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At least 451 records · Page 25Linked to original sources
PubMed2006

Response to bortezomib (velcade) in a case of advanced bronchiolo-alveolar carcinoma (BAC). A case report.

A 65-year-old male with 40-pack year smoking history presented with exertional dyspnea and was subsequently diagnosed with bronchiolo-alveolar carcinoma (BAC). He did not respond to first line therapy with geftinib, but he achieved disease stabilization with gemcitabine and carboplatin for 4 months before developing symptomatic worsening requiring oxygen supplementation. He responded dramatically to bortezomib with rapid symptom improvement. The follow-up computerized tomography revealed partial response that was maintained for 11 months. Based on observations like this and those seen in phase I studies with bortezomib, this agent is being studied now in patients with bronchio-alevolar cancer.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2003

Cloning of the genomes of human cytomegalovirus strains Toledo, TownevarRIT3, and Towne long as BACs and site-directed mutagenesis using a PCR-based technique.

The 230-kb human cytomegalovirus genome is among the largest of the known viruses. Experiments to determine the genetic determinants of attenuation, pathogenesis, and tissue tropism are underway; however, a lack of complete sequence data for multiple strains and substantial problems with genetic instability during in vitro propagation create serious complications for such studies. For example, recent findings suggest that common laboratory strains Towne and AD169 passaged in cultured human fibroblasts are missing up to 15 kb of genetic information relative to clinical isolates. To establish standard, genetically stable genomes that can be sequenced, disseminated, and repeatedly reconstituted to produce virus stocks, we have undertaken to clone two variants of Towne, designated Towne(long) and Towne(short) (referred to as TownevarRIT3) (A., Proc. Natl. Acad. Sci. USA 98, 7829-7834), and the pathogenic strain Toledo into bacterial artificial chromosomes (BACs). We further demonstrate the ease with which mutagenesis can be achieved by deleting 13.5 kb from the Toledo genome using a PCR-based technique.

Cell Line↗
PubMed1999

Zebrafish YAC, BAC, and PAC genomic libraries.

Numerous positional cloning projects directed at isolating genes responsible for the myriads of observed developmental defects in the zebrafish are anticipated in the very near future. In this chapter, we have reviewed the YAC, BAC, and PAC large-insert genomic resources available to the zebrafish community. We have discussed how these resources are screened and used in a positional cloning scheme and have pointed out frequently formidable logistical considerations in the approach. Despite being extremely tedious, positional cloning projects in the zebrafish will be comparatively easier to accomplish than in human and mouse, because of unique biological advantages of the zebrafish system. Moreover, the ease and speed at which genes are identified and cloned should rapidly increase as more mapping reagents and information become available, thereby paving the way for meaningful biological studies.

Animals↗
PubMed2000

Forward with BACs: new tools for herpesvirus genomics.

The large, complex genomes of herpesviruses document the high degree of adaptation of these viruses to their hosts. Not surprisingly, the methods developed over the past 30 years to analyse herpesvirus genomes have paralleled those used to investigate the genetics of eukaryotic cells. The recent use of bacterial artificial chromosome (BAC) technology in herpesvirus genetics has made their genomes accessible to the tools of bacterial genetics. This has opened up new avenues for reverse and forward genetics of this virus family in basic research, and also for vector and vaccine development.

Alleles↗
PubMed2003

Rescue of the neural tube defect of loop-tail mice by a BAC clone containing the Ltap gene.

The mouse mutant loop-tail (Lp) is an accepted model for the study of neural tube defects (NTDs) in humans. Whereas Lp/+ heterozygotes show a mild tail defect (looped), homozygous Lp/Lp embryos show a very severe form of NTD, with a completely open neural tube from the hindbrain region to the caudal portion of the spinal cord (craniorachischisis). We have recently identified a positional candidate for Lp on chromosome 1, designated as Ltap. Here, we have used an in vivo complementation approach in transgenic mice to attempt to correct the looped-tail phenotype with a bacterial artificial chromosome clone (BAC280A23) that harbors a full-length copy of the Ltap gene. Genotype:phenotype correlations in Lp/+ heterozygotes carrying BAC280A23 show that this clone can rescue the looped-tail phenotype in two independent founder lines (P < 0.05 and P < 0.0001). Importantly, BAC280A23 is also observed to rescue the lethal NTD of Lp/Lp homozygotes, because several viable transgenic Lp/Lp mice could be identified and appeared normal (P < 0.05). Results from these gain-of-function transgenic animals strongly suggest that the positional candidate Ltap present in this BAC is indeed the gene that is defective in loop-tail.

Animals↗
PubMed2006

BAC-MP4 predictions of thermochemistry for gas-phase antimony compounds in the Sb-H-C-O-Cl system.

Calibrated by both experimental data and high-level coupled-cluster calculations, the BAC-MP4 methodology was applied to 51 SbL(n) (L = H, CH(3), C(2)H(5), Cl, and OH, n = 1-5) molecules, providing calculated heats of formation and associated thermodynamic parameters. These data identify a linear variation in heats of formation with ligand substitution, trends in bond dissociation energies (BDEs) with ligand identity [BDE(Sb-C(2)H(5)) < BDE(Sb-CH(3)) < BDE(Sb-H) < BDE(Sb-Cl) < BDE(Sb-OH)], and a monotonic decrease in BDE upon successive ligand elimination. The linear variation in BDE is consistent with the behavior of other group V elements, in contrast to the characteristic high-low-high trend of adjacent group III (In) and group IV (Sn) elements. Additionally, these data complement those of previous studies of metal-organic species and provide a foundation of thermochemical data that can aid in the selection of CVD precursors and deposition conditions for the growth of antimony-containing materials.

Journal Article↗
PubMed2001

Size matters: use of YACs, BACs and PACs in transgenic animals.

In 1993, several groups, working independently, reported the successful generation of transgenic mice with yeast artificial chromosomes (YACs) using standard techniques. The transfer of these large fragments of cloned genomic DNA correlated with optimal expression levels of the transgenes, irrespective of their location in the host genome. Thereafter, other groups confirmed the advantages of YAC transgenesis and position-independent and copy number-dependent transgene expression were demonstrated in most cases. The transfer of YACs to the germ line of mice has become popular in many transgenic facilities to guarantee faithful expression of transgenes. This technique was rapidly exported to livestock and soon transgenic rabbits, pigs and other mammals were produced with YACs. Transgenic animals were also produced with bacterial or P1-derived artificial chromosomes (BACs/PACs) with similar success. The use of YACs, BACs and PACs in transgenesis has allowed the discovery of new genes by complementation of mutations, the identification of key regulatory sequences within genomic loci that are crucial for the proper expression of genes and the design of improved animal models of human genetic diseases. Transgenesis with artificial chromosomes has proven useful in a variety of biological, medical and biotechnological applications and is considered a major breakthrough in the generation of transgenic animals. In this report, we will review the recent history of YAC/BAC/PAC-transgenic animals indicating their benefits and the potential problems associated with them. In this new era of genomics, the generation and analysis of transgenic animals carrying artificial chromosome-type transgenes will be fundamental to functionally identify and understand the role of new genes, included within large pieces of genomes, by direct complementation of mutations or by observation of their phenotypic consequences.

Animals↗
PubMed1999

BAC-mediated gene-dosage analysis reveals a role for Zipro1 (Ru49/Zfp38) in progenitor cell proliferation in cerebellum and skin.

Genetic analysis in mice has most commonly employed two general strategies: phenotypic screens for spontaneous or induced mutations and genotypic analysis using homologous recombination or gene trapping to produce deletion or insertion mutants. Here we use bacterial artificial chromosome (BAC)-mediated gene-dosage analysis in transgenic mice to reveal novel genetic functions that are not evident from conventional loss-of-function mutations. We demonstrate a role for the zinc-finger transcription factor Zipro1 (formerly Ru49 and Zfp38) in the proliferation of granule cell precursors in the developing cerebellum, and document the contribution of this process to the final stages of cerebellar morphogenesis. We also show that Zipro1 is expressed in skin, and increased Zipro1 dosage results in a hair-loss phenotype associated with increased epithelial cell proliferation and abnormal hair follicle development.

Animals↗
PubMed2005

Epigenome analyses using BAC microarrays identify evolutionary conservation of tissue-specific methylation of SHANK3.

CpG islands are present in one-half of all human and mouse genes and typically overlap with promoters or exons. We developed a method for high-resolution analysis of the methylation status of CpG islands genome-wide, using arrays of BAC clones and the methylation-sensitive restriction enzyme NotI. Here we demonstrate the accuracy and specificity of the method. By computationally mapping all NotI sites, methylation events can be defined with single-nucleotide precision throughout the genome. We also demonstrate the unique expandability of the array method using a different methylation-sensitive restriction enzyme, BssHII. We identified and validated new CpG island loci that are methylated in a tissue-specific manner in normal human tissues. The methylation status of the CpG islands is associated with gene expression for several genes, including SHANK3, which encodes a structural protein in neuronal postsynaptic densities. Defects in SHANK3 seem to underlie human 22q13 deletion syndrome. Furthermore, these patterns for SHANK3 are conserved in mice and rats.

Animals↗
PubMed2001

Characterization of trichobakin, a type I ribosome-inactivating protein from Trichosanthes sp. Bac Kan 8-98.

We have isolated a genomic clone encoding trichobakin (TBK), a type I ribosome-inactivating protein from the plant Trichosanthes sp. Bac Kan 8-98 (family Cucurbitaceae), by PCR using specific primers designed from the cDNA sequences of alpha-trichosanthin. The sequence encoding mature TBK was constructed in the pET-21d(+) vector for overexpression in Escherichia coli strain BL21(DE3). The recombinant protein was purified to homogeneity by CM-Sepharose chromatography on FPLC with a final yield of about 55 mg/l of culture. The protein has a molecular mass of about 27 kDa, as shown by SDS/PAGE and matrix-assisted laser-desorption ionization MS. It was found that the protein inhibited luciferase mRNA translation in the rabbit reticulocyte cell-free system with an IC(50) value (that which causes a 50% reduction of residual translational activity) of about 3.5 pM. The rRNA N-glycosidase activity of the protein was also proved at the above-mentioned concentration after rRNAs were treated with acid aniline.

Amino Acid Sequence↗
PubMed1998

Integration of chicken cytogenetic and genetic maps: 18 new polymorphic markers isolated from BAC and PAC clones.

As an approach to integrate the chicken genetic and cytogenetic maps, bacterial artificial chromosome (BAC) and P1-derived artificial chromosome (PAC) clones were localized by fluorescence in situ hybridization (FISH) on chromosomes and by genetic mapping on the East Lansing and Compton reference families. Some of the clones used in this study were previously selected for the presence of potentially polymorphic (CA)n repeats and a microsatellite marker was developed when possible for genetic mapping. For other clones, a single strand conformational polymorphism (SSCP) was developed and used for this purpose. Between the two approaches, 18 markers linking the cytogenetic and genetic maps, seven on macrochromosomes and 11 on microchromosomes, were generated. Our results enabled the assignment and orientation of a linkage group to chromosome 3, together with the assignment of linkage groups to eight different microchromosomes, a fraction of the genome lacking mapping data and for which the degree of coverage by the genetic map was not well estimated previously.

Animals↗
PubMed2002

A BAC contig of approximately 400 kb contains the classical class I major histocompatibility complex (MHC) genes of cattle.

A cattle BAC library derived from an MHC homozygous animal was screened for MHC class I genes. This revealed at least nine class I-related genes in a contig spanning approximately 400 kb, and several additional genes on other clones. The three classical class I genes expressed on this haplotype (A14) were shown to be distributed over a region at most 212 kb apart.

Animals↗
PubMed2005

VIS-O-BAC: exploratory visualization of functional genome studies from bacteria.

UNLABELLED: The visualization-aided exploration of complex datasets will allow the research community to formulate novel functional hypotheses leading to a better understanding of biological processes at all levels. Therefore, we have developed a web resource termed VIS-O-BAC designed for the functional investigation of expression data for model systems, such as bacterial pathogens based on a graphical display. Genome-scale datasets derived from typical 'omic' approaches can directly be explored with respect to three biologically relevant aspects, the genome structure (operon organization), the organization of genes in pathways (KEGG) and the gene function with Gene Ontology (GO) terms. The integrated viewers can be used in parallel and combine expression data and functional annotations from different external data repositories. The graphical visualizations evidently accelerate both the validation of regulatory information and the detection of affected biological processes. AVAILABILITY: http://leger2.gbf.de/cgi-bin/vis-o-bac.pl. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Chromosome Mapping↗
PubMed1999

Sequence-ready 1-Mb YAC, BAC and cosmid contigs covering the distal imprinted region of mouse chromosome 7.

We have constructed approximately 1-Mb contigs of yeast artificial chromosome (YAC), bacterial artificial chromosome (BAC) and cosmid clones covering the imprinted region in mouse chromosome band 7F4/F5. This region is syntenic to human chromosome 11p15.5, which is associated with Beckwith-Wiedemann syndrome (BWS) and certain childhood and adult tumors. These contigs provide the basis for genomic sequencing, identification of genes and their regulatory elements, and functional studies in transgenic and knockout mice, which should be of help to understand not only the mechanisms of imprinting but also the molecular events involved in the genesis of BWS and tumors.

Animals↗
PubMed2000

Structural analysis of Arabidopsis thaliana chromosome 3. II. Sequence features of the 4,251,695 bp regions covered by 90 P1, TAC and BAC clones.

To deduce the entire sequence of the top arm of the Arabidopsis thaliana chromosome 3, the sequence determination was performed on a total of 90 P1, TAC and BAC clones chosen according to our sequencing strategy. Sequence features of the resulting 4,251,695 bp regions were analyzed with various computer programs for similarity search and gene modeling. As a result, a total of 941 potential protein-coding genes were identified. The average density of the genes identified was 1 gene per 4210 bp. Introns were observed in 73% of the genes, and the average number per gene and the average length of the introns were 3.6 and 159 bp, respectively. These sequence features are essentially identical to those of chromosomes 3 and 5 in our previous reports. The regions also contained 14 tRNA genes when searched by similarity to reported tRNA genes and the tRNA scan-SE program. The sequence data and information on the potential genes are available through the World Wide Web database KAOS (Kazusa Arabidopsis data Opening Site) at http://www.kazusa.or.jp/kaos/.

Arabidopsis↗
PubMed2004

Direct subcloning of target region from BAC insert using restriction enzymes that produce non-identical cohesive ends.

Type IIS or interrupted palindrome restriction endonuclease digestion produces unique cohesive ends. Utilization of this feature of BglI, SfiI and BstXI has led to direct subcloning of 28.5-kb and 22.9-kb regions, which contains candidate genes for medaka Double anal fin (Da) mutant, from a 229-kb BAC insert. This method does not contain gel-fractionation of the fragments and time-consuming screening process using hybridization. Non-recombinant backgrounds were distinguished from recombinant clones by introducing GFPuv gene into the subcloning vector. This strategy was successfully applicable even when the target region was cut into three fragments by these enzymes.

Animals↗
PubMed1989

Bio-adhesio-chemo (BAC) therapy for patients with malignant pleural effusion.

Eighteen patients with serious pleuritis carcinomatosa with remarkable pleural effusion were treated with a new pleurodesic therapy, and all the patients treated obtained favorable results. After removing pleural effusion, fibrinogen solution was intrapleurally instilled and then, our newly devised material, G.T.XIII and an anticancer drug, Adriamycin (ADM), were administered as chemosclerosing agents in an attempt to prevent recurrence of the effusion and also to provide locoregional antineoplastic effects. Recurrence of pleural effusion was nil in all patients treated, and subjective complaints of the patients were remarkably relieved. There were 14 patients evaluable, and all the response of these patients resulted in partial response (PR) according to the World Health Organization (WHO) criteria. Improvement of performance status (PS) was observed in 61% (11/18). Eight patients could be discharged. Three patients have remained alive. Fifteen patients died after the therapy, and their median survival was 67 days. Eight patients were autopsied. The postmortem examinations confirmed that fibrous adhesion in the pleural cavity with these materials was significant, and evidence of recurrence of pleural fluid was not seen. Topical oncolytic effects of the ADM were histologically remarkable. This pleurodesis was called "Bio-adhesio-chemo (BAC) therapy."

Adult↗
PubMed2000

Optical mapping of BAC clones from the human Y chromosome DAZ locus.

The accurate mapping of clones derived from genomic regions containing complex arrangements of repeated elements presents special problems for DNA sequencers. Recent advances in the automation of optical mapping have enabled us to map a set of 16 BAC clones derived from the DAZ locus of the human Y chromosome long arm, a locus in which the entire DAZ gene as well as subsections within the gene copies have been duplicated. High-resolution optical mapping employing seven enzymes places these clones into two contigs representing four distinct copies of the DAZ gene and highlights a number of differences between individual copies of DAZ.

Chromosome Mapping↗