Effect of withdrawal of arginine and other amino acids on the synthesis of tumour and viral antigens of SV 40 virus.
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Biomedical subjects
Publications and source records attributed to Y Becker.
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The HSV-1 thymidine kinase (TK) gene of Herpes simplex virus was inserted into plasmids pBR322, pMOB45 and pHA10. The recombinant hybrid plasmids were used to transfect a tdk- mutant of Escherichia coli (Ky895) and the synthesis of the viral TK in the bacterial host was studied. Recombinant plasmids containing the entire BamHI-BamHI DNA fragment carrying the viral TK gene and the upstream sequences containing its promoter were able to produce the thymidine kinase, but removal of the BamHI-BglII DNA fragment containing the viral promoter of the TK gene resulted in enhanced expression of the viral gene, originating from the pBR322 tetr gene promoter. When the BglII-BamHI DNA fragment containing the viral TK gene was cloned in a plasmid with temperature-dependent copy number control (pMOB45), expression of the TK gene was enhanced fourfold by the temperature shift. Cloning of the HSV-1 TK gene in plasmid pHA10 showed that the lambda pL promoter allowed transcription of the viral gene but not the synthesis of active TK. The BamHI-BglII DNA fragment containing the viral upstream sequences with the promoter of the TK gene was found to contain transcription-termination sequences that prevented expression of the lambda kil gene of pHA10 in the presence of lambda N function.
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Varicella-zoster virus (VZV) causes chickenpox and shingles. Clinical and epidemiological evidence indicates that following an episode of childhood chickenpox (varicella), VZV becomes latent, presumably in dorsal root ganglia, and is reactivated many years later to produce shingles (zoster) in adults. VZV has been demonstrated in ganglia by electron microscopy and by indirect immunofluorescence, and infectious viral particles have been isolated from acutely infected ganglia of patients who died of disseminated VZV infection. However, VZV has not been detected in the ganglia of humans without recent exposure to VZV. Tissue culture explant methods that have been successful in the isolation of herpes simplex virus from ganglia have so far failed in the isolation or reactivation of VZV from trigeminal and other dorsal root ganglia. We describe here the detection of VZV DNA sequences in an acutely infected human sacral ganglion and in normal trigeminal ganglia. These findings support the hypothesis that VZV is latent in normal human ganglia.
Familial dysautonomia (FD) patients have diminished sensory C-fibers. Calcitonin gene related peptide (CGRP) is a widely distributed neuropeptide and prominent neurotransmitter in C-fibers. We show that plasma CGRP levels measured by radioimmunoassay is significantly lower in 51 FD patients compared to controls (P<0.001). In 11/51 FD patients with FD crisis and in 19/51 FD patients with pneumonia, the mean CGRP levels rose significantly as compared to their baseline (P<0.003, P<0.001, respectively). The deficiency of CGRP in FD patients is consistent with their depletion of C-fibers, and may explain some of their symptoms, either directly or via modulation of sympathetic activity.
Herpesviruses evolved from an ancestral viral genome that contained five blocks of genes which provide the members of this family of viruses with structural and enzymatic properties. These genes allow the herpesviruses to infect a host by entering into the nuclei of the cells, the site of replication and transcription of the viral DNA. The viral mRNAs are released into the cell cytoplasm where synthesis of enzymatic and structural proteins occurs. The latter proteins are responsible for the formation of the infectious virions. Herpesviruses that were able to adapt to different hosts during the evolution of the species (speciation) had acquired additional genes from transposons or retrotransposons that allowed them to successfully maintain their hold in the specific vertebrate host. The present overview deals with molecular differences between Marek's disease virus type 1 (MDV-1) and herpes simplex virus type 1 (HSV-1) and the specialized genes that differentiate MDV-1 from HSV-1, the promoters of the viral genes that control gene expression and the nuclear localization signals. Dynamic changes in the viral genomes that may occur during viral DNA replication and recombination and their effects on virus pathogenicity and genome evolution will be discussed.
The bone marrow-derived dendritic cells (DL/LC) are antigen-presenting accessory cells functioning as part of the immune system. In addition, DC/LC in epithelial tissues may have the capacity to be involved in cellular interactions which may have regulatory functions. Such properties can also be noted when LC/DC interact with cancer cells in tumors. The present review summarizes reports which suggest that the outcome of a primary tumor in patients depends on the presence or absence of DC/LC in the tumor. The evidence showing that the presence of DC/LC in primary tumors indicates that a good prognosis may be reached are presented and discussed. Based on these observations and the ability of immunomodulators to enhance the activity of DC/LC and the ability of these cells to enter into tumors, it is suggested that the molecular basis of DC/LC activity against primary tumors cells should be investigated. It is possible that activation of DC/LC, thereby enhancing their ability to enter primary tumors, and the abrogation of the ability of DC/LC-resistant tumors to destroy or prevent DC/LC from entering the tumor, could be developed as an effective anti-cancer approach.
Persons with the genetic, autosomal recessive human disorder ataxia-telangiectasia (A-T) have a predisposition to cancer, though the reason for this is not understood. Studies carried out in recent years have provided evidence that cultured skin fibroblasts from A-T patients are hypersensitive to X-radiation and radiomimetic drugs. These cells were also found to release a clastogenic factor and an angiogenesis-like factor into the conditioned medium. Similar factors present in the plasma of A-T patients may be the cause of chromosomael breakage and blood vessel proliferation respectively. It is suggested to that continual chromosomal breakage in lymphocytes, induced by the clastogenic factor, leads to a selection of T or B lymphocytes with neoplastic properties. Future studies should be directed towards skin Langerhans cells to determine their role in the immune deficiency and their interaction with other cellular elements in the skin of A-T patients. Furthermore, T and B lymphocytes from A-T patients with tumors should be cultivated in vitro to study the nature of the activated oncogenes and the possible role of viruses in blood neoplasms in A-T patients.
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