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Biomedical subjects

A J Cochran

Publications and source records attributed to A J Cochran.

At least 127 records · Page 7Linked to original sources

Incidence and type of tumors induced in C57BL bg/bg mice and +/bg littermates by oral administration of DMBA.

As an attempt to study the effect of the beige (bg) mutation on chemical carcinogenesis, 65 C57Bl/bg/bg mice and 83 +/bg littermate controls received DMBA in five weekly intragastric doses. The incidence of tumors of different histological types was monitored through observation periods ranging between 165 and 500 days. By 165 days after the first DMBA feeding, 18% of the +/bg and 31% of the bg/bg mice had developed tumors. The beige mice had a higher incidence of epithelial and non-epithelial tumors arising in cutaneous or subcutaneous sites than the controls. The total incidence of lymphomas was similar in the two groups. However, lymphomas appeared somewhat earlier in beige than in control mice. Altogether 33 +/bg and 27 bg/bg mice were followed for 500 days. By this time, 73% of the +/bg and 78% of the bg/bg mice had developed tumors. The beige group showed a higher incidence of non-thymic lymphomas than the controls. In contrast, the incidence of thymic lymphoma, cutaneous epithelial tumors and bile-duct adenomas was similar in the two groups or higher in +/bg that in bg/bg mice. The results suggest that the bg mutation causes a certain defect in a mechanism that may prevent or delay the onset of non-thymic lymphomas and of epithelial and non-epithelial cutaneous tumors in DMBA-treated mice. The differences between the two groups were smaller than those previously reported in relation to the increased susceptibility of beige mice to certain transplanted tumors, attributed to the known defect in natural killer (NK) activity in the beige mice. The reduced differential in the DMBA system may be due to the partial reduction of NK activity, induced by the carcinogen, as reported previously (Ehrlich et al., 1980) and confirmed in the present study.

9,10-Dimethyl-1,2-benzanthracene↗

A comparison of the macrophage electrophoretic mobility test and the leukocyte migration inhibition test in the detection of histocompatibility antigens on tumor cells.

Lymph node cells from mice sensitized by rejection of skin allografts were incubated in vitro with tumor cells carrying the sensitizing alloantigens. Products of the lymphocyte--antigen interaction released into the culture medium were simultaneously assessed by the macrophage electrophoretic mobility test and the leukocyte migration inhibition assay. Both macrophage slowing factor (MSF) and a factor which inhibited leukocyte migration (LIF) were produced. The release of both factors was detectable after comparable periods of incubation; their production was transient and ceased within 24 hours after it started.

Animals↗

Tumor-directed immunity in neuroblastoma patients and their related and unrelated contacts.

Tumor-directed cell-mediated and humoral immunity were assessed in vitro in neuroblastoma (NB) patients, and also in their relatives and genetically unrelated contacts, using the one-stage, direct, capillary leukocyte migration inhibition (LMI) test and the indirect, membrane, immunofluorescence test (IFT), respectively. Leukocytes from 83% and sera from 50% of NB patients examined were selectively reactive with NB cells, and materials derived from them. Genetically unrelated contacts as well as relatives of NB patients showed NB-directed immunity, the frequency of which increased with increasing closeness of contact with these patients. These findings suggest that the environment of NB patients may contain some tumor-derived material which induces detectable sensitization in those sharing that environment. Such tumor-derived material would appear to have a high degree of infectivity, low degree of oncogenicity, and probably also a low general pathogenicity.

Antibody Formation↗

In vitro reaction of cancer patients and others to Bacillus Calmette-Gueérin.

We examined the in vitro reaction of leukocytes from 71 cancer patients and 121 control donors (disease-free individuals or patients with non-malignant non-debilitating conditions) against Bacillus Calmette-Guérin using a one-stage capillary leukocyte migration assay. The proportion of reactive cancer patients and control donors increased with increasing BCG concentration, but the proportion of patients who reacted was less than that of control donors at all concentrations of BCG. As cancer stage advanced and the volume of clinically detectable tumor increased, the proportion of reactive patients decreased. There was a small age-related decline in reactivity in the control population. The results of simultaneous in vitro tests and Mantoux reactions were concurrent in a majority of normal individuals so tested.

Adolescent↗

Indirect leukocyte migration assay in patients with malignant melanoma.

Leukocytes from 72 melanoma patients and 75 control donors were examined in a two-stage (indirect) leukocyte migration assay, using formalin-fixed melanoma cells (FMC) and control, normal or non-melanoma tumour cells (FCC) as the source of antigen. Inhibitory supernatants were produced significantly more often by cultures of melanoma leukocytes and FMC than by melanoma leukocytes and FCC or control leukocytes and FMC or FCC. Reactive leukocytes were most frequently derived from stage II patients (65%), followed by stage I patients with tumour present (58%), stage III patients (29%) and stage I patients without detectable tumour (20%). The likelihood that a melanoma patient's leukocytes would react increased progressively with the number of different FMC preparations tested. A similar, though less steep increase in reactivity was seen with control donor leukocytes and different FMC preparations. No significant increase in reaction frequency was seen with melanoma or control leukocytes exposed to increasing numbers of different FCC preparations. Significant discrimination between melanoma patients' and control donors' leukocytes was achieved with FMC from both primary and metastatic tumours. Concordance of positivity or negativity was seen in 60% of concurrent one-stage and two-stage leukocyte migration assays.

Adult↗

Cellular fine structure in the invasive nodules of different histogenetic types of malignant melanoma.

Ultrastructural studies were carried out on the invasive nodule of forty malignant melanomas. The findings support the concept that the fine structure of lentigo maligna melanoma is often characteristic, and differs from that of superficial spreading and nodular melanoma. The melanosomes in lentigo maligna melanoma are usually ellipsoidal and resemble those of normal melanocytes, whereas the melanosomes in superficial spreading and nodular melanoma are most often spheroidal and abnormal in appearance. Superficial spreading and nodular melanomas cannot be distinguished reliably by their ultrastructure. Melanosomal appearances could not be related to the presence of a pre-existing naevus or the depth of invasion of the tumour nodule.

Humans↗

Leukocyte migration inhibition by cancer patients' sera.

Sera from 38 of 89 melanoma patients, 4 of 15 patients with other cancers and 3 of 43 control donors inhibited the migration of autologous leukocytes. Sera from patients with clinically detectable metastatic disease and from the recipients of BCG were most frequently inhibitory. Autologous sera from 31 of 71 melanoma patients and 3 of 31 control donors increased the leukocyte migration inhibition induced by formalinized melanoma cells. This activity occurred in sera from patients at all stages of malignancy, whether bearing detectable tumour or not and whether receiving BCG or not. Abrogation of tumour-cell-induced leukocyte migration inhibition by serum was less frequent, occurring with 8 of 71 melanoma patients (6 Stage III, 1 Stage I and 1 Stage II) and no control sera. Preincubation of formalinized tumour cells had no effect on their activity in the leukocyte migration assay but the preincubation of melanoma leukocytes with either autologous serum or foetal calf serum inhibited leukocyte reactivity in around 50% of tests. However, this was also seen with control leukocytes and the effect appears to be immunologically non-specific.

Animals↗

An examination of the immunology of cancer patients.

We have examined 111 cancer patients and 111 control individuals for general immunocompetence (haematological values, "recall" antigen skin tests, PHA and PPD induced lymphocyte transformation, serum Ig levels and lymphocyte subpopulations), for evidence of sensitisation to tumour-associated antigens (leucocyte migration test, serum inhibition of autologous leucocyte migration, lymphocytotoxicity, membrane immunofluorescence and immune adherence) and for evidence of continuing immune reactions (alterations of complement components and anticomplementary activity). Major differences between the cancer patients and controls were demonstrated by several tests of sensitisation and these also detected differences between patients with and without metastases. The only differences detected between cancer patients and controls by the tests of general immunocompetence were in serum IgG and IgA (higher in the cancer patients) and lymphocyte subpopulations ("active" T, autorosetting lymphocytes and lymphocytes forming "super-rosettes" increased in cancer patients). In a comparison of cancer patients with and without metastases, patients with metastases were less often reactive to the Candida DHS and streptokinase-streptodornase antigens and had raised circulating Fc positive cells. Abnormalities of the individual components of complement occurred in about half the cancer patients, but were equally common in those with and without metastases. Serum anti-complementary activity was very rarely detected. The tests of specific sensitisation correlated reasonably well but correlations of tests of general immunocompetence were infrequent.

Adolescent↗

Sensitisation of neuroblastoma patients and related and unrelated contacts to neuroblastoma extracts.

Sensitisation to neuroblastoma extracts was tested by the leucocyte migration inhibition technique in 8 neuroblastoma patients, 22 relatives, and 49 unrelated contacts. All three groups showed a high frequency of positive reactions compared with 61 controls having no exposure to neuroblastoma. The frequency of sensitisation could be related to closeness of contact, but the nature of the sensitising material and its mode of transmission are unknown. Virus studies by the sensitive techniques of tumour virology are suggested. The absence of case clustering and the low familial incidence of neuroblastoma indicate that simple exposure to the tumour is not a major oncogenic factor.

Age Factors↗