Cytotoxic activities of recombinant immunotoxins composed of pseudomonas toxin or diphtheria toxin toward lymphocytes from patients with adult T-cell leukemia

We have previously shown that the recombinant single-chain immunotoxin anti-Tac (Fv)-PE40, composed of the variabe domains of the anti-Tac monoclonal antibody in a single-chain form joined to a derivative of pseudomonas exotoxin (PE), is cytotoxic toward malignant cells form adult T-cell leukemia (ATL) patients. Using this assay, we have now compared the activity of anti-Tac(Fv)-PE40 with that of an improved version, anti-Tac (Fv)-PE40KDEL which contains an altered carboxyl terminus, and also with two chimeric toxins made with diphtheria toxin (DT). One of these is a fusion of amino acids 1-388 of DT with anti-Tac(Fv) and is termed DT388-anti-Tac(Fv). The other, DT388-IL2, contains interleukin 2 (IL2) at the carboxyl terminus of the same DT derivative. We incubated these toxin with malignant ATL peripheral blood mononuclear cells (PBMCs) for 1-3 days and then measured [3H]leucine incorporation. We found that anti-Tac(Fv)-PE40KDEL was the most cytotoxic agent and was followed in decreasing order of activity by anti-Tac(Fv)-PE40, DT388-anti-Tac(Fv), and finally DT388-IL2. Trypan blue staining showed that inhibition of protein synthesis correlated with cell death. Time course studies show that the recombinant toxins containing anti-Tac(Fv)-PE40DEL was 30 minutes. Normal PBMCs were resistant to all four toxins. Recombinant immunotoxins made with anti-Tac merit further study as potential reagents in the treatment of ATL.(AU)

Small bowel morphology in British Indian and Afro Caribbean subjects: evidence of tropical enteropathy

Distal duodenal biopsy specimens taken from 30 white, 35 Indian, and 20 Afro-Caribbean residents of West Birmingham during routine endoscopy for dyspepsia, were assessed by disecting microscopy and morphometry. Finger-shaped villi were significantly less frequent in the Indian and Afro-Caribbean subjects than in the white subjects when assessed by disecting microscopy (p<0.005), and both immigrant groups had decreased mucosal thickness (p<0.01), villous height (p<0.001), villous:crypt ratios (p<0.01) and enterocyte height (p<0.05) compared with the white group. In the Indian subjects villous height and villous:crypt ratios correlated significantly with the time since the last visit to the Indian subcontinent (p<0.005). Serum alkaline phosphatase values were significantly higher in the Indian subjects compared with the white (p<0.02), and serum globulins were increased in both the Afro-Caribbean and Indian subjects (p<0.01). There were no correlations between morphometric indices and body habitus or biochemical or haematological indices and the long term effect of the morphological changes is not clear. (AU)

Studies in healthy human T-cell-leukemia lymphoma virus (HTLV-I) carriers from the Caribbean

Six healthy relatives of 3 adult T-cell leukemia lymphoma (ATLL) patients and 6 members of a Caribbean family immigrant to the UK have been investigated for the presence of HTLV-I and expression of interleukin 2(IL-2) receptors. Serum antibodies to HTLV-I were detected in all but 4 samples. Four to 10 percent of circulating cells from 3/4 seropositive donors studied displayed IL-2 receptors (anti-Tac+) and were shown to be convoluted lymphocytes by light microscopy morphology and immunoelectromicroscopy. After 5 to 28 days in culture, cells from 4 seropositive donors reacted with monoclonal antibodies (MAbs) against the HTLV-I core proteins, p19 and p24, and released retrovirus particles. Simmilar experiments with blood from 3 seronegative donors from the same families and 4 normal controls proved negative. Our findings indicate that seropositive individuals harbour the virus in a population of T-lymphocytes which may then acquire receptors for IL-2. These individuals are at risk of developing ATLL. (AU)

Morphology of the lymph nodes draining renal adenocarcinoma in relation to immunological functions

One hundred and thirty-four lymph nodes from forty-seven patients with renal adenocarcinoma and the same number of regional nodes from sixty-one patients with gastric ulcer were evaluated histologically by using the standardized reporting system introduced by Cottier, Turk & Sobin (1973). Special attention was focused on the morphologic features which correlate with the immunological responses of the antibody response were found to be active more often in the ulcer series than in the cancer series. On the other hand, the constituents of the cell-mediated immune system were depressed more often in the nodes draining renal carcinomas. The significance of the different immune responses evoked by these two diseases is discussed and the conclusion is drawn that there is some degree of derangement of both humorlal and cell-mediated immune systems in the regional lymph nodes of renal adenocarcinoma. The applicability of the reporting system used in assessing the morphology of human lymph nodes is to be emphasized.(AU)

Fibroxanthomatous pseudotumour of the lung

The clinical, radiological and pathological features of fibroxanthomatous pseudotumour of the lung in a 17-year-old Jamaican female Negro are described. The patient was symptom-free 4 years after treatment by conservative surgery. The condition is extremely rare. Its aetiology and pathogenesis are discussed. (Summary)

Circulating lymphocyte response during acute infection - abstract

The circulating lymphocytes in peripheral blood comprise a group of cells with different origins, life span, fine structure, and proliferative capacity. Under normal circumstances, these lymphocytes do not divide and peripheral blood from healthy individuals contains only about 0.1 percent of lymphocytes in DNA synthesis. This proportion is much increased in infectious mononucleosis, several viral, bacterial and rickettsial diseases and is even greater in acute and chronic myeloid leukaemia and other reticuloses. This study was undertaken to assess the DNA-synthesising ability of lymphocytes in peripheral blood of patients with infectious diseases and to ascertain if the proliferative response was related to the nature of the infecting agent. The agents studied included leptospira, proteus, pneumococcus, staphylococcus, streptococcus, tetanus, klebsiella and some viruses. DNA synthesis was assessed by the ability of the cells to incorporate tritiated thymidine (H3T) or I125 deoxyuridine (I125DU) into DNA, following a one-hour pulse in vitro I125 DU uptake was measured by scintillation counting which provided an index of the per cent isotope incorporation in a given population of cells. By H3T autoradiography, specific cell types undergoing DNA synthesis were identified and quantitated by the Labelling Index (number of cells labelled/total cells counted). A total of 84 patients and 16 normal control subjects were studied. The results by both method indicated a definite increase in percentage of DNA-Synthesising cells in all infected patients, the greatest response being in leptospira, proteus and pneumococcus infections. Response was low in klebsiella infections and in sickle cell anaemia patients with infected leg ulcers. The labelling indices showed a mean of 3.01 + 019 percent and 0.04ñ0.09 percent in leptospirosis and sickle cell anaemia respectively, as compared with a 0.3 percentñ0.00 percent in normals. These studies demonstrated that lymphoid elements stimulated in vivo initiate a phase of proliferation in what is apparently an immunologic reaction mounted against the foreign infectious agents. This proliferative response may provide a means of increasing the numbers of antigenically-activated cells or may function in a reparative way. The measurement of DNA-synthesising cells represents a sensitive tool in the investigation of inflammatory and immunoproliferative disorders (AU)