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Biomedical subjects

J S Duke-Cohan

Publications and source records attributed to J S Duke-Cohan.

27 records · Page 2Linked to original sources
PubMed1989

Use of an autologous reaction in vitro to assess contributions of T and B lymphocytes to immune hyperreactivity of atopics.

The in-vitro proliferation reaction of peripheral blood lymphocytes (measured by [3H]thymidine incorporation) to autologous pokeweed mitogen (PWM)-induced lymphoblasts (PWM-lymphoblast-stimulated autologous mixed leucocyte reaction, PWM.AMLR) was used as a measure of immune hyperreactivity for comparison of atopic with non-atopic individuals. Accordingly, 10/24 non-atopics responded in the PWM.AMLR, and 19/19 atopics reacting to inhaled allergens responded. Autologous stimulation was associated with release of mitogenic factors from the PWM-activated stimulating cells (2/15 non-atopics, 9/15 atopics). For non-atopics, stimulation delivered by staphylococcus A (SAC)-activated cells was similar to that delivered by PWM-induced cells, while in atopics, the SAC.AMLR was never more than 50% of the PWM.AMLR, indicating a possible T cell component. Separation by panning of the stimulation cells into lymphocyte subsets supported the notion that stimulation involved a cooperation between B and T4+ T cells. It is proposed that a positive PWM.AMLR is dependent upon an initial B cell activation followed by the PWM stimulus dependent upon a previous T cell activation, where atopics have more lymphocytes in an activated state than healthy non-atopics. Such a baseline priming may contribute to an innate sensitivity of atopics to environmental allergens.

Adolescent↗
PubMed1988

Observations on the contributions of environmental restraints and innate stem cell ability to hematopoietic regeneration.

A competitive repopulation assay utilizing chromosome markers was used to assay the reconstituting potential of hematopoietic populations. The test populations consisted of tibial murine marrow locally irradiated with doses ranging from 1.5 Gy to 8.5 Gy and of marrow generated from either murine splenic or marrow stem cells. The purpose of this assay was to assess the innate proliferative potential and microenvironmental influences on the ability to repopulate. Regardless of origin, spleen repopulating ability consistently agreed with spleen colony-forming unit (CFU-s) content. Doses of radiation from 5 Gy to 8.5 Gy diminished, by a factor of 2, the ability to repopulate marrow despite maintenance of CFU-s levels. Marrow generated from splenic stem cells had one-fifth the repopulating ability of marrow derived from marrow stem cells, even though CFU-s levels were equivalent. The results imply that the splenic environment can only maintain stem cells at the level of the CFU-s, even if the stem cells were originally of higher quality, and that their original potential cannot be regained in a marrow environment. Nevertheless, the marrow can maintain more primitive stem cells, but this reserve is drained to support CFU-s levels.

Animals↗
PubMed1987

On the immune reaction to autologous human lymphoblasts: evidence for the stimulation by activating factors rather than induction by autoantigens.

This report questions the nature of stimulation in the lymphoblast-induced autologous mixed leukocyte reaction (AMLR). Using immobilized phytohemagglutinin (PHA) and pokeweed mitogen (PWM), we show that the AMLR generated with PHA lymphoblasts (PHA X AMLR) was not significantly different from the AMLR generated with untreated stimulators. The PWM lymphoblasts of 15 out of 33 apparently normal blood donors generated an AMLR (PWM X AMLR) greater than their respective normal AMLR. The positive PWM X AMLR was not related to the expression of HLA-DR or surface IgM, since expression of both was increased by both PHA and PWM, yet only PWM blasts stimulated in the AMLR. Fixation of PWM-stimulated cells prior to the AMLR completely abolished stimulatory capacity, indicating further against new or increased antigen expression. Inactivation by uv irradiation of surface HLA-D on the stimulators had no effect upon the PWM X AMLR, while intact protein synthesis was required in order to stimulate. The ability of cells to stimulate was associated with the release of soluble helper factors capable of stimulating autologous cells independently. These factors were neither contaminating PWM nor secreted IL-1 or IL-2, although IL-1-like activity was released by all cells regardless of their ability to stimulate. The individual variation in the PWM X AMLR response and secretion of helper factors is discussed in relation to B-cell hyperproliferation and altered immunoglobulin production in autoimmune manifestations.

Adult↗
PubMed1986

The multifactorial nature of osteoporosis: the potential of corticosteroid-binding globulin as a unifying regulator.

Accelerated bone loss often accompanies the menopause, and may also affect a significant proportion of ageing women. This osteoporosis can also be an accompaniment of several other pathological manifestations. It is difficult to imagine that each process alters bone resorption and renewal by a separate mechanism; in all probability a common mechanism may operate in some of the instances where osteoporosis is observed. It is proposed that chronic alterations in the levels of circulating physiologically-active cortisol could account for some of the osteoporoses. These alterations need not necessarily affect total plasma cortisol values, but rather affect the relationship of cortisol to its plasma carrier protein, transcortin, since changes in this relationship are a common occurrence in many of the conditions associated with osteoporosis.

Calcitonin↗
PubMed1986

Determination of ABO blood group zygosity by an antiglobulin rosetting technique and cell-based enzyme immunoassay.

Two methods were employed to determine the zygosity of A and B red cells, the rosetting antiglobulin test and the enzyme-linked immunoadsorbent assay (ELISA) technique. By means of the rosetting antiglobulin test, clear differences between AA and AO as well as BB and BO could be shown; however, this method could not define the variation in the amount of the H antigen as a complimentary means of differentiating AA from AO and BB from BO. The ELISA test could quantitatively estimate the level of expression of H antigen, and using anti-A and anti-B reagents in a simultaneous assay, a specific pattern could be generated for each phenotype. Both rosette and ELISA approaches offer easy and inexpensive means of determining zygosity within the ABO system for use in paternity exclusion.

ABO Blood-Group System↗
PubMed1985

Heterogeneity within the hematopoietic stem cell compartment: evidence for a marrow-seeding stem cell distinct from CFU-s.

Using a chromosome marker within a syngeneic system, we investigated the seeding characteristics of murine hematopoietic stem cells after transplantation to irradiated hosts. The chromosome-marked test cells were allowed to compete with normal marrow cells in repopulating the spleen and marrow of irradiated mice. Although the seeding behavior of normal marrow could be predicted from the number of colony-forming units-spleen (CFU-s) transplanted, the marrow seeding of melphalan-treated marrow was 7-fold greater than expected. Repopulation of marrow by spleen cells was less effective than expected from the CFU-s content, while the reverse was true after repopulation by fetal liver cells. These differences were emphasized after treatment of cell donors with melphalan. The results were due primarily to differences in the lodging properties of the transplanted cells, those seeding in the marrow were less sensitive to melphalan than CFU-s. In some instances marrow-repopulating ability could be separated from peak CFU-s activity on a density gradient, suggesting a marrow-repopulating cell exists that is distinct from CFU-s.

Animals↗
PubMed1985

Immunological function in osteoporosis.

An imbalance of osteoblastic bone formation and osteoclastic bone resorption is thought to be responsible for the osteoporotic condition. The pathological events leading to this disorder are, in most instances, uncertain. A defect in the ability of osteoporotic patients to respond to foreign histocompatibility antigens in a mixed leukocyte reaction is reported here. The results further show that this defect is due both to a poorly responding lymphocyte population as well as to a suppressor factor in osteoporotic sera. In addition, there is a significant increase in the relative and absolute numbers of T cells in the patients' peripheral blood, while serum IgG, IgA, and IgM remain within the normal range. These findings are discussed in the light of a common immunopathological pathway regulating osteoclastic activity and leading to the osteoporotic condition.

Adult↗