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V A Tron

Publications and source records attributed to V A Tron.

At least 37 records · Page 2Linked to original sources
PubMed1996

Neutrophilic spongiosis in pemphigus herpetiformis.

Pemphigus herpetiformis is a rare pemphigus variant with light microscopic features that have historically been described as either "acantholytic dermatitis herpetiformis" or as "eosinophilic spongiosis in pemphigus". The clinical features of this form of pemphigus are reminiscent of dermatitis herpetiformis; however, the direct immunofluorescence finding of epidermal inter-cellular IgG deposition is that of the pemphigus group. We report two patients with clinical presentations suggestive of dermatitis herpetiformis in whom the histopathologic features were those of a neutrophilic intraepidermal blistering disorder. Biopsies showed marked epidermal spongiosis with midepidermal acantholytic vesicles containing predominantly neutrophils and a few eosinophils. Direct immunofluorescence was positive for epidermal intercellular IgG; IgA deposition was not present. Neutrophilic spongiosis, in the absence of a prominent eosinophilic infiltrate, should be recognized as an early finding in some cases of pemphigus, and immunofluorescence studies are justified when this histologic feature is encountered in a skin biopsy.

Acantholysis↗
PubMed1996

Decreased DNA repair but normal apoptosis in ultraviolet-irradiated skin of p53-transgenic mice.

p53 tumor suppressor plays a vital role in the cellular responses to genotoxic stress. It is believed that p53 regulates the cell cycle by activating the G1 checkpoint after exposure to agents like ionizing radiation, ultraviolet (UV) radiation, or genotoxic chemicals. Recently, it is conjectured that p53 may have additional functions in DNA repair and apoptosis. Previously, we demonstrated that p53-transgenic mice that carry mutant alleles of a p53 gene developed twice as many skin tumors as control mice after UV exposure. To elucidate the molecular mechanisms of mutant p53 in skin cancers, we studied DNA repair efficiency and the rate of apoptosis in murine keratinocytes after UV irradiation. In this report, we show that mutant p53-transgenic mouse skin has reduced repair of UV-induced DNA damage in both in vivo and in vitro radioimmunoassays. In control mice, DNA repair is associated with increased amounts of wild-type P53 protein. Unexpectedly, mutant p53-transgenic mice had slightly increased apoptosis after UV irradiation, suggesting that the wild-type p53 protein in the cells still functions in inducing apoptosis, or that this cell death results from p53-independent mechanisms. These results suggest that mutant p53 interferes with wild-type p53 in the repair of UV-induced DNA damage but not in apoptosis.

Animals↗
PubMed1996

Differentiation-associated overexpression of the cyclin-dependent kinase inhibitor p21waf-1 in human cutaneous squamous cell carcinoma.

p21waf-1 negatively regulates the cell cycle by inhibiting the activity of cyclin-dependent kinases. As p21waf-1 is a probable tumor suppressor, we sought to determine whether this cyclin-dependent kinase inhibitor is abnormally regulated in human cutaneous squamous cell carcinoma (SCC). An immunohistochemical technique was employed to assay p21waf-1 protein in SCCs chosen from sun-exposed and anogenital sites. We observed that p21waf-1 was greatly overexpressed in SCC versus adjacent benign epithelium. Furthermore, expression of p21waf-1 was consistently elevated in the superficial, differentiated cells versus basal keratinocytes. p21waf-1 expression correlated with the proliferative state of the cancers as measured by MIB-1 immunostaining. In vitro, keratinocytes grown in supplemented media upregulated p21waf-1 during differentiation, supporting our in vivo observations. We conclude that p21waf-1 overexpression is associated with differentiation in proliferating SCC but is not sufficient to suppress cancer development.

Aged↗
PubMed1995

Ultraviolet radiation induction of squamous cell carcinomas in p53 transgenic mice.

Mutations of the p53 gene have been implicated in the pathogenesis of cutaneous squamous cell carcinoma (SCC). To examine the role of p53 in skin carcinogenesis, we observed the development of skin cancers in p53 transgenic mice which carry multiple copies of a mutant allele of the p53 gene with or without chronic UVB radiation. Thirty-one tumors developed in 19 UV-irradiated p53 transgenic mice versus 14 of 19 in the control group; 9 p53 transgenic mice but none of the control mice developed multiple tumors. Histologically. 14 of 14 tumors in the CD-1 mice were SCCs. In the p53 transgenic mice, 25 of 31 tumors were SCCs, and 6 were benign tumors. The mean time to appearance of tumors did not differ between CD-1 mice (26.3 weeks) and the p53 transgenic mice (25.7 weeks; P = 0.512). The p53 protein, which was undetectable by immunohistochemistry in the keratinocytes of CD-1 mice, was elevated in 93% (13 of 14) of tumors from CD-1 mice. These data indicate that mutation of the p53 gene is an important step in the development of SCC. p53 mutations do not alter the latent period of UV-induced SCC but significantly increase the number of tumors and the propensity for multiple tumor development.

Animals↗
PubMed1995

Site-specific comparison of p53 immunostaining in squamous cell carcinomas.

The p53 tumor suppressor gene is believed to be the most commonly mutated gene in human cancer. p53 is thought to function as a negative regulator of the cell cycle, arresting cells in the G1 phase. This study examined the effects of different mutagenic environments on the incidence of p53 overexpression in squamous cell carcinomas (SCCs) from sun exposed and non-sun exposed squamous epithelium. An immunohistochemical analysis was undertaken in an attempt to assay SSC for p53 overexpression, an indirect measure of missense mutant p53. Positive nuclear staining for p53 was observed in 14 of 21 sun exposed SCCs, two of 19 vulvar/perianal SCCs, and 15 of 20 oral cavity SCCs. The number of positive anogenital tumors was low compared with that of both sun exposed (chi-squared, 1 df, P = .0004) and oral (chi-squared, 1 df, P < .0001) sites. It was concluded that p53 protein accumulation is common in sun-exposed cutaneous SCC and oral SCC compared with anogenital SCC, and thus it is hypothesized that the nature of the mutagenic environment in which SCC develops directly affects the incidence of immunohistochemically detectable p53-positive cells.

Adult↗
PubMed1995

Eosinophilic ulcer of the oral mucosa.

BACKGROUND: The eosinophilic ulcer is a rare lesion of the oral mucosa that has been infrequently described in the literature. OBJECTIVE: We attempted to characterize the history, demographics, clinical features, histologic features, pathogenesis, and treatment of the eosinophilic ulcer. METHODS: We observed three new cases of eosinophilic ulcer and reviewed the English-language literature. RESULTS: Eosinophilic ulcer occurs in any age group, without sex preference. The most common site in the oral cavity is the tongue, and the average size at diagnosis is 1.6 cm2. These lesions are often ulcerated, may be tender, and are sometimes multiple. The histologic features are characteristic but likely represent a spectrum of related disorders. Most eosinophilic ulcers will resolve spontaneously within a month. Recurrences are uncommon (< 15%). CONCLUSION: The eosinophilic ulcer is a benign, self-limited, reactive process of the oral mucosa of unknown origin. Its histologic features are characteristic but may be confused with atypical histiocytic granuloma and angiolymphoid hyperplasia with eosinophilia or, more importantly, lymphoma. This condition most likely represents a spectrum of related disorders with overlapping clinical and histologic features. After the diagnosis has been histologically confirmed, conservative management is suggested.

Adolescent↗
PubMed1995

Sinonasal malignant melanoma--a clinicopathologic analysis of 18 cases.

Sinonasal melanoma is a rare malignancy. We present the clinicopathologic review of 18 cases seen at the British Columbia Cancer Agency between 1976 and 1992: 13 men and five women, mean age 66 years (range 32-88). Patients presented with nasal obstruction and bleeding (n = 8), obstruction alone (n = 4), bleeding alone (n = 5) or pain (n = 1). Those with bleeding presented with a shorter duration of symptoms than those with obstruction alone. All patients with obstruction alone died of their disease, while all patients with bleeding alone are alive or have died of an unrelated cause; four out of eight patients with both obstruction and bleeding are alive. There was no significant relationship between treatment modality and outcome. Histologic subtypes included epithelioid (n = 10), spindle-cell (n = 4), small-cell (n = 3) and pleomorphic (n = 1). Eight out of 11 cases from whom samples of paraffin-embedded tissue were available showed more prominent staining for HMB-45 than for S-100. In two cases, only rare (< 0.1%) cells stained for S-100. Cell type, mitotic rate and P53 expression were unrelated to disease outcome. Six out of seven patients with < or = 10% of cells showing intense staining for PCNA were alive or had died of an unrelated cause, while three out of four with > 10% staining died of their disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Localized chrysiasis induced by laser therapy.

BACKGROUND: Chrysiasis is a rare blue-gray skin discoloration that occurs in sun-exposed sites of some patients who receive gold salts. A unique case of localized chrysiasis developed immediately after Q-switched ruby laser (694 nm) irradiation for postinflammatory hyperpigmentation secondary to granuloma faciale in a patient who was receiving long-term gold sodium thiomalate therapy for psoriatic arthritis. Skin biopsy specimens showed striking changes in the ultrastructural characteristics of cutaneous gold deposits following laser treatment. OBSERVATIONS: A blue-gray skin discoloration developed immediately after laser exposure and persisted unchanged after 1 year. Transmission electron microscopy of skin biopsy specimens showed electron-dense gold deposits. Before laser irradiation, these deposits were 106 +/- 35 (mean +/- SD) nm in diameter and faceted, consistent with a crystalline structure. Posttreatment deposits were round, smaller, measured 16 +/- 4 nm, and resembled colloidal gold. Identical findings were observed in an area of sun-protected skin treated with the Q-switched ruby laser; irradiation with a pulsed dye laser at 585 nm had no effect. CONCLUSIONS: Localized chrysiasis was induced in a patient receiving parenteral gold therapy who underwent treatment with a Q-switched ruby laser. This form of chrysiasis resulted from a structural alteration in dermal gold deposits. A similar physiochemical modification in gold deposits induced by UV light may explain the localization of chrysiasis to sun-exposed skin in affected patients.

Arthritis, Psoriatic↗
PubMed1995

Immunohistochemical analysis of Bcl-2 protein regulation in cutaneous melanoma.

Cutaneous melanoma is becoming increasingly common. Genetic and environmental factors are thought to play a role in its pathogenesis. We have previously shown that normal human melanocytes strongly express the oncoprotein, Bcl-2. To determine the role of Bcl-2 in melanocytic tumors, we studied human benign nevi and melanomas for expression of Bcl-2 protein using immunohistochemistry. Our results show that benign melanocytes from 3 of 4 normal skin biopsies and 5 of 7 common acquired nevi strongly express Bcl-2. Conversely, only 3 of 23 primary cutaneous melanomas and 3 of 9 metastatic melanomas showed strong staining in comparison with melanocytes from normal skin and common acquired nevi (chi 2, P = 0.0021). Interestingly, 0 of 6 dysplastic nevi, a precursor of melanoma, demonstrated strong staining as compared with melanocytes and nevi (8 of 11; chi 2, P = 0.02), but similar expression to that of melanoma (6 of 32; chi 2, P = 0.6). We conclude that Bcl-2 expression decreases in malignant melanoma and suggest that this may be related to the autonomous growth characteristics of malignant melanoma.

Humans↗
PubMed1994

Dermal vascularity in lentigo maligna.

Lentigo maligna (LM) may represent a tumour arrested in an in situ phase, lacking the angiogenic capacity and underlying dermal neovascularization required for invasive growth. The acquisition of an angiogenic phenotype might be associated with the development of lentigo maligna melanoma (LMM). To investigate this thesis, sections of formalin-fixed, paraffin-embedded tissue from 15 LMMs, and 11 LM excision specimens were stained with the vascular endothelial marker Ulex europaeus agglutinin I. Dermal vessels were counted and vascular morphometry was performed. In specimens in which LMM was present, dermal vascularity was significantly increased in LM compared with normal skin. The most significant increases were found for dermal vascular density (39 per cent increase, P = 0.008) and for total vessel surface area (62 per cent increase, P = 0.005). However, when no LMM was present, the vascular density underlying LM (79 +/- 9 vessels/mm2) did not differ significantly from that of adjacent normal skin (67 +/- 6 vessels/mm2), although focal 'hot spots' of increased vascularity were present. We conclude that increased dermal vascularity is present beneath in situ LM and that this increased vascular density is closely associated with the presence of invasive LMM in the same specimen.

Humans↗
PubMed1994

Histopathology in erythroderma: review of a series of cases by multiple observers.

This study examines the utility of objective histopathological studies in the evaluation of adult patients with erythroderma. A series of 56 skin biopsies, from 40 erythrodermic patients, was reviewed sequentially by 4 Canadian dermatopathologists who were unaware of clinical details of the cases. The final diagnosis (gold standard), in each instance, had already been determined by others, based on clinicopathologic data and response to therapy. Direct comparison revealed that the mean accuracy of the histopathological diagnoses was 53% (range: 48-66%), a favorable result in view of the difficulty of the task at hand. Additional points of information which evolved from the study are as follows: (i) identification, by microscopy alone, of spongiotic dermatitis, cutaneous T-cell lymphoma and psoriasis, as underlying causes of erythroderma was more successful than that of drug eruptions and pityriasis rubra pilaris; (ii) the epidermotropism which characterizes cutaneous T-cell lymphoma may be mistaken for inflammatory interface changes seen in drug eruptions and vice versa, thus constituting a pitfall in diagnosis; (iii) finally, it appears that submission of multiple simultaneous biopsies, rather than a single specimen, from patients with erythroderma would be likely to enhance the accuracy of histopathological diagnosis.

Adult↗
PubMed1994

Melanocytes in human skin express bcl-2 protein.

The bcl-2 gene was initially identified through its participation in the translocation 14:18 in B-cell lymphomas of follicular center cell origin. This classic translocation juxtaposes the transcriptionally active immunoglobulin heavy-chain locus on chromosome 14 to the bcl-2 gene on chromosome 18, resulting in overexpression of bcl-2 protein. The oncogene bcl-2 is thought to prolong cell survival through interference with programmed cell death. To date, bcl-2 expression has been reported in normal lymphoid, hemopoietic, neural, breast and prostatic tissues. Since melanocytes are neural crest derivatives and have an extended life-span, our objective was to determine whether the bcl-2 protein is expressed in human melanocytes. We analyzed normal skin biopsies for bcl-2 expression using standard immunohistochemistry. As hypothesized, dendritic cells in the basal epidermal layer stained strongly for bcl-2. The distribution and morphology of these cells was typical for melanocytes. Additionally, eccrine sweat glands, lymphocytes and the dermal papilla of hair follicles demonstrated bcl-2 positivity. We believe this to be the first report of bcl-2 expression in normal melanocytes.

Humans↗
PubMed1993

A putative marker for human melanoma. A monoclonal antibody derived from the melanoma gene in the Xiphophorus melanoma model.

A MoAb was raised against a peptide corresponding to an exposed domain of the putative tyrosine kinase receptor protein encoded by Xmrk, a gene involved in melanoma formation and/or progression in the Xiphophorus fish melanoma model. The antibody reacts specifically with cells from human melanocytic lesions, ie, common acquired nevi, primary and metastatic melanoma biopsies. No reactivity with other cells, including normal melanocytes, was observed in the biopsies or with cells in biopsies from normal tissue (skin, liver, lung, spleen) and from other malignancies including those of neuroectodermal origin. The reactivity was very weak and variable in metastatic melanomas but very strong and characteristic of a receptor-type antigen in primary melanomas, a stage in melanoma progression in which cells have acquired metastasizing potential. It is suggested that the antigen recognized may be involved in growth promotion and represents the human equivalent of the fish melanoma gene product.

Animals↗
PubMed1991

Analysis of HMB-45 immunoreactivity in common and cellular blue nevi.

HMB-45 is generally thought of as a melanoma specific antibody; however, there are certain exceptions. It is known that most dermal nevi show no reactivity; however, the dermal nevus component within dysplastic nevi and certain Spitz nevi show positive reactivity. In order to further examine this observation, we undertook a study to examine blue nevi, both common and cellular, for the expression of HMB-45. Cases were stained with antibodies directed at both HMB-45 and S100 protein. Of 16 common blue nevi studied, 14 were positive with HMB-45, as were 6 of 6 cellular blue nevi. Staining for HMB-45 was quite variable in intensity amongst cases labelled common blue nevi. In contrast, cellular blue nevi were uniformly strongly positive. It is therefore concluded that blue nevi, including cellular blue nevi, exhibit an activated phenotype as demonstrated by HMB-45 reactivity.

Antibodies, Monoclonal↗
PubMed1990

Expression and modulation of nerve growth factor in murine keratinocytes (PAM 212).

Nerve growth factor (NGF) is a polypeptide that is required for normal development and maintenance of the sympathetic and sensory nervous systems. Skin has been shown to contain relatively high amounts of NGF, which is in keeping with the finding that the quantity of NGF in a tissue is proportional to the extent of sympathetic innervation of that organ. Since the keratinocyte, a major cellular constituent of the skin, is known to produce other growth factors and cytokines, our experiments were designed to determine whether keratinocytes are a source of NGF. Keratinocyte-conditioned media from the keratinocyte cell line PAM 212 contained NGF-like activity, approximately 2-3 ng/ml, as detected by the neurite outgrowth assay. Freshly isolated BALB/c keratinocytes contained approximately 0.1 ng/ml. Using a cDNA probe directed against NGF, we demonstrated the presence of a 1.3-kb NGF mRNA in both PAM 212 and BALB/c keratinocytes. Since ultraviolet radiation (UV) is a potentially important modulating factor for cytokines in skin, we examined the effect of UV on NGF mRNA expression. Although UV initially inhibited the expression of keratinocyte NGF mRNA (4 h), by 24 h an induction of NGF mRNA was seen. The NGF signal could also be induced by phorbol esters. Thus, keratinocytes synthesize and express NGF, and its expression is modulated by UVB and phorbol esters.

Animals↗
PubMed1988

Chemotactic activity of endothelial cell-derived interleukin 1 for human tumor cells.

Endothelium and the vascular basement membrane form important barriers between the circulation and extravascular compartment. Cancer cell motility contributes to the passage of metastatic cells across this barrier, an essential step in tumor dissemination. In this study we found that the conditioned media of human endothelial monolayers contained a chemoattractant for neoplastic cells and that the chemoattractant activity was greater in the media of cultures which had been stimulated 4 h previously with 10 micrograms/ml bacterial lipopolysaccharide or the peptide formyl-L-methionyl-L-leucyl-L-phenylalanine at a concentration of 10(-6) M. The generation of this activity correlated with the expression of intracellular mRNA for interleukin 1 (IL-1) and with the presence of IL-1 biological activity in the conditioned media. The chemotactic activity in these media was lost after they had been incubated with anti-IL-1. Finally, recombinant human IL-1 alpha and IL-1 beta stimulated dose-dependent, random, and directed migration of human tumor cell populations in the Boyden chamber assay. Thus, this paper describes a mechanism by which the production of IL-1 by endothelial cells could modulate the behavior of tumor cells within the circulation.

Cell Movement↗
PubMed1988

In situ detection of interleukin-1 mRNA in human monocytes.

The interleukin-1 (IL-1) family of soluble pleiotropic immunoregulatory and proinflammatory peptides has at least two distinct members, alpha IL-1 and beta IL-1. Since beta IL-1 is the predominant species in human monocytes, this study was undertaken to identify its mRNA in monocytes using in situ hybridization with a 35S-dCTP labelled beta IL-1 cDNA probe. Grain count analysis demonstrated that adherent lipopolysaccharide-stimulated monocytes were positive, while unstimulated monocytes, lymphocytes and neutrophils, and cells probed with vector only (35S-labelled pBR322) were all negative. We have also shown that in situ hybridization is approx. 13-fold more sensitive than conventional hybridization and in addition this technique allows visualization of mRNA coding for IL-1 in individual cells with morphology preserved. We conclude that in situ hybridization is a specific and sensitive technique for the detection of beta IL-1 mRNA in individual human peripheral blood monocytes.

Autoradiography↗