日本血吸虫合成表位肽疫苗对小鼠的保护性免疫

为观察日本血吸虫合成表位多肽疫苗诱导的保护性免疫,将用日本血吸虫抗原免疫血清筛选噬菌体随机12肽库得到的、具有较好免疫保护性的4个模拟抗原表位短肽进行人工合成,用酶联免疫吸附实验(ELISA)检测它们的抗原性.将合成多肽分别与钥孔戚血蓝蛋白(KLH)连接后免疫昆明小鼠,第3次免疫后收集血清,检测其针对各个多肽和可溶性成虫抗原(AWA)的IgG抗体滴度,以及补体介导的小鼠体外杀日本血吸虫童虫作用.结果显示,4个合成多肽均能被相应的抗体识别,具有良好的抗原性;能诱导产生特异性IgG抗体.这些抗体在补体参与下能在体外有效毒杀血吸虫童虫.与正常小鼠血清比较,4个合成多肽免疫血清的杀童虫率分别为31.7%,41.3%,21.1%和17.3%,均具有显著性;与KLH免疫血清相比时,杀童虫率分别为23.7%,34.4%,11.8%(P=0.077,无显著性)和7.5%(P=0.102,无显著性).这些结果表明,这4个合成表位多肽具有良好的抗原性和免疫原性,与KLH连接后能诱导明显的抗体反应和显著的细胞毒作用.     

Reactivated triton-extracted models o paramecium: modification of ciliary movement by calcium ions

Triton-extracted models of Paramecium were reactivated to swim in solutions of adenosine triphosphate and magnesium ions. The cilia beat in the normal direction (toward the rear) when the calcium ion concentration was less than 10-(6)M, and they beat in the "reversed" direction (toward the front) when calcium ion concentration was raised above 10-(6)M. These results support the proposal that ciliary reversal, hence backward swimming, of live paramecia is mediated by an increased cytoplasmic calcium concentration around the ciliary system by calcium-dependent membrane responses to external stimuli.     

Dissociation of the visual placing response into elicited and guided components

Kittens reared without sight of their limbs extended their forelimbs when carried down toward the edge of a horizontal surface. However, unlike normally reared kittens, they were not capable of guiding their paws accurately to the solid parts of an interrupted surface. This fractionation of the visually controlled placing response reveals that the guided reach requires an integration of sensorimotor systems not necessary for development of the elicited extension response.     

Reversal of phenylalkylamine tachyphylaxis by norepinephrine

Since the responses to "neurosympathomimetic amines" are reduced in the reserpinized animal and restored by norepinephrine administration, it was postulated that norepinephrine might also affect the development of their tachyphylaxis. We found that norepinephrine infusion restored, at least partially, certain tachyphylactic responses to amphetamine or ephedrine and fully prevented the development of tachyphylaxis to tyramine.     

Reversal of thyroxine-induced hypermetabolism by puromycin

Previous studies have demonstrated that in addition to its effects on metabolic rate, thyroxine stimulates protein biosynthesis. The administration of puromycin, a drug which blocks protein synthesis and, therefore, the thyroxine effect on protein synthesis, acutely reverses the hypermetabolism induced in rats by prior administration of thyroxine and restores the oxygen consumption of the thyrotoxic rats to the euthyroid level. The results suggest that a larger fraction of the total body basal oxygen consumption in hyperthyroidism is related to the process of protein synthesis than in the euthyroid state and that the calorigenic effect of thyroxine is secondary to its effect on protein synthesis.     

Reversal of chloroquine resistance in Plasmodium falciparum by verapamil

The parasite Plasmodium falciparum, like neoplastic cells, develops resistance to multiple structurally unrelated drugs. If the mechanisms by which P. falciparum and neoplastic cells become resistant are similar, then it may be possible to reverse the resistance in the two types of cells by the same pharmacological agents. Verapamil, a calcium channel blocker, completely reversed chloroquine resistance in two chloroquine-resistant P. falciparum clones from Southeast Asia and Brazil. Verapamil reversed chloroquine resistance at the same concentration (1 X 10(-6)M) as that at which it reversed resistance in multidrug-resistant cultured neoplastic cells. This same concentration of verapamil had no effect on chloroquine-sensitive parasites. Hence, chloroquine resistance in P. falciparum may fit the criteria for the multidrug-resistant phenotype.     

Arterial hypertension elicited by subpressor amounts of angiotensin

Long-term infusion of amounts of angiotensin insufficient at the beginning to raise arterial pressure results, after several days in sustained arterial hypertension in unanesthetized dogs. This hypertension is to a large degree dependent on environmental stimuli, and results chiefly from increase in peripheral resistance. As in dogs with renal hypertension, there is increased pressor responsiveness to tyramine. This indirect action of angiotensin to increase total peripheral resistance and arterial pressure by an action on the sympathetic nervous system, along with an upward resetting of the carotid sinus buffering mechanism, might logically account for the neural component of chronic renal hypertension. Such a proposal integrates the humoral and neural elements of the mosaic describing the mechanisms of tissue perfusion.     

Reversal of adriamycin resistance by verapamil in human ovarian cancer

The effectiveness of adriamycin in the treatment of ovarian cancer and other human tumors has been limited by the development of drug resistance. Verapamil, a calcium channel blocking agent, completely reversed adriamycin resistance in human ovarian cancer cells with moderate (three- to sixfold) degrees of resistance and partially reversed resistance in highly (150-fold) resistant cells. The potentiating effect of verapamil was due to inhibition of adriamycin efflux in the resistant cells. These results have led to a clinical trial of adriamycin and verapamil in refractory ovarian cancer patients.     

Reversal of chloroquine resistance in malaria parasite Plasmodium falciparum by desipramine

Desipramine and several other tricyclic antidepressant drugs reverse chloroquine resistance in Plasmodium falciparum in vitro at concentrations observed in the plasma of human patients treated for depression. Reversal of resistance is associated with increased chloroquine accumulation in the parasite, probably because of inhibition of a putative chloroquine efflux pump. When owl monkeys (Aotus lemurinus lemurinus) infected with chloroquine-resistant Plasmodium falciparum were treated with chloroquine plus desipramine, their parasitemias were rapidly suppressed. Desipramine was found to be one of the most effective compounds yet described for the reversal of chloroquine resistance both in vitro and in vivo.     

Reversal of the TCR stop signal by CTLA-4

The coreceptor cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is pivotal in regulating the threshold of signals during T cell activation, although the underlying mechanism is still not fully understood. Using in vitro migration assays and in vivo two-photon laser scanning microscopy, we showed that CTLA-4 increases T cell motility and overrides the T cell receptor (TCR)-induced stop signal required for stable conjugate formation between T cells and antigen-presenting cells. This event led to reduced contact periods between T cells and antigen-presenting cells that in turn decreased cytokine production and proliferation. These results suggest a fundamentally different model of reverse stop signaling, by which CTLA-4 modulates the threshold for T cell activation and protects against autoimmunity.     

Reversal of experimental parkinsonism by lesions of the subthalamic nucleus

Although it is known that Parkinson's disease results from a loss of dopaminergic neurons in the substantia nigra, the resulting alterations in activity in the basal ganglia responsible for parkinsonian motor deficits are still poorly characterized. Recently, increased activity in the subthalamic nucleus has been implicated in the motor abnormalities. To test this hypothesis, the effects of lesions of the subthalamic nucleus were evaluated in monkeys rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The lesions reduced all of the major motor disturbances in the contralateral limbs, including akinesia, rigidity, and tremor. This result supports the postulated role of excessive activity in the subthalamic nucleus in Parkinson's disease.     

Modification of motivated behavior elicited by electrical stimulation of the hypothalamus

Previous reports demonstrated that hypothalamic stimulation may elicit either eating, drinking, or gnawing and emphasized both the specificity of the neural circuits mediating these behaviors and the similarity to behavior during natural-drive states such as hunger and thirst. We find that, after a period of very consistent elicitation of one of these behaviors, the animal may exhibit an equally consistent alternate behavior. A learning component is implicated in the association of hypothalamic stimulation with a particular behavior pattern.     

维拉帕米和三苯氧胺逆转卵巢癌细胞对阿霉素耐药性的实验研究

目的 了解维拉帕米和三苯氧胺体外逆转卵巢癌细胞阿霉素耐药性的效果及临床意义.方法 分别以阿霉素、维拉帕米和三苯氧胺作用于人卵巢癌亲本细胞SKOV3和阿霉素耐药细胞SKOV3/ADM后,采用MTI法检测药物对癌细胞的抑制作用,以细胞内阿霉素聚集量测定和流式细胞术检测凋亡.结果 维拉帕米和三苯氧胺能部分逆转耐药细胞对阿霉素的耐药性,且维拉帕米能显著增加耐药细胞内阿霉素的聚集量并促进其凋亡.结论 虽然维拉帕米和三苯氧胺能部分逆转耐药细胞对阿霉素的耐药性,但用于临床的意义不大.     

Behavioral acts elicited by stimulation of single, identifiable brain cells

By stimulation of and recording from all of the nerve trunks and from over 50 of the large nerve cell bodies in the isolated brain of the nudibranch Tritonia gilberti a map of the axonal paths and synaptic connections has been constructed. The nervous correlates of sensory and motor activities can be monitored in single cells of the intact animal. Similarly, discrete responses in local muscles of the body wall and complex behavioral sequences such as turning and swimming are triggered by stimulation of single identifiable units.     

Reversal of catecholamine refractoriness by inhibitors of RNA and protein synthesis

The generation of adenosine 3',5'-monophosphate (cyclic AMP) in response to catecholamines in the 2B subclone of RGC6 rat glioma cells previously exposed to norepinephrine and refractory to further norepinephrine addition is substantially increased by addition of inhibitors of RNA and protein synthesis. The time course of the effect of these inhibitors on cyclic AMP concentration suggests that rapid protein synthesis and turnover are involved in catecholamine refractoriness. Norepinephrine induction of cyclic nucleotide phosphodiesterase is demonstrable in RGC6 cells but not in the 2B subclone. Thus, catecholamine refractoriness cannot be attributed to induction of phosphodiesterase. This implies that induction of a protein or proteins, important in catecholamine refractoriness, affects the synthesis rather than the degradation of cyclic AMP.