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Biomedical subjects

L D Wilson

Publications and source records attributed to L D Wilson.

54 records · Page 3Linked to original sources
PubMed1988

Mechanism of induction of class I major histocompatibility antigen expression by murine leukemia virus.

Alterations in expression of major histocompatibility complex (MHC) antigens on tumor cells clearly correlate with the tumorgenicity and metastatic potential of those cells. These changes in the biological behavior of the tumor cells are presumably secondary to resulting changes in their susceptibility to immune recognition and destruction. Murine leukemia viruses (MuLV) exert regulatory effects on class I genes of the MHC locus. MuLV infection results in substantial increases in cell surface expression of all three class I MHC antigens. These viral effects on MHC antigen expression profoundly influence immune-mediated interaction with the infected cells, as assessed by cytotoxic T lymphocyte recognition and killing. Control of class I MHC and beta-2 microglobulin genes by MuLV takes place via a trans-acting molecular mechanism. MuLV controls expression of widely separated endogenous cellular MHC genes, transfected xenogeneic class I MHC genes, and unintegrated chimeric genes consisting of fragments of class I MHC genes linked to a bacterial reporter gene. These findings indicate that MuLV exerts its effects on MHC expression via a trans mechanism. The MuLV-responsive sequences on the MHC genes appear to lie within 1.2 kilobases upstream of the initiation codon for those genes.

Animals↗
PubMed1987

Murine retroviruses control class I major histocompatibility antigen gene expression via a trans effect at the transcriptional level.

Moloney murine leukemia virus (M-MuLV) and Moloney murine sarcoma virus (M-MSV) exert a regulatory effect on the class I genes of the murine major histocompatibility complex (MHC). We have previously shown that M-MuLV infection of mouse fibroblasts results in a substantial increase in cell surface expression of H-2K, H-2D, and H-2L proteins, whereas M-MSV, upon coinfection of the same cells, is apparently able to override the MuLV-induced increase in H-2 expression. As a result of this modulation, immune recognition of the infected cells is profoundly altered. Our efforts have been directed toward elucidating the molecular basis for this phenomenon. We report here that stimulation of interferon production as a result of infection with MuLV does not occur and, therefore, is not the cause of MuLV-induced enhancement of MHC expression. Control of H-2 class I and beta 2-microglobulin gene expression by M-MuLV, and probably by M-MSV, takes place at the transcriptional level as indicated by nuclear runoff studies and analysis of steady-state mRNA levels. Our demonstration that M-MuLV controls expression of widely separated endogenous cellular genes (those coding for H-2D, H-2K, H-2L, and beta 2-microglobulin), transfected class I MHC genes, and unintegrated chimeric genes consisting of fragments of class I MHC genes linked to sequences encoding a procaryotic enzyme, chloramphenicol acetyltransferase, suggests that M-MuLV exerts its effect in trans and not by proviral integration in the vicinity of the H-2 gene complex. Finally, we show that the sequences of at least one MHC gene, which are responsive to trans regulation by M-MuLV, lie within 1.2 kilobases upstream of the initiation codon for that gene.

Acetyltransferases↗
PubMed1984

Monoclonal antibodies specific for the virion polypeptide, p27, of avian retroviruses.

The major component of the core structure of avian sarcoma leukosis viruses is a 27 kD molecular weight polypeptide, p27. Spleen cells from mice immunized with the Schmidt-Ruppin strain of Rous sarcoma virus (RSV) were fused with mouse myeloma cells (SP2/0), and hybridoma cell lines producing monoclonal antibodies to p27 were isolated. The monoclonal antibodies were all of the IgG1 subclass with kappa light chains. These antibodies immunoprecipitated p27 and its precursor proteins from extracts of RSV-transformed cells. Reciprocal competitive binding experiments defined five nonoverlapping antigenic determinants within p27. The monoclonal antibodies also immunoprecipitated the transforming protein, p110gag-myc, from avian myelocytomatosis virus transformed cells. Their usefulness in studies of virion maturation and viral oncogenesis is discussed.

Alpharetrovirus↗
PubMed1982

Immune responses to complex protein antigens I. MHC control of immune responses to bovine albumin.

Murine T cell proliferative and antibody responses to the multi-determinant protein bovine serum albumin (BSA) are controlled by Ir genes mapping within the H-2 gene complex. Strains possessing the H-2k, H-2a, and H-2d haplotypes are classified as high responders to BSA. In contrast, H-2b strains are low responders to BSA. Genetic mapping experiments employing strains with recombinant H-2 haplotypes indicate that both T cell proliferative and antibody responses are at least in part regulated by genes within the I-A subregion. Studies on the inhibition of T cell proliferation by monoclonal anti-Ia antibodies are consistent with the assignment of an Ir gene for BSA to the I-A subregion and strongly suggest a role for genes within the I-E/C subregions as well. The MHC-mediated control of antibody responses did not affect the affinity or the isotype of the antibody produced. The relative quantities of antibody specific for each of the three domains of BSA appears to be regulated by H-2-linked BSA Ir genes, and domain III antigenic determinants were found to be dominant in the responses of low-responder mice and in the early response of high-responder mice. This domain III epitope dominance essentially disappears by the tertiary response of high-responder mice.

Animals↗
PubMed1975

Purification and characterization of adrenodoxin reductase from bovine adrenal cortex.

NADPH-adrenodoxin reductase from steer adrenal cortex mitochrondria has been purified to homogeneity (on sodium dodecyl sulfate polyacrylamide gel electrophoresis) by chromatography on DEAE-cellulose, Sephadex, and hydroxylapatite. A molecular weight of 51,500 was determined from sodium dodecyl sulfate polyacrylamide gel electrophoresis, while sedimentation equilibrium ultracentrifugation gave a value of 49,500. All of the flavine present was identified as FAD; 1 mol/52,000 g of protein. The reductase contained 1.7% carbohydrate (using glucose as standard) by weight. Homogeneous adrenodoxin reductase exhibited a typical oxidized flavoprotein absorbance spectrum, with maxima at 270, 376, and 450 nm, and gave an absorbance ratio A450/A270 of 0.122-0.128 (depending on the preparation). Reduction of the flavoprotein with NADPH or dithionite gave progressive bleaching of the 450-nm peak. The reductase was absolutely required, in the presence of adrenodoxin, for electron transfer from NADPH to cytochrome c or to particulate cytochrome P450. Adrenodoxin refuctase is obligatory for reconstitution of 11beta-hydroxylation activity using deoxycorticosterone as substrate, and for the side-chain cleavage of 20alpha-hydroxycholesterol or cholesterol. The specific activity of the homogeneous preparation in cytochrome c reduction is at least 17,000 nmol min-1 mg of protein-1, corresponding to a turnover number of 850 min-1. No evidence for the existence of multiple forms or subunits was obtained.

Adrenal Cortex↗
PubMedDate not supplied

Complications from the use of thrombolytic agents in patients with cocaine associated chest pain.

Previous investigators have noted that patients with cocaine associated chest pain frequently have abnormal electrocardiograms, including ST segment elevation, in the absence of ongoing myocardial ischemia. The effects of these nonischemic ST segment elevations have not been evaluated. We report two patients with cocaine associated chest pain and ST segment elevations who received thrombolytic agents in the absence of myocardial ischemia. Neither patient sustained a myocardial infarction, nor had clinical evidence of reperfusion. The ST segment elevations persisted after resolution of chest pain in both patients, and both of the patients experienced complications of thrombolytic therapy. One patient sustained a hemorrhagic stroke and one had minor oral-pharyngeal bleeding. Given the lack of documented efficacy, concerns about safety, and poor specificity of the electrocardiogram for myocardial ischemia in patients with cocaine associated chest pain, thrombolytic therapy should be used with caution in these patients.

Adult↗
PubMedDate not supplied

Rapid progression of coronary artery disease in the setting of chronic cocaine abuse.

Two cases of rapidly progressing coronary artery disease in the setting of chronic cocaine abuse are presented. One patient, a 39-year-old female, developed a significant left anterior descending artery (LAD) stenosis over a 10-month period and suffered an acute myocardial infarction (MI). The second patient, a 35-year-old male, developed significant progression of three vessel coronary artery disease (CAD) over 16 months and also suffered an MI temporally related to cocaine use. Though recent cocaine use is typically considered a risk factor for acute cardiac events, chronic use may contribute to the development or rapid progression of coronary artery disease in young patients.

Adult↗
PubMedDate not supplied

Evaluation of T-cell receptor gene rearrangements in patients with recurrent patch/plaque (T2) CTCL (mycosis fungoides).

Cutaneous T-cell lymphoma is typically a clonal neoplasm of epidermotropic CD4+ T-lymphocytes that includes the entity mycosis fungoides (MF). After identification of patients with recurrent MF treated with total skin electron beam therapy (TSEBT) at the Yale University School of Medicine, this study attempted to compare T-cell receptor (TCR) gamma gene rearrangements via polymerase chain reaction (PCR) in both original and recurrent skin biopsies from these patients. Between 1974 and 1996, a total of 95 T2 MF patients were treated with TSEB, and four of these were identified for the study. Slides and tissue samples of both primary and recurrent skin biopsies for each patient were confirmed as being consistent with ME DNA for PCR was isolated from paraffin-embedded tissue samples. Using consensus primers that hybridize with conserved regions of the TCR gene, these regions of the genome were amplified. The PCR products were then analyzed by acrylamide gel electrophoresis. Of the primary and recurrent samples from four patients with a median disease-free interval (DFI) of 1222 days, only two showed evidence of a dominant TCR clone. A number of factors, including lack of sequence homology between the primers and the gene segments, the existence of multiple neoplastic cell lines, DNA degradation in the archival samples, and the presence of reactive as well as malignant lymphocytes, may have prevented the detection of dominant TCR rearranged clones in the samples. Despite the results of this study, TCR analysis via PCR and gel electrophoresis continues to be of utility in the evaluation of patients with MF when used in conjunction with other diagnostic modalities and in cases with nonspecific clinical, histopathological, and immunophenotyping findings.

Adult↗