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51.
Currently, the treatment of falciparum malaria is seriously compromised by spreading drug resistance. We studied the effects of camptothecin, a potent and specific topoisomerase I inhibitor, on erythrocytic malaria parasites in vitro. In Plasmodium falciparum, camptothecin trapped protein-DNA complexes, inhibited nucleic acid biosynthesis, and was cytotoxic. These results provide proof for the concept that topoisomerase I is a vulnerable target for new antimalarial drug development.  相似文献   
52.
In sickness-conditioned learning, animals become ill after sampling a new substance and develop an aversion that is expressed as avoidance of that substance in subsequent presentations. We examined the parameters of a one-trial, nongustatory, sickness-conditioned learning task in day-old chicks. Chicks pecked a bead and were made ill by i.p. injection of lithium chloride (LiCl). Both 0.5 and 1.0 M LiCl (0.1 ml) produced reliable avoidance at test. Chicks injected with LiCl between 15 and 45 min after training avoided the bead at test, whereas those injected within 5 or 10 min or more than 45 min after training did not. Avoidance was present until 24 h posttraining and absent after 48 h. Therefore, robust learning of the sickness-conditioned learning task occurs in one trial without the need for gustatory cues, and memory for the task lasts at least 24 h. Uses of this task to study memory formation in the day-old chick are discussed.  相似文献   
53.
Implant micromotion is considered to be a major factor in the loosening of cementless total hip replacements. Translational micromotion at the bone-implant interface generally occurs in all three spatial directions. Under physiological loading, the interfacial micromotion consists of a cyclic amplitude and changes in the mean, which, in the cranio-caudal direction, represents subsidence of the prosthesis. Existing measurement strategies, which are based on dial gauges, extensometers, LVDTs, hall-effect transducers or strain gauge techniques provide information about only one component of the general three-dimensional micromovement. Moreover, in the majority of the studies, the data are difficult to interpret due to the measured motions being composed of interfacial micromotion and femoral strains. A new transducer was designed that allows the accurate measurement of all three isolated components of micromotion. An optoelectronic approach, based on silicon position-sensitive detectors (PSD) in combination with high precision mechanical parts, was chosen. To exclude thermodrifts during long-term testing, a thermistor was integrated in the sensor. Validation experiments on a precision positioning table indicated the high precision and resolution of the developed sensors. Furthermore, in-vitro tests on a standard press-fit prosthesis demonstrated the easy handling and reliability of the system.  相似文献   
54.
The CO17-1A/GA733 antigen is associated with human carcinomas and some normal epithelial tissues. This antigen has shown promise as a target in approaches to passive and active immunotherapy of colorectal cancer. The relevance of animal models for studies of immunotherapy targeting this antigen in patients is dependent on the expression of the antigen on normal animal tissues. Immunohistoperoxidase staining with polyclonal rabbit antibodies to the human antigen revealed the human homologue on normal small intestine, colon and liver of mice, rats and non-human primates, whereas mouse monoclonal antibodies to the CO17-1A or GA733 epitopes on the human antigen did not detect the antigen. Polyclonal rabbit antibodies, elicited by the murine antigen homologue derived from recombinant baculovirus-infected insect cells, immunoprecipitated the antigen from mouse small intestine, colon, stomach, kidney and lung. The isolated recombinant murine protein bound polyclonal, but not monoclonal, antibodies to the human CO17-1A/GA733 antigen, and recombinant human antigen bound polyclonal antibodies elicited by the murine antigen homologue. Thus, the antigen homologue expressed by animal tissues is similar, but not identical, to the human antigen. These results have important implications for experimental active and passive immunotherapy targeting the CO17-1A/GA733 antigen.  相似文献   
55.
An original quantitative examination of oxidation-reduction enzymes activity in endotheliocytes of hemomicroclrculatory vessels of jejunum and rectum submucosal base in normal state and in portal hypertension was performed by the authors. Comparative analysis of the activity of the enzymes studied revealed different metabolic processes intensity in these organs, dependent on current hemodynamic conditions. Cytochemical changes in hemomicrocirculatory bed are consistent with structural reorganizations that arise in the wall of vessels studied, consist of several phases and may be used as an assessment criterion for defining the portal hypertension stage.  相似文献   
56.
57.
In neonates and infants, hearing impairment leads to impaired language and cognitive development. For that reason, early detection of this sensory deficit is of outstanding importance, particularly in pre-term neonates, who constitute a high risk population in regard to very early acquired hearing loss. Evoked (EOAE) and spontaneous otoacoustic emission (SOAE) recording in 93 pre-term and full-term neonates revealed that this technique is potentially useful for auditory screening in neonatology units. EOAEs and SOAEs can be recorded successfully from 30 weeks of conceptional age. SOAEs were found to be prevalent in females and presented higher peak numbers in right than in left ears. Furthermore, SOAE incidence in pre-term and full-term neonates was found to be high in EOAE positive ears, associated with strong and robust EOAEs.  相似文献   
58.
Belyaev  B. M.  Patrikeev  V. G.  Lichko  A. A. 《Measurement Techniques》2001,44(11):1161-1165
ISO documents and standards are compared for calculating flow rates and amounts on the basis of gas distribution data for Moscow region. It is shown to be best to introduce Changes 1 into MI 2588-2000, which have been accepted by most of the TC 30 countries.  相似文献   
59.
The contributions of 23 insertion, deletion, or missense mutations within an 81-bp fragment of rpoB, the gene encoding the beta-subunit of the DNA-dependent RNA polymerase of Mycobacterium tuberculosis, to the development of resistance to rifamycins (rifampin, rifabutin, rifapentine, and KRM-1648) in 29 rifampin-resistant clinical isolates were defined. Specific mutant rpoB alleles led to the development of cross-resistance to all rifamycins tested, while a subset of mutations were associated with resistance to rifampin and rifapentine but not to KRM-1648 or rifabutin. To further study the impact of specific rpoB mutant alleles on the development of rifamycin resistance, mutations were incorporated into the rpoB gene of M. tuberculosis H37Rv, contained on a mycobacterial shuttle plasmid, by in vitro mutagenesis. Recombinant M. tuberculosis clones containing plasmids with specific mutations in either codon 531 or 526 of rpoB exhibited high-level resistance to all rifamycins tested, whereas clones containing a plasmid with a mutation in codon 516 exhibited high-level resistance to rifampin and rifapentine but were susceptible to both rifabutin and KRM-1648. These results provided additional proof of the association of specific rpoB mutations with the development of rifamycin resistance and corroborate previous reports of the usefulness of rpoB genotyping for predicting rifamycin-resistant phenotypes.  相似文献   
60.
alpha-Conotoxin MII, a 16-residue polypeptide from the venom of the piscivorous cone snail Conus magus, is a potent and highly specific blocker of mammalian neuronal nicotinic acetylcholine receptors composed of alpha3 beta2 subunits. The role of this receptor type in the modulation of neurotransmitter release and its relevance to the problems of addiction and psychosis emphasize the importance of a structural understanding of the mode of interaction of MII with the alpha3 beta2 interface. Here we describe the three-dimensional solution structure of MII determined using 2D 1H NMR spectroscopy. Structural restraints consisting of 376 interproton distances inferred from NOEs and 12 dihedral restraints derived from spin-spin coupling constants were used as input for simulated annealing calculations and energy minimization in the program X-PLOR. The final set of 20 structures is exceptionally well-defined with mean pairwise rms differences over the whole molecule of 0.07 A for the backbone atoms and 0.34 A for all heavy atoms. MII adopts a compact structure incorporating a central segment of alpha-helix and beta-turns at the N- and C-termini. The molecule is stabilized by two disulfide bonds, which provide cross-links between the N-terminus and both the middle and C-terminus of the structure. The susceptibility of the structure to conformational change was examined using several different solvent conditions. While the global fold of MII remains the same, the structure is stabilized in a more hydrophobic environment provided by the addition of acetonitrile or trifluoroethanol to the aqueous solution. The distribution of amino acid side chains in MII creates distinct hydrophobic and polar patches on its surface that may be important for the specific interaction with the alpha3beta2 neuronal nAChR. A comparison of the structure of MII with other neuronal-specific alpha-conotoxins provides insights into their mode of interaction with these receptors.  相似文献   
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