The negative influence of N-mediated TMV resistance on yield in tobacco: linkage drag versus pleiotropy.

Resistance to tobacco mosaic virus (TMV) is controlled by the single dominant gene N in Nicotiana glutinosa L. This gene has been transferred to cultivated tobacco (N. tabacum L.

EMSY links the BRCA2 pathway to sporadic breast and ovarian cancer.

The BRCA2 gene is mutated in familial breast and ovarian cancer, and its product is implicated in DNA repair and transcriptional regulation. Here we identify a protein, EMSY, which binds BRCA2 within a region (exon 3) deleted in cancer. EMSY is capable of silencing the activation potential of BRCA2 exon 3, associates with chromatin regulators HP1beta and BS69, and localizes to sites of repair following DNA damage.

Pharmacokinetics in vivo and pharmacodynamics ex vivo/in vitro of meropenem and cefpirome in the Yucatan micropig model: continuous infusion versus intermittent injection.

OBJECTIVE: To investigate the pharmacodynamic disposition of two recently developed beta-lactam antibiotics, meropenem and cefpirome, in the Yucatan micropig model, and to compare the bactericidal activity of these drugs against bacteria in this in vitro/ex vivo micropig model after administration by both intermittent injection and continuous infusion. METHODS: Cefpirome (1 g) was given to the micropig over a 12-h period by direct intravenous injection and 6-h continuous infusion (500 mg). Meropenem (250 mg) was administered either by 30-min intravenous and 8-h continuous infusion.

Evidence for a true post-beta-lactamase-inhibitor effect of clavulanic acid against Klebsiella pneumoniae and Haemophilus influenzae.

Objective: The purpose of this study was to investigate and characterize in vitro the post-beta-lactamase inhibitor effect (PLIE) of clavulanic acid against two beta-lactamase-producing species of bacteria.

Methods: The PLIE was investigated against one strain of Klebsiella pneumoniae and one strain of Haemophilus influenzae. A stationary-phase inoculum of about 107 colony-forming units per mL of each bacterium was pre-exposed for 2 h to clavulanic acid, either alone or in combination with amoxicillin at various concentrations.

Mutations truncating the EP300 acetylase in human cancers.

The EP300 protein is a histone acetyltransferase that regulates transcription via chromatin remodelling and is important in the processes of cell proliferation and differentiation. EP300 acetylation of TP53 in response to DNA damage regulates its DNA-binding and transcription functions. A role for EP300 in cancer has been implied by the fact that it is targeted by viral oncoproteins, it is fused to MLL in Leukaemia and two missense sequence alterations in EP300 were identified in epithelial malignancies.

[In vitro demonstration of a true post-beta-lactamases inhibitor effect (PLIE) of clavulanic acid on Klebsiella pneumoniae and Haemophilus influenzae].

In vivo, serum concentrations of beta-lactamase inhibitors measured during the last part of the dosing interval are below the levels associated with in vitro activity. Nevertheless, beta-lactam plus beta-lactamase inhibitor combinations remain active in vivo throughout the dosing interval. One of the many reasons for this contradiction may be the PLIE.

In vitro time-kill curves of cefepime and cefpirome combined with amikacin, gentamicin or ciprofloxacin against Klebsiella pneumoniae producing extended-spectrum beta-lactamase.

Extended-spectrum beta-lactamases (ESBLs) are found in numerous Enterobacteriaceae, mainly in Klebsiella pneumoniae. We investigated the pharmacodynamics of two new extended-spectrum cephalosporins, cefepime and cefpirome, alone and combined with either amikacin or gentamicin or ciprofloxacin by means of time-kill curves against ESBL-producing, aminoglycoside-resistant K. pneumoniae.

[In vivo pharmacokinetic of amikacin and its pharmacodynamic in combination with cefepime, cefpirome and meropenem in an in vitro/ex vivo micropig model].

Three female Yucatan micropigs were included and received a single dose of amikacin (15 mg/kg) by short infusion (30 min) combined either with a single dose of cefepime or cefpirome (30 mg/kg/12 h) or meropenem (7 mg/kg/8 h). The beta-lactams were administered either by intravenous intermittent injection or by continuous infusion. The mean elimination half-life and clearance value of amikacin were 1.

High-performance liquid chromatographic assay for cefepime in serum.

A simple, rapid, specific and sensitive high-performance liquid chromatographic method was developed for the determination of cefepime 1-[[(6R, 7R)-7-[2-(2-amino-4-thiazolyl) glyoxylamido]-2-carboxy-8-oxo-5-thia-1-azabicyclo- [4.2.0]oct-2-en-3-yl]methyl]-1-methylpyrrolidinium hydroxide, inner salt, 7(2)-(Z)-(O-methyloxime) in human serum.

High-performance liquid chromatographic assay for meropenem in serum.

High-performance liquid chromatographic procedures have been developed for the measurement of meropenem in serum. The separation was performed on an Ultrasphere XL-ODS analytical column (75 x 4.6 min I.

[Kinetics of bactericidal activity of cefepime and cefpirome alone or combined with gentamicin, amikacin or ciprofloxacin against Acinetobacter baumannii, Stenotrophomonas maltophilia and Enterobacter cloacae hyperproductive in cephalosporinase].

Nosocomial infections encountered in intensive care units are frequently due to Gram negative bacilli among which Stenotrophomonas maltophilia, Acinetobacter sp., and Enterobacter sp. The aim of the present study was to evaluate the in vitro bactericidal activity of the new broad spectrum cephalosporins cefepime (FEP) and cefpirome (CPO) alone or in combination with amikacin (AKN), gentamicin (GTN) or ciprofloxacin (CIP) against Acinetobacter baumannii, Stenotrophomonas maltophilia and Enterobacter cloacae producing a derepressed cephalosporinase.

High-performance liquid chromatography for the determination of three new fluoroquinolones, fleroxacin, temafloxacin and A-64730, in biological fluids.

High-performance liquid chromatographic procedures have been developed for the measurement of three new fluoroquinolones, fleroxacin, temafloxacin and A-64730, in serum, urine and bile. The sample treatment consists of a two-step chemical extraction. The three molecules are chromatographed on a C18 reversed-phase analytical column with spectrofluorimetric detection.