Search PubMed⌕ Search

Biomedical subjects

J D Fine

Publications and source records attributed to J D Fine.

At least 91 records · Page 5Linked to original sources
PubMed1989

Natural killer cell activity is reduced in patients with severe forms of inherited epidermolysis bullosa.

Natural killer (NK) cell activity was evaluated in 34 patients with inherited forms of epidermolysis bullosa (EB). While the NK activity of EB simplex patients did not differ from that of control subjects, persons with more severe forms of EB demonstrated significant reductions in NK activity. The degree of this reduction was directly related to the severity of the skin involvement by EB with recessive dystrophic EB patients having the lowest NK activity. The absolute number of cells bearing NK surface markers in the peripheral blood of patients with recessive dystrophic EB did not differ from that of normal control subjects. This reduced NK activity may be at least partially responsible for the occurrence of septicemia in some persons with severe forms of EB and for the development of metastatic squamous cell carcinoma in patients with dystrophic EB.

Adult↗
PubMed1989

Blood vitamin and trace metal levels in epidermolysis bullosa.

Plasma or erythrocyte levels of ten nutrients (vitamins A, C, B12 and B6; folate; thiamine; riboflavin; zinc; copper; iron) were assayed in 73 patients with various forms of inherited epidermolysis bullosa (EB). Whereas the mean level for each nutrient was within its normal range, deficient levels were noted in individual EB subsets for selected nutrients. Notable abnormalities included low levels of plasma iron and zinc (in junctional EB and recessive dystrophic EB), vitamin C (primarily in EB simplex), vitamin A (in junctional and recessive dystrophic EB), vitamin B12 (primarily in EB simplex), and vitamin B6 (especially in recessive dystrophic EB). With the exception of low plasma iron and zinc levels in junctional and recessive dystrophic EB, however, only a minority of patients in any of the EB subsets had low levels of most of the other nutrients, and an apparent correlation with malabsorption was possible with only selected nutrients.

Adolescent↗
PubMed1988

Pemphigus vulgaris. Combined treatment with intravenous corticosteroid pulse therapy, plasmapheresis, and azathioprine.

A 13-year-old child is described who presented with generalized pemphigus vulgaris associated with extraordinarily high titers of circulating autoantibodies against the pemphigus antigen. Because of the lack of response to treatment with reasonably high doses of oral corticosteroids, as well as the very high titer of circulating autoantibodies observed, this patient was treated with intravenous corticosteroid pulse therapy followed by plasmapheresis and then by combination immunosuppressive therapy (prednisone and azathioprine). A rapid clinical response was induced, correlating with reduction and subsequent elimination of the circulating pemphigus autoantibodies. Using such combination therapy, a remission of 12 months was achieved, and prednisone therapy was completely, albeit temporarily, tapered and then discontinued. Subsequent disease flare was then easily controlled with a short course of low-dose oral corticosteroid therapy.

Adolescent↗
PubMed1988

Autoantibodies to extracellular collagen matrix components in epidermolysis bullosa and other bullous diseases.

In order to determine whether autoantibodies are present in sera from normal individuals and/or patients with selected bullous disorders, a highly sensitive solid-phase radioimmune assay was established using purified native collagen types I-VI, laminin, and fibronectin as substrates. Sixty-four sera were utilized, representing 12 normal controls as well as 4 patients with extensive thermal burns, 18 with autoimmune bullous diseases (11 bullous pemphigoid, 5 pemphigus vulgaris, and 2 epidermolysis bullosa acquisita), and 30 with non-autoimmune mechanobullous diseases [epidermolysis bullosa (EB): 20 simplex, 4 junctional, and 6 dystrophic]. In general, autoantibodies to types I, II and VI collagen and fibronectin were undetectable in any of the patient or control groups. In contrast, autoantibodies to types III and V collagen were noted in 87.5% (28/32) and 90.6% (29/32) of EB sera, respectively, while being only rarely noted in sera from other patient groups. Similarly, autoantibodies to type IV collagen and laminin were detected in 50% (16/32) and 40.6% (13/32) of EB sera, especially from patients with simplex and dystrophic forms of the disease. These data suggest that selected interstitial and basement membrane-associated collagens and laminin may become autoimmunogenic in all three forms of inherited EB in contrast to their relative lack of immunogenicity in at least some of the other intraepidermal and subepidermal blistering disorders. The role, if any, of these autoantibodies in the induction or perpetuation of blistering in EB awaits further studies.

Adult↗
PubMed1988

Chondroitin-6-sulfate-containing proteoglycan: a new component of human skin dermoepidermal junction.

A murine monoclonal antibody (3B3) has been produced with specificity for chondroitin-6-sulfate (C-6-S) and proven binding to rodent basement membranes, presumably detecting a population of C-6-S-containing proteoglycans. Utilizing this antibody, we sought to determine whether a basement membrane chondroitin sulfate proteoglycan is present in adult, neonatal, and/or fetal skin, and if present, its ultrastructural localization. Indirect immunofluorescence was performed on human adult, neonatal, and fetal skin. To detect the antigen, specimens were pretreated with chondroitinase ABC; absence of enzyme treatment served as negative control. Chondroitin sulfate proteoglycan was detectable in linear homogeneous array along the dermoepidermal junction and within vascular (and when present, adnexal) basement membranes in both adult and neonatal skin. In fetal skin, basement membrane staining was noted as early as 54 gestational days. Indirect immunoelectron microscopy and NaCl-split skin studies were performed to ultrastructurally localize the antigen; immune deposits were detectable within the lamina densa in chondroitinase-treated skin. These findings demonstrate that chondroitin sulfate proteoglycan is present within all skin basement membranes; that it is present in the region of the lamina densa; and that similar to some other ubiquitous basement membrane antigens, it is present early in the developing fetus.

Adult↗
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

Prenatal diagnosis of dominant and recessive dystrophic epidermolysis bullosa: application and limitations in the use of KF-1 and LH 7:2 monoclonal antibodies and immunofluorescence mapping technique.

Prenatal diagnosis is now possible for junctional and recessive dystrophic forms of epidermolysis bullosa (EB); however, there is no similar published experience for dominant dystrophic EB, although data with KF-1 monoclonal antibody suggests that both forms of dystrophic EB can be identified at least postnatally with this unique probe. We now report our experience with light microscopy, electron microscopy, immunofluorescence mapping, and KF-1 and LH 7:2 monoclonal antibodies, in both a mother with dominant dystrophic EB and her fetus at risk, and in a fetus previously shown to be affected with recessive dystrophic EB. KF-1 and LH 7:2 antigens were absent in recessive dystrophic EB fetal skin, identical to findings observed postnatally. LH 7:2 was normally expressed in a mother with dominant dystrophic EB and in her fetus at risk for this disease. In contrast, while KF-1 antigen was abnormally expressed in the affected mother, it was normally expressed in only 1/7 fetal biopsies despite the fact that this fetus was shown by light and electron microscopy and immunofluorescence mapping to be unaffected with dominant dystrophic EB. We conclude that 1) transmission electron microscopy can be used to prenatally exclude the diagnosis of dominant dystrophic EB (Cockayne-Touraine variety), 2) immunofluorescence mapping is an accurate technique for prenatal as well as postnatal diagnosis of EB, and 3) KF-1 cannot by itself be used as an accurate probe for the prenatal diagnosis of dominant dystrophic EB, due to the apparent variability in the time for the normal expression of KF-1 in fetal skin during the second trimester.

Adult↗
PubMed1988

Evaluation of the efficacy of topical bufexamac in epidermolysis bullosa simplex. A double-blind placebo-controlled crossover trial.

Although, as yet, there is no specific treatment of epidermolysis bullosa (EB) simplex, anecdotal reports suggest the possible efficacy of one of the newer topical nonsteroidal anti-inflammatory agents, bufexamac. To determine whether bufexamac has any role in the management of this disease, a double-blind placebo-controlled crossover clinical trial was undertaken with ten patients (nine, Weber-Cockayne variant; one, generalized EB simplex). Each of the two preparations was applied four times daily during the 2 four-week treatment periods. Weekly assessments included counts of blisters, crusts, and erosions, and assessments of alterations in cutaneous pain, healing times, and activity times before further blister formation. Although considerable variability in individual responses was noted, no significant difference was detectable between the active drug and its matched placebo. On the basis of these findings, it was concluded that 5% topical bufexamac is ineffective in the treatment of EB simplex.

Administration, Cutaneous↗
PubMed1988

Persistent subepidermal blistering in split-thickness skin graft sites. Ultrastructural and antigenic features simulating dystrophic or immunofluorescence-negative acquired epidermolysis bullosa.

We describe a child who began developing subepidermal blisters in the recipient sites of split-thickness skin grafts; this process has continued for almost a year and continues to spare nongrafted skin. Routine histologic and immunofluorescence mapping studies demonstrated this disorder to be a relatively noninflammatory one characterized by sub-lamina densa blister formation. Results of direct immunofluorescence were negative. By electron microscopy, anchoring fibrils were sparse in number and in some areas appeared malformed; otherwise, the basement membrane zone was morphologically unremarkable. Bullous pemphigoid antigen, laminin, type IV collagen, epidermolysis bullosa acquisita antigen, and LDA-1 were all normally expressed along the dermoepidermal junction. In contrast, KF-1 antigen was absent. These findings suggest a disease process confined to skin graft recipient sites with features identical to those previously described with recessive dystrophic or immunofluorescence-negative acquired epidermolysis bullosa.

Antigens↗
PubMed1988

Development of neuroendocrine (Merkel cell) carcinoma mixed with squamous cell carcinoma in erythema ab igne.

Squamous cell carcinoma and neuroendocrine (Merkel cell) carcinoma are cutaneous neoplasms that have only occasionally been reported to coexist. Squamous cell carcinoma, but not neuroendocrine (Merkel cell) carcinoma, is a rare complication of erythema ab igne. This report describes the development of both neoplasms arising within the same tumor mass in an area of erythema ab igne.

Aged↗
PubMed1988

Efficacy of systemic phenytoin in the treatment of junctional epidermolysis bullosa.

Oral phenytoin has been shown to be effective in the treatment of recessive dystrophic epidermolysis bullosa (EB). To determine the possible efficacy of this drug in junctional forms of this disease, we treated four children (two with generalized atrophic benign EB [GABEB] and two with Herlitz disease) with two 16- to 20-week treatment periods with phenytoin separated by an eight- to 12-week drug-free period. Phenytoin was administered to achieve serum levels similar to those previously proved effective in treating recessive dystrophic EB. Serial counts were made of lesions (blisters, crusts, and erosions); surface areas of granulation tissue, when present, were also serially measured. In addition, changes in the percentage of surface area involved with scarring as well as changes in extracutaneous disease activity were similarly assessed. Both patients with GABEB showed excellent response during each course of phenytoin, with average reductions in lesion counts of 70% and 38%. In addition, subjectively, the healing times also appeared to be reduced. During the "wash-out" period, total lesional counts returned toward pretreatment levels. Both patients with GABEB subsequently have received phenytoin for an additional two years off of protocol, with continued excellent response. In contrast, the conditions of both patients with the Herlitz variant worsened while taking phenytoin, with increases in overall lesional counts of 31% and 72%. Also, the surface areas of exuberant granulation tissue either remained unchanged or increased during the course of phenytoin treatment. We conclude that phenytoin is effective in at least some patients with the GABEB subset of junctional EB, whereas no efficacy has been noted in patients with the more severe Herlitz variant.

Administration, Oral↗
PubMed1987

The skin basement membrane zone.

The basement membrane zone of skin is a complex, highly compartmentalized structure composed of many distinct antigens. As illustrated in epidermolysis bullosa, alteration in one or more of these antigens may result in abnormal integrity of the dermoepidermal junction, leading to increased mechanical fragility and blister formation. In addition, autoimmunization to basement membrane components, as in the case of bullous pemphigoid and EBA antigens, may result in the development of selected bullous diseases. To date, little is known about the functions and interactions of the antigens identified within human skin basement membrane. It is likely that future studies will provide not only these answers but also additional insight into other diseases associated with basement membrane involvement.

Animals↗
PubMed1987

Childhood epidermolysis bullosa acquisita. Detection in a 5-year-old girl.

A 5 1/2-year-old girl with a blistering disease involving the skin and the oral, ocular, and anogenital mucosa is described. The initial clinical, histologic, and immunofluorescence findings suggested a diagnosis of cicatricial pemphigoid. However, immunoelectron microscopy demonstrated linear deposits of several immunoreactants within the sub-lamina densa region of the dermoepidermal junction, consistent with the diagnosis of epidermolysis bullosa acquisita. Although epidermolysis bullosa acquisita is considered a disease of adult onset, it should be included in the differential diagnosis of blistering diseases in children.

Basement Membrane↗