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Biomedical subjects

W J Halliday

Publications and source records attributed to W J Halliday.

At least 55 records · Page 3Linked to original sources

Regulation of cell-mediated immunologic reactivity to Moloney murine sarcoma virus-induced tumors. II. Nature of blocking and unblocking factors in serum.

Serum blocking factors, detected in sera of inbred CBA and BALB/c mice with progressing virus-induced tumors by their interference with leukocyte-adherence inhibition (LAI) with the use of syngeneic leukocytes, were found to be strain related: No blocking occurred with allogeneic leukocytes. Furthermore, the unblocking factors of regressor serum were also strain related: No unblocking of allogeneic progressor serum was observed. There was no requirement for H-2 compatibility between leukocytes and tumor cells from which the LAI-inducing antigen was obtained. Absorption of CBA blocking serum with anti-I-Jk antiserum (and with anti-Ik containing this antibody specificity) removed blocking activity; absorption of regressor serum did not reduce its unblocking activity. These observations indicated that certain blocking factors resembled other suppressor factors in possessing antigenic determinants coded by the I-J subregion of the major histocompatibility complex. Their strain restriction and antigen specificity suggested combination with reactive lymphocytes in blocking LAI. The properties of unblocking factors suggested they combine with blocking factors and resemble antiidiotypic antibodies.

Animals↗

Augmentation of E-rosette formation by lymphocytes of cancer patients stimulated in vitro with tumor extracts.

The ability of tumour extracts to augment E-rosette formation by cancer patients' lymphocytes was demonstrated for colorectal carcinoma, breast carcinoma and melanoma. Positive augmentation reactions were obtained with 14 to 20 patients tested with extracts related to their own tumour types. Some lack of specificity was suggested by 5 positive reactions in the same patients tested with unrelated extracts. No false positives were found in normal subjects. The technique is simple, rapid and appears to depend on tumour-associated antigens in the extracts. Simultaneous leucocyte adherence inhibition tests on split samples of blood had a high degree of sensitivity and specificity, confirming the potential reactivity of the leucocytes and extracts used.

Humans↗

Properties of a murine lymphokine that augments E-rosette formation.

Antigenic stimulation of spleen mononuclear cells from contact-sensitized mice produced a soluble factor that enhanced the formation of E-rosettes by human lymphocytes in vitro. Production of this murine E-rosette augmenting factor (E-RAF) occurred over a narrow range of antigen concentrations, was hapten-specific, and depended on T-lymphocytes. The factor was not dialysable, in contrast to other substances extracted from normal leucocytes. Murine E-RAF is thus a lymphokine whose action is not species restricted. It was readily detected 30 min after contact of cells with antigen. E-RAF formation by spleen cells and delayed-type hypersensitivity reactions were elicited over a similar period after contact sensitization of mice.

Animals↗

Leukocyte adherence inhibition: tumor specificity of cellular and serum-blocking reactions in human melanoma, breast cancer, and colorectal cancer.

Blood samples were obtained from hosptial patients suspected of having cancer (colorectal carcinoma, breast carcinoma, or melanoma) or from patients after surgical treatment for these cancers. Leukocytes were tested for reactivity with appropriate tumor extracts by leukocyte adherence inhibition (LAI), without knowledge of the diagnosis. Leukocytes from each patient were tested with the specific related extract corresponding to the suspected tumor type and with at least one unrelated extract. Each patient's serum was tested for its effect on the adherence of autologous leukocytes with specific tumor extract. Detailed leukocyte adherence data are presented for each of the 110 patients. Of the 75 patients eventually diagnosed as having cancer of one of the above types, 67 (89.3%) gave positive specific LAI reactions and only 5 (6.7%) reacted nonspecifically. Of the 35 patients with benign, unrelated, or unidentified disease, 10 (28.6%) gave positive reactions; most of these were patients with benign breast disease reacting with breast tumor extract. Leukocyte reactions with related extracts were almost always blocked by autologous serum (only two exceptions). When tested with allogeneic leukocytes reacting with their corresponding extracts, sera never blocked leukocytes of a different tumor type; in some cases they also failed to block leukocytes of the same tumor type although autologous leukocytes were blocked.

Antigens, Neoplasm↗

The nature of piecemeal necrosis in chronic active hepatitis.

On the basis of histological studies, it is proposed that the type of liver-cell death in piecemeal necrosis is apoptosis. The characteristic inconspicuousness of apoptosis explains why the mode of hepatocyte elimination in piecemeal necrosis has hitherto remained obscure. Cell-mediated immune attack induces apoptosis, not classical necrosis, and the occurrence of apoptosis in piecemeal necrosis links the observed morphological changes in chronic active hepatitis with the other evidence for an autoimmune pathogenesis. It is significant that apoptosis does not evoke inflammation or fibroplasia. In attempting to elucidate the cause of the fibrosis that accompanies progression to cirrhosis in chronic hepatitis, it may thus be more relevant to study the effect on fibroblasts of substances liberated during lymphocyte-hepatocyte interactions than the death of the hepatocytes.

Autoimmune Diseases↗

Tumor-associated immunity in bovine ocular squamous cell carcinoma detected by leukocyte adherence inhibition microassay.

A microplate modification of the leukocyte adherence inhibition (LAI) assay was used with blood leukocytes from cattle with ocular squamous cell carcinomas (OSCC); control groups were cattle with ocular or cutaneous lesions (not carcinoma) and healthy normal cattle. For the assay, saline extracts of OSCC and skin from the same donor, lymphosarcoma, and mastocytoma (M) were used as antigens. Specific LAI reactivity to OSCC extract (but not to skin extract) was detected in 14 of 18 animals with squamous cell carcinoma. One animal with OSCC showed LAI reactivity to OSCC extract, but 1 clinically normal cow had LAI with the M-extract. Leukocyte adherence stimulation reactions with the various antigens were seen in all groups of animals.

Animals↗

The cellular mechanism of leukocyte adherence inhibition.

Human blood leukocytes from three subjects who had been contact sensitized to dinitrochlorobenzene were used in direct and indirect leukocyte-adherence-inhibition (LAI) reactions in an attempt to elucidate the cellular mechanism of reactivity. The leukocytes were separated and purified by standard procedures. In direct LAI, only T cells or populations containing T cells gave positive reactions (significantly reduced adherence) with the antigen. Supernatants from suitable leukocyte-antigen mixtures contained a soluble leukocyte-adherence-inhibition-factor (LAIF) that reduced the adherence of normal leukocytes. Only T cells or populations containing T cells were active in LAIF production; B cells, granulocytes, and monocytes were inactive. The cellular requirement for the action of preformed LAIF was not restricted: all major types of blood leukocytes were susceptible to its effect.

B-Lymphocytes↗

Historical background and aspects of the mechanism of leukocyte adherence inhibition.

The development of leukocyte adherence inhibition is traced from early experiments with murine tumors to recent applications in human cancer and in cell-mediated immunity in general. Arbitrary experimental conditions (serum in culture medium, preincubation, and tumor extracts at a single concentration) were initially set up and permitted detection of specific inhibition of adherence of sensitized leukocytes reacting with antigen of the tumor extracts. Blocking serum completely or partially restored adherence. It was readily demonstrated that leukocyte adherence inhibition was mediated by a soluble lymphokine-like factor [leukocyte adherence inhibition factor (LAIF)]. Recent studies suggest that serum is important in enabling detection of LAIF; this may explain the inability of some other workers to confirm our findings. Serum appears to protect LAIF from enzymatic destruction in mixtures containing tumor extracts. Complex cell interactions are involved in LAIF production. With mouse cells in vitro, macrophages are required for production by both T- and B-lymphocytes, and there is evidence for suppressor cells also.

Animals↗

Hemocytometer leukocyte adherence inhibition technique.

The hemocytometer leukocyte adherence inhibition technique was employed in a criss-cross experimental design with two cancer patients (melanoma and colon carcinoma) and the corresponding tumor extracts. These extracts had been repeatedly tested for specific reactivity and lyophilized before transport to the workshop. The patients' leukocytes were mixed singly with each extract in the presence of normal serum, and the adherences of the cells were determined in hemocytometer chambers. Actual cell counts (total cells before washing and adherent cells after washing) are given in detail for the first time. Blood samples and reaction mixtures were coded by an independent observer. Determination of mean % adherence (+/- S.E.) showed that the melanoma patient's leukocytes (original adherence 70.8 +/- 2.8) reached with the melanoma extract (40.7 +/- 2.9; p less than 0.001) but not significantly with the colon carcinoma extract (61.5 +/- 4.1; p greater than 0.05). Similarly, the colon carcinoma patient's leukocytes (original adherence 68.6 +/- 2.7) reacted with the colon carcinoma extract (43.2 +/- 2.3; p less than 0.001) but adherence was not inhibited by the melanoma extract (76.9 +/- 2.6). The cancer patients were thus correctly identified with regard to tumor type in a simple blind trial.

Antigens, Neoplasm↗

Cell-mediated immunity to bacterial flagellin as assessed by leucocyte adherence inhibition.

Leucocyte adherence inhibition (LAI) was used to detect cell-mediated immunity of mice to Salmonella adelaide polymeric flagellin and its monomeric derivative. In the direct LAI technique, antigen inhibited the in vitro adherence to glass of peritoneal cells (PC) from antigen-primed mice which were capable of exhibiting in vivo delayed hypersensitivity reactions to the same antigen. In the indirect technique, primed PC exposed to antigen in vitro released a soluble factor, which inhibited the adherence of normal PC. Production of the factor was prevented by prior treatment of primed PC with anti-theta serum, indicating the participation of T-lymphocytes. The LAI reaction could be blocked by serum from mice which had been re-injected with antigen 72 h after a priming injection. Features of the production and biological properties of serum blocking activity suggest that it may be attributed to antigen-antibody complexes.

Animals↗

Studies of contact hypersensitivity and tolerance in vivo and in vitro. I. Basic characteristics of the reactions and confirmation of an immune response in tolerant mice.

Contact hypersensitivity to dinitrochlorobenzene (DNCB), picryl chloride (PCl) or oxazolone was induced in mice by skin painting with these agents, and was measured by skin testing in vivo using the ear swelling method. Prior administration of dinitrobenzene sulfonate (DNBS) or picryl sulfonic acid prevented sensitization to DNCB and PCl, respectively. Both this tolerization and the original sensitization were specific for the hapten used. Cyclophosphamide given before sensitization enhanced skin reactions, but when given before tolerization it interfered with establishment of tolerance. Cells from both sensitized and tolerized mice were shown to be reactive with the corresponding haptens in vitro in the leukocyte adherence inhibition (LAI) reaction. LAI specificity was similar to that found for cutaneous reactivity. The reaction of DNCB-sensitized cells with DNBS led to the production of a soluble mediator which induced LAI in normal cells. The demonstration of potentially reactive cells in mice judged to be tolerant by skin testing indicates the concomitant existence of suppressor factors.

Animals↗

A modified leukocyte adherence inhibition test in the laboratory investigation of gastrointestinal cancer.

A modification of the leukocyte adherence inhibition (LAI) technique has been used to test 60 hospital patients with gastrointestinal symptoms, for specific immunoreactivity against extracts of tumours of colon, pancreas and stomach. The modified technique employed mononuclear cells and soluble tumour extracts in glass test tubes, the non-adherent cells being enumerated in an electronic counter. Laboratory tests were completed before the eventual diagnosis was known. Groups of patients with adenocarcinoma of colon or rectum (11), carcinoma of pancreas (3) and adenocarcinoma of stomach (6) were clearly distinguished from each other and from patients with non-malignant diseases or with neoplasms of different histological type.

Adenocarcinoma↗

An evaluation of leukocyte adherence inhibition in the immunodiagnosis of colorectal cancer.

The leukocyte adherence inhibition technique was used to assess cell-mediated immunoreactivity and serum-blocking factors related to adenocarcinoma of the colon or rectum. In the group of 48 patients with confirmed tumors of this type, 36 of 38 had reactive leukocytes and 46 of 47 had serum-blocking factors. Patients whose tumors had been removed surgically, with no sign of recurrence, retained their leukocyte activity for up to 3.5 years in 6 of 6 cases, but only a small proportion (7 of 30) retained blocking factors. In 67 controls (who were patients with nonmalignant gastrointestinal disorders, patients with gastrointestinal tumors other than colorectal adenocarcinoma, patients with other cancers, or healthy volunteers), negative reactions were obtained, with diverticular disease the only prominent exception. The leukocyte adherence inhibition test appeared to be highly sensitive and specific. Application to the immunodiagnosis of colorectal cancer thus seems to be warranted.

Adenocarcinoma↗