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Biomedical subjects

R Gonzalez-Amaro

Publications and source records attributed to R Gonzalez-Amaro.

10 recordsLinked to original sources
PubMed2000

Multidrug resistance-1 (MDR-1) in rheumatic autoimmune disorders. Part I: Increased P-glycoprotein activity in lymphocytes from rheumatoid arthritis patients might influence disease outcome.

BACKGROUND: Multidrug resistance (MDR) is characterized by overexpression of P-glycoprotein, a pump molecule that decreases intracellular drug concentrations by increasing drug efflux from cells. OBJECTIVE: To look for correlations between clinical status and P-glycoprotein activity and/or TNF-alpha mRNA levels in patients with rheumatoid arthritis. METHODS: Sixteen patients were studied. Based on response to therapy, eight were refractory and eight nonrefractory to treatment. Findings were compared to those in 24 healthy controls. Flow cytometry was used to evaluate P-glycoprotein activity in peripheral blood mononuclear cells isolated by gradient centrifugation and incubated with the P-glycoprotein substrate daunorubicin. TNF-alpha mRNA levels were determined using quantitative PCR. RESULTS: Patients with rheumatoid arthritis showed an increased number of lymphocytes with high P-glycoprotein activity (p = 0.0001) as compared to the normal controls. P-glycoprotein activity was higher in the refractory than in the non-refractory patient subgroup (p = 0.006). Also, TNF-alpha mRNA levels were markedly higher in the refractory subgroup than in the nonrefractory subgroup, and were undetectable in the normal controls. CONCLUSIONS: Enhanced P-glycoprotein activity may be closely related to an unfavorable clinical course and a poor response to treatment. Increased TNF-alpha expression and chronic exposure to various drugs, including glucocorticoids, may contribute to increase P-glycoprotein activity. Both high P-glycoprotein activity and excessive amounts of TNF-alpha seem associated with poor outcome in rheumatoid arthritis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Involvement of cell adhesion and activation molecules in the pathogenesis of erythema dyschromicum perstans (ashy dermatitis). The effect of clofazimine therapy.

OBJECTIVES: To assess the expression of several cell adhesion and lymphocyte activation molecules in erythema dyschromicum perstans lesions, and to evaluate the effect of clofazimine therapy on the expression of these molecules. DESIGN AND METHODS: A prospective study. Skin biopsy samples were obtained from patients before and after 3 months of clofazimine therapy, and the expression of cell adhesion and activation molecules was assessed by an immunohistochemical technique. SETTING: This study was performed in a clinical referral center and an immunology research laboratory. PATIENTS: We studied 6 patients with erythema dyschromicum perstans. A diagnosis was made on the basis of clinical and histological criteria. Two patients discontinued participation in the study: one because of adverse effects and the other for unknown reasons. INTERVENTIONS: Patients were treated with clofazimine, 100 mg/d, for 3 months. MAIN OUTCOME MEASURES: Expression of cell adhesion and lymphocyte activation molecules in skin biopsy specimens before and after clofazimine therapy. RESULTS: Before clofazimine therapy, we detected a noticeable expression of intercellular adhesion molecule 1 and major histocompatibility complex class II molecules (HLA-DR) in the keratinocyte basal cell layer. In addition, CD36, a thrombospondin receptor that is not expressed by normal skin, was detected in the strata spinosum and granulosum. The dermal cell infiltrate expressed the activation molecule AIM/CD69 and the cytotoxic cell marker CD94. After clofazimine therapy, the expression of intercellular adhesion molecule 1 and HLA-DR disappeared, as well as the mononuclear cell infiltrate. CONCLUSIONS: Our results suggest that some cell adhesion and activation molecules are involved in the pathogenesis of erythema dyschromicum perstans. Clofazimine appears to have an important effect on the inflammatory phenomenon of erythema dyschromicum perstans.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Lack of expression of intercellular adhesion molecule ICAM-1 in lepromatous leprosy patients.

It is conceivable that an abnormal expression of cell-adhesion molecules can contribute to the poor inflammatory response seen in some inflammatory skin diseases. Adhesins are cell-surface molecules that are expressed by many cell types. The main function of adhesins appears to be the promotion of cellular interactions, such as those occurring between immune cells. The epidermis of patients with inflammatory skin diseases exhibits an increased expression of ICAM-1, and it has been postulated that such increased expression can be important in the genesis of cutaneous inflammation. The expression of cell-adhesion molecules (LFA-1, LFA-2, LFA-3 and ICAM-1) in skin lesions of leprosy patients was studied, as well as the in vitro expression of these molecules induced with gamma interferon (IFN-gamma). A lack of expression of ICAM-1 in the epidermis of lepromatous patients was noted; in addition, no expression of ICAM-1 was seen in the nearly normal skin from these patients incubated with IFN-gamma. A similar expression of the four molecules studies was noted in the dermis of both the lepromatous and tuberculoid types of leprosy. The epidermis of the lepromatous leprosy patients appears to have a defective expression of ICAM-1.

Antigens, CD↗
PubMed1993

Methotrexate therapy in childhood systemic lupus erythematosus.

We evaluated the therapeutic potential of methotrexate (MTX) in patients with systemic lupus erythematosus (SLE). Their serious disease ruled out further treatment with prednisone or prednisone plus cyclophosphamide. Low dose oral MTX (5-10 mg/week) was added to the therapy (prednisone or prednisone plus cyclophosphamide) of 10 selected patients with SLE. Eight of them showed marked improvement and we were able to taper prednisone and completely discontinue cyclophosphamide therapy. Our results suggest that the use of oral MTX in low, weekly doses can be useful as adjunctive therapy for selected cases of childhood SLE.

Administration, Oral↗
PubMed1988

Mononuclear cell-fibroblast interactions in scleroderma.

We studied cell proliferation and collagen biosynthesis in cocultures of dermal fibroblasts with peripheral blood mononuclear cells (MNC) from scleroderma patients and from age-matched normal controls. Autologous one-way mixed MNC-fibroblast cultures revealed that fibroblasts do not stimulate MNC proliferation. Conversely, MNC stimulate autologous fibroblasts from scleroderma patients as well as from normal controls. This effect is increased in cells from scleroderma patients in which it seems to be mediated both by cell-to-cell interaction and through the production of soluble factors by MNC. In normal control cell systems we found no proliferative effect of supernatants of unstimulated cells or from those stimulated in autologous mixed-lymphocyte reactions. Coculture of fibroblasts with autologous MNC resulted in increased [14C]proline incorporation into both collagenic and noncollagenic proteins. This effect was mediated mostly by soluble factors that are released into the culture medium. Protein synthesis by MNC-fibroblast cocultures from scleroderma patients was significantly greater than protein synthesis by those from normal controls. Culture supernatants from unstimulated MNC or from autologous mixed-lymphocyte cultures caused a slight decrease in collagenic protein synthesis by cultured fibroblasts from scleroderma patients but not by those from normal controls. This effect of culture supernatants could be reproduced, and magnified, with purified IL-1 on cells from either patients or controls. Our findings indicate abnormal MNC-fibroblast interactions in scleroderma that could play an important role in the pathogenesis of fibrosis, the hallmark of this condition.

Adult↗
PubMed1988

Natural killer cell activity in the systemic connective tissue diseases.

By doing 51Cr release assays with K562 cells and single natural killer (NK) cell assays with and without interleukin-2 (IL-2) containing supernatants, we were able to establish differences and similarities in NK cell function of patients with systemic connective tissue diseases. Decreased NK cell activity in systemic lupus erythematosus was found to be due to a paucity of active NK cells, with increased proportions of inactive and IL-2 unresponsive NK cells. The few active NK cells responded well to IL-2 by increasing their recycling capacity. Patients with mixed connective tissue disease had a normal baseline NK cell activity that responded poorly to IL-2 at the single cell level. This apparent normalcy was found to be maintained by few NK cells with high recycling activity that could not be increased further with IL-2. Patients with primary Sjögren's syndrome had very low NK activity carried out by few NK cells, with low recycling indices and poor response to IL-2. Patients with scleroderma had normal NK cell functions throughout, and patients with active dermatomyositis/polymyositis were found to have diminished NK cell function with low numbers of NK cells that reverted to normal upon disease inactivation.

Adult↗
PubMed1987

Natural killer cell activity in dermatomyositis-polymyositis.

We examined the baseline natural killer (NK) function and its modulation by interleukin-2 (IL-2) in 16 patients with dermatomyositis/polymyositis (DM/PM). Patients with active untreated disease had low baseline NK activity, while in patients with inactive and untreated disease, it was akin to the controls. Patient's cells with low NK activity responded less to IL-2 than those with normal NK activity. Studies at the single cell level revealed decreased target binding and killing cells with a normal recycling capacity. Our findings indicate an association between disease activity and decreased NK function in patients with DM/PM that could play a role in its association with malignancy.

Adolescent↗
PubMed1983

T-lymphocyte subsets in leprosy.

Immunologic abnormalities in T cells have been reported in patients with lepromatous leprosy. Ten patients with leprosy (eight lepromatous, one dimorphous, one tuberculoid) were studied in order to detect the proportions of total T lymphocytes and helper as well as suppressor subsets, using monoclonal antibodies in an indirect immunofluorescence test. Percentages of total T cells, suppressor cells, as well as helper subsets were similar in leprosy patients as compared with age-matched controls. This study could be considered a preliminary one to be followed by functional assays.

Adolescent↗
PubMedDate not supplied

An immunohistochemical study of UV-induced skin lesions in actinic prurigo. Resistance of langerhans cells to UV light.

Actinic prurigo is an inflammatory disease of the skin that appears to be mediated by an abnormal immune response. Cell adhesion molecules play a key role in the induction of the immune response as well as in the pathogenesis of inflammation. We investigated the expression of cell adhesion and activation molecules, as well as the density of Langerhans cells in skin from patients with actinic prurigo. Skin biopsies from ultraviolet light-induced lesions, and non-irradiated areas from 10 actinic prurigo patients were studied; in addition, several spontaneous skin lesions were studied. Skin biopsies from normal individuals were used as controls. The expression of ICAM-1, ICAM-3, LFA-3, CD2, LFA-1, VLA-4, CD1a, VCAM-1, CD69, and activated b1 integrins were assessed by immunostaining. An increased expression of LFA-1, LFA-2, ICAM-3, VLA-4, and activated b1 integrins was observed in the cell infiltrate of actinic prurigo lesions and an up-regulated expression of ICAM-1 was detected in keratinocytes from these specimens. Interestingly, the number of Langerhans cells (CD1a + ) in actinic prurigo skin was not significantly affected by ultraviolet irradiation, a phenomenon that was not observed in normal controls. The increased expression of adhesion molecules in the cell infiltrate of actinic prurigo, indicates that these cells are activated and suggests that they are involved in the skin damage seen in these patients. The resistance of Langerhans cells from patients with actinic prurigo to ultraviolet light may have an important role in the pathogenesis of this condition. The involvement of keratinocytes in the pathogenesis of actinic prurigo is suggested by the expression of ICAM-1 on these cells.

Antibodies, Monoclonal↗