MOSAIC study

A very comprehensive multicenter, randomized, double-blind study of two parallel treatment arms (the MOSAIC study MOxifloxacin compared to Standard therapy in Acute Infectious exacerbations of Chronic infections) demonstrated the powerful clinical activity of moxifloxacin for the treatment of AECB. Five-day treatment with moxifloxacin (400 mg, once daily for 5 days) was found to produce clinical cure rates that were superior to those achieved with 7-day treatment with a standard antibiotic (amoxicillin 500 mg three times daily for 7 days clarithromycin 500 mg twice daily for 7 days cefuroxime 250 mg twice daily for 7 days) [184]. 

Biological membranes provide the essential barrier between cells and the organelles of which cells are composed. Cellular membranes are complicated extensive biomolecular sheetlike structures, mostly fonned by lipid molecules held together by cooperative nonco-valent interactions. A membrane is not a static structure, but rather a complex dynamical two-dimensional liquid crystalline fluid mosaic of oriented proteins and lipids. A number of experimental approaches can be used to investigate and characterize biological membranes. However, the complexity of membranes is such that experimental data remain very difficult to interpret at the microscopic level. In recent years, computational studies of membranes based on detailed atomic models, as summarized in Chapter 21, have greatly increased the ability to interpret experimental data, yielding a much-improved picture of the structure and dynamics of lipid bilayers and the relationship of those properties to membrane function [21]. 

Extracts from 152 plant species, representing 46 different families, were screened for effects on tobacco mosaic virus (TMV) replication in cucumber cotyledons. Twenty species have shown enough activity to warrant further study. Several members of the Caprifoliaceae family increased virus replication. An extract of Lonicera involucrata enlarged the virus lesions in local lesion hosts and produced a thirty fold increase in virus titer, but had no effect on virus replication in systemic hosts. The active material appears to affect the virus defense mechanism of local lesion hosts. An extract of common geranium is an active virus inhibitor. It inactivates TMV and TMV-RNA (ribonucleic acid) in vitro by forming non-infectious complexes. In vivo, it also inhibited starch lesion formation in cucumber cotyledons incited by TMV infection. 

The first membrane model to be widely accepted was that proposed by Danielli and Davson in 1935 [528]. On the basis of the observation that proteins could be adsorbed to oil droplets obtained from mackerel eggs and other research, the two scientists at University College in London proposed the sandwich of lipids model (Fig. 7.2), where a bilayer is covered on both sides by a layer of protein. The model underwent revisions over the years, as more was learned from electron microscopic and X-ray diffraction studies. It was eventually replaced in the 1970s by the current model of the membrane, known as the fluid mosaic model, proposed by Singer and Nicolson [529,530]. In the new model (Fig. 7.3), the lipid bilayer was retained, but the proteins were proposed to be globular and to freely float within the lipid bilayer, some spanning the entire bilayer. 

Wisniewska, A., J. Draus, and W. K. Subczynski. 2006. Is fluid mosaic model of biological membranes fully relevant Studies on lipid organization in model and biological membranes. Cell. Mol. Biol. Lett. 8 147-154. 

The first hurdle encountered during the development of alfalfa as a recombinant protein production system was the relative inefficiency of the available expression cassettes. A study in which a tomato proteinase inhibitor I transgene was expressed in tobacco and alfalfa under the control of the cauliflower mosaic virus (CaMV) 35S promoter showed that 3-4 times more protein accumulated in tobacco leaves compared to alfalfa leaves [5]. Despite the low efficiency of the CaMV 35S promoter in alfalfa, bio-pharmaceutical production using this system has been reported in the scientific literature. Such reports include expression of the foot and mouth disease virus antigen [6], an enzyme to improve phosphorus utilization [7] and the anti-human IgG C5-1 [8]. In this last work, the C5-1 antibody accumulated to 1% total soluble protein [8]. 

The majority of viruses that infect plants have single-stranded, positive-sense RNA genomes. It has therefore been necessary to use infectious cDNA clones for the in vitro manipulation of RNA viruses, allowing them to be developed as effective tools for the commercial production of target proteins in plants. This approach has also been used to study the genetic and metabolic profiles of both viruses and their host plants. Siegel [14] conceptualized the potential use of RNA viruses as expression vectors. Brome mosaic virus (BMV) and Tobacco mosaic vims (TMV) were the first two RNA viruses to be converted into expression vectors. These vectors have since been pro-... 

Within each species, individual promoters resulted in distinct, tissue-dependent accumulation patterns. The cauliflower mosaic virus (CaMV) 35S promoter, for example, led to high-level accumulation in callus and leaves whereas the maize ubiqui-tin-1 promoter was the best choice for producing recombinant proteins in cereal seeds even though it is not in itself seed-specific [23]. The lack of such comparative studies for proteins other than rAbs makes it difficult to generalize an optimal expression strategy for all proteins. Tables 7.1 and 7.2 list recombinant proteins expressed in plants and provide details of the production system, promoters and other regulatory elements used in each case. 

Fate of plant viruses after a soil solarization treatment was almost completely ignored by researchers, as only one study documented a stabilizing effect of heat treatment on tobacco mosaic virus degradation in a sandy loam soil (Triolo and Materazzi 1992). 

Fleming, S.J. and Swann C.P. (1999). Roman mosaic glass a study of production processes, using PIXE spectrometry. Nuclear Instruments and Methods in Physics Research B 150 622-627. 

Detection of chromosome fragments. Individuals with Turner s syndrome are, in some cases, mosaic for a portion of or for the entire Y chromosome (46,XY/45,X). Since such individuals may be at increased risk for gonadal tumors, Southern blot or PCR analysis has been used to detect the presence of Y chromosome segments in studies of DNA from peripheral blood samples. Similarly, the fetal sex as well as the presence of some aneuploid states (e.g., trisomy 18) can be determined by analysis of DNA from chorionic villi or amniotic fluid cells. 

Gryns (1896), Hedin (1897), and especially Overton (1900) looked at the permeability of a wide range of different compounds, particularly non-electrolytes, and showed that rates of penetration of solutes into erythrocytes increased with their lipid solubility. Overton correlated the rate of penetration of the solute with its partition coefficient between water and olive oil, which he took as a model for membrane composition. Some water-soluble molecules, particularly urea, entered erythrocytes faster than could be attributed to their lipid solubility—observations leading to the concept of pores, or discontinuities in the membrane which allowed water-soluble molecules to penetrate. The need to postulate the existence of pores offered the first hint of a mosaic structure for the membrane. Jacobs (1932) and Huber and Orskov (1933) put results from the early permeability studies onto a quantitative basis and concluded molecular size was a factor in the rate of solute translocation. 

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