Biomedical subjects

Claudia Hernandez

Publications and source records attributed to Claudia Hernandez.

7 recordsLinked to original sources

PubMed2006

Toll-like receptor-2 expression is upregulated in antigen-presenting cells from patients with psoriatic arthritis: a pathogenic role for innate immunity?

OBJECTIVE: To study Toll-like receptor-2 (TLR-2) and TLR-4 expression in antigen-presenting cells from patients with psoriatic arthritis (PsA). METHODS: We measured expression of TLR-2 and TLR-4 in monocyte-derived dendritic cells from patients with PsA and with rheumatoid arthritis (RA), and in healthy controls. Dendritic cells were obtained from freshly isolated monocytes, stimulated with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin 4 (IL-4) after 6 days in culture. To obtain mature dendritic cells, lipopolysaccharide stimulation and 2 additional days in culture were necessary. The expression of TLR-2, TLR-4, HLA-DR, and CD86 was studied at baseline, at 6 days, and at 8 days by flow cytometry. To establish the functional properties of TLR expression we studied the following cytokines in cell supernatants: tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, and GM-CSF. TLR-2 expression was confirmed by Western blot analysis. RESULTS: Ten PsA patients with active disease and 8 healthy controls were studied, along with 4 patients with RA. TLR-2 expression was increased in immature dendritic cells from patients with PsA. Monocytes and mature dendritic cells did not show statistically significant differences. No difference was observed in the expression of TLR-4 in any cell type. The supernatant expression of cytokines showed a Th1 pattern, mostly with increased expression of TNF-alpha, IFN-gamma, and IL-2. Western blot analysis confirmed the increased expression of TLR-2. CONCLUSION: Upregulation of TLR-2 expression provides support for a role of the innate immune system in the pathogenesis of PsA.

Adult↗

PubMed2006

Therapeutic implications of autoimmune vitiligo T cells.

Vitiligo is an autoimmune disease presenting with progressive loss of skin pigmentation. The disease strikes 1% of the world population, generally during teenage years. The progressive loss of melanocytes from depigmenting vitiligo skin is accompanied by cellular infiltrates containing both CD4+ and CD8+ T lymphocytes. Infiltrating cytotoxic T cells with high affinity T cell receptors have likely escaped clonal deletion in the thymus, allowing such T cells to enter the circulation. Through the expression of CLA, these T cells home to the skin where they express type 1-cytokine profiles and mediate melanocyte apoptosis via the granzyme/perforin pathway. T cells found juxtapositionally apposed to remaining melanocytes can be isolated from the skin. Vitiligo T cells have demonstrated reactivity to antigens previously recognized as target antigens for T cells infiltrating melanoma tumors. In a comparison to existing melanoma-derived T cells, vitiligo T cells displayed superior reactivity towards melanoma cells. It is thought that genes encoding the TCRs expressed by vitiligo skin infiltrating T cells can be cloned and expressed in melanoma T cells, thereby generating a pool of circulating T cells with high affinity for their targets that can re-direct the immune response towards the tumor.

Animals↗

PubMed2005

Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion.

Myeloid suppressor cells with high arginase activity are found in tumors and spleen of mice with colon and lung cancer. These cells, described as macrophages or immature dendritic cells, deplete arginine and impair T cell proliferation and cytokine production. Although arginase activity has been described in cancer patients, it is thought to originate from tumor cells metabolizing arginine to ornithine needed to sustain rapid cell proliferation. The goal of this study was to determine whether myeloid suppressor cells producing high arginase existed in renal cell carcinoma patients. Peripheral blood mononuclear cells from 123 patients with metastatic renal cell carcinoma, prior to treatment, were found to have a significantly increased arginase activity. These patients had a markedly decreased cytokine production and expressed low levels of T cell receptor CD3zeta chain. Cell separation studies showed that the increased arginase activity was limited to a specific subset of CD11b+, CD14-, CD15+ cells with a polymorphonuclear granulocyte morphology and markers, instead of macrophages or dendritic cells described in mouse models. Furthermore, these patients had low levels of arginine and high levels of ornithine in plasma. Depletion of the CD11b+, CD14- myeloid suppressor cells reestablished T cell proliferation and CD3zeta chain expression. These results showed, for the first time, the existence of suppressor myeloid cells producing arginase in human cancer patients. In addition, it supports the concept that blocking arginase may be an important step in the success of immunotherapy.

Arginase↗

PubMed2005

4-Tertiary butyl phenol exposure sensitizes human melanocytes to dendritic cell-mediated killing: relevance to vitiligo.

The trigger initiating an autoimmune response against melanocytes in vitiligo remains unclear. Patients frequently experience stress to the skin prior to depigmentation. 4-tertiary butyl phenol (4-TBP) was used as a model compound to study the effects of stress on melanocytes. Heat shock protein (HSP)70 generated and secreted in response to 4-TBP was quantified. The protective potential of stress proteins generated following 4-TBP exposure was examined. It was studied whether HSP70 favors dendritic cell (DC) effector functions as well. Melanocytes were more sensitive to 4-TBP than fibroblasts, and HSP70 generated in response to 4-TBP exposure was partially released into the medium by immortalized vitiligo melanocyte cell line PIG3V. Stress protein HSP70 in turn induced membrane tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression and activation of DC effector functions towards stressed melanocytes. Melanocytes exposed to 4-TBP demonstrated elevated TRAIL death receptor expression. DC effector functions were partially inhibited by blocking antibodies to TRAIL. TRAIL expression and infiltration by CD11c+ cells was abundant in perilesional vitiligo skin. Stressed melanocytes may mediate DC activation through release of HSP70, and DC effector functions appear to play a previously unappreciated role in progressive vitiligo.

Adenoviridae↗

PubMed2004

Erythromycin-resistant Streptococcus pyogenes in Argentina.

Erythromycin (ERY) resistance in Streptococcus pyogenes has recently emerged as a problem of growing concern all through the world. We are presenting the comparison of results of the continuous surveillance of erythromycin resistance in S. pyogenes performed since 1989 in the Hospital de Pediatría J.P. Garrahan of Buenos Aires City, with independently observed rates in other five centers of Buenos Aires and seven centers of six other Argentinian cities, obtained between 1999 and 2001. A significant increase of erythromycin resistance was observed among S. pyogenes isolated in the Hospital Garrahan (6.6% in 1998-1999 to 9.9% in 2000). Similar trends were also detected in other centers of other Argentinian cities when recent data were compared to results of a multicenter study performed in 1995. However, lower rates of resistance were recorded in Mendoza, Cipolletti and Neuquén in comparison with data of 1995, 1998 and 1998 respectively. The reason of such decreasing resistance rates deserves to be investigated. The average of ERY-resistance rates obtained in the surveyed centers was 6.7% (range 0.5-14.1%). Control of antimicrobial use should be performed to warrant the future effectiveness of macrolide antibiotics regarding the positive association between use and resistance. These results also suggest that susceptibility tests for macrolides should be performed whenever S. pyogenes is isolated in Argentina.

Anti-Bacterial Agents↗

PubMed2003

Topical and light-based treatments for basal cell carcinoma.

Nonsurgical methods of treatment providing cure rates approaching those provided by surgery offer a significant advantage to patients with basal cell carcinoma (BCC) in certain anatomic locations. While intralesional interferon has been used to treat BCC with some success, the deliver method requires multiple visits to the doctor's office, which makes compliance a challenge for the patient. Initial success with light-based therapy of BCC over a decade ago has not evolved to the point where it is an effective, widely available treatment. The new class of immune response modifiers, represented by topical imiquimod cream, shows promise for providing topical treatment of early BCC. It is hoped that further developments of the class of drugs will produce an agent with fewer side effects and improved efficacy for nodular BCC.

Adjuvants, Immunologic↗

PubMedDate not supplied

Contact dermatitis to white petrolatum.

A 31-year-old Caucasian woman presented with a 20-year history of presumed atopic dermatitis. She complained of severe pruritus and the presence of extensive patches of erythema and scale. Her previous treatments included: multiple topical corticosteroids, tacrolimus 0.1% ointment, pimecrolimus 1% cream, and cyclosporine with no improvement of her symptoms. Her past medical history was unremarkable and she was on no other oral medications, including over-the-counter products. On physical examination, multiple erythematous, scaly patches were present on the chest, abdomen,back, and upper extremities. Lichenification of both antecubital fossa was present. Extensive excoriations on her arms and abdomen were also noted. Although the patient had a long-standing history of presumed atopic dermatitis, she had never undergone a skin biopsy. A skin biopsy was performed which demonstrated a perivascular lymphocytic infiltrate with eosinophils and dermal edema (Figures 1, 2). The biopsy was suggestive of possible hypersensitivity dermatitis. The patient then underwent patch testing. The following patch tests were applied to normal back skin using IQ chambers:North American Contact Dermatitis Group (NACDG) expanded standard, textile, fragrance trays, and ingredients found in her products (Chemotechnique, Malmo, Sweden). A total of 89 patches were applied, removed at 48 hours, and read both at 48 and 96 hours. At 48 hours, a total of 70 allergens were positive, 69 of those allergens were in a petrolatum vehicle. There were 50, 3+ reactions to sites of allergens in petrolatum (Figure 3). There were only two sites with petrolatum that were negative: budesonide (a corticosteroid) and melamine formaldehyde. In contrast, all of the sites where there were allergens in liquid vehicles were negative, with the exception of a 1+ reaction to cocamidopropyl betaine. At 48 hours,four additional patch tests were applied to plain petrolatum. Two of these patches were in plastic IQ chambers and two in aluminum Finn Chambers. At 48 hours, all four of the sites showed 3+ reactions (Figure 4). By 96 hours, all of the patch test sites that were positive at 48 hours, and much of the surrounding skin, showed a diffuse "angry back" reaction, which made an accurate 96-hour reading impossible.

Adult↗