Effects of maternal antibodies on protection and development of antibody responses to human rotavirus in gnotobiotic pigs

Although maternal antibodies can protect against infectious disease in infancy, they can also suppress active immune responses. The effects of circulating maternal antibodies, with and without colostrum and milk antibodies, on passive protection and active immunity to human rotavirus (HRV) were examined in gnotobiotic pigs. Pigs received intraperitoneal injections of high-titer serum (immune pigs [groups 1 and 2]) from immunized sows, low-titer serum from naturally infected sows (control pigs [groups 3 and 4]), or no serum (group 5). Immune or control colostrum and milk were added to the diet of groups 2 and 4, respectively. After inoculation (3 to 5 days of age) and challenge (postinoculation day [PID] 21) with virulent HRV, the effects of maternal antibodies on protection (from diarrhea and virus shedding), and on active antibody responses (measured by quantitation of antibody-secreting cells [ASC] in intestinal and systemic lymphoid tissues by ELISPOT) were evaluated. Groups 1 and 2 had significantly less diarrhea and virus shedding after inoculation but higher rates of diarrhea and virus shedding after challenge than did groups 3 and 5. Group 1 and 2 pigs had significantly fewer immunoglobulin A (IgA) ASC in intestinal tissues at PID 21 and at postchallenge day (PCD) 7 compared to group 5. Significantly fewer IgG ASC were present in the intestines of group 2 pigs at PID 21 and PCD 7 compared to group 5. There was a trend towards fewer ASC in intestinal tissues of group 2 than group 1, from PID 21 on, with significantly fewer IgA ASC at PCD 7. IgG ASC in the duodenum and mesenteric lymph nodes of group 3 and 4 pigs were significantly fewer than in group 5 at PCD 7. These decreases in ASC emphasize the role of passive antibodies in impairing induction of ASC rather than in merely suppressing the function of differentiated B cells. To be successful, vaccines intended for populations with high titers of maternal antibodies (infants in developing countries) may require higher titers of virus, multiple doses, or improved delivery systems, such as the use of microencapsulation or immune stimulating complexes, to overcome the suppressive effects of maternal antibodies.     

The family history component of cancer genetic risk counseling

This study evaluated effective resistances on the ventricular surfaces of arterially-perfused rabbit hearts. Effective resistances were determined with a four-electrode array that was parallel or perpendicular to epicardial fibers. Resistance along or across epicardial fibers was determined by applying current to the epicardium with two parallel line electrodes and measuring potentials in the region between the electrodes. Computer simulations were performed to gain insight into the distribution of current in the ventricular wall. The effective resistances were not different along versus across fibers. Simulations showed that transmural rotation of fibers causes current to be distributed differently when the electrode is oriented perpendicular versus parallel to epicardial fibers. When the array is oriented so that epicardial current is across fibers, the fraction of current that flows transmurally and along the deeper fibers increases while the fraction of current that flows epicardially decreases. This introduces isotropy of the effective resistance. Thus, in contrast to isolated cardiac fibers, the ventricular epicardium exhibits isotropic effective resistance due to transmural rotation of fibers. The rotation and isotropic resistance may be important for cardiac electrical behavior and effects of electrical current in the ventricles.     

Spontaneous propeptide processing of mini-stromelysin-1 mutants blocked by APMA ((4-Aminophenyl)mercuric acetate)

Human stromelysin-1 (SL-1) is a member of the stromelysin subfamily of matrix metalloproteinases (MMPs). The MMPs play a major role in the degradation of the extracellular matrix (ECM) during normal and pathological conditions. SL-1 like the other MMPs can be activated in vitro by the stepwise removal of the propeptide that contains a single unpaired cysteine which coordinates the active site zinc. Other residues in the propeptide also play a role in maintaining the latency of the enzymes. Deletion mutants and single-site amino acid replacements within the propeptide of a carboxyl-terminally truncated stromelysin-1 (mini-SL-1) were constructed and expressed in Escherichia coli to further examine what amino acids within the propeptide of SL-1 are important for maintaining latency. While the natural enzyme displayed some limited tendency to spontaneously (autolytically) convert to lower Mr in a stepwise manner and finally to the fully processed form, all of the truncation mutants of more than 19 amino acids generated in E. coli showed greatly accelerated self-cleavage indicative of diminished stability and/or resistance to proteolysis of the residual propeptide. Mutant Delta63 as well as other mutants in which most of the propeptide had been deleted no longer responded to exposure to the organomercurial APMA by accelerated autolytic processing. Rather, APMA inhibited the autolytic processing in these mutants, further confirming the complexity of the action of this organomercurial in the activation of pro-MMPs.     

Ability of naloxone to enhance the colonoscopic appearance of normal colon vasculature and colon vascular ectasias

OBJECTIVE: To compare the safety and efficacy of high-dose intravenous (IV) nitroglycerin with those of IV magnesium sulfate for acute tocolysis of preterm labor. METHODS: Thirty-one women with preterm labor before 35 weeks' gestation were assigned randomly to IV magnesium sulfate or IV nitroglycerin for tocolysis. Preterm labor was defined as the occurrence of at least two contractions in 10 minutes, with cervical change or ruptured membranes. Acute tocolysis was defined as tocolysis for up to 48 hours. Magnesium sulfate was administered as a 4-g bolus, then at a rate of 2-4 g/h. Nitroglycerin was administered as a 100-microg bolus, then at a rate of 1- to 10-microg/kg/min. The primary outcome measure was achievement of at least 12 hours of successful tocolysis. RESULTS: Thirty patients were available for analysis. There were no significant differences in gestational age, cervical dilation, or incidence of ruptured membranes between groups at the initiation of tocolysis. Successful tocolysis was achieved in six of 16 patients receiving nitroglycerin, compared with 11 of 14 receiving magnesium sulfate (37.5 versus 78.6%, P = .033). Tocolytic failures (nitroglycerin versus magnesium sulfate) were due to persistent contractions with cervical change or rupture of previously intact membranes (five of 16 versus two of 14), persistent hypotension (four of 16 versus none of 14), and other severe side effects (one of 16 versus one of 14). Maternal hemodynamic alterations were more pronounced in patients who received nitroglycerin, and 25% of patients assigned to nitroglycerin treatment had hypotension requiring discontinuation of therapy. CONCLUSION: Tocolytic failures were more common with nitroglycerin than with magnesium sulfate. The hemodynamic alterations noted in patients receiving nitroglycerin, including a 25% incidence of persistent hypotension, might limit the usefulness of IV nitroglycerin for the acute tocolysis of preterm labor.     

Intralenticular implant study in pigmented rabbits: opacity lensmeter assessment

PURPOSE: To quantitatively analyze the clarity of regenerated lens material after endocapsular lens extraction and restoration of the lens capsular bag with and without implantation of an intralenticular disc lens. SETTING: Shepherd Research Center, Allergan, Irvine, California, USA. METHOD: The clarity of regenerated lens material was evaluated by Interzeag Opacity Lensmeter 701 (OLM) recordings after endocapsular lens extraction in New Zealand/Dutch Belt pigmented rabbits with (n = 21) and without (n = 16) placement of a disc-shaped intralenticular implant in the capsular bag. Postoperative objective measurements were performed at 1, 2, and 3 weeks and 1, 2, 3, and 6 months. Comparisons were made between young and adult rabbits. RESULTS: Mean OLM results were similar in both groups at weeks 1, 2, 3, and 4. After 1 month, progressive central compaction of early irregular regenerated lens fibers was associated with increased OLM readings that were higher in the intralenticular implant group than in the control group. Regenerated lens opacification was greater in tissue posterior to the intralenticular lens than in that anterior to the disc lens. CONCLUSION: Insertion of an intralenticular disc lens into the lens capsule bag was associated with poor optical clarity primarily of the posterior regenerated lens tissue. The OLM was useful in assessing the degree of opacification of the regenerated lenses.     

Crystal structure studies on plate/shelf like disodium ditungstate

The structure of plate/shelf like disodium ditungstate (Na₂W₂O₇) synthesized by new method in the process of ultrasonic spray pyrolysis using acidified aqueous solutions of tungsten (VI) oxide clusters as a precursor was refined down to the R-factor of 8.9 %. X-ray diffraction analysis undoubtedly confirmed formation of orthorhombic Na₂W₂O₇ and refinement of the diffraction data showed that Na₂W₂O₇ powder belongs to the base-centred orthorhombic type of structure with 64 space group, Cmca. The structure of Na₂W₂O₇ can be described as infinite chains formed from tetrahedral (WO₄) and octahedral (WO₆) building units joined together. It was found that the basic units of the precursor complexes exist in the structure of Na₂W₂O₇. Scanning electron microscopy confirmed formation of plate/shelf like Na₂W₂O₇ particles with an average thickness of about 1.2 μm.     

发挥咨询业作用,推进工程项目管理

承包商对工程的具体掌控力要远高于业主方,业主方面对工程实施中的各种问题往往鞭长莫及。为了帮助业主方从源头上实现项目的成功管理,就要发挥工程咨询机构的作用。本文论述了工程咨询机构在招标阶段项目管理的核心内容,指明了其在招标阶段的关键工作,在一定程度上实现了项目资源的优化配置,为业主节约了成本和效益最大化。同时,也分析了我国目前项目管理发展中存在的问题,并参照国内外先进管理思想和管理模式提出了我国工程咨询机构的发展方向及相应对策,对我国工程咨询业的发展有一定的参考价值。     

GPU accelerated online multi-particle beam dynamics simulator for ion linear particle accelerators

An online beam dynamics simulator is being developed for use in the operation of an ion linear particle accelerator. By employing Graphics Processing Unit (GPU) technology, the performance of the simulator has been significantly increased over that of a single CPU and is therefore viable in the demanding accelerator operations environment. Once connected to the accelerator control system, it can rapidly respond to any control set point changes and predict beam properties along an ion linear accelerator in pseudo-real time. This simulator will be a virtual beam diagnostic tool which is especially useful when direct beam measurements are not available. Details about the code structure design, physics algorithms, GPU implementations, and performance are presented.     

A study of material flow systems (input/output) in high-bay warehouses

A method of planning and designing product sorting systems in warehousing is described. The theoretical background of the analytical models and simulation modelling is given. A calculation of the capacity of elements for joining and dividing for different priorities of material flow is described. New parameters are introduced in the formula for calculating the average number of unit loads in a system for joining, in the direction of the slave flow and for a simple analytical model for joining material flows with two different priorities with an exponential distribution of inter-arrival time. Simulation results are obtained using the GPSS/FON simulation language. Some characteristic results, used in the process of planning and design of two new distribution centres in Belgrade, are shown.     

2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline reduces glial loss and acute white matter pathology after experimental spinal cord contusion

Focal microinjection of 2, 3-dihyro-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), an antagonist of the AMPA/kainate subclass of glutamate receptors, reduces neurological deficits and tissue loss after spinal cord injury. Dose-dependent sparing of white matter is seen at 1 month after injury that is correlated to the dose-related reduction in chronic functional deficits. To determine whether NBQX exerts an acute effect on white matter pathology, female, adult Spague Dawley rats were subjected to a standardized weight drop contusion at T-8 (10 gm x 2.5 cm) and NBQX (15 nmol) or vehicle (VEH) solution focally injected into the injury site 15 min later. At 4 and 24 hr, tissue from the injury epicenter was processed for light and electron microscopy, and the histopathology of ventromedial white matter was compared. The axonal injury index, a quantitative representation of axoplasmic and myelinic pathologies, was significantly lower in the NBQX group at 4 hr (2.7 +/- 0.24, mean +/- SE) and 24 hr (1.4 +/- 0.19) than in VEH controls (3.8 +/- 0.33 and 2.1 +/- 0.20, respectively). Counts of glial cell nuclei indicated a loss of at least 60% at 4 and 24 hr after injury in the VEH group compared with uninjured controls. NBQX treatment reduced this glial loss by half. Immunohistochemistry revealed that the spared glia were primarily oligodendrocytes. Thus, the chronic effects of NBQX in reducing white matter loss after spinal cord injury appear to be attributable to the reduction of acute pathology and may be mediated through the protection of glia, particularly oligodendrocytes.