University of Alabama School of Medicine.
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Alabama↗
Biomedical subjects
D W Boulware
Publications and source records attributed to D W Boulware.
Meeting the challenges of teaching in ambulatory settings: a national, collaborative approach for internal medicine.
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Ambulatory Care↗
Calciphylaxis mimicking skin lesions of connective tissue diseases.
Calciphylaxis is a rare condition found in patients with end-stage renal disease and secondary hyperparathyroidism. We describe two cases of prominent cutaneous manifestations of calciphylaxis in which skin lesions were refractory to topical treatments. We also include a brief description of calciphylaxis.
Adult↗
Control of IL-6 expression and response in fibroblasts from patients with systemic sclerosis.
Systemic sclerosis (SSc) is an autoimmune connective tissue disease of unknown etiology in which aberrant fibroblast function results in fibrosis of the skin and internal organs. A distinguishing feature of dermal fibroblasts cultured from SSc lesions is that they produce constitutively, i.e., without exogenous stimulation, as much as 30-fold more interleukin-6 (IL-6) than do normal fibroblasts. The present study indicates that the mechanism of constitutive IL-6 secretion involves the accumulation of IL-6 mRNA in affected SSc fibroblasts, mediated by the constitutive binding of nuclear factors to the IL-6 promoter. DNA-protein complexes formed using nuclear extracts of constitutively expressing cells are distinct from those using extracts of normal cells, with or without exogenous stimulation of IL-6; thus, the mechanisms which regulate constitutive and inducible IL-6 gene expression are apparently distinct. The data also demonstrate that dermal fibroblasts respond very rapidly to IL-6 by increasing expression of the IL-6 gene, thus suggesting a mechanism for the establishment and/or persistence of constitutive expression. The constitutive secretion of IL-6 may play an important role in the perpetuation of the local immune dysregulation and fibroblast activation in the SSc lesion.
Adult↗
Pulmonary manifestations of rheumatic disease.
The lungs are a common target in many rheumatic diseases. Treatment of the primary rheumatic disease is often all that is required to control lung involvement. Physicians must be careful not to attribute lung disease to the underlying rheumatic disorder, because interstitial lung disease can be a complication of drug therapy.
Arthritis, Rheumatoid↗
Expression of c-myc, c-myb, and c-sis in fibroblasts from affected and unaffected skin of patients with systemic sclerosis.
We examined c-sis, c-myc, and c-myb proto-oncogene expression in fibroblasts cultured from affected and unaffected skin of patients with systemic sclerosis (SSc), and from healthy donor skin. Total cellular RNA from cultured dermal fibroblasts was used in slot blot analysis and scanning densitometry or phosphorimaging to quantify steady-state levels of proto-oncogene mRNAs. PDGF B-chain levels in culture supernatants of fibroblasts were determined by ELISA. Our results demonstrate that steady-state levels of c-myc and c-myb mRNA were elevated 1.5- to 5.6-fold in intralesional fibroblasts from SSc patients as compared to other cells examined. Levels of c-sis mRNA and PDGF-B protein were comparable regardless of source. Elevated c-myc and c-myb expression may be indicative of, and may contribute to, fibroblast activation in SSc.
Adult↗
Human recombinant interleukin-4 induces proliferation and interleukin-6 production by cultured human skin fibroblasts.
The effect of human recombinant interleukin-4 (hrIL-4) on normal human adult dermal fibroblasts in terms of proliferation and IL-6 production was studied. Fibroblasts were exposed to different concentrations of IL-4 for various periods of time. Proliferation was measured using a [3H]thymidine incorporation assay. IL-6 production was measured at the transcriptional, protein, and functional levels by Northern blot analysis, radioimmunoassay, and B9 bioassay, respectively. Our results show that hrIL-4 significantly stimulated (two- to fivefold) fibroblasts to increase the incorporation of [3H]thymidine in a dose- and time-dependent manner. However, hrIL-1, hrIL-2, hrIL-5, or hrTNF alpha, at the same concentration (100 U/ml) and for the same time period (4 days), did not. In addition, IL-4 significantly induced (four- to eightfold) the production of immunoreactive and biologically functional IL-6. However, IL-4 was not as potent an inducer of IL-6 as IL-1. The IL-4-induced IL-6 production was dose and time dependent and was due, at least in part, to a dramatic increase in the steady-state levels of IL-6 mRNA. This is the first report describing the ability of IL-4 to activate human dermal fibroblasts in terms of proliferation and IL-6 production.
Adult↗
Mechanisms of pathogenesis in scleroderma. I. Overproduction of interleukin 6 by fibroblasts cultured from affected skin sites of patients with scleroderma.
Fibroblasts were cultured from affected skin sites of patients with progressive systemic sclerosis (PSS), from unaffected skin sites of the same patients, and from a healthy donor. The concentration of interleukin 6 (IL-6) in culture medium conditioned by the growth of early passage cells was determined by radioimmunoassay and by quantitative bioassay. Results demonstrated that fibroblasts from affected PSS skin produce from 6 to 30-fold higher levels of biologically active IL-6 compared to unaffected and control cells. In contrast, serum IL-6 concentrations in 6 of 8 patients examined were not significantly different from healthy donors. Serum IL-6 levels were elevated 2 to 3-fold in 2 of 8 patients examined. Thus, the overproduction of IL-6 by affected scleroderma fibroblasts does not necessarily correlate with a systemic increase in IL-6, but may increase its concentration locally. In view of its biological activities, including stimulation of antibody production and T cell activation, the overproduction of IL-6 by PSS fibroblasts in the lesions may play a significant role in the pathogenesis of PSS and may profoundly influence the course of the disease.
Adult↗
Mechanisms of pathogenesis in scleroderma. II. Effects of serum and conditioned culture medium on fibroblast function in scleroderma.
Scleroderma (progressive systemic sclerosis; PSS) is a connective tissue disorder in which excessive collagen is deposited in the skin and internal organs. Mediators of abnormal fibroblast function in PSS have not yet been identified. Our objective was to examine the possibility that factors present in serum from patients with PSS, or in culture medium conditioned by PSS fibroblast growth, serve to regulate fibroblast function. Fibroblasts from affected and unaffected skin sites of patients with PSS and from normal adult skin were cultured in the presence of various human sera or conditioned media. Results indicate that (1) the proliferative influence of serum of patients with PSS is not different from that of normal donors, (2) increased proliferation and procollagen gene expression are not linked in affected or unaffected dermal fibroblasts, and (3) affected PSS fibroblasts produce a stimulatory factor(s) for procollagen gene expression to which they are differentially sensitive.
Adult↗
A case report of giant cell arteritis of the uterus and adnexa.
Giant cell arteritis of the uterus and adnexa is a rare disorder, which is generally asymptomatic and occasionally associated with temporal arteritis. The true clinical significance of this dramatic microscopic finding remains obscure, but arteritis of the uterus and adnexa may be associated with later development of giant cell arteritis elsewhere in the body.
Adnexal Diseases↗
Monthly cyclophosphamide in lupus pneumonitis and myositis.
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Adult↗
The fibromyalgia syndrome. Could you recognize and treat it?
Many of your patients may complain of innumerable "aches and pains." One possible diagnosis for these symptoms is the fibromyalgia syndrome, a common musculoskeletal condition. This article provides information to help you increase your ability to recognize, understand, and treat this condition.
Fibromyalgia↗
Lupus pneumonitis and anti-SSA(Ro) antibodies.
Interstitial pneumonitis has previously been thought to be an uncommon feature in systemic lupus erythematosus (SLE). A review of 63 patients with SLE from 1984 to 1987 at Tulane University revealed a frequency of 25.4% (N = 16) of lupus pneumonitis. Serologic testing for antibodies to SSA(Ro) revealed that 81% (13 of the 16) of the patients with lupus pneumonitis have anti-SSA(Ro) antibodies, compared to a frequency of 38% (24 of the 63) for the entire group with SLE (p less 0.001). The association of lupus pneumonitis and anti-SSA(Ro) antibodies is discussed in light of a speculative immunopathogenic role for the antibody to SSA(Ro) antigen.
Adolescent↗
Interstitial pneumonitis in antinuclear antibody-negative systemic lupus erythematosus: a new clinical manifestation and possible association with anti-Ro (SS-A) antibodies.
The clinical manifestations of patients with systemic lupus erythematosus (SLE) and negative fluorescent antinuclear antibody have been well documented. This report describes 2 cases of antinuclear antibody-negative SLE with antibodies only to Ro (SS-A) and the previously unreported clinical manifestation of lupus interstitial pneumonitis. A review of all SLE patients from 1984-1986 with interstitial pneumonitis revealed that 10 of the 12 patients had antibodies to Ro (SS-A). The frequency of anti-Ro (SS-A) with interstitial pneumonitis in SLE patients suggests a possible association between the two.
Adult↗
Pulmonary hypertension in primary Sjögren's syndrome.
The clinical course of a patient with pulmonary hypertension associated with Sjögren's syndrome is reported. The clinical features and outcome of this case are compared with those of two other reported cases in the Spanish and Japanese published work. Thus far, pulmonary hypertension has not been reported with primary Sjögren's syndrome in English publications. These three cases suggest that the development of pulmonary hypertension in primary Sjögren's syndrome is uncommon but should be included as part of the clinical spectrum.
Adult↗
Sarcoidosis presenting as antinuclear antibody positive glomerulonephritis.
A 43 year old woman who initially presented with the nephrotic syndrome, glomerulonephritis, and antinuclear antibodies (ANAs) was given the diagnosis of systemic lupus erythematosus (SLE). One year later the patient developed progressive subcutaneous nodules on her forearms, with histopathology of non-caseating granulomas. Further evaluation of the patient showed mediastinal lymphadenopathy and interstitial lung disease with numerous granulomas, establishing the diagnosis of sarcoidosis. The presence of autoimmune antibodies and glomerulonephritis has been reported in sarcoidosis, but this case is believed to be the first in which both glomerulonephritis and ANAs are present in a sarcoid patient.
Adult↗
Pulmonary manifestations of the rheumatic diseases.
The collagen vascular diseases represent a heterogeneous group of multisystem disorders with a wide range of clinicopathologic features. Although these diseases represent distinct clinical entities, a great deal of overlap exists between them. For example, the diffuse interstitial fibrosis of SLE, RA, DM-PM, PSS, and MCTD are indistinguishable clinically, radiographically, and histologically. Conversely, the pulmonary manifestations of the various vasculitides all differ significantly from each other in their clinicopathologic presentation, as well as in their response to therapy. For diagnostic purposes, histologic evidence will usually be required for the pulmonary manifestations of the rheumatic diseases. Therapy must then be individualized for each of these entities, as the protocol and response are variable.
Arthritis, Rheumatoid↗
Cyanogen bromide cleaves Fc fragments of pooled human IgG at both methionine and tryptophan residues.
An attempt was made to obtain fragments containing the C gamma 2 region by selectively cleaving human Fc fragments prepared from pooled IgG at Met residues using cyanogen bromide. Based on the known locations of Met residues in the Fc regions of human IgG subclasses, fragments between Met 252 and 358, comprising the C gamma 2 domains, were expected from IgGl Gm -1, IgG2, IgG3 and IgG4. Greater fragmentation of the Fc fragments occurred, however, than was predicted. Automated N-terminal sequencing identified five major points (Trp 381, 313 and 277, and Met 397 and 252) and two minor points of cleavage (Met 428 and Trp 417). The majority of cleavage points occurred at Trp rather than Met. Furthermore, cleavage at Met 358, necessary to produce C gamma 2 domains, was not detected. Control experiments verified the integrity of the Fc fragments handled in exactly the same manner without cyanogen bromide exposure and the ability of the same cyanogen bromide preparation to produce the expected cleavages at Met of sperm whale apomyoglobin without fragmentation at Trp. Cleavage at Met 358 did not occur presumably because of the difficulty associated with cyanogen bromide cleavage at Met-Thr peptide bonds. Cleavage at Trp probably occurred by way of halogen promoted oxidation of the indole nucleus with resultant peptide bond fissure. These observations show that cyanogen bromide cleavage of pooled human Fc fragments is not selective for Met, but also cleaves at Trp residues. The resultant fragmentation of the C gamma 2 region coupled with the inability to make the required cleavage at the 358-359 Met-Thr bond resulted in the inability to produce fragments comprising the C gamma 2 domains. The reasons for the selective cleavage at Met in some proteins and the cleavage at both Trp and Met in others are not known.
Chemical Phenomena↗