Search PubMed⌕ Search

Biomedical subjects

C W Todd

Publications and source records attributed to C W Todd.

At least 37 records · Page 2Linked to original sources
PubMed1984

Production of mitogen-free immune interferon and T-cell growth factor by human peripheral blood lymphocytes induced with biotin-labeled staphylococcal enterotoxin A.

A method for the facile removal of mitogens or inducers of lymphokine production from cell culture medium of stimulated cells is described. The technique is based on the covalent attachment of biotin to mitogen or inducer and the removal of the biotinylated products from stimulated cell culture medium using immobilized avidin. Using this procedure, biotin-labeled staphylococcal enterotoxin A (SEA-B) was shown not to differ significantly from unmodified SEA in its capacity to stimulate mitogenesis and induce production of immune interferon (IFN) and T-cell growth factor (TCGF) in cultures of human mononuclear cells from peripheral blood. SEA-B was also shown not to differ from SEA in its binding to SEA antibodies. Results of mitogenicity studies and competitive radioimmune assay (RIA) measurements indicate that SEA-B is essentially completely removed from stimulated cell culture medium by absorption with avidin coupled to Sepharose 4B.

Biotin↗
PubMed1984

Acid treatment enhances IL-2 activity of conditioned medium.

Although conditioned medium (CM) from human lymphocytes or mononuclear cells is the most readily available source of interleukin-2 (IL-2) for human T cell culture, its IL-2 activity in our experience is inconsistent. It is likely that this is, at least in part, due to the presence of toxic substances in the CM. Using CM from TPA/SEA induced human mononuclear cells, we have found that acid treatment (pH 2.0, greater than 30 min) significantly improves its ability to promote T cell growth. It is postulated that the selection process which occurs in cultures of mitogen stimulated T cells may result in cells which are sensitive to mitogen-induced lymphotoxins and that these are inactivated by the acid treatment. Since acid treatment did not similarly improve the T cell growth promoting ability of PHA induced, lectin-free commercial IL-2, there must be other differences between it and our CM, which play a role in T cell growth.

Cell Survival↗
PubMed1984

Megaesophagus and seroreactivity to Trypanosoma cruzi in a rural community in northeast Brazil.

The relationship of symptoms and radiographic abnormalities suggestive of esophageal motility disorders with electrocardiographic (ECG) alterations and seroreactivity to Trypanosoma cruzi was studied in a defined population in a rural area endemic for Chagas' disease in Bahia, Brazil. Between January and June 1981, 680 individuals 5 years of age or older were examined with serologic tests, ECGs and questionnaires for esophageal motility disorder. Of these, 39.9% were seropositive for Chagas' disease. Symptoms of dysphagia occurred 2.5 times more frequently among seropositive individuals than among seronegative individuals. Radiographic esophageal abnormalities were 3.6 times more frequent among seropositive individuals than among seronegative individuals in the symptomatic group. Symptoms and radiographic abnormalities were more common in men than in women although this was not statistically significant. Among seropositive individuals the percentage with symptoms of dysphagia increased with age, with a peak prevalence rate of 23.9% in the 45- to 64-year-old age group. Also, in the seropositive group, 41.7% with X-ray abnormalities of the esophagus and 26.3% with symptoms of dysphagia presented an abnormal ECG.

Adolescent↗
PubMed1983

The effects of indomethacin on in vitro peripheral blood mononuclear cell reactivity in human schistosomiasis.

The peripheral blood mononuclear cell (PBMN) proliferative responses of cells from patients with schistosomiasis were studied in the presence and absence of indomethacin in the culture medium. PBMN cultures were exposed to antigenic extracts of either adult S. mansoni worms (SWAP) or cercariae (CAP), and assayed for the incorporation of tritiated thymidine. More than 70% of the 48 patients studied with SWAP and the 40 patients studied with CAP, were not substantially effected by the addition of indomethacin to the cultures. The remainder (less than 30%) was augmented more than 50% by indomethacin and comprise a group which gave initially low responses to these antigenic preparations. Further analysis indicated that in some schistosomal patients the effect of an adherent suppressor cell population may, in part, be based on a prostaglandin-mediated, indomethacin-sensitive suppressive mechanism. However, the majority of patients, most of whom display adherent suppressor cells, are unaffected by indomethacin. Apparently, other adherent cell suppressor mechanisms are responsible for the regulation observed.

Adolescent↗
PubMed1983

Do lymphocytes from Chagasic patients respond to heart antigens?

Lymphocyte transformation studies of nonadherent lymphocytes from chronic Chagasic and uninfected persons demonstrated that responses of all individuals to a mouse heart homogenate showed a correlation with responses to streptococcal antigens. Considering the known cross-reactions between streptococcal and cardiac antigens and the high reactivity of Chagasic patients to streptococcal antigens, it is possible that positive lymphocyte transformation to unfractionated heart antigen preparations may not represent specific reactivity to heart antigens.

Adult↗
PubMed1982

Serum levels of carcinoembryonic antigen and a tumor-extracted carcinoembryonic antigen-related antigen in cancer patients.

Levels of carcinoembryonic antigen (CEA) and a tumor-extracted CEA-related antigen (TEX) were determined in sera from patients with carcinomas of the breast, colon, lung, head and neck, and a number of miscellaneous categories. The purpose of this study was to compare the levels of each antigen at various stages of malignant disease. Competitive radioimmunoassays developed in our laboratory were shown to be sufficiently specific to detect either of these two antigens independent of each other. The results indicate that: (a) with our specific assays, CEA was not significantly elevated in smoker controls, but TEX was elevated in 29% of smoker controls; (b) TEX was equivalent to CEA as a tumor marker for colonic cancer. TEX was better than CEA as a marker for lung cancer and, based on limited data, there is a possibility that TEX is a significantly better tumor marker than is CEA in early lung cancer; (c) TEX was superior to CEA as a tumor marker for breast and head and neck cancers; (d) there is a strong indication that serial determinations of TEX can be used as effectively as CEA in the monitoring of disease progress. These preliminary results must be confirmed by increasing the number of cancer patients and including nonmalignant disease controls.

Antigens↗
PubMed1981

Comparison of whole blood cultures and peripheral blood mononuclear cell cultures for evaluation of lymphocyte reactivity during chronic schistosomiasis.

Lymphocyte blastogenesis during chronic schistosomiasis has been evaluated previously by either whole blood or peripheral blood mononuclear cell (PBMN) culture techniques. These two methods were compared in the present study. Blastogenesis to the mitogen phytohaemagglutinin was greater in the whole blood cultures at the time assayed. Substantial antigen-induced lymphocyte transformation was elicited in both culture systems using cells from uninfected patients. However, patients' responses to schistosome-derived antigenic preparations as determined by whole blood culture were greatly reduced compared with PBMN cultures. In view of the known immunoregulatory activities associated with sera and cells from infected patients the whole blood technique may better reflect in vivo lymphocyte reactivity. The PBMN cultures are better suited to examine the immunoregulatory activities which may develop during this chronic infection.

Cells, Cultured↗
PubMed1981

Sensitive detection of carbohydrate determinants on carcinoembryonic antigen preparations by lectin and antibody binding using polyethylene glycol.

Blood group determinants have been found in five carcinoembryonic antigen (CEA) preparations with a lectin and antibody-binding assay using polyethylene glycol 6000 to separate free from bound radiolabeled antigen. The assay described gives excellent sensitivity for the binding or inhibition of binding of various lectins or antibodies to CEA. One of the CEA preparations investigated has an A1 determinant, another has a B determinant, and all have H, Lea, Leb, and MN blood group determinants. In addition, all of the preparations tested bound concanavalin A. These findings are consistent with the idea that incomplete or unexpected glycosylation patterns occur in glycoproteins produced by tumor cells. Since antibodies directed against blood group substances cross react with carbohydrate determinants on CEA, clinical determinations of CEA or anti-CEA levels in serum may be adversely affected.

Carbohydrates↗
PubMed1981

Demonstration of elevated anti-Lewis antibodies in sera of cancer patients using a carcinoembryonic antigen-polyethylene glycol immunoassay.

The serum levels of carcinoembryonic antigen (CEA) and CEA-binding proteins of 68 controls and 170 cancer patients were determined. The CEA levels were determined by a double-antibody radioimmunoassay using radiolabeled CEA, and the CEA-binding proteins were determined by an immunoassay utilizing radiolabeled CEA and polyethylene glycol. The major CEA-binding proteins in serum were anti-blood group antibodies as demonstrated by differential binding of serum proteins from A, B, or O positive individuals to radiolabeled CEA's which were previously shown to carry specific blood group determinants. No statistically significant differences were observed for the binding of control versus cancer patient sera to CEA-A (carrying blood group A1), except, as expected, A negative (O or B positive) individuals gave high binding to CEA-A, while A positive individuals gave low binding to CEA-A. Statistically significant differences were observed for controls versus cancer patients for binding to CEA-Lewisab (CEA-Leab). CEA-Leab-binding activity was higher in females and smokers in the control group, but this distinction was not found in the cancer patients. The high levels of anti-Leab antibodies may be explained in females by exposure to fetal antigens during pregnancies and in smokers or cancer patients by exposure to precursors to blood group substances. The sera of 7% of the patients with colonic carcinoma, 18% of the patients with breast carcinoma, and 23% of the patients with bronchogenic carcinoma bound more CEA-Leab than did the serum of the highest male control. A correlation between CEA-Leab-binding activity and the levels of serum CEA was found for patients with colonic carcinoma but was not significant for the groups with other cancers or the control group. Serial determinations of CEA-Leab-binding activity for 21 patients with bronchogenic carcinoma changed congruently with the serum levels of CEA in 12 cases. The significance of these results in terms of expression of immature blood group antigens, the subsequent production of antibodies against them, and the prognostic value of this response is discussed.

Breast Neoplasms↗
PubMed1980

Immune responses during human schistosomiasis mansoni. VII. Further analysis of the interactions between patient sera and lymphocytes during in vitro blastogenesis to schistosome antigen preparations.

The lymphocyte blastogenic responses of chronic schistosomiasis mansoni patients were tested in vitro in medium supplemented with either normal human serum or patients' serum (either autologous or third party). As expected, when patients' lymphocytes were cultured in patient sera, many of them (75--78%) displayed reduced responsiveness to schistosome antigens (derived from either the cercariae, adult worms or eggs of Schistosoma mansoni), but not to Candida albicans extract. For decreased blastogenesis to be manifest, a combination of both suppressive sera and suppressible cells was required; however, some patients had nonsuppressible cells and not all sera were suppressive. In an attempt at classification, four categories of patient responsiveness concerning serosuppression are proposed. The categories depend on the suppressive capabilities of patient sera and the response of patient lymphocytes to suppressive sera. By individually testing the capabilities of each patient's lymphocytes and sera in relationship to each antigenic preparation, we were able to assign the majority of patient responses to a given category. It is hoped that by using these categories, a better understanding of the mechanisms concerning serosuppression will be obtained.

Antigens↗
PubMed1979

Immune responses during human schistosomiasis mansoni. VI. In vitro nonspecific suppression of phytohemagglutinin responsiveness induced by exposure to certain schistosomal preparations.

Simultaneous in vitro exposure of human peripheral blood mononuclear cells to phytohemagglutinin-P (PHA) and either soluble schistosomal egg antigenic preparation (SEA) or soluble cercarial antigenic preparation (CAP) obtained from Schistosoma mansoni resulted in decreased responsiveness as compared to exposure to PHA alone. The addition of a soluble adult worm antigenic preparation (SWAP) did not predictably alter PHA responses in this system. The suppression due to in vitro exposure to either SEA or CAP was expressed whether the lymphocyte donors were S. mansoni patients (early infection, chronic, or treated), or uninfected subjects. The degree of suppression was related to the concentration of SEA used, and the timing of exposure. Preexposure to SEA for 3 days before the addition of PHA resulted in more potent suppression. However, a delay in the time of the addition of SEA of 6 and 24 hr after PHA exposure decreased and eliminated, respectively, its suppressive capacity. SEA and CAP were not directly toxic to responding cells, and appeared to exert their nonspecific suppressive influences through T lymphocyte-related mechanisms. It was observed that although these suppressive events could be induced and observed in vitro, the responsiveness of S. mansoni patient lymphocytes to PHA was equal with that of uninfected controls.

Antigens↗
PubMed1978

Amino-terminal sequence of a carcinoembryonic antigen-like glycoprotein isolated from the colonic lavages of healthy individuals.

A glycoprotein has been isolated from the colonic lavages of healthy individuals that is immunologically equivalent to carcinoembryonic antigen purified from tumor tissue. The NH2-terminal sequence of the glycoprotein from normal colon lavages is Lys-Leu-Thr-lle-Glu-Ser-Thr-Pro-Phe-(Asn)-Val-Ala-Glu-Gly-Lys-Glu-Val-(Leu,lle)-(Leu,lle)-(Leu,lle)-Val-(His,Arg?)-?-(Leu,lle). This is homologous to the NH2-terminal sequence of 23 of the first 24 amino acids of carcinoembryonic antigen isolated from tumor tissue.

Amino Acid Sequence↗