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Biomedical subjects

F Fernández-Madrid

Publications and source records attributed to F Fernández-Madrid.

8 recordsLinked to original sources
PubMed2002

Autoimmunity to the M(r) 32,000 subunit of replication protein A in breast cancer.

PURPOSE: We sought to identify autoantigens recognized by antibodies in breast cancer patient sera with potential diagnostic or prognostic significance. EXPERIMENTAL DESIGN: Serum from a female breast cancer patient exhibiting a high titer antinuclear antibody was used to screen a HeLa cDNA expression library, leading to the cloning of a cDNA for the M(r) 32,000 subunit of replication protein A (RPA32). RPA32 expression and localization were assayed in autologous tumor by monoclonal antibody staining. A specific ELISA using recombinant protein was used to screen sera from 801 breast cancer patients and 65 controls. RESULTS: A relationship between anti-replication protein A (RPA) antibodies and the ductal breast carcinoma of the proband was suggested by overexpression and aberrant localization of RPA32 in tumor cells as compared with surrounding normal ductal tissue and by the presence of anti-RPA32 antibodies before the diagnosis. The prevalence of anti-RPA32 antibodies was significantly higher (P < 0.01) among breast cancer patients (87 of 801 patients) than among noncancer controls (0 of 65 controls). Similarly, anti-RPA32 antibodies were present in 4 of 39 patients with intraductal in situ carcinoma. No associations were found between anti-RPA antibodies and survival, occurrence of a second tumor, metastases, or antibodies to p53. Reactivity to RPA32 also was detected in sera from 3 of 47 patients with other cancers. CONCLUSIONS: In view of the central role of RPA in DNA replication, recombination, and repair, we suggest that autoimmunity to RPA32 may reflect molecular changes involved in the process of tumorigenesis. The finding of antibodies to RPA32 before diagnosis and their prevalence in in situ carcinoma suggest that they are potentially useful markers of early disease.

Antigens, Neoplasm↗
PubMed1999

Antinuclear antibodies as potential markers of lung cancer.

There are multiple case reports of antinuclear antibodies (ANAs) in patients with malignancies, yet to date there has not been a systematic survey of ANAs in lung cancer. We have previously reported that autoantibodies to collagen antigens resembling those found in the connective tissue diseases are consistently detected in the sera from lung cancer patients. In this work, we looked for the presence of ANAs in the sera from these same patients. Sera from 64 patients with lung cancer and 64 subjects without a history of cancer were retrospectively tested for reactivity on immunoblots of nuclear extracts of HeLa, small cell carcinoma, squamous cell carcinoma, adenocarcinoma, large cell carcinoma of the lung, and of normal lung cells. Associations were sought between the reactivities on immunoblots and lung cancer cell type, diagnosis, and progression-free survival by the method of classification and regression trees (CARTs). Cross-validated CART analyses indicated that reactivities to certain bands in immunoblots are associated with different types of lung cancer. Some of these autoantibodies were associated with a prolonged survival without disease progression. Our data suggest that autoimmunity is often a prominent feature of lung cancer and that molecular characterization of these antigens may lead to the discovery of proteins with diagnostic and prognostic value.

Adult↗
PubMed1998

Periarticular osteoporosis in osteoarthritis of the knee.

OBJECTIVE: To test the hypothesis that bone mineral density (BMD) in periarticular subchondral regions of the knee joint is abnormal in patients with osteoarthritis (OA). METHODS: Sixty-two knees from patients with relatively mild OA (primarily radiographic grades 0, 1, 2) of the knee were compared with 62 knees from normal subjects matched for age, sex, race, and body side (right or left). BMD of the lumbar spine, distal femoral shaft, and several periarticular subchondral regions of the knee were determined by dual energy x-ray absorptiometry (DXA). To facilitate increased accuracy of BMD values, lateral DXA of the knees was also performed and used to provide a third dimension to the usual two-dimensional anterior-posterior g/cm2, producing measurements as g/cm3. Subchondral bone regions included both superficial and deep regions of the medial femoral, medial tibial, and lateral tibial compartments. RESULTS: BMD (g/cm3) was lower than normal in 6 subchondral bone regions of the knees (n=43) of white female patients with OA (average decrease -13.3%), significant in all 6 subchondral regions (p=0.001 to p=0.047). Two-dimensional BMD (g/cm2) was lower than normal in 6 subchondral regions of the knees (n=43) of white female patients with OA (average decrease -7.3%), significant in only 2 of 6 subchondral regions (p=0.011 to p=0.014). BMD (g/cm3) was lower than normal in 6 subchondral regions of the knees (n=19) of African American female patients with OA (average decrease -9.1%), significant in only one of the 6 subchondral regions (p=0.016). There was no significant difference in spinal BMD (L1-L4) or femoral shaft BMD between normal and OA for either racial group. About 13% of the OA patients had osteoporosis at the spine. CONCLUSION: A significant decrease in periarticular subchondral BMD is present in female patients with relatively mild OA of the knee whether or not they had osteoporosis based on a spine BMD measurement.

Absorptiometry, Photon↗
PubMed1997

T cell receptor (V beta) bias in the response of rheumatoid arthritis synovial fluid T cells to connective tissue antigens.

T cell receptor (V beta) use in the response to type II collagen and cartilage proteoglycans was analysed in peripheral blood and synovial fluid T cells from RA patients. T cells from RA patients with an immune response to connective tissue antigens, and paired PB and SF samples were stimulated in vitro with type II collagen, high density aggrecan proteoglycans (PG), and the T cell mitogen concanavalin A. After short term culture, mRNA was extracted from cells and a reverse transcription-polymerase chain reaction was performed, using primers specific for eight TCR V beta determinants. Blood cells stimulated with ConA generated strong bands with virtually all the V beta primers tested, but the TCR (V beta) expression by SF T cells stimulated with mitogen was biased, suggesting a selection process during joint infiltration. The V beta phenotypes of cells responding to PG was restricted in individual RA patients, but the pattern of V beta use in the the RA population was not consistent. In contrast, the V beta phenotypes of SF cells responding to CII was highly biased in both individual patients and the RA population, with V beta 14, V beta 17, and V beta 8 phenotypes predominant. We conclude that the T cell response to connective tissue antigens is restricted compared with mitogen stimulation, with the highest degree of TCR bias seen in the response of SF T cells to stimulation with type II collagen.

Aged↗
PubMed1992

Dependence of proteoglycan induced arthritis in BALB/c mice on the development of autoantibodies to high density proteoglycans.

BALB/c mice were immunised with high or low density native human cartilage proteoglycans, or the respective core proteins obtained from chondroitin ABC lyase digestion. Mice injected with high density native proteoglycans developed arthritis whereas mice injected with low density proteoglycans or with core proteins did not. Analysis of the immune response by enzyme linked immunosorbent assay (ELISA) and western blot showed a stronger and more polyspecific response in animals injected with low density proteoglycans compared with mice with arthritis which had been injected with high density proteoglycans. Autoantibodies to mouse high density proteoglycans were only present in mice injected with native human high density proteoglycans, however. The data suggest that an arthritogenic epitope lies within the glycosaminoglycan rich region of the native proteoglycan molecule, which may induce an autoantibody response and subsequently arthritis in BALB/c mice.

Animals↗
PubMed1967

Biochemical and physicochemical characterization of collagen-synthesizing polyribosomes.

Synthesis of collagen on polyribosomes has been demonstrated in vitro in chick embryo corium by radioisotope incorporation, zone centrifugation through sucrose gradients, and analytical ultracentrifugation. Collagen synthesis was associated with polyribosomes ranging in size, as reflected by their sedimentation constants, from about 180S to approximately 1600S. Most of the newly formed collagen, hydroxyproline, was present on the largest polyribosome aggregates ( approximately 350-1600S), but small polyribosomes ( approximately 180-200S) also contained collagen. On the basis of the proline-(14)C/hydroxyproline-(14)C ratios and the disrupting effect of collagenase, the proposal is made that the 350-1600S polyribosomes from this tissue are involved predominantly in collagen synthesis. The large polyribosomes are disrupted extensively by collagenase but only partially by ribonuclease and trypsin. Therefore, it appears that they are stabilized by the interaction of newly forming collagen chains. Evidence is presented consistent with the hypothesis that these large polyribosomes are formed by the aggregation of small polyribosomes (180-200S) through the interaction of collagen polypeptides. It is suggested that these small polyribosomes might be involved in the synthesis of subunits of the collagen alpha chain.

Animals↗