The Alcohol Tolerant (AT) and Alcohol Nontolerant (ANT) rats, selectively bred for ethanol-induced ataxia on the inclined plane at ALKO in Finland, were moved to the University of Colorado in 1998. The selection phenotype was tested on generation 60 animals in Colorado. In week one, ataxia was measured on the inclined plane 30 minutes after an intraperitoneal dose of 2 g/kg 15% w/v ethanol. Differences in ethanol-induced ataxia between the AT and ANT lines at the University of Colorado were similar to those in the original lines in Finland. In week two, ataxia was measured on the inclined plane at 5 and 30 minutes, and tolerance was measured as the time to regain the original angle of sliding. The AT rats rapidly developed tolerance to 2 g/kg ethanol on the inclined plane; tolerance development was significantly slower in the ANT rats. In week three, the animals were tested for the duration of loss of righting reflex (LORR) and blood ethanol concentration at regain of the righting reflex (BECRRR) following a dose of 3.5 g/kg. The AT rats had a significantly higher BECRRR than did the ANT rats, but did not differ in LORR. A separate experiment with previously untreated rats demonstrated that naïve animals of the two lines did not differ in BECRRR or LORR. AT and ANT rats were genotyped for the mutation that occurs in the gene for the α6 subunit of the GABAA receptor, a natural mutation that is known to affect benzodiazepine responses. All ANT animals tested carried the mutant allele, whereas some AT families carried the mutation and others were wild type. There was no effect of the mutation in AT rats for any of the phenotypes that were tested. After several generations of brother–sister mating, the AT and ANT lines were more than 90% inbred as determined by genotyping. One AT (wild-type) line and one ANT (mutant) line were selected for breeding an F2 intercross generation of 1200 animals. They were phenotyped for sensitivity and tolerance to ethanol on each of three consecutive weeks. Order of testing had a modest effect on some of the phenotypes: when tested during the third week as compared to weeks one or two, BECRRR was increased, 30-minute sensitivity was increased, and development of acute tolerance was increased. Statistically significant correlations were found between tolerance and sensitivity at both 5 and 30 minutes, and between LORR and BECRRR. The smaller (or absence of) significant correlations between others of the phenotypes indicate(s) that they are most likely controlled by different sets of genes. 相似文献
We have examined the effects of 4-aminopyridine (4-AP) on single ATP-dependent potassium channels in patches excised from frog skeletal muscle. 4-AP applied to the internal face of the membrane caused a flickery block. We could not detect any flickery block when 10 mM 4-AP was applied to the external surface of the membrane. The reduction in mean unitary current by internal 4-AP was consistent with 11 binding with a Kd of 3.3 mM at 0 mV. The block was voltage-dependent, increasing with depolarization with an effective valency of 0.57. Rate constants for blocking and unblocking by 4-AP were obtained by fitting functions to the distribution of current amplitudes. Both rate constants were voltage-dependent. At 0 mV they were 17 mM–1 ms–1 and 61 ms–1. Simulation of the block using these rate constants produced a flickery block very similar to that observed experimentally. 相似文献
A scheme of administration of nicotinic acid by mouth is suggested in order to prevent any increase in the free fatty acid concentration in the serum after intravenous injection of heparin or triiodothyronine, prolonged starvation, and thyroid feeding.Laboratory of Pathological Physiology, Institute of Experimental Endocrinology and Hormone Chemistry, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Yudaev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 78, No. 8, pp. 122–125, August, 1974. 相似文献
Summary: Various poly(ε‐caprolactone‐block‐1,4‐dioxan‐2‐one) (P(CL‐block‐PDX)) block copolymers were prepared according to the living/controlled ring‐opening polymerization (ROP) of 1,4‐dioxan‐2‐one (PDX) as initiated by in situ generated ω‐aluminium alkoxides poly(ε‐caprolactone) (PCL) chains in toluene at 25 °C. 1 1H NMR, PCS and TEM measurements have attested for the formation of colloids attributed to a growing PPDX core surrounded by a solvating PCL shell during the polymerization of PDX promoted by ω‐Al alkoxide PCL chains in toluene. The thermal behavior of the P(CL‐block‐PDX) copolymers was studied by DSC; showing two distinct melting temperatures (as well as two glass transition temperatures) similar to those of the respective homopolyesters. Finally, the thermal degradation of the P(CL‐block‐PDX) block copolymers was investigated by TGA simultaneously coupled to a FT‐IR spectrometer and a mass spectrometer for evolved gas analysis (EGA). The degradation occurred in two consecutive steps involving a first unzipping depolymerization of the PPDX blocks followed by the degradation of the PCL blocks via both ester pyrolysis and unzipping reactions.
TEM observation of P(CL‐block‐PDX) block copolyesters ( = 11 600 and = 22 100) as formed by vaporization starting from a diluted suspension in toluene/TCE mixture solvent (50/50 v/v). 相似文献
Summary: Bis(hydroxy)telechelic bisphenol A polycarbonate (PC) was prepared via melt polycondensation of bisphenol A (BPA) and diphenyl carbonate (DPC) using lanthanum(III ) acetylacetonate as a catalyst for transesterification. Subsequently, the polycarbonate was converted to a bifunctional macroinitiator for atom transfer radical polymerization (ATRP) with the reagent, α‐chlorophenylacetyl chloride. The macroinitiator was used for the polymerization of styrene (S) and methyl methacrylate (MMA) to give PS‐block‐PC‐block‐PS and PMMA‐block‐PC‐block‐PMMA triblock copolymers. These block copolymers were characterized by NMR and GPC. When styrene and methyl methacrylate were used in large excess, significant shifts toward high molecular weights were observed with quantitative consumption of the macroinitiator. Several ligands were studied in combination with CuCl as the ATRP catalyst. Kinetic studies reveal the controlled nature of the polymerization reaction for all the ligands used.
Formation of a bifunctional ATRP macroinitiator by esterification of bis(hydroxy)telechelic PC with α‐chlorophenylacetyl chloride. 相似文献
Radiofrequency catheter ablation of the atrioventricular (AV) node or bundle of His was performed in 12 adult mongrel dogs. The aim was to create chronic incomplete AV block (first- and second-degree AV block) and to examine the histopathology of the ablated lesions. However, the late electrophysiological results (2 4 weeks follow up) were various: normal in 2 dogs, mild PR prolongation (< 50%) in 2 dogs, first-degree AV block (PR prolongation a 50%) in 2 dogs, second degree AV block in 2 dogs, complete AV block in 4 dogs. The maximally ablated area (%) of the atrioventricular conduction system in serial histologic sections from dogs with these conditions was 69%, 75%, 89.5%, 95% and 99.5%, respectively. The number of intact conduction cells at the maximally ablated site varied from 6 to 30 in the four cases of incomplete AV block. The mean ablated volume (%) of either the AV node or penetrating His bundle correlated roughly with the degree of AV block. The ablated lesions were well demarcated and almost replaced by dense fibrous tissue at 4 weeks. Interruption (3 dogs) or thinning (1 dog) of the endocardial elastic lamellae was detected, in association with endocardial thickening (mean 913 μm). Endocardial thrombi were found in 3 dogs (2 fresh, 1 organized). We conclude that radiofrequency catheter ablation does not cause severe complicated lesions. Several possible conditions for creating chronic incomplete AV block are discussed. Acta Pathol Jpn 41: 487–498, 1991. 相似文献
The region spanning the tumor necrosis factor (TNF) cluster in the human major histocompatibility complex (MHC) has been implicated in susceptibility to numerous immunopathological diseases, including type 1 diabetes mellitus and rheumatoid arthritis. However, strong linkage disequilibrium across the MHC has hampered the identification of the precise genes involved. In addition, the observation of "blocks" of DNA in the MHC within which recombination is very rare, limits the resolution that may be obtained by genotyping individual SNPs. Hence a greater understanding of the haplotypes of the block spanning the TNF cluster is necessary. To this end, we genotyped 32 human leukocyte antigen (HLA)-homozygous workshop cell lines and 300 healthy control samples for 19 coding and promoter region SNPs spanning 45 kb in the central MHC near the TNF genes. The workshop cell lines defined 11 SNP haplotypes that account for approximately 80% of the haplotypes observed in the 300 control individuals. Using the control individuals, we defined a further six haplotypes that account for an additional 10% of donors. We show that the 17 haplotypes of the "TNF block" can be identified using 15 SNPs. 相似文献