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Biomedical subjects

D W Thomas

Publications and source records attributed to D W Thomas.

At least 217 records · Page 12Linked to original sources

T lymphocyte recognition of peptide antigens: evidence favoring the formation of neoantigenic determinants.

To more precisely define the nature of exogenous antigenic determinants recognized by T cells, the response to fibrinopeptide fragment B beta 7-14 and a peptide of the inverted amino acid sequence of B beta 7-14 was examined. Strain 2 guinea pig T cells immunized with B beta 7-14 showed in vitro proliferative responses with B beta 7-14, but failed to respond to the inverted B beta 7-14 peptide. Moreover, the inverted B beta 7-14 peptide was nonimmunogenic and failed to prime strain 2 T cells for responses to native or inverted B beta 7-14. These results suggest that T cell recognition of peptide antigens involves more than simple interactions with amino acid side chains and that the ordering of the amino acids within the peptide is critical. One interpretation of these results is that T cells exhibit polarity in reading of antigenic determinants and peptides become associated with self in some fashion to form a neoantigenic determinant. To test this possibility, a Gly residue was added to the carboxyl end of B beta 7-14 (B beta 7-15), which is the likely site of attachment to self. It was found that strain 13 guinea pigs, which are totally unresponsive to B beta 7-14, produced T cell responses to B beta 7-15. This observation is consistent with the interpretation that Gly spaces the B beta 7-14 away from self to form an antigenic determinant complementary to strain 13 T cell antigen recognition structures. These results are discussed with respect to several mechanisms for immune response gene control of T cell responses.

Amino Acid Sequence↗

Spectrum of amebiasis in children.

In 11 patients with childhood amebiasis, only two had dysentery. Additional clinical findings included hematochezia without diarrhea (four patients), dysentery with appendicitis (one patient), exacerbation of ulcerative colitis (two patients), and disseminated infantile amebiasis (two patients). All patients with hematochezia examined by proctosigmoidoscopy had colitis. The diagnosis of amebiasis was confirmed by microscopic examination of fresh stool specimens, pathologic findings, and/or serologic titers. Amebiasis should be considered in the differential diagnosis of infants and children with hematochezia or hepatomegaly, especially in endemic areas.

Adolescent↗

Characterization of a 75,000 mol. wt glycoprotein synthesized by guinea-pig T-lymphocytes: a possible homologue of Lyt-1 antigen.

A xenoantiserum raised in rabbits by immunization with strain 13 guinea-pig antigen-activated T-lymphocytes was previously found to recognize a non-immunoglobulin, 75,000 mol. wt glycoprotein synthesized by guinea-pig T-cells. This protein, p75, has been further characterized to determine its biochemical properties and its expression by various cell types. p75 was found to be a single-chain protein which could be bound by the lectin Lens culinaris hemagglutinin. It has an apparent mol. wt slightly greater than mu-chain as assessed by SDS-polyacrylamide gel electrophoresis and could not be precipitated by anti-guinea-pig immunoglobulin reagents. It exhibited considerable charge heterogeneity during isoelectric focusing and was not affected by neuraminidase treatment, p75 was synthesized by thymus, spleen and lymph node cells, by antigen-stimulated T-cells from strain 13 and strain 2 guinea-pigs, and by guinea-pig B-cell L2C leukemia lines, but not by normal B-lymphocytes or macrophages. No differences between the isoelectric focusing patterns of p75 molecules isolated from different cell types could be demonstrated. The chemical properties of p75 and its expression by the cell types so far examined indicate that p75 is a possible candidate for the guinea-pig homologue of the murine Lyt-1 antigen.

Animals↗

Hypercalcemia associated with parenteral amino acid and dextrose infusion.

A patient receiving parenteral nutrition with an amino acid dextrose solution developed hypercalcemia which seemed related to the rate of nutrient infusion. In a retrospective study of patients receiving parenteral nutrition over a 3-month period six of 72 (8%) developed hypercalcemia. After changes in infusion rate there were corresponding changes in the serum calcium concentration. There was a significant correlation between the serum calcium concentration and the average infusion rate over the preceding four days (p = 0.012). This was even more significant (p less than 0.005) when ionized calcium was calculated to diminish the effects of calcium binding by proteins.

Adolescent↗

Evaluation of an immunological test for occult bleeding from colorectal neoplasia.

A study to determine the reliability of a recently described test, the faecal human haemoglobin test (FHH), specific for human blood, in the detection of colorectal neoplasia, is reported. All of nineteen patients with proven cancers studied were shown to have detectable blood in the stools. Three of five patients with polyps in this series also had detectable blood in the stools by this test. Although three of nineteen control subjects had positive tests, two of these were subsequently found to have bleeding sites, and the third was normal on follow up some weeks later. The findings are discussed in relation to the Hemoccult II (H-O) test results obtained in these subjects, and the implications for the possible future role for this test in screening for colorectal neoplasia.

Adenocarcinoma↗

Evidence for covert cellular interaction sites expressed by activated T lymphocytes.

In this report we examined the effects of trypsin treatment of immune guinea pig T lymphocytes on their binding to syngeneic macrophages. Immune T cells positively selected by culture for 1 wk with antigen and treated with trypsin showed dramatic binding to macrophages in the absence of additional antigen. This binding was rapid and greatest at 1 hr after the addition of trypsin-treated T cells to macrophages. Thereafter, the bound T cells dissociated from the macrophages and did not rebind. Dissociation of macrophage-bound T cells appeared to be an active process that could be inhibited by blocking T cell protein synthesis. Macrophage binding by trypsin-treated T cells was dependent on prior in vitro stimulation; similar treatment of immune T cells taken directly from the animal did not augment binding, and treatment of T cells cultured without antigen resulted in only modest binding. In addition, the trypsin-induced binding phenomenon showed elements of genetic restrictions. Trypsin treatment of immune T cells selected by culture for 1 wk with antigen resulted in preferential binding to syngeneic macrophages. In addition, immune F1 T cells selected by culture with antigen-pulsed parental macrophages preferentially bound to macrophages of the haplotype used for selection. Evidence is presented suggesting that the trypsin-induced binding was not simply due to antigen carry-over from the trypsinized lymphocytes and favoring the possibility that this binding may be antigen-independent. These results suggest that antigen-activated T cells express covert interaction sites for macrophages and that these sites are actively covered-up by other membrane components.

Animals↗

Perinatal transmitted acute icteric hepatitis B in infants born to hepatitis B surface antigen-positive and anti-hepatitis Be-positive carrier mothers.

Three infants born to mothers who were hepatitis B surface antigen (HBsAg) positive and had antibody to hepatitis Be antigen (anti-HBe), developed acute icteric hepatitis B within three months of birth. All three infants clinically recovered and developed circulating anti-HBs. Contrary to previous studies, these three cases indicate that mother-infant transmission of the hepatitis B virus (HBV) does occur in infants born to HBsAg-positive, HBe-Ag-negative carrier mothers, and these infants may develop severe acute icteric hepatitis. Therefore, immunoprophylaxis in such newborns may be indicated.

Adult↗

Fine specificity of genetic regulation of guinea pig T lymphocyte responses to angiotensin II and related peptides.

Guinea pig T lymphocyte responses to the octapeptide antigen angiotensin II (NH(2)-Asp(1)-Arg(2)-Val(3)-Tyr(4)-Ile(5)-His(6)-Pro(7)-Phe(8)-OH; AII) were examined using various synthetic peptide analogues and homologues. Each peptide antigen was assessed for immunogenicity and antigenicity in strain 2 and strain 13 guinea pigs as determined by in vitro T cell proliferative responses. The genetic control of T cell responses to these peptides was found to be highly specific and capable of distinguishing subtle differences in the antigens. For example, strain 2 guinea pigs responded to AII and were low responders to [Val(5)]-AII, whereas strain 13 animals responded to [Val(5)]-AII but not to AII. The genetic control in this case involved the difference of one methyl group between Val(5) and Ile(5). Differences in T cell responsiveness by strain 2 and strain 13 guinea pigs were also observed with analogues involving para substitutions on the phenyl ring of Tyr(4) and of Phe(8). However, the genetic regulation of T cell responses did not seem to be based on a single peptide residue. For example, removal of Asp(1) allowed strain 13 animals to respond to the Ile(5)-containing analogue, but eliminated responsiveness to the Val(5)-containing analogue. Thus, the first and fifth AII residues are both involved in the regulation of strain 13 T cell responses. Substitutions for Tyr(4) and Phe(8) suggested that the same residue may serve to alter the specificity of T cell responses in one strain, and determine responsiveness or unresponsiveness in the other strain. One of the most striking observations is that T cell responsiveness to the various AII analogues and homologues randomly fluctuates between strain 2 and strain 13 guinea pigs, and in general neither strain responds to the same peptide antigens. This suggests that strain 2 and strain 13 T cell responses are rarely directed against the same antigenic determinants, and that the T cell antigen-combining diversity is usually exclusive between these two strains. These results are discussed with respect to the specificity of Ir gene control and the relationship between Ir gene function and antigen recognition by T cells. Note added in proof: More recent experiments using a new lot of [Val(5)]- AII have indicated that [Val(5)]-AII-immune strain 2 T cells show significant stimulation with AII but remain relatively low responders with [Val(5)]-AII, as shown in Table I. The difference in priming for cross-reactivity for AII with the different lots of [Val(5)]-AII is at present unknown.

Angiotensin II↗

A pilot study of some associations between behavioural stressors and physiological processes in healthy men.

A study was made of the physiological effects of smoking, psychological stressors, heat, exercise, and fat ingestion on 12 healthy men. Repeated measurements were made of cardiovascular, neuroendocrine, enzyme, lipid, and other variables in all stressor situations. The main findings were that psychological stressors and exercise were associated with more and larger physiological changes than the other stressors, and widespread response differences in addition to those in lipids were identified between subgroups of seven normolipidaemic men and five hypertriglyceridaemic men.

Adrenal Cortex Hormones↗