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Biomedical subjects

B R Smoller

Publications and source records attributed to B R Smoller.

At least 37 records · Page 2Linked to original sources

Immunofluorescent microscopic investigation of the distal arrector pili: a demonstration of the spatial relationship between alpha5beta1 integrin and fibronectin.

Currently there is limited knowledge regarding the anatomy of the distal arrector pili (AP) muscle. A previous study implicated fibronectin and alpha5beta1 integrin binding as the anchor between the AP and the extracellular matrix (ECM). The purpose of this study was to strengthen this hypothesis. Serial frozen sections of human scalp skin were double-labeled via immunofluorescent staining for alpha5beta1 with fluorescein and fibronectin with rhodamine, followed by fluorescent microscopy. Granular staining for alpha5beta1 with fluorescein and smooth staining for fibronectin with rhodamine were seen at the periphery of the AP muscle bundles and along the distal fibers. Precise co-localization of alpha5beta1 and fibronectin was observed at the AP-ECM interface by means of a dual filter. Analysis of variance was used on the relative density of staining for each epitope. Staining for both epitopes was significantly brighter at the distal fibers than at the middle or proximal portions of the muscle. A computerized three-dimensional reconstruction provides a detailed picture of the microanatomy of the distal AP, which allows mathematical evaluation of the forces of contraction. The anatomic co-localization between alpha5beta1 and fibronectin strengthens our hypothesis that interaction of these epitopes mediates the attachment of the distal AP to the ECM.

Fibronectins↗

Syndecan-1 expression is decreased with increasing aggressiveness of basal cell carcinoma.

Syndecans, a family of cell-surface proteoglycans of which syndecan-1 is the prototypical member, play an important role in limiting tumor growth and invasive capacity through their actions as receptors for growth factors and extracellular matrix. Cutaneous biopsy specimens of basal cell carcinoma, including superficial, nodular, infiltrative, and morpheic subtypes, were assessed regarding the pattern of syndecan-1 expression. We found that with increasing aggressiveness of basal cell carcinomas, syndecan-1 expression is lost from the surface of the neoplastic cells. However, within the dermis, which is normally devoid of syndecan-1 expression, immunopositivity for syndecan-1 is present in areas adjacent to aggressive tumors. This pattern of staining indicates that syndecan-1 expression is produced by stromal cells rather than being shed by the carcinoma cells into the stroma.

Basal Cell Carcinoma↗

Delayed-type hypersensitivity to recombinant HIV envelope glycoprotein (rgp160) after immunization with homologous antigen.

Delayed-type hypersensitivity (DTH) responses to intradermal recombinant HIV envelope glycoprotein (rgp160) may assess cell-mediated immune responses to HIV envelope. In three studies, DTH and lymphocyte proliferation responses to rgp160 were obtained in a total of 106 HIV-seropositive subjects with CD4+ counts >400 cells/mm3. Several subjects participated in more than one study. Before immunization, DTH responses were seen in 5 of 56 (9%) of HIV-infected study subjects. After immunization with an alum-adjuvanted experimental rgp160 vaccine, DTH responses were seen in 46 of 52 (89%). Using in vitro lymphocyte proliferation activity (LPA) to rgp160 as an indication of cellular immune response, skin testing has a sensitivity of 0.75 (95% confidence Interval [CI], 0.59-0.88) and a specificity of 0.84 (95% CI, 0.72-0.92). Biopsy samples of skin that had tested positive confirmed the presence of a DTH reaction with a predominance of CD4+ T cells in the perivascular, inflammatory infiltrate. Skin testing before and after immunization with candidate AIDS vaccines could provide a simple method in the field to assess new cell mediated immune responses.

AIDS Vaccines↗

Immunohistochemical evaluation of androgen receptors in genital and extragenital lichen sclerosus: evidence for loss of androgen receptors in lesional epidermis.

BACKGROUND: Reduction of lichen sclerosus has been seen with topical testosterone, and spontaneous resolution has been attributed to increasing androgen levels. OBJECTIVE: Our purpose was to investigate the role of androgens in lichen sclerosus by studying lesional skin and site-specific normal skin for the presence of androgen receptors. METHODS: Immunoperoxidase staining for androgen receptors was performed on lesional tissue from 31 patients and microscopically compared with site-specific normal skin. RESULTS: Androgen receptors were present in normal genital and extragenital skin. Lesional genital and extragenital areas showed decreased staining compared with site-specific controls. Finally staining was decreased in histologically well-developed lesions compared with early lesions. CONCLUSION: This study provides evidence for the loss of androgen receptors with disease progression in both genital and extragenital skin affected by lichen sclerosus. These findings support a hormonal pathogenesis of lichen sclerosus and may be significant in the treatment of the disease.

Female↗

Basal cell carcinoma: a comparison of shave biopsy versus punch biopsy techniques in subtype diagnosis.

BACKGROUND: There are two standard ways to obtain tissue for histologic classification of a clinically suspected basal cell carcinoma: shave and punch biopsy. However, information on the value of each method is limited. OBJECTIVE: The purpose of this study was to identify accuracy rates of two standard biopsy techniques in diagnosing subtypes of basal cell carcinoma. METHODS: A total of 86 cases were identified that had received either a punch or a shave biopsy with subsequent total excision of tumor. The biopsy specimens and excisions were compared for histologic correlation. RESULTS: Analysis of specimens from punch and shave biopsies produced equivalent diagnostic accuracy rates: 80.7% and 75.9%, respectively. There was no statistically significant tendency to overcall or undercall any particular tumor subtype on the basis of the type of biopsy procedure used. CONCLUSION: For histologic classification of basal cell carcinoma, there is an approximately 80% accuracy rate with both the shave and the punch biopsy. Therefore either biopsy technique is appropriate.

Biopsy↗

Immunohistochemistry in diagnostic dermatopathology.

This article briefly reviews many immunohistochemical stains that have been in use for years, emphasizing their diagnostic use and potential pitfalls. Several newer immunostains are described in a more comprehensive fashion, including brief summaries from recently published studies.

Biomarkers, Tumor↗

Spiders and Borrelia burgdorferi: no evidence of reservoir occurrence in central Arkansas.

BACKGROUND: Although Ixodes ticks are considered the chief vector for Borrelia burgdorferi in the USA, B. burgdorferi has also been identified in mosquitoes, horse flies, and deer flies. We examined the possibility of these organisms being harbored in two species of spider in central Arkansas. METHODS: Ten wolf spiders (Lycosa gulosa) and two brown recluse spiders (Loxosceles reclusa) were collected in central Arkansas during early summer and fixed in formalin. Paraffin-embedded sections of the spiders were examined for spirochetes using the modified Steiner spirochete staining method and examined for B. burgdorferi using immunohistochemistry. RESULTS: All 12 spiders from both species were found to be negative for all spirochetes including B. burgdorferi. CONCLUSIONS: Spiders in our sample appeared not to harbor B. burgdorferi. Further studies utilizing larger sample sizes, more sensitive testing measures, or spiders from an area more endemic with B. burgdorferi may further prove or disprove that spiders are capable of harboring this organism.

Animals↗

Increased p53 staining in normal skin of posttransplant, immunocompromised patients and implications for carcinogenesis.

The p53 tumor suppressor gene is a transcriptional activator involved in control of cell cycle. Nonmelanoma skin cancers and premalignant lesions in transplant patients have been associated with an increased rate of p53 mutation. It is possible that normal skin in transplant patients also has a more labile p53 tumor suppressor gene, predisposing them to the development of nonmelanocytic cutaneous malignancies. To test this hypothesis, we looked at p53 expression in normal skin from posttransplant, immunocompromised patients and compared this to p53 expression in normal skin from immunocompetent patients. Twenty-three skin biopsies of normal, non-sun-exposed skin from 23 immunosuppressed transplant patients and 6 skin biopsies of normal, non-sun-exposed skin from 3 immunocompetent patients were stained for p53 immunoreactivity. The skin biopsies from the immunocompromised patients showed increased staining for p53 when compared to the skin biopsies from the immunocompetent patients (mean = 7.52/mm for the immunocompromised patients and mean = 1.05/mm for the normal control group). Background levels of p53 mutation may be increased in normal skin of posttransplant immunocompromised patients. This background increase in p53 expression could reflect mutation of the gene, which may play a role in the subsequent development of cutaneous malignancies in this subgroup of patients.

Bone Marrow Transplantation↗

Aggressive cutaneous NK and NK-like T-cell lymphomas: clinicopathologic, immunohistochemical, and molecular analyses of 12 cases.

Natural killer (NK) and NK-like T-cell lymphomas are rare hematolymphoid malignancies that predominate in the upper aerodigestive system. They also involve other extranodal sites, including the skin. Primary cutaneous manifestations of NK and NK-like T-cell lymphomas are uncommon, and the clinicopathologic features are poorly understood. We have studied 12 patients of varied ethnic backgrounds with CD56-positive lymphomas in the skin. Six patients subsequently progressed to disseminated disease. These lymphomas showed the following immunophenotype: CD56+, CD43+, TCRb-, CD3-/+, CD20-, CD30-/+, CD4-, and CD8-. Two cases exhibited T-cell receptor gene rearrangements supporting a T-cell origin for these lymphomas, whereas the remaining 10 cases were likely derived from NK cells. Our results show inconsistent association of these lymphomas with Epstein-Barr virus (EBV), the multidrug resistance phenotype, and expression of P53. In addition, we found a previously unreported correlation between lymphomas harboring EBV mRNA and the expression of the multidrug resistance phenotype. These lymphomas were aggressive and were associated with rapid clinical progression, treatment failure, multiple relapses, and an average survival of 15 months from the time of diagnosis. Our results indicate the importance of recognizing this disease as a distinct subset of aggressive cutaneous lymphomas that may be diagnosed on the basis of morphology, immunophenotype, and gene rearrangement studies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Microcystic adnexal carcinoma arising in the setting of previous radiation therapy.

While there are several reports of microcystic adnexal carcinoma developing in patients within sites of previous therapeutic irradiation, this relationship is not well described in the dermatologic literature. We report a case of a 42-year-old man with a remote history of therapeutic irradiation following surgical resection of periorbital rhabdomyosarcoma. Subsequently, he developed multiple basal cell carcinomas and a microcystic adnexal carcinoma within the field of irradiation. The histologic features were those of a classic microcystic adnexal carcinoma, with well differentiated nests and cords of keratinocytes displaying follicular and ductular differentiation infiltrating diffusely into the reticular dermis. Dense fibrosis was present surrounding the neoplastic keratinocytes. Nuclear atypia and mitotic figures were not identified. A carcinoembryonic antigen (CEA) stain demonstrated glandular differentiation. It is important for dermatologists to be aware of the apparent relationship between the rare microcystic adnexal carcinoma with its innocuous scar-like clinical appearance and prior local radiation therapy.

Adult↗

Syndecan-1 expression is diminished in acantholytic cutaneous squamous cell carcinoma.

Syndecan-1 is a cell surface proteoglycan predominantly expressed on the surface of adult epithelial cells, and is normally present in all epidermal layers except for the most superficial terminally differentiated cells. Syndecan-1 mediates cell-cell and cell-extracellular matrix adhesion, thereby influencing cell morphology and growth characteristics. In addition, in vitro studies have shown that expression of syndecan-1 on tumor cells inhibits their invasion into the extracellular matrix. A total of 23 cutaneous biopsies of squamous cell carcinoma, including acantholytic squamous cell carcinoma, invasive squamous cell carcinoma which was not acantholytic, and squamous cell carcinoma in situ were examined for syndecan-1 immunoreactivity. The level of syndecan-1 expression was related to the degree of squamous cell dyshesion, with expression being greatest in the in situ lesions and least in the acantholytic lesions. The loss of syndecan-1 expression with increasing dyshesion of squamous cell carcinoma may be a mechanism for loosening of intercellular and cell-extracellular matrix attachments, thereby promoting the invasion of neoplastic cells into the dermis.

Acantholysis↗

Vascular endothelial growth factor expression in malignant melanoma: prognostic versus diagnostic usefulness.

Vascular endothelial growth factor (VEGF), an endothelial cell mitogen, plays a role in angiogenesis and progression in malignant melanoma. VEGF expression was examined in 62 biopsy specimens of melanocytic proliferations, including 45 malignant melanomas, 3 cellular blue nevi, 12 atypical compound nevi, and 2 Spitz nevi. The cases of malignant melanoma included 11 in situ melanomas, 18 Clark Level II, 9 Clark Level III, and 7 Clark Level IV tissue samples. All of the specimens were fixed in formalin and embedded in paraffin. Cytoplasmic immunoreactivity for VEGF was demonstrated in 19 (42%) of 45 melanoma samples, but there was no immunoreactivity for VEGF exhibited by any of the atypical compound melanocytic nevi, cellular blue nevi, or Spitz nevi (P < .009). Immunoreactivity for VEGF was found to be related to tumor thickness (as evidenced by Clark level [P < .03]) and to absence of regression (P < .04). Although VEGF is not a useful prognostic indicator for malignant melanoma, it may be useful as a discriminating factor between malignant melanoma and benign melanocytic lesions, and it may offer some insight into tumor growth.

Diagnosis, Differential↗

Plaque-like erythema with milia: a noninfectious dermal mucinosis mimicking cryptococcal cellulitis in a renal transplant recipient.

Cellulitis of the skin is most commonly a bacterial infection caused by either staphylococcal or streptococcal species. However, in immunocompromised patients, cellulitis may be a harbinger of more ominous disease. In these patients, rapid clinical diagnosis and treatment is necessary. We describe an immunosuppressed renal transplant recipient with the clinical diagnosis of cryptococcal cellulitis who was found to have a heretofore unreported dermal mucinosis of the upper chest associated with milia. We believe that cyclosporine was a significant pathogenic factor. This entity, which should be included in the clinical differential diagnosis of cryptococcal cellulitis, has a benign nature and does not require treatment.

Aged↗

Role of cellular proliferation and apoptosis in the growth of xanthogranulomas.

We examined a total of 13 xanthogranulomas in order to examine the mechanism by which these lesions grow. Six xanthogranulomas from children < 2 years of age were compared with lesions from seven patients > 10 years of age. All lesions were stained with antibodies directed against Ki-67 and bcl-2 protein. There were no significant differences between the two groups. There was a slight trend toward higher rates of proliferating histiocytes within lesions from children (p < 0.18). It is unclear from our data whether this higher rate is correlated more with the age of the patient or with the duration of the lesion. Inhibition of cellular apoptosis, as demonstrated by expression of bcl-2, appears to play a minor role in the growth of xanthogranulomas in either children or adults. Xanthogranulomas appear to be tumors that grow by proliferation of "histiocytes," independent of the age of onset.

Adult↗

Estrogen and progesterone receptors in androgenic alopecia versus alopecia areata.

In some situations, hair growth is under hormonal control. Androgenic alopecia is characterized as hormonally driven hair loss in the genetically susceptible individual. During pregnancy, hair growth is increased, as estrogen appears to prolong the anagen phase. However, postpartum hair loss is common, and thus may be related to a decrease in estrogen and or progesterone levels. In contrast, alopecia areata is not considered to be under hormonal control. We compared the immunohistochemical staining characteristics of nine cases of androgenic alopecia with those of 13 cases of alopecia areata using estrogen receptor (ER) and progesterone receptor (PR) markers. Estrogen receptor positivity in the dermal papilla was found in only two of 13 cases of alopecia areata, and in one case of androgenic alopecia. Six of 13 cases of alopecia areata demonstrated focal reactivity with the progesterone marker in a similar location, while only three cases of androgenic alopecia showed positivity with this antibody. Examination of the perifollicular fibroblasts for the ER marker showed positivity in one of 13 cases of alopecia areata and in one case of androgenic alopecia. Two cases of alopecia areata revealed focal staining in this location for the PR marker, while the androgenic alopecia cases failed to stain. These results indicate that estrogen and progesterone receptor expression is not significantly increased or decreased in the pilosebaceous units or surrounding mesenchymal cells in androgenic alopecia vs. alopecia areata. Therefore, an indirectly mediated process of estrogen/progesterone control on hair growth and development must be presumed for cases of androgenic alopecia.

Adolescent↗