Biomedical subjects
Publications and source records attributed to R M Grant.
A 11-year-old boy developed purpura on the back and chest on more than 5 occasions following vigorous exercise. This eruption should be added to the list of differential diagnosis of the dermatosis experienced by athletes.
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Forty-nine percent of homosexual/bisexual men were positive for antibody to the human immunodeficiency virus (HIV) in a population-based probability sample of 1034 single men recruited from San Francisco. All heterosexual men were negative. Among seropositive men, marked lymphadenopathy was present in 29%, and 16% had at least two other symptoms or signs suggestive of HIV infection. However, lymphadenopathy alone failed to indicate severity of immune impairment. The occurrence of two or more clinical signs and symptoms, except for marked lymphadenopathy, correlated with HIV infection, diminished skin test reactivity, and reduction in Leu 3a T cells. Twenty-nine percent of seropositive men had fewer than 400 absolute Leu 3a T helper cells per microliter (less than 0.4 X 10(9)/L). Seronegative homosexual/bisexual men did not differ from heterosexual men in any clinical or laboratory variables except for increased numbers of suppressor Leu 2a T suppressor cells per microliter.
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The concentration of drug after oral administration of 1 g misonidazole to patients undergoing neurosurgery has been studied in samples taken from intracerebral tumours, normal brain, cerebrospinal fluid and brain tumour cyst fluid. A total of 31 patients yielded samples at various times 2-8 h after drug administration. Results show a considerable range of tumour/plasma percentages but from about 2-5 h after drug administration this averaged between 65-80%. Normal brain and CSF showed similar good penetration but drug entry into cyst fluid was lower (30-50%). A further study with desmethylmisonidazole given to 11 additional patients showed a similar range of tumour penetration but lower concentrations in CSF and cyst fluid (10-20%). Low values were also seen in some but not all of the normal brain tissue samples. Necrotic tumour also had much lower concentrations than macroscopically viable tissue. These results are discussed in terms of their clinical relevance to sensitiser studies on patients with brain tumours with drugs of different lipophilicities.
Selected monoclonal antibodies (McAbs) isolated after immunization of rats with a human colonic carcinoma membrane preparation, have been screened on frozen and paraffin sections of colonic tissue, using immunohistochemical techniques, in order to provide additional information with regard to specificity and crossreactivity with normal tissues.Of 10 McAbs previously shown to bind to a colonic carcinoma membrane preparation in a radioimmunoassay, 7 show specific staining when tested by indirect immunofluorescence on crysotat sections of colonic tissue. Three of these 7 show activity on both normal and malignant colonic epithelium, and the remaining 4 stain normal epithelium, with little or no activity on malignant tissue. In the indirect immunofluorescent and immunoperoxidase techniques on paraffin sections of the same material, only 2 McAbs retain activity; one detects an antigen in colonic mucus, and the other recognises an antigen which is sparse on normal colonic epithelium and abundant on colonic tumours.We conclude that screening of McAbs on frozen tissue sections, using indirect immunofluorescence, is a useful adjunct to conventional screening methods, e.g. binding to membrane preparations and/or cell lines in a radioimmunoassay. These techniques distinguish McAbs with similar binding values in conventional assays, identify their activity on a wide range of normal and malignant tissues, demonstrate antigens that are lost or gained in malignant transformation and finally assist in the selection of McAbs for further extensive study before possible clinical use.
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.
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Immunization studies indicate that formalinized tumour cells retain at least part of their gross membrane structure and antigenicity; they are relatively easy to prepare and store well over a period of months. We have used formalinized tumour cells as antigen in the leucocyte migration inhibition test. Leucocyte migration inhibition occurred in leucocytes from thirty-eight out of sixty-nine malignant melanoma patients and from fifty-five out of eight-one breast cancer patients when in contact with formalinized tumour cells of a histologically similar type. Melanoma patients' and breast cancer patients' leucocytes were infrequently inhibited on contact with cells from histologically dissimilar human tumours and from xenogeneic mouse melanomas. Other advantages of formalinized cells over antigens prepared by homogenizing tumour tissue include a greater degree of inhibition and the ability to demonstrate a dose-response relationship between the ratio of leucocytes:tumour cells and the migration index.
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