Biomedical subjects

A Z Chaudhry

Publications and source records attributed to A Z Chaudhry.

7 recordsLinked to original sources

PubMed1999

Nuclear factor I-mediated repression of the mouse mammary tumor virus promoter is abrogated by the coactivators p300/CBP and SRC-1.

To better understand the function of nuclear factor I (NFI) proteins in transcription, we have used transient transfection assays to assess transcriptional modulation by NFI proteins on the NFI-dependent mouse mammary tumor virus (MMTV) promoter. Expression of NFI-C or NFI-X, but not NFI-A or NFI-B proteins, represses glucocorticoid induction of the MMTV promoter in HeLa cells. Repression is DNA binding-independent as a deletion construct expressing the NH2-terminal 160 residues of NFI-C represses but does not bind DNA. Repression by NFI-C is cell type-dependent and occurs in HeLa and COS-1 cells but not 293 or JEG-3 cells. NFI-C does not repress progesterone induction of the MMTV promoter in HeLa cells, suggesting that progesterone induction of the promoter differs mechanistically from glucocorticoid induction. NFI-C-mediated repression is alleviated by overexpression of glucocorticoid receptor (GR), suggesting that NFI-C represses the MMTV promoter by preventing GR function. However, repression by NFI-C occurs with only a subset of glucocorticoid-responsive promoters, as the chimeric NFIGREbeta-gal promoter that is activated by GR is not repressed by NFI-C. Since the coactivator proteins p300/CBP, SRC-1A, and RAC3 had previously been shown to function at steroid hormone-responsive promoters, we asked whether they could influence NFI-C-mediated repression of MMTV expression. Expression of p300/CBP or SRC-1A alleviates repression by NFI-C, whereas RAC3 has no effect. This abrogation of NFI-C-mediated repression by p300/CBP and SRC-1A suggests that repression by NFI-C may occur by interference with coactivator function at the MMTV promoter.

Animals↗

PubMed1999

Exon structure of the nuclear factor I DNA-binding domain from C. elegans to mammals.

The Nuclear Factor I (NFI) family of DNA-binding proteins is essential for adenovirus DNA replication and the transcription of many cellular genes. Mammals have four genes encoding NFI proteins, C. elegans has only a single NFI gene, and prokaryotes have none. To assess the relationship between members of this unusually small family of transcription/replication factors, we mapped the chromosomal locations of the four murine NFI genes and analyzed the exons encoding the DNA-binding domains of the mouse, Amphioxus, and C. elegans NFI genes. The four murine NFI genes are on Chrs 4 (Nfia and Nfib), 8 (Nfix), and 10 (Nfic), suggesting early duplication of the genes and dispersal throughout the genome. The DNA-binding domains of all four NFI genes are encoded by large (532 bp) exons with identical splice acceptor and donor sites in each. In contrast, the C. elegans nfi-1 gene has four phased introns interrupting this DNA-binding, domain-encoding exon, and the last exon extends 213 bp past the splice site used in all four murine genes. In addition, the introns present in C. elegans nfi-1 are missing from the NFI genes of Amphioxus and all mammalian genomes examined. This analysis of the exon structure of the C. elegans and murine NFI genes indicates that the murine genes were probably generated by duplication of a C. elegans-like ancestral gene, but that significant changes have occurred in the genomic organization of either the C. elegans or murine NFI genes during evolution.

Animals↗

PubMed1998

Nuclear factor I (NFI) isoforms differentially activate simple versus complex NFI-responsive promoters.

Promoter-specific differences in the function of transcription factors play a central role in the regulation of gene expression. We have measured the maximal transcriptional activation potentials of nuclear factor I (NFI) proteins encoded by each of the four identified NFI genes (NFI-A, -B, -C, and -X) by transient transfection in JEG-3 cells using two model NFI-dependent promoters: 1) a simple chimeric promoter containing a single NFI-binding site upstream of the adenovirus major late promoter (NFI-Ad), and 2) the more complex mouse mammary tumor virus long terminal repeat promoter. The relative activation potentials for the NFI isoforms differed between the two promoters, with NFI-X being the strongest activator of NFI-Ad and NFI-B being the strongest activator of the MMTV promoter. To determine if these promoter-specific differences in activation potential were due to the presence of glucocorticoid response elements (GREs), we added GREs upstream of the NFI-binding site in NFI-Ad. NFI-X remains the strongest activator of the GRE containing simple promoter, indicating that differences in relative activation potential are not due solely to the presence of GREs. Since NFI proteins bind to DNA as dimers, we assessed the activation potentials of NFI heterodimers. Here, we show that NFI heterodimers have intermediate activation potentials compared with homodimers, demonstrating one potential mechanism by which different NFI proteins can regulate gene expression.

Animals↗

PubMed1997

Expression patterns of the four nuclear factor I genes during mouse embryogenesis indicate a potential role in development.

The nuclear factor I (NFI) family of site-specific DNA-binding proteins is required for both the cell-type specific transcription of many viral and cellular genes and for the replication of adenovirus DNA. Although binding sites for NFI proteins within the promoters of several tissue-specific genes have been shown to be essential for their expression, it is unclear which NFI gene products function in specific tissues during development. We have isolated cDNAs from all four murine NFI genes (gene designations Nfia, Nfib, Nfic, and Nfix), assessed the embryonic and postnatal expression patterns of the NFI genes, and determined the ability of specific NFI proteins to activate transcription from the NFI-dependent mouse mammary tumor virus (MMTV) promoter. In adult mice, all four NFI genes are most highly expressed in lung, liver, heart, and other tissues but only weakly expressed in spleen and testis. The embryonic expression patterns of the NFI genes is complex, with NFI-A transcripts appearing earliest-within 9 days postcoitum in the heart and developing brain. The four genes exhibit unique but overlapping patterns of expression during embryonic development, with high level expression of NFI-A, NFI-B, and NFI-X transcripts in neocortex and extensive expression of the four genes in muscle, connective tissue, liver, and other organ systems. The four NFI gene products studied differ in their ability to activate expression of the NFI-dependent MMTV promoter, with the NFI-B protein being most active and the NFI-A protein being least active. These data are discussed in the context of the developmental expression patterns of known NFI-responsive genes. The differential activation of an NFI-dependent promoter, together with the expression patterns observed for the four genes, indicate that the NFI proteins may play an important role in regulating tissue-specific gene expression during mammalian embryogenesis.

Amino Acid Sequence↗

PubMed1990

Antistaphylococcal activities of sparfloxacin (CI-978; AT-4140), ofloxacin, and ciprofloxacin.

The activity of sparfloxacin (CI-978; AT-4140) was compared with those of ofloxacin and ciprofloxacin against clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis. All 10 ciprofloxacin-resistant staphylococci had reduced susceptibility to sparfloxacin and ofloxacin. Against 105 ciprofloxacin-susceptible strains of S. aureus, the sparfloxacin MIC for 90% of strains tested was at least fourfold lower than those of ciprofloxacin and ofloxacin, while against 104 ciprofloxacin-susceptible strains of S. epidermidis, the MIC of sparfloxacin for 90% of strains tested was twofold lower than that of ciprofloxacin and fourfold lower than that of ofloxacin. MBCs of sparfloxacin were less than or equal to 4 x MICs. The effects of inoculum size and pH variations, as well as the presence of serum, on the MICs of sparfloxacin were minimal. Subinhibitory concentrations of sparfloxacin did reduce adherence of S. epidermidis.

Anti-Infective Agents↗

PubMed1989

Cutaneous manifestations of intestinal helminthic infections.

Several intestinal helminths may involve the skin. In cutaneous larva migrans and enterobiasis this is often the only organ involved, whereas hookworm and trichinosis are characterized by multisystem disease. The clinical spectrum of strongyloidiasis may range from a low-grade chronic dermatitis to a fulminant, often fatal, hyperinfection syndrome in the immunocompromised host. In the absence of recent breakthroughs in diagnostic testing, a meticulous history and knowledge of the life cycles and the often characteristic skin manifestations of these parasites remain essential to prompt diagnosis and effective treatment.

Antiparasitic Agents↗

PubMedDate not supplied

Papillary microcarcinoma of the thyroid: a clinico-pathologic and prognostic review.

Papillary microcarcinoma (PMC) of the thyroid is the most common form of thyroid cancer, which usually remains clinically silent until its incidental histologic diagnosis in autopsy or surgical material. Autopsy incidence varies from 3%-36%. PMC may, however, present with clinical symptoms, the commonest of which is cervical lymphadenopathy with or without palpable thyroid nodules. Other reported presentations include cystic neck mass, pulmonary mass (es), metastases in the skull or vertebral column. The upper limit of size to define PMC is 10 mm in most studies but many studies include lesions up to 15 mm in diameter. Histologic variants include encapsulated and partially encapsulated papillary carcinoma, circumscribed microcarcinoma and occult sclerosing carcinoma. Younger age and size less than 10 mm (< 15 mm in other studies) are considered to be favorable prognostic factors. Size alone, however, cannot be regarded as a determinant of prognosis. Older age, larger tumor size, distant metastases, capsular invasion and multifocality indicate unfavorable prognosis. Loss of heterozygosity (LOH) is an infrequent finding, since small deletions may be missed by southern blot analysis. Activation of oncogenes ret and trk have been reported in papillary carcinoma. Some authors advocate conservative while others favor aggressive therapy including total thyroidectomy with or without Iodine 131ablation. Additional investigative techniques are needed to identify the subset of PMC cases with a potential for aggressive clinical course, thereby targeting more aggressive therapy to an appropriate subset of tumors.

Carcinoma, Papillary↗