RESUMEN
An ultraviolet radiation (UVR)-induced Sencar mouse skin carcinogenesis model was established to investigate the expression of Hras-p21 and keratin K13 in different stages of carcinogenesis, including UV-exposed nontumor skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). Expression of Hras-p21 and K13 was examined in paraffin-embedded tumor sections by using immunohistochemical, immunofluorescent, and double staining techniques with specific antibodies. Positive Hras-p21 staining was detected in 1/3 (33%) papillomas, 24/36 (67%) of SCCs, but not in UVR-exposed nontumor skin or SCTs. Positive staining of the malignant progression marker K13 was found in 22/36 (61%) of SCCs only. Coexpression of Hras-p21 and K13 was found in 17/36(47%) SCCs. H-ras exons 1 and 2 were amplified from skin/tumor sections by using nested polymerase chain reaction (PCR). PCR-based single-strand conformation polymorphism (SSCP) analysis and gene sequencing revealed three point mutations, one in UVR-exposed nontumor skin (codon 56), and two in SCCs (codons 13 and 21). There were no clear relationships between point mutations of H-ras and the positive staining of Hras-p21 and K13. These results indicate that overexpression of ras-p21 in conjunction with aberrant expression of K13 is a frequent event in UVR-induced SCCs in Sencar mouse skin. Point mutation of the H-ras gene appeared to be a rare event in UVR skin carcinogenesis and not to be responsible for overexpression of Hras-p21.
Asunto(s)
Queratinas/metabolismo , Neoplasias Inducidas por Radiación/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Neoplasias Cutáneas/metabolismo , Rayos Ultravioleta/efectos adversos , Animales , Femenino , Ratones , Ratones Endogámicos SENCAR , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias Cutáneas/etiologíaRESUMEN
Alterations of the tumor suppresser gene p53 have been found in ultraviolet radiation (UVR) related human skin cancers and in UVR-induced murine skin tumors. However, links between p53 gene alterations and the stages of carcinogenesis induced by UVR have not been clearly defined. We established a chronic UVR exposure-induced Sencar mouse skin carcinogenesis model to determine the frequency of p53 gene alterations in different stages of carcinogenesis, including UV-exposed skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). A high incidence of SCCs and SCTs were found in this model. Positive p53 nuclear staining was found in 10/37 (27%) of SCCs and 12/24 (50%) of SCTs, but was not detected in normal skin or papillomas. DNA was isolated from 40 paraffin-embedded normal skin, UV-exposed skin, and tumor sections. The p53 gene (exons 5 and 6) was amplified from the sections by using nested polymerase chain reaction (PCR). Subsequent single-strand conformation polymorphism (SSCP) assay and sequencing analysis revealed one point mutation in exon 6 (coden 193, C-->A transition) from a UV-exposed skin sample, and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C-->T, two C-->A, one C-->G, and one A-->T transition, respectively) from four SCTs, two SCCs and one UV-exposed skin sample. These experimental results demonstrate that alterations in the p53 gene are frequent events in chronic UV exposure-induced SCCs and later stage SCTs in Sencar mouse skin.
Asunto(s)
Genes p53/efectos de la radiación , Neoplasias Inducidas por Radiación/genética , Neoplasias Cutáneas/genética , Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Animales , Carcinoma/genética , Carcinoma de Células Escamosas/genética , Núcleo Celular , ADN/genética , ADN/aislamiento & purificación , Modelos Animales de Enfermedad , Exones , Femenino , Amplificación de Genes/genética , Amplificación de Genes/efectos de la radiación , Genes p53/genética , Humanos , Inmunohistoquímica , Ratones , Ratones Endogámicos SENCAR , Papiloma/genética , Adhesión en Parafina , Mutación Puntual/genética , Mutación Puntual/efectos de la radiación , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Estándares de ReferenciaRESUMEN
To investigate the skin immune responses induced by intradermal injections of interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma), normal C3H mice were injected intradermally with murine recombinant interferon-alpha (rIFN-alpha), interferon-gamma (rIFN-gamma), or the combination of rIFN-alpha and rIFN-gamma, three times per week for 2 or 4 weeks. Contralateral sites were similarly injected with placebo (saline). The results showed that after 6 or 12 injections of rIFN-alpha (10,000 IU/per injection), epidermal ATPase+ and Ia+ Langerhans cells (LGs) decreased significantly (p < 0.01 and p < 0.05) but dermal lymphocytic infiltrates, including CD3+ (pan-T cells), L3T4+ (T helper cells), Lyt-2+ (T suppressor/cytotoxic cells), MOMA+ (macrophages and monocytes), and dermal Ia+ cells, increased significantly (p < 0.01) compared with both saline injection sites and untreated skin. In contrast to rIFN-alpha, 6 injections of 10,000 IU rIFN-gamma failed to induce significant changes in either epidermal LGs or dermal lymphocytic infiltrates, except for an increase in dermal MOMA+ cells. High-dose rIFN-gamma injections (50,000 IU) strongly enhanced the expression of Ia antigen in epidermal keratinocytes (KCs), increased dermal lymphocytic infiltrates, and decreased the LGs in a similar pattern to that of rIFN-alpha. Furthermore, rIFN-gamma (50,000 IU) injections induced Ia antigen expression on the KCs in the contralateral saline injection areas, suggesting a systemic effect. Injections of a combination of rIFN-alpha and rIFN-gamma failed to show synergism for induction of skin immune responses.
Asunto(s)
Interferón Tipo I/farmacología , Interferón gamma/farmacología , Queratinocitos/inmunología , Células de Langerhans/inmunología , Linfocitos/inmunología , Piel/inmunología , Adenosina Trifosfatasas/biosíntesis , Animales , Movimiento Celular/inmunología , Femenino , Antígenos de Histocompatibilidad Clase II/biosíntesis , Inyecciones Intradérmicas , Interferón Tipo I/administración & dosificación , Interferón gamma/administración & dosificación , Ratones , Ratones Endogámicos C3H , Proteínas RecombinantesRESUMEN
An example of interdisciplinary problem solving by occupational health professionals is presented. Approximately one dozen employees in an aircraft wire harness assembly line complained of dermatitis, alleging workplace exposures as causation. The plant's and consulting industrial hygienists prepared toxicology and exposure assessments for all process materials, manufacturing procedures, and protective equipment used. They identified no common elements in the work environment that may have caused the dermatitis, suggesting multiple causation and possible individual worker sensitivities. An investigative team composed of the industrial hygienists and physicians in outside practice, including dermatologists and occupational medicine physicians, conducted a review of plant operations and proposed that workers with dermatitis complaints receive diagnostic medical examinations. An initial examination medically documented each worker's complaint, and a follow-up included patch testing for selected process materials. The physicians diagnosed a variety of mainly nonoccupationally induced illnesses such as fungal infections, skin cancer (solar induced), acne, etc., confirming the industrial hygienists' original assessment. One case appeared directly work-related and to be a specific assembly component sensitivity. Although several cases with a nonoccupational origin could have been aggravated by working conditions, these workers showed no sensitivity to the component when patch tested.
Asunto(s)
Dermatitis Profesional/diagnóstico , Dermatitis/diagnóstico , Acné Vulgar/diagnóstico , Aeronaves , Dermatología , Diagnóstico Diferencial , Eccema Dishidrótico/diagnóstico , Estudios de Seguimiento , Vidrio , Humanos , Aceites Industriales/efectos adversos , Metales/efectos adversos , Metacrilatos/efectos adversos , Exposición Profesional , Salud Laboral , Medicina del Trabajo , Grupo de Atención al Paciente , Solución de Problemas , Ácidos Esteáricos/efectos adversos , Tiña/diagnóstico , SoldaduraRESUMEN
BACKGROUND: Sweet syndrome (acute febrile neutrophilic dermatosis) may occur as a cutaneous paraneoplastic syndrome. This condition has been associated with hematologic malignancies and, to a lesser extent, with solid tumors. METHODS: The authors report two patients with malignancy-associated Sweet syndrome: a 66-year-old man in whom the onset of Sweet syndrome preceded the diagnosis of an adenocarcinoma of unknown primary by 3 months and a 69-year-old woman in whom a workup after the appearance of Sweet syndrome skin lesions revealed an unsuspected recurrent squamous cell carcinoma of the larynx. The authors review the reports of the other 39 patients with solid tumor-associated Sweet syndrome that have been published in the world literature. RESULTS: The most common malignancies were carcinomas of the genitourinary organs (37%), breast (23%), and gastrointestinal tract (17%). Typical clinical features and laboratory findings in these patients included tender erythematous plaques located on the upper extremities (97%); elevated erythrocyte sedimentation rate (95%); anemia (83%); fever (79%); and neutrophilia (60%). The symptoms and lesions of Sweet syndrome resolved after treatment with corticosteroids, potassium iodide, or colchicine. Sweet syndrome preceded the initial diagnosis of cancer or the detection of asymptomatic metastatic, persistent, or recurrent tumor, or a hematologic malignancy (in an individual with a previously diagnosed solid tumor) in 61% of the patients. In the other 39% of patients, diagnosis of Sweet syndrome followed the development of a solid tumor. CONCLUSION: The search for a neoplasm of the genitourinary organs and breast cancer in women and a gastrointestinal tract carcinoma in men should be emphasized in the evaluation for a solid tumor in patients with Sweet syndrome without a prior diagnosis of malignancy.
Asunto(s)
Neoplasias/complicaciones , Síndrome de Sweet/complicaciones , Adenocarcinoma/complicaciones , Anciano , Carcinoma de Células Escamosas/complicaciones , Femenino , Humanos , Neoplasias Laríngeas/complicaciones , Masculino , Neoplasias Primarias Desconocidas/complicaciones , Síndrome de Sweet/patologíaRESUMEN
The effects of intradermal injection of interferon alpha-2 beta on normal human skin were studied in 12 healthy adult volunteers using 500,000 international units recombinant human interferon alpha-2 beta, 3 times a week for five injections (n = 6) and nine injections (n = 6). Saline injections served as control sites. Lymphocytic infiltrates and the population of epidermal Langerhans' cells in the injection areas were observed. The results showed that epidermal Langerhans' cells (both adenosine triphosphatase positive and CD-1+) decreased significantly whereas human leukocyte antigen-DR expression in keratinocytes was enhanced. Dermal CD-3+ (Pan T cells), CD-4+ (T helper cells) and human leukocyte antigen DR+ cells increased. No significant differences in the number of CD-19+ (B cells) and CD-57+ (NK cells) were observed. There were no significant differences between the five-injection and nine-injection groups.
Asunto(s)
Antígenos CD/análisis , Antígenos HLA-DR/análisis , Interferón-alfa/farmacología , Células de Langerhans/inmunología , Adenosina Trifosfatasas/análisis , Adulto , Anticuerpos Monoclonales , Antígenos CD19 , Antígenos de Diferenciación de Linfocitos B/análisis , Antígenos de Diferenciación de Linfocitos T/análisis , Biopsia , Complejo CD3/análisis , Antígenos CD4/análisis , Antígenos CD57 , Antígenos CD8/análisis , Femenino , Humanos , Inmunohistoquímica , Inyecciones Intradérmicas , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Células de Langerhans/citología , Células de Langerhans/efectos de los fármacos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Valores de ReferenciaRESUMEN
An atypical case of adult T-cell leukemia/lymphoma (ATL) associated with human T-cell lymphotropic virus type I (HTLV-I) occurred in a 46-year-old Inupiat Eskimo man with no behavioral risk factors for HTLV-I infection. The case was characterized by lack of atypical circulating lymphocytes, hypercalcemia, and opportunistic infections; and by complete remission of the initial renal parenchymal lymphoma. The lymphoma cells had a helper T-cell (CD4) immunophenotype. Serum antibodies to HTLV I/II, detected by Western immunoblot, were identified in specimens collected 31 months before the onset of illness, at the time of diagnosis, and up to 37 months later, shortly before the patient's death. Polymerase chain reaction was used to identify HTLV-I DNA in peripheral blood mononuclear cells and in lymphoma in involved skin. Clinicians should be alert to sporadic cases of both atypical and classic ATL, even in populations in which the prevalence of HTLV-I infection is low.
Asunto(s)
Inuk , Neoplasias Renales/patología , Leucemia-Linfoma de Células T del Adulto/patología , Alaska , Linfocitos T CD4-Positivos/patología , ADN Viral/análisis , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Neoplasias Renales/microbiología , Leucemia-Linfoma de Células T del Adulto/microbiología , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Prevalencia , Neoplasias Craneales/patología , Linfocitos T Colaboradores-Inductores/patologíaRESUMEN
In a clinical trial of 172 patients at four medical centers, interferon alfa-2b (1.5 x 10(6) IU) or a placebo was injected directly into biopsy-proved noduloulcerative or superficial basal cell carcinomas three times weekly for 3 weeks, for a cumulative dose of 13.5 million IU. Efficacy of treatment was determined at 16 to 20 weeks by examination of biopsy specimens that demonstrated cure of lesions in 86% of interferon-treated patients and in only 29% of placebo-treated patients. During the treatment course and follow-up, an initial inflammatory response was observed at the treatment sites, followed by diminished erythema, improvement in overall appearance, and a decrease in size of lesions. Side effects of treatment, mainly flu-like symptoms, were usually mild and transient and occurred more commonly in the interferon-treated group. Only three patients, all in the interferon-treated group, discontinued therapy because of side effects. One year after initiation of therapy, 81% of interferon recipients and 20% of those given the placebo remained tumor free. Noduloulcerative and superficial lesions were equally responsive to treatment with interferon. For some patients with noduloulcerative or superficial basal cell carcinomas, intralesional interferon alfa-2b may be an alternative, effective treatment.
Asunto(s)
Carcinoma Basocelular/terapia , Interferón-alfa/administración & dosificación , Neoplasias Cutáneas/terapia , Carcinoma Basocelular/patología , Método Doble Ciego , Eritema/inducido químicamente , Eritema/patología , Femenino , Humanos , Inyecciones Intralesiones , Interferón alfa-2 , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Neoplasias Cutáneas/patologíaRESUMEN
Intralesional interferon alfa-2b has been proven effective in the treatment of basal cell carcinomas. Because nine injections over a 3-week period have been necessary to produce clinically significant cure rates, a sustained-release protamine zinc chelate interferon formulation has been developed. In this study, 65 basal cell carcinomas were treated in one of two dosing schedules with intralesional sustained release interferon alfa-2b (10 million IU per injection). Thirty-three patients received a single injection and 32 patients received one injection per week for 3 weeks. At study week 16, 80% of evaluable tumors treated with three injections and 52% treated with one injection were cured histologically. Two patients discontinued injections because of side effects. A sustained-release protamine zinc preparation of interferon alfa-2b shows promise as a practical, effective, and cosmetically elegant treatment for basal cell carcinoma.
Asunto(s)
Carcinoma Basocelular/terapia , Interferón Tipo I/uso terapéutico , Interferón-alfa/uso terapéutico , Neoplasias Cutáneas/terapia , Adulto , Anciano , Carcinoma Basocelular/patología , Quelantes/administración & dosificación , Preparaciones de Acción Retardada , Esquema de Medicación , Estética , Humanos , Inyecciones Intralesiones , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Persona de Mediana Edad , Protaminas/administración & dosificación , Distribución Aleatoria , Proteínas Recombinantes , Neoplasias Cutáneas/patología , Factores de TiempoRESUMEN
Eleven patients with alopecia areata, ranging from patchy disease to alopecia universalis, were treated with intralesional interferon alfa-2 on a selected area of alopecia. Follow-up at 3 months revealed local terminal hair growth in one patient. At 12 months, variable disease activity was seen. Regional lymphadenopathy, a new finding with interferon, was seen in four patients during the treatment. Immunohistochemical studies showed some changes in the inflammatory infiltrates and in HLA-DR expression that may be related to the interferon or to the dynamics of the inflammatory infiltrate in alopecia areata. Interferon, at the dosage and treatment schedule used in our trial, had no significant effect on alopecia areata.
Asunto(s)
Alopecia Areata/terapia , Interferón Tipo I/uso terapéutico , Adulto , Alopecia Areata/patología , Femenino , Estudios de Seguimiento , Antígenos HLA-DR/análisis , Humanos , Técnicas para Inmunoenzimas , Inyecciones Intralesiones , Interferón Tipo I/administración & dosificación , Macrófagos/patología , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Linfocitos T/patologíaRESUMEN
Each occupational setting has unique risks for occupational skin disease based on the materials used, the workplace environment, and the skin type of each worker. Virtually all programs for the prevention of skin disease can be designed around the principles outlined in this article. Most problems can be eliminated by well-designed prevention programs. All workers are entitled to a safe working environment that reduces to the extent possible the risks of acquiring occupational skin disease.
Asunto(s)
Dermatitis Profesional/prevención & control , Acné Vulgar/prevención & control , Industria Química , Dermatitis Atópica/prevención & control , Fármacos Dermatológicos/uso terapéutico , Ambiente , Dermatosis de la Mano/prevención & control , Herbicidas/efectos adversos , Humanos , Higiene , Educación del Paciente como Asunto , Ropa de Protección , Derivación y Consulta , SeguridadRESUMEN
A patient with right thalamic hemorrhage developed left-sided hemi-inattention, indifference, motor neglect, and hypokinesia. He also developed a severe memory deficit at the time of hemorrhage. Observations in this patient suggest that, in addition to a syndrome of neglect and hypokinesia, an amnesic syndrome can arise from unilateral lesions involving the right thalamus.
Asunto(s)
Amnesia/diagnóstico , Hemorragia Cerebral/diagnóstico , Hemiplejía/diagnóstico , Enfermedades Talámicas/diagnóstico , Atención , Enfermedades de las Arterias Carótidas/cirugía , Arteria Carótida Interna/cirugía , Constricción Patológica/cirugía , Dominancia Cerebral , Endarterectomía , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Complicaciones Posoperatorias/diagnóstico , Tomografía Computarizada por Rayos XRESUMEN
The rabbit ear comedogenicity assay is useful as a screening procedure for evaluating agents that come in contact with human skin. Controversy exists regarding the reliability of this assay because of differences in results from various laboratories. The subjective nature of the standard method of grading may also contribute to this variation. We use a more objective comedogenicity assay that utilizes increasing follicular orifice size on the rabbit ear as a measure of comedogenic activity. A generally linear increase in the degree of follicular orifice area was noted with several agents evaluated over a four-week application period. Further, a noninvasive Silastic elastomer mold was used to allow measurement of the same follicular orifice areas over time.
Asunto(s)
Acné Vulgar/inducido químicamente , Fármacos Dermatológicos/toxicidad , Pruebas Cutáneas/métodos , Animales , Alquitrán/toxicidad , Oído Externo , Femenino , Foliculitis/inducido químicamente , Miristatos/toxicidad , Naftalenos/toxicidad , Bifenilos Policlorados/toxicidad , Propilenglicol , Glicoles de Propileno/toxicidad , ConejosRESUMEN
This study examined the differential effects of frustration on normal children and those diagnosed as having Attention Deficit Disorder with Hyperactivity. Each group consisted of 16 boys between the ages of 6 and 8 years who were prematched for age, grade, and classroom placement. All children completed a series of arithmetic problems in order to earn toy rewards. Using a variant of Mischel's (1974) delay-of-gratification paradigm, children were presented with two choice-of-delay conditions in a randomly assigned, counterbalanced sequence: a free-choice conflict situation involving a long-passive or short-active reward delay, and a short-active delay. Results showed that a significantly greater proportion of hyperactive children chose to complete problems for an immediate reward compared to their normal control counterparts (p less than .01). Group differences were no longer apparent in the short-active delay trial. The results are discussed in terms of frustration tolerance and contributing factors such as cognitive-attentional style. Implications for treatment and future directions are delineated.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/psicología , Frustación , Niño , Conducta de Elección , Humanos , Masculino , Recompensa , Factores de TiempoAsunto(s)
Enfermedades del Colágeno/diagnóstico , Enfermedades de la Piel/diagnóstico , Piel/lesiones , Adulto , Enfermedades del Colágeno/etiología , Enfermedades del Colágeno/patología , Humanos , Masculino , Recurrencia , Piel/patología , Enfermedades de la Piel/etiología , Enfermedades de la Piel/patologíaRESUMEN
Synthetic pyrethroids are neurotoxic insecticides with a low mammalian toxicity. Prior investigations have found these agents to be neither cutaneous irritants nor sensitisers. Clinically demonstrable inflammation, as judged by erythema, oedema, or vesiculation, has not been apparent. Nevertheless, paraesthesia does result from cutaneous exposure. In this investigation technical grade flucythrinate was applied to the forearms of human participants twice daily for five consecutive days. Laser Doppler velocimeter measurements were made before each topical application, with histamine phosphate being intradermally injected on termination of the study. Results of both laser Doppler velocimetry and histamine induced axon reflex vasodilatation were not statistically significant at an alpha = 0.05 level. This investigation suggests that the synthetic pyrethroids have little influence on neurogenic vasodilatation on topical exposure.