Biomedical subjects
Publications and source records attributed to M de Sousa.
Lymphocytopenias, unlike deficiencies of other blood cells, may not reflect actual reductions in the cell populations. Because of the constant interchange of lymphocytes between the blood and lymphatic circulation, their absence from the blood often reflects sequestration in lymphoid tissues. The significance of such imbalances in a number of disease states is being probed.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Spleen cells from BN rats were separated in a discontinuous density gradient. Cells from different fractions were shown to be functionally diverse, light cells enhancing DNA synthesis and cell division of the dense cell fractions, while dense cells suppressed DNA synthesis and cell division of light cells. Both these effects were also present in the absence of cell stimulation, were proportional to the number of modulating cells added to the cultures, and totally independent of the magnitude of response of controls. In Con A-stimulated cultures, mitogen dose also influenced the intensity of help and suppression. Both these effects are blocked by cell treatment with cycloheximide and can be mediated by cell supernatants. A T cell seems to be responsible for both helper and suppressor effects.
Lactoferrin (LF), the iron-binding protein present in the specific granules of mature granulocytes has been identified as colony inhibitory factor (CIF) which suppresses granulocyte--macrophage colony stimulating activity (CSA) production by monocytes and macrophages in vitro and rebound granulopoiesis in vivo. Separation of LF and CIF by isoelectric focusing confirmed that the regions of inhibitory activity corresponded in both to a pH of congruent to 6.5. In addition, the purified immunoglobulin fraction of rabbit anti-human LF antiserum, but not rabbit anti-transferrin (TF), inactivated the capacity of LF and CIF to inhibit CSA production, an effect blocked by prior incubation of anti-LF with neutralizing concentrations of LF. Suppression of CSA production correlated with the iron-saturation of LF; APO-LF (depleted of iron) was only active concentrations greater than 10(-7) M, native LF (8% iron saturated) was active at 10(-15) M, and fully iron-saturated LF inhibited at 10(-17) M. Suppression of CSA production occurred within a 1/2-h preincubation period with human blood monocytes but was reversed by bacterial lipopolysaccharide (LPS). This reversal was dependent on the relative concentrations of LF to LPS. Serum TF, a biochemically similar iron-binding protein which is antigenically distinct from LF, was only minimally active at concentrations greater than 10(-6) M. LF did not inhibit exogenously stimulated human granylocyte and macrophage colony-forming cells or erythropoietin-dependent human or murine erythroid colony- or erythroid burst-forming cells. Microgram quantities of LF acted in vivo to inhibit rebound granulopoiesis and CSA production in CD1 and C57Bl/6 mice pretreated with cyclophosphamide. These results strongly implicate LF as a physiological regulator of granulopoiesis.
Explore the source record for details and available documents.
A study of peripheral blood lymphocyte populations in 27 children with Hodgkin's disease (HD) and 13 age-matched control subjects is presented. The absolute numbers and percentages of T and B lymphocytes identified by their surface marker characteristics were determined. In addition, in 13 HD children the percentages of T and B lymphocytes were estimated in the spleens removed at staging laparotomy. No differences were observed between the total peripheral blood lymphocyte counts of HD and control children, and we found no evidence of progressive lymphopenia with advancing stages of the disease. No decrease in the numbers of peripheral blood T lymphocytes was seen in this group of HD children. In contrast, the proportions and absolute numbers of B lymphocytes tended to be significantly lower in the children with HD than in the control subjects. In 9 of the 13 spleens studied high percentages of T lymphocytes were seen; low percentage of B lymphocytes were found in all spleens examined.
In the present paper we apply the "ecotaxis hypothesis" to the analysis of lymphocyte distribution in Hodgkin's disease and other forms of lymphoid malignancy. The results lead us to consider the possiblity that metal-binding proteins, namely ferritin, transferrin and lactoferrin, play a role in lymphocyte ecotaxopahty. It is suggested that in Hodgkin's disease, a failure of lymph node and spleen monocytes to handle iron normally could explain most of the hematologic, immunologic, pathologic, and epidemiologic features of the disease.
Over the past 5 years, parameters of immunological function have been determined in all children with biopsy-proven Hodgkin's disease in the Department of Pediatrics, Memorial Sloan-Kettering Cancer Center. This report summarizes the in vitro responses of lymphocytes to stimulation by mitogens and antigens (between January 1975 and December 1976) in 33 of these previously untreated patients. In nine of these patients, responses of the splenic lymphocytes were studied concomitantly with the responses of peripheral blood lymphocytes. Peripheral blood from normal children and adults was used as the control. Our results have demonstrated no significant differences between the responses of normal children and adult controls. The absolute necessity for concomitant studies of the controls and the patients was shown. The value of examining multiple concentrations of a single mitogen was also well defined. In the children with Hodgkin's disease, there was a consistent failure of the peripheral blood lymphocytes to respond to the lower concentration dose of phytohemagglutinin. However, this abnormality was not found in the splenic lymphocytes.
Explore the source record for details and available documents.
The effect of in vitro treatment of mouse lymph node cell populations with lipopolysaccharide (LPS) on their migration in syngeneic recipients was studied. LPS-exposed cells had a decreased lymph node localization and an increased spleen distribution when compared to control untreated cells, after intravenous injection into syngeneic recipients. This effect of LPS on cell traffic was maximal at 24 h and could not be detected at either 1 or 72 h after cell transfer. These changes induced on cell distribution by LPS treatment are interpreted as the consequence of a modified interaction between the circulating lymphocytes and the resident cells within the spleen of the recipients.
Glycoproteins have so far been the only surface components thought to be of importance in the process of recognition between circulating lymphocytes and endothelial cells of the lymph node post-capillary venules and thus in the control of lymphocyte traffic. In this paper the effect of in vitro treatment of 51Cr-labeled mouse lymph node cells with phospholipases (PL) (A and C) on their migration into syngeneic recipients was investigated. PL-A and PL-C treated cells migrated differently from control (untreated) cells. Diminished numbers of PL-A-treated lymphocytes were found in the lymph nodes at 1, 6 and 24 h after cell transfer with a simultaneous increase in the lungs at 1 h, and spleen at 6 h after transfer. PL-C-treated cells remained in the blood longer than untreated cells. We conclude that factors other than the integrity of surface glycoproteins are involved in the control of lymphocyte traffic. The roles played by cell adhesion, in particular cell-to-cell interactions in regulating the rate of cell migration, are discussed.
Explore the source record for details and available documents.