Search PubMed⌕ Search

Biomedical subjects

Q Liu

Publications and source records attributed to Q Liu.

At least 649 records · Page 36Linked to original sources
PubMed1994

A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.

A strong candidate for the 17q-linked BRCA1 gene, which influences susceptibility to breast and ovarian cancer, has been identified by positional cloning methods. Probable predisposing mutations have been detected in five of eight kindreds presumed to segregate BRCA1 susceptibility alleles. The mutations include an 11-base pair deletion, a 1-base pair insertion, a stop codon, a missense substitution, and an inferred regulatory mutation. The BRCA1 gene is expressed in numerous tissues, including breast and ovary, and encodes a predicted protein of 1863 amino acids. This protein contains a zinc finger domain in its amino-terminal region, but is otherwise unrelated to previously described proteins. Identification of BRCA1 should facilitate early diagnosis of breast and ovarian cancer susceptibility in some individuals as well as a better understanding of breast cancer biology.

Alleles↗
PubMed1994

BRCA1 mutations in primary breast and ovarian carcinomas.

Loss of heterozygosity data from familial tumors suggest that BRCA1, a gene that confers susceptibility to ovarian and early-onset breast cancer, encodes a tumor suppressor. The BRCA1 region is also subject to allelic loss in sporadic breast and ovarian cancers, an indication that BRCA1 mutations may occur somatically in these tumors. The BRCA1 coding region was examined for mutations in primary breast and ovarian tumors that show allele loss at the BRCA1 locus. Mutations were detected in 3 of 32 breast and 1 of 12 ovarian carcinomas; all four mutations were germline alterations and occurred in early-onset cancers. These results suggest that mutation of BRCA1 may not be critical in the development of the majority of breast and ovarian cancers that arise in the absence of a mutant germline allele.

Adult↗
PubMed1994

Inhibition by FK506 of formyl peptide-induced neutrophil activation and associated protein synthesis.

The macrolide FK506 inhibited, by up to 50%, neutrophil migration and the production of the superoxide radical in response to the formyl peptide, formyl-methionyl-leucyl-phenylalanine (FMLP). The production of the superoxide radical in response to phorbol 12-myristate 13-acetate (PMA) was unaffected by FK506. The inhibition of neutrophil functions was accompanied by a partial reversal of FMLP-induced synthesis of cellular proteins, despite a rise in intracellular Ca2+. Neutrophils treated with FK506 demonstrated a small (average 23%) though significant decrease in formyl-peptide receptor numbers but receptor binding affinity was unaffected. The effects of FK506 on neutrophil activation appear to be analogous to those in T-lymphocytes. The incomplete inhibition, by FK506, of neutrophil responses suggests further that activation by FMLP is mediated via distinct multiple signalling pathways, including protein kinase activation and protein synthesis. The inability of FK506 to reduce FMLP-induced rises in cellular Ca2+ or PMA-induced activation of neutrophils suggests that its action is distal to Ca2+ mobilization and distinct from pathways relying on PKC activation. Thus the immunosuppressive effects of FK506 in vivo might be mediated through the inhibition of inflammatory cells other than lymphocytes and the drug therefore has therapeutic potential in a variety of inflammatory conditions. The drug also has potential in vitro for the characterization of signalling pathways from the plasma membrane to the nucleus.

Calcium↗
PubMed1994

Localization of the VHR phosphatase gene and its analysis as a candidate for BRCA1.

The VH1-related human protein (VHR) gene was localized to human chromosome 17q21 in a region thought to contain the BRCA1 locus, a locus that confers susceptibility to breast and ovarian cancer. VHR encodes a phosphatase with dual specificity for tyrosine and serine residues. Thus it is a plausible candidate for a tumor suppressor gene such as BRCA1. To test this possibility, the VHR coding sequence was screened in individuals with familial breast cancer and in sporadic breast tumor and breast cancer cell lines. No mutations were detected, suggesting that the VHR gene is not BRCA1.

BRCA1 Protein↗
PubMed1994

A cell cycle regulator potentially involved in genesis of many tumor types.

A putative tumor suppressor locus on the short arm of human chromosome 9 has been localized to a region of less than 40 kilobases by means of homozygous deletions in melanoma cell lines. This region contained a gene, Multiple Tumor Suppressor 1 (MTS1), that encodes a previously identified inhibitor (p16) of cyclin-dependent kinase 4. MTS1 was homozygously deleted at high frequency in cell lines derived from tumors of lung, breast, brain, bone, skin, bladder, kidney, ovary, and lymphocyte. Melanoma cell lines that carried at least one copy of MTS1 frequently carried nonsense, missense, or frameshift mutations in the gene. These findings suggest that MTS1 mutations are involved in tumor formation in a wide range of tissues.

Base Sequence↗
PubMed1994

Kinase activity of the type V transforming growth factor beta receptor.

The type V TGF-beta receptor purified from bovine liver plasma membranes catalyzed the phosphorylation of casein using [gamma-32P]ATP as co-substrate (Km,app approximately 10 microM). TGF-beta stimulated the casein phosphorylation by the type V receptor with a half-optimal concentration of approximately 0.3 nM. Both TGF-beta-stimulated and -unstimulated phosphorylations occurred at serine residues. Amino acid sequences of 32P-labeled peptides from reverse phase HPLC of the tryptic digests of casein 32P-phosphorylated by the type V receptor were analyzed by automated Edman degradation. Alignment of phosphorylation site amino acid sequences of the 32P-labeled peptides revealed a recognition motif (S-X-E/S(P)) for the kinase activity of the type V receptor. The type V receptor catalyzed the phosphorylation of an octadecapeptide designated peptide SESTE (SKDIGS*ESITEDQAMEDKK) (the asterisk indicates the phosphorylated residue) containing the major phosphorylation site sequence of casein. The Km,app and Vmax for peptide SESTE were determined to be 0.3 microM and 2.2 nmol of 32P incorporation/min/mg of enzyme, respectively. The phosphorylation of peptide SESTE by the type V receptor was stimulated by TGF-beta or polylysine but inhibited by heparin. Like intact casein, peptide SESTE was phosphorylated at 2 close serine residues (-S*-E-S*-T-E-) by the type V receptor. The type V receptor also phosphorylated a variant of peptide SESTE, peptide AESTE (SKDIGAES*TEDQAMEDKK). However, the type V receptor appeared not to phosphorylate peptide SEATE (SKDIGSEATEDQAMEDKKK) in which an alanine residue replaced 1 of the 2 close serine residues (at the C-terminal side) of peptide SESTE. These results suggest that the type V receptor is capable of exerting interdependent phosphorylation.

Amino Acid Sequence↗
PubMed1994

Quantitative characterization of the eddy current fields in a 40-cm bore superconducting magnet.

The temporal and spatial dependence of the eddy current fields, generated by switching off x, y, and z gradients in a 40-cm bore Bruker superconducting magnet, have been studied by measuring the offset frequency of the proton FID obtained from a small spherical sample. The measurements were made with the pre-emphasis unit deactivated. The data obtained at each location were well fitted to a sum of four exponentially decaying components. The shortest decay is, in each case, associated with the decay of the current in the gradient coil itself, while the other decays are associated with three eddy currents with decay times ranging from 13 to 480 ms. Each of the three eddy currents generates an essentially uniform gradient for at least 4 cm on either side of the isocenter. However, when the eddy currents are generated by either the vertical transverse gradient or the longitudinal gradient, the eddy current gradients are also accompanied by a field shift.

Magnetic Resonance Imaging↗
PubMed1994

Cryopreservation of coronary endothelium and endothelial-mediated responses.

Limited availability of functionally viable biological tissues for graft transplantation and scientific research necessitates the development of an effective storage method for preserving existing tissue samples. In this report we briefly reviewed recent attempts in the cryopreservation of coronary endothelium and endothelial-mediated vasoregulatory function. In contrast to partial preservation of vascular smooth muscle cell function, cryostorage of coronary arteries in dimethyl sulfoxide and fetal calf serum resulted in a near complete preservation of the endothelium and its vasoregulatory function. This protection was observed in both animal and human epicardial conduit coronary arteries, as well as in dog intramyocardial resistance arteries. The apparent better preservation of the latter resistance arteries, with a luminal diameter less than 50 microns, is consistent with earlier findings that cryopreservation efficacy improves with fewer and less packing of cells. To further investigate the cryopreservation of endothelial function, we cryostored canine cardiac valves and evaluated the vasorelaxant effects of valvular endothelium-derived vasoactive factors using a bioassay system. As was observed with intact coronary arteries, a near complete preservation of valvular endothelium and its production of vasoactive factors was noted following the freeze and thaw procedures. Thus, these results demonstrate that cryopreservation may provide a useful and efficient storage method for the conservation of limited supplies of biological vascular tissues for graft transplantation and scientific research.

Acetylcholine↗
PubMed1994

Novel zinc finger proteins that interact with the mouse gamma F-crystallin promoter and are expressed in the sclerotome during early somitogenesis.

Lens-specific expression of the mouse gamma-F-crystallin gene is determined, at least in part, by a 23-bp DNA element, the gamma F-1-binding motif, located in the promoter region of the gene. To characterize the transcription factors that regulate gamma F-crystallin gene expression through this element, we have isolated three chicken cDNAs that encode proteins capable of binding specifically to the gamma F-1-binding motif. These three cDNAs represent differential splicing products from a single gene, gamma FBP. The protein isoforms encoded by two of these cDNAs differ in their ability to modulate the activity of promoters containing the gamma F-1-binding motif. Among them, gamma FBP-B functions as a transcriptional repressor in lens cells, and it's expression is developmentally regulated during lens development, suggesting a role for this isoform in the spatial regulation of gamma F-crystallin gene expression. We also show that expression of the different mRNA transcripts are differentially regulated in various tissues. Furthermore, gamma FBP transcripts are highly expressed in presomitic mesoderm and then over the entire epithelial somite. During somitic differentiation, gamma FBP expression becomes restricted to the sclerotome. These expression patterns suggest a regulatory role for the gamma FBP isoforms in sclerotome specification and/or differentiation.

Alternative Splicing↗
PubMed1994

Theoretical and functional aspects of measuring insulin-like growth factor-I mRNA expression in myeloid cells.

This article presents a detailed overview of the conceptual and technical considerations involved in the measurement of insulin-like growth factor-I (IGF-I) mRNAs in leukocytes. Two different quantitative techniques that take advantage of the in vitro synthesis of antisense and sense synthetic IGF-I RNA, respectively, are described: the ribonuclease protection assay (commonly referred to as solution hybridization) and competitive RT-PCR. We have improved the ribonuclease protection assay by constructing tandem, cassette riboprobes to generate multigene antisense RNAs of varying sizes. This approach permits the simultaneous quantitation of two or more mRNAs in a single RNA sample, one of which can serve as an internal standard for comparison of IGF-I transcripts among various treatments. The second approach of competitive RT-PCR represents an improvement in previous technologies by cloning a competing IGF-I sequence into an RNA expression vector. The resulting synthetic sense competitor IGF-I RNA (1.1 kb) serves as an internal standard during both the reverse transcription and amplification steps. We have used both the ribonuclease protection assay and competitive RT-PCR to define the macrophage as the major cellular source of leukocyte-derived IGF-I and to characterize these macrophage-derived mRNAs as being derived almost exclusively from exon 1. In addition, these techniques have allowed us to study the ontogeny of IGF-I expression in differentiating bone marrow macrophages and show that hematopoietic progenitors are induced to express abundant IGF-I transcripts as they differentiate into macrophages in the presence of CSF-1. These techniques can be readily adapted for measuring steady-state transcripts for a variety of leukocyte-derived hormones.

Animals↗
PubMed1994

In vitro resolution of the dimer bridge of the minute virus of mice (MVM) genome supports the modified rolling hairpin model for MVM replication.

Previous characterization of the terminal sequences of the minute virus of mice (MVM) genome demonstrated that the right hand palindrome contains two sequences, each the inverted complement of the other. However, the left hand palindrome was shown to exist as a unique sequence [Astell et al., J. Virol. 54: 179-185 (1985)]. The modified rolling hairpin (MRH) model for MVM replication provided an explanation of how the right hand palindrome could undergo hairpin transfer to generate two sequences, while the left end palindrome within the dimer bridge could undergo asymmetric resolution and retain the unique left end sequence. This report describes in vitro resolution of the wild-type dimer bridge sequence of MVM using recombinant (baculovirus) expressed NS-1 and a replication extract from LA9 cells. The resolution products are consistent with those predicted by the MRH model, providing support for this replication mechanism. In addition, mutant dimer bridge clones were constructed and used in the resolution assay. The mutant structures included removal of the asymmetry in the hairpin stem, inversion of the sequence at the initiating nick site, and a 2-bp deletion within one stem of the dimer bridge. In all cases, the mutant dimer bridge structures are resolved; however, the resolution pattern observed with the mutant dimer bridge compared with the wild-type dimer bridge is shifted toward symmetrical resolution. These results suggest that sequences within the left hand hairpin (and hence dimer bridge sequence) are responsible for asymmetric resolution and conservation of the unique sequence within the left hand palindrome of the MVM genome.

Animals↗
PubMed1994

Isolation and expression analysis of two rice genes encoding the major intrinsic protein.

We isolated two rice cDNAs (rMip1 and rTip1) which are homologous to the genes encoding the major intrinsic protein (Mip) (soybean nod-26 and Arabidopsis gamma-Tip), respectively. Expression of rTip1 in shoots and roots of rice seedlings was enhanced by water stress, salt stress and exogenous ABA. rMip1 was expressed only in shoots. Although mRNA level of rMip1 in shoots was induced to a small extent by exogenous ABA, it did not show any increase under water or salt stress over the course of 12 h. On the basis of the differential expression patterns and evolutional distinctions, it is suggested that the possible channel proteins encoded by rMip1 and rTip1 genes may function in different transport systems.

Abscisic Acid↗
PubMed1994

Expressed sequence tags from cultured cells of rice (Oryza sativa L.) under stressed conditions: analysis of transcripts of genes engaged in ATP-generating pathways.

Large-scale sequencing of randomly selected cDNA clones was used to isolate numerous genes in rice (Oryza sativa L.). Total RNA used for cDNA synthesis was prepared from suspension-cultured cells of rice grown under stressed conditions, such as in saline or nitrogen-starvation conditions. A total of 780 cDNA clones were partially sequenced and about 15% could be identified as putative genes. In the library constructed under saline conditions, we identified several genes associated with signal transduction, such as protein kinase and small GTP-binding protein genes. Many stress-related genes were isolated from both the saline and nitrogen-starvation libraries. These results indicate that stress treatment of suspension-cultured cells makes it possible to efficiently isolate various types of plant genes. To examine the usefulness of such tagged cDNAs for the study of gene expression in a specific metabolic pathway, we analyzed mRNA levels of genes engaged in the ATP-generating pathways in cultured cells of rice under different stresses, such as 20% sucrose, salt stress, cold stress and nitrogen-starvation stress. The results suggest that the coordinated induction of several genes in key steps under stressed conditions may be essential for activation of the entire energy-producing pathway to maintain homeostasis in rice cells. Expressed sequence tags identified by random cDNA sequencing provide the opportunity to generate a transcript map of rice genes.

Adaptation, Biological↗
PubMed1994

Intestinal venous drainage through the liver is a prerequisite for oral tolerance induction.

One feature of enteric mucosal immunity is oral tolerance (OT), a state of diminished systemic immune responsiveness to an antigen induced by previous oral feeding of that antigen. Because OT induction requires an interaction between the intestinal and systemic immune systems, the authors plan to use it as a method in experimental small bowel transplantation (SBT) to evaluate the ability of the intestinal allograft to cooperate immunologically with the host. Two different methods have been used in experimental SBT to establish graft venous drainage: anastomosis of the graft mesenteric vein to the recipient portal vein or to the inferior vena cava. This experiment was designed to examine the role of the intestinal venous drainage routes in OT induction. Rats with a surgically created mesenterico-caval shunt (MCS) and their sham controls received an immunization protocol to induce OT to ovalbumin. The results showed that OT was readily induced in the sham animals, but not in the animals with MCS. These results indicate that intestinal venous drainage through the liver plays a central role in OT induction. Therefore, future analyses of OT in allogeneic SBT will require an animal model with portal venous drainage of the intestinal graft.

Administration, Oral↗
PubMed1994

Lack of graft-versus-host disease after fetal intestine transplantation.

Clinical small bowel transplantation has often been complicated by lethal graft-versus-host disease (GVHD), attributed to the numerous allogeneic immunocompetent lymphocytes contained in the graft. Because the fetal immune system is relatively immature, the authors hypothesized that the risk of GVHD after small bowel transplantation might be diminished by using the fetal intestine as the donor organ. This experiment tested this hypotheses in a rat model. Jejunoileal segments harvested from Lewis (LEW) rat fetuses were transplanted subcutaneously into adult recipients of either syngeneic LEW or semiallogeneic LEW x Brown-Norway F1 (LBNF1) strains. The recipients had follow-up for 21 days after transplantation to assess the growth of the intestinal grafts ("neogut") and evaluate for GVHD. Growth of the intestinal grafts was observed in 65% (53 of 82) of the recipients, with a neogut weight of 4.5 +/- 3.7 g and length of 2.8 +/- 2.1 cm. No significant difference in graft survival rate or neogut weight and length was found between the LEW and LBNF1 recipients. Histopathologic examination of the neogut showed a mature intestinal architecture similar to that of normal adult rat intestine, with well-developed enteric lymphoid tissues including Peyer's patches. However, no clinical or histopathologic evidence of GVHD was found in any of the LBNF1 recipients. These results are consistent with the author's hypothesis and suggest that the use of fetal donor intestine for small bowel transplantation might have some immunologic advantages over the adult (immunologically mature) donor intestine.

Animals↗