Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The epidermodysplasia verruciformis-associated human papillomavirus type 8 (HPV-8) poses a high risk for malignant conversion of skin lesions in patients with epidermodysplasia verruciformis. For seroepidemiological studies, the HPV-8 open reading frames for E1, E2, E4, E6, E7, and L1 were bacterially expressed as beta-galactosidase fusion proteins, which were purified by preparative gel electrophoresis. Cleavage with the protease FXa at the engineered recognition site separated the beta-galactosidase polypeptide part from the viral polypeptide. Western blot analysis of 445 serum samples from a randomly selected population with the entire L1 as antigen revealed HPV-8-specific immunoglobulin G antibodies in 20% of the samples. The percentage of positive sera did not significantly differ in different age groups. In some sera, we could also detect immunoglobulin M antibodies. The use of two shortened L1 polypeptides as antigen indicated that there are at least two reactive epitopes in the case of HPV-8 L1. Several sera contained antibodies to the early proteins E1, E2, E4, and E7. E1 and E7 were predominantly detected by sera which were negative for L1. In one case, we found antibodies to E6. Two of four sera of patients with epidermodysplasia verruciformis reacted with HPV-8 L1. The prevalence of anti-HPV-8-L1 antibodies in patients with malignant melanomas was comparable to that in the normal population (27.8%) but was significantly higher in patients with cervical cancer (37.5%), basaliomas (40%), and squamous cell skin carcinomas (72.7%) and in immunocompromised patients with Hodgkin's disease (47.7%).
 ...
PMID:Prevalence of antibodies to human papillomavirus type 8 in human sera. 216 21

The Sf9 insect Spodoptora frugiperda cell line was used for heterologous expression of the cloned human cystic fibrosis transmembrane conductance regulator (CFTR) cDNA, or the cloned beta-galactosidase gene, using the baculovirus Autographa califonica as the infection vector. Using application of the patch-clamp technique, evidence for functional expression of CFTR was obtained according to the following three criteria. Firstly, whole-cell currents recorded 2 days after infection with CFTR revealed a statistically significant increase of membrane conductance, approximately 25 times above that of mock-infected control cells, with the reversal potential of the major current component being governed by the chloride equilibrium potential (ECl). Secondly, in contrast to uninfected cells and cells infected with beta-galactosidase, the membrane conductance to chloride of CFTR-injected cells was stimulated by cytosolic adenosine 3',5'-cyclic monophosphate (cAMP), which was raised by exposing the cells to 10 microM forskolin. Thirdly, recordings of currents through single channels in excised outside-out membrane patches of CFTR-infected cells revealed channels which were clearly different from the native insect chloride channel. Excised outside-out patches of CFTR-infected and forskolin-stimulated cells exhibited wave-like gating kinetics of well-resolved current transitions. All-point Gaussian distributions revealed contributions from several (five to nine) identical channels. Such channels, in excised outside-out patches, studied with a pipette [Cl-] = 40 mM and a bath [Cl-] = 150 mM, rectified the current in agreement with simple electrodiffusion and with a single-channel Goldman-Hodgkin-Katz permeability, PCl = 1. 34 x 10(-14) +/- 0.23 x 10(-14 )cm3/s (n = 5), corresponding to a physiological single-channel conductance of 2.8 +/- 0.5 pS (VM = ECl) and a limiting conductance, gamma150/150, = 7.7 +/- 1.3 pS ([Cl-]Bath = [Cl-]Cell = 150 mM). Currents recorded from multichannel excised outside-out patches could shift from the above mode of resolvable unitary conductance transitions to one which was too fast to reveal the dwell-times of closed and open states. During periods characterized by noisy currents, the variance (sigma2) of current fluctuations about their stationary mean value depicted a U-shaped function of membrane potential, with a minimum value at a pipette potential where the chloride current was shown to be zero. Thus, it can be concluded that the current fluctuations are caused by fast gating of channels specific for chloride ions. Switching back and forth between the two gating modes of clusters of chloride channels occurred from moment to moment in excised patches when the membrane potential was held at a constant value indicating cooperative gating as a result of interaction between neighbouring chloride channels.
 ...
PMID:Clusters of Cl- channels in CFTR-expressing Sf9 cells switch spontaneously between slow and fast gating modes. 876 14

The endogenous Cl- conductance of Spodoptera frugiperda (Sf9) cells was studied 20-35 h after plating out of either uninfected cells or cells infected by a baculovirus vector carrying the cloned beta-galactosidase gene (beta-Gal cells). With the cation Tris+ in the pipette and Na+ in the bath, the reversal potential of whole-cell currents was governed by the prevailing Cl- equilibrium potential and could be fitted by the Goldman-Hodgkin-Katz equation with similar permeabilities for uninfected and beta-Gal cells. In the frequency range 0.12 < f < 300 Hz, the power density spectrum of whole-cell Cl- currents could be fitted by three Lorentzians. Independent of membrane potential, >50% of the total variance of whole-cell current fluctuations was accounted for by the low frequency Lorentzian (fc = 0.40 +/- 0.03 Hz, n = 6). Single-Cl- channels showed complex gating kinetics with long lasting (seconds) openings interrupted by similar long closures. In the open state, channels exhibited fast burst-like closures. Since the patches normally contained more than a single channel, it was not possible to measure open and closed dwell-time distributions for comparing single-Cl- channel activity with the kinetic features of whole-cell currents. However, the power density spectrum of Cl- currents of cell-attached and excised outside-out patches contained both high and low frequency Lorentzian components, with the corner frequency of the slow component (fc = 0.40 +/- 0.02 Hz, n = 4) similar to that of whole-cell current fluctuations. Chloride channels exhibited multiple conductance states with similar Goldman-Hodgkin-Katz-type rectification. Single-channel permeabilities covered the range from approximately 0.6.10(-14) cm5/s to approximately 6.10(-14) cm3/s, corresponding to a limiting conductance (gamma 150/150) of approximately 3.5 pS and approximately 35 pS, respectively. All states reversed near the same membrane potential, and they exhibited similar halide ion selectivity, P1 > PCl approximately PBr. Accordingly, Cl- current amplitudes larger than current flow through the smallest channel unit resolved seem to result from simultaneous open/shut events of two or more channel units.
 ...
PMID:Endogenous chloride channels of insect sf9 cells. Evidence for coordinated activity of small elementary channel units. 878 71

Plasmids carrying the Epstein-Barr virus (EBV) latent gene EBNA1 and the EBV latent origin of replication (oriP) stay in transfected human cells as autonomously replicating extrachromosomal genetic units. They thus might represent a suitable tool for cytokine gene introduction into human tumor cells with the prospect of therapeutic antitumor vaccination. The aim of this study was to analyze whether such plasmids permit stable and efficient expression of cytokine genes in human non-Hodgkin lymphoma cells. We tested physical stability and expression levels of plasmids carrying EBNA1 and oriP for episomal maintenance, immunoglobulin light chain enhancer elements for augmentation of expression, and cytokine or marker genes after introduction into human NHL cell lines in vitro and in vivo after inoculation into nude mice. Data obtained with these EBV-based vectors were compared with another plasmid, not carrying EBNA1 and oriP. cDNAs coding for GM-CSF, IL6, TNF alpha, the chloramphenicolacetyltransferase (CAT) and the beta-galactosidase (lacZ) gene were transfected into the EBV-positive Burkitt's lymphoma cell line BL60 and the EBV-negative B cell lymphoma cell line BJA-B. EBV-derived vectors permitted a high, host cell independent transfection efficiency and high and host cell independent levels of expression. After removal of the selection pressure (hygromycin B) cytokine expression could be detected for several weeks in vitro and in vivo but, however, declined continuously. These experiments suggest that episomal BC-derived vectors represent an effective tool for cytokine gene transfer in human lymphoma cells.
 ...
PMID:Suitability of Epstein-Barr virus-based episomal vectors for expression of cytokine genes in human lymphoma cells. 908 10

We have hypothesized that adenoviral vectors might mediate gene transfer into cell lines derived from human lymphocytic malignancies, such as lymphoma, lymphocytic leukemia, and myeloma. A panel of 33 cell lines was studied for their ability to be transduced by an adenoviral (AD) vector encoding the Escherichia coli beta-galactosidase gene (AD-betagal). A cytochemical assay and a flow cytometry assay both demonstrated that a subset of lymphocytic cell lines can be efficiently transduced by adenoviral vectors. In particular, three of three anaplastic large cell lymphoma lines, two of two Hodgkin's disease cell lines, two of seven Burkitt's lymphoma cell lines, and three of five myeloma cell lines exhibited efficient gene transfer. The ability of an AD vector expressing the thymidine kinase (tk) gene from herpes simplex virus-1 (AD-tk) followed by ganciclovir (GCV) to kill 11 of these lymphocytic cell lines was studied. In eight of the cell lines tested, more than 68% of the cells were killed by AD-tk/GCV. Similar results were obtained using an adenoviral vector expressing the wild-type p53 tumor suppressor gene (AD-p53). Thus, AD-tk/GCV and AD-p53 both demonstrated efficient killing of these cell lines. These data document that adenoviral vectors are valuable reagents for the introduction of genes into selected lymphocytic cell lines. These data also suggest that adenoviral vectors might be useful for gene therapy of subsets of lymphocytic malignancy.
 ...
PMID:Adenoviral vectors efficiently target cell lines derived from selected lymphocytic malignancies, including anaplastic large cell lymphoma and Hodgkin's disease. 981 92