[Skin cancer in patients submitted to organ transplantation: a growing problem].
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Biomedical subjects
Publications and source records attributed to C Ferrándiz.
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AIMS: Alterations of cell-cycle regulatory molecules in tumorigenesis may predict the biological behaviour of neoplasms and greatly contribute to their proper classification. Since the behaviour of proliferating trichilemmal tumour (PTT) is controversial, we decided to explore the possible significance of altered p53 and p27Kip1 immunohistochemical expression patterns in PTT. METHODS AND RESULTS: We evaluated the percentage and distribution of positive tumour cells and compared the results with those obtained from usual trichilemmal cysts (TC) and squamous cell carcinomas with trichilemmal differentiation (SCCT). PTT showed p53 immunoreactivity (50.4 +/- 29.6, mean +/- standard deviation) that was not statistically different from that seen in SCCT (75.2 +/- 36.3). On the other hand, p53 immunostaining was virtually absent in TC cases (positivity for p53 was observed in only one instance in < 1% of cells). As for p27Kip1, the mean percentage of positive cells in PTT (82.7 +/- 9.9) was slightly lower than in TC (90.6 +/- 4.6) but significantly higher than in SCCT (53.4 +/- 30). CONCLUSIONS: The similar p53 immunoreactivity in both PTT and SCCT favour the interpretation of the former as carcinoma, albeit one whose behaviour would be tempered by the well-known regulatory effect exerted by p27Kip1 on the cell cycle.
APETALA1 (AP1) and its homologue SQUAMOSA (SQUA) are key regulatory genes specifying floral meristem identity in the model plants Arabidopsis and Antirrhinum. Despite many similarities in their sequence, expression and functions, only AP1 appears to have the additional role of specifying sepal and petal identity. No true AP1/SQUA-functional homologues from any other plant species have been functionally studied in detail, therefore the question of how the different functions of AP1-like genes are conserved between species has not been addressed. We have isolated and characterized PEAM4, the AP1/SQUA-functional homologue from pea, a plant with a different floral morphology and inflorescence architecture to that of Arabidopsis or Antirrhinum. PEAM4 encodes for a polypeptide 76% identical to AP1, but lacks the C-terminal prenylation motif, common to AP1 and SQUA, that has been suggested to control the activity of AP1. Nevertheless, constitutive expression of PEAM4 caused early flowering in tobacco and Arabidopsis. In Arabidopsis, PEAM4 also caused inflorescence-to-flower transformations similar to constitutive AP1 expression, and was able to rescue the floral organ defects of the strong ap1-1 mutant. Our results suggest that the control of both floral meristem and floral organ identity by AP1 is not restricted to Arabidopsis, but is extended to species with diverse floral morphologies, such as pea.
BACKGROUND: Various national and international studies are under way to obtain reliable data on the epidemiological features of psoriasis. OBJECTIVES: The purpose of this study was to determine the prevalence of psoriasis in the general population in Spain as well as its variations according to sex, age and distribution in different geographical areas. MATERIAL AND METHODS: A random sample (12,938 subjects from 4027 households), representative of the general population, was the basis for a cross-sectional survey through telephone calls performed by trained non-medical interviewers using a specific questionnaire. RESULTS: The prevalence of psoriasis, similar in both sexes, was estimated to be 1.17-1.43%. The highest prevalence rates were shown among 20-50-year-old subjects. Distribution of psoriatic patients was not homogeneous throughout the country and prevalence was shown to be higher in the central dry region of the country. CONCLUSIONS: In a population of about 40 million inhabitants, 470,000-570,000 psoriatic subjects constitute an important target for health care issues and further epidemiological studies.
BACKGROUND: Various alloplastic injectable implants have been developed for soft tissue augmentation without surgery, but different local or systemic adverse reactions have limited their use for cosmetic purposes. OBJECTIVE: To examine the problems associated with silicone injection. METHODS: Case report and literature review. RESULTS: We describe an adverse granulomatous reaction after the injection of liquid silicone for lip augmentation, causing facial disfigurement. Although the initial response to steroids was poor, after 3 years of follow-up the nodules have almost disappeared spontaneously. CONCLUSION: We advise that silicone injection be performed solely by trained physicians using medical-grade silicone or consider other injectable materials.
The terminal step of fruit development in Arabidopsis involves valve separation from the replum, allowing seed dispersal. This process requires the activities of the SHATTERPROOF MADS-box genes, which promote dehiscence zone differentiation at the valve/replum boundary. Here we show that the FRUITFULL MADS-box gene, which is necessary for fruit valve differentiation, is a negative regulator of SHATTERPROOF expression and that constitutive expression of FRUITFULL is sufficient to prevent formation of the dehiscence zone. Our studies suggest that ectopic expression of FRUITFULL may directly allow the control of pod shatter in oilseed crops such as canola.
In order to investigate the importance of timing in the immunophenotypical characteristics of the inflammatory infiltrate and in the adhesion molecules expression in cutaneous necrotizing vasculitis (CNV) we carried on an immunohistopathologic study. An avidin-biotin-streptavidin peroxidase technique was performed on 21 lesional skin biopsy specimens obtained sequentially at 0 to 24, 72 and 120 hours from seven patients with a CNV presenting as palpable purpura. A panel of monoclonal antibodies specific for inflammatory cells (T lymphocytes, polymorphonuclear leukocytes, macrophages, dendritic cells) and different adhesion molecules (E-selectin, ICAM-1, VCAM-1, LFA-1, VLA-4) was used. Moreover, HECA-450 monoclonal antibody was used to identify cutaneous lymphocyte antigen (CLA) in the inflammatory infiltrate. In all cases, polymorphonuclear leukocytes predominated in the early phase of CNV and their number decreased significantly with time (p = 0.0001). The T lymphocytes were present from the beginning and their number remained stable or increased slightly in time (p = 0.1), thus becoming predominant in the perivascular infiltrate in older lesions. Macrophages were scattered on interstitium since the early phase and they showed a time-dependent increase (p = 0.0003). E-selectin (ELAM-1) expression was detected at the first biopsy and it decreased depending on the age of the evolving vasculitis (p = 0.0033). The expression of CLA decreased also with time in 5 of the 7 cases (p = 0.0001). Our study supports the existence of an unique histopathologic pattern in CNV, in which the inflammatory infiltrate varies with time at the expense of the number of polymorphonuclear cells and macrophages.
Activation tagging using T-DNA vectors that contain multimerized transcriptional enhancers from the cauliflower mosaic virus (CaMV) 35S gene has been applied to Arabidopsis plants. New activation-tagging vectors that confer resistance to the antibiotic kanamycin or the herbicide glufosinate have been used to generate several tens of thousands of transformed plants. From these, over 30 dominant mutants with various phenotypes have been isolated. Analysis of a subset of mutants has shown that overexpressed genes are almost always found immediately adjacent to the inserted CaMV 35S enhancers, at distances ranging from 380 bp to 3.6 kb. In at least one case, the CaMV 35S enhancers led primarily to an enhancement of the endogenous expression pattern rather than to constitutive ectopic expression, suggesting that the CaMV 35S enhancers used here act differently than the complete CaMV 35S promoter. This has important implications for the spectrum of genes that will be discovered by this method.
The transition from vegetative to reproductive phases during Arabidopsis development is the result of a complex interaction of environmental and endogenous factors. One of the key regulators of this transition is LEAFY (LFY), whose threshold levels of activity are proposed to mediate the initiation of flowers. The closely related APETALA1 (AP1) and CAULIFLOWER (CAL) meristem identity genes are also important for flower initiation, in part because of their roles in upregulating LFY expression. We have found that mutations in the FRUITFULL (FUL) MADS-box gene, when combined with mutations in AP1 and CAL, lead to a dramatic non-flowering phenotype in which plants continuously elaborate leafy shoots in place of flowers. We demonstrate that this phenotype is caused both by the lack of LFY upregulation and by the ectopic expression of the TERMINAL FLOWER1 (TFL1) gene. Our results suggest that the FUL, AP1 and CAL genes act redundantly to control inflorescence architecture by affecting the domains of LFY and TFL1 expression as well as the relative levels of their activities.
BACKGROUND: In order to plan the pertinent surgical technique for each patient with melanoma or other skin malignancies, it is mandatory to identify those lymphatic basins at risk for metastases. The advent of radiotracers for functional studies of the cutaneous lymphatic system during the last decade has resulted in the disclosure of an unexpected interindividual variability of the lymphatic drainage in both head and neck and trunk. OBJECTIVE: To ascertain the usefulness of lymphoscintigraphy for depicting the cutaneous lymphatic draining basins in patients with primary melanoma of the head, trunk and limbs, and to compare the observed lymphatic drain with the expected pattern of lymph flow according to the classical anatomical studies. MATERIAL AND METHODS: Prospective study in a university hospital (Barcelones Nord area). Consecutive patients with the diagnosis of cutaneous melanoma were recruited after excisional biopsy of the primary tumor. Every patient was intradermally injected with rhenium-sulfide colloids or colloidal technetium labelled with Tc-99m in four quadrant doses of 0.3 ml around the lesions or its excisional scar. Scintigraphic imaging of the migrating radiotracer resulted in a flow pattern that was compared with its "classical" expected counterpart. RESULTS: Altogether, 55 lesions were studied, including 9 in the head, 21 in the trunk and 25 in the limbs (7 upper and 18 lower). The scintigraphic drain pattern did not match the expected classical pattern in 37.0% of the lesions overall (14% upper limbs, 42% truncal lesions out from an area 2.5 cm at both sides of Sapey's line or the midline, 16.6% lower limbs and 89% head and neck). CONCLUSIONS: Lymphatic drain of the skin shows a very high intrapersonal variability leading to the need for an individual work-up in order to know the lymphatic basins at risk for metastases. The high rate of unexpected or non-matching patterns casts some doubts over those previous studies that did not include lymphoscintigraphy on a patient-basis.
Two patients with keratosis punctata of the palmar creases are described. The association with ichthyosis vulgaris and other disorders of keratinization is discussed. In both cases, histopathology revealed a close relation between the keratotic plug and the sweat glands. The role of genetic factors and manual activity in the pathogenesis is discussed. Treatment with oral etretinate resulted in a good improvement in the first patient, but prolonged low-dose maintenance therapy was required to prevent recurrence.
BACKGROUND: Current evidence suggests that p53 accumulation is critical to the development of skin cancer in the general population. It is possible, however, that the molecular steps involved in transplant-associated and non-transplant-associated skin carcinogenesis may differ. OBJECTIVE: Our purpose was to examine p53 expression in premalignant and malignant skin lesions from renal transplant recipients (RTRs) in their first 3 years of immunosuppression, as well as in equivalent lesions from immunocompetent normal individuals. METHODS: p53 expression was examined by routine immunohistochemical methods using the anti-p53 monoclonal antibody DO7. RESULTS: p53 immunoreactivity was more prevalent in dysplastic epidermal keratoses and cutaneous carcinomas from RTRs than in equivalent lesions from nontransplant controls. Statistical analysis revealed significant differences, however, only in premalignant skin lesions (p = 0.03). CONCLUSION: This study demonstrates that accumulation of p53 protein is frequently encountered in both premalignant and malignant skin lesions of RTRs, and that this may occur as an early step in transplant-associated skin carcinogenesis.
The fruit is a highly specialized plant organ that occurs in diverse forms among the angiosperms. Fruits of Arabidopsis thaliana, which are typical of the > 3000 species of Brassicaceae, develop from a gynoecium that consists of two fused carpels. The mature gynoecium of Arabidopsis is composed of an apical stigma, a short style, and a basal ovary that contains the developing ovules. After the ovules are fertilized, the fruit elongates and differentiates a number of distinct cell types, allowing for the successful maturation and the eventual dispersal of the seeds. Although the processes involved in carpel and fruit morphogenesis are not well understood, recent studies have identified a large number of mutants that display abnormal gynoecium and fruit development. The detailed phenotypic description of these mutants together with recent cloning of many of these genes has begun to shed light on this interesting and complex developmental process. Here we review the growing collection of Arabidopsis genes known to control the initiation and development of the gynoecium and resulting fruit.
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Human papillomavirus (HPV) is able to subvert the host cell replication machinery so as to foster viral reproduction. Specifically, HPV infection is known to induce expression of proliferation antigens such as Ki67 and proliferative cell nuclear antigen (PCNA) in differentiated keratinocytes which have ceased to replicate. In order to determine whether cyclin D1 or cyclin E deregulation is also a feature of HPV infection, an immunohistochemical investigation of cyclin D1, cyclin E, Ki67, and PCNA expression has been carried out in 38 cases of HPV 6/11-related condyloma acuminatum (CA). Results were compared with those obtained from 15 psoriatic proliferative lesions. Whereas 35 (92.1 per cent) CA samples exhibited positive nuclear immunostaining for cyclin E, no cyclin D1 immunoreaction was detected in any of the CA samples studied. All psoriatic lesions showed immunostaining for both cyclins. All CA cases revealed a positive immunoreaction for Ki67 and 33 for PCNA, both in the parabasal and in the differentiated upper epithelial layers. Parabasal keratinocytes of psoriatic lesions were always positive for both Ki67 and PCNA. These results indicate that in the onslaught of HPV 6/11 upon the keratinocyte replication machinery, cyclin E, PCNA, and Ki67 are amongst the targeted cell cycle modulators, whereas cyclin D1 is spared the main effects of virus-cell interplay. In contrast, both cyclins seem to be induced in psoriasis, a non-viral proliferative skin condition.
We describe a 46-year-old woman with multiple symmetrical papulocystic lesions on the face, neck, chest, back, and upper arms since childhood. Vermiculate atrophoderma, entropion, and progressive loss of eyelashes was also noted. Since the age of 30, 12 basal cell carcinomas have developed on the face. Histopathologic examination revealed multiple anastomosing nests and strands that arose from the lower part of a hair follicle in early lesions. In more advanced lesions, multiple keratinizing microcysts within a moderately sclerotic stroma were noted in the upper and mid dermis. In some biopsy specimens, focal areas showing sweat gland (ductal) and sebaceous differentiation were also observed. Basal cell carcinomas developed from the basaloid component of the hamartomatous proliferation.
Hypotrichosis is a relatively common feature of a number of complex hereditary syndromes. However, the isolated variant, called hereditary hypotrichosis simplex (HHS), is especially uncommon. We present a Spanish family with 8 of 19 persons covering 4 generations affected by HHS. No associated ectodermal or other defects were noted. The pedigree was compatible with an autosomal dominant inheritance with variable penetrance.
Fruit morphogenesis is a process unique to flowering plants, and yet little is known about its developmental control. Following fertilization, fruits typically undergo a dramatic enlargement that is accompanied by differentiation of numerous distinct cell types. We have identified a mutation in Arabidopsis called fruitfull (ful-1), which abolishes elongation of the silique after fertilization. The ful-1 mutation is caused by the insertion of a DsE transposable enhancer trap element into the 5' untranslated leader of the AGL8 MADS-box gene. beta-glucuronidase (GUS) reporter gene expression in the enhancer trap line is observed specifically in all cell layers of the valve tissue, but not in the replum, the septum or the seeds, and faithfully mimics RNA in situ hybridization data reported previously. The lack of coordinated growth of the fruit tissues leads to crowded seeds, a failure of dehiscence and, frequently, the premature rupture of the carpel valves. The primary defect of ful-1 fruits is within the valves, whose cells fail to elongate and differentiate. Stomata, which are frequent along the epidermis of wild-type valves, are completely eliminated in the ful mutant valves. In addition to the effect on fruit development, ful cauline leaves are broader than those of wild type and show a reduction in the number of internal cell layers. These data suggest that AGL8/FUL regulates the transcription of genes required for cellular differentiation during fruit and leaf development.