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Biomedical subjects

J Zhou

Publications and source records attributed to J Zhou.

At least 703 records · Page 39Linked to original sources
PubMed1996

Complement-activating antibodies in sera from infected individuals and vaccinated volunteers that target human immunodeficiency virus type 1 to complement receptor type 1 (CR1, CD35).

Complement receptor type 1 (CR1) plays a central role in clearing immune complexes from the circulation and probably contributes to the retention of immune complexes on the surface of follicular dendritic cells. Virus-specific, complement-activating antibodies can target human immunodeficiency virus type 1 (HIV-1) to CR1-bearing cells but the potential impact that these antibodies have on HIV-1 pathogenesis is unknown. To study these antibodies, an assay was developed in which immune complexes containing HIV-1, antibody, and complement were formed in vitro and captured on the surface of 96-well immunoplates coated with recombinant soluble human CR1 (rsCR1). Captured virus was detected by p24 immunoassay or by infection of human CD4+ lymphocytes. Two laboratory strains of HIV-1 (IIIB and MN) and primary isolates could be captured using sera from infected individuals or vaccinated volunteers as a source of complement-activating antibodies. HIV-1 immune complexes captured by solid-phase rsCR1 could be transferred to MT-2 cells for productive infection. Antibodies had no activity in this assay when the normal human serum used as a source of complement had been heat-inactivated or depleted of complement component C3, confirming a requirement for complement. These complement-activating antibodies in sera from infected individuals showed strong cross-reactivity with HIV-1 IIIB, MN, and a heterologous primary isolate, but reacted poorly with the autologous isolate obtained at the time of serum collection. Average titers of these antibodies measured with HIV-1 IIIB were moderately lower in HIV-1-infected progressors compared to nonprogressors. In contrast to sera from infected individuals, sera from gp160IIIB-vaccinated volunteers showed specificity for the vaccine strain of virus. These results provide supporting evidence that envelope-specific, complement-activating antibodies induced by infection or gp160 immunization can target HIV-1 immune complexes to CR1. In addition, they demonstrate that such antibodies may sometimes be type-specific and that HIV-1 immune complexes bound to CR1 are infectious.

AIDS Vaccines↗
PubMed1996

A gene similar to PKD1 maps to chromosome 4q22: a candidate gene for PKD2.

We report a partial cDNA sequence that encodes a protein, dubbed "polycystwin," with 21% identify and 46% similarity to amino acids 3688-4109 of the carboxyl terminus of polycystin, the gene product of the autosomal dominant polycystic kidney disease locus located on chromosome 16 at band p13 (PKD1). Northern analysis demonstrates that the R48321 gene is expressed in all tissues examined, including both adult and fetal kidneys. Finally, in situ hybridization studies localize this novel gene to 4q22, where PKD2, the second most common locus for ADPKD, is known to map. Therefore, R48321 is an excellent candidate gene for PKD2.

Amino Acid Sequence↗
PubMed1996

Carboxyl terminus of bovine papillomavirus type-1 L1 protein is not required for capsid formation.

The papillomavirus major capsid protein L1 can assemble into capsids in vitro. To identify areas within the bovine papillomavirus type-1 L1 (BPV L1) protein that are important for virus assembly, we constructed a set of 24 baculovirus recombinants expressing BPV L1 deletion mutants that span the entire L1 open reading frame. Virus-like particle (VLP) formation of the L1 mutants was examined by electron microscopy. Wild-type (wt) BPV L1 expressed in recombinant baculovirus formed VLPs, while capsomeres and aggregates were seen for most of the mutants screened. However, the C-terminal truncation mutant, lacking the last 24 amino acids (delta C2), was observed to form VLPs (threefold more efficiently than wt BPV L1). This suggests that this C-terminal region of L1 protein is not critical for capsid formation. As capsids assembled from BPV L1 are able to agglutinate mouse red blood cells (RBC) by binding to a membrane protein, we tested the ability of the mutants to hemagglutinate mouse RBCs. Most aberrant capsids or aggregates derived from deletion mutants were unable to agglutinate the RBCs with the exception of deletion mutants delta 11 (aa 231-271), delta 14 (aa 291-331), delta 21 (aa 431-471), and the carboxyl-terminus truncation mutant delta C2.

Amino Acid Sequence↗
PubMed1996

Overexpression of glutamine:fructose-6-phosphate amidotransferase in transgenic mice leads to insulin resistance.

The hexosamine biosynthetic pathway has been hypothesized to be involved in mediating some of the toxic effects of hyperglycemia. Glutamine:fructose-6-phosphate amidotransferase (GFA), the first and rate limiting enzyme of the hexosamine biosynthetic pathway, was overexpressed in skeletal muscle and adipose tissue of transgenic mice. A 2.4-fold increase of GFA activity in muscle of the transgenic mice led to weight-dependent hyperinsulinemia in random-fed mice. The hyperinsulinemic-euglycemic clamp technique confirmed that transgenic mice develop insulin resistance, with a glucose disposal rate of 68.5 +/- 3.5 compared with 129.4 +/- 9.4 mg/kg per min (P < 0.001) for littermate controls. The decrease in the glucose disposal rate of the transgenic mice is accompanied by decreased protein but not mRNA levels of the insulin-stimulated glucose transporter (GLUT4). These data support the hypothesis that excessive flux through the hexosamine biosynthesis pathway mediates adverse regulatory and metabolic effects of hyperglycemia, specifically insulin resistance of glucose disposal. These mice can serve as a model system to study the mechanism for the regulation of glucose homeostasis by hexosamines.

Adipose Tissue↗
PubMed1996

The gap protein knirps mediates both quenching and direct repression in the Drosophila embryo.

Transcriptional repression is essential for establishing localized patterns of gene expression during Drosophila embryogenesis. Several mechanisms of repression have been proposed, including competition, quenching and direct repression of the transcription complex. Previous studies suggest that the knirps orphan receptor (kni) may repress transcription via competition, and exclude the binding of the bicoid (bcd) activator to an overlapping site in a target promoter. Here we present evidence that kni can quench, or locally inhibit, upstream activators within a heterologous enhancer in transgenic embryos. The range of kni repression is approximately 50-100 bp, so that neighboring enhancers in a modular promoter are free to interact with the transcription complex (enhancer autonomy). However, kni can also repress the transcription complex when bound in promoter-proximal regions. In this position, kni functions as a dominant repressor and blocks multiple enhancers in a modular promoter. Our studies suggest that short-range repression represents a flexible form of gene regulation, exhibiting enhancer- or promoter-specific effects depending on the location of repressor binding sites.

Amino Acid Sequence↗
PubMed1996

Purification and characterization of a protein that permits early detection of lung cancer. Identification of heterogeneous nuclear ribonucleoprotein-A2/B1 as the antigen for monoclonal antibody 703D4.

We have reported that a mouse monoclonal antibody 703D4, detects lung cancer 2 years earlier than routine chest x-ray or cytomorphology. We purified the 703D4 antigen to elucidate its role in early lung cancer biology, using Western blot detection after SDS-polyacrylamide gel electrophoresis. Purification steps included anion exchange chromatography, preparative isoelectric focusing, polymer-based C18-like, and analytical C4 reverse phase high performance liquid chromatography. After 25-50,000-fold purification, the principal immunostaining protein was > 95% pure by Coomassie staining. The NH2 terminus was blocked, so CNBr digestion was used to generate internal peptides. Three sequences, including one across a site of alternate exon splicing, all identified a single protein, heterogeneous nuclear ribonucleoprotein-A2 (hnRNP-A2). A minor co-purifying immunoreactive protein resolved at the final C4 high performance liquid chromatography step is the splice variant hnRNP-B1. Northern analysis of RNA from primary normal bronchial epithelial cells demonstrated a low level of hnRNP-A2/B1 expression, consistent with immunohistochemical staining of clinical samples, and increased hnRNP-A2/B1 expression was found in lung cancer cells. hnRNP-A2/B1 expression is under proliferation-dependent control in normal bronchial epithelial cell primary cultures, but not in SV40-transformed bronchial epithelial cells or tumor cell lines. With our clinical data, this information suggests that hnRNP-A2/B1 is an early marker of lung epithelial transformation and carcinogenesis.

Amino Acid Sequence↗
PubMed1996

Structure of the human type IV collagen COL4A6 gene, which is mutated in Alport syndrome-associated leiomyomatosis.

Basement membrane (type IV) collagen, a subfamily of the collagen protein family, is encoded by six distinct genes in mammals. Three of those, COL4A3, COL4A4, and COL4A5, are linked with Alport syndrome (hereditary nephritis). Patients with leimoyomatosis associated with Alport syndrome have been shown to have deletions in the 5' end of the COL4A6 gene, in addition to having deletions in COL4A5 (Zhou et al., Science 261: 1167-1169, 1993). The human COL4A6 gene is reported to be 425 kb as determined by mapping of overlapping YAC clones by probes for its 5' and 3' ends. In the present study we describe the complete exon/intron size pattern of the human COL4A6 gene. The 12 lambda phage clones characterized in the study spanned a total of 110 kb, including 85 kb of the actual gene and 25 kb of flanking sequences. The overlapping clones contained all 46 exons of the gene and all introns, except for intron 2. Since the total size of the exons and all introns except for intron 2 is about 85 kb, intron 2 must be about 340 kb. All exons of the gene were assigned to EcoRI restriction fragments to facilitate analysis of the gene in patients with leiomyomatosis associated with Alport syndrome. The exon size pattern of COL4A6 is highly homologous with that of the human and mouse COL4A2 genes, with 27 of the 46 exons of COL4A6 being identical in size between the genes.

Amino Acid Sequence↗
PubMed1996

Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation.

We report the cloning of a transcription-associated histone acetyltransferase type A(HAT A). This Tetrahymena enzyme is strikingly homologous to the yeast protein Gcn5, a putative transcriptional adaptor, and we demonstrate that recombinant Gcn5p possesses HAT activity. Both the ciliate enzyme and Gcn5p contain potential active site residues found in other acetyltransferases and a highly conserved bromodomain. The presence of this domain in nuclear A-type HATs, but not in cytoplasmic B-type HATs, suggests a mechanism whereby HAT A is directed to chromatin to facilitate transcriptional activation. These findings shed light on the biochemical function of the evolutionarily conserved Gcn5p-Ada complex, directly linking histone acetylation to gene activation, and indicate that histone acetylation is a targeted phenomenon.

Acetylation↗