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971.
Extrapolation of pharmacologic data: lower animals to man   总被引:1,自引:0,他引:1  
  相似文献   
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The concentration of FSH and LH in peripheral plasma was studied in sheep from 8 h before to 17.5 h after injection (i.v.) with antisera to the steroids androstenedione, oestradiol, oestrone and testosterone. The fitted mean concentration of LH increases after all treatments and the increase was associated with a higher frequency of LH pulses. The greater concentration was evident for all groups by the period 3.5-6.5 h after injection, but by the end of the sampling period the concentration had returned to or towards the values in the controls. For FSH, significant change was limited to those animals given anti-oestrogen sera but it was more rapid than for LH, both groups receiving anti-oestrogen sera showing an increase during the period 0.5-3.0 h after injection. The ovulation rate was increased by treatment and an effect close to 0.75 corpora lutea per ewe was maintained by treatment in subsequent oestrous cycles. This declined to 0.25 corpora lutea after two oestrous cycles without treatment.  相似文献   
976.
An electron microscopy study of synaptonemal complexes in two men carrying reciprocal translocations, a t(19;22) and a t(17;21), is reported. It is shown that a delay in synapsis affects the segments corresponding to the short arms of the acrocentrics involved in the formation of quadrivalents. This appears to provoke an interaction with the sex bivalent which could lead to a failure of spermatogenesis. A study of the literature comparing reciprocal translocations that do and do not involve acrocentrics in sterile and fertile men shows the existence of a significant association between the presence of an acrocentric in the rearrangement and sterility. These results on reciprocal translocations involving at least one acrocentric chromosome correspond to those obtained in cases of Robertsonian translocations.  相似文献   
977.
Ian Carr 《CMAJ》1980,123(6):533-534
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The peptidolytic reaction of HIV-1 protease has been investigated by using four oligopeptide substrates, Ac-Ser-Gln-Asn-Tyr-Pro-Val-Val-NH2, Ac-Arg-Ala-Ser-Gln-Asn-Tyr-Pro-Val-Val-NH2, Ac-Ser-Gln-Ser-Tyr-Pro-Val-Val-NH2, and Ac-Arg-Lys-Ile-Leu-Phe-Leu-Asp-Gly-NH2, that resemble two cleavage sites found within the naturally occurring polyprotein substrates Pr55gag and Pr160gag-pol. The values for the kinetic parameters V/KEt and V/Et were 0.16-7.5 mM-1 s-1 and 0.24-29 s-1, respectively, at pH 6.0, 0.2 M NaCl, and 37 degrees C. By use of a variety of inorganic salts, it was concluded that the peptidolytic reaction is nonspecifically activated by increasing ionic strength. V/K increased in an apparently parabolic fashion with increasing ionic strength, while V was either increased or decreased slightly. From product inhibition studies, the kinetic mechanism of the protease is either random or ordered uni-bi, depending on the substrate studied. The reverse reaction or a partial reverse reaction (as measured by isotope exchange of the carboxylic product into substrate) was negligible for most of the oligopeptide substrates, but the enzyme catalyzed the formation of Ac-Ser-Gln-Asn-Tyr-Phe-Leu-Asp-Gly-NH2 from the products Ac-Ser-Gln-Asn-Tyr and Phe-Leu-Asp-Gly-NH2. The protease-catalyzed exchange of an atom of 18O from H2 18O into the re-formed substrates occurred at a rate which was 0.01-0.12 times that of the forward peptidolytic reaction. The results of these studies are in accord with the formation of a kinetically competent enzyme-bound amide hydrate intermediate, the collapse of which is the rate-limiting chemical step in the reaction pathway.  相似文献   
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