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Biomedical subjects

J M MacSween

Publications and source records attributed to J M MacSween.

At least 37 records · Page 2Linked to original sources
PubMed1983

Immunoglobulin secretory function of B cells from untreated patients with chronic lymphocytic leukemia and hypogammaglobulinemia: role of T cells.

The mechanism of the hypogammaglobulinemia in patients with chronic lymphocytic leukemia (CLL) was studied by determining the generation of specific immunoglobulin-secreting cells in response to mitogen and antigen stimulation in culture. Normal peripheral blood B lymphocytes from 18 normal subjects cocultured with equal numbers of autologous T cells generated cells secreting 2,542 +/- 695 IgG, 2,153 +/- 615 IgA, and 2,918 +/- 945 IgM. Normal B lymphocytes cocultured with normal allogeneic T cells generated similar numbers. However, B lymphocytes from patients with chronic lymphocytic leukemia cocultured with T cells from the same patient generated only 0.5% as many cells secreting IgG and 11% and 23% as many secreting IgA and IgM, respectively. The reason for this markedly defective generation of immunoglobulin-secreting cells was investigated by evaluating T-helper, T-suppressor, and B-cell function using B cells from tonsil and T and B cells from peripheral blood of normal and leukemic individuals. T cells from patients with chronic lymphocytic leukemia provided somewhat greater help than did normal T cells to normal peripheral blood B cells and normal help to tonsil B cells, whether stimulated with mitogen or antigen. T cells from patients with chronic lymphocytic leukemia did not demonstrate increased suppressor function compared to normals with B cells from normal peripheral blood. The hypogammaglobulinemia in these patients therefore was associated with a markedly defective generation of immunoglobulin secreting cells, and as there was normal or increased T-cell helper activity without excessive suppressor activity, it seems likely that this was due to an intrinsic B-cell defect.

Adult↗
PubMed1982

Macrophage migration inhibition factor (MIF): reducing the variables.

While the phenomenon of macrophage migration inhibition is a useful indicator of lymphokine release, it may be caused by other substances, it is subject to considerable variability, and it may be masked by the concomitant presence of substances stimulating migration. We have investigated certain aspects of the lymphokine macrophage interaction in order to circumvent these problems. Cells from the murine macrophage cell line RAW 264-7 migrated with less variability than fresh guinea pig peritoneal macrophages and were more sensitive target cells for human macrophage migration inhibition factor (MIF). Assays were performed with serum-free and endotoxin-free medium and in all cases in the presence and absence of L-fucose. This added specificity to the assay in that biological MIF activity was invariably blocked by L-fucose whereas migration inhibition produced by antigen complexed antibody, endotoxin, and periodate was not affected by L-fucose. It was also possible to demonstrate MIF activity in mixtures of MIF and migration stimulation factor by using L-fucose. We suggest that MIF activity is determined with less variability by using a macrophage cell line as indicator cells and performing the assays in the presence and absence of L-fucose.

Animals↗
PubMed1982

Lymphokine responses to mitogenic and antigenic stimulation. Predictive value in renal transplantation.

Immune responsiveness of recipients of renal transplants from cadaver donors was monitored by measuring lymphokine responses to specific (donor antigen) and nonspecific (concanavalin A (Con A)) stimuli. Production of migration inhibition factor (MIF) in response to stimulation by Con A before and 3 days after transplantation correlated strongly with graft rejection and production of migration stimulation factor (MSTF) with graft acceptance. This pattern continued at later time intervals but was more variable. An initial vigorous MIF response to donor cell extract was associated with rejection but subsequent responses to donor extract in the 1st month after transplantation were variable and not predictive of the outcome. In some cases, there was clearly a dissociation of lymphokine responses to donor-specific and nonspecific stimuli.

Animals↗
PubMed1981

Increased T-cell reactivity to leukemic B cells in chronic lymphocytic leukemia with change of stable disease to its progressive form.

Some patients with chronic lymphocytic leukemia (CLL) have a relatively stable clinical course without treatment, but many of these eventually develop progressive disease. We have followed 68 patients over 5 1/2 years by employing conventional surface markers and lymphocyte reactivity, including that of separate enriched T cells to their own leukemic B cells, to phytohemagglutinin (PHA), and to normal allogeneic B cells; we have observed an unusual response in each of the seven patients who developed progressive disease over this period of time. During the stable phase of the disease the T cells from 27 leukemic subjects did not respond to their own leukemic B cells in culture. In the seven patients who developed progressive disease, a significant reactivity of their enriched T cells to their own leukemic B cells occurred. There was no consistent change in T-cell reactivity to PHA or to allogeneic B cells, suggesting a change in the leukemic B-cell populations that was not detected morphologically. The change in reactivity of T cells to leukemic B cells occurred prior to evidence of clinical or laboratory deterioration in one of the seven cases; there was increasing lymphocytosis and lymphadenopathy in six and two instances, respectively; and anemia and thrombocytopenia in the three and one cases, respectively.

Aged↗
PubMed1981

The suppressive effects of monocytes in the autologous mixed lymphocyte reaction.

The response of isolated T cells to autologous non-T mononuclear cells is called the autologous mixed lymphocyte reaction (AMLR). The responding T cells show immunological memory and specificity. This reaction was present in all thirty normal individuals tested. Since the AMLR in the absence of evidence of in vivo excessive lymphoproliferation must somehow be controlled, we have studied the interactions of enriched T cells, B cells and monocytes in culture as possible means of regulation of this reaction. Increased rate of [3H] thymidine incorporation by T lymphocytes were observed when they were cultured with mitomycin-treated autologous non-T cells. This was increased when the stimulating cells were enriched for B lymphocytes and was significantly decreased when the stimulating cells were enriched for monocytes. Addition of monocyte-enriched cells to B-enriched cells in a 1:1 ratio, significantly suppressed the AMLR (P- less than 0.01). Equivalent numbers of monocytes did not suppress T-cell responses to phytohaemagglutinin (PHA). Monocyte-enriched cells were separated from stimulating B-enriched cells by nucleopore (0.6 mu) or dialysis tubing (0.12 mu) in Marbrook chambers. Soluble products released from monocyte-enriched cells also suppressed the AMLR. The significance of the AMLR in vivo is uncertain but it may be important in immunoregulation, monocytes playing an important role.

Adult↗
PubMed1980

Decreased autologous mixed lymphocyte reaction with aging.

The responses of T cells to autologous non-T mononuclear cells is called the autologous mixed lymphocyte reaction (AMLR). It seems to be an immunological response, as there is evidence of both immunologic specificity and memory. The AMLR is absent in systemic lupus erythematosis and chronic lymphocytic leukemia, and our data in normal human show that AMLR decreases with aging. Reactive T cells in the AMLR are subsequently cytotoxic to autologous B cells. We propose that the AMLR may be a protective phenomenon particularly against aberrant or neoplastic clones of B cells; and its decrease in the elderly may play an important permissive role for the development of either increased autoantibodies and/or B cell neoplasias.

Adult↗
PubMed1980

Immunoglobulins associated with human tumours in vivo: IgG concentrations in eluates of colonic carcinomas.

The concentrations of IgG in acidic and 3MKCl eluates of resected colonic carcinomas and adjacent normal tissue were determined by radioimmunoassay. The mean concentration of IgG was significantly higher in both acidic and KCl eluates of primary Dukes Stage C tumours than Dukes Stage A tumours. These results provide direct evidence for increased fixation of IgG in vivo by human colonic cancers which had metastasized. Our results also raise the possibility that IgG is more tightly bound to the Stage C tumours. It is likely that this tumour-associated Ig represents antibody to tumour antigens or antigen-antibody complexes, bound to Fc receptors in the tumour.

Aged↗
PubMed1980

Characterization of null cells in chronic lymphocytic leukaemia with B-cell allo- and hetero-antisera.

Chronic lymphocytic leukaemia peripheral blood mononuclear cells (CLL-PBMN) were separated into B, T and Null-enriched lymphocyte sub-populations using sequential mouse and sheep red blood cell rosetting depletions on Hypaque-Ficoll gradients. The procedure produced viable cell populations with mean percentage purities of 90, 87 and 75 for B, T and non-rosetting (Null-enriched) sub-populations, respectively. More than 80% of PBMN cells were generally accounted for by mouse and sheep rosetting. The purified lymphocyte sub-populations were examined with a panel of B-cell specific alloantisera obtained from kidney transplant recipients and a rabbit antiserum to B cell antigen isolated from a human B-lymphoblastoid line. The results illustrated that the antigens detected by these sera also have potential as a marker for characterizing the CLL population. Where conventional markers were weak or absent, B cell antigens were readily detected in both fluorescent and cytotoxic tests. The majority of the non-rosetting cells (less than 90%) in CLL followed similar patterns of reactivity to the purified B cells, suggesting they are a subset of B cells. A small residual population (0--5% of PBMN) did not react with the antisera, the significance of which is unknown.

B-Lymphocytes↗
PubMed1980

Restricted genetic heterogeneity in families of patients with acute lymphocytic leukemia.

HLA antigens of the A and B loci were determined on the lymphocytes of 30 patients with acute lymphocytic leukemia (A.L.L.), as well as all of their mothers and 26 of the fathers. Seven of the 26 parents shared a common haplotype. This incidence of 269 per 1,000 contrasts with an expected incidence of 90.7 per 1,000, calculated from haplotype frequencies in a North American population (X2=7.61, P smaller.than 0.01) and a frequency of one in 27 in parents of patients with renal failure in the local population (X2=3.91, P smaller than 0.05). There was no statistical difference between the latter group and the North American controls (X2=0.39, P greater than 0.10). This suggests that the genetic background of a large proportion of patients with A.L.L. has restricted heterogeneity, presumably leading to the increased expression of leukemia associated recessive genes.

Female↗
PubMed1980

Lithium and T cell colonies.

In humans, therapeutic doses of lithium causes granulocytosis and lymphopenia. In vitro increased numbers of colony forming units (CFU-GM) are observed. The effect of lithium on lymphocyte colonies is unknown. We grew T cell colonies from normal individuals and patients who were on lithium only and found that T cell colony numbers were decreased in patients who were taking lithium. Recent evidence suggests that there is a PRECURSOR common to the granulocytic and lymphocytic cell lines. Since lithium causes increased granulocytic colonies and seems to decrease lymphocyte colonies we propose that lithium may have an effect on the precursor cell resulting in preferentially shifting maturation from the lymphocytic to the granulocytic series.

Hematopoietic Stem Cells↗
PubMed1980

Salivary carcinoembryonic antigen (CEA) in cystic fibrosis.

Increased concentrations of carcinoembryonic antigen (CEA) have been reported in the sera and sputum of patients with cystic fibrosis. We have found significantly higher concentrations of CEA in both extracted and unextracted saliva of patients with cystic fibrosis compared to age-matched controls and a comparable group of patients with bronchial asthma. The mean CEA concentrations in saliva were also somewhat higher in patients with more severe respiratory disease. The concentration of CEA in the saliva of obligate heterozygotes was similar to healthy controls. This suggests that increased salivary CEA in patients with cystic fibrosis relates to the expression of the disease rather than the genetic predisposition.

Adult↗