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Biomedical subjects

W R Gammon

Publications and source records attributed to W R Gammon.

At least 55 records · Page 3Linked to original sources
PubMed1988

Increased frequency of HLA-DR2 in patients with autoantibodies to epidermolysis bullosa acquisita antigen: evidence that the expression of autoimmunity to type VII collagen is HLA class II allele associated.

Epidermolysis bullosa acquisita (EBA) is a chronic blistering disease characterized by circulating and tissue bound IgG auto-antibodies to the basement membrane zone (BMZ) of stratified squamous epithelium. Recent studies have shown that antibodies recognize epitopes present in the noncollagenous carboxyl-terminal domain of type VII collagen, a BMZ matrix protein. Antibodies with identical specificity also have been detected in patients with the rare blistering disease, bullous systemic lupus erythematosus (bullous SLE), suggesting EBA and bullous SLE are immunologically related diseases. In this study we determined the major histo-compatibility antigen types of 29 EBA patients and 6 patients with bullous SLE. Analysis of the results showed HLA-DR2 was significantly increased in both black EBA patients, P = 0.013 (corrected, RR = 4.8) and white EBA patients, P = 0.0008 (corrected, RR = 13.1). Five of the six bullous SLE patients also were positive for the DR2 antigen, P = 0.009. These results show the expression of autoimmunity to type VII collagen is HLA class II allele associated and that EBA and bullous SLE are immunogenetically related diseases.

Adolescent↗
PubMed1988

A comparison of Cleocin T Solution, Cleocin T Gel, and placebo in the treatment of acne vulgaris.

A twelve-week study in which investigators were blinded to the agents studied included 135 patients (aged twelve to thirty-five years) with moderately severe acne vulgaris. Patients were randomized into groups to compare the efficacy and local tolerance of 1 percent clindamycin phosphate gel, 1 percent clindamycin phosphate solution, and the gel vehicle which served as a placebo. One hundred and twenty-eight patients who completed at least six weeks of treatment were evaluated for efficacy of these agents. Both the solution and the gel were equivalent in reducing papule and pustule counts and results were superior to those produced by the placebo. All three treatments were tolerated well.

Acne Vulgaris↗
PubMed1988

Systemic lupus erythematosus presenting as a bullous eruption in a child.

An 8-year-old girl presented with a generalized bullous eruption clinically resembling bullous pemphigoid or chronic bullous disease of childhood. Further study revealed immunopathologic findings seen in patients with epidermolysis bullosa acquisita or bullous systemic lupus erythematosus (SLE). Although she did not fulfill the American Rheumatism Association (Atlanta) criteria for SLE at her presentation, one year later she went on to do so. As well as being the youngest patient reported with bullous SLE, our patient is noteworthy because the bullous eruption was the initial manifestation of her SLE. Bullous SLE should be considered in the differential diagnosis of children presenting with generalized bullous eruptions.

Age Factors↗
PubMed1987

Functional heterogeneity of immune complexes in epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita is an inflammatory subepidermal bullous disease characterized by circulating and tissue-bound complement-binding anti-basement membrane zone autoantibodies to type VII procollagen. Lesions are characterized by neutrophil-predominant inflammation in some patients, but not in others. These features suggest complement activation and generation of complement-derived chemotactic factors for leukocytes by basement membrane zone immune complexes may contribute to inflammation, but that complexes may be heterogeneous in the ability to express that function. In this study, we measured the ability of basement membrane zone complexes from patients with (n = 4) and without (n = 6) neutrophil predominant inflammation to activate complement and generate complement-derived chemotactic activity using a complement-dependent neutrophil attachment assay. The results showed considerable heterogeneity in neutrophil attachment among EBA patients and that both the incidence (4/4 vs 2/6) and magnitude (81 +/- 34 vs 12 +/- 10 neutrophils/mm basement membrane zone) of attachment were greater in patients with neutrophil-predominant inflammation. Functional heterogeneity appeared to be due to differences in the amounts of complement-activating complexes formed at the basement membrane zone, which in turn appeared to be due to differences in the availability of circulating complement-binding anti-basement membrane zone antibodies. This was suggested by a positive correlation (r = 0.72, p less than 0.01) between neutrophil attachment and complement-binding anti-basement membrane zone antibody titers and the observation that high levels of neutrophil attachment could be generated in skin from patients with epidermolysis bullosa acquisita who did not have neutrophil-predominant inflammation by treating their skin in vitro with complement-binding anti-basement membrane zone antibodies. These results suggest tissue complexes in epidermolysis bullosa acquisita are heterogeneous in the ability to activate complement and generate complement-derived chemotactins (C5a, C5a des arg), and that functional heterogeneity contributes to histologic heterogeneity. The functional immunologic-pathologic correlations observed in this study suggest epidermolysis bullosa acquisita is an autoimmune "collagen" disease.

Antigen-Antibody Complex↗
PubMed1987

Production of fibronectin by epithelium in a skin equivalent.

Although human keratinocytes in vitro have been shown to produce fibronectin, whether keratinocytes can contribute fibronectin to the dermal-epidermal junction or wound matrix is unknown. In order to approach this problem experimentally, we used the "skin equivalent" model composed of a native collagen gel populated with cultured fibroblasts and covered by cultured keratinocytes. By using bovine fibroblasts to populate the gel, fetal bovine serum in the culture medium, and human keratinocytes to form the epithelium, we were able to be certain that any human fibronectin produced in the culture was synthesized by the keratinocytes. A monoclonal antibody to fibronectin was found to recognize human but not bovine fibronectin. When the skin equivalent was stained by indirect immunofluorescence with antifibronectin, fibronectin was visible as an intensely staining band at the dermal-epidermal junction. In sections in which the dermis and epidermis had separated, the staining was usually limited to the dermal aspect of the skin equivalent. The results indicate that epithelium can contribute fibronectin to the dermal-epidermal junction and suggest that dermal staining in skin sections may originate from the epidermis. Since the developing skin equivalent has a rapidly growing epithelium and simulates a healing wound, contribution of fibronectin by the epithelium, in addition to that possibly contributed by serum and fibroblasts, may be of importance in wound healing.

Animals↗
PubMed1987

Neonatal foreskin substrate has limitations for the immunofluorescent screening of monoclonal antibodies.

Two monoclonal antibodies to type IV collagen showed a marked decrease in the labeling of the dermal-epidermal junction of neonatal foreskin while the basement membrane around dermal blood vessels was brightly stained. In contrast, these antibodies labeled the junction and dermal blood vessels with approximately equal intensity when adult skin of nonforeskin site was used as substrate. Other antibodies to matrix molecules (bullous pemphigoid antigen, epidermolysis bullosa acquisita antigen, and laminin) showed excellent staining of both the dermal-epidermal junction and dermal blood vessels in both neonatal foreskin and adult skin. Further, the ultrastructural appearance of the substrates appeared identical. The implication is that neonatal foreskin is not a good substrate to use for the routine screening of monoclonal antibodies to matrix components by indirect immunofluorescence since a "false negative" evaluation may occur.

Adult↗
PubMed1987

Specific affinity between fibronectin and the epidermolysis bullosa acquisita antigen.

Autoantibodies in the skin and sera of patients with epidermolysis bullosa acquisita bind to a large matrix molecule within the lamina densa region of skin basement membrane. At the site of these immune complexes, the epidermis separates from the dermis, which creates a subepidermal blister just below the lamina densa. The target molecule for the autoantibodies is in close apposition to fibronectin, a major extracellular matrix molecule that is abundant in the upper dermis of skin. In this report, we show specific affinity between fibronectin and the 290,000-D chain of the epidermolysis bullosa acquisita antigen, and that this affinity is mediated by the gelatin/collagen-binding domain of fibronectin (Mr = 60,000). Since blistering in epidermolysis bullosa acquisita often occurs in the absence of clinical and histological inflammation, a direct interruption in the fibronectin-epidermolysis bullosa acquisita antigen bond may be involved in the pathogenesis of epidermal-dermal disadherence that occurs in this bullous disease.

Autoantibodies↗
PubMed1987

Leukemia cutis in acute myelomonocytic leukemia. Preferential localization in a recent Hickman catheter scar.

We describe a patient with myelomonocytic leukemia who demonstrated striking leukemic infiltration in the scar of a recent Hickman catheter placement. This cutaneous involvement occurred initially without signs of systemic relapse. A comparative review of leukemic cell physiology provides several possible reasons for this extramedullary infiltration, including the greater functional maturity, deformability, adhesiveness, and ability to cluster of myelomonocytic and monocytic leukemia cells relative to other leukemias. A careful cutaneous examination, with particular attention to recent scars, may provide the only evidence of relapse in adult leukemia.

Aged↗
PubMed1986

Comparative efficacy of oral erythromycin versus oral tetracycline in the treatment of acne vulgaris. A double-blind study.

The efficacy of erythromycin base (E-Mycin tablets, 333 mg) and the efficacy of tetracycline hydrochloride (Panmycin tablets) were compared in this double-blind, randomized study. Two hundred patients with moderate to moderately severe acne vulgaris were randomly assigned to the study. One hundred patients received 1 gm of erythromycin base by mouth per day for 4 weeks, followed by 333 mg/day for 8 weeks, plus placebo for tetracycline. The second group of patients received 1 gm of tetracycline by mouth per day for 4 weeks, followed by 500 mg/day for 8 weeks, plus placebo for erythromycin. Both drugs reduced acne severity to the same extent. Pustules, papules, and open comedo counts decreased significantly over the 12-week period. Seventy-seven percent of the erythromycin-treated patients and 89% of the tetracycline-treated patients stated that their acne was markedly improved or improved by week 12. Most of the side effects in patients treated with erythromycin were gastrointestinal symptoms. Among the side effects in patients treated with tetracycline were Candida vaginitis in one patient and pseudotumor cerebri in one patient.

Acne Vulgaris↗
PubMed1986

A case of linear IgA disease presenting initially with IgG immune deposits.

We describe a case of linear IgA bullous disease initially presenting with histopathologic and immunofluorescent findings consistent with bullous pemphigoid. Initial immunofluorescent studies demonstrated a predominance of linear IgG at the basement membrane zone (BMZ) of perilesional skin and a low titer circulating IgG anti-BMZ antibody. Repeat studies 3 years later revealed a predominance of linear IgA immune deposits at the BMZ and no circulating anti-BMZ antibody. Dapsone therapy was initiated at this time with a good therapeutic response noted. Suction blister studies, immunoelectron microscopy, split skin immunofluorescent studies and Western immune blot were performed and provided indirect evidence that the BMZ antigen in this case is distinct from the bullous pemphigoid antigen component of the BMZ.

Aged↗
PubMed1986

Bullous systemic lupus erythematosus: an unusual clinical course and detectable circulating autoantibodies to the epidermolysis bullosa acquisita antigen.

Bullous systemic lupus erythematosus is a newly recognized form of systemic lupus erythematosus characterized by a skin eruption clinically and histologically resembling dermatitis herpetiformis and responsive to dapsone. We report on a patient with bullous systemic lupus erythematosus who initially presented with lesions clinically resembling erythema multiforme, experienced exacerbation of her disease with dapsone, and had detectable circulating autoantibodies to the epidermolysis bullosa acquisita antigen.

Adolescent↗
PubMed1986

Epidermolysis bullosa acquisita antigen, a new major component of cutaneous basement membrane, is a glycoprotein with collagenous domains.

The epidermolysis bullosa acquisita antigen is a major constituent of the basement membrane zone beneath stratified squamous epithelium. The antigen which is recognized in extracts of skin basement membrane by Western blot analysis with polyclonal or monoclonal antiepidermolysis bullosa acquisita antigen antibodies as 2 chains (a major chain of 290,000 and a minor chain of 145,000) has a native molecular weight over 800,000. Both epidermolysis bullosa acquisita antigen chains contain carbohydrate and the 290K chain is sensitive to collagenase.

Adult↗
PubMed1986

Organ-specific, phylogenetic, and ontogenetic distribution of the epidermolysis bullosa acquisita antigen.

The organ-specific, phylogenetic, and ontogenetic distribution of the epidermolysis bullosa acquisita (EBA) antigen, a newly recognized basement membrane component, was determined using polyclonal sera from patients with EBA and a mouse monoclonal antibody, H3a. Both antibodies are distributed at the basement membrane zone of skin, oral, anal, and vaginal mucosae, and esophagus, but not in kidney, urinary bladder, lymph nodes, placenta, or blood vessels. Both polyclonal and monoclonal EBA antibodies react with a basement membrane antigen in primate and other mammalian skin, but not in avian, amphibian, or reptilian skin. The antigen is present initially in the 8-week-old human fetus, and increases in density until the adult linear pattern is reached at 15 weeks' gestational age.

Animals↗
PubMed1986

Epidermolysis bullosa acquisita antigen, a major cutaneous basement membrane component, is synthesized by human dermal fibroblasts and other cutaneous tissues.

The epidermolysis bullosa acquisita (EBA) antigen is identified as 2 chains: a 290,000-dalton protein and a less prominent 145,000-dalton protein. The 290,000-dalton chain is synthesized by human keratinocytes in culture. In this study, we show that the 290,000-dalton chain is synthesized by human skin fibroblasts and cutaneous human tumors. In contrast, HT1080 cells, a human sarcoma cell line known to produce matrix molecules (such as laminin and type IV collagen), does not synthesize the EBA antigen. Further, the EBA antigen is absent from serum and blood components, placenta, amnion, lung, and the EHS tumor, a murine sarcoma that produces large amounts of laminin, type IV collagen, nidogen, entactin, and basement membrane proteoglycan but is present in cutaneous tumors of adnexal and epithelial origin. These data suggest that while the EBA antigen is synthesized by both human skin keratinocytes and fibroblasts and is therefore not specific for a primordial germ layer, it does appear to be specific for tissue containing a stratified squamous epithelium.

Antigens↗