Based on UV cross-linking experiments, it has been reported that the C protein tetramer of 40 S heterogeneous nuclear ribonucleoprotein complexes specifically interacts with stem-loop I of U2 small ...nuclear RNA (snRNA) (Temsamani, J., and Pederson, T. (1996)J. Biol. Chem. 271, 24922–24926), that C protein disrupts U4:U6 snRNA complexes (Forne, T., Rossi, F., Labourier, E., Antoine, E., Cathala, G., Brunel, C., and Tazi, J. (1995) J. Biol. Chem. 270, 16476–16481), that U6 snRNA may modulate C protein phosphorylation (Mayrand, S. H., Fung, P. A., and Pederson, T. (1996) Mol. Cell. Biol. 16, 1241–1246), and that hyperphosphorylated C protein lacks pre-mRNA binding activity. These findings suggest that snRNA-C protein interactions may function to recruit snRNA to, or displace C protein from, splice junctions. In this study, both equilibrium and non-equilibrium RNA binding assays reveal that purified native C protein binds U1, U2, and U6 snRNA with significant affinity (∼7.5–50 nm) although nonspecifically. Competition binding assays reveal that U2 snRNA (the highest affinity snRNA substrate) is ineffective in C protein displacement from branch-point/splice junctions or as a competitor of C protein's self-cooperative RNA binding mode. Additionally, C protein binds snRNA through its high affinity bZLM and mutations in the RNA recognition motif at suggested RNA binding sites primarily affect protein oligomerization.
CNTO 95 is a fully human monoclonal antibody that recognizes αv integrins. Previous studies have shown that CNTO 95 exhibits both anti-tumor and anti-angiogenic activities (Trikha M et al., Int J ...Cancer 110:326–335, 2004). In this study we investigated the biological activities of CNTO 95 on breast tumor cells both in vitro and in vivo. In vitro treatment with CNTO 95 decreased the viability of breast tumor cells adhering to vitronectin. CNTO 95 inhibited tumor cell adhesion, migration, and invasion in vitro. CNTO 95 treatment also induced tyrosine dephosphorylation of focal adhesion kinase (FAK), and the docking protein paxillin that recruits both structural and signaling molecules to focal adhesions (Turner CE, Int J Biochem Cell Biol 30:955–959, 1998; O’Neil GM et al., Trends Cell Biol 10:111–119, 2000). These results suggest that CNTO 95 inhibits breast tumor cell growth, migration and invasion by interruption of αv integrin mediated focal adhesions and cell motility signals. In vivo studies of CNTO 95 were conducted in an orthotopic breast tumor xenograft model. Treatment with CNTO 95 resulted in significant inhibition of both tumor growth and spontaneous metastasis of MDA-MB-231 cells to the lungs. CNTO 95 also inhibited lung metastasis in a separate experimental (tail vein injection) model of metastasis. The results presented here demonstrate the anti-tumor and anti-metastatic activities of CNTO 95 in breast cancer models and provide insight into the cellular and molecular mechanisms mediating its inhibitory effects on metastasis.
To evaluate the interlaboratory and intralaboratory agreement in the performance of Lyme disease serological testing, we sent serum specimens from 132 outdoor workers in New Jersey to as many as four ...independent laboratories. These included one state department of health laboratory, one large commercial laboratory, and two research laboratories. The measurement of agreement employed, the kappa statistic, ranged from .45 to .53 among the four laboratories and from .50 to .54 within the commercial laboratory. These values represent low levels of agreement. The data suggest that Lyme disease serological testing procedures should be standardized so that Lyme disease test results are more comparable between laboratories.
Putative structural genes encodingMycobacterium bovisBCG gyrase A and gyrase B subunits were expressed inEscherichia coliunder the control of a regulated promoter. Upon induction, high levels of ...proteins ofMr92,000 and 75,000 were generated. Purification and reconstitution of these proteins yielded an enzyme with bacterial DNA gyrase activity. DNA supercoiling activity of the mycobacterial enzyme required ATP, Mg2+, and spermidine. Like other bacterial DNA gyrases, the supercoiling activity of the mycobacterial enzyme was inhibited by low concentration of the classical gyrase B subunit inhibitors novobiocin and coumermycin. Older gyrase A subunit inhibitors, nalidixic and oxolinic acid, had no effect on the supercoiling activity at 400 to 800 μg/ml. However,in vitroassays to show the inhibition of supercoiling activity and stimulation of cleavable complex formation demonstrated that ciprofloxacin is a potent inhibitor of mycobacterial DNA gyrase. The availability of highly purified mycobacterial DNA gyrase could aid in future investigations of quinolone derivatives targetingMycobacteriumspecifically.
CNTO 95 is a fully human monoclonal antibody that recognizes αv integrins. Previous studies have shown that CNTO 95 exhibits both anti-tumor and anti-angiogenic activities (Trikha M et al., Int J ...Cancer 110:326-335, 2004). In this study we investigated the biological activities of CNTO 95 on breast tumor cells both in vitro and in vivo. In vitro treatment with CNTO 95 decreased the viability of breast tumor cells adhering to vitronectin. CNTO 95 inhibited tumor cell adhesion, migration, and invasion in vitro. CNTO 95 treatment also induced tyrosine dephosphorylation of focal adhesion kinase (FAK), and the docking protein paxillin that recruits both structural and signaling molecules to focal adhesions (Turner CE, Int J Biochem Cell Biol 30:955-959, 1998; O'Neil GM et al., Trends Cell Biol 10:111-119, 2000). These results suggest that CNTO 95 inhibits breast tumor cell growth, migration and invasion by interruption of αv integrin mediated focal adhesions and cell motility signals. In vivo studies of CNTO 95 were conducted in an orthotopic breast tumor xenograft model. Treatment with CNTO 95 resulted in significant inhibition of both tumor growth and spontaneous metastasis of MDA-MB-231 cells to the lungs. CNTO 95 also inhibited lung metastasis in a separate experimental (tail vein injection) model of metastasis. The results presented here demonstrate the anti-tumor and anti-metastatic activities of CNTO 95 in breast cancer models and provide insight into the cellular and molecular mechanisms mediating its inhibitory effects on metastasis. PUBLICATION ABSTRACT
CNTO 95 is a fully human monoclonal antibody that recognizes alphav integrins. Previous studies have shown that CNTO 95 exhibits both anti-tumor and anti-angiogenic activities (Trikha M et al., Int J ...Cancer 110:326-335, 2004). In this study we investigated the biological activities of CNTO 95 on breast tumor cells both in vitro and in vivo. In vitro treatment with CNTO 95 decreased the viability of breast tumor cells adhering to vitronectin. CNTO 95 inhibited tumor cell adhesion, migration, and invasion in vitro. CNTO 95 treatment also induced tyrosine dephosphorylation of focal adhesion kinase (FAK), and the docking protein paxillin that recruits both structural and signaling molecules to focal adhesions (Turner CE, Int J Biochem Cell Biol 30:955-959, 1998; O'Neil GM et al., Trends Cell Biol 10:111-119, 2000). These results suggest that CNTO 95 inhibits breast tumor cell growth, migration and invasion by interruption of alphav integrin mediated focal adhesions and cell motility signals. In vivo studies of CNTO 95 were conducted in an orthotopic breast tumor xenograft model. Treatment with CNTO 95 resulted in significant inhibition of both tumor growth and spontaneous metastasis of MDA-MB-231 cells to the lungs. CNTO 95 also inhibited lung metastasis in a separate experimental (tail vein injection) model of metastasis. The results presented here demonstrate the anti-tumor and anti-metastatic activities of CNTO 95 in breast cancer models and provide insight into the cellular and molecular mechanisms mediating its inhibitory effects on metastasis.
Premarital HIV-1 testing in New Jersey Altman, R; Shahied, S I; Pizzuti, W ...
Journal of acquired immune deficiency syndromes (1988),
1992, Letnik:
5, Številka:
1
Journal Article
Recenzirano
To answer questions related to the usefulness of premarital testing for human immunodeficiency virus type 1 (HIV-1), two "blinded" or "nonlinked" HIV-1 serosurveys were done in New Jersey, a state ...with a high incidence of AIDS, on blood specimens submitted for a premarital serologic test for syphilis. The first survey involved premarital blood specimens submitted to the New Jersey Department of Health laboratory for the year starting September 1987. The second survey involved premarital specimens submitted to five private or hospital clinical laboratories in the spring of 1989, of which approximately 1,000 consecutive premarital specimens from each laboratory were sent to the Department of Health laboratory for HIV-1 testing. Of 4,247 specimens tested in the 1987-1988 survey, 21 (0.49%) were positive for antibodies to HIV-1, while among 4,696 specimens in the 1989 survey, 29 (0.62%) were positive. When the survey results were weighted by the number of marriages by geographic regions of the state, the weighted premarital HIV-1 seroprevalence was 0.55% for the 1987-1988 survey and 0.62% for the 1989 survey. The male/female ratio of positive tests was 2.7:1 in 1987-1988 and 1.6:1 in 1989. Of the 8,943 specimens in both surveys, 5 (0.06%) gave an indeterminate immunoblot result, compared with 50 positive results. These percentages of premarital HIV-1 infections are much higher than earlier estimates and reports and are of the same magnitude as recently reported blinded premarital HIV-1 testing elsewhere. Results of this magnitude support a recommendation in New Jersey of voluntary HIV-1 counseling and testing for marriage applicants.
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