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Biomedical subjects

M C Cid

Publications and source records attributed to M C Cid.

At least 55 records · Page 3Linked to original sources
PubMed1994

The role of basement membrane in angiogenesis and tumor growth.

Expansion of the tumor-cell mass is dependent on both the degree of tumor vascularization and the rate of angiogenesis. Blood vessel growth is controlled, in part, by the matrix surrounding it, in particular, the basement membrane underlying the endothelium. Here we illustrate that laminin, a major component of basement membrane, has several biologically active sites that can bind to endothelial and tumor cells, and have the ability to regulate angiogenesis and tumor growth. We show that synthetic peptides at two sites in the laminin B1 chain (the RGD and YIGSR sequences) inhibit angiogenesis, whereas a third site in the A chain, designated SIK-VAV, stimulates vessel and tumor cell growth. By developing strategies that promote or inhibit the activities of these sites in laminin, we may obtain methods to inhibit angiogenesis and subsequent tumor growth.

Amino Acid Sequence↗
PubMed1994

Antibodies to endothelial cells in Behçet's disease: cell-binding heterogeneity and association with clinical activity.

OBJECTIVES: To investigate the prevalence and characteristics of antibodies to endothelial cells (aEC) from large vessel and from microvasculature in a group of patients with Behçet's disease (BD) to determine the relationship of these antibodies with clinical and laboratory features of the disease. METHODS: Thirty patients with BD were prospectively and consecutively studied. The aEC were determined by enzyme-linked immunosorbent assay (ELISA) using endothelial cells derived from human umbilical vein (large vessel) as well as from retroperitoneal adipose tissue (microvasculature). RESULTS: Fifteen patients (50%) had aEC, either directed to large vessel [8(26%) patients] or microvascular [13(43%) patients] endothelial cells. The percentage of active patients was significantly higher in the aEC-positive group [12(80%) patients] compared with the aEC-negative group [5(33%) patients] (p < 0.05). CONCLUSIONS: Patients with BD have a high prevalence of aEC when microvascular endothelial cells are used in the assay. These antibodies seem to be a marker of disease activity in this condition, previously considered as negative for autoantibodies.

Adipose Tissue↗
PubMed1994

Estradiol enhances leukocyte binding to tumor necrosis factor (TNF)-stimulated endothelial cells via an increase in TNF-induced adhesion molecules E-selectin, intercellular adhesion molecule type 1, and vascular cell adhesion molecule type 1.

Adhesion of leukocytes to endothelial cells is a critical step in the development of acute and chronic inflammatory lesions. We report here that estradiol treatment of cultured human umbilical vein endothelial cells stimulated up to a twofold increase in TNF-induced adhesion of both polymorphonuclear leukocytes and PMA-activated peripheral blood mononuclear cells. This effect was more evident (threefold increase) when endothelial cells were cultured on the basement membrane glycoprotein laminin. Progesterone, but not testosterone, had a similar stimulatory effect. Estradiol also promoted a slight increase in interferon gamma-stimulated endothelial cell adherence for peripheral blood mononuclear cells, but no effect of estradiol was observed when adhesion of leukocytes to endothelial cells was stimulated with IL-1 or IL-4. The estradiol-induced increase in leukocyte binding to human umbilical vein endothelial cells was partially blocked by antibodies to the adhesion molecules E-selectin, intercellular adhesion molecule type 1 (ICAM-1), and vascular cell adhesion molecule type 1 (VCAM-1). Indirect immunofluorescence techniques showed that estradiol produces an increase in TNF-induced cell surface expression of these molecules. Northern blot analysis demonstrated a transient increase in TNF-induced expression of mRNA for E-selectin, ICAM-1, and VCAM-1 in endothelial cells treated with estradiol. Our data demonstrate that estradiol has important regulatory functions in promoting leukocyte-endothelial cell interactions that might contribute to the observed predominance in females of some autoimmune inflammatory diseases.

Adipose Tissue↗
PubMed1993

Identification of haptoglobin as an angiogenic factor in sera from patients with systemic vasculitis.

Angiogenesis is an important process in chronic inflammatory diseases. We observed that sera from patients with systemic vasculitis stimulated angiogenesis in an in vitro model using human umbilical vein endothelial cells cultured on a basement membrane (Matrigel) substrate. After 40% ammonium sulfate precipitation, angiogenic activity remained in the low molecular weight fraction and could be inactivated by heat. SDS-page of serum FPLC fractions exhibiting maximal angiogenic activity demonstrated two prominent species of 45 and 16-20 kD in patients' sera. These bands were much less apparent in sera obtained from control subjects. Amino-terminal sequencing of the 45-kD protein demonstrated that it was haptoglobin. Purified haptoglobin stimulated angiogenesis in a dose-dependent manner. The angiogenic activity of vasculitis patients' sera was partially inhibited by an antihaptoglobin antibody. Furthermore, serum haptoglobin levels in vasculitis patients correlated both with disease and angiogenic activity. Haptoglobin angiogenic activity was confirmed in two in vivo models using an implanted disc and a subcutaneous injection of basement membrane. Stimulation of angiogenesis is a newly recognized biological function of haptoglobin. The increased levels of haptoglobin found in chronic inflammatory conditions may play an important role in tissue repair. In systemic vasculitis, haptoglobin might also compensate for ischemia by promoting development of collateral vessels.

Amino Acid Sequence↗
PubMed1992

Adenovirus-mediated transfer of a recombinant human alpha 1-antitrypsin cDNA to human endothelial cells.

To evaluate the feasibility of using a replication-deficient recombinant adenovirus to transfer human genes to the human endothelium, human umbilical vein endothelial cells were infected in vitro with adenovirus vectors containing the lacZ gene or a human alpha 1-antitrypsin (alpha 1AT) cDNA. After in vitro infection with the lacZ adenovirus vector, cultured endothelial cells expressed beta-galactosidase. In parallel studies with the alpha 1AT adenovirus vector, infected cells expressed human alpha 1AT transcripts, as evidenced by in situ hybridization and Northern analysis, and de novo synthesized and secreted glycosylated, functional alpha 1AT within 6 hr of infection, as shown by [35S]methionine labeling and immunoprecipitation. Quantification of the culture supernatants demonstrated 0.3-0.6 micrograms of human alpha 1AT secreted per 10(6) cells in 24 hr, for at least 14 days after adenovirus vector infection. To demonstrate the feasibility of direct transfer of genes into endothelial cells in human blood vessels, lacZ or alpha 1AT adenovirus vectors were placed in the lumen of intact human umbilical veins ex vivo. Histologic evaluation of the veins after 24 hr demonstrated transfer and expression of the lacZ gene specifically to the endothelium. alpha 1AT adenovirus infection resulted both in expression of alpha 1AT transcripts in the endothelium and in de novo synthesis and secretion of alpha 1AT. Quantification of alpha 1AT in the vein perfusates showed average levels of 13 micrograms/ml after 24 hr. These observations strongly support the feasibility of in vivo human gene transfer to the endothelium mediated by replication-deficient adenovirus vectors.

Adenoviruses, Human↗
PubMed1991

Malignant histiocytosis as a fatal complication of systemic lupus erythematosus.

We present the case of a 26-year-old Caucasian woman with systemic lupus erythematosus (SLE) of 9 years duration, mainly involving the kidney. Her clinical course was complicated in the last year by several infectious and noninfectious events, and after pancytopenia, fever, and extremely high levels of lactate dehydrogenase developed, the woman died. Light and electron microscopy of bone marrow, together with immunophenotyping, disclosed malignant histiocytosis, a complication of SLE that has not been reported.

Adult↗
PubMed1991

Immunopathologic study of skin lesions in dermatomyositis.

To determine the phenotype of skin infiltrates in affected and uninvolved skin from patients with dermatomyositis, immunohistochemical studies with 10 murine monoclonal antibodies were carried out on 25 skin biopsy specimens. Dermal infiltrates consisted predominantly of HLA-DR-expressing macrophages and T lymphocytes, especially of the CD4 subset. B lymphocytes, as defined by positive staining for Leu-12, were absent. Epidermal Langerhans cells were absent or decreased in some areas of affected skin but the total number was normal. OKT6+ cells were present in some dermal mononuclear infiltrates in close contact with lymphocytes. We observed reduced HLA-DR positivity of dermal capillary endothelia. These findings are apparently different from dermatomyositis muscle infiltrates but are similar to those in skin affected by cutaneous lupus erythematosus. Our observations support the concept that, in autoimmune diseases, cellular infiltrates may be more organ-specific than disease-specific.

Antibodies, Monoclonal↗
PubMed1989

Immunohistochemical analysis of lymphoid and macrophage cell subsets and their immunologic activation markers in temporal arteritis. Influence of corticosteroid treatment.

To determine the phenotype of infiltrating mononuclear cells in patients with temporal arteritis (TA), we performed immunohistochemical studies on temporal artery biopsy specimens from 24 patients with biopsy-proven TA. Interdigitating reticulum cells (IRC) were observed in 41% of the patients; disease duration was significantly shorter in these patients than in patients lacking IRC (mean 1.5 months versus 3.8 months). Infiltrating cells consisted predominantly of HLA-DR-expressing macrophages and T lymphocytes, especially of the CD4 subset. There were few B cells and no K cells. No relationship between cellular distribution and disease duration or treatment was found. Interleukin-2 receptor expression was observed in 87.5% of biopsy specimens obtained prior to or within the first 4 days of treatment with prednisone, but in only 14% of specimens obtained later. The presence of IRC in patients with TA suggests an autoimmune reaction directed against an antigenic substance that resides in the arterial wall and is presented and processed in situ. DR-expressing macrophages activated by CD4+ T lymphocytes may contribute to arterial damage in TA. Corticosteroids do not modify cellular distribution but induce important functional changes, as demonstrated by the disappearance of interleukin-2 receptor expression in patients treated for more than 4 days.

Antibodies, Monoclonal↗
PubMed1988

Polymyalgia rheumatica: a syndrome associated with HLA-DR4 antigen.

HLA class II antigens were determined in 65 patients with biopsy-proven giant cell arteritis (GCA). An increase in DR4 antigen frequency was found in the patients (40%) compared with that in 200 healthy controls (20%) (Pcorr less than 0.05). DR4 was significantly more frequent in GCA patients with polymyalgia rheumatica (PMR) than in those without PMR (58.8% versus 19.3%) (P less than 0.005). HLA-DR4 frequency in GCA patients without PMR was similar to that in the control population (20%). Patients with severe, disabling PMR had DR4 more frequently (90%) than did those with moderate symptoms who required medical care because of cranial arteritis manifestations (41.6%) (P less than 0.05). We conclude that, in GCA patients, association with DR4 is mainly related to the manifestation of the disease as PMR. We discuss clinical and immunogenetic similarities between PMR and other DR4-associated rheumatic disorders. Common immunopathogenic mechanisms leading to clinical overlap among them are suggested.

Female↗
PubMed1987

Clinical usefulness of temporal artery biopsy.

To assess the diagnostic usefulness of temporal artery biopsy in temporal arteritis (TA) and establish clinical features capable of predicting its positivity we have retrospectively studied the biopsy specimens and the clinical features of 103 patients who had undergone temporal artery biopsy. Temporal artery biopsy reached a positive predictive value of 90.2% with respect to the final diagnosis based on the criteria proposed by Ellis and Ralston and the clinical course. The simultaneous presence of recent onset headache, jaw claudication, and abnormalities of the temporal arteries on physical examination had a specificity of 94.8% with respect to the histological diagnosis and of 100% with respect to final diagnosis. The presence of any of these clinical features, though of little specificity (34.4%), had a sensitivity of 100% with respect to histological diagnosis, selecting a group of patients in whom temporal artery biopsy has more discriminative value.

Adult↗
PubMed1987

HLA class II antigens (DR, DQ loci) and peripheral arthritis in ankylosing spondylitis.

Fifty one patients with ankylosing spondylitis (AS) were typed for HLA-A, B, C, DR, and DQ antigens. The antigen frequencies were compared with those of a normal population and with a B27 positive control group. All but one of the patients with AS were HLA-B27 positive. A positive linkage disequilibrium between Cw1, Cw2, DR1, and the B27 antigen was observed. Patients with AS showed a significant increase in DQw2 antigen compared with the B27 positive control group. No differences in antigenic frequencies were observed in patients having peripheral arthritis and patients with only axial involvement. Seven out of nine patients (78%) with an erosive peripheral arthritis were DR7 positive, suggesting that DR7 or genes closely linked could be related with a more aggressive peripheral joint involvement in patients with AS.

Arthritis↗