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At least 469 records · Page 26Linked to original sources
PubMed2003

Antiviral and immunological benefits in HIV patients receiving intranasal peptide T (DAPTA).

D-Ala-Peptide T-amide (DAPTA), the first viral entry inhibitor, blocks chemokine (CCR5) receptors, not CD4. Early investigators could not "replicate" DAPTAs potent in vitro antiviral effect using the lab-adapted, X4, peptide T-insensitive strain, IIIB, delaying clinical virological studies. We now report that DAPTA, administered to eleven long-term infected (mean=17 years) patients with stable persistent plasma "virus" for up to 32 weeks did not change this level. Infectious virus could not be isolated from their plasma suggesting HIV RNA was devoid of replicative capacity. Progressively less actual virus (P<0.01) could be isolated from white blood cells (PBMCs). DAPTA flushed the monocyte reservoir to undetectable viral levels in most patients. Five of eleven had a mean CD4 increase of 33%. Immune benefits also included a four-fold increase in gamma-interferon-secreting T-cells (antiviral cytotoxic T-cells) in the absence of drug-related toxicity. All five CD4 responders had increases in antiviral T cells and decreases in infected monocytes, an argument for initiating further studies promptly.

Administration, Intranasal↗
PubMed2003

Congenital duplication of the palm in a patient with multiple anomalies.

In 1995, Parr and McMahon described a syndrome of congenital duplication of footpads in mice which lacked a protein called 'Wingless-type mouse mammary tumour virus integration site family member 7a" (Wnt-7a). This syndrome has not been described in humans and the following report describes a similar syndrome in a Saudi girl. The role of Wnt-7a in the development of the limb along the dorso-ventral axis is discussed, along with interaction between the Wnt-7a and other axes of limb growth.

Abnormalities, Multiple↗
PubMed1997

A novel in vitro and in vivo breast cancer model for testing inhibitors of estrogen biosynthesis and its action using mammary tumor cells with an activated int-5/aromatase gene.

We recently showed that the cellular gene int-5/aromatase in BALB/c mammary alveolar hyperplastic nodule (D2 HAN/D2 tumor cells) is activated as a result of mouse mammary tumor virus integration within the 3' untranslated region of the aromatase gene. In the present study, we evaluated the effect of various aromatase inhibitors on androstenedione-mediated tumor cell growth. Also, we compared the effect of the non-steroidal aromatase inhibitor (CGS 16949A) on the inhibition of tumor growth. Our results show that D2 tumor cells respond well to various aromatase inhibitors and antiestrogens. We examined the usefulness of this model by using D2 tumor cells to simulate postmenopausal breast cancer employing both in vitro cell culture and in vivo ovariectomized (OVX) nude mouse. Unlike DMBA-induced tumors or other models, D2 tumor cells form very rapid tumors within a few days in intact mice or OVX nude mice with androstenedione supplementation and respond well to an aromatase inhibitor. This model with its known mechanism of aromatase activation should be useful for studying the role of intra-tumoral estrogen in mammary cancer, for evaluating the effects of aromatase inhibitors and antiestrogens, and for comparing breast cancer treatments.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1998

Hepatitis B viruses and cancerogenesis.

Hepatitis B virus (HBV) is a small, enveloped DNA virus which primarily infects liver cells and causes acute and persistent liver disease. Chronic HBV infection, frequently associated with cirrhosis and eventually hepatocellular carcinoma (HCC), represents a major health problem in the world. HBV is the prototype member of the hepadnavirus family, which includes several related mammalian viruses also implicated in liver carcinogenesis in the host. Although epidemiological evidence has clearly linked HBV infection with HCC development, the precise role of the virus and the molecular mechanisms of liver cell transformation remain elusive. Here we discuss potential oncogenic strategies of HBV, ranging from indirect mechanisms related to chronic necroinflammatory disease and to the effects of viral gene products on cell proliferation and apoptosis, to direct insertional activation of cellular (onco)genes. Presently, vaccination of high risk populations represents a major way to prevent the development of HBV-related liver cancer.

Animals↗
PubMed1995

Mutual adaptation of bacteriophage fd, pfd plasmids and their host strains.

The synthetic plasmid pfdC1 with the replication origin of phage fd and fd gene 2 grows autonomously in E. coli cells. DNA sequencing revealed several mutations compared to the fd genome causing reduced expression of viral gene 2 protein, which can be toxic for the host cell. Another adaptation was noticed for E. coli strains with a copy of fd gene 2 on the F-episome and a pfdA-plasmid with a minimal fd replication origin, when maintained at 42 degrees C. The carrier cells adjusted their cellular metabolism to these stress conditions, whereas replication functions of the plasmid or expression of fd gene 2 on the F-episome were not changed. The filamentous bacteriophages tend to reduce their genome size into miniphages, which was also observed for phages with an antibiotic resistance gene. Bacteriophages with a transposon insertion in the viral gene 2 had a tendency to restore the mutated gene by exchange with the functional gene 2 carried in recA-host cells. Mobilization of pfd-plasmids with RP4 transfer functions was reduced due to interference of replication and transfer in the rolling circle mode. The vectors used in these studies can also be applied as cloning vectors, which are compatible with many other plasmid vectors.

Adaptation, Physiological↗
PubMed2003

Insider information: what viruses tell us about endocytosis.

Viruses have long served as tools in molecular and cellular biology to study a variety of complex cellular processes. Currently, there is a revived interest in virus entry into animal cells because it is evident that incoming viruses make use of numerous endocytic pathways that are otherwise difficult to study. Besides the classical clathrin-mediated uptake route, viruses use caveolae-mediated endocytosis, lipid-raft-mediated endocytic pathways, and macropinocytosis. Some of these are subject to regulation, involve novel endocytic organelles, and some of them connect organelles that were previously not known to communicate by membrane traffic.

Animals↗
PubMed1992

Interaction between bacteriophage lambda and its Escherichia coli host.

Bacteriophage lambda relies to a large extent on processes requiring interactions between viral- and host-encoded proteins for its lytic growth, establishment of lysogeny, and release from the prophage state. Both biochemical and genetic studies of these interactions have yielded new information about important host and lambda functions. In particular, mutations in Escherichia coli that compromise lambda DNA replication, genome packaging, transcription elongation, and site-specific recombination have led to the identification of bacterial genes whose products are chaperones, transcription factors, or DNA-binding proteins.

Bacterial Proteins↗
PubMed1995

HIV-1 virology. Simply Marvelous nuclear transport.

HIV-1 MA protein is a viral membrane protein, but it is also involved in nuclear import of the preinitiation complex; the latter requires transfer of some MA molecules to the maturing core particle during virus assembly.

Biological Transport↗
PubMed1991

Linkage of loci associated with two pigment mutations on mouse chromosome 13.

Progeny from one intra- and two inter-specific backcrosses between divergent strains of mice were typed to map multiple markers in relation to two pigment mutations on mouse chromosome 13, beige (bg) and pearl (pe). Both recessive mutants on a C57BL/6J background were crossed separately with laboratory strain PAC (M. domesticus) and the partially inbred M. musculus stock PWK. The intra- and inter-specific F1 hybrids were backcrossed to the C57BL/6J parental strain and DNA was prepared from progeny. Restriction fragment length polymorphisms were used to follow the segregation of alleles in the backcross offspring at loci identified with molecular probes. The linkage analysis defines the association between the bg and pe loci and the loci for the T-cell receptor gamma-chain gene (Tcrg), the spermatocyte specific histone gene (Hist1), the prolactin gene (Prl), the Friend murine leukaemia virus integration site 1 (Fim-1), the murine Hanukuh Factor gene (Muhf/Ctla-3) and the dihydrofolate reductase gene (Dhfr). This data confirms results of prior chromosomal mapping studies utilizing bg as an anchor locus, and provides previously unreported information defining the localization of the prolactin gene on mouse chromosome 13. The relationship of multiple loci in relation to pe is similarly defined. These results may help facilitate localization of the genes responsible for two human syndromes homologous with bg and pe, Chediak-Higashi syndrome and Hermansky-Pudlak syndrome.

Animals↗
PubMed1999

Dynamical behaviour of viral cycle and identification of steady states.

The molecular biology of viruses can be effectively described by kinetic logic as several feedback loops are implicated in all viral cycles and as viral proteins generally display several functions. We applied this method to the study of the rhabdovirus cycle. Formally, the dynamics of the model are explored on the basis of a discrete caricature (kinetic logic), with special emphasis on the role of the constitutive feedback loops to determine the essential dynamical behaviour of the viral cycle. From a biological point of view, our model accounts for several stable regimes or attractors: healthy cells, acute infection and different kinds of persistent infections, a multistationarity in good agreement with the existence of several positive feedback loops in our system.

Animals↗
PubMedDate not supplied

A novel steroid thyroid hormone receptor-related gene inappropriately expressed in human hepatocellular carcinoma.

We have previously isolated from a human hepatocellular carcinoma a hepatitis B virus integration in a 147-base-pair cellular DNA fragment, similar to steroid- and c-erb-A/thyroid-hormone receptor genes. We have now cloned the corresponding complementary DNA from a human-liver cDNA library. Nucleotide sequence analysis revealed that the overall structure of the cellular gene, which we have named hap, is similar to that of the DNA-binding hormone receptors. That is, it displays two highly conserved regions identified as the putative DNA-binding and hormone-binding domains of the c-erb A/steroid receptors. Six out of seven hepatoma and hepatoma-derived cell-lines express a 2.5-kilobase (kb) hap messenger RNA species which is undetectable in normal adult and fetal livers but present in all non-hepatic tissues analysed. The data suggest that the hap gene product may be a novel ligand-responsive regulatory protein whose inappropriate expression in liver may relate to the hepatocellular carcinogenesis.

Amino Acid Sequence↗
PubMed1997

Functional genomics in mice by tagged sequence mutagenesis.

Most mammalian genes will soon be characterized as cDNA sequences with little information about their function. To utilize this sequence information for large-scale functional studies, a gene trap retrovirus shuttle vector has been developed to disrupt genes expressed in murine embryonic stem (ES) cells. A library of mutant clones was isolated, and regions of genomic DNA adjacent to 400 independent provirus inserts were cloned and sequenced. The flanking sequences, designated 'promoter-proximal sequence tags', or PSTs, identified 63 specific genes and anonymous cDNAs disrupted as a result of virus integration. The efficiency of tagged sequence mutagenesis suggests that many of the 10,000-20,000 genes expressed in ES cells can be targeted, providing defined mutations for the analysis of gene functions in vivo. In addition, PSTs provide the first expressed sequence tags derived from genomic DNA, and define gene features such as exon boundaries and promoters that are missing from cDNA sequences.

Animals↗
PubMed2006

Structure and E3-ligase activity of the Ring-Ring complex of polycomb proteins Bmi1 and Ring1b.

Polycomb group proteins Ring1b and Bmi1 (B-cell-specific Moloney murine leukaemia virus integration site 1) are critical components of the chromatin modulating PRC1 complex. Histone H2A ubiquitination by the PRC1 complex strongly depends on the Ring1b protein. Here we show that the E3-ligase activity of Ring1b on histone H2A is enhanced by Bmi1 in vitro. The N-terminal Ring-domains are sufficient for this activity and Ring1a can replace Ring1b. E2 enzymes UbcH5a, b, c or UbcH6 support this activity with varying processivity and selectivity. All four E2s promote autoubiquitination of Ring1b without affecting E3-ligase activity. We solved the crystal structure of the Ring-Ring heterodimeric complex of Ring1b and Bmi1. In the structure the arrangement of the Ring-domains is similar to another H2A E3 ligase, the BRCA1/BARD1 complex, but complex formation depends on an N-terminal arm of Ring1b that embraces the Bmi1 Ring-domain. Mutation of a critical residue in the E2/E3 interface shows that catalytic activity resides in Ring1b and not in Bmi1. These data provide a foundation for understanding the critical enzymatic activity at the core of the PRC1 polycomb complex, which is implicated in stem cell maintenance and cancer.

Amino Acid Sequence↗
PubMed2006

Novel role of WD40 and SOCS box protein-2 in steady-state distribution of granulocyte colony-stimulating factor receptor and G-CSF-controlled proliferation and differentiation signaling.

Signals induced by granulocyte colony-stimulating factor (G-CSF), the major cytokine involved in neutrophil development, are tightly controlled by ligand-induced receptor internalization. Truncated G-CSF receptors (G-CSF-Rs) that fail to internalize show sustained proliferation and defective differentiation signaling. Steady-state forward routing also determines cell surface levels of cytokine receptors, but mechanisms controlling this are poorly understood. Here, we show that WD40 and suppressor of cytokine signaling (SOCS) box protein-2 (Wsb-2), an SOCS box-containing WD40 protein with currently unknown function, binds to the COOH-terminal region of G-CSF-R. Removal of this region did not affect internalization, yet resulted in increased membrane expression of G-CSF-R and enhanced proliferation signaling at the expense of differentiation induction. Conversely, Wsb-2 binding to the G-CSF-R reduced its cell surface expression and inhibited proliferation signaling. These effects depended on the SOCS box involved in ubiquitylation and on cytosolic lysines of G-CSF-R and imply a major role for ubiquitylation through the G-CSF-R C-terminus in forward routing of the receptor. Importantly, the Wsb-2 gene is commonly disrupted by virus integrations in mouse leukemia. We conclude that control of forward routing of G-CSF-R is essential for a balanced response of myeloid progenitors to G-CSF and suggest that disturbance of this balance may contribute to myeloid leukemia.

Animals↗