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J D Fine

Publications and source records attributed to J D Fine.

At least 37 records · Page 2Linked to original sources
PubMed1995

Defective in vivo expression and apparently normal in vitro expression of a newly identified 105-kDa lower lamina lucida protein in dystrophic epidermolysis bullosa.

We have previously identified a novel 105-kDa lower lamina lucida protein detected by the autoantibodies from a group of patients who developed a unique immune-mediated subepidermal bullous dermatosis. We sought to determine if this novel basement membrane zone (BMZ) protein is normally expressed in the skin of patients with various subsets of epidermolysis bullosa (EB). Indirect immunofluorescence microscopy performed on non-lesional skin sections from patients with three major EB subsets revealed absence or significantly reduced expression of this novel BMZ protein in 20 out of 23 skin sections from patients with generalized dominant and recessive dystrophic EB. However, immunoblot analyses with the autoantibodies on Western-blotted proteins revealed that a comigrating 105-kDa protein is present in both cytosol extracts (n = 6) and conditioned media (n = 3) of cultured dermal fibroblasts derived from patients with dystrophic EB, as well as those cultured from two healthy individuals. Although the reason for such disparate findings is not known, the defective in vivo expression of this novel 105-kDa protein in dystrophic EB is presumably not due to a failure of fibroblasts to synthesize or secrete the protein. It is possible, however, that the 105-kDa protein may be unable to incorporate into the BMZ because it is produced in a dysfunctional form, or its BMZ binding site is missing. It is also possible that other structural alterations in skin BMZ, which occur in dystrophic EB, result in masking of the antigenic binding by the autoantibody when intact BMZ is probed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Remission of severe epidermolysis bullosa acquisita induced by extracorporeal photochemotherapy.

We report a patient with severe epidermolysis bullosa acquisita (EBA) whose disease was refractory to conventional treatments. New bullae continued to develop over greater than 50% of his body surface area despite therapy. His course was complicated by hyperglycaemia, sepsis, hypoxia caused by pulmonary Aspergillus infection and an idiopathic cardiomyopathy. His EBA resolved after treatment with extracorporeal photochemotherapy (ECP). Hence, ECP may be effective in the treatment of severe EBA which has failed to respond to standard treatment regimens.

Acute Disease↗
PubMed1995

Epidermolysis bullosa. Application of epidemiologic principles to the study of a group of rare diseases via a disease registry.

The study of rare diseases may provide unique insights into new mechanisms of disease. Such research is difficult to perform, however, owing to a variety of problems associated with patient recruitment and classification, and the biases that are frequently associated with the study of rare diseases. Despite its many limitations, establishment of disease registries may facilitate this research, as evidenced by the depth and breadth of findings recently obtained in inherited epidermolysis bullosa via such a mechanism.

Epidemiologic Methods↗
PubMed1994

Ultrastructural and immunohistochemical characterization of basal cells in three-dimensional culture models of the skin.

Keratinocytes were cultured on fibroblast-free dermal substitutes made of type I collagen film (collagen dermal substitute) and an extracellular matrix gel film (matrix dermal substitute), each of which was laid on a lyophilized type I collagen sponge. The morphology of the basal keratinocytes in these three-dimensional culture models of the skin was studied ultrastructurally and immunohistochemically to assess their differentiation to basal cells. The basal keratinocytes in the artificial epidermis cultured on the collagen dermal substitute showed poorly organized tonofibril networks and desmosomes. Neither the tonofibril-hemidesmosome complex nor the lamina densa were detected along the interface, where many cytoplasmic projections of basal keratinocytes were noted. There were no detectable antigens of type IV or VII collagen, LDA-1, or laminin in the interface. Bullous pemphigoid (BP) and 1-2B7B antigens and integrins were expressed along the cytoplasmic membrane and the projections of the basal keratinocytes. A high molecular weight keratin (keratin 1, 68 kDa, 34 beta B4) was detected only in part of the uppermost layers of this artificial epidermis. In contrast, basal keratinocytes in the artificial epidermis on the matrix dermal substitute developed tonofibril networks radiating to desmosomes and hemidesmosomes, under which a primitive lamina densa was present. Basement membrane zone antigens, such as type IV and VII collagens, LDA-1 and laminin were noted along the interface as were 1-2B7B and BP antigens and integrins. Laminin and type VII collagen were also detected along or in the membrane of the endoplasmic reticulum of basal keratinocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Basement Membrane↗
PubMed1994

Prenatal exclusion of pyloric atresia-junctional epidermolysis bullosa syndrome.

BACKGROUND: The pyloric atresia--junctional epidermolysis bullosa (PA-JEB) syndrome is an autosomal recessive disorder with a poor prognosis. Electron microscopy of fetal skin has been the only reliable method for prenatal diagnosis. OBJECTIVE: The purpose of this study was to make the prenatal diagnosis of PA-JEB syndrome with a more reliable method by means of immunocytochemical probes. METHODS: Expression of a range of basement membrane antigens was examined in different types of JEB. On the basis of the results, a fetal skin biopsy specimen was obtained for prenatal diagnosis. RESULTS: In PA-JEB syndrome (n = 2), GB3 antigen (BM600) was normally expressed; the 19-DEJ-1 antigen was completely absent. In fetal skin at risk for PA-JEB syndrome, the 19-DEJ-1 antigen was normally expressed, and no ultrastructural abnormality was found by electron microscopy. A normal male infant was delivered at 38 weeks of pregnancy. CONCLUSION: 19-DEJ-1 monoclonal antibody serves as a useful probe for the prenatal diagnosis of PA-JEB syndrome.

Adult↗
PubMed1994

The National Epidermolysis Bullosa Registry.

Since its inception in 1986, the NEBR has proved to be an excellent example of how a relatively small allocation of federal research funds for the development of a registry of cases of a single rare disease can have a major impact on the rapid expansion in the depth of knowledge of not only the disease itself but of a number of associated biologic principles, including keratinization and epithelial cell-extracellular matrix interactions. At present, the NEBR is generating extensive clinical, laboratory, and demographic data, both from cross-sectional and longitudinal perspectives, as well as establishing a centralized cell and tissue bank that will serve the scientific community at large as a valuable resource for future basic research on this oftentimes devastating genetic disease.

Data Collection↗
PubMed1994

International symposium on epidermolysis bullosa. The William and Ida Friday Continuing Education Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, April 25-26, 1994. Abstracts.

An international symposium on inherited epidermolysis bullosa was held at the University of North Carolina at Chapel Hill on April 25-26, 1994. All areas currently of clinical and research interest pertinent to this disease were discussed, ranging from basic epidemiologic issues to the definition of molecular defects in each of the three major types of epidermolysis bullosa and the potential for gene therapy. A major focus of this meeting was the presentation of data collected by the National Epidermolysis Bullosa Registry.

Epidermolysis Bullosa↗
PubMed1994

Immunoelectron microscopy of skin basement membrane zone antigens: a pre-embedding method using 1-nm immunogold with silver enhancement.

There is no single immunoelectron microscopical method for invariably effective localization of both intracellular and extracellular antigens. We describe a simple and practicable immunogold technique that can be used to localize various skin basement membrane zone antigens at the ultrastructural level. Small pieces of skin were incubated with primary antibodies recognizing epitopes on a range of basement membrane zone-related antigens (two different lamina lucida-associated antigens, laminin, type VII collagen, fibrillin and keratin 14). This was followed by incubation with 1-nm colloidal gold-conjugated secondary antibody and subsequent silver intensification. The specimens were then processed for transmission electron microscopy. Precise immunolocalization with good ultrastructural preservation was achieved for all basement membrane zone antibodies tested. The results of basal cell keratin immunostaining showed that this microscopic approach could also be applied to some extent in the characterization of intracellular antigens. This immunoelectron microscopy technique provides a useful approach to the study of macromolecules at the basement membrane zone.

Antigens↗
PubMed1994

Hereditary epidermolysis bullosa.

Epidermolysis bullosa (EB) is a diverse group of disorders having blister formation as their common feature. Tissue separation occurs at variable depths in the skin and/or mucosa depending on the specific EB type. Marked oral involvement of the soft and hard tissues can produce potentially devastating alterations, with oral tissue fragility and blistering common to all EB types. Oral debilitation resulting from soft tissue scarring is limited primarily to the recessive dystrophic EB subtypes. Individuals with generalized recessive dystrophic EB typically have microstomia, obliteration of the oral vestibule, and ankyloglossia. Generalized enamel hypoplasia appears to be limited to junctional EB, whereas rampant dental caries afflicts many individuals having either junctional or generalized recessive dystrophic EB. Although systemic treatment remains primarily palliative, it is possible to prevent destruction and subsequent loss of the dentition through appropriate interventions and dental therapy. The severely affected soft and/or hard tissues frequently seen in patients having generalized recessive dystrophic and junctional EB often require aggressive dental intervention to maintain optimal oral health. Even the most severely affected individuals with EB can retain their dentition through the use of modern dental restorative techniques delivered using general anesthesia.

Dental Enamel Hypoplasia↗
PubMed1994

Laboratory tests for epidermolysis bullosa.

Determination of the correct diagnosis and subclassification of inherited and acquired forms of epidermolysis bullosa (EB) can be exceedingly challenging because the clinical morphologic findings and routine histology are frequently nonspecific. The most precise means of diagnosing inherited EB involves the assessment of a combination of ultrastructural and antigenic features by transmission electron microscopy, immunofluorescence antigenic mapping, and EB-related monoclonal antibody studies. Acquired EB can usually be diagnosed by split skin indirect or direct immunofluorescence. When necessary, immunoelectron microscopy, immunoprecipitation, and immunoblot can be used.

Antibodies, Monoclonal↗
PubMed1993

Oral involvement of recessive dystrophic epidermolysis bullosa inversa.

The inversa subtype of autosomal recessive dystrophic epidermolysis bullosa (EBDR-I) is a rare variant characterized by lesions involving primarily the flexural areas of the body. The purpose of this investigation was to characterize the oral manifestations of this unusual dermatologic condition. Ten individuals having EBDR-I were evaluated and compared with an age and sex-matched population of unaffected individuals that served as controls. The diagnosis of EBDR-I was confirmed by skin biopsy that demonstrated tissue separation below the lamina densa and the clinical presentation of blister formation that typically localized to flexural areas. There was clinical variability in the severity and distribution of skin involvement; however, none of the affected individuals demonstrated pronounced digital webbing, severe generalized blistering or growth retardation characteristic of the Hallopeau-Siemens form of EBDR. Oral involvement was seen in all cases with ankyloglossia, loss of tongue papillae and obliteration of the oral vestibule between the lips and gingiva being typical. The oral opening was significantly reduced in older EBDR-I individuals compared with matched controls, confirming that acquired microstomia is a characteristic of EBDR-I. The teeth were not clinically abnormal or malformed and showed no evidence of generalized enamel hypoplasia. Despite this, the prevalence of dental caries in EBDR-I individuals was significantly higher than the control group. The inversa form of EBDR presents with oral findings that are similar but generally milder than those seen in the Hallopeau-Siemens variant of EBDR.

Epidermolysis Bullosa Dystrophica↗
PubMed1993

The genetic basis of Weber-Cockayne epidermolysis bullosa simplex.

Epidermolysis bullosa simplex (EBS) is a group of autosomal dominant skin diseases characterized by blistering, due to mechanical-stress-induced degeneration of basal epidermal cells. Recently, it was discovered that the more severe types, Dowling-Meara and Koebner, are genetic disorders of the basal epidermal keratins, keratin 5 (K5) and keratin 14 (K14). Here, we show that the mildest type of EBS, Weber-Cockayne, is also a disorder of these keratins. Affected members of two unrelated families with Weber-Cockayne EBS had a T-->G point mutation in the second base position of codon 161 of one of two K5 alleles, leading to an Ile-->Ser mutation. This mutation was not present in unaffected members or in 156 alleles from normal individuals. Linkage analyses mapped the defect to the type II keratin gene cluster on chromosome 12q11-q13 (peak logarithm of odds score at theta = 0 of 3.0), providing strong additional evidence that this mutation is responsible for the Weber-Cockayne EBS phenotype. Conserved among type II keratins, Ile-161 is in the nonhelical head domain of K5, a region previously shown to be important for 10-nm filament assembly. The mutation generates a potential substrate site for protein kinase C, which could influence intermediate filament architecture, perhaps leading to the intrafilament association seen ultrastructurally in patients with the mutation.

Amino Acid Sequence↗
PubMed1993

Development defects of enamel in humans with hereditary epidermolysis bullosa.

Developmental defects of enamel are often reported as a feature of the more severe forms of epidermolysis bullosa (EB). The purpose of this investigation was to determine the prevalence and character of enamel defects in each of the major hereditary EB types. Clinical evaluations were made on 237 individuals representing all of the major EB types and 58 unaffected individuals. All EB cases were categorized by phenotype, mode of inheritance and skin biopsy. The frequency of individuals having developmental enamel defects ranged from 8.6% in recessive dystrophic EB to 100% in junctional EB; 27.5% of the control population had these defects. Generalized hypoplasia characterized by either severe pitting and/or thin enamel was seen in all junctional EB cases but not in any other EB type. There was a tendency for the severe Herlitz form of junctional EB to have thin enamel while non-Herlitz junctional EB cases had less severe pitting and generally no reduction in enamel thickness. The prevalence of individuals with hypoplastic enamel bands was greater in the EB population (9.7%) than controls (1.9%). Thus individuals with simplex and dominant dystrophic EB typically have enamel defects that are similar in frequency and distribution to those of unaffected individuals. Developmental defects of enamel are a consistent feature of junctional EB, although the clinical expression is highly variable.

Adolescent↗
PubMed1993

Normal molecular weight of type VII collagen produced by recessive dystrophic epidermolysis bullosa keratinocytes.

Studies of the recessive dystrophic form of epidermolysis bullosa (RDEB) have suggested that an abnormality in type VII collagen may be involved in the pathogenesis of this disorder. Indirect immunofluorescence studies have shown that the staining for type VII collagen along the dermal-epidermal junction is markedly reduced or absent in all but rare cases of severe, generalized RDEB. These findings imply that the genetic defect may involve type VII collagen but do not exclude the possibility that the alterations demonstrated are secondary, for example, to nonspecific proteolysis of type VII collagen. To evaluate the ability of cells of affected patients to produce type VII collagen, we cultured keratinocytes from a severely affected patient and immunoprecipitated type VII collagen from the cells. Keratinocytes were metabolically labelled with 35S-methionine, and solubilized cell extracts were reacted with antibody to type VII collagen. The results indicate that the patient's keratinocytes synthesize type VII collagen and that the M(r) of the protein synthesized does not differ from that of an unaffected control. Because cultured cells from a patient severely affected with recessive dystrophic epidermolysis bullosa produce type VII collagen, the genetic defect, at least in this patient, is unlikely to reside in a major truncation of the type VII collagen molecule.

Collagen↗
PubMed1993

Intracytoplasmic retention of type VII collagen and dominant dystrophic epidermolysis bullosa: reversal of defect following cessation of or marked improvement in disease activity.

It has been recently shown that the presence of perinuclear "stellate bodies" within the epidermis in patients with a form of dominant dystrophic epidermolysis bullosa named "transient bullous dermolysis of the newborn" corresponds to collections of type VII collagen. To determine the temporal relationship of this unique immunohistochemical defect with course of clinical disease activity, we have longitudinally studied the expression of two epitopes of type VII collagen (LH 7:2; L3d) in nine patients in four such kindreds by immunofluorescence and immunoelectron microscopic technique. In every infant so studied at the time of active blistering, type VII collagen was detectable primarily within basilar and, to a lesser extent, suprabasilar keratinocytes. In contrast, type VII collagen was detectable solely in linear array along the dermoepidermal junction in skin from each patient following complete cessation or at least marked diminution of visible clinical disease activity. These findings support the hypothesis that the temporary mechanical fragility and blistering of the skin in infants with this rare subset of dominant dystrophic epidermolysis bullosa reflect the presence of reduced amounts of type VII collagen along the dermoepidermal junction, and that this diminution may be the result of either a delay in transport and integration of type VII collagen from basilar keratinocytes into the skin basement membrane or excessive phagocytosis of type VII collagen.

Adult↗
PubMed1993

Identification and partial characterization of a novel 105-kDalton lower lamina lucida autoantigen associated with a novel immune-mediated subepidermal blistering disease.

Certain skin basement membrane components, such as bullous pemphigoid antigens and epidermolysis bullosa acquisita antigen, were discovered as a result of an autoimmune reaction. In this report, we describe a unique lamina lucida determinant associated with a novel immune-mediated subepidermal bullous dermatosis. This unique bullous dermatosis resembled severe toxic epidermal necrolysis clinically. The histologic findings resemble dermatitis herpetiformis. Direct immunofluorescence microscopy detected linear immunoglobulin G (IgG) and C3 deposition at the cutaneous basement membrane zone of lesional and perilesional skin. Direct and indirect immunoelectron microscopy localized the IgG deposits to the lowest portion of the lamina lucida. The patient's autoantibodies, belonging to the IgG1 subclass, labeled basement membrane zone of normal intact human skin, oral mucosa, and conjunctiva, and localized to the dermal side of salt-split normal adult and neonatal human skin, but failed to react with human fetal skin up to 142 gestational days. The patient's autoantibodies failed to react with bullous pemphigoid antigens or epidermolysis bullosa acquisita antigen (type VII collagen) by immunoblotting. Instead, the patient's autoantibodies unequivocally labeled a 105-kilodalton (kD) protein in cellular extracts and conditioned media of human cultured keratinocytes and dermal fibroblasts. The titer of the patient's antibody against the cutaneous basement membrane zone and the intensity of the antibody reactivity against the 105-kD protein paralleled the patient's disease activity. Thus, this 105-kD lower lamina lucida protein represents a novel autoantigen and this patient's disease represents a novel autoantigen and this patient's disease represents a deep lamina lucida pemphigoid, distinguishable from all other known autoimmune bullous dermatoses.

Autoantigens↗
PubMed1992

Autosomal dominant erythromelalgia.

We present a kindred of 29 persons affected with erythromelalgia (erythermalgia) in 5 generations. This paper updates the family reported by Burbank et al. [1966]. Patients have symptoms of intermittent intense burning limb pain related to increased skin temperature. No successful treatment has been identified, and the pathogenetic mechanism has not been established. Most affected individuals are female.

Adult↗