Biomedical subjects
Publications and source records attributed to M G Fleming.
Digital dermatoscopic images are acquired with digital cameras or video camera and frame grabber combinations. These images can be compressed, transmitted, or archived; combined with clinical anamnestic information for medical record purposes; or attached to body surface diagrams for mole mapping applications. Image analysis software, which might interpret the images to produce a computer-assisted or fully automated diagnosis, is under development.
Bullous pemphigoid (BP) is an inflammatory subepidermal blistering disease associated with an IgG autoimmune response to the hemidesmosomal protein BP180. Passive transfer of antibodies to the murine BP180 (mBP180) ectodomain triggers a blistering skin disease in mice that depends on complement activation and neutrophil infiltration and closely mimics human BP. In the present study, we show that mast cells (MCs) play a crucial role in experimental BP. Wild-type mice injected intradermally with pathogenic anti-mBP180 IgG exhibited extensive MC degranulation in skin, which preceded neutrophil infiltration and subsequent subepidermal blistering. In contrast, mice genetically deficient in MCs or MC-sufficient mice pretreated with an inhibitor of MC degranulation failed to develop BP. Further, MC-deficient mice reconstituted in skin with MCs became susceptible to experimental BP. Despite the activation of complement to yield C3a and C5a, in the absence of MCs, accumulation of neutrophils at the injection site was blunted. The lack of response due to MC deficiency was overcome by intradermal administration of a neutrophil chemoattractant, IL-8, or by reconstitution of the injection sites with neutrophils. These findings provide the first direct evidence to our knowledge that MCs play an essential role in neutrophil recruitment during subepidermal blister formation in experimental BP.
We describe an 81-year-old white man in whom a subepidermal bullous eruption developed that clinically resembled bullous pemphigoid. The eruption promptly responded to oral tetracycline and niacinamide and topical clobetasol. Histologic examination of perilesional skin revealed neutrophilic infiltration with formation of papillary microabscesses and subepidermal cleavage. Direct immunofluorescence showed linear deposition of IgG and C3 along the basement membrane zone. By indirect immunofluorescence, circulating IgG autoantibodies bound exclusively to the dermal side of salt-split normal human skin. Immunoblot analysis demonstrated that the patient's autoantibodies reacted with a 200 kd dermal protein that was different from type VII collagen, the epidermolysis bullosa acquisita autoantigen. This patient represents the first confirmed case from the United States with a recently reported novel autoimmune subepidermal bullous disease associated with IgG autoantibodies to a 200 kd dermal antigen.
Malignant sweat gland tumors are rare tumors of the extremity. Their insidious growth patterns and often confusing pathological characteristics can cause confusion with more common benign tumors. However, these tumors cannot be neglected because they do have a propensity to metastasize. Presented is a 56-year-old woman with a malignant clear-cell hidradenoma of the foot actually presenting as a benign lesion.
Because of the dental profession's increased utilization of light-cured restorative materials, there has been a corresponding increase in research into the light sources used to initiate polymerization. The argon laser is one promising source, as the wavelength of light emitted by this laser is optimal for the initiation of polymerization of composite resins. The literature reflects a strong divergence of opinion about many aspects of the effectiveness of laser curing compared to conventional light curing. Research indicates that the argon laser offers a greater depth and degree of polymerization, less time required and an enhancement of the physical properties of composite resins polymerized. These advantages are offset by reports that the increased polymerization caused by the laser results in increased shrinkage, brittleness and marginal leakage. Dentists interested in the new technology need to monitor ongoing studies.
Image cytometry was used to measure the size, shape, and texture of lymphocyte nuclei in 24 skin biopsy specimens retrospectively selected from patients with early, nonspecific, graft-versus-host disease (GVHD)-like eruptions. Half of these patients had progressed to overt GVHD, whereas half had never developed more than a mild nonspecific eruption. Significant differences were detected in the nuclear texture of the eruptions of the two groups, but the differences were not consistent enough to suggest that image cytometry might play a significant role in recognition of early GVHD.
Eighteen cases of early mycosis fungoides were compared with 18 cases of eczematous dermatitis by multiparametric image cytometry. A minimum of 100 lymphocytes was measured in each case. A large number of measurements was acquired for each lymphocyte, characterizing nuclear DNA content, area, shape, and texture. There were significant differences between the two groups, especially in nuclear DNA content and texture. These differences allowed the two groups of nuclei to be distinguished with 78% accuracy. The two groups of lesions were distinguished with 94% accuracy, using neural network analysis.
A relatively inexpensive, non-proprietary high resolution color pathology workstation is described. Hardware consists of a JVC frame capture camera with adjustable resolution up to 4416 x 3456, matching frame grabber and a Unix workstation. Analytic software was developed using Khoros 1.0.5, a powerful and flexible system for the development of image analysis applications that is based on a visual programming language. Applications have been developed for DNA ploidy, quantitative immunohistochemistry and texture and shape analysis. The instrument's software is uniquely extensible and transparent, and has been made publicly available over the Internet.
BACKGROUND: We describe a new variant of inherited epidermolysis bullosa and elucidate the clinical, histologic, and ultrastructural features of this condition. OBSERVATIONS: This form of epidermolysis bullosa displays an autosomal dominant inheritance pattern, is characterized by acral bullae, and histologically demonstrates suprabasal clefting with acantholysis. Ultrastructural findings are nonspecific but reminiscent of those observed in benign familial pemphigus. CONCLUSION: Acantholytic epidermolysis bullosa is a rare but distinct clinicopathologic entity that warrants inclusion in the nosologic classification of epidermolysis bullosa.
Expression of IGF-I mRNA and protein was evaluated in pigmented lesions by in situ hybridization and immunohistochemistry. An IGF-I cDNA clone (phigf1) was subcloned into pBluescript KS II-. Both sense and antisense 35S riboprobes were prepared and used for in situ hybridization on formalin-fixed, paraffin-embedded specimens. Control hybridizations with a beta-actin probe were also performed. Grains were counted in 787-microns2 melanocytic areas of sections hybridized with the antisense IGF-I probe. Seven common nevi contained a mean of 218 grains; nine dysplastic nevi, a mean of 463 grains; eight early primary melanomas, a mean of 402 grains; five advanced primary melanomas, a mean of 217 grains; and nine metastatic melanomas, a mean of 194 grains. The differences between common and dysplastic nevus, common nevus and early melanoma, early and advanced primary melanoma, and early primary melanoma and metastatic melanoma were statistically significant. Keratinocytes also expressed abundant IGF-I message. IGF-I protein was demonstrable by immunohistochemistry in melanocytes and keratinocytes. These results suggest that progression-associated variation occurs in the net expression of IGF-I mRNA in melanocytic tumors.
Multiparametric image cytometry was applied to 10 examples each of malignant melanoma and common, Spitz, and dysplastic nevus. DNA index, area, and 21 parameters describing chromatin texture were measured for 50 nuclei in each lesion. Linear discriminant analysis was used to derive discriminant functions based on the measured parameters. The analysis demonstrated that chromatin texture provides more diagnostic information than either DNA index or nuclear area. The discriminant functions allowed 68% of nuclei to be accurately classified among the four groups, and allowed 37 of the 40 lesions to be accurately classified as nevus or melanoma.
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Eight common nevi and 11 dysplastic nevi were evaluated for the presence of basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor-alpha, interleukin-1-alpha, and interleukin-1-beta by immunohistochemical labelling with highly specific monoclonal antibodies. Basic fibroblast growth factor was abundant in the nevus cells and keratinocytes of nevi. Dysplastic nevus cells on average stained less intensely for basic fibroblast growth factor than did common nevus cells. In both types of nevi, basic fibroblast growth factor was identified in the basement membranes at the dermoepidermal junction and surrounding nevus cell nests and individual nevus cells. Labelling of nevus cells for transforming growth factor-alpha was variable, while there was moderate labelling for platelet-derived growth factor and light labelling for interleukin-1-alpha. Only two nevi, both dysplastic, stained (very faintly) for interleukin-1-beta. It is possible that these cytokines, especially basic fibroblast growth factor, act in autocrine fashion to maintain nevocellular growth and may also contribute to the epidermal hyperplasia and fibrosis frequently observed in nevi.
The percentage of keratinocytes in the proliferative phase of the cell cycle (S + G2 + M) was measured by DNA flow cytometry in sun-exposed, non-exposed, and tretinoin-treated skin. Before tretinoin treatment, the percentage of keratinocytes actively cycling was higher in sun-exposed than in non-sun-exposed skin (p = .002) and was correlated with clinically assessed photodamage (p = .007). Subsequently, tretinoin-treated sun-exposed skin was compared to the pre-treatment sun-exposed skin. Overall, there was no statistically significant change. However, there was a trend toward a decrease in the percentage of keratinocytes in the S + G2 + M phases immediately after four months of tretinoin use that was limited to the most severely damaged patients. This effect was no longer evident two months after discontinuing treatment. This is the first study, to our knowledge, utilizing flow cytometry to investigate the effects of tretinoin in patients with varying degrees of photodamage.
A 34-year-old man with X-linked infantile hypogammaglobulinemia, bronchiectasis, and chronic liver disease had a papular eruption on the trunk and upper extremities. A biopsy specimen revealed caseating granulomas, but special stains, cultures, and electron microscopy failed to reveal an infectious organism. Immunohistochemistry showed that the lymphocytes within the granulomas were almost exclusively of the CD8+ cytotoxic/suppressor T phenotype. Phenotypic analysis of the circulating lymphocytes showed normal numbers of CD4+ (helper/inducer) and CD8+ T cells, whereas B cells were undetectable. Other examples of noninfectious granulomatous disease have been reported in patients with primary hypogammaglobulinemia, but this is the first case of caseating cutaneous granulomatous disease to be reported in a patient with X-linked infantile hypogammaglobulinemia.
Five patients with the L-tryptophan-related eosinophilia-myalgia syndrome had a generalized eruption of flesh-colored papules. In all patients, histologic examination revealed a focal accumulation of mucin in the upper mid dermis, associated with increased dermal cellularity. The mucin was composed predominantly of hyaluronic acid, with small amounts of sulfated acid mucopolysaccharides. The cells within the lesion were fibroblasts. The lesions slowly regressed after L-tryptophan was discontinued. Proposed explanations for the L-tryptophan-related eosinophilia-myalgia syndrome have centered on contaminants, chemically related to L-tryptophan, introduced in the manufacturing process. Tryptophan metabolites have been linked with sclerotic cutaneous diseases but have not been previously implicated in cutaneous mucinoses.
Image cytometry was used to assess seasonal variation in the proliferation fraction of Australian common nevi. Twenty pairs of nevi were evaluated. One member of each pair had been excised during the Australian summer, and the other member of the pair had been excised during the winter. The nevi were matched for age, sex, and body site. From each nevus, 6-microns sections were Feulgen-stained and evaluated with a CAS 200 image analyzer, which was used to obtain DNA histograms. Proliferation fractions were calculated from the histograms. The proliferation fraction of the nevi removed during the winter was 1.65 +/- 0.32%, whereas the proliferation fraction of the nevi removed during the summer was 1.95 +/- 0.42% (p = 0.41). For nevi from sun-exposed sites only, the proliferation rate of nevi excised during the winter was 1.81 +/- 0.39%, and 2.58 +/- 0.39% for nevi excised during the summer (p = 0.11). For nevi from sun-protected sites, there was no difference between winter and summer. When nevi excised during the summer were compared by site, sun-exposed nevi had a proliferation rate of 2.60 +/- 0.48% (p = 0.04). For nevi excised during the winter, there was a much smaller difference between sun-exposed and sun-protected nevi.