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Biomedical subjects

A Mayne

Publications and source records attributed to A Mayne.

At least 37 records · Page 2Linked to original sources
PubMed1994

The absence of constitutive and induced expression of critical cell-adhesion molecules on human cardiac myocytes. Its role in transplant rejection.

Fetal human cardiac myocytes (FHCM) and a cell line derived from FHCM, termed W1, constitutively express low levels of MHC class I antigens and significant levels of ICAM-1 (CD54), and LFA-3 (CD58) but do not express LFA-1 alpha (CD11a), LFA-1 beta (CD18), GMP-140 (CD62), BB1-B7, VCAM-1, and ELAM-1. In vitro incubation of FHCM or the W-1 cell line for varying periods with varying concentrations of IFN-gamma, TNF-alpha, Poly IC, LPS, IL-alpha, IL-1 beta, PMA, PDBu, and supernatant fluids from Con A-activated PBMC or allogeneic MLR cultures failed to induce cell adhesion molecules (CAMs) or costimulatory molecules that are not constitutively expressed on these cells except for MHC class II antigens. In addition, IFN-gamma, Con A, and MLR supernatant fluids (in order of biological activity) not only induced MHC class II antigens but also markedly increased the mean density of expression per cell of MHC class I and ICAM-1. Analysis of the stability of MHC class I/II molecules using agents like brefeldin-A and Western blot analysis of MHC class II molecules suggest that these ligands are very stably expressed on myocytes. Our previous studies have documented the failure of MHC-expressing FHCM to induce an alloproliferative response. The results of the present studies show that this failure is not secondary to the absence of ICAM-1 or LFA-3 or the presence of unstable MHC molecules but is most likely due to the absence of other CAMs/costimulatory molecules that are critically required for inducing allogeneic activation.

Cell Adhesion Molecules↗
PubMed1993

Host T-cell primary allosensitization to MHC class-I- and class-II-expressing human cardiac myocytes requires the presence of a second signal.

Normal FHCMs, or transformed cell lines derived from FHCMs, such as W1, even after induction of MHC antigens by pretreatment with IFN-gamma, failed to induce proliferation of allogeneic human PBMCs in vitro. To test the hypothesis that antigen-specific T-cell activation and proliferation require not only the binding of the TCR with its ligand, the MHC molecule, but also a second signal that involves the interaction of T-cell surface molecules with their natural ligands on the stimulating cells, a mAb against CD28 was used. Cocultures of allogeneic PBMCs with IFN-gamma-pretreated irradiated FHCMs or the W1 cell line in microtiter plates containing immobilized anti-CD28 mAb induced marked stimulator cells MHC class-II-specific proliferative responses. The W1 cell line and FHCMs failed to express detectable levels of the BB1/B7 molecule (the natural ligand for CD28) as determined by flow microfluorometry or mRNA levels coding for BB1/B7 as determined by RT-PCR. These data suggest that one of the probably reasons for the failure of MHC-expressing cardiac myocytes to induce allogeneic activation is the absence of costimulatory signals.

Base Sequence↗
PubMed1993

Qualitative and quantitative studies of cytokines synthesized and secreted by non-human primate peripheral blood mononuclear cells.

Non-human primates are being utilized in a variety of pre-clinical studies, including those involved with mechanisms of organ transplant rejection and those being used as models to test the efficacy of vaccines against a variety of infectious diseases, most notably AIDS. These studies clearly involve immunological effector mechanisms, which include the interaction between T cells, B cells, monocytes, and cytokines that regulate these interactions. However, there is very little known about assays and quantitation of cytokines from non-human primates. In attempts to address this issue, bioassays, commercially available EIA kits, and primer pairs and probes specific for human cytokines were evaluated for their ability to detect and quantitate the non-human primate homologues. Data suggest that although the EIA kits that were evaluated for human IL-1 alpha, IFN-gamma, and TNF-beta failed, the EIA kits for IL-1 beta, IL-2, IL-4, IL-6, and TNF-alpha, the bioassays and RT-PCR assays for each of the cytokines were successful in detection and most likely quantitation of the non-human primate cytokine homologues. These assays will greatly facilitate future studies on the role of cytokines in these non-human primate studies.

Animals↗
PubMed1991

Establishment of a human fetal cardiac myocyte cell line.

Human cardiac myocytes undergo degeneration, cytolysis, and necrosis in a number of clinical disease conditions such as myocarditis, dilated cardiomyopathy, and during episodes of cardiac allograft rejection. The precise cellular, biochemical, and molecular mechanisms that lead to such abnormalities in myocytes have been difficult to investigate because at present it is not possible to obtain and maintain viable cell cultures of human adult cardiac myocytes in vitro. However, human fetal cardiac myocytes are relatively easy to maintain and culture in vitro, but their limited availability and growth, variability from one preparation to another, and varying degrees of contamination with endothelial and epithelial cell types have made it difficult to obtain reliable data on the effect of cardiotropic viruses and cardiotoxic drugs on such myocytes. These thoughts prompted us to attempt to derive a cell line of human cardiac origin. Highly enriched human fetal cardiac myocytes were transfected with the plasmids pSV2Neo and pRSVTAg and gave rise to a cell line (W1) which has been maintained in culture for 1 yr. Morphologic and phenotypic analyses of W1 cells by flow microfluorometry and immunoperoxidase techniques indicate that the W1 cell line shares many properties of human fetal cardiac myocytes, but appears not to react with specific antibodies known to react with markers unique to human endothelial, epithelial, skeletal muscle, and dendritic cells. These preliminary data suggest that the W1 cells may provide a unique source of an established cell line that shares many properties ascribed to human cardiac myocytes.

Blotting, Northern↗
PubMed1991

Abnormal expression of histocompatibility and mitochondrial antigens by cardiac tissue from patients with myocarditis and dilated cardiomyopathy.

Autoantibodies against the adenine nucleotide translocator (ANT), the branched chain alpha-ketoacid dehydrogenase (BCKD) complex proteins, and myosin have been implicated in the pathogenesis of human dilated cardiomyopathy (DCM). Cardiac tissue from patients with DCM and, for control purposes, cardiac tissue from patients with other forms of cardiomyopathy and from patients with no history of cardiac disease were stained with heterologous and ANT-, BCKD-, and myosin-specific affinity-purified sera from DCM patients. Data demonstrate that although anti-myosin stains tissues from both patients and normal controls, the ANT- and BCKD-specific heterologous and affinity-purified sera from DCM patients stain only cardiac tissues from DCM patients. Intense staining in patchy areas of cardiac tissue suggests that abnormal increased expression of these putative autoantigens occurs in discrete areas of cardiac myocytes. The reactivity of the antisera was organ specific and only seen in tissues from DCM patients. The organ and disease specificity of these findings suggests that such expression may play an important role in the pathogenesis of human DCM.

Adult↗
PubMed1990

Hepatitis B vaccine in the prevention of perinatally transmitted hepatitis B virus infection: final report on a West Midlands pilot study.

A four-dose vaccination schedule was used to interrupt perinatal transmission of hepatitis B virus from carrier mothers to their babies. Of 49 babies immunised and successfully followed up, 43 (88%) became immune: 15 out of 21 (71%) of babies born to HBeAg + mothers became immune, the other 6 becoming the only carrier babies in the study. Without immunisation a carrier rate in excess of 70% would have been expected in this high-risk group. Vaccine alone, given in a rapid immunisation schedule, protected the majority of babies at risk. In those babies in whom the carrier state occurred in spite of immunisation, infection may have taken place in utero, or the infant may have failed to produce adequate antibody in response to the vaccine.

Carrier State↗
PubMed1990

The influence of MHC and non-MHC genes on the nature of murine cardiac allograft rejection. I. Kinetic analysis of mononuclear cell infiltrate and MHC-class I/class II expression in donor tissue.

While normal cardiac tissue expresses low levels of MHC-class I, undetectable levels of MHC-class II antigens, and no mononuclear cell infiltrates, posttransplantation allogeneic donor cardiac tissue demonstrates dramatic increases of MHC-class I/class II expression coincident with the infiltration of the tissue with mononuclear cells. Results of this study demonstrate that the kinetics of MHC-class I/II antigen expression and the phenotype of mononuclear cell infiltrate are influenced, to a great degree, by the genetic H-2, intra-H-2 and non-H-2 incompatibility between donor and recipient strains of mice. Increases of MHC-class I precede class II expression in cells from donor cardiac tissue from completely allogeneic BALB/c, H-2-disparate B10.D2, B10.BR, and K, I-A and I-E-disparate B10.T (6R) strains of mice implanted in B10 recipients. In contrast, increase in the level of MHC-class II precedes MHC-class I increases in donor cardiac tissue from H-2-identical but non-H-2-incompatible A. By and the I-E + H-2D end-different B10.A(5R) donor tissue. The completely allogeneic, H-2-disparate or K, I-A, I-E-disparate donor cardiac tissue induced the infiltration of predominantly CD8+ T cells, whereas the non H-2 and I-E + H-2D end-different donor cardiac tissue induced the infiltration of predominantly CD4+ T cells. Finally, whereas bm1 donor cardiac tissue is rejected by B6 recipients by day 32, the (bm1 x bm12)F1 allografts are rejected by day 20, and both express MHC-class I antigens followed by MHC-class II antigens, and contain predominantly CD8+ T cells. In contrast, bm12 allografts are not rejected by B6 recipients, express chronic low levels of both MHC-class I and II antigens, and contain predominantly CD4+ T cells. Of interest is our preliminary finding that bm12 allografts placed in one ear of B6 recipients appear to modify the kinetics of MHC antigen expression and the predominant phenotype of mononuclear cell infiltrates in bm1 allografts placed in the opposite ear. Cumulatively, these data suggest that the type of genetic disparity between cardiac donor and recipient greatly influences the quantitative and qualitative host responses.

Animals↗
PubMed1989

Subglottic haemangioma in the infant: contribution by CO2 laser.

The availability of the low intensity CO2 laser beam, and the possibility of defocalization that is associated with control of subglottic high frequency jet ventilation, requires a more interventionist attitude regarding dyspnoea caused by a subglottic haemangioma in the infant. It is indeed possible reliably to reduce the size of the subglottic haemangioma, and thus to avoid a lengthy period of intensive care, as well as the problems of prolonged intubation or tracheostomy for drainage, while also avoiding long term steroid therapy. This approach in no way affects the spontaneous evolution of subglottic haemangioma in the infant; there is a tendency for the haemangioma to regress after the age of one year. The treatment does, however, permit a considerable improvement in the comfort of the infant's life during this difficult period between 3 and 12 months. We illustrate this new attitude by presenting a report on four cases.

Carbon Dioxide↗
PubMed1988

Neuralgia following lumbar sympathectomy.

Between March and October 1986, 33 consecutive patients underwent unilateral lumbar sympathectomy in the Thoracic and Cardiovascular Surgical Unit of the Catholic University in Louvain, Belgium. Ten patients experienced postsympathectomy neuralgia. After a single epidural injection of fentanyl, 50 micrograms, and methylprednisolone 80 mg, pain disappeared completely in six patients. Neuralgia recurred in four patients requiring repeat epidural injection with relief of residual symptoms. Epidural infiltration is a reliable treatment for neuralgia after lumbar sympathectomy.

Drug Therapy, Combination↗
PubMed1987

Halothane versus isoflurane for short ENT procedures with spontaneous respiration in children.

This study compares halothane with isoflurane for short ENT procedures performed under spontaneous breathing in 80 children. Monitoring included ECG, arterial pressure, PECO2 and respiratory rate. Induction, maintenance and recovery durations were recorded. Induction time was further subdivided into an initial phase followed by a plateau according to delivered halogen concentrations. Inhalation induction was possible with isoflurane without major side effects as long as the drug concentration was increased slowly. This precaution was not needed with halothane. No respiratory depression could be attributed to either of the tested drugs. Isoflurane elicited a significant drop in arterial pressure with a concomitant increase in heart rate. Recovery times were shorter in the isoflurane group.

Anesthesia, Inhalation↗
PubMed1986

Pulmonary edema following acute upper airway obstruction.

During recovery, our patient presented an acute upper airway occlusion. After the removal of the airway obstruction, he developed a massive bilateral pulmonary edema with an acute hypoxemia. Hemodynamic measures following this incident show that mean and wedged pulmonary pressures are in the normal ranges. Several cases, associating acute upper airway obstruction, massive bilateral pulmonary edema and low or normal filling pressures, have been reported in literature. Three mechanisms have been postulated to explain this phenomenon; a dramatic increase of the negativity of the interstitial pulmonary pressure, a significative augmentation of the after-load and the hypoxic pulmonary reflex vasoconstriction.

Aged↗
PubMedDate not supplied

Cloning, sequencing, and homology analysis of nonhuman primate Fas/Fas-ligand and co-stimulatory molecules.

The finding that a single administration of select recombinant human cytokines to nonhuman primates leads to potent cytokine-neutralizing antibody responses in the heterologous host despite >95% homology at the nucleotide and protein level prompted our laboratory to clone, sequence, and prepare recombinant nonhuman primate cytokines, chemokines, growth factors, and other immunoregulatory molecules. In the present report, we present findings on the gene sequences encoding the nonhuman primate homologues of human CD80, CD86, their ligands CD28 and CD152, CD154, CD95, and CD95-L from rhesus macaques and for phylogenetic analysis from pig-tailed macaques, African sooty mangabey monkeys, baboons, and vervets as well as select molecules from the New World aotus and marmoset monkeys. With the exception of CD95, the homology between nonhuman primate and human co-stimulatory molecules was above 95%. In contrast, CD95 was only 89.2% homologous to human CD95, but the differences were essentially found in the transmembrane and intracellular (death) domains. The extracellular portion of CD95 was more homologous which was in accordance with approximately 98% homology between Old World monkey and human CD95-L. In general, sequences from the New World monkey species appeared equidistant to sequences from Old World species and humans in terms of homology suggesting distinct evolutionary patterns. Of interest was the isolation of various splice variants of monkey CD86, CD152 (CTLA-4), CD154, and CD95 transcripts. This is also the first report documenting the occurrence of natural CD86 variants with deleted transmembrane domains, found both in sooty mangabeys and baboon RNA samples. Monkey CD95 showed various deletions and addition of residues in the transmembrane and intracytoplasmic domains compared with human CD95 and between Old and New World species. Subcloning of rhesus CD154 into an expression vector demonstrated expression of a functional protein in cell culture. The other genes are being cloned into expression vectors for the preparation and biological characterization of the nonhuman primate molecules. These investigations will provide novel reagents for in vivo use as immunomodulatory reagents in nonhuman primates in studies which may provide a rationale for their use in humans.

Abatacept↗
PubMedDate not supplied

TH1/TH2 subset analysis. I. Establishment of criteria for subset identification in PBMC samples from nonhuman primates.

Cloned T-cell lines from two nonhuman primate species were phenotyped and their mRNA analyzed for cytokine profiles by RT-PCR procedures. PBMC from rhesus macaques showed a relatively high frequency of cloned T-cell lines with a TH1-like profile; PBMC from sooty mangabeys showed a relatively high frequency of TH2-like cloned T-cell lines. In vitro activated macaque PBMC also resulted in a high frequency of CD4+, CD8+ dual marked cells. These findings suggest that cytokine analysis of cloned T-cell lines from nonhuman primates provides a means to distinguish subsets of both CD4+ and CD8+ T cells.

Animals↗