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991.
Enhanced molecular volume of conservatively pegylated Hb: (SP-PEG5K)6-HbA is non-hypertensive 总被引:2,自引:0,他引:2
Acharya SA Friedman JM Manjula BN Intaglietta M Tsai AG Winslow RM Malavalli A Vandegriff K Smith PK 《Artificial cells, blood substitutes, and immobilization biotechnology》2005,33(3):239-255
Recent studies have suggested that the "pressor effect" of acellular Hb is a consequence of perturbation of the macro-and microcirculatory system in multiple ways, and that PEGylation is an effective approach for controlling the same. In an attempt to confirm this concept, a new and simple thiolation mediated, maleimide chemistry-based conservative PEGylation protocol has been developed to conjugate multiple copies of PEG-chains to Hb. This approach combines the high reactivity of maleimides towards thiols with the propensity of iminothiolane to derivatize the epsilon-amino groups of proteins into reactive thiol groups, with conservation of their positive charge. One of the PEGylated products, namely (SP-PEG5K)6-HbA, that carries on an average six copies of PEG5000 chains per Hb, is non-hypertensive in hamster top load and in rat 50% exchange transfusion models. This hexa-PEGylated-Hb has (i) a hydrodynamic volume corresponding to that of an oligomerized Hb of 256kDa, (ii) a molecular radius of approximately 6.8 nm, (iii) high oxygen affinity, (iv) lowered Bohr effect, and (v) increased viscosity and colloidal osmotic pressure. These properties of (SP-PEG5K)6-HbA are consistent with the emerging new paradigms for the design of Hb based oxygen carriers and confirm the concept that the "pressor effect" of Hb is a multifactorial event. The thiolation mediated maleimide chemistry-based PEGylation protocol described here for the generation of (SP-PEG5K)6-Hb is simple, highly efficient, and is carried out under oxy conditions. The results demonstrate that a non-hypertensive PEG-Hb can be generated by conjugation of a lower number of PEG chains than previously reported. 相似文献
992.
993.
Chun Chang John Lipian Dennis A. Barnes Larry Seger Cheryl Burns Brian Bennett Laura Bonney Larry F. Rhodes George M. Benedikt Robert Lattimer Shyhchang S. Huang Victor W. Day 《Macromolecular chemistry and physics.》2005,206(19):1988-2000
Summary: Homopolymers of a bis‐trifluorocarbinol substituted norbornene ( 1 ) (α,α‐bis(trifluoromethyl)bicyclo[2.2.1]hept‐5‐ene‐2‐ethanol or HFANB) and copolymers of 1 with t‐butyl ester of 5‐carboxylic acid ( 2 , t‐BuEsNB) were produced using palladium catalysts and olefinic chain transfer agents such as 1‐hexene and ethylene to control molecular weight. However, these low‐molecular‐weight polymers exhibited relatively low optical transparencies at 193 nm. In fact, the opacity (measured as optical densities in absorbance units per micron) of thin films of these homo‐ and co‐polymers was inversely proportional to their molecular weight. This relationship is consistent with an end group contribution to the film opacity. Spectroscopic analysis of these polymers by 1H NMR and MALDI‐TOF MS confirmed that 1‐hexene and ethylene chain transfer agents generated olefin‐terminated vinyl addition polymers. The olefinic end group contribution to optical density can be eliminated by appropriate chemical modification. Both epoxidation and hydrogenation of the polymer olefinic end groups generated very low optical density materials, independent of molecular weight, that are suitable as 193‐nm photoresist binder resins.
994.
Ilia Frolov Vladimir Kleiner Boris Krentsel Robert Mardanov Kalyan Munshi Gennady Bukatov Vladimir Zakharov Sergey Sergeev 《Macromolecular chemistry and physics.》1993,194(8):2309-2321
In order to find out correlations between the structure of an external donor and the obtained polymer, the effects of different external donors on the activity and stereospecificity of the MgCl2/TiCl4 catalytic system in the bulk polymerization of 4-methyl-1-pentene (4MP) were carefully studied. Different silane compounds of the structure RnSi(OR')4-n (where: n = 1–3, R = alkyl/phenyl, R = alkyl) and Al(i-Bu)3 (TIBA) were used as external donors and cocatalyst, respectively. The effect of the donor/TIBA mole ratio on the activity and stereospecificity of the catalytic system was studied. Some major effects were observed for the three different external donors, namely, Me3Si(OMe), Me2Si(OMe)2, and Me3Si(OBu)3, in the 4MP polymerization process. It was observed that the effect of the external silane donor on the polymerization strongly depends upon the size of the alkoxy and hydrocarbon (alkyl/phenyl) groups which are attached to the silicon atom. A selective deactivation of the non-stereospecific centers, as well as a transformation of the non-stereospecific into isospecific centers, is assumed to occur. On the basis of the obtained results and literature data available for the propene polymerization, the concept of structural conformity between the ligand-surrounded active center and the monomer molecule was carried forward. 相似文献
995.
Robert F. Hink Wayne H. Fenton Jr. Adolph Pfefferbaum Jared R. Tinklenberg Bert S. Kopell 《Psychophysiology》1978,15(5):466-473
In order to determine the extent to which distraction disrupts performance when attention is divided, the distribution of attention across five auditory input channels was assessed using the N1 component of the human auditory evoked potential. In addition, the possibility that methylphenidate (Ritalin) affects the distribution of attention across input channels was tested. Sixteen subjects performed a tone discrimination task under conditions of focused attention and divided attention, both with and without the presence of stimuli interposed between the points to be attended. The subjects performed in two sessions during which they received either methylphenidate (10 mg) or a placebo in a double-blind design. The results showed that the interposed stimuli were receiving some attention resulting in a disruption of performance. Methylphenidate did not affect the distribution of attention as reflected in the N1 wave. The data are interpreted as showing that: 1) distraction plays a major role in producing performance deficits observed with divided attention; and 2) methylphenidate does not appreciably affect the distribution of attention across input channels. 相似文献
996.
Robert J. Stephens Marlene F. Sloan Michael J. Evans Gustave Freeman 《The American journal of pathology》1974,74(1):31-58
The epithelial response in the terminal bronchioles and alveoli was examined after exposure to approximately 0.5 and 0.9 ppm ozone (O3). Loss of ciliated cells from the terminal bronchiole was pronounced after 6 to 10 hours of exposure; however, nonciliated cells were resistant to injury from O3. In contrast, type 1 alveolar lining cells were very sensitive to O2 and were severely damaged or removed from significant areas of the proximal alveoli after as little as 2 hours of exposure to 0.5 ppm. The basement lamina was left devoid of an epithelium with the exception of type 2 cells, which were very resistant and retained a relatively normal appearance. Under continuous exposure, repair of the lesion area was accomplished in approximately 48 hours through proliferation of the type 2 cells. The new cells were cuboidal at first but subsequently became more squamous in appearance. Exposure for 8 to 10 hours followed by residence in clean air resulted in a proliferative response at 48 hours, about equal to that observed after continuous exposure. 相似文献
997.
Antibody to Mycoplasma pneumoniae in Nasal Secretions and Sputa of Experimentally Infected Human Volunteers 总被引:8,自引:7,他引:8 下载免费PDF全文
Helmut Brunner Harry B. Greenberg Walter D. James Robert L. Horswood Robert B. Couch Robert M. Chanock 《Infection and immunity》1973,8(4):612-620
After experimental infection with Mycoplasma pneumoniae, 42% of 67 volunteers developed a threefold or greater rise in antibody in nasal secretions as measured by radioimmunoprecipitation. Development of an antibody increase in sputum was detected more often, i.e., in 73% of the volunteers. Each of the antibody increases involved immunoglobulin (Ig) A. Twelve rises in IgG antibody were detected in the specimens which exhibited a rise in IgA antibody. In almost every instance the rise in IgA antibody exceeded that seen with IgG antibody. Analysis of the response to experimental challenge with M. pneumoniae of volunteers with different levels of preexisting respiratory tract IgA antibody suggested that this secretory antibody was related to host resistance to M. pneumoniae disease. Further, respiratory tract IgA antibody appeared to be more directly related to host resistance than was antibody in serum. 相似文献
998.
999.
Paul E. Baer Lisa Berg Garmezy Robert J. McLaughlin Alex D. Pokorny Mark J. Wernick 《Journal of behavioral medicine》1987,10(5):449-466
This study examined alcohol use among seventh graders in relation to life events, daily hassles, the supportive quality of the family environment, coping, and anxiety. Four hundred twenty-five students participated, 228 girls and 197 boys. Stepwise regression and discriminant function analyses indicated that the students reported more alcohol use if they also reported more life events, more daily hassles, and more conflict in the family. A stress-buffering effect of low family conflict on life events could not be substantiated for extent of alcohol use. The results are discussed in the context of the developmental transitions of adolescence. 相似文献
1000.