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C Beck

Publications and source records attributed to C Beck.

At least 73 records · Page 4Linked to original sources
PubMed1996

Coexpression of interleukin-4 and B7.1 in murine tumor cells leads to improved tumor rejection and vaccine effect compared to single gene transfectants and a classical adjuvant.

To improve the vaccine potency of gene-modified tumor cells, using retroviruses, we have expressed the B7.1 gene in J558L cells and a subline previously transfected with the gene for interleukin-4 (IL-4). Complete longterm tumor eradication occurred in only 73-82% of syngeneic BALB/c mice injected with IL-4 or B7.1 transfectants or tumor cells mixed with the adjuvant Corynebacterium parvum. In contrast, none of the mice injected with J558-IL4/B7.1 cells developed a tumor, thus demonstrating that IL-4 and B7.1 together induced a more potent antitumor immune response compared to either molecule alone. Immunization/challenge experiments demonstrated that IL-4/B7.1 co-transfected cells possessed improved and tumor-specific vaccine potency when compared to single gene transfectants and, more importantly, to a tumor cell/C. parvum mixture. Furthermore, irradiation of vaccine cells almost completely abrogated the vaccine effect. Together, our results mean a step toward an improved tumor cell vaccine that acquires efficacy by the concerted action of IL-4 and B7.1 and the use of viable cells.

Adjuvants, Immunologic↗
PubMed1996

Bradyrhizobium japonicum possesses two discrete sets of electron transfer flavoprotein genes: fixA, fixB and etfS, etfL.

A group of four co-regulated genes (fixA, fixB, fixC, fixX) essential for symbiotic nitrogen fixation has been described in several rhizobial species, including Bradyrhizobium japonicum. The complete nucleotide sequence of the B. japonicum fixA, fixB and fixC, genes is reported here. The derived amino acid sequences confirmed the previously noted sequence similarity between FixA and the beta-subunit and between FixB and the alpha-subunit of mammalian and Paracoccus denitrificans electron transfer flavoproteins (ETF). Since the classical role of ETF is in beta-oxidation of fatty acids, a process unrelated to nitrogen fixation, we rationalized that B. japonicum ought to contain bona fide etf genes in addition to the etf-like genes fixA and fixB. Therefore, we identified, cloned, sequenced, and transcriptionally analyzed the B. japonicum etfSL genes encoding the beta- and alpha-subunits of ETF. The etfSL genes, but not the fix genes, are transcribed in aerobically grown cells. An amino acid sequence comparison between all available ETFs and ETF-like proteins revealed the existence of two distinguishable subfamilies. Group I comprises housekeeping ETFs that link acyl-CoA dehydrogenase reactions with the respiratory chain, such as in the fatty acid degradation pathway. B. japonicum EtfS and EtfL clearly belong to this group. Group II contains ETF-like proteins that are synthesized only under certain specific growth conditions and receive electrons from the oxidation of specific substrates. The products of the anaerobically induced fixA and fixB genes of B. japonicum are members of that group. B. japonicum is the first example of an organism in which genes for proteins of both groups I and II of the ETF family have been identified.

Amino Acid Sequence↗
PubMed1995

G protein subunit G alpha 16 expression is restricted to progenitor B cells during human B-cell differentiation.

Recently G alpha 16, a new guanosine triphosphate (GTP) binding protein alpha subunit has been described to be specifically expressed in human hematopoietic cells. Expression of G alpha 16 was observed in human cell lines of myelomonocytic and T-lymphocytic origin, but not in human B-cell lines Raji and IM9. We studied the expression of G alpha 16 in human B cells corresponding to different stages of B-cell differentiation by means of reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. The human Burkitt's lymphoma cell lines Raji, Ramos, BJAB, the lymphoblastoid cell line SKW6.4, and the plasmocytoma cell line U266 were devoid of G alpha 16. In contrast, G alpha 16 was detected in the human progenitor B cell lines Reh and Nalm-6. Using the mu+, k- cell line BLIN-1 (pre-B cell phenotype) and its derived subclone 1E8 (surface mu+, k+; B-cell phenotype) G alpha 16 expression was found to disappear on transition from pre-B to B-cell differentiation stage. The analysis of a broad panel of human neoplastic B lymphocytes ranging from progenitor B-acute lymphatic leukemia (pre-pre-B-ALL), common acute leukemias (cALL), pre-B-ALL, mature B-ALL to low grade B-cell lymphoma (chronic lymphocytic leukemia of B-cell type, leukemic centrocytic non-Hodgkins lymphoma [NHL], hairy cell leukemia) showed that G alpha 16 expression is limited to progenitor and pre-B-ALL cells. Therefore, we conclude that within B-cell differentiation, G alpha 16 is expressed solely during early B cell ontogeny and downregulated during differentiation. Thus, G alpha 16 might be an important regulator involved in signaling processes in progenitor B cells.

B-Lymphocytes↗
PubMed1995

Lafora disease is not linked to the Unverricht-Lundborg locus.

Lafora disease and Unverricht-Lundborg disease are two forms of progressive myoclonus epilepsies (PME). Recently the gene for Unverricht-Lundborg disease (EPM1) was mapped to chromosome 21q22.3. Using three highly polymorphic DNA markers (D21S212, PFKL, and D21S171) which flank the EPM1 locus, we performed linkage analysis to investigate whether or not the EPM1 gene is also implicated in Lafora disease. Linkage was excluded in three North-African pedigrees each comprising at least two affected individuals. This result suggests that differential diagnosis of Lafora disease and Unverricht-Lundborg disease may be facilitated by molecular genetic analysis.

Adolescent↗
PubMed1995

Tumor cells cotransfected with interleukin-7 and B7.1 genes induce CD25 and CD28 on tumor-infiltrating T lymphocytes and are strong vaccines.

Interleukin-7 (IL-7) and the membrane molecule B7 are both able to provide proliferation and activation signals for T cells. However, tumor cells transfected to express either molecule alone are not reliably rejected in syngeneic hosts or are not sufficiently immunogenic to serve as potent tumor vaccines. Since IL-7 and B7 have shown synergistically to induce activation and proliferation of T cells in vitro, we have expressed B7.1 by means of a retrovirus in the mammary adenocarcinoma TS/A which arose spontaneously in a BALB/c mouse and in the plasmacytoma J558L and their IL-7-transfected sublines to improve vaccine efficacy. Expression of IL-7 or B7.1 alone in tumor cells decreased tumorigenicity, but nevertheless tumors grew in a substantial number of mice. In contrast, IL-7/B7.1 cotransfected cells did not grow as tumor in a single case. This inhibition of tumor growth was completely T cell dependent, because TS/A-IL-7/B7.1 cells retained their full tumorigenic potential in T cell-deficient mice. Analysis of tumor-infiltrating T lymphocytes revealed increased numbers of T cells in B7, IL-7 and IL-7/B7 transfected compared to parental tumors. In IL-7/B7 transfected tumors, T cell numbers were not further increased compared to that in single-gene-transfected tumors. However, T cells in B7 and IL-7 transfected tumors differed phenotypically with respect to activation markers. In B7 transfected tumors, T cells were predominantly CD28+ and CD25-, while in IL-7 transfected tumors, T cells were mainly CD28- and CD25+. In IL-7/B7 cotransfected tumors, the majority of T cells was CD28+ and CD25+. Thus, IL-7 and B7 induced an anti-tumor immune response by complementary T cell directed pathways in a cooperative fashion. Importantly, immunization of mice with the transfected cells and subsequent contralateral challenge with parental tumor cells showed that IL-7/B7 co-expressing cells induced the most strongly protective immunity, which is superior to that induced by single-gene transfectants and to the adjuvant Corynebacterium parvum. Vaccine efficacy was abrogated when irradiated cells were used for vaccination. Together, our results show that IL-7 and B7.1 transfected tumor cells induce strong T cell activation and tumor immunity.

Animals↗
PubMed1995

Subcutaneous pretibial cyst formation associated with anterior cruciate ligament allografts: a report of four cases and literature review.

Four clinical cases are described in which patients who had undergone anterior cruciate ligament reconstruction developed ganglion-like cysts at the external aparature of the tibial channel. All patients underwent operative treatment including curettage and bone grafting with the successful resolution of the cysts. A proposal, based on the incomplete incorporation of allograft tissues within bone tunnels, is given for the pathogenisis of these cysts, accompanied by a detailed description of the relevant literature.

Achilles Tendon↗
PubMed1995

The thymidine kinase/ganciclovir-mediated "suicide" effect is variable in different tumor cells.

The herpes simplex virus thymidine kinase (HSV-TK) converts ganciclovir (GCV) into a toxic product and allows selective elimination of TK+ cells in vitro and in vivo. It is currently being used in clinical gene therapy trials as a therapeutic gene or as a safety marker. We have analyzed the susceptibility of different tumor cell lines to the TK/GCV-mediated "suicide" effect. Therefore, tumor cells TSA, J558L, EB, and ESB and, as a control, NIH-3T3 cells were infected with a retrovirus containing a hygromycin/TK fusion gene. All cell lines were sensitive to GCV in vitro; however, the concentration of GCV and the time needed to eliminate tumor cells completely considerably varied between different tumor cell lines. TSA-TK cells were completely eliminated within 10 days in 1 microg/ml GCV, whereas ESB-TK cells required 22 days in 10 microg/ml GCV. When two cell lines were examined, the differing sensitivity to GCV in vitro correlated with the ability to eradicate TK+ tumors in vivo. TSA-TK tumors could be eliminated in almost all animals by systemic GCV administration, whereas ESB-TK tumors were completely resistant. Different sensitivity to GCV was not due to different TK expression levels because the cells were similarly resistant to hygromycin, and Western blot analysis with an anti-TK antiserum revealed similar protein amounts in TSA/TK and ESB-TK cells. Together, the results demonstrate that tumor cells are highly different concerning the susceptibility to the TK/GCV effect, which, however, may be tested for in vitro.

3T3 Cells↗
PubMed1995

A single rRNA gene region in Bradyrhizobium japonicum.

Bradyrhizobium japonicum contains only a single rRNA (rrn) gene region, despite its comparatively large genome size of 8,700 kb. The nucleotide sequence revealed an organization of rRNA and tRNA genes that is frequently found in bacteria: 5'-rrs (16S rRNA)-ileT (tRNA(Ile))-alaT (tRNA(Ala))-rrl (23S rRNA)-rrf (5S rRNA)-3'. The 5' end of the primary transcript, one of the 16S rRNA processing sites, and the 5' end of the mature 16S rRNA were determined by primer extension. DNA hybridization experiments showed that the slowly growing Bradyrhizobium strains generally have only a single copy of the 16S rRNA gene, whereas the faster-growing Rhizobium species contain three rrs copies.

Base Sequence↗
PubMed1994

Lymphotoxin-alpha/beta heterodimer is expressed on leukemic hairy cells and activated human B lymphocytes.

The expression of human lymphotoxin (LT) alpha/beta cell-surface complex was studied in human B-cell lines as well as in normal and neoplastic human B lymphocytes. In the absence of TNF receptors, only the human hairy-cell leukemia (HCL)-derived cell line JOK-I revealed constitutive cell-surface expression of LT but not TNF-alpha. Immunoprecipitation experiments with anti-LT monoclonal antibody (MAb) 9B9 from cell-surface radioiodinated JOK-I cells revealed that a cell-surface lymphotoxin molecule (25 kDa) is expressed in association with a 33-kDa molecule. Enzymatic digestion with F/N-glycosidase and O-glycosidase showed that both proteins contained N-linked carbohydrate residues, whereas only the 25-kDa molecule contained O-linked sugar residues. Analysis of mRNA expression revealed specific transcripts of LT-alpha and LT-beta in JOK-I cells. Resting tonsillar B cells did not express cell-surface LT. However, LT-beta mRNA was observable in unstimulated tonsillar B cells, whereas LT-alpha mRNA, cell-surface LT and LT secretion could only be detected upon in vitro activation. Thus LT-beta and alpha appear to be sequentially expressed in human B cells. Neoplastic B cells from chronic lymphocytic leukemia (BCLL), being devoid of constitutive cell-surface LT expression, could be induced to express surface LT by in vitro stimulation with Staphylococcus aureus Cowan I (SAC). Constitutive LT-beta transcripts, however, could also be detected in 4 out of 5 cases of BCLL. In contrast, human HCL cells displayed constitutive cell expression of lymphotoxin-alpha and beta. These findings demonstrate that cell-surface LT-alpha is expressed in association with LT-beta on activated normal B cells and neoplastic B cells representing an activated state.

B-Lymphocytes↗