AZT + 3TC: early results promising.
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Biomedical subjects
Publications and source records attributed to R Colvin.
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Depression has been previously associated with immunologic dysfunction. The lymphocyte subsets of 10 patients with major depression were found to show a mean T4-T8 (helper-suppressor) ratio lower than that of controls, a difference attributable to increased numbers of suppressor cells in the depressed group. One possible cause of increased suppressor cells is prior or current viral infection.
The accuracy of chest computerized tomography (CT) in detecting malignant hilar and mediastinal involvement by squamous cell carcinoma of the lung is examined. The preoperative chest CT scans of 74 patients with pathologically proven squamous cell lung carcinoma were prospectively and retrospectively reviewed. Criteria for the diagnosis of malignant hilar involvement were nonvascular mass enlarging the hilum; local alteration of hilar contour; adenopathy greater than 1 cm; thickened posterior wall of the bronchus intermedius and distal upper lobe bronchi; and bronchial displacement, compression, and obstruction. Criteria for the diagnosis of malignant mediastinal involvement were confluence of tumor with the mediastinum, altered contour of the azygoesophageal recess, thickened posterior wall of the proximal main stem bronchi, and mediastinal adenopathy greater than 1 cm. Calcified hilar and mediastinal nodes were considered benign. Our results, corrected for reader error, were 92% sensitive, 92% specific, and 96% accurate in the hilum and 95% sensitive, 77% specific, and 82% accurate in the mediastinum. These data support a significant role for chest CT in the preoperative staging of non small cell lung carcinoma.
To better understand the immunologic effects of lymphoid irradiation (LI), blood levels of T cell subsets were sequentially monitored in 15 patients before, during, and after irradiation treatment for Hodgkin's disease. Blood levels of all lymphocytes, T cells, and T cell subsets (defined by OKT4 and OKT8) fell dramatically and in similar proportions during early therapy, reaching levels less than 20 to 25% of control by the completion of mantle irradiation, and continuing at very depressed levels through the completion of therapy. Blood levels of OKT8-reactive (OKT8+) cells returned to pretreatment levels (402 +/- 38/mm3 vs 360 +/- 32/mm3 pretreatment) between 6 to 8 mo after LI, whereas blood levels of OKT4-reactive (OKT4+) cells returned to only 42% of previous values (242 +/- 22/mm3 vs 584 +/- 34/mm3 pretreatment) over the same period. The pre-LI ratio of OKT4+ to OKT8+ cells was 1.85 +/- 0.24 and fell to 0.65 +/- 0.05 between 6 to 8 mo after LI. During the recovery period, discrepancies of 208 +/- 32 cells/mm3 (3 to 5 months post LI) and 198 +/- 32 cells/mm3 (6 to 8 mo post LI) developed between the blood levels of OKT3+ cells and the sum of OKT4+ and OKT8+ cells. This suggests the emergence of OKT4+/OKT3-, OKT8+/OKT3-, and/or OKT4+/OKT8+ cells. In five patients, the sum of OKT4+ and OKT8+ cells was compared with the number of cells simultaneously co-stained by OKT4 and OKT8. It appeared that a significant proportion of the cells were OKT4+/OKT3- and OKT8+/OKT3- lymphocytes. We concluded that LI is similarly cytotoxic to peripheral blood T cell subpopulations. The reversed ratio after LI is a result of a slower repopulation of the peripheral blood by OKT4+ cells relative to OKT8+ cells. T cells after LI show a high degree of antigenic immaturity. It is postulated that the bone marrow that lies outside the fields of treatment and contains predominantly immature OKT8+/OKT3- cells is a major source of T cells repopulating the peripheral blood after LI.
An ovarian carcinoma cell line (OVCA 432) and a B-lymphocyte line (LAZ 446) were established from the same donor. A heteroantiserum (D-100) was prepared in rabbits against OVCA 432 and absorbed with LAZ 446, human AB erythrocytes, and the CX-1 colorectal cell line. After absorption, D-100 reacted by indirect immunofluorescence with six of six epithelial ovarian carcinoma cell lines and cryostat sections of 18 of 18 epithelial ovarian tumors but bound to zero of 12 nonovarian tumor cell lines. Despite a lack of reactivity with nonovarian tumor cell lines, D-100 reacted with epithelial components of normal ovary, fallopian tube, endometrium, endocervix, breast, colon, and epididymis. A murine monoclonal antibody (OC 133) was also raised against OVCA 432 and selected for lack of reactivity with the autologous B-lymphocyte line LAZ 446. OC 133 reacted with six of six ovarian carcinoma cell lines and cryostat sections of seven of 19 ovarian tumors, but it also reacted with five of five nonovarian tumor cell lines. Of 12 normal tissues examined, OC 133 reacted with endometrium and endocervix only. Whereas D-100 bound to serous, mucinous, endometrioid, and clear cell ovarian neoplasms, OC 133 bound only to serous tumors. In developing monoclonal reagents, cell lines may provide a useful source of antigen, but promising antibodies should be screened for reactivity with sections of normal and malignant human tissues.
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Antibody-mediated rejection appears to constitute the major difference between concordant xenografts and allografts in nonhuman primates. Consistent with its known effect on antibody responses, 5-7 addition of DSG to the conditioning regimen has extended concordant primate xenograft survival for up to 6 months after discontinuation of conventional immunosuppression. In contrast to our observations in recipients of renal allografts, donor-specific skin graft rejection can occur and even in long-term recipients may induce rejection of a previously accepted renal xenograft.