Search PubMed⌕ Search

Biomedical subjects

C M Walker

Publications and source records attributed to C M Walker.

At least 55 records · Page 3Linked to original sources
PubMed1994

An epitope in the V1 domain of the simian immunodeficiency virus (SIV) gp120 protein is recognized by CD8+ cytotoxic T lymphocytes from an SIV-infected rhesus macaque.

Cytotoxic T-lymphocyte (CTL) responses against the external envelope glycoprotein (gp120) of the simian immunodeficiency virus (SIV) were studied in a rhesus macaque infected with SIVmac/239. CD8+ T cells enriched from concanavalin A-stimulated peripheral blood mononuclear cells lysed autologous target cells infected with recombinant vaccinia virus vectors expressing the SIVmac/239 or SIVsm/H4 envelope protein, which share approximately 80% identity in amino acid sequence. A CD8+ CTL line derived by limiting dilution culture of the concanavalin A-stimulated lymphocytes was also specific for the envelope proteins of both SIV isolates. Mapping studies revealed that this cell line recognized an epitope between amino acids 113 and 121 (CNKSETDRW) in the V1 domain of gp120. Amino acid substitutions are observed at positions 116 and 120 among viruses of the SIVsm/mac/human immunodeficiency virus type 2 group, and thus synthetic peptides representing these variants were tested for the ability to sensitize target cells for lysis by the CTL line. Autologous target cells sensitized with a synthetic peptide representing the SIVmac/239 sequence were efficiently killed. In contrast, recognition of target cells was reduced or abolished when peptides representing the amino acid substitutions at position 116 or 120 of other SIVmac, SIVsm, SIVmne, or SIVstm strains were tested. Further studies of CTL responses against this epitope could provide insights into mechanisms of variability within the gp120 V1 domain and its importance in evasion of immunity in infected or vaccinated monkeys.

Amino Acid Sequence↗
PubMed1994

Management of the coronary-subclavian steal syndrome with balloon angioplasty. A case report and review of the literature.

A fifty-two-year-old woman with angina pectoris due to coronary-subclavian steal syndrome through a left internal mammary artery graft placed distal to a left anterior descending artery stenosis is presented. Retrograde flow through the mammary artery graft due to severe left subclavian stenosis was observed angiographically. Accordingly, left subclavian balloon angioplasty was performed, restoring normal antegrade flow through the internal mammary artery graft and resulting in resolution of the patient's symptoms. The patient was subsequently discharged with no evidence of angina. Carotid-subclavian bypass surgery was avoided, reducing patient discomfort, procedural risk, and expense.

Angina Pectoris↗
PubMed1993

Fate of lesion-related side branches after coronary artery stenting.

OBJECTIVES: The aim of this study was to assess the immediate and long-term patency of lesion-associated side branches after coronary artery stenting. BACKGROUND: The possible adverse effects related to implantation of coronary stents are not completely known. An important potential complication of stenting is side branch occlusion due to mechanical obstruction or thrombosis. METHODS: Serial coronary angiography was performed in 153 patients (167 lesions) at baseline, after conventional balloon angioplasty, immediately after Palmaz-Schatz stent placement and at 6 months. The patency of side branches, where present, was analyzed at each of these points. RESULTS: Of 167 lesions stented, 57 stent placements spanned 66 side branches with a diameter > or = 1 mm. Twenty-seven (41%) of these side branches had > or = 50% ostial stenosis before standard balloon angioplasty. Six side branches became occluded after standard balloon angioplasty and remained occluded after stenting. Of the 60 side branches patent after conventional angioplasty, 57 (95%) remained patent immediately after stenting. All three side branches that became occluded after stenting had > or = 50% ostial stenosis at baseline. All 60 side branches, including the 3 initially occluded after stenting, were patent at 6-month follow-up. CONCLUSIONS: These findings demonstrate that 1) acute side branch occlusion due to coronary stenting occurs infrequently; 2) when side branch occlusion occurs, it is associated with intrinsic ostial disease; and 3) the patency of side branch ostia is well maintained at long-term follow-up.

Adult↗
PubMed1993

Hepatitis C virus-specific CTL responses in the liver of chimpanzees with acute and chronic hepatitis C.

Hepatitis C virus (HCV)-specific CTL responses were evaluated in two chimpanzees (Pan troglodytes) during the acute and chronic phases of HCV infection. CD8+ T lymphocytes were isolated from liver tissue homogenates using anti-CD8 antibody-coated magnetic beads and then stimulated with anti-CD3 antibodies, IL-2, and irradiated human PBMC using limiting dilution culture conditions. HCV-specific cytotoxic activity of expanding CD8+ cell lines was assessed against autologous lymphoblastoid cell lines infected with recombinant vaccinia virus vectors encoding HCV Ag. CD8+ T cell lines specific for structural and nonstructural proteins of HCV were established from both animals. Cytolytic activity was blocked with anti-CD8 or anti-class I MHC antibodies, indicating that class I MHC molecules were involved in presentation of viral Ag to the CTL. Overlapping synthetic peptides were used to define a 12 amino acid segment of the nonstructural 3 (NS3) protein recognized by CTL lines from both chimpanzees. Studies with truncated peptides revealed that these CD8+ cell lines were directed against overlapping epitopes presented by distinct class I restriction elements of the chimpanzee MHC complex. CD8+ cell lines with identical specificities for an NS3 epitope were generated from one chronically infected animal at 16 and 28 wk postinfection. These results indicate that virus-specific CTL populations persist in the liver for months, but are unable to resolve chronic HCV infection.

Acute Disease↗
PubMed1993

Non-cytolytic control of HIV replication by CD8+ T cells.

Replication of the human immunodeficiency virus (HIV) in CD4+ cells is suppressed in the presence of CD8+ cells from asymptomatic HIV-infected individuals. Although these CD8+ cells mediate HIV-specific, class I MHC restricted CTL activity, the predominant mechanism for inhibiting virus replication requires neither contact nor MHC matching between the CD8+ effector cells and CD4+ targets. Based on these data, a model involving two tiers of control on HIV replication by CD8+ cells is proposed. The first level would be mediated by a diffusible CD8+ cell-derived factor that prevents expression of the retroviral genome in a non-MHC restricted fashion. When this transcriptional control is lost, production of HIV proteins would sensitize the cell for lysis by class I MHC restricted, virus-specific CTL.

Animals↗
PubMed1993

Class I major histocompatibility complex-restricted cytotoxic T cell responses to vaccinia virus in humans.

Cytotoxic T lymphocyte (CTL) responses to vaccinia virus (VV) were studied in human subjects receiving smallpox vaccine by dermal scarification. After in vitro restimulation with VV, peripheral blood mononuclear cells (PBMCs) from three of six vaccinated subjects killed virus-infected target cells. VV-specific, HLA-restricted CTL activity was mediated primarily by CD8+ cells, although low levels of lytic activity by CD4+ cells were observed in some experiments. Two of the three responders had no history of exposure to VV prior to vaccination, whereas all three non-responders were vaccinated against smallpox during childhood. PBMCs from an additional three subjects who had received smallpox vaccine at least 20 years previously were negative for CTL activity. These data suggest that the duration of memory CTL populations against VV in the peripheral blood is limited, and that pre-existing immunity to VV may interfere with boosting of the CTL response upon revaccination.

CD8 Antigens↗
PubMed1992

Primary chimpanzee skin fibroblast cells are fully permissive for human cytomegalovirus replication.

Cytomegaloviruses generally display a host range restricted to differentiated cell types from the species they infect. For human cytomegalovirus (HCMV) this has meant that with few exceptions tissue culture systems have relied on the use of primary foreskin fibroblast (HF) cells or primary human embryonic lung cells to study gene expression and virus replication functions. We have observed that primary skin fibroblast (CF) cells derived from the chimpanzee (Pan troglodytes) support the replication of a laboratory strain (Towne) of HCMV. The kinetics of gene expression of the Towne strain grown in CF or HF cells appeared to be equivalent. Titres of progeny virions grown in CF cells appeared to be reduced 10-fold relative to those of virus grown in HF cells. In contrast, replication of the Towne virus was not supported by growth in WES cells (ATCC no. CRL 1609), a chimpanzee skin fibroblast cell line transformed by an adenovirus 12-simian virus 40 hybrid. This study shows that HCMV is less parochial in its host range than previously thought.

Animals↗
PubMed1992

Emergent use of balloon-expandable coronary artery stenting for failed percutaneous transluminal coronary angioplasty.

BACKGROUND: The balloon-expandable intracoronary stent developed by Palmaz and Schatz is undergoing clinical evaluation for use in unfavorable anatomic situations and in the prevention of restenosis. Because the stent's mechanism of action would suggest effectiveness in salvaging certain percutaneous transluminal coronary angioplasty (PTCA) failures, we retrospectively examined the results of emergency unplanned coronary artery stenting for failed PTCA procedures, including acute occlusion. METHODS AND RESULTS: The study population consisted of all US patients receiving emergency unplanned stent implantation in a nonrandomized fashion at seven centers over a 2 1/2-year period (n = 56). All available medical records and angiograms were reviewed to determine retrospectively the reason for stenting: Group 1 consisted of 23 patients with a suboptimal angioplasty result; group 2 included patients with evidence of impending vessel closure after PTCA (n = 15); and group 3 were patients with frank acute occlusion after PTCA (n = 18). The immediate and final (30-day) results of stenting were examined with respect to major complications, which included death, need for coronary artery bypass graft surgery, and occurrence of myocardial infarction. Finally, restenosis rates (greater than or equal to 50% stenosis) based on follow-up angiography were calculated. Baseline characteristics of the study population included a mean +/- SD age of 58 +/- 11 years and a large prevalence of angiographic characteristics generally considered unfavorable for PTCA, which include lesion eccentricity (49%), intimal dissection (9%), or angiographically visible thrombus (6%). After conventional balloon angioplasty, there was an increased incidence of intimal dissection (74%) and thrombus formation (38%), and overall stenosis severity was unchanged (75 +/- 12% versus 70 +/- 27%, p = NS). Successful stent deployment was achieved in 55 (98%) of 56 patients with initial success (freedom from death, surgery, and infarction) in 52 (93%) of 56 patients. The success rate at 1 month fell to 71% primarily because of the occurrence of subacute stent thrombosis (16%) and its associated complications. Overall, major complications occurred in 16 (29%) of 56 patients within 30 days. The only predictor of subacute stent thrombosis in multiple stepwise logistic regression analysis was the presence of angiographically visible thrombus after stenting (p = 0.03). Angiographic restenosis was documented in eight (23%) of 35 eligible patients. CONCLUSIONS: Emergency stenting may be a useful and effective treatment for failed angioplasty. High initial success rates (greater than 90%) can be achieved, but subsequent complications, often related to subacute thrombosis, occur in a substantial portion of patients. Patients who receive stents on an emergency basis, particularly those with previous acute occlusion, should be considered to be at greater than usual risk for complications and receive more careful anticoagulation and follow-up.

Aged↗
PubMed1991

Effect of intracoronary stenting on intimal dissection after balloon angioplasty: results of quantitative and qualitative coronary analysis.

The effect of the Palmaz-Schatz stent on the angiographic appearance and residual luminal stenosis in patients with intimal dissection after balloon angioplasty was evaluated in 84 consecutive patients (90 lesions). Coronary angiography was performed before angioplasty, after conventional angioplasty and after stent implantation. The degree of intimal disruption was assessed as follows: grade 0, no dissection; grade 1, simple dissection (intraluminal linear defect or extraluminal cap extravasation); or grade 2, complex dissection (nonlinear spiral defect or luminal defect with multiple irregular borders). Quantitative coronary analysis of digitized cineangiograms was performed with use of a computerized automatic edge detection algorithm. After balloon angioplasty, 31 (34%) of 90 lesions demonstrated intimal dissection (18 simple, 13 complex). After stent implantation, intimal dissection improved by greater than or equal to 1 grade in 29 (94%) of the 31 lesions with 27 (87%) reduced to grade 0 (that is, no dissection). Dissection grade improved after stenting in 16 (89%) of 18 simple dissections and in all 13 complex dissections. Mean diameter stenosis was 77 +/- 17% before angioplasty, 47 +/- 17% after angioplasty and 14 +/- 10% after stenting (before angioplasty vs. after angioplasty and after angioplasty vs. after stenting, p less than 0.0001). In conclusion, intracoronary stenting is effective in reducing the residual luminal stenosis and in improving the angiographic appearance of intimal dissections after conventional balloon angioplasty.

Adult↗
PubMed1991

CD8+ T cells from HIV-1-infected individuals inhibit acute infection by human and primate immunodeficiency viruses.

T lymphocytes expressing the CD8 surface antigen block HIV replication in CD4+ peripheral blood cells from HIV-infected individuals. We report here that CD4+ cells from HIV seronegative donors, when infected in vitro with HIV, also do not replicate virus when cocultured with CD8+ T cells from HIV-infected individuals. CD8+ cells from HIV-uninfected donors did not show this effect on virus replication. HLA-restriction of the antiviral response was not observed, and virus-containing cells were not eliminated from culture. The antiviral activity was broadly cross-reactive, as CD8+ cells from individuals infected only with HIV-1 suppressed the replication of diverse strains of HIV-1 and HIV-2, as well as the simian immunodeficiency virus. This ability of CD8+ cells to control HIV replication could play an important role in the maintenance of an asymptomatic state in HIV-infected individuals.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

Suppression of human immunodeficiency virus replication by CD8+ cells from infected and uninfected chimpanzees.

Over a 4-year period, infectious human immunodeficiency virus type 1 (HIV-1) has been recovered from cultured peripheral blood mononuclear cells (PBMC) of virus-infected animals only intermittently and at relatively low titers. In examining the possible mechanism for this observation, CD4+ cells or CD8+ cells were removed by panning from the PMBC before culture. A dramatic increase in frequency of HIV-1 recovery as well as in the level of virus replication was observed in the CD4+ cell-enriched or CD8+ cell-depleted cultures of PBMC from 3/3 infected animals. Moreover, addition of purified CD8+ effector cells from all 6 HIV-infected and 5/10 uninfected animals to an equal number of HIV-1 acutely infected purified CD4+ target cells resulted in 75-100% suppression of virus production. CD8+ cells from 3 additional uninfected animals caused delayed replication kinetics and moderate to low suppression of peak virus production. These findings contrast with the previously recognized absence of this HIV-1-suppressing activity of CD8+ cells from seronegative humans. This CD8+ cell-mediated suppression of viral replication could help explain the natural resistance of chimpanzees to HIV-induced disease.

Animals↗
PubMed1991

Inhibition of human immunodeficiency virus replication in acutely infected CD4+ cells by CD8+ cells involves a noncytotoxic mechanism.

The mechanism by which CD8+ T cells from human immunodeficiency virus (HIV)-infected individuals suppress HIV replication in acutely infected CD4+ T cells was investigated. Cytotoxicity was not involved, as the antiviral activity of the CD8+ cells did not correlate with the ability to lyse HIV-infected or uninfected CD4+ T cells. In addition, the frequency of HIV-infected CD4+ cells increased during coculture with CD8+ T cells even in the absence of detectable levels of virus replication. Moreover, separation of the CD4+ and CD8+ cells by a 0.4-micron-pore-size filter delayed HIV replication, indicating a role, at least in part, for a soluble factor. However, cell contact was required for optimal antiviral activity. These results extend further the observation on the mechanism of antiviral HIV activity by CD8+ cells from infected individuals. They support the conclusion that CD8+ cells can play a major role in preventing development of disease in HIV-infected individuals.

Antibodies, Monoclonal↗
PubMed1990

CD8+ lymphocytes suppress HIV production by autologous CD4+ cells without eliminating the infected cells from culture.

Studies of separated peripheral blood mononuclear cell subsets have indicated that the CD8+ lymphocyte is the primary cell type responsible for suppressing human immunodeficiency virus (HIV) replication by infected CD4+ cells. The effect of this antiviral activity is dose-dependent and does not involve killing of the infected cell. These observations indicate that this response is distinct from the anti-HIV cytotoxic mechanisms also described for human CD8+ cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1990

Coronary stents: a review of recent developments.

Coronary stent placement is one of the newest treatments for occlusion of the coronary arteries. This technique has the potential to minimize restenosis and reduce or eliminate abrupt closure, common complications of percutaneous transluminal coronary angioplasty (PTCA). Initial studies in Europe in the mid-1980s indicated a problem with restenosis due to thrombosis and intimal hyperplasia in stented arteries. Recent investigational studies of the Palmaz balloon-expandable stent in the United States, however, show great promise in solving those problems. It is hoped that coronary stenting may be used for lesions now treated by coronary artery bypass graft surgery, as well as for improving the outcome of PTCA.

Animals↗
PubMed1990

Recent developments in coronary atherectomy.

Percutaneous coronary atherectomy (PCA) is one of the newest treatments for coronary artery disease. In this technique, arterial plaque is mechanically removed from the interior of the artery by a tool located on the tip of a catheter placed inside the coronary artery nonsurgically. Clinical studies of several coronary atherectomy devices are in process in the United States and abroad. As atherosclerotic material is removed or debulked, abrupt reclosure or restenosis rates may potentially be lower compared with conventional percutaneous transluminal coronary angioplasty (PTCA). PCA may also clear longer and more diffuse lesions, with long-term clinical success, than are successfully being treated by PTCA. Due to the rigidity of the atherectomy catheter, only lesions in major coronary arteries may be approached with these devices at present. It is hoped that PCA may supplement current methods of treating coronary artery disease, including coronary artery bypass graft surgery and PTCA.

Angioplasty, Balloon, Coronary↗
PubMed1989

CD8+ T lymphocyte control of HIV replication in cultured CD4+ cells varies among infected individuals.

Production of the human immunodeficiency virus (HIV) by cultured peripheral blood mononuclear cells (PMC) from many seropositive individuals is inhibited by the presence of CD8+ T lymphocytes. In a study of 10 subjects, high levels of virus replication could be detected in cultures of purified CD4+ cells, but not in unseparated PMC. Addition of highly purified, autologous CD8+ cells to the enriched CD4+ cells resulted in a dose-dependent inhibition of HIV growth and revealed that for some individuals, even low numbers of CD8+ cells can prevent replication of the virus. The data also indicated that culturing enriched CD4+ cells could greatly enhance detection of infectious virus in blood specimens and demonstrated that the CD4+ molecule is expressed on infected T cells isolated directly from the peripheral blood.

Acquired Immunodeficiency Syndrome↗