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121.
J Markussen I Diers A Engesgaard M T Hansen P Hougaard L Langkjaer K Norris U Ribel A R S?rensen E S?rensen 《Protein engineering》1987,1(3):215-223
It has previously been found that insulins, to which positive charge has been added by substitutions in position B30, thus raising the isoelectric point towards pH 7, had a prolonged action when injected as slightly acidic solutions because such derivatives crystallize very readily upon neutralization. Positive charge has now been added by substituting the B13 and A17 glutamic acid residues with glutamines and B27 threonine with lysine or arginine. These substitutions were introduced by site-specific mutagenesis in a gene coding for a single-chain insulin precursor. By tryptic transpeptidation the single-chain precursors were transformed to the double-chain insulin structure, concomitantly with incorporation of residue B30. Thus insulins combining B13 glutamine, A17 glutamine and B27 lysine or arginine with B30 threonine, threonine amide or lysine amide were synthesized. The time course of blood glucose lowering effect and the absorption were studied after subcutaneous injection in rabbits and pigs. The prolonged action of B30-substituted insulins was markedly enhanced by B27 lysine or arginine substitutions and by B13 glutamine. The B27 residue is located on the surface of the hexamer, so a basic residue in this position presumably promotes the packing of hexamers at neutral pH. The B13 residues cluster in the centre of the hexamer. When the electrostatic repulsive forces from six glutamic acid residues are abolished by substitution with glutamine, a stabilization of the hexamer can be envisaged.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
122.
The dose of intravenous diazepam required for sedation was estimated in a series of 78 patients aged 17-85 years given the drug for dental and endoscopic procedures. Multiple regression analysis showed a significant correlation (r = 0.71; p less than 0.001) between dose and age, body weight, the taking of regular sedation, and the taking of more than 40 g alcohol daily, but there were no differences in the doses required between men and women, smokers and non-smokers, inpatients and outpatients, or dental and endoscopy patients. Patients aged 80 required an average dose of 10 mg and patients aged 20 an average dose of 30 mg, and the dose required was much higher in those receiving regular sedation or having a high alcohol intake. Plasma total and free diazepam concentrations were measured in the second half of the series of patients (n = 37). Plasma concentrations required for sedation fell twofold to threefold between the ages of 20 and 80 and were significantly higher in those taking regular sedation or alcohol. Differences in the acute response to diazepam appeared to be due to differences in the sensitivity of the central nervous system (pharmacodynamic tolerance) rather than to differences in pharmacokinetic factors. 相似文献
123.
I P Grigor'ev A A Neokesari?ski? 《Biulleten' eksperimental'no? biologii i meditsiny》1986,102(9):288-289
The effects of different concentrations of L-ascorbic acid (Asc) on Na+-dependent binding of 3H-GABA and 3H-DL-glutamic acid to rat brain cortical synaptosomes were studied. Asc, at a concentration nearly equal to brain extracellular one (3 X 10(-4) M), had no effect on specific and nonspecific 5H-GABA binding. At higher concentrations (10(-3) M) Asc strongly inhibited, and at lower concentrations (10(-6) M) considerably stimulated 3H-GABA binding. At a concentration of 10(-5)-10(-3) M Asc tended to decrease 3H-DL-glutamic acid binding. 相似文献
124.
D G Astaf'ev I V Maianskaia A K Akatov A N Maianski? 《Zhurnal mikrobiologii, epidemiologii, i immunobiologii》1986,(7):48-51
In investigations based on the use of a highly sensitive test system permitting the detection of normal human antibodies to S. aureus peptidoglycan, the antigenic relationships between the peptidoglycans of S. aureus and other representatives of the genus Staphylococcus have been studied. Among other staphylococcal species, S. simulans, S. xylosus, S. hyicus, S. cohnii, S. hyicus s. s. chromogenes have been found to possess peptidoglycans most closely related to S. aureus peptidoglycans, while S. warneri and S. epidermidis peptidoglycans have proved to be least closely related to it. 相似文献
125.
A procedure for the stimulation of axillary bud developmentfrom young shoots of maize, their subculture to root-inducingmedia and transfer as rooted plants to soil is described. Axillarybud development was enhanced by the addition of kinetin andauxin to the culture medium. Root initiation on explanted axillarybuds, while successful with some cultivars, was variable. Anumber of mature plants with normal tassels and ears were producedfrom the lowermost buds of an original stem explant. Buds fromhigher positions on the explant exhibited different potentialitieswith some, those normally from cob producing nodes, producingshort-stalked plants with terminal female influorescences. Agradient of bud potentiality along the stem appears to be establishedextremely early after each is initiated. Zea mays., corn, maize, shoot tip culture, clone, vegetative propagation 相似文献
126.
127.
E. B. Burova I. S. Smirnova A. N. Shatrova I. V. Gonchar N. N. Nikolskii 《Cell and Tissue Biology》2011,5(1):9-14
Interferon gamma (IFNγ) is known to inhibit the proliferation of some transformed cell lines. Recently, we demonstrated the
transactivation of the epidermal growth factor receptor (EGFR) in response to IFNγ (Burova et al., 2007) and provided direct
evidence for the dependence of IFNγ-induced EGFR transactivation on the EGFR expression level in epithelial cells (Gonchar
et al., 2008). This study examines an antiproliferative effect of IFNγ on human epithelial cell lines—A431 and HeLa that express
high levels of EGFR, as well as HEK293 that expresses low levels of EGFR. To characterize the IFNγ-induced changes in these
cells, we studied cell growth, the cell cycle, and induction of apoptosis. The response to IFNγ differed in the compared cell
lines; cell growth was inhibited in both A431 and HeLa cells, but not in HEK293 cells, as was shown by the cell count and
MTT. The cell-cycle phases analyzed by flow cytometry were disturbed in A431 and HeLa cells in response to IFNγ. On the contrary,
in HEK293 cells, the IFNγ treatment did not alter distribution by cell cycle phases. Our results indicate that IFNγ produces
an antiproliferative effect that depends on the increased expression of EGFR in A431 and HeLa cells. Furthermore, it was demonstrated
that IFNγ induced the caspase 3 activation in A431 cells, which suggests the involvement of active caspase 3 in the IFNγ-induced
apoptosis. 相似文献
128.
129.
130.
S. T. Zakhidov T. L. Marshak E. A. Malolina A. Yu. Kulibin I.A. Zelenina S. M. Pavluchenkova V. M. Rudoi O. V. Dement’eva S. G. Skuridin Yu. M. Evdokimov 《Biochemistry (Moscow) Supplemental Series A: Membrane and Cell Biology》2010,4(3):293-296
The effect of gold nanoparticles on mouse epididymal sperm has been studied using the model system of nuclear chromatin decondensation
in vitro. It is shown that the treatment of gametes, preliminary membrane-freed by sodium dodecyl sulfate, in the mediums
containing gold nanoparticles (with diameter ∼2.5 nm) in concentrations 1.0 × 1015 or 0.5 × 1015 particles/ml and following incubation in dithiothreitol solution (DTT) resulted in failure of chromatin decondensation process
and nucleus structure. We conclude that gold nanoparticles possess spermatotoxicity. The mechanism of cytotoxic effect of
gold nanoparticles may be related with their interaction with molecules of double-helix DNA. The model system studied in this
research is applicable for further investigations of cytotoxic effects of nanoparticles of different origin and made of different
metals. 相似文献