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Biomedical subjects

A M Vazquez

Publications and source records attributed to A M Vazquez.

At least 19 recordsLinked to original sources

Immunogenetic analysis of variable regions encoding AB1 and gamma-type AB2 antibodies from the NeuGc-containing ganglioside family.

The variable regions from P3, a murine monoclonal antibody (MAb) against NeuGc-containing gangliosides, and two anti-idiotype MAbs directed to P3 MAb were cloned and sequenced. Comparisons with previously reported sequences showed that P3 is a germline antibody encoded by genes from the V(H)Q52 and V(kappa)19 families. Analysis of nucleotides at the heavy chain CDR3 (H-CDR3) showed the presence of an extensive 3' N region that contains almost 50% of the nucleotides of this CDR. In addition, amino acid sequence analysis of the H-CDRs of this MAb revealed the presence of three arginines, two of which are present in the H-CDR3, that could be involved in the interaction of P3 MAb with its electronegative epitope on gangliosides. Anti-idiotype 1E10, which seems to define a "regulatory" idiotope on P3 MAb (it induces Id+ Ab3), represents a germline Ab2 that belongs to the V(H)J558 and V(kappa)10 gene families. By contrary, the anti-idiotype 3B11 is an extensively mutated antibody that belongs to the V(H)3660 and V(kappa)4/5 gene families, defining a "private" idiotope on P3 MAb. Even when different V genes contribute to the variable regions of 1E10 and 3B11 MAbs, they share an acidic motif E/D-D-Y/D-Y-D in H-CDR3, suggesting that both Ab2s recognize paratope positive residues on the Ab1. Therefore, complementary electrostatic interactions involving H-CDR3 from both Ab1 and Ab2, might provide a clue to understand the molecular basis for the generation of gamma-type anti-idiotype antibodies to V regions recognizing glycolylated ganglioside antigens.

Amino Acid Sequence↗

Characterization of the colorectal antigen IOR-C2.

A colorectal antigen (IOR-C2) was characterized by a monoclonal antibody produced against the colon cancer cell line SW1116. By immunohistochemical staining the antigen was abundant and strongly expressed in epithelium of normal colon whereas colorectal carcinomas showed a more variable and heterogenous reactivity to the antibody (IOR-C2). Radioimmunoprecipitates of SW1116 cell homogenates showed a 160-200 kD band in SDS gels. Physicochemical characterization indicate that at least two IOR-C2 reactive sites are present on the antigen tested and that it is mainly an 0-linked glycoprotein carbohydrate chain which can also be N-linked to the protein. The expression of IOR-C2 mimics that of the colon associated antigen (CAA) and NCC-CO-450 antigen but is distinct from these with regard to its expression in carcinomas as well as its physicochemical characteristics.

Animals↗

Toxic effects of interleukin-2-activated lymphocytes on vascular endothelial cells.

IL-2-activated lymphocytes (LAK cells) show increased adherence to, and killing of, human vascular endothelial cells compared to resting lymphocytes. In the present work, we have found that supernatants from LAK cell cultures also are toxic to human umbilical vein endothelial cells (HUVEC) when tested for 48 h in a neutral red uptake assay. Recombinant TNF-alpha and IFN-gamma at high concentrations are also toxic under the same test conditions, and TNF-alpha was directly detected in LAK cell supernatants. An inconsistent inhibition of toxicity was found with anti-TNF-alpha whereas anti IFN-gamma antibodies had a partial inhibitory effect. The susceptibility of HUVEC to cellular killing by LAK cells could be up- and down-regulated with insulin-like growth factor I and IFN-gamma, respectively. It is concluded that damage to vascular endothelium during high dose IL-2 treatments may be partially related to an excessive production of lymphokines such as IFN-gamma and TNF-alpha. IFN-gamma may, in addition, be protective for HUVEC during cellular interactions with LAK cells.

Culture Media↗

Experimental methods for kinetic study of suicide substrates.

The kinetic study of the enzymatic inactivation originated by suicide substrates can be carried out by means of two alternative approaches. One method considers the substrate concentration as practically constant during the assay time and provides explicit equations of product concentration vs. time. The other method involves the significant consumption of the substrate, yielding implicit equations of time vs. product concentration. The utility of both methods is discussed and adequate experimental conditions for their correct application are established.

Enzyme Inhibitors↗

A medical information system for ambulatory care, research, and curriculum in an army family practice residency: 51,113 patient problems.

Over a 16-month period, the Family Practice Residency at Madigan Army Medical Center coded 51,113 ambulatory problems using the International Classification of Health Problems in Primary Care (ICHPPC) coding scheme. The demography of this defined active duty, retired, and dependent population is described as well as the rank order of the major diagnostic categories and top 25 individual diagnoses. A plot of the major diagnostic categories seen by month over a 16-month period is presented. Comparisons between similar curves are made. Physician compliance to coding approached 75 percent and an average of 1.42 problems were dealt with (coded) per visit. Fifty percent of all patient problems recorded fell into 25 descriptive diagnoses. Ninety percent of all patient problems recorded fell into 163 descriptive diagnoses. These data compare favorably to the Virginia study. Comparison of the top 25 patient problems also revealed similarities between this and the Virginia study. Difficulties arise in comparing data because of the differences in coding schemes (RCGP vs ICHPPC). A universally adopted code for all family practice and ambulatory care research would help in overcoming this problem.

Adolescent↗