Survival after liver transplantation in diabetics.
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Diabetes Complications↗
Biomedical subjects
C Rosen
Publications and source records attributed to C Rosen.
Structural requirements for trans activation of human immunodeficiency virus type 1 long terminal repeat-directed gene expression by tat: importance of base pairing, loop sequence, and bulges in the tat-responsive sequence.
In order to elucidate the molecular mechanisms of action of the tat-responsive sequence, mutational analysis of the tat-responsive sequence was carried out. The most critical region comprised nucleotides +18 to +44 and included the 3-nucleotide bulge at positions +23 to +25, the loop sequence, and an intact stem. In addition, base pairing up to nucleotide +52 was required for the full magnitude of the trans-activation response. Single-nucleotide bulges at positions +5 to +17 were dispensable. Analysis of truncated and full-length transcripts demonstrated that a transcriptional antitermination model does not fully account for trans activation.
Base Composition↗
Age-related changes in serum insulin-like growth factor-binding proteins in women.
Plasma insulin-like growth factor-I (IGF-I) concentrations are reported to decline with advancing age. Five IGF-binding proteins (IGF-BPs) have recently been characterized in human serum, although their biological role beyond circulatory transport of IGF-I is unknown. We studied plasma IGF-I (by RIA) and serum IGF-BPs (by Western ligand blotting) in healthy elderly (n = 21) and healthy young (n = 22) women to determine if aging alters IGF-I and its high affinity BPs. Plasma IGF-I was significantly lower in the elderly than in the young group (0.78 +/- 0.08 vs. 1.22 +/- 0.11 U/ml; P less than 0.005). The number and size of IGF-BPs did not differ between age groups, but the IGF-BP binding ratios (binding of one BP fraction/binding of all fractions) for the BP-53 acid-stable complex (41.5K and 38.5K BPs), the 30K IGF-BP, and the 24K IGF-BP were all lower in the elderly than in the young group (P less than 0.01 for each fraction, elderly vs. young). In contrast, the 34K IGF-BP binding ratio was significantly greater in the elderly than in the young (0.30 +/- 0.03 vs. 0.12 +/- 0.01; P less than 0.001) and correlated closely with advancing age (r = 0.64; P less than 0.01). The changes in IGF-BPs found in the elderly are quite similar to alterations in serum IGF-BPs previously reported in GH deficiency. Since several IGF-BPs in vitro have been shown to modulate the mitogenic activity of IGF-I, the serum IGF-BP changes noted above may be important for the growth and maintenance of connective tissue, muscle, and bone during the aging process.
Adult↗
Disparate effects of two herpesvirus [corrected] immediate-early gene trans-activators on the HIV-1 LTR.
The BMLF1 region of the Epstein-Barr virus (EBV) genome and the immediate-early (IE) region of human cytomegalovirus (HCMV) both encode proteins which can trans-activate heterologous promoter/chloramphenicol acetyl transferase (CAT) constructs, including a human immunodeficiency virus type-1 promoter/CAT construct. We demonstrate here that this trans-activation by the EBV BMLF1 gene product, which we have previously shown to be largely post-transcriptional, is reporter gene dependent. In contrast, trans-activation by the HCMV-IE gene product(s), previously shown to be mediated at the RNA level, is seen regardless of whether CAT, human growth hormone, or beta-galactosidase is used as the reporter gene. Mutational analysis revealed no specific cis-acting sequences within the HIV-1 promoter which were required for trans-activation by the HCMV-IE gene product(s).
Carcinoma↗
Photo-induced drug eruptions.
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Drug Hypersensitivity↗
Mutational analysis of the 5' non-coding region of human immunodeficiency virus type 1: effects of secondary structure on translation.
The first 111 nt from the 5' end of human immunodeficiency virus type 1 (HIV-1) mRNAs are shown to have a strong inhibitory effect on the translation of mRNA in in vitro translation extracts as well as in Xenopus oocytes. Mutations in the sequence of the 5' untranslated region (UTR) designed to disrupt predicted secondary structure of this region relieve the inhibition. Inhibition is restored by mutations that reconstruct the predicted secondary structure. The accessibility of the 5'-terminal cap structure was also found to be increased by some of these mutations. We conclude that secondary structure in the 5' UTR of HIV-1 mRNAs and resultant inaccessibility of the cap structure is responsible for the inhibition of translation. The implications of these findings for the understanding of the life cycle of HIV-1 are discussed.
Animals↗
The art gene product of human immunodeficiency virus is required for replication.
A mutation that alters the initiation codon of the art gene of the human immunodeficiency virus renders the virus replication defective. The replication defect of this mutation can be complemented in trans by the art gene product. These findings indicate that the art protein is essential for replication and, as such, represents a good target for development of new antiviral agents that could be useful in the control of human immunodeficiency virus infection.
Cells, Cultured↗
A pharyngostomy technique for chronic oral dosing of rabbits.
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Administration, Oral↗
Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1.
The envelope of the human immunodeficiency virus type 1 (HIV-1) plays a central role in the process of virus entry into the host cell and in the cytopathicity of the virus for lymphocytes bearing the CD4 molecule. Mutations that affect the ability of the envelope glycoprotein to form syncytia in CD4+ cells can be divided into five groups: those that decrease the binding of the envelope protein to the CD4 molecule, those that prevent a post-binding fusion reaction, those that disrupt the anchorage of the envelope glycoprotein in the membrane, those that affect the association of the two subunits of the envelope glycoprotein, and those that affect post-translational proteolytic processing of the envelope precursor protein. These findings provide a functional model of the HIV envelope glycoprotein.
Amino Acid Sequence↗
HIV envelope-CD4 interaction not inhibited by synthetic octapeptides.
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Antibodies, Monoclonal↗
Replication and pathogenesis of the human T-cell leukemia/lymphotropic retroviruses.
The broad outlines of mechanisms of tumorigenesis by the HTLV-I family of viruses are beginning to emerge. The viruses encode at least three genes in addition to the genes (gag, pol, and env) required for virus replication. These additional genes encoded for by the X region are likely to affect in a specific fashion the growth of lymphocytes. The tat gene appears to mimick at least part of the response of mature lymphocytes to recognition of the cognate antigen. That is, in T-lymphocytes the tatI gene seems to induce the IL-2 and IL-2 receptor genes (W. Greene et al. 1986). The alternative reading-frame proteins, pp21 and pp27, have some similarity of cellular proteins that are associated with G0 to G1 transitions and may contribute to the transformed phenotype in cooperation with the tat gene. The expression of viral genes in infected lymphocytes, the tat gene and pp21 and pp27 proteins, and possibly other viral genes (since the coding capacity of the X region is not exhausted by the tat and pp21 and pp27 proteins) may be sufficient to account for the transformation of T cells in culture. A secondary change in the infected cells in culture is not required to explain the outgrowth of cells which are clonal with respect to the site of viral genomic integration, as selection of the most rapidly growing infected cell could account for this observation. The case of infected patients is more complex. Infection of T cells with the HTLV-I or -II virus is not sufficient to produce malignant disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Deltaretrovirus↗
Inhibition of human immunodeficiency virus syncytium formation and virus replication by castanospermine.
Castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine) is a plant alkaloid that modifies glycosylation by inhibiting alpha-glucosidase I. Castanospermine is shown to inhibit syncytium formation induced by the envelope glycoprotein of the human immunodeficiency virus and to inhibit viral replication. The decrease in syncytium formation in the presence of castanospermine can be attributed to inhibition of processing of the envelope precursor protein gp160, with resultant decreased cell surface expression of the mature envelope glycoprotein gp120. In addition, castanospermine may cause defects in steps involved in membrane fusion after binding of CD4 antigen. The antiviral effects of castanospermine may be due to modifications of the envelope glycoprotein that affect the ability of the virus to enter cells after attachment to the CD4 cell receptor.
Alkaloids↗
Replicative and cytopathic potential of HTLV-III/LAV with sor gene deletions.
The genome of the human T-lymphotropic virus type III (HTLV-III/LAV) has the potential to encode at least three polypeptides in addition to those encoded by the gag, pol, and env genes. In this study, the product of the sor (short open reading frame) region, which overlaps the 3' end of the pol gene, was found to be a protein with a molecular weight of 23,000. An assay was developed for testing the ability of cloned HTLV-III proviruses to produce viruses cytopathic for T4+ lymphocytes. In the cell line used, C8166, neither the HTLV-III sor gene product nor the complete 3'-orf gene product were necessary for the replication or cytopathic effects of the HTLV-III.
Cell Line↗
Identification of a protein encoded by the trans activator gene tatIII of human T-cell lymphotropic retrovirus type III.
The human T-cell lymphotropic virus type III (HTLV-III/LAV) is a retrovirus associated with acquired immune deficiency syndrome. The region on the viral genome that is necessary for trans-activation of the HTLV-III/LAV long terminal repeat called tatIII has previously been determined to lie between nucleotides 5365 and 5607. Here we report that a bacterial fusion protein containing amino acid sequences specified by the first coding exon of the tatIII gene is recognized by some patient antisera. We also demonstrate that lymphoid and epithelial cells that express the trans activator function express a 14-kilodalton (kDa) protein recognized by a patient antiserum that reacts with the bacterial tatIII fusion protein. Cells transiently transfected with a deletion mutant of the trans activator protein produce a 12-kDa protein rather than the 14-kDa protein. These observations indicate that the tatIII region contains a functional gene and is capable of expressing a protein that migrates with an apparent molecular size of 14 kDa in some lymphoid and epithelial cells transfected with plasmids containing the tatIII region. We propose that the product of the trans activator gene be designated p14tat-III.
Acquired Immunodeficiency Syndrome↗
Location of the trans-activating region on the genome of human T-cell lymphotropic virus type III.
The retrovirus involved in acquired immune deficiency syndrome (HTLV-III/LAV) contains a region that is necessary for stimulation of gene expression directed by the viral long terminal repeat. This region is located between nucleotides 5365 and 5607, immediately 5' to the envelope gene. A doubly-spliced message containing this region could encode an 86-amino acid protein with structural features similar to those of nucleic acid-binding proteins.
Base Sequence↗
A transcriptional activator protein encoded by the x-lor region of the human T-cell leukemia virus.
Human T-cell leukemia viruses type I and II (HTLV-I and -II) exhibit several features characteristic of this retroviral family: the presence of an x-lor gene encoding a nuclear protein, transformation properties suggesting the involvement of a virus-associated trans-acting factor, and transcriptional trans-activation of the long terminal repeat (LTR) in infected cells. In the study described here the HTL x-lor products, in the absence of other viral proteins, were able to activate gene expression in trans directed by HTLV LTR. The regulation of the expression of particular genes in trans by HTLV x-lor products suggests that they play a role in viral replication and possibly in transformation of T lymphocytes.
Deltaretrovirus↗
Subcellular localization of the product of the long open reading frame of human T-cell leukemia virus type I.
Human T-cell leukemia virus type I (HTLV-I) is a retrovirus associated with adult T-cell leukemia and lymphoma. In addition to containing the gag, pol, and env genes of the chronic leukemia viruses, the genome of HTLV-I contains a long open reading frame (LOR) located between the 3' end of the envelope gene and the 3' long terminal repeat sequence (LTR). It has been suggested that a protein of 42 kilodaltons that is encoded by the LOR region may participate in both trans-acting transcriptional regulation of the viral LTR as well as in the transforming properties of HTLV-I. It is reported here that a significant fraction of the 42-kilodalton HTLV LOR product is located in the nucleus of HTLV-I-infected transformed lymphocytes, a finding that is consistent with its proposed functions.
Cell Fractionation↗
Trans-acting transcriptional regulation of human T-cell leukemia virus type III long terminal repeat.
Human T-cell leukemia virus type III (HTLV-III) was recently identified as the probable etiologic agent of the acquired immune deficiency syndrome (AIDS). Here it is shown that, in human T-cell lines infected with HTLV-III, gene expression directed by the long terminal repeat sequence of this virus is stimulated by more than two orders of magnitude compared to matched uninfected cells. The rate of transcription of the HTLV-III long terminal repeat is more than 1000 times that of the SV40 early promoter in one infected cell line. Thus, HTLV-III, like HTLV-I, HTLV-II, and the bovine leukemia virus, is characterized by trans-activation of transcription in infected cells. The efficiency of trans-activation in the case of HTLV-III may account, at least in part, for the virulent nature of HTLV-III infection.
Acetyltransferases↗