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Biomedical subjects

D Gray

Publications and source records attributed to D Gray.

At least 163 records · Page 9Linked to original sources
PubMed1993

Repair of the anterior mitral leaflet.

BACKGROUND: Repair rather than replacement of the diseased mitral valve has been the goal of the cardiac surgeon. Although well accepted for posterior leaflet pathology, a diseased anterior leaflet was believed by some to be irreparable. AIMS: To assess the result of reconstructive mitral valve surgery involving the anterior mitral leaflet in a selected group of patients. METHODS: Twenty consecutive patients with degenerative (19), ischaemic (one) and congenital/calcific mitral regurgitation were evaluated. There were five females and 15 males with a mean age of 62 +/- 12 years (41-75 years). The technique used to repair these valves included chordal transposition, leaflet plication commissuroplasty and a new technique we call leaflet repositioning. RESULT: There were no deaths, follow-up is complete with mean follow-up of 31 +/- five months (two-102) months. All patients have had 2DE and 13 TOE as well. There have been no reoperations due to failure of the repair, 95% of patients are in NYHA Class I-II post operative, while 15% have significant residual regurgitation.

Chordae Tendineae↗
PubMed1993

Immunological memory.

The past five or six years has seen a resurgence of interest in immunological memory. Areas in which important advances have been made of late or in which problems in understanding persist are covered here: (i) Selection of virgin B cells for entry into the peripheral pool. (ii) Expression of immunoglobulin isotypes and other markers on memory B cells. (iii) Development of memory B cells as a separate lineage from primary response B cells. (iv) Sites of production of memory B cells. (v) Signals that rescue mutating B cells in germinal centers, forming the basis of affinity selection, and programming further differentiation. (vi) The myriad markers of memory T cells, in particular CD45R isoforms. (vii) Selective migration pathways of memory T cells and its possible molecular basis. (viii) The lifespan of memory cells and factors that influence their long-term survival. The data accumulated during this period which have vastly increased our understanding of memory have at the same time highlighted unresolved problems that could block further progress in the field. The thorny question that we cannot at present answer is: How does a memory cell differ from an activated cell and, in the case of T cells, from an effector cell? The problem bears on the interpretation of any study that sets out to correlate memory phenotype with memory function. Immunologists may have donned an intellectual straitjacket in their search for the memory cell.

Animals↗
PubMed1993

Demand for hospital services following admission with suspected myocardial infarction in 1983 and 1989.

Formulation of business plans by National Health hospitals requires information on likely demands for the services they provide. Two cohorts of patients admitted to the Nottingham hospitals in 1983 and 1989 with suspected myocardial infarction were sampled to determine the workload implications due to initial in-hospital tests, subsequent readmission and outpatient investigations. The results show that attendance in the first year after discharge related principally to cardiac problems, while in subsequent years non-cardiac problems predominated. An estimation of the total workload, based upon 1,000 patients admitted in 1989, suggests that demands for hospital services in the following year include over 4,000 electrocardiographs, 1,400 chest X-rays and 18,000 laboratory tests, and only 118 exercise tests and 37 cardiac catheterisations. Admission with suspected myocardial infarction makes great demand on hospital services in the year after discharge. Any change in practice, which increases the potential demand for cardiac investigations, could have important financial implications for Nottingham hospitals.

England↗
PubMed1992

CD45RA and CD45RBhigh expression induced by thymic selection events.

CD45 is a protein tyrosine phosphatase involved in T and B cell signaling. While peripheral T cells switch CD45 isoforms upon activation, events leading to exon switching during T cell development in the thymus have not been determined. The expression of high molecular weight isoforms of CD45 was examined on thymocytes from nontransgenic and T cell receptor (TCR) transgenic mice. All thymocytes from nontransgenic mice were CD45RB+ as assessed by staining with MB23G2, an anti-CD45RB-specific monoclonal antibody. Interestingly, there was a small population (1-3%) of thymocytes that displayed a higher intensity of staining with MB23G2, CD45RBhigh. CD45RBhigh thymocytes were found in all subsets defined by CD4 and CD8 expression and were also present within the TCR-alpha/beta high population. To analyze whether or not CD45 expression correlated with thymic selection events, expression of CD45RBhigh and a second isoform, CD45RA, was examined on thymocytes from H-Y and 2C TCR transgenic mice and found to correlate with positive and negative selection events but did not occur in nonselecting backgrounds. CD45RA and CD45RBhigh upregulation was also not observed in transgenic mice backcrossed into CD8-deficient mice, a scenario in which there is no positive selection of transgene-expressing thymocytes. These data suggest that modulation of CD45 isoform expression may be involved in thymic selection events.

Animals↗
PubMed1992

Less mortality but more relapses in experimental allergic encephalomyelitis in CD8-/- mice.

Mice lacking in CD8 were generated from homologous recombination in embryonal stem cells at the CD8 locus and bred with the experimental allergic encephalomyelitis (EAE)-susceptible PL/JH-2u through four backcross generations to investigate the role of CD8+ T cells in this model of multiple sclerosis. The disease onset and susceptibility were similar to those of wild-type mice. However, the mutant mice had a milder acute EAE, reflected by fewer deaths, but more chronic EAE, reflected by a higher frequency of relapse. This suggests that CD8+ T lymphocytes may participate as both effectors and regulators in this animal model.

Animals↗
PubMed1992

Follicular dendritic cell-dependent adhesion and proliferation of B cells in vitro.

In response to an antigenic challenge, B cells proliferate in germinal centers within secondary lymphoid tissue. Specialized accessory cells, follicular dendritic cells (FDC), and T cells are necessary to drive this reaction. Indirect evidence suggests that FDC provide signals which not only induce B cell proliferation but can rescue B cells programmed to die by apoptosis. An in vitro system was developed to: 1) define the role of FDC and 2) identify molecules involved in this response. Activated, low density B cells and T cells were coisolated with FDC from immune mouse lymph nodes. Upon culturing, large cellular aggregates formed, composed of 1 to 3 FDC interdigitating between 30 to 90 B cells and 1 to 5 T cells. Many of these B cells were undergoing DNA synthesis. Depleting FDC or T cells from the cultures immediately stopped cluster formation and proliferation. Separating clustered vs nonclustered cells revealed that the FDC-associated population remained viable, whereas cells in suspension became apoptotic. The adhesion/activation molecules ICAM-1, LFA-1, and CD44 supported both cluster formation and proliferation. In addition, anti-class II and anti-kappa L chain mAb interfered dramatically with DNA synthesis. This model mimics many of the features of a germinal center and can be used to further study B cell activation, proliferation, and differentiation in vitro.

Animals↗
PubMed1992

Netwhat?

The hallmark of an antibody response is considered to be its specificity for the immunogen. Nonetheless, most antibody elicited by an immunogen has been reported to be unreactive with it. We have evaluated specificity by characterizing the primary antibody response of mice to heat-aggregated human gamma-globulin with four approaches: (a) quantification of antibody-producing cells; (b) hybridoma analysis; (c) in situ antigen binding and (d) analysis of secreted antibody. The results show that the nonspecific component of this response is negligible. These observations suggest that such a component is not a basic feature of the antibody response and it is discussed that nonantigen-specific antibody may arise from a variety of causes many of which are artifactual.

Animals↗
PubMed1992

Activated human T cells express a ligand for the human B cell-associated antigen CD40 which participates in T cell-dependent activation of B lymphocytes.

To identify the ligand for the B cell-associated antigen CD40, we constructed a chimeric immunoglobulin molecule where the extracellular portion of the CD40 protein replaced the normal immunoglobulin variable region. No binding was detected on resting peripheral blood T cells. However, following T cell activation with phorbol esters and ionomycin, the chimeric protein bound specifically to activated human T cells and precipitated a 35-kDa protein from such cells. The induction of the CD40 ligand was detectable on the cell surface after 1 h, with maximal expression after 8 h of stimulation. The T cells expressing CD40 ligand were predominantly CD4 positive, although a proportion of CD8-positive cells also expressed the protein. There was no particular correlation with CD45 phenotype. Finally, we found that soluble CD40 inhibited T-dependent B cell proliferation. The results are discussed in the context of cognate interactions between B and T cells.

Adult↗
PubMed1992

Long saphenous vein storage after femoro-distal bypass grafting.

Segments of long saphenous vein generated during the preparation of conduits for femoro-distal bypasses can be stored in saline at 4 degrees C. Two occasions on which such stored vein segments have proved valuable in graft revision after early graft thrombosis are described.

Anastomosis, Surgical↗
PubMed1992

Signals involved in germinal center reactions.

Many of the features observed in the in vitro cultures discussed in this review coincide with characteristics described for an in vivo germinal center response. FDC and T cells are required to maintain B-cell proliferation which is confined to a finite amount of time (i.e. less than 2 wk). Large cellular aggregated form which contain many blasting cells undergoing DNA synthesis. In addition to proliferation, apoptosis is also occurring in the cultures but appears to be limited to the population which is not in contact with the FDC. The system can be driven by specific antigen, suggesting that clonal expansion is occurring. As in other immunological systems, there is an important role for adhesion molecules both for cluster formation and DNA synthesis. Antigen processing and presentation is a major event since blocking this through several mechanisms ends the stimulation. The role of T cells is essential both in vivo and in vitro; however, their exact contribution is still not well understood. It is interesting that blocking IL4 usage either by neutralizing the molecule or its receptor by monoclonal antibodies has no effect on the system. Which interleukins are important for germinal centers remains on open question. Evidence continues to accumulate on the important role of FDC and the molecules they express. Not only are the immune complexes an essential part, but it seems that molecules yet to be defined have an effect. For many practical reasons these have remained a mystery, but using our various systems we are attempting to reveal them. Two intriguing questions which remain include: 1. the molecular nature of the signalling between the FDC and B cell; and 2. how does the FDC retain the antigen in a native form for such long periods of time? An understanding of both mechanisms will provide us with a better appreciation for the events leading to a germinal center response and the immunological phenomenon referred to as memory.

Animals↗
PubMed1992

Immunohistochemical localization of basic fibroblast growth factor within the mouse uterus.

Uterine samples were either rapidly frozen in liquid nitrogen or placed in Bouin's fixative. A commercial primary polyclonal antibody made in rabbits against human recombinant basic fibroblast growth factor (bFGF) was used. Western blot analysis indicated that the antibody was specific for bFGF and did not react with acidic FGF. The primary antibody was followed by either goat anti-rabbit immunoglobulin G (IgG) conjugated to the fluorescent phycobiliprotein tracer phycoerythrin or biotinylated goat anti-rabbit IgG and a biotin-avidin-peroxidase complex. Specificity controls using adjacent sections were carried out by (i) substituting normal rabbit sera for the primary antisera, (ii) omitting the primary antisera or (iii) extracting sections with NaCl (2 mol l-1) prior to the immunochemical procedures. No binding of the antibody was observed with any of the specificity control sections. The connective tissue stroma and the basal lamina associated with uterine glandular and surface epithelial layers were positive for bFGF. Localization was not observed within surface or glandular epithelial cells. The basal lamina and endothelial cells associated with blood vessels within the uterus and the smooth muscle cells of the myometrium were positive for bFGF. There were no differences in uterine localization patterns or intensity during the oestrous cycle or after ovariectomy and steroid hormone supplementation. These studies demonstrate the specific localization of bFGF within the mouse uterus.

Animals↗
PubMed1992

The acute phase response in autologous bone marrow transplantation.

Due to the stress imposed by the process of bone marrow transplantation (BMT), we hypothesized that individuals receiving such a transplant underwent an acute phase response (APR). Circulating levels of C-reactive protein (CRP), haptoglobin (HAP), alpha-1 acid glycoprotein (AAG), ceruloplasmin (CER), zinc (Zn), copper (Cu), interleukin-6 (IL-6), albumin (ALB), and thyroxine-binding prealbumin (TBPA), were measured at baseline (Day -7), Day -4, Day 0 (Transplant Day), Day +2, +7, and weekly until day 28 in 14 adults receiving an autologous bone marrow transplant as Phase 1 treatment for various hematologic or solid tumor malignancies. Ten of 14 recipients survived, 9 of which had a significant increase in CRP (p = 0.012), HAP (p = 0.011), AAG (p = 0.002), and decrease in ALB (p = 0.002) and TBPA (p = 0.004) on Day +7, but not Day 0, after bone marrow reinfusion. These findings document the presence of an APR and suggest that the bone marrow transplant process (post reinfusion) initiates a stress response in the recipient.

Acute-Phase Reaction↗
PubMed1992

Myocardial infarction in patients over 75 1982-1990.

Admissions to hospital of patients aged 75 or over with symptoms suggestive of acute myocardial infarction have increased markedly since 1982. Patients over 75 present to hospital as soon after the onset of symptoms as do younger patients; they require more treatment with diuretics and digoxin than do younger patients and their fatality rate is higher. Despite this, the chance of patients over 75, especially women, being admitted to a Coronary Care Unit, and so being treated with a thrombolytic and being monitored closely for the complications of acute infarction are much less than those for patients under 75. If we are confident that we can influence the outcome of and reduce fatality from acute myocardial infarction, we should be prepared to offer elderly patients the same opportunities for treatment that we currently afford to younger patients.

Age Factors↗
PubMed1992

The dynamics of immunological memory.

Memory has long been thought of as a stable phenomenon within the immune system: once generated it lasts for a very long time. This static view of immunological memory predicts that an established population of memory cells is independent of outside influences. Recent findings, concerning the population kinetics of the peripheral pool of lymphocytes and, more directly, concerning the influence of antigen on memory cell survival, are forcing us to reassess this idea. I present here a dynamic view of immunological memory which takes into account an immune system that appears in continual flux and whose constituent cells may rely upon recurrent signals for their survival. This view of memory also makes certain predictions and these are considered.

Animals↗
PubMed1991

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

Immunological memory has generally been ascribed to the development of long-lived memory cells that can persist for years in the absence of renewed antigenic encounter. In the experiments reported here, we have adoptively transferred memory T cells in the presence and absence of priming antigen and assessed their functional survival. The results indicate that, in contrast to the traditional view, the maintenance of T cell memory requires the presence of antigen, suggesting that memory, like tolerance, is an antigen-dependent process rather than an antigen-independent state.

Animals↗
PubMed1991

Mice lacking MHC class II molecules.

We have produced mice that lack major histocompatibility complex class II antigens, permitting us to evaluate the role of these molecules in diverse aspects of T and B cell differentiation. The mutant mice show near-complete elimination of CD4+ T lymphocytes from the spleen and lymph nodes; the few remaining CD4-positive cells are preferentially localized to B cell follicles. Surprisingly, substantial numbers of CD4 single-positive cells reside in the thymus; however, these are not mature thymocytes as we currently recognize them. B lymphocytes occur in normal numbers and are capable of terminal differentiation to plasma cells. Nevertheless, several aberrations in the B cell compartment are demonstrable: a lack of germinal centers, fewer IgM+IgD+ cells in certain individuals, reduced production of serum IgG1, and complete inability to respond to T-dependent antigens. In short, the class II-negative mice have confirmed some old ideas about lymphocyte differentiation, but have provided some surprises.

Animals↗