Expression of Helenium virus S coat protein in Escherichia coli, in vitro in rabbit reticulocyte lysate and transgenic tobacco.

The coat protein open reading frame (ORF) sequence of Helenium virus S (HelVS) was cloned and expressed in E. coli, rabbit reticulocyte and transgenic tobacco. In E. coli the size of the protein was identical to that obtained for the coat protein from purified virus particles and less than that predicted for the fusion protein. This may be due to ribosome binding at a potential ribosome binding site present on the viral sequence, approximately 45 nucleotides upstream from the initiating methionine of the coat protein ORF. This region of HelVS, equivalent to the 1.5 kb subgenomic RNA, also produced high levels of protein when transcribed and translated in vitro. When introduced into Nicotiana tabacum by leaf disk transformation via Agrobacterium tumefaciens, high levels of stable coat protein were detected which were identical in molecular weight to that of HelVS coat protein and constituted approximately 0.1-0.5% of the total extracted protein.     

PARS INTERARTICULARIS STRESS AND DISC DEGENERATION IN CRICKET'S POTENT STRIKE FORCE: THE FAST BOWLER

Cricket fast bowlers are the potent strike force in a multidiscipline team. They subject their spines to repetitive sagittal plane and rotatory movements over many years. The effect of this repetitive stress has not previously been analysed. This study examined 20 former fast bowlers to determine the incidence of spondylolysis, spondylolisthesis and degenerative change. Fast bowlers are noted to have an increased incidence of spondylolysis. A mixed front/side bowling style involving more lumbar hyperextension or rotation has significant association with spondylolysis when compared with side-on bowling styles. There was a high incidence of radiological thoracolumbar degenerative facet joint and disc disease in former fast bowlers.     

In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease.     

Effect of Rb+ on cromakalim-induced relaxation and ion fluxes in guinea pig trachea.

The effects of cromakalim, verapamil and salbutamol have been examined in guinea pig trachealis smooth muscle in both Krebs physiological salt solution and Krebs solution where K+ has been replaced by Rb+. Cromakalim-induced relaxation in the presence of Rb+ was reduced in extent and became transient, whilst the relaxation response to verapamil was enhanced and that to salbutamol unaffected. The transient relaxation occurring in Rb+ was blocked by quinidine and glibenclamide. The presence of extracellular Rb+ also prevented cromakalim-stimulated efflux of both 86Rb+ and 42/43K+. There was, however, no effect on cromakalim-stimulated 86Rb+ uptake. It is proposed that cromakalim is opening two populations of potassium channel in guinea pig tracheal smooth muscle, one of which is susceptible to blockade by Rb+ and one of which is not. The latter channel appears to play the dominant role in cromakalim-stimulated uptake, and is responsible for the transient relaxation response in the presence of rubidium, whilst the former is responsible for the maintained relaxation.     

Fleroxacin pharmacokinetics in patients with liver cirrhosis.

In this open-label study, the disposition of fleroxacin in liver disease in 12 healthy male volunteers, 6 male cirrhotics without ascites (group A), and 6 male cirrhotics with ascites (group B) was evaluated. Fleroxacin (400 mg) was administered orally and intravenously to each subject in a random crossover fashion. Fleroxacin was completely absorbed and achieved similar peak concentrations in plasma in all three study groups (P greater than 0.05). The volume of distribution exceeded 1 liter/kg in healthy controls and was not affected by liver impairment (P greater than 0.05). Only group B demonstrated differences in the pharmacokinetic parameters evaluated: the systemic and renal clearances of fleroxacin and the renal clearances and clearances of the two major metabolites of fleroxacin formed, N-demethyl fleroxacin and fleroxacin N-oxide, were significantly lower and the half-lives of the parent drug and its metabolites were significantly longer in group B than in healthy controls and group A (P less than 0.05). The elimination of the two metabolites appeared to be formation rate limited in all three study groups. It was concluded from this study that a 50% reduction in the fleroxacin maintenance dose in patients with liver disease appears justified only in patients with ascites. However, no change in the fleroxacin loading dose is needed in patients with compromised liver function.     

Vitamin A2-based visual pigments in fully terrestrial vertebrates.

As part of a broad study of the ocular and extraocular photoreceptors of reptiles, we have used high performance liquid chromatography (HPLC) to identify the retinoids present in whole eye extracts of the arboreal lizard Anolis carolinensis and the non-arboreal ruin lizard Podarcis sicula. Unexpectedly, only vitamin A2-derived chromophore was detected in Anolis, while a mixture of vitamin A1- and vitamin A2-derived chromophores was detected in Podarcis. These are the first examples of fully terrestrial vertebrates using vitamin A2-derived chromophore for visual pigment generation. Furthermore, microspectrophotometric (MSP) data for Anolis show a class of photoreceptor having a visual pigment with maximum absorbance at about 625 nm, some 40 nm further into the red than has been found in any terrestrial vertebrate examined to date.     

Use of a Strecker oesophageal stent in the treatment of benign oesophageal stricture

The use of self-expanding prostheses in the management of malignant oesophageal strictures has become well established. The majority of benign peptic oesophageal strictures can be successfully managed using endoscopic or fluoroscopically guided balloon oesophageal dilatation combined with long-term drug therapy, particularly using proton pumper inhibitors. Although endoscopic oesophageal dilatation can be performed on an outpatient basis, it requires repeated hospital visits. There is a small risk of oesophageal perforation whilst cardio-respiratory complications may be encountered during the use of intravenous sedation in an elderly population. The use of a self-expanding Strecker stent in a 98 year old woman with a benign oesophageal stricture is described.