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Biomedical subjects

C Guillén

Publications and source records attributed to C Guillén.

At least 19 recordsLinked to original sources
PubMed2006

HLA class II polymorphisms in Spanish melanoma patients: homozygosity for HLA-DQA1 locus can be a potential melanoma risk factor.

BACKGROUND: The association of melanoma with HLA class II loci is under extensive debate. Different investigators have found discrepant results due to, at least in part, sample size, patient series heterogeneity, choice of control population and differences in the techniques employed for the detection of HLA antigens and alleles. OBJECTIVES: This study was designed to analyse the possible association of melanoma with HLA class II loci with regard to different clinic pathological factors and to investigate other risk factors for melanoma susceptibility, such as HLA homozygosity. PATIENTS AND METHODS: HLA-DRB1, -DQA1 and -DQB1 genotyping was performed for 117 eastern Spanish patients presenting with primary melanoma. RESULTS: Although there were no significant alterations in the phenotypic frequencies of HLA-DQA1, -DQB1 or -DRB1 alleles in any subgroup of patients when compared with controls, patients exhibited a statistically significant increase in HLA-DQA1 homozygosity rate. This DQA1 homozygosity-specific association was particularly dependent on some features in melanoma patients such as light hair colour, skin type I or II, early age at diagnosis, absence of atypical naevi, or abscence of atypical naevus syndrome phenotype (aetiological fractions about 10-20%). Analysis of homozygosity for single DQA1 alleles showed an increased homozygosity rate for DQA1*0505 and DQA1*0301 in comparison with controls. These DQA1 alleles are in strong linkage disequilibrium with DQB1*0301 in white populations, and DQB1*0301 homozygous individuals were significantly increased in red in or fair-haired patients (relative risk 5.65). CONCLUSIONS: Our results indicate that the contribution of HLA class II alleles to primary melanoma incidence is not significant in the Spanish population. However, homozygosity for the HLA-DQA1 locus (and, perhaps, for the HLA-DQB1*0301 allele) might be considered a potential risk factor for developing melanoma depending on the person's genetic background and, perhaps, on certain environmental conditions.

Adult↗
PubMed2006

Clinical, dermoscopy and histological correlation study of melanotic pigmentations in excision scars of melanocytic tumours.

BACKGROUND: Melanotic pigmentations in scars consecutive to the excision of melanocytic tumours can be secondary to a reactive phenomenon related to the scar tissue or to a recurrence of the melanocytic lesion excised in the first case. Recurrent naevi may sometimes adopt unusual features that make them difficult to differentiate from a melanoma. OBJECTIVES: To describe the clinical, dermoscopic and histological features of melanotic pigmentations in scars consecutive to the excision of melanocytic tumours, and to correlate the histological diagnosis with the dermoscopic features. METHODS: This was a prospective cohort study using macrophotography, dermoscopy and histopathological study. Ninety-five melanotic pigmentations (77 patients) in scars secondary to the excision of melanocytic tumours were prospectively collected in the Department of Dermatology at the Instituto Valenciano de Oncología in Valencia, Spain. Histopathological study was performed in 57 scars. RESULTS: Thirteen dermoscopic structures were identified. Four criteria allowed a differentiation between reactive and specific melanocytic pigmentations. Presence of globules and presence of heterogeneous pigmentation were features associated with specific melanocytic pigmentations (P < 0.0001). Presence of a regular network and presence of streaks were more frequently found in reactive pigmentations (P = 0.023 and 0.026, respectively). CONCLUSIONS: Dermoscopic examination of melanotic pigmentations in excision scars of melanocytic tumours provides useful information about the origin of that pigmentation. Based on such information, recurrent naevi can be differentiated from reactive pigmentations in most cases. Excision and histopathological diagnosis continue to be imperative in some cases of recurrent naevi with atypical clinical features.

Cicatrix↗
PubMed2005

An amalgam tattoo on the oral mucosa related to a dental prosthesis.

A 60-year-old woman presented with a pigmented lesion on the upper left gingival mucosa of 2 years duration. The lesion was in an area where a dental metallic prosthesis had been inserted into a nearby tooth several years earlier. A biopsy of the affected mucosa showed aggregates of pigmented granules varying in size in the dermis, extracellular matrix and within macrophages; these did not stain with melanin stains. The diagnosis was consistent with an amalgam tattoo.

Biopsy↗
PubMed2005

Vesiculous prurigo pigmentosa in a 13-year-old girl: good response to isotretinoin.

Prurigo pigmentosa is a rare inflammatory disease of unknown origin, first reported from Japan, with only 33 cases described in non-Japanese patients. We describe a 13-year-old girl with a pruriginous symmetrical eruption of papules and vesicles affecting her back, neck and chest of 1 month duration. She remembered a similar, but lighter eruption, 2 months before. As the initial diagnosis was of a vesiculobullous form of Darier disease, treatment with isotretinoin 40 mg/day was started with good response. Histological study showed a superficial perivascular and interstitial dermatitis composed predominantly of lymphocytes. The epidermis was spongiotic, with exocytosis of lymphocytes and some neutrophils and necrotic keratinocytes. All these findings were consistent with prurigo pigmentosa. The lesions resolved leaving a light brown reticulate hyperpigmentation. Prurigo pigmentosa has never been reported in prepubescent patients, the vesiculobullous forms are unusual, and the only treatments used previously are sulphonamides, tetracyclines and macrolides. We report a 13-year-old Caucasian girl with vesiculobullous prurigo pigmentosa successfully treated with isotretinoin.

Administration, Cutaneous↗
PubMed2004

The interleukin-6/soluble interleukin-6 receptor system induces parathyroid hormone-related protein in human osteoblastic cells.

In the present in vitro study, we tested the hypothesis that parathyroid hormone-related protein (PTHrP) might be a mediator of interleukin-6 (IL-6) and its soluble receptor (IL-6sR) in osteoblasts. We found that IL-6, within 1-20 ng/mL, added together with IL-6sR (100 ng/mL), rapidly (1 hour) increased PTHrP mRNA in human osteoblastic osteosarcoma MG-63 cells and human osteoblastic (hOB) cells from trabecular bone. PD098059, a mitogen-activated protein kinase (MAPK) kinase inhibitor, at 10 microM, and two inhibitors of protein prenylation and thus Ras activation, simvastatin (1 microM) and a farnesyltransferase (FTase) inhibitor (100 nM), but not the phosphatidylinositol 3-kinase inhibitor wortmannin, blocked the IL-6/IL-6sR-induced PTHrP expression in these cells. In addition, PD098059 as well as simvastatin and the FTase inhibitor abolished alkaline phosphatase activity and/or osteocalcin mRNA induction by the IL-6/IL-6sR in these cells. Our results support the role of the Ras/MAPK pathway as a major mechanism in the modulation of both PTHrP expression and differentiation in human osteoblasts.

Aged↗
PubMed2002

Molecular genetic analysis of HLA-DR and -DQ alleles in Spanish patients with melanoma.

Controversial data have been reported about HLA alleles and susceptibility to melanoma. The relationship between distribution of HLA alleles in patients with melanoma and susceptibility to tumour was analysed, to study the possible correlation between HLA class II DQA1, DQB1 and DRBI genes and melanoma in a Spanish population. Genomic DNA from 82 patients with melanoma and 367 random healthy donors, from the same geographic area, were typed by PCR-SSP (sequence specific primers). The patients were also divided into different groups according to the age and presence of cancer relatives, and compared with the controls. None of these HLA class II alleles showed significant positive or negative associations with either the overall population of patients with melanoma or the considered subgroups. Moreover, values for relative risk of DQB1*0301, DQB1*0302, DQB1*0303, DQB*05, DQA1*0401, DQA1*0101/0104 and DRB*08, which have been reported to be increased or decreased in patients with melanoma, were very low and of no statistical significance. Our results indicate that HLA class II alleles may not contribute to a strong susceptibility to melanoma in the Spanish population, although further studies on larger series are needed to corroborate this. Key words:

Adolescent↗
PubMed2001

Antitumor effect of B16 melanoma cells genetically modified with the angiogenesis inhibitor rnasin.

The growth of new blood vessels is an essential condition for the development of tumors with a diameter greater than 1-2 mm and also for their metastatic dissemination. RNasin, the placental ribonuclease inhibitor, is known to have antiangiogenic activity through the inhibition of angiogenin and basic fibroblast growth factor. Nevertheless, the administration of the recombinant form of a protein poses several limitations; as a result, we have studied the antitumor effect of RNasin in a murine gene therapy model. RNasin cDNA was subcloned into the pcDNA3 expression vector, and the resulting recombinant plasmid was used to transfect the B16 murine melanoma cell line. An RNasin inverted construction was used as control. Mice intravenously injected with clones expressing RNasin showed a significant inhibition of tumor metastatic progression with respect to control groups (P<.001) and survived longer (P<.001). Tissue sections from RNasin-expressing cell tumors showed a lower number of blood vessels when compared to tissue sections from mice lungs that had been inoculated with control cell lines. The results of these experiments show that the genetic modification of tumor cells with RNasin cDNA yields a significant antitumor effect, and suggest that this effect is at least partially the result of angiogenesis inhibition.

Angiogenesis Inhibitors↗
PubMed2001

C-terminal parathyroid hormone-related protein (PTHrP) (107-139) stimulates intracellular Ca(2+) through a receptor different from the type 1 PTH/PTHrP receptor in osteoblastic osteosarcoma UMR 106 cells.

Studies were undertaken to determine whether PTH-related protein (PTHrP) (107-139) mobilizes [Ca(2+)](i) in osteoblastic osteosarcoma UMR 106 cells. PTHrP (107-139), in a manner similar to PTHrP (107-111), induced a rapid [Ca(2+)](i) response in these cells that was dose dependent (EC(50) of approximately 0.1 pM) and more efficient than that of PTHrP (1-36) (EC(50) of approximately 1 nM). This effect of PTHrP (107-139) was abrogated by micromolar doses of verapamil or nifedipine. However, it was unaffected by 10 microM U73122 (a phospholipase C inhibitor), 100 microg/ml heparin (an inositol 1,4,5-trisphosphate receptor inhibitor), or 400 ng/ml pertussis toxin (a G(i) inhibitor), which inhibited the [Ca(2+)](i) response to PTHrP (1-36), or by either 25 nM bisindolylmaleimide I (BIM), a protein kinase (PK) C inhibitor, or 1 microM phorbol-12-myristate-13-acetate preincubation (22 h). PTHrP (107-139) and PTHrP (1-36), at 100 nM, desensitized the [Ca(2+)](i) response to a second challenge with the same peptide, but not with the other peptide in these cells. PTHrP (7-34), a type 1 PTH/PTHrP receptor (PTH1R) antagonist, decreased the effect of PTHrP (1-36) on [Ca(2+)](i). In contrast, PTHrP (107-111), but neither PTHrP (109-138) nor PTHrP (7-34), abolished this effect of PTHrP (107-139). Both PTHrP (107-139) and PTHrP (1-36), added together at submaximal doses, induced a higher [Ca(2+)](i) response. Moreover, PTHrP (107-139) increased the efficacy of PTHrP (1-36) on [Ca(2+)](i), but decreased its induced increase in PKA activity in these cells. Verapamil or nifedipine (at 50 microM) or 25 nM BIM, but not 25 microM adenosine 3',5'-cyclic monophosphorothioate, Rp-isomer, a PKA inhibitor, abolished the PTHrP (107-139)-induced increase in interleukin 6 messenger RNA (assessed by RT, followed by PCR) in UMR 106 cells. This peptide also increased c-fos messenger RNA in these cells; an effect inhibited by BIM, but unaffected by either verapamil or EGTA. These findings support the existence of high-affinity receptors for PTHrP (107-139), associated with an induced Ca(2+) influx, different from the PTH1R in UMR 106 cells. The present results suggest that PTHrP could affect bone turnover by interacting with the PTH1R and other yet unknown receptors in bone cells through complex mechanisms.

Animals↗
PubMed2000

Benign lymphangioendothelioma of the thigh simulating a low-grade angiosarcoma.

Benign lymphangioendothelioma (BL) is a rare vascular neoplasm that can histopathologically mimic a low-grade angiosarcoma or the patch stage of Kaposi sarcoma. We report on the case of a 49-year-old man with a benign lymphangioendothelioma on the right thigh that evolved on a vascular birthmark after a trauma. Because of constant pain and the slow but progressive growth of the lesion, we decided to excise the tumor. Three stages of surgery were needed to obtain negative margins. We review the reports of BL to date, with special attention to those that developed after trauma and those that had a preexistent vascular lesion, and expound on the histopathologic differential diagnosis with low-grade angiosarcoma.

Biomarkers, Tumor↗
PubMed1999

Melanotic pigmentation in excision scars of melanocytic and non-melanocytic skin tumors.

The appearance of pigmented lesions in melanoma surgical scars is a frequent finding that in some instances may cause confusion with a melanoma persistence. Nevertheless, only a few papers have dealt with this subject in the dermatologic literature. The melanoma surgical scars of 60 consecutive patients were reviewed with special attention to the presence of pigmentation and its clinical characteristics. Simultaneously, the scars of 60 consecutive patients who had been subjected to excision of a non-melanoma skin tumor were also studied. Biopsies were performed in representative clinical cases of pigmented lesions arising on the scars of both groups, as well as in non-pigmented scars, and processed for hematoxylin-eosin and immunohistochemistry. Pigmented lesions were present in a similar percentage in both groups (30% in melanoma scars (18/60) and 25% in non-melanoma scars (15/60)). Clinically, three types of clinical pigmentation were observed: lentigine-like lesions; pigmented streaks in scars after direct closure; and diffuse pigmentation in grafts. Histologically, two patterns emerged: one with lentiginous epidermal hyperplasia, hyperpigmentation, and a normal or moderately increased number of melanocytes; and a second one characterized by melanocytic hyperplasia of a variable degree. The scar process itself, irrespective of the tumor excised, seems to be responsible for the pigmentation. We suggest the existence of an induction process of scar tissue acting on melanocytes of the overlying epidermis.

Adult↗
PubMed1998

Altered pattern of cytokine production by peripheral blood CD2+ cells from B chronic lymphocytic leukemia patients.

To determine if activation-induced cytokine production is altered in CD2+ lymphocytes from B-CLL patients, cytokine levels were determined by ELISA in supernatants of PHA-stimulated cultures of CD2+ cells from 33 B-CLL patients and 22 healthy controls. The production of Interferon gamma (IFN-gamma) and Tumor Necrosis Factor (TNF-alpha) by mitogen-activated CD2+ lymphocytes from B-CLL patients was higher than that found in healthy controls, while no differences were found in TNF-beta production. IFN-gamma and TNF-alpha levels determined at 72 h in PHA-stimulated CD2+ cell cultures from B-CLL patients statistically correlated with the percentages of CD3+CD45RO+ and CD3-CD56+ lymphocytes, respectively. Although there were differences in the production kinetics of interleukins (ILs) 2 and 4 between B-CLL patients and the healthy controls, no differences were found at the time when the levels of both interleukins peak. The production of both IFN-gamma and IL-4 by PHA-stimulated CD2+ lymphocytes from non-smouldering B-CLL patients was significantly higher than that from smouldering B-CLL patients while no significant differences were found in the production of IL-2, TNF-alpha, and TNF-beta between the two B-CLL patient groups. These data suggest that functional alterations in the production of cytokines by CD2+ cells from B-CLL patients could help to explain the expansion of leukemic cells in B-CLL patients.

Adult↗
PubMed1998

Iron, lactoferrin and iron regulatory protein activity in the synovium; relative importance of iron loading and the inflammatory response.

OBJECTIVES: To determine the ability of lactoferrin in rheumatoid arthritis (RA) synovial fluid to bind "free" iron, and to study the regulatory mechanisms therein that control iron homeostasis. METHODS: "Free" iron was determined by the bleomycin assay and lactoferrin concentrations by enzyme linked immunosorbent assay. The activities of iron regulatory protein (IRP) and NF-kappa B in synovial fluid cells were assayed by mobility shift assay. RESULTS: 30% of synovial fluids contained "free" iron and in these, lactoferrin concentrations were significantly lower than in those with no "free" iron (p < 0.01). Addition of exogenous lactoferrin consistently reduced the amount of "free" iron in positive synovial fluids. IRP activity in synovial cells did not correlate with synovial fluid iron concentrations but did correlate with NF-kappa B activation and with serum C reactive protein. CONCLUSION: Lactoferrin may prevent iron mediated tissue damage in RA by reducing "free" synovial iron concentration when inflammatory stimuli have disregulated IRP mediated iron homeostasis.

Adult↗
PubMed1986

Therapeutic effect of danazol on metrorrhagia in patients with idiopathic thrombocytopenic purpura (ITP).

Idiopathic thrombocytopenic purpura (ITP) is more frequently seen in young females than in any other age or sex group. Danazol, an impeded androgen with a decreased masculinizing potential, has been described as useful in ITP. A total of 25 women 16 to 41 years of age, with chronic ITP were studied. All patients were refractory to treatments with glucocorticoids and splenectomy; 19 were inadequately controlled by immunosuppressants, vinblastine or vincristine-loaded platelets, the radioimmune method, colchicine, plasmapheresis, or surgery for accessory spleens. Danazol was given at a daily dosage of 600 mg for 4 months. All showed clinical improvement, as indicated by cessation or decrease of bleeding, and 12 (48%) cases obtained a drug-dependent excellent or good response of their ITP. Therapy produced amenorrhea or oligomenorrhea in 21 patients (84%) and 7 cases of chronic metrorrhagia were successfully controlled. The drug was well tolerated. Accordingly, danazol may be an effective treatment for ITP or related conditions, especially in adult females with uncontrollable metrorrhagia.

Adolescent↗