大鼠脑组织单胺类递质及其代谢产物的检测方法研究

目的 :研究大鼠脑组织中单胺类递质及其代谢产物的高效液相反相离子对色谱测定法。方法 :采用LiChrosorbC18,10 μm色谱柱 ,流动相为甲醇 :水 (4 0 :60 ) ,含 0 .0 2 8g LEDTANa2 ,0 .15g LSDS ,0 .2ml LH2 SO4(pH 2 .5～ 3 ) ,荧光检测波长 :λEX=2 85 ,λEM=3 3 3。结果 :对 87只大鼠脑组织中 4种单胺类递质及其代谢产物的含量进行了同时测定 ,高香草酸 (HVA) 2 .5 0～ 40 .0 μg ml、去甲肾上腺素 (NE) 0 .0 1～ 0 .5 0 μg ml、多巴胺 (DA)0 .0 5～ 1.0 0 μg ml、5 羟色胺 (5 HT) 0 .0 2 5～ 0 .5 0 μg ml,峰面积与其含量呈良好的线性关系。 结论 :该法操作简便、快速、准确 ,为组织中单胺类递质及其代谢产物检测的一种理想方法 ,并适用于临床相关研究。     

Virulence of Candida albicans mutants

Mutant strains of the fungal pathogen Candida albicans blocked in pyrimidine transport and salvage metabolism were tested for virulence in various animal models. The growth rate, germination and proteolytic enzyme production did not correlate with the virulence of the strains. However, a defect in the uridine transport system significantly decreased virulence in murine candidosis, although it had no effect in vaginal candidosis or in a Candida cyst model. It remains unclear whether this is due to the differing host defence mechanisms involved in systemic and superficial mycoses, or to the different requirements of the fungal systems for adherence and tissue invasion in the two types of infection.     

思他宁对人胰腺癌细胞株ASPC-1的生长调控

目的:观察思他宁对人胰腺癌细胞ASPC-1的生长作用.方法:细胞培养,分别加入不同浓度的思他宁.应用MTT法来观察细胞增殖程度;放免法测定细胞内cAMP含量;荧光法测定[Ca2 ]i.结果:不同浓度的思他宁(10-11～10-6mol/L)均能有效地抑制ASPC-1的生长,能抑制ASPC-1细胞内cAMP生成和细胞内钙离子水平,cAMP生成量和细胞内钙离子水平与思他宁浓度呈负相关.结论:思他宁能抑制ASPC-1细胞的生长,经过特异性受体调节.     

The regulation of pulmonary vascular tone

1 The ability to manipulate pharmacologically pulmonary vascular tone independent of effects on systemic blood vessels is a desirable objective. Elucidation of the biochemical mechanisms underlying hypoxia-induced pulmonary vasoconstriction (HPV) may permit preferential targeting of the pulmonary circulation.
2 Here we review our studies of the role of locally synthesized candidate vasoactive factors in HPV. In addition, we present data demonstrating an attenuated pressor response to hypoxia in the pulmonary circulation of Fischer 344 rats compared with the Wistar-Kyoto (WKY) rat strain.
3 We propose that a systematic genome-wide search using the HPV phenotype and a panel of highly informative microsatellite markers will elucidate the genetic loci underlying the difference in susceptibility to HPV in these two rat strains and provide a valuable and novel insight into the factors that determine the HPV response.     

Labyrinth Exploration, Emotional Reactivity, and Conditioned Fear in Young Roman/Verh Inbred Rats

An inbreeding program has been carried out with the Swiss sublines of Roman high- and low-avoidance rats since 1993. The present study reports the first experiments conducted with young animals of those inbred strains (RHA-I/Verh and RLA-I/Verh, respectively) from the sixth and seventh inbreeding generations. The results confirmed expected behavioral profiles. Compared to the RHA-I/Verh strain, RLA-I/Verh rats showed decreased entries into the illuminated central arena of an hexagonal tunnel maze, as well as decreased spontaneous locomotor activity and increased defecations, in two independent experiments. Young RLA-I/Verh females explored less than did their RHA-I/Verh counterparts during session 1 of a conditioned-fear experiment preceding shock administration, and in session 2 (conducted 24 h after the application of three footshocks), they showed greater conditioned behavioral inhibition (i.e., reduced amount of rearing), as well as higher defecation scores, than did RHA-I/Verh females.Karl Bättig tragically and unexpectedly died on December 27, 1996     

Genetic factors controlling inheritance of susceptibility to 1,2-dimethylhydrazine

Summary Reciprocal crosses were made between AKR/J, a 1,2-dimethylhydrazine (DMH)-resistant mouse strain, and SWR/J, a sensitive strain. The F1 hybrids were tested with DMH and methylazoxymethanol (MAM), two colon carcinogens. Either DMH (20 mg/kg body weight) or MAM (35 mg/kg body weight), a metabolic derivative of DMH, was injected weekly for 10 weeks. In each group of 35 mice, 10 were injected with tritiated thymidine (25 Ci) 1 week after the sixth injection of DMH and MAM for the evaluation of proliferative characteristics and the number of foci of dysplasia occuring in 325 m of distal colonic mucosa. At 27 weeks after the first injection of the carcinogen, the colons of remaining mice were opened longitudinally and the number of tumors enumerated. Compared with DMH-treated mice, the number of foci of dysplasia per mouse, the percentage of tumor-bearing mice, the number of tumors per animal, and the number of tumors per tumor-bearing animal induced by MAM were severalfold higher. This would suggest the presence of a gene(s) repressing metabolism of DMH to MAM. Moreover, differences in response to the carcinogens were observed between the sexes. In contrast to males, females treated with both DMH and MAM had significantly greater numbers of tumors per animal, tumors per tumor-bearing mice, and a greater proliferative response with extension of S-phase cells to the upper third and luminal surface of crypts. Among males, those with the X^AKR/Y^SWR heritage appeared more resistant than X^SWR/Y^AKR males, particularly in their response to MAM. A twofold difference in the number of foci of dysplasia per mouse, tumors per animal, and the number of tumors per tumor-bearing animals was seen. Analyses of the response to DMH and MAM by F1 reciprocal hybrids of the AKR and SWR strains have shown a complex inheritance pattern governing susceptibility to DMH. Resistance to the carcinogen is provided by at least two specific repressor genes, one governing metabolism of carcinogen from DMH to MAM, and the other controlled by gender. Genetic factors contributed by the AKR female appear to convey additional resistance to male progeny, suggesting more than one gender-related gene.Supported in part by CA 08748 from the National Cancer Institute and by CA 26674 from the National Cancer Institute through the National Large Bowel Cancer Project     

Evolution of North American PVYNTN Strain Tu 660 from Local PVYN by Mutation rather than Recombination

A North American (NA) isolate of tobacco veinal necrotic strain of Potato virus Y (PVY^N) (N-Jg) and a NA isolate of potato tuber necrotic strain of Potato virus Y (PVY^NTN) (Tu 660) were tested for their phenotypes by inoculation to potato plants of three potato cultivars. Upon inoculation with Tu 660, tubers of the cultivars Norchip and Ranger Russet developed potato tuber necrotic ringspot disease (PTNRD) but not the tubers of Russet Burbank. N-Jg failed to induce PTNRD in the tested cultivars. The genomic RNAs of both strains were completely sequenced and analysed. High homology (98% and 99% identity on nucleotide and polyprotein, respectively) was found between Tu 660 and N-Jg. When polyproteins were compared with other isolates, high identity was observed between Tu 660 and an European (Eu) PVY^N-605 (98%) and with an Eu-PVY^NTN-H (96%). However, when individual mature proteins were compared, much lower identities (86.5–94%) were found between Tu 660 and PVY^NTN-H compared to 98–99.5% between Tu 660 and PVY^N-605 in the P3, 6K1 and CI regions. Further sequence analysis indicated that the PVY^NTN-H is a hybrid molecule of the genomic RNA recombination of PVY^O and Eu-PVY^N as shown by Glais et al. (Arch Virol 147, 363–378), whereas NA-PVY^NTN Tu 660 is free of recombination points. Phylogenetic analysis confirmed this observation, and suggested that, in light of high homology, the Tu 660 might have evolved from NA-PVY^N by mutations rather than the genome recombinations. The non-recombinant nature of NA-PVY^NTN Tu 660 strongly suggests that the recombinant structure of genome is not a necessary prerequisite for the PTNRD phenotype.     

Influence of neonatal sympathectomy on proximal renal resistance artery function in spontaneously hypertensive rats

Renal transplantation experiments have shown that the kidney contributes to chronic sympathectomy-induced arterial pressure reduction in spontaneously hypertensive rats (SHR). The underlying mechanisms are currently unclear but may include alterations in the function of small renal arteries. Neonatal SHR were sympathectomized by intraperitoneal guanethidine injections and removal of adrenal medullary tissue. Controls were sham- or hydralazine-treated. At 12 weeks of age, distal interlobar artery segments were investigated using small-vessel wire myography. Vessels from sympathectomized animals showed increased sensitivity to noradrenaline (NE). Vasopressin- and endothelin-1-induced vasoconstriction was similar in all groups (as reflected by the pD₂, i.e. –logEC₅₀, where EC₅₀ is the molar concentration of agonist eliciting a half-maximal response). Maximum vasopressin-induced tension was similar in all groups while endothelin-1-induced maximum tension was significantly higher in sympathectomized than in sham-treated SHR. The sensitivity of NE-induced vasoconstriction to extracellular Ca²⁺ did not differ between groups while sensitivity to L-type Ca²⁺ channel activation was significantly higher in both sympathectomized and hydralazine-treated animals than in sham-treated animals. Endothelium-dependent and independent vasodilation were similar in all groups. Sequential blockade of NO-synthase and cyclooxygenase had similar effects in all groups. In conclusion, neonatal sympathectomy does not induce any changes in the function of isolated proximal renal resistance arteries from SHR that could explain the blood pressure lowering effect of a kidney graft from sympathectomized SHR.     

Characterization of bacteriophages fromtox-containing, non-toxigenic isolates ofCorynebacterium diphtheriae

Non-toxigenic strains ofCorynebacterium diphtheriaecontinue to cause disease within immunized populations. A subset of these corynebacteria carry the diphtheria toxin gene but in a cryptic form. To determine whether such strains might contribute to the re-emergence of functional toxin genes, the phages andtoxmutations within three clone types were examined.tox-containing, β-related phages were isolated from two of the strain types. The third isolate appeared to harbour a defective prophage. One of thetox⁻phages encoded truncated, yet enzymatically-active, forms of diphtheria toxin, suggesting that it had sustained a point mutation within the latter half of its toxin gene. In contrast, the other mutant phage did not elicit the production of either a cross-reacting material or an ADP-ribosylating activity. Complementation tests employing a series of double lysogens confirmed that the mutations responsible for the non-toxigenic phenotype of all of the phages werecisdominant. Given these findings, it is reasonable to hypothesize thattox⁺genes can arise within human populations by either homologous recombination between two distincttox⁻phages or spontaneous reversion within a single mutant allele.