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Biomedical subjects

R M Taylor

Publications and source records attributed to R M Taylor.

At least 91 records · Page 5Linked to original sources
PubMed1993

Renal allograft rejection: examination of adhesion blockade by antilymphocyte antibody drugs.

An assay was developed to investigate the binding of lymphocytes to cultured human renal epithelial cells. This binding was increased following lymphocyte activation by culture either with a polyclonal mitogen or with allogeneic stimulator cells. It was shown that such activation increased lymphocyte expression of the adhesion molecules CD2, LFA-1, and VLA-4. The ligand for each of these molecules was demonstrated on the surface of cultured renal epithelial cells. Polyclonal antilymphocyte antibody (ALA) preparations are used frequently to reverse intractable episodes of acute renal allograft rejection. It was demonstrated that such agents reduce the binding of activated lymphocytes to renal epithelial cells and subsequent cell lysis with a similar dose-response curve. Application of this assay may allow improved evaluation and titration of therapeutic antibody preparations. A range of monoclonal antibodies specific for components of the three adhesion molecule systems investigated in this work were added to lymphoid cell binding assays. It was found that combinations of these antibodies designed to interfere simultaneously with each of these adhesion interactions inhibited binding less well than the ALA preparation. It is likely that the superior inhibition of binding produced by ALA is due to the polyclonality of the antibodies which can block multiple epitopes on a wide range of potential adhesion molecules.

Antibodies, Monoclonal↗
PubMed1993

Renal allograft rejection: expression and function of VCAM-1 on tubular epithelial cells.

The interaction between vascular cell adhesion molecule-1 (VCAM-1) and very late antigen-4 (VLA-4) is known to play an important role in stabilizing the adhesion of lymphocytes to endothelial cells. Such cellular adhesion is crucial to many immunological processes including lymphocyte-mediated cell lysis. In this study the expression of VCAM-1 on renal tubular epithelial cells is demonstrated on biopsy sections recovered during acute renal allograft rejection. Experiments performed using epithelial cells cultured from renal tubules show that VCAM-1 is up-regulated by addition of the inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). Combination of TNF-alpha and IFN-gamma synergized to induce high levels of VCAM-1 expression. Further experiments demonstrated that the cytokines produced by activated lymphocytes in mixed leucocyte culture also up-regulate expression of VCAM-1. Assays of the adhesion of lymphoid cells to cultured renal epithelial cells showed that cytokine pretreatment of the renal cells enhanced the binding of lymphoid cells. The proportion of bound lymphoid cells was significantly reduced by addition of an antibody capable of blocking the interaction of VCAM-1 with VLA-4. This result indicated that the VCAM-1 induced on renal epithelial cells by inflammatory cytokines is functionally capable of binding VLA-4, thereby enhancing the adhesion of potentially graft-damaging lymphoid cells.

Cell Adhesion↗
PubMed1993

Experimental renal transplantation: IgG antibodies which bind to graft tubular epithelial cells cannot be detected in the serum of recipient rats after pre-operative transfusion of donor blood.

Transfusion of donor blood 7 days prior to renal transplantation between certain rat strain combinations can delay subsequent graft rejection. The mechanism responsible for this increased graft tolerance remains largely unclear. In this paper it is demonstrated that IgG antibodies with affinity for cultured donor renal epithelial cells develop in the plasma of recipient PVG rats within 7 days of transplantation of a DA rat kidney. These IgG antibodies are not specific for kidney cell-restricted antigens as the activity can be completely absorbed using cells which express donor class-I MHC antigens. However, the IgG may contribute to the acute rejection of graft cells by activating antibody-dependent cell-mediated cytolytic (ADCC) mechanisms. Transfusion of donor blood 7 days prior to renal transplantation between DA and PVG rats prevented the development of IgG antibodies which bind to resting or cytokine-activated donor renal epithelial cells. Serum taken 7 days after the transplantation of animals which had been previously transfused with donor blood was not able to activate ADCC mechanisms of donor cells. The donor blood transfusion-mediated abrogation of IgG binding to graft cells may delay the onset of graft rejection by preventing antibody-dependent graft cell lysis.

Animals↗
PubMed1993

Interaction between T lymphocytes and kidney epithelial cells during renal allograft rejection.

Cultured human renal epithelial cells were treated with the cytokines IFN-gamma and TNF-alpha and alteration in expression and function of markers including Classes I and II MHC antigens and the adhesion molecules LFA-3 and ICAM-1 was examined. It was found that a mixture of IFN-gamma and TNF-alpha induced Class II MHC antigens, up-regulated expression of Class I, LFA-3 and ICAM-1 molecules and enhanced binding of 51Cr-labeled mononuclear immune cells. However, lymphocytes failed to proliferate in response to allo-stimulation by renal epithelial cells. Lymphocytes recovered after four days in mixed culture with allogeneic renal cells were purified and re-stimulated with irradiated spleen cells for five days prior to measurement of proliferation. These lymphocytes failed to proliferate if the spleen cells were syngeneic with the renal cells used in the primary stimulation. However, if the renal cells were from a third-party donor the lymphocytes showed a normal proliferative response to the allogeneic spleen cells. It has been demonstrated that cytokine-stimulated renal epithelial cells bind, but fail to initiate proliferation of, resting allogenic lymphocytes and that activated renal cells can specifically anergise potentially graft damaging allospecific T lymphocytes.

Antigens, CD↗
PubMed1993

Sensitive monitoring of polyclonal antilymphocyte agents in renal transplantation.

Recently, our unit has used a polyclonal antilymphocyte agent frequently to treat steroid-resistant rejection or induce immunosuppression. A system of monitoring has been developed to govern the use of this powerful agent. This technique has allowed reduction in the total dose of ATG with no loss of efficacy but a decrease in the rate of serious viral infection. Powerful polyclonal agents remain an important element of immunosuppression provided that the dose of the agent is tailored to the individual response.

Animals↗
PubMed1993

Early melanoma: diagnosis and treatment. A synopsis of conference findings with relevant literature citations.

In summary, 13 panelists and 23 featured speakers convened in late January 1992 in an attempt to define early melanoma clinically and histologically; develop treatment guidelines including follow-up for early melanoma; wrestle with the controversial issues of dysplastic nevus and dysplasia; formulate plans, present and future, for public education and screening of early melanoma; and list future directions for research and primary prevention in early melanoma. The panel accomplished its goals all within the incredibly short time of three days (January 27-29, 1992). While criticism has been raised with regard to the panel's findings, the medical community owes a debt of gratitude to the participants for the selfless giving of time, energy and expertise.

Dysplastic Nevus Syndrome↗
PubMed1993

Renal allograft rejection: protection of renal epithelium from natural killer cells by cytokine-induced up-regulation of class I major histocompatibility antigens.

The potential of natural killer (NK) cells to contribute to renal allograft rejection was modelled by mixing NK cells with cultured renal epithelial cells. It was found that the renal cells were readily lysed by cytokine-activated NK cells. Renal cells which were previously stimulated by culture with either interferon-gamma (IFN-gamma) or supernatant from mixed leucocyte cultures (MLC) were relatively resistant to such lysis; stimulation with tumour necrosis factor-alpha (TNF-alpha) had no effect. None of these cytokine preparations had any effect on the lysis of renal cells by either specific cytotoxic T lymphocytes or the antibody-dependent cell-mediated cytotoxic mechanism. The expression of class I major histocompatibility complex (MHC) antigens was up-regulated by stimulation of renal cells with either IFN-gamma or MLC supernatant; treatment with TNF-alpha had no effect on the expression of these antigens. Protection from NK cell-mediated lysis appeared to correlate with the expression of class I MHC antigens by the renal cells. Artificial removal of these MHC antigens by treatment with citric acid significantly increased the susceptibility of cytokine-stimulated renal cells to lysis by activated NK cells. This increase was not caused by enhanced binding of NK cells to acid-treated renal cell targets. These results suggest that high levels of class I MHC antigen expression block NK cell triggering after engagement with renal epithelial cells. It is concluded that cytokines present within the renal microenvironment during rejection protect graft cells from lysis by NK cells by causing local upregulation of the expression of class I MHC molecules.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1992

Ceroid lipofuscinosis in the border collie dog: retinal lesions in an animal model of juvenile Batten disease.

Ceroid lipofuscinosis, an inherited disorder of lipopigment accumulation, was identified in a group of Border Collie dogs. The dogs developed mental, motor, and visual signs between age 15 and 22 months and progressed rapidly to severe neurological disease. The principal signs were blindness and gait and behavioural abnormalities with progressive dementia. Lipopigment accumulation was severe in neurones and glial cells of the central nervous system and was present in some visceral cells. Inclusions with variable ultrastructure were common in all cells of the retina, but the pigment accumulation did not damage the retinal architecture. The cytoplasmic inclusions were granular, sudanophilic, eosinophilic, and autofluorescent. Ultrastructural morphology varied, but fingerprint and curvilinear patterns predominated. The retinal lesions in the Border Collies were similar to those in English Setters with ceroid lipofuscinosis, but were much less severe than in juvenile human ceroid lipofuscinosis. This disorder bears a close resemblance to ceroid lipofuscinosis in English Setters and is another useful model for Batten's disease.

Animals↗
PubMed1992

Amelioration of clinical disease following bone marrow transplantation in fucosidase-deficient dogs.

Canine fucosidosis was studied as an animal model for the treatment of neurovisceral lysosomal storage disease. Following successful bone marrow engraftment, dogs with fucosidosis had increased levels of alpha-L-fucosidase enzyme activity in leukocytes, plasma, and neural and visceral tissues. This widespread increase in enzyme activity was accompanied by a rapid improvement in the peripheral nerve and visceral lesions of fucosidosis and a more gradual improvement in the central nervous system pathology. Long-term engraftment from an early age reduced the severity and slowed the progression of clinical neurological disease. Transplantation after the onset of clinical signs was not effective. These findings suggest that the neurological damage caused by some inherited metabolic disorders, such as fucosidosis, may be preventable but emphasise the need for early diagnosis and treatment.

Animals↗
PubMed1992

Flow cytometric crossmatching and outcome one year after renal transplantation.

Previous studies have shown that flow cytometric crossmatch assays can identify an at risk population in renal transplantation. We used the assay for recipient selection for 1 year. Recipients with donor T cell directed IgG were excluded from transplantation and those with B cell directed IgG were treated with increased immunosuppression. The transplants performed over this period (n = 126) were compared with an earlier series (n = 118) in which flow cytometric crossmatch results did not influence patient management. The results were evaluated for mortality and graft outcome at 3 months and 1 year. In addition, postoperative complications and duration of hospital stay were also assessed.

Antilymphocyte Serum↗
PubMed1992

Zinc monoglycerolate--a slow-release source of therapeutic zinc: solubilization by endogenous ligands.

A combination of 65Zn-tracer determinations, oxidative analyses for glycerol, and a bioassay for uncomplexed Zn2+ have shown that: (i) zinc monoglycerolate (ZMG) dissolves in aqueous salt solutions/physiological media by dissociation into zinc ions and glycerol, but the rate and extent of ZMG dissolution depend upon pH, and/or concentration and complexing efficiency of zinc-ligands; (ii) under physiological conditions certain ligands present in skin and blood (e.g. citrate, lactate, albumin, histidine, glutathione and other thiols and, to a lesser extent, amino acids) accelerate ZMG dissolution; and (iii) there is a general correlation between the conditional stability constants (pH 7.3, 25 degrees C) of zinc-ligand complexes and the ability of given ligands to (a) solubilize ZMG in vitro and (b) mask the irritancy of Zn2+ in vivo. These observations indicate a mechanism for the transformation of ZMG applied transdermally or subcutaneously, to bioactive zinc (anti-arthritic nutritional supplement, etc.).

Animals↗
PubMed1992

Research in social work practice: benefits of and obstacles to implementation in the Department of Veterans Affairs.

Although research is an important part of social work practice in health care, there is little systematic information that sheds light on research productivity, the benefits of conducting research, or the obstacles that must be overcome. This article represents the viewpoints of nearly all the directors of social services departments in the largest multihospital system in the United States, the Department of Veterans Affairs. The organizational characteristics of hospitals and the attitudes of the directors about research were important correlates of research productivity. Although lack of time, resources, and interest were cited as common obstacles, more than one-third of the departments were conducting or involved in at least one study. Information about the research efforts of other social services departments was considered an important resource, particularly for departments with no ongoing studies. The implications of these findings for social work research in health care are discussed.

Attitude↗
PubMed1992

Culture of bovine pulmonary artery endothelial cells on Gelfoam blocks.

Conventional methods of endothelial cell culture on monolayers and beads require enzymatic digestion, traumatic scraping, or centrifugation to transfer cells to other experimental systems. Gelfoam, a porous gelatin block, not only supports the growth of bovine pulmonary artery endothelial cells but also allows the rapid transfer of cell-laden blocks from one experimental system to another with minimal intervention. This property has been shown to be especially useful for the rapid fixation of endothelial cells for microscopy using standard histologic methods. Histology confirmed that the trabecular nature of the substrate allows endothelial cells to line the interstices of the sponge matrix and grow in a configuration that simulates the appearance of the endothelium in small vessels and capillaries. The inoculation of 1 x 10(5) endothelial cells on 7.5 mg Gelfoam (24 x 8 x 2 mm blocks) was enhanced by fibroblast growth factor and resulted in cell attachment by day 2 with a cell doubling time of 1.7 days. In addition, endothelial cells completely infiltrated 1, 5 and 7.5 mg Gelfoam blocks, as verified by histology. Assays to quantify cell number and protein were easily performed. To facilitate cell counting, the Gelfoam matrix was rapidly removed by the addition of 0.05 mg/ml collagenase, a concentration that interfered minimally with the assay for cellular protein concentration. The data demonstrate that Gelfoam is a suitable support growth matrix for the in vitro culture of bovine pulmonary artery endothelial cells.

Animals↗
PubMed1992

Improved graft outcome and reduced complications due to flow cytometric crossmatching and DR matching in renal transplantation.

Several previous studies, including our own, have indicated that flow cytometric assays can identify an at-risk population of kidney transplant recipients. We used the assay for recipient selection for a period of twelve months. Recipients with donor T cell-directed IgG were excluded from transplantation and those with B cell-directed IgG were treated with increased immunosuppression. The transplants performed over this period (n = 126) were compared with an earlier series (n = 118) where, although the flow cytometric crossmatches were performed, the results did not influence patient management. In the series where the flow cytometric crossmatch was used in management, a lower failure rate was found at three months (P = 0.037 chi square), primary non-function was reduced (P less than 0.0001, Mann-Whitney), rejection episodes were reduced (P less than 0.0001, Mann-Whitney) and the hospital stay was shorter (P less than 0.0001, Student's t). The risk factors of ischemic times, panel reactivity, exposure to previous grafts and A/B locus matching were identical between the two groups. However DR matching was found to be higher in the series with the improved results (P less than 0.0001, Mann-Whitney). In view of the significant improvement in graft success and low complication rate, we intend to continue with the policy of recipient selection by flow cytometric crossmatching and DR matching.

Adult↗
PubMed1992

Renal allograft rejection: induction and function of adhesion molecules on cultured epithelial cells.

The interaction of graft-infiltrating immune cells with donor parenchymal cells is an important early event in allograft rejection. This binding is stabilized by interaction of antigen-independent 'adhesion' molecules expressed on the two cell types. As the level of expression of these molecules can be altered during inflammation, a series of experiments was performed to examine the effects of the inflammatory cytokines interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) on adhesion molecules expressed by cultured human renal tubular epithelial cells. These cells constitutively expressed ICAM-1 and LFA-3. Incubation with IFN-gamma increased expression of ICAM-1 but had no significant effect on expression of LFA-3 (P greater than 0.05). Incubation with TNF-alpha increased expression of both ICAM-1 and LFA-3; IFN-gamma synergized with TNF-alpha to further augment expression of these molecules. Peripheral blood lymphocytes (PBL) showed an enhanced binding to allogeneic renal epithelial cell monolayers which had been pretreated with IFN-gamma or TNF-alpha. MoAbs specific for ICAM-1 or its ligand LFA-1 inhibited adhesion of PBL to either IFN-gamma- or TNF-alpha-pretreated renal cells. By contrast, antibodies specific for LFA-3 or its ligand CD2 only significantly blocked PBL adhesion to renal cells which had been pretreated with TNF-alpha. Combination of antibodies specific for multiple components of the adhesion systems produced greater inhibition of adhesion than was produced by any single MoAb. These results suggest that the inflammatory cytokines IFN-gamma and TNF-alpha up-regulate expression of functional ICAM-1 and LFA-3 molecules which can augment the binding of potentially graft-damaging lymphoid cells to renal tubular epithelial cells.

Antigens, CD↗