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Biomedical subjects

C Burg

Publications and source records attributed to C Burg.

At least 19 recordsLinked to original sources

Involvement of histo-blood-group antigens in the susceptibility of colon carcinoma cells to natural killer-mediated cytotoxicity.

The susceptibility to natural-killer-cell lysis and expression of histo-blood-group antigens of 2 clones from a rat colon adenocarcinoma, of variants derived from them and of 17 human colon carcinoma cell lines were assessed in an attempt to determine if the major glycosidic tissue antigens of epithelial cells could influence the NK susceptibility of tumor target cells of epithelial origin. The rat REGb clone, which is relatively NK-sensitive, expressed higher levels of precursor structures T and Tn and lower levels of H antigenic determinants than the PROb clone, which displays higher resistance to NK-cell lysis. Cell variants were obtained from these 2 clones; it appeared that whether the cell variants were selected on the basis of expression of a blood-group antigenic determinant or on the basis of altered susceptibility to NK-cell lysis, there was a link between increased resistance and higher expression of cell-surface A and H histo-blood-group antigens, or conversely, between increased sensitivity and higher expression of precursor structures. Similar conclusions were obtained upon study of the human cell lines, since a significant correlation was found between the level of expression of T or Tn antigens and sensitivity to NK-cell lysis. A significant relationship was found between the expression of Lewis antigens and increased resistance to NK-cell-mediated cytotoxicity.

ABO Blood-Group System

Relationship between sensitivity to natural killer cells and MHC class-I antigen expression in colon carcinoma cell lines.

The sensitivity of colorectal tumors to NK-cell-mediated cytotoxicity and their expression of major histocompatibility complex (MHC) class-I antigens were studied in an attempt to determine whether such antigens play a role in the susceptibility of colorectal tumors to NK-cell lysis. In a rat colon-carcinoma model, 2 clones differing in their sensitivity to NK-cell-mediated cytotoxicity were tested for class-I expression; it was seen that the more sensitive cells (REGb) expressed less class-I products than did the resistant cells (PROb). However, when MHC class-I antigen expression was increased by IFN-gamma treatment, no change in NK-cell lysis was found with the PROb cells, while an increase in cytotoxicity was obtained with the REGb cells. After in vivo or in vitro selection of NK-resistant REGb cells, we observed in the selected cells an important decrease in RT-I class-I antigen expression. Fifteen different human colorectal cell lines were also studied for HLA class-I expression and NK-cell susceptibility, and no quantitative correlation between these 2 features was seen. However, cell lines which were deficient in HLA class-I antigens were more sensitive than class-I-positive cells.

Animals

Identification and characterization of a rat protein (p 105) auto-antigenic in rats bearing a progressive syngeneic colon carcinoma.

Sera from BDIX rats inoculated with 2 tumor clones derived from a single syngeneic colon carcinoma were assayed by Western blotting for the presence of antibodies against the grafted tumor. The PROb clone is progressive and produces metastases. We observed that rats bearing this tumor developed antibodies against an unglycosylated water-soluble protein of 105 kDa. The magnitude of this humoral response, as assessed by the intensity of the signal on immunoblots, was inversely correlated with survival of the rats. Furthermore, rats inoculated with the REGb clone, which is immunologically rejected, never developed detectable antibodies against the tumor. Antisera from rats injected with PROb tumor detected p105 antigen in cellular extracts from the REGb clone and from a series of rat and human cell lines. This protein was also detected in variable amounts in some normal adult and fetal tissues. Treatment of PROb or REGb cells by either interferon-gamma or heat shock did not significantly alter the expression of the p105 auto-antigen.

Adenocarcinoma

[Characterization of autoantigen (p105) in a model of colonic adenocarcinoma in the rat].

Sera from BDIX rats bearing the syngeneic colon tumors PROb or REGb were analysed by Western blotting in order to detect a possible humoral response against the grafted tumor. The PROb clone grows progressively in syngeneic hosts and metastasizes, whereas the REGb clone grows slowly and then is rejected. This model was developed by F Martin and his group in Dijon, France. We observed that rats bearing PROb tumors only develop an antibody response against a water-soluble protein of 105 kDa (p105) which is expressed by both tumor clones. This antibody response has never been detected in rats bearing REGb tumors. The antigen p105 was also expressed by normal adult colon as well as some other foetal or adult tissues. It is also present in extracts from several tumor cell lines including human colorectal carcinoma cell lines. Moreover, the titer of detected antibody at day 30 was inversely correlated with the survival of rats after tumor inoculation, suggesting a possible facilitating role of this antibody response.

Adenocarcinoma

Pharmacokinetic studies of mouse monoclonal antibodies to a rat colon carcinoma: I. Comparison of biodistribution in normal rats, syngeneic tumor-bearing rats, or tumor-bearing nude mice.

The pharmacokinetics of two iodine-131-(131I) labeled murine anti-rat colon carcinoma monoclonal antibodies (D3 and E4) were compared in normal Sprague Dawley rats, syngeneic BDIX rats, or nude mice bearing that tumor. Results of antibody uptake after i.v. administration were analyzed in terms of accumulation and localization indices for normal tissues and tumor. Statistically significant differences between rat and mouse tissue biodistribution were found. D3, which reacts in vitro with the tumor and several normal rat tissues, cleared quickly from the blood of rats and was specifically targeted to several normal tissues, notably the lung. Virtually no targeting to the tumor was observed. Nude mice, however, showed a slower blood clearance and specific antibody targeting only in the tumor. Similar results were seen after injection of another antibody, E4, which is tumor-specific in vitro. Data suggest that studies on the xenogeneic nude mouse model may not necessarily be relevant to the choice of monoclonal antibodies for clinical diagnostic imaging or therapy.

Adenocarcinoma

Monoclonal antibodies to a rat colon carcinoma: model for monoclonal antibody therapy of solid tumors.

Tumor progression, lung metastasis, and death occur in tumor-bearing BD IX syngeneic rats in a fashion similar to the course of patients with metastatic colon cancer. In an effort to establish a relevant model for monoclonal antibody (MoAb) therapy of tumors, we generated murine MoAb against DHD/TR, a dimethylhydrazine-induced rat colon carcinoma which has been adapted to cell culture. Murine MoAb 17B10 E4 (E4) reacts with the TR tumor and shows weak immunoperoxidase reactivity with normal rat tissues. Murine MoAb 5F7 D3 (D3) reacts with the tumor and a variety of normal rat epithelia. Both are IgG2a and mediate cytotoxicity by rat peripheral blood mononuclear cells. 18D5 F6 (F6) also reacts with the tumor and normal tissues but is an IgG2b and does not mediate cytotoxicity in the presence of rat effector cells. Iodinated E4 and D3 antibodies retained their immunoreactivity. E4 revealed 9.8 x 10(5) antigenic sites per TR cell, with an affinity constant of 9.35 x 10(7) M-1, while D3 demonstrated 2.5 x 10(6) antigenic sites and an affinity constant of 4.2 x 10(7) M-1. Immunoblotting showed that the antigens recognized by D3 and E4 are glycoproteins with molecular weights of 27,000 and 66,000, respectively. F6 failed to react with its antigen present in the blot. This rat colon carcinoma and the monoclonal antibodies described here may provide experimental data useful for implementing monoclonal antibodies in cancer therapy.

Animals

Cerebrospinal fluid neuron-specific enolase is reduced in Alzheimer's disease.

Neuron-specific enolase (NSE), a glycolytic enzyme enolase found in brain, was examined in the cerebrospinal fluid and serum of 30 patients with presumptive Alzheimer's disease (AD) and of 13 healthy controls and evaluated as a measure of neuronal functional activity associated with AD. The cerebrospinal fluid NSE levels of patients with AD were significantly reduced and serum NSE levels were significantly increased from controls. Cerebrospinal fluid NSE levels may be representative of central nervous system cell loss or a decrease in neuronal functional activity associated with AD.

Aged

Newborn minor physical anomalies and prediction of infant behavior.

The relationship between a newborn score of minor physical anomalies (MPAs) and behavior at ages 1 and 2 was examined. From an initial screening population of 933, 63 high anomaly and 78 low anomaly infants were followed until age 2 by examiners blind for the newborn anomaly score. High anomaly infants were more likely to be temperamentally difficult as rated by parent interview and direct observation. A subgroup of six infants who were considered irritable at both ages 1 and 2 were all from the high anomaly group. However, there was little agreement between behavioral ratings across situations and over time, and there were no significant predictors of behavior problems at age 2 based on any newborn or 1-year measure. These results indicate that the newborn anomaly score by itself is unlikely to prove clinically useful in predicting preschool behavior problems for an unselected population. The usefulness of this measure for other, "high-risk," populations remains to be explored.

Child Behavior

Stability and comparability of intellectual measures for cerebral-palsied preschoolers.

Intelligence test scores on the Stanford-Binet Intelligence Scale and the Merrill Palmer Scale were studied for 23 cerebral-palsied children to determine the stability and comparability of these measures during the preschool years as well as the relationship of pyschological gains or losses to clinical diagnoses of the children. Test and posttest data were analyzed for subjects who had participated for one year in a special preschool program for children with neuromotor problems. A high correlation was found between the two intelligence tests both on pretesting (r = .89) and posttesting (r = .83). No significant differences were observed between IQs attained at the three-year level and IQs attained at the four-year level. No associative pattern between etiology of the disability, neuromotor involvement, and intelligence test patterns was determined.

Cerebral Palsy

ACTH4-10: cognitive and behavioral effects in hyperactive, learning-disabled children.

A single dose of 30 mg i.m. ACTH4-10 or placebo was given to a sample of 20 hyperactive, learning-disabled children. No significant drug effects were obtained on measures of visual and auditory memory, new learning, impulsivity, attention, perceptual motor skills, anxiety, or behavior during testing. There was a slight increase in pulse rate for drug compared with the placebo group. These findings are in keepeing witth other recent reports of limited or insignificant cognitive effects in adults of a single dose of this peptide.

Adolescent