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Biomedical subjects

J D Fine

Publications and source records attributed to J D Fine.

At least 109 records · Page 6Linked to original sources

Sequence of reconstitution of seven basement-membrane components following split-thickness wound induction in primate skin.

Recent studies have shown an orderly sequence of expression of structural antigens within the skin basement-membrane zone of the human fetus. Interestingly, these findings differ from those reported following split-thickness would induction in Yorkshire pigs. To readdress this apparent disparity, as well as to further extend such studies to include other basement-membrane antigens more recently identified, we produced split-thickness wounds in a primate species and serially examined the wounds by immunofluorescence technique for the expression of seven antigens normally found in intact primate skin basement membrane. By the fourth day following wounding, laminin, type-IV collagen, and fibronectin were all detectable along the dermoepidermal junction. In contrast, bullous pemphigoid antigen, epidermolysis bullosa acquisita antigen, cicatricial pemphigoid antigen, and KF-1 antigen were undetectable until days 6, 8, 10, and 11, respectively. These latter findings are in complete agreement with those previously reported in the developing human fetus. On the basis of the results of this study, we would suggest that primate rather than pig skin may be a more appropriate animal model for wound-healing studies. These data are consistent with previous reports suggesting that the basement-membrane antigens recognized by bullous pemphigoid and cicatricial pemphigold autoantibodies are indeed distinct. Finally, these data bring into question the functional role of bullous pemphigoid antigen during the early phase of wound healing in humans.

Animals↗

LDA-1 monoclonal antibody. An excellent reagent for immunofluorescence mapping studies in patients with epidermolysis bullosa.

To determine the diagnostic usefulness of a monoclonal antibody to the LDA-1 antigen, a newly defined noncollagenous component of the lamina densa of human basement membrane, we examined skin specimens from 20 patients with epidermolysis bullosa (simplex type, eight patients; junctional type, four patients; dystrophic type, eight patients) by the indirect immunofluorescence technique. We compared this antibody to polyclonal antibodies with three other antigens routinely examined in diagnostic immunofluorescence mapping studies. The antigen defined by the LDA-1 monoclonal antibody was expressed normally in all specimens examined, regardless of the type of epidermolysis bullosa present. Furthermore, no disparity was noted between the LDA-1 monoclonal antibody and a polyclonal antibody to type IV collagen in the microscopic localization of binding within induced skin blisters. These findings suggest that the LDA-1 monoclonal antibody is an excellent immunoreagent for diagnostic immunofluorescence mapping studies.

Antibodies, Monoclonal↗

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↗

LDA-1: a ubiquitous noncollagenous lamina densa component of basement membrane detected by monoclonal antibody technique.

Using monoclonal antibody technology, a new basement membrane antigen, designated as LDA-1, has been identified. This antigen is expressed in all human tissues thus far examined; within skin it is detectable not only within the dermal-epidermal junction but also within dermal vascular and appendageal basement membranes. In addition to human skin, LDA-1 is also detectable within rabbit but not monkey, rat, mouse, guinea pig, or cow skin. This antigen has been ultrastructurally localized to the lamina densa and to a much lesser extent, the adjacent sublamina densa region. ELISA (enzyme-linked immunosorbent assay) revealed no cross-reactivity between LDA-1 and type IV collagen, laminin, fibronectin, and heparan sulfate proteoglycan. In vitro enzymatic studies suggest that LDA-1 is noncollagenous in nature.

Animals↗

Distinctive eruption characterized by linear supravenous papules and erythroderma following broxuridine (bromodeoxyuridine) therapy and radiotherapy.

A distinctive cutaneous eruption occurred in two patients with central nervous system tumors who were treated with broxuridine (bromodeoxyuridine) and radiotherapy. Findings included the initial appearance of papular lesions within skin directly overlying acral superficial veins and the later development of a more generalized eruption eventuating into exfoliative erythroderma.

Brain Neoplasms↗

The generalized atrophic benign form of junctional epidermolysis bullosa. Experience with four patients in the United States.

We encountered four patients in the United States with the generalized atrophic benign form of junctional epidermolysis bullosa (epidermolysis bullosa atrophicans generalisata mitis, nonlethal junctional epidermolysis bullosa). Prior to the performance of definitive diagnostic studies, each patient had been thought for at least a decade to have either a dystrophic or simplex form of epidermolysis bullosa. Each patient had generalized blisters since birth that healed with atrophy and mild scarring but without milia or contractures. Two of the four patients had experienced laryngeal involvement during childhood. In each patient, correct diagnosis was finally established by either electron microscopic examination or immunofluorescence mapping of skin sections from induced blisters.

Adolescent↗

Herpes gestationis. Persistent disease activity 11 years post partum.

A patient had herpes gestationis that had persisted for over 11 years post partum despite aggressive therapy with corticosteroids, dapsone, and various immunosuppressants. Postpartum exacerbation is a characteristic feature of herpes gestationis. However, it usually is of short duration and is responsive to conventional therapy.

Adolescent↗

Dystrophic epidermolysis bullosa. A new variant characterized by progressive symmetrical centripetal involvement with scarring.

A patient is reported with a form of epidermolysis bullosa, hitherto undescribed to the best of our knowledge, characterized by the slow centripetal progression of symmetrical blister formation, milia, scarring, atrophy, and nail dystrophy. Electron microscopy, immunofluorescence mapping, and KF-1 monoclonal antibody studies confirm this disease to be a form of dystrophic epidermolysis bullosa, probably of autosomal recessive transmission despite the absence of acral deformities, contractures, mucosal involvement, and growth retardation.

Antibodies, Monoclonal↗

Cicatricial pemphigoid, bullous pemphigoid, and epidermolysis bullosa acquisita antigens: differences in organ and species specificities and localization in chemically-separated human skin of three basement membrane antigens.

Bullous pemphigoid, cicatricial pemphigoid, and epidermolysis bullosa acquisita are three autoimmune diseases characterized by the presence of subepidermal blisters, in vivo-bound immunoreactants along the dermoepidermal junction, and variably detectable circulating anti-basement membrane autoantibodies. In order to better characterize the antigen(s) defined by cicatricial pemphigoid sera, indirect immunofluorescence was performed on a variety of human organs, skins of different animals, and on human skin chemically-split within the lamina lucida, comparing sera from cicatricial pemphigoid patients with sera from these two other blistering diseases. Sera from patients with each disease bound to the dermoepidermal junction of every laboratory animal species examined. In contrast, more mucosal tissues were bound by anti-basement membrane autoantibodies from patients with cicatricial pemphigoid and epidermolysis bullosa acquisita than from patients with bullous pemphigoid, consistent with the marked tendency for mucosal involvement in patients with the former two diseases. In addition, one of the cicatricial pemphigoid sera stained basal cell surfaces as well as dermoepidermal junction. Differences were also apparent in the staining of chemically-split human skin. The combined findings suggest that cicatricial pemphigoid and bullous pemphigoid antigens are distinct despite their common localization within the lamina lucida of the dermoepidermal junction. These data also suggest the presence of at least two different cicatricial pemphigoid antigens.

Adult↗

The TORCH syndrome: a clinical review.

Several infections contracted in utero result in similar physical and laboratory findings during the neonatal period; the TORCH syndrome encompasses such patients. Skin lesions are a frequent finding and the dermatologist may play an important role in the early evaluation of these infants. In this review we discuss etiology, epidemiology, clinical, laboratory, radiologic, and pathologic findings, differential diagnosis, therapy, course, and prognosis of each of these congenital infections.

Adolescent↗

Monoclonal antibodies in dermatologic research. Studies with a unique cell-surface antigen defined specifically for keratinocytes by a monoclonal antibody.

Basic principles of production of monoclonal antibodies are discussed in this paper. In order to illustrate the usefulness of such production, studies of a new monoclonal antibody designated KF-2 which defines a unique cell-surface antigen found exclusively in the stratum spinosum of man and lower primates are recounted.

Acantholysis↗

Monoclonal antibodies and the skin biopsy: current and potential clinical applications.

Monoclonal antibodies are becoming increasingly useful in the clinical diagnosis and/or treatment of a number of unrelated diseases. Discussion will be directed to those monoclonal antibodies recognizing antigens within the skin which appear to have either proven or potential application in the diagnostic evaluation of the skin biopsy.

Antibodies, Monoclonal↗

Epidermolysis bullosa: variability of expression of cicatricial pemphigoid, bullous pemphigoid, and epidermolysis bullosa acquisita antigens in clinically uninvolved skin.

Indirect immunofluorescence was performed on skin from 13 patients with epidermolysis bullosa (EB) (simplex, 6; junctional, 2; dystrophic, 5) to compare the expression of 3 basement membrane components, bullous pemphigoid (BP) antigen, cicatricial pemphigoid (CP) antigen, and epidermolysis bullosa acquisita (EBA) antigen, in clinically uninvolved tissue. In addition, expression of laminin, type IV collagen, and KF-1 antigen was also evaluated. Whereas laminin, type IV collagen, and KF-1 antigen were each detectable in EB skin in a manner identical to that previously reported, marked variability was noted in the expression of BP, CP, and EBA antigens. However, no correlation was noted comparing lack of expression of any one of these latter antigens with either of the remaining two. Of these 3 antigens, BP antigen was the least often detectable, particularly in skin from patients with EB simplex. The lack of detectable BP antigen in EB simplex skin appeared to correlate with more extensive disease involvement and/or younger patient age. These findings may, therefore, limit the usefulness of BP serum in immunofluorescence mapping. Additionally, the disparity in expression of basement membrane antigens defined by BP and CP sera suggests that BP antigen and CP antigen are distinct entities.

Antigens↗

A specific defect in glycosylation of epidermal cell membranes. Definition in skin from patients with epidermolysis bullosa simplex.

Why blister formation occurs within the epidermis in epidermolysis bullosa (EB) simplex is not known. One possibility is that there are diminished amounts, absence, or biochemical alterations of one or more structural components of epidermal cell membranes, thereby leading to increased skin fragility. In order to test this hypothesis, biopsy specimens were obtained from clinically normal-appearing skin of patients with simplex, junctional, and dystrophic forms of EB and normal adult volunteers. Immunofluorescence studies were performed on each specimen using eight fluorescein-labeled affinity-purified lectins shown to bind uniformly to epidermal cell membranes of normal human adult skin and neonatal foreskin. To examine the epidermal cytoskeleton, each tissue specimen was also examined using two antikeratin monoclonal antibodies. Irregular and focally granular epidermal membrane staining was noted in each EB simplex specimen examined with the lectin-peanut agglutinin. In contrast, uniformly crisp membrane staining was seen in each specimen from patients with junctional or dystrophic EB and from normal volunteers. This epidermal cell membrane glycosylation defect appears to have the restricted carbohydrate specificity of peanut agglutinin since staining of EB simplex skin with each of the remaining seven lectins was indistinguishable from that seen in skin from patients with the other forms of EB and normal adult skin. Furthermore, the epidermis in EB simplex skin appears to be selectively abnormal since the same tissue specimens demonstrated normal keratin cytoskeleton staining.

Antibodies, Monoclonal↗

The use of monoclonal antibodies in skin basement membrane research.

Recent experiments have indicated that it is possible to uncover new antigens within both the basement membrane zone and the epidermis of normal adult human skin by producing murine anti-human monoclonal antibodies following immunization with human skin preparations. Already one such monoclonal antibody has defined a biochemical defect that may be important in the pathogenesis of one of the more severe blistering skin diseases, dystrophic epidermolysis bullosa. It is likely that further attempts at hybridoma production using basement membrane extracts of skin will lead not only to the identification of other as yet unknown components of the human dermo-epidermal junction, but may also shed insight into the biochemical basis of one or more cutaneous diseases involving that region of the skin.

Antibodies, Monoclonal↗

KF-1 monoclonal antibody defines a specific basement membrane antigen defect in dystrophic forms of epidermolysis bullosa.

The monoclonal antibody, KF-1, identifies a noncollagenous constituent of the lamina densa of the basement membrane zone (BMZ) of skin. In order to determine whether this BMZ constituent is affected in epidermolysis bullosa (EB), a mechanobullous skin disease often resulting in marked disfigurement, we have examined skin from patients with various forms of this disease for binding by KF-1 as well as for binding by polyclonal antibodies to laminin, type IV collagen, and bullous pemphigoid antigen, three other known BMZ components of normal skin. In all specimens from patients with simplex and junctional forms of EB, all four antibodies bound normally. In contrast, absent or diminished KF-1 binding was noted in all skin specimens from patients with dystrophic EB; antibodies directed against the other BMZ constituents, however, bound normally. This suggests that KF-1 may play a role in the structural integrity of normal skin and its absence or diminution may be important in the pathogenesis of lesion formation in dystrophic EB.

Antibodies, Monoclonal↗