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Biomedical subjects

L J Meyer

Publications and source records attributed to L J Meyer.

At least 37 records · Page 2Linked to original sources
PubMed1994

Antigenic specificity of antibodies from patients with linear basement membrane deposition of IgA.

We reviewed the immunoreactivity of sera binding to the epidermal side of basement membrane split skin from 13 adults and 8 children with IgA alone, 9 adults with IgA and IgG and 7 adults with IgA and ocular pemphigoid. Immunoblots were done against previously described 45-, 97-, 180- and 230-kD antigens, and reactivity was confirmed by elution of antibody from nitrocellulose and binding to the basement membrane. Ten of 13 adults and 7 of 8 children reacted with the 97-kD antigen. Sera with both IgA and IgG reacted in varying patterns and on occasion with more than 1 antigen. All 7 patients with ocular cicatricial pemphigoid reacted uniquely with a 45-kD antigen.

Adult↗
PubMed1993

Antigen identification in drug-induced bullous pemphigoid.

Immunobullous diseases usually develop spontaneously, but drug-induced bullous disease develops in a small subgroup of patients. We examined a patient in whom bullous pemphigoid developed after she received enalapril for treatment of hypertension. IgG antibody directed against a 230 kd antigen was identified. The eluted IgG autoantibody was shown to bind to the basement membrane zone on split skin. This study demonstrates that drug-induced bullous pemphigoid autoantibody in this patient was directed against the same antigen as the spontaneous bullous pemphigoid antigen.

Aged↗
PubMed1993

Identification of a basement membrane zone antigen reactive with circulating IgA antibody in ocular cicatricial pemphigoid.

Ocular cicatricial pemphigoid is a rare vesiculobullous disease characterized by linear deposition of IgG and/or IgA along the basement membrane zone of conjunctival biopsies. This study identifies a tissue antigen detected by ocular cicatricial pemphigoid patient sera. Patient selection was based on the presence of only ocular involvement and a positive direct immunofluorescence of conjunctiva. We evaluated patient and control sera using indirect immunofluorescence of basement membrane zone separated skin, Western blot, and purified antibodies from nitrocellulose and epidermal sheets. Direct immunofluorescence performed on the patients' conjunctival biopsy showed linear deposition of IgA along the basement membrane zone in all seven patients, and five of seven also demonstrated deposition of IgG along the basement membrane zone. Indirect immunofluorescence performed on the patients' sera demonstrated linear deposition of IgA along the epidermal side of the basement membrane zone of ethylenediaminetetraacetic acid-separated skin in all seven patients. IgA titers ranged from 1:20 to 1:80. No IgG was detected. Immunoblots detected IgA binding to a 45-kD antigen in all patients as well as sporadic IgA binding to a number of other proteins. Immunoblots stained with sera from patients did not show reactivity to the 230- or 180-kD bullous pemphigoid antigens or the 97-kD linear IgA bullous dermatosis antigen. Eluting IgA from the 45-kD region and other regions revealed that only antibodies eluted from the 45-kilodalton region bound linearly to the basement membrane on separated skin. Purification of IgA using epidermal sheets confirmed that the antibody responsible for staining on indirect immunofluorescence bound to the 45-kD region on Western blot. Sera from normals and patients with bullous pemphigoid, dermatitis herpetiformis, and linear IgA bullous dermatosis failed to demonstrate basement membrane zone IgA on elution of the 45-kD region. We conclude that these ocular cicatricial pemphigoid sera contain a unique IgA antibody that binds to a 45-kD basement membrane zone antigen.

Antibodies, Anti-Idiotypic↗
PubMed1992

Assignment of a locus for familial melanoma, MLM, to chromosome 9p13-p22.

Linkage analysis of ten Utah kindreds and one Texas kindred with multiple cases of cutaneous malignant melanoma (CMM) provided evidence that a locus for familial melanoma susceptibility is in the chromosomal region 9p13-p22. The genetic markers analyzed reside in a candidate region on chromosome 9p21, previously implicated by the presence of homozygous deletions in melanoma tumors and by the presence of a germline deletion in an individual with eight independent melanomas. Multipoint linkage analysis was performed between the familial melanoma susceptibility locus (MLM) and two short tandem repeat markers, D9S126 and the interferon-alpha (IFNA) gene, which reside in the region of somatic loss in melanoma tumors. An analysis incorporating a partially penetrant dominant melanoma susceptibility locus places MLM near IFNA and D9S126 with a maximum location score of 12.71. Therefore, the region frequently deleted in melanoma tumors on 9p21 presumably contains a locus that plays a critical role in predisposition to familial melanoma.

Adolescent↗
PubMed1992

The incidence and prevalence of dermatitis herpetiformis in Utah.

BACKGROUND AND DESIGN: The incidence and prevalence of dermatitis herpetiformis has never been formally evaluated in any area of the United States. Several northern European studies have shown prevalence rates ranging from 1.2 per 100,000 to 39.2 per 100,000. The present study was performed to evaluate the incidence and prevalence of dermatitis herpetiformis in Utah. Information from 240 patients diagnosed with dermatitis herpetiformis was compiled from hospital records throughout Utah, as well as the sole private dermatopathologist in the state, and from the university referral center of the state. Criteria for inclusion in the study were a clinical diagnosis of dermatitis herpetiformis plus granular deposition of IgA in dermal papillae by direct immunofluorescence of uninvolved skin, or histopathologic findings consistent with the disease. Clinical diagnosis and response to dapsone alone was considered insufficient for inclusion in the study. On the basis of these criteria, as well as exclusion of non-Utah residents, 188 of the original 240 patients qualified for the study. RESULTS: The prevalence of dermatitis herpetiformis in Utah in 1987 was 11.2 per 100,000. The mean incidence for the years 1978 through 1987 was 0.98 per 100,000 per year. The mean age at onset of symptoms for male patients was 40.1 years, and that for female patients was 36.2 years. The male-female ratio was 1.44:1. CONCLUSIONS: This represents the first evaluation of the incidence and prevalence of dermatitis herpetiformis in the United States. These results are similar to those of the previous studies, probably because of Utah's largely northern European ancestry. This population base, plus a much smaller than average black and Oriental population, is likely to have produced a higher incidence and prevalence in Utah than would be seen in other areas of the United States.

Adult↗
PubMed1991

Inheritance of nevus number and size in melanoma and dysplastic nevus syndrome kindreds.

Previous studies of the genetics of melanoma have focused on the dysplastic nevus syndrome (DNS). The variability in clinical and histopathological expression of affected individuals, however, has made definition and diagnosis of the syndrome difficult and subjective. Independent of the DNS, case-control studies have demonstrated the total number of nevi to be a significant risk factor for melanoma. In this article, we report results of genetic analyses of two quantitative nevus phenotypes that can be measured objectively in all subjects: the total number of nevi on an individual (TNN) and total nevus density (TND), a derived phenotype which incorporates both number and size of nevi. Ten kindreds ascertained for multiple cases of DNS-melanoma (multiplex ascertainment) and 16 kindreds and 19 solitary cases ascertained from a sequential list of melanoma cases without regard for family history (simplex ascertainment) were studied. Both phenotypes exhibited increased levels in relatives of probands compared with those in spouse controls. While neither TNN nor TND exhibited evidence for a major factor in the simplex pedigrees, a major factor was strongly indicated in the multiplex kindreds for TND. When both phenotypes were examined in more detail in the multiplex kindreds, the phenotype incorporating nevus size, TND, fit a mendelian pattern of inheritance better than the TNN. Significant residual familial correlations were found for both phenotypes. Parameter estimates from the best fitting genetic model indicated that a major gene may be responsible for 55% of the phenotypic variability of TND in the multiplex kindreds.

Adolescent↗
PubMed1991

Bullous pemphigoid antigens: extraction and degradation of antigens during epidermal preparation.

Although two groups of bullous pemphigoid antigens have been well characterized, different research groups have shown strikingly different prevalence rates of antibodies to these antigens in their patients. Potential explanations for this phenomena include a patient population that has different prevalence of antibodies, or that the antigen preparations used by the different groups contain different relative amounts of these antigens. We have compared the relative concentration of the different bullous pemphigoid antigens in epidermal extract preparations made by three different procedures commonly used to separate dermis from epidermis: NaCl, ethylenediaminetetraacetic acid (EDTA), and heat. We have found that the amount of the 180-kD antigen present in extracts is dependent on the techniques involved in separation of the epidermis from dermis. NaCl- and EDTA-separation procedures result in partial proteolysis of the 180-kD antigen to smaller forms, including major brands at 160 kD and 97 kD in the EDTA preparation. Fragments of the 180-kD antigen are present in both the separation and wash fluids, associated with a significant reduction of the 180-kD form in the extract of the NaCl-separated skin. We conclude that the native molecular weight of the previously described minor bullous pemphigoid antigen is 180 kD, and that the apparent difference in patient reaction to the 180-kD antigen may be due to different preparations of the antigen rather than underlying differences in seropositivity in the patient population.

Autoantigens↗
PubMed1991

The effect of an elemental diet with and without gluten on disease activity in dermatitis herpetiformis.

Elemental diets are reported to decrease activity of patients with dermatitis herpetiformis. We tested the hypothesis that gluten, given in addition to an elemental diet, is responsible for the intestinal abnormalities, cutaneous immunoreactant deposition, and skin disease activity in dermatitis herpetiformis. At entry eight patients with dermatitis herpetiformis, who were consuming unrestricted diets, were stabilized on their suppressive medications at dosage levels that allowed individual lesions to erupt. Six patients were then given an elemental diet plus 30 of gluten for 2 weeks, followed by the elemental diet alone for 2 weeks. Conversely, two patients received an elemental diet alone for 2 weeks followed by an elemental diet plus gluten during the final 2 weeks. Small bowel biopsies, skin biopsies, and clinical assessments were done at 0, 2, and 4 weeks. Suppressive medication dose requirement decreased over the 4 weeks by a mean of 66%. Six of eight subjects significantly improved clinically during the gluten-challenge phase of the elemental diet and all were improved at the end of the study. The amount of IgA in perilesional skin did not change significantly, but the amount of C3 increased in five of seven evaluable subjects after gluten challenge. Circulating anti-gluten and anti-endomysial antibodies were not significantly affected by the diets. All subjects completing evaluable small bowel biopsies (seven of seven) demonstrated worsening of their villus architecture (by scanning electron microscopy and intraepithelial lymphocyte counts) during gluten challenge and improvement (six of six subjects) after 2 weeks of elemental dietary intake. We conclude that 1) there is a significant improvement in clinical disease activity on an elemental diet, independent of gluten administration, 2) small bowel morphology improves rapidly on an elemental diet, and 3) complement deposition but neither IgA deposition nor circulating antibody levels correlate with gluten intake. It seems likely that dietary factors other than gluten are important in the pathogenesis of the skin lesions in dermatitis herpetiformis.

Adult↗
PubMed1991

HMB-45 staining of dysplastic melanocytic nevi in melanoma risk groups.

To evaluate the hypothesis that reactivity of the intradermal component of melanocytic nevi to the monoclonal antibody HMB-45 correlates with melanoma risk, dysplastic compound melanocytic nevi were examined for expression of the HMB-45 epitope in three subject groups differing in epidemiological risk for melanoma. The study groups consisted of 10 subjects with dysplastic nevi and a personal history of melanoma, 25 subjects with dysplastic nevi and a history of melanoma in one or more first degree relatives, and 15 population control subjects with sporadic dysplastic nevi. For each case, sections from one lesion, immunohistochemically processed for HMB-45 binding, were evaluated by two pathologists without knowledge of the clinical data. Of all dysplastic nevi, 98% showed diffusely positive cytoplasmic staining of the junctional nevomelanocytes and 90% had such positive staining of those cells within the superficial dermis. Nevus cells within the deeper dermis did not stain positively in any case. Furthermore, the data showed no differences in frequency, pattern, or intensity of HMB-45 reactivity between the subject groups. These observations indicate that evaluation of dysplastic nevi with the monoclonal antibody HMB-45, an apparent marker of proliferative or otherwise stimulated melanocytes, has no discriminating value for identifying subjects at increased historical risk for melanoma. The data, however, support the concept that so-called dysplasia within nevi, as defined by histologic criteria, actually represents the active or proliferative phase of melanocytic nevi.

Antibodies, Monoclonal↗
PubMed1990

Psoriasis: the application of genetic technology and mapping.

Recent progress in molecular genetics has led to the creation of a map of the human genome utilizing RFLP. Given a sufficient family structure, genetic diseases can now be placed on this map. Genetic studies of psoriasis can both help resolve and be confounded by problems of disease heterogeneity, environmental effects on disease expression, and lack of a clear mode of inheritance.

Alleles↗
PubMed1990

Two groups of bullous pemphigoid antigens are identified by affinity-purified antibodies.

The bullous pemphigoid antigen was originally described as a 240-kD protein extracted from human epidermis, but a subsequent report has described patients' sera which react with epidermal proteins of molecular masses 240, 200, 180, 97, and 77 kD. We have evaluated the heterogeneity of the pemphigoid antigens identified by the sera of 10 patients with clinically typical bullous pemphigoid. We used indirect immunofluorescence and Western immunoblots of epidermal extracts prepared from epidermis separated by either 1 M salt or 20 mM EDTA to characterize the reactivity of both crude sera and affinity-purified antibodies. Affinity purification of antibodies was performed with either normal human epidermis or protein bands blotted onto nitrocellulose as immunoabsorbents. The anti-basement membrane antibody titers determined by indirect immunofluorescence on the saline- and EDTA-separated epidermis were identical. Despite this, Western blots of extracts prepared from EDTA-separated epidermis demonstrated greater amounts of the 240-kD antigen than saline split skin. Multiple antigens were recognized in epidermal extracts on Western blots by most crude BP sera, including bands at 240, 200, 160, and 100 kD. Different sera reacted with these antigens with a markedly different intensity, falling into two major groups, those bearing antibodies to the 240-200-kD antigens and those with antibodies to the 160-100-kD components. When epidermis was used as a substrate for affinity purification of bullous pemphigoid antibodies, the eluted antibodies reacted with multiple bands on Western blots, demonstrating the reactivity of anti-basement membrane zone antibodies with multiple proteins. Antibodies eluted from several individual bands of immunoblots were found to react with the basement membrane on indirect immunofluorescence. When these nitrocellulose-purified antibodies were reapplied to Western blots, they cross-reacted within two groups, the 240-200 kD antigens and the 160-100 kD antigens. We conclude that pemphigoid antigens are best demonstrated when EDTA-split skin is used for extraction and that different pemphigoid sera may contain antibodies to two separate groups of basement membrane zone antigens.

Antibodies↗
PubMed1990

Identification of the cutaneous basement membrane zone antigen and isolation of antibody in linear immunoglobulin A bullous dermatosis.

Linear IgA bullous dermatosis (LABD) is a rare blistering skin disease characterized by basement membrane zone deposition of IgA. This study identifies a tissue antigen detected by patient serum and then isolates the autoantibody using epidermis and protein bands blotted on nitrocellulose as immunoabsorbents. Sera from 10 patients (9 with cutaneous disease and 1 with cicatrizing conjunctivitis) were evaluated. Indirect immunofluorescence revealed an IgA anti-basement membrane antibody in 6 of 10 sera with monkey esophagus substrate and 9 of 10 sera with human epidermal substrate. Immunoblotting was performed on epidermal and dermal extracts prepared from skin separated at the basement membrane zone with either sodium chloride or EDTA. Saline-separated skin expressed a 97-kD band in dermal extract alone that was recognized by 4 of 10 sera. EDTA-separated skin expressed the 97-kD band in both epidermal (4 of 10 sera) and dermal (6 of 10 sera) extract. Immunoabsorption of positive sera with epidermis purified an IgA antibody that reacted uniquely with the 97-kD band. In addition, IgA antibody bound to nitrocellulose was eluted from the 97-kD band and found to uniquely bind basement membrane zone. It is likely that the 97-kD protein identified by these techniques is responsible for basement membrane binding of IgA in LABD.

Adult↗
PubMed1990

Evidence against the reported linkage of the cutaneous melanoma-dysplastic nevus syndrome locus to chromosome Ip36.

The reported linkage between cutaneous melanoma and the dysplastic nevus syndrome (CM/DNS) to markers located on the distal portion of the short arm of chromosome 1 was examined in three Utah kindreds ascertained for multiple cases of melanoma. Family members in these kindreds were genotyped for the two markers reported to be most closely linked in the Bale study, PND and D1S47. Both melanoma alone and a combined melanoma/DNS phenotype were analyzed; no evidence for linkage was found. By multipoint linkage analysis the CM/DNS locus was excluded from an area of 55 cM containing the PND-D1S47 region. Diagnostic or genetic heterogeneity are alternate explanations for the discrepancy between our observations and those of Bale et al.

Chromosome Mapping↗
PubMed1990

Histopathologic characteristics of dysplastic nevi. Limited association of conventional histologic criteria with melanoma risk group.

Studies of dysplastic melanocytic nevi (DMN) have suggested that lesions from patients with a personal or family history of malignant melanoma are histologically more atypical than are those from control populations without such histories. To evaluate this possibility, we examined histologic sections of DMN that had been removed from patients in three groups. Group A consisted of 17 subjects with a past history of melanoma; group B comprised 79 subjects with DMN and a family history of melanoma in first-degree relatives; group C consisted of 64 subjects who were unrelated spouses of members of groups A and B. For each group, sections of DMN were initially selected on the basis of architectural atypia as defined by the National Institutes of Health Consensus Conference. All biopsy material was then further evaluated for four histologic features suggested to be discriminatory for DMN associated with increased melanoma risk; the features are degree of junctional activity, irregularity of melanocytic nests, presence of dusty melanin, and size of melanocytic nuclei. A subjective rating was given for each on a 0 to 3 scale of increasing severity. Three pathologists individually rated the specimens without knowledge of the patient group. The means of the individual observer cumulative scores of the four histologic criteria for each biopsy specimen and the average of these means from the three observers exhibited a trend to increasing values from groups C to A, but none of the differences reached statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1989

The dysplastic melanocytic nevus: a prevalent lesion that correlates poorly with clinical phenotype.

We estimated the prevalence of persons with histologic dysplasia in at least one of two nevi examined by biopsy to be 53% in Utah's caucasians. This apparently high prevalence indicates that such lesions may represent a normal variant of a melanocytic nevus, perhaps those in the process of active proliferation. Regardless of the apparent ubiquity of these lesions, examination of biopsy specimens led to a grading scheme of histologic dysplasia that may reflect chronologic stages in the neoplastic development of melanocytic nevi. Comparison of these histologic findings with the clinical examination yielded the unexpected result that dysplasia and lesion size are independent of each other. Lesions 3 mm in diameter or smaller were as likely to be dysplastic as those much larger. There was, however, a statistically significant relationship between histologic dysplasia of a nevus examined by biopsy and the person's total number of melanocytic lesions. This finding indicates that the pathology grading scheme may be useful. The high prevalence of dysplastic nevi dilutes the clinical significance of a dysplastic nevus as an isolated finding and thereby lessens the importance of pathologic findings in the diagnosis of dysplastic nervus syndrome.

Adolescent↗