-DQA1*0501 allele. The purpose of this study was to determine whether there is evidence for linkage between JDMS and the DQA1*0501 allele in JDMS families. METHODS: The study population included 18 unrelated patients with JDMS, their parents, and 49 unaffected siblings. Using molecular genetic techniques, we studied the HLA genes, DRB1, DQA1, and tumor necrosis factor-alpha. RESULTS: Using the transmission disequilibrium test, we confirmed our earlier observations that the HLA-DQA1*0501 allele confers primary susceptibility to JDMS. CONCLUSION: DQA1*0501 confers genetic risk for JDMS; we cannot exclude the effects of alleles at other linked loci that were not studied or interactive effects between DQA1 alleles and alleles at other loci.

Alleles↗
PubMed1997

Diminished class II-associated Ii peptide binding to the juvenile dermatomyositis HLA-DQ alpha 1*0501/DQ beta 1*0301 molecule.

HLA class II molecules bind and present peptide Ags to T cells, binding specific sets of peptides due to polymorphism in the peptide binding groove. Class II proteins associate with the invariant chain (Ii chain) and its derived class II-associated Ii peptide (CLIP). Ii chain association is important for normal trafficking of class II proteins to the peptide loading vesicles and for blocking premature access of peptides to HLA class II molecules during maturation. We have previously shown that juvenile dermatomyositis is associated with the HLA-DQA1*0501 allele. There is limited information available about the interaction of any DQ molecule with the Ii chain and little information about binding of individual peptides to HLA-DQalpha1*0501/DQbeta1*0301. We sequenced peptides eluted from the juvenile dermatomyositis-associated class II allele HLA-DQalpha1*0501/DQbeta1*0301. Surprisingly, we found no Ii chain or CLIP. Further examination of peptide binding to the HLA-DQalpha1*0501/DQbeta1*0301 molecule demonstrated poor CLIP binding. However, newly synthesized HLA-DQalpha1*0501/DQbeta1*0301 molecules do associate with intact Ii chain. Molecular modeling suggests that CLIP binds differently to HLA-DQalpha1*0501/DQbeta1*0301 than to DR molecules. The lack of CLIP association suggests that HLA-DQalpha1*0501/DQbeta1*0301 has access to peptides earlier in the processing pathway and so might encounter novel peptides that induce autoimmunity.

Alleles↗
PubMed1997

Development of validated disease activity and damage indices for the juvenile idiopathic inflammatory myopathies: I. Physician, parent, and patient global assessments. Juvenile Dermatomyositis Disease Activity Collaborative Study Group.

OBJECTIVE: To determine the reliability, content validity, and responsiveness of physician global assessments of disease activity and damage in the juvenile idiopathic inflammatory myopathies (IIM), and to investigate concordance among physician, parent, and patient global ratings. METHODS: Sixteen pediatric rheumatologists rated 10 juvenile IIM paper patient cases for global disease activity and damage, and assessed the importance of 51 clinical and laboratory parameters in formulating their global assessments. Then, 117 juvenile IIM patients were enrolled in a protocol to examine the relationship between Likert and visual analog scale global assessments, their sensitivity to change, and the comparability of physician, parent, and patient global ratings. RESULTS: Pediatric rheumatologists demonstrated excellent interrater reliability in their global assessments of juvenile IIM disease activity and damage (97.7% and 94.7% agreement among raters, respectively), and agreed on a core set of clinical parameters in formulating their judgments. Likert scale ratings correlated with those on a visual analog scale, and both were comparable in responsiveness (standardized response means -0.56 for disease activity, 0.02 [Likert] and 0.14 [visual analog] for damage, measured over 8 months). Parent global ratings of disease activity correlated with physician assessments, but were not colinear (Spearman's correlation [r] = 0.41-0.45). Patient global disease activity assessments correlated with those done by parents (r = 0.57-0.84) and physicians (r = 0.37-0.63), but demonstrated less responsiveness (standardized response means -0.21 and -0.12, respectively, over 8 months). CONCLUSION: Physician global assessments of juvenile IIM disease activity and damage demonstrated high interrater reliability and were shown to be comprehensive measures. Both physician and parent disease activity assessments should be considered valuable as quantitative measures for evaluating therapeutic responses in juvenile IIM patients.

Arthritis, Juvenile↗
PubMed1996

The 8.5-kb PstI allele of the stress protein gene, Hsp70-2: an independent risk factor for systemic lupus erythematosus in African Americans?

SLE is dramatically more prevalent in persons of African descent than in other populations. Several genes in the class III region of the MHC have been considered as potential susceptibility loci for this disorder, but the primary association(s) remains unknown. The stress protein gene, hsp70-2, is of special interest in this regard because it encodes a protein functionally relevant to antigen processing and presentation and has itself been identified as a putative susceptibility locus in organ-specific autoimmune diseases in Caucasians. To clarify the relationship of the hsp70-2 gene to SLE in African Americans, genomic DNA from 46 patients and 42 appropriately matched control subjects was analyzed for an RFLP of the hsp70-2 gene using the probe pH2.3 and the restriction endonuclease PstI, which identifies alleles of 8.5 and 9.0 kb. The 8.5-kb hsp70-2 allele was associated with SLE in this population (X2 = 8.2473, p = 0.0044). This association was not due to linkage disequilibrium with the C4A deletion or with HLA-DR3, as has been reported in Caucasians with IDDM. These data suggest that the 8.5-kb hsp70-2 allele may be an independent susceptibility marker for SLE in African Americans.

Alleles↗
PubMed1995

Association of the HLA-DQA1*0501 allele in multiple racial groups with juvenile dermatomyositis.

We wanted to determine if HLA-DQA1*0501 is as strongly associated with JDMS in Hispanic and African Americans as it is Caucasians. Using DNA sequencing and oligonucleotide typing, the DNA of 70 JDMS subjects was studied. The HLA-DQA1 allelle DQA1*0501 was present in 13 out of 15 (87%) of the African-American JDMS subjects vs 9 out of 27 (33%) of the African-American controls (p < 0.0009), 12 out of 13 (92%) of the Hispanic JDMS subjects vs 5 out of 18 (28%) of the Hispanic controls (p < 0.0004), and 36 out of 42 (86%) of the Caucasian JDMS subjects vs 36 out of 78 (46%) of the Caucasian controls (p < 0.0009).

Alleles↗
PubMed1995

Breast feeding and the development of juvenile rheumatoid arthritis.

OBJECTIVE: To determine if children with juvenile rheumatoid arthritis (JRA) are less likely to have been breast fed than controls. METHODS: Case-control study of data obtained from a survey of mothers 54 children with JRA and 79 playmates regarding breast feeding. Duration of breast feeding was tabulated and odds ratios (OR) with 95% confidence intervals (CI) were determined. RESULTS: OR for breast feeding in children with JRA was 0.40 (0.20-0.81, 95% CI) compared to playmates. For pauciarticular JRA (N = 28) OR was 0.31 (0.10-0.93); in polyarticular JRA (N = 24) OR was 0.60 (0.21-1.70). Lower OR for increased durations of breast feeding were noted in children with JRA. CONCLUSION: Children who have had JRA, especially pauciarticular JRA, are less likely to have been breast fed than controls, suggesting that breast feeding may have a protective effect on the development of JRA.

Adolescent↗
PubMed1995

FDDI information management system for centralizing interactive, computerized multimedia clinical experiences in pediatric rheumatology/Immunology.

This paper describes the design, authoring, and development of interactive, computerized, multimedia clinical simulations in pediatric rheumatology/immunology and related musculoskeletal diseases, the development and implementation of a high speed information management system for their centralized storage and distribution, and analytical methods for evaluating the total system's educational impact on medical students and pediatric residents. An FDDI fiber optic network with client/server/host architecture is the core. The server houses digitized audio, still-image video clips and text files. A host station houses the DB2/2 database containing case-associated labels and information. Cases can be accessed from any workstation via a customized interface in AVA/2 written specifically for this application. OS/2 Presentation Manager controls, written in C, are incorporated into the interface. This interface allows SQL searches and retrievals of cases and case materials. In addition to providing user-directed clinical experiences, this centralized information management system provides designated faculty with the ability to add audio notes and visual pointers to image files. Users may browse through case materials, mark selected ones and download them for utilization in lectures or for editing and converting into 35mm slides.

Allergy and Immunology↗
PubMed1993

Repair of osteopenia in children with juvenile rheumatoid arthritis.

To test the hypothesis that the presence of osteopenia in juvenile rheumatoid arthritis is directly correlated with clinical disease activity and therefore reversible, we prospectively studied cortical bone mineral density (BMD) serially in 27 children. Twenty-four (89%) had BMD > or = 2 SD below age-related normal values (disease duration 49.3 +/- 7.7 months) at the beginning of the study. Of 27 children who had clinical disease improvement measured by a disease activity score during our study period, 17 (63%) had significant improvement or significant normalization, or both, of their BMD (0.34 +/- 0.13 gm/cm2 at initiation and 0.41 +/- 0.17 gm/cm2 at completion, p < 0.05; disease activity score of 3.4 +/- 0.2 at initiation and 1.4 +/- 0.2 at completion, p < 0.005). The increase in BMD was associated with a similar directional change in serum osteocalcin concentrations (4.6 +/- 1 ng/ml at initiation vs 9.1 +/- 1.1 ng/ml). The 10 patients whose disease became or remained active had a decreased or unchanged low serum osteocalcin level and BMD (BMD 0.37 +/- 0.17 gm/cm2 at initiation and 0.37 +/- 0.16 gm/cm2 at completion; disease activity score of 3.1 +/- 0.3 at initiation and 3.4 +/- 0.2 at study completion). We conclude that children with JRA who have improvement in their disease activity have an improvement in BMD heralded by an increase in serum osteocalcin values.

Adolescent↗
PubMed1992

Testing intelligent wound dressings.

While occlusive wound dressings help provide patients with moist wound healing to reduce pain and increase reepithelialization rate, the moisture vapor transmission rate (MVTR) of these dressings remains constant even though wound exudate levels may vary with time and from wound to wound. The clinician is therefore faced with exudate buildup in heavily exuding wounds and desiccation in lightly exuding wounds-a situation requiring frequent patient monitoring and dressing changes. Am "intelligent" wound dressing would have the ability to automatically respond to a wound's exudate level by self-adjusting its MVTR to maintain a constant moist wound environment. Such a dressing could help ensure that exudate buildup or wound desiccation is reduced or avoided. Three commercial wound dressings (hydrocolloid, thin film, and membrane laminate) were studied for their ability to alter their MVTR in response to varying moisture level. An efficient test methodology and experimental design was developed, which involved direct and indirect fluid contact with the dressings using two temperatures and two test methods. One dressing, a membrane laminate, was found to exhibit intelligent MVTR behavior. Data is presented which shows this dressing's ability to adjust its MVTR nearly eight-fold as a function of hydration level. Information regarding the mechanism of action of this intelligent dressing is also presented.

Biocompatible Materials↗
PubMed1992

Biostable polyurethane elastomers.

The generic term polyurethane represents the most versatile family of synthetic polymers. The unsurpassed physical and chemical properties of polyurethanes, coupled with their biocompatibility, have led to their use in a wide range of biomedical applications. Although polyurethanes have been shown to be stable in vitro for many years, they can undergo rapid microcracking when implanted. These microcracks not only weaken the polymer but also serve as nucleation sites for thrombus formation and lead to catastrophic failure. In this article, the authors report on the development and testing of a new ether-free polyurethane that does not exhibit surface microcracking under accelerated in vivo condition.

Animals↗