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Biomedical subjects

D Gray

Publications and source records attributed to D Gray.

At least 199 records · Page 11Linked to original sources
PubMed1988

B-cell memory is short-lived in the absence of antigen.

Primary encounter with antigen stimulates specific B cells not only to differentiate into cells that produce antibody at a high rate (plasma cells), but also to give rise to populations of memory cells. These cells have many characteristics that differ from virgin B cells, including their lifespan. When re-exposed to antigen, memory cells generate secondary IgG responses that are enhanced in rate, titre and affinity. At present they are considered as small resting lymphocytes which survive for long periods in a quiescent state between each antigen encounter. However, the fact that an individual may continue to make an antibody response for many months following a single injection of antigen is often overlooked. This continued antibody production is probably due to repeated stimulation of antigen-specific B cells and raises the question of whether memory B-cell clones require antigen for their maintenance. Here we show that they do, and that following transfer, in the absence of antigen, memory B-cell populations are lost from the adoptive host after 10-12 weeks.

Animals↗
PubMed1988

Population kinetics of rat peripheral B cells.

Currently available estimates of B cell life span vary from 4 d to 6 wk. The discrepancy may have arisen out of the selective effects of stress and drug cytotoxicity on short-lived populations. In this report, bromodeoxyuridine (BUdR), a drug that incorporates into the DNA of dividing cells, has been fed to rats in their drinking water, eliminating stressful injection procedures. Labeled cells in the recirculating B cell pool are identified in tissue sections using an mAb to BUdR. BUdR is shown to have no cytostatic effects at the dose used. Over a 5-d period of infusion, only 20% of the peripheral recirculating pool incorporate label (approximately 4% per day); labeling over various periods indicates that the peripheral B cell pool turns over in approximately 4 wk. To distinguish between turnover due to incorporation of new B cells into the peripheral pool and division of antigen-activated B cells rats underwent two consecutive periods of labeling, first with [3H]thymidine for 5 d and then with BUdR for a further 5 d. Virgin B cells newly derived from dividing precursors in the bone marrow do not continue to proliferate in the periphery, while activated cells undergo several rounds of division during both labeling periods. The results indicate that 3-4% of the peripheral pool is replaced by new B cells each day, while 0.3-0.6% become part of activated clones every day. Assuming that the peripheral pool of the rat contains 10(9) B cells, then 3-4 X 10(7) new B cells become stably incorporated per day. This represents approximately 10% of the putative output of the bone marrow.

Animals↗
PubMed1988

Renal transplantation in patients over 55 years old.

From 1975 to 1987, 507 patients, of whom 63 (12.4 per cent) were over 55 years old at the time of operation, received first cadaver renal transplants. The annual percentage of recipients given transplants after the age of 55 has risen from 0 per cent in 1975 to 44 per cent in 1987. Of the 63 older patients, 41 had at least one serious non-renal disease at the time of transplantation. Perioperative mortality rate was 3 per cent. After successful transplantation these patients remained subject to a significant number of serious complications, even in the cyclosporin era. Despite these adverse factors, actuarial graft survival for the population over 55 years of age was no worse than for those patients receiving first cadaver grafts who were under 55 years old, although patient survival was poorer in the former group (P = 0.027). Analysis of the subgroup of 56 patients treated with an immunosuppression protocol containing cyclosporin failed to show any adverse effect of age on either graft or patient survival. It is concluded that renal transplantation can be as successful in patients over 55 years of age as it is in younger patients and, given an adequate supply of kidneys, should be considered the treatment of choice for the elderly patient with end-stage renal failure.

Age Factors↗
PubMed1988

B cell memory to thymus-independent antigens type 1 and type 2: the role of lipopolysaccharide in B memory induction.

Several studies have indicated that thymus-independent (TI) antigens, unlike their thymus-dependent (TD) counterparts, are poor at generating memory antibody responses (Immunol. Today 1981. 3:217). In contrast to this view, the present report shows that the TI type 1 (TI-1) antigen, 2,4,6-trinitrophenyl-lipopolysaccharide (TNP-LPS), elicits good secondary responses in rats. These secondary antibody responses are not only greater in magnitude than the primary responses, but display a different pattern of Ig classes with more IgG and IgA antibodies produced. In transfer experiments between congenic strains of rats which differ in their kappa light chain Ig allotype, it is shown that this memory is attributable to persistent B cell clones. The TI-2 antigen, 2,4-dinitrophenyl-hydroxyethyl starch (DNP-HES), given alone did not elicit B cell memory. However, when DNP-HES is presented to the immune system in association with LPS, the pattern of the anti-DNP response is similar to that elicited by TNP-LPS. The capacity to generate TI memory is associated with the appearance of hapten-specific B cells in the marginal zones of the spleen. Hapten-binding cells were induced in the marginal zones following immunization with TNP-LPS, but not by DNP-HES. However, concurrent immunization with DNP-HES and LPS which were not covalently linked was found to induce DNP-binding cells in the marginal zone. There is complete correlation between the appearance of hapten-binding memory B cells in the marginal zone and the capacity of these antigens to induce secondary responses.

Animals↗
PubMed1988

Studies on the relationship of human natural killer and lymphokine-activated killer cells with lysosomal staining and analysis of surface marker phenotypes.

We have previously demonstrated that natural killer (NK) cells are lysosome-rich and stain more intensely with lysosomotropic agents such as neutral red and quinacrine (Qu) than do non-NK cells. In this study we combined the quantitation of Qu staining with surface marker staining to define subpopulations of NK cells. While all NK activity was contained within the Qu+ population, most but not all NK cells expressed the surface marker CD16. A subpopulation of NK cells was found to be Qu+CD16- composed of medium- to large-sized cells with a granular appearance on Giemsa staining. Culture with interleukin-2 (IL-2) induced enhanced cytotoxicity in peripheral blood lymphocytes (PBL) against NK-sensitive and NK-resistant tumor cells. Like NK cells, these lymphokine-activated killer (LAK) cells were predominantly Qu+CD16+. However, some LAK cells were Qu+CD16-. The Qu+CD16+ cells were typical large granular lymphocytes (LGL). The Qu+CD16- cells were also large lymphocytes, more than 50% of which were proliferating. However, the granulation in some Qu+CD16- cells, as detected by Giemsa staining, was more prominent and numerous than others in the same population. No LAK activity was ever detected in Qu- cells, which were uniformly small lymphocytes. Quantitation of Qu staining in effector cells was therefore demonstrated to have a good correlation with NK and LAK functions, and with surface markers can help to characterize both types of cells. Moreover, these results indicate that both NK and LAK populations include a small subset of CD16- cells in each.

Antigens, Surface↗
PubMed1988

Recruitment of virgin B cells into an immune response is restricted to activation outside lymphoid follicles.

The site and mechanism of recruitment of short-lived new B cells from the bone marrow into the longer-lived recirculating B-cell pool were studied by using kappa-allotype-distinct congenic rats to construct bone marrow chimeras. Chimeras were immunized with antigen in the form of an antigen-antibody complex that is largely restricted to lymphoid follicles, rapidly localizing to follicular dendritic cells (FDC). This form of antigen, although a potent stimulator of memory B cells, was shown to be a very poor inducer of virgin B-cell responses. This was not due solely to differences in receptor affinity, as complexes in which the hapten epitopes were unmasked also evoked little virgin B-cell response. The inability of virgin B cells to be activated by FDC-bound antigen seems to relate to the fact that they are not part of the recirculating pool and do not migrate through lymphoid follicles; restriction of antigen to a draining lymph node also precluded virgin B-cell activation. The evidence presented suggests that activation of virgin B cells at extrafollicular sites in the spleen (red pulp, marginal zone, outer periarteriolar lymphocytic sheath) is required for both their incorporation into immune responses and into the recirculating pool. These experiments also show that established immune responses are maintained by clones activated soon after immunization and not by continued incorporation of new clones.

Animals↗
PubMed1987

A comparative cost analysis of terminal cancer care in home hospice patients and controls.

A comparison is made between the expenditure during the last 90 days of life on 98 terminal cancer patients cared for by a home based hospice service and that on matched patients dying without the home hospice service. The control patients were matched for site of primary cancer, age and sex. The individual records of both groups of patients were analyzed and costed. It was found that the costs of providing 24 hour comprehensive medical and nursing care at home to those dying of cancer and support for their families was no more expensive than traditional institutional care.

Australia↗
PubMed1987

Greater in vivo than in vitro pulsatility of insulin secretion with synchronized insulin and somatostatin secretory pulses.

To examine the control of pulsatile insulin secretion by an intrapancreatic pacemaker, samples at minute intervals were taken from the portal vein in dogs in vivo and from an isolated perfused pancreas preparation in vitro. Anesthetized dogs had high amplitude pulsatile insulin secretion which was not consistently regular. Fourier transform analysis showed dominant 20- and 10-min periods of spectral power (P less than 0.01). After vagotomy, the relative oscillatory power was reduced from 83% to 42%, about a lower mean concentration with abolition of the 20-min oscillations. The isolated perfused dog pancreas also had oscillatory insulin secretion with oscillatory power of 12%. Autocorrelation showed regularity of in vitro insulin secretion with a period of 10-11 min (P less than 0.0001). In addition, somatostatin was secreted from the in vitro pancreas in pulses in phase with insulin (cross-correlation P less than 0.0001). These data are in accord with the theory that the pancreas has an internal pacemaker which controls insulin secretion, and that the amplitude of the oscillations is modulated by vagal control. The pacing of the islets may be coordinated by a neural network, whereas coincident pulsatile somatostatin release may temporarily suppress islet secretion and help to synchronize hormonal oscillations.

Animals↗