Inhibition of clonogenic growth of fresh leukemia cells by unstimulated and IL-2 stimulated NK cells of normal donors

We have demonstrated that unstimulated highly-enriched NK cells have the capability to inhibit the growth of fresh clonogenic leukemic cells from AML, CML and preleukemic patients. The NK-cell population mediating antileukemic reactivity exhibited LGL morphology and NKH1 and CD16 phenotype. The inhibition of leukemic growth could be mediated by cell-to-cell contact or by soluble factor produced by NK cells. Antileukemia activity was only detectable when enriched population of LGL was utilized; NW-filtered lymphocyte population did not exhibit leukemia-inhibitory effect. However, such activity could be generated after culture of the latter effector cells with IL-2. The leukemia directed IL-2 activated effector cells were characterized as NK cells. The data reported here provide new insight into host factors which may control leukemia growth and indicate the possible future application of NK cells for therapy of leukemia.     

鲎试剂用于细菌内毒素检测碳酸氢钠注射液的研究

目的：通过试验以确定碳酸氢钠注射液可用细菌内毒素代替传统的热原检查法。方法：用鲎试剂和家兔做对照试验确定灵敏度。结果：用灵敏度为０１２５ＥＵ·ｍｌ－１的鲎试剂进行内毒素检查比家兔灵敏度高１２倍。结论：细菌内毒素检查法可以代替热原检查法。     

Perchloric acid-soluble proteins from goat liver inhibit chemical carcinogenesis of Syrian hamster cheek-pouch carcinoma.

Chemically induced Syrian hamster cheek-pouch squamous cell carcinoma is very similar to the corresponding human tumour. This paper describes a blind study in which inhibition of dimethylbenzanthracene-induced cheek-pouch tumours by a goat liver extract denominated UK101 was investigated. Less than 40% of animals treated with UK101 developed tumours compared with 100% of the controls. Intermediate results (80%) were noted in a positive control group treated with Calmette-Guerin bacillus. Immunocytochemical testing of cheek-pouch mucosa by Mib5 showed significantly less proliferating cells in UK101 animals than in the controls. The effect of UK101 was completely reversed when dexamethasone was added in a third control group. A significant difference in complement-mediated cytotoxicity was noted in the sera of UK101-tested and control animals. These findings suggest that an immune mechanism is responsible for the inhibition of hamster cheek-pouch carcinoma by UK101.     

哌立福辛抑制胃癌细胞SGC7901增殖及其作用机制

目的:探讨哌立福辛对体外培养的人胃癌SGC7901细胞生长增殖的影响并探讨其机制?方法:分别用不同浓度的哌立福辛 (0.125?0.250?0.500?0.750?1.500 ?滋mol/L) 对SGC7901细胞进行干预后,采用磺酰罗丹明B (SRB)法检测细胞增殖变化;平板克隆实验检测细胞克隆形成能力;Real－time PCR?Western blot法检测癌症相关基因eIF4E及AEG－1 mRNA及蛋白表达?结果:哌立福辛呈时间及浓度依赖性抑制胃癌SGC7901细胞的增殖,并降低细胞的克隆形成能力;细胞内AKT信号通路中AEG－1?eIF4E的表达明显降低?结论:哌立福辛具有抑制胃癌SGC7901细胞增殖的作用;通过降低AKT信号通路中AEG－1和eIF4E的mRNA及蛋白表达可能是发挥增殖抑制作用的机制之一?     

Intracellular acidification in neurons induced by ammonium depends on KCC2 function

The Cl(-)-extruding neuron-specific K(+)-Cl(-) cotransporter KCC2, which establishes hyperpolarizing inhibition, can transport NH(4) (+) instead of K(+). It is, however, not clear whether KCC2 provides the only pathway for neuronal NH(4) (+) uptake. We therefore investigated NH(4) (+) uptake in cultured rat brain neurons. In neurons cultured for > 4 weeks, the response to NH(4)Cl applications (5 mM) consisted of an alkaline shift which reversed to an acid shift within seconds. Rebound acid shifts which followed brief applications of NH(4)Cl were blocked by furosemide (100 microM). They were rather insensitive to bumetanide (1 and 100 microM), in contrast to those induced in cultured glial cells. Rebound acid shifts persisted in the presence of 1 mM Ba(2+) and in Na(+)-free solution but were inhibited by extracellular K(+). In neurons with depolarizing GABA responses, indicating the absence of functional KCC2, applications of NH(4)Cl barely induced an acidosis. However, large rebound acid shifts occurred in neurons that had changed their GABA response from Ca(2+) increases to Ca(2+) decreases. Rebound acid shifts continued to increase even after the change in the GABA response had occurred and could be induced earlier in neurons transfected with KCC2 cDNA. We conclude that KCC2 provides the main pathway for fast neuronal NH(4) (+) uptake. Therefore, NH(4)Cl-induced rebound acid shifts can be used to indicate the development of KCC2 function. Further, the well known up-regulation of KCC2 function during development has the inevitable consequence of opening a major pathway for NH(4) (+) influx, which can be relevant under pathophysiological conditions.     

Behavioral inhibition and clinical outcomes in children with cochlear implants

OBJECTIVES/HYPOTHESIS: Individual speech and language outcomes of deaf children with cochlear implants (CIs) are quite varied. Individual differences in underlying cognitive functions may explain some of this variance. The current study investigated whether behavioral inhibition skills of deaf children were related to performance on a range of audiologic outcome measures. DESIGN: Retrospective analysis of longitudinal data collected from prelingually and profoundly deaf children who used CIs. METHODS: Behavioral inhibition skills were measured using a visual response delay task that did not require hearing. Speech and language measures were obtained from behavioral tests administered at 1-year intervals of CI use. RESULTS: Female subjects showed higher response delay scores than males. Performance increased with length of CI use. Younger children showed greater improvement in performance as a function of device use than older children. No other subject variable had a significant effect on response delay score. A series of multiple regression analyses revealed several significant relations between delay task performance and open set word recognition, vocabulary, receptive language, and expressive language scores. CONCLUSIONS: The present results suggest that CI experience affects visual information processing skills of prelingually deaf children. Furthermore, the observed pattern of relations suggests that speech and language processing skills are closely related to the development of response delay skills in prelingually deaf children with CIs. These relations may reflect underlying verbal encoding skills, subvocal rehearsal skills, and verbally mediated self-regulatory skills. Clinically, visual response delay tasks may be useful in assessing behavioral and cognitive development in deaf children after implantation.     

Selective dopamine D4 receptor antagonists reverse apomorphine-induced blockade of prepulse inhibition

 Recent evidence suggests that the dopamine D₄ receptor may play a role in schizophrenia, and that the atypical properties of the antipsychotic clozapine may be attributable in part to its antagonistic actions at this receptor. In the present study, clozapine and three other compounds having D₄ dopamine receptor antagonist properties were examined for their effectiveness in reducing losses in prepulse inhibition (PPI) induced in rats by the dopamine receptor agonist apomorphine. Previously, activity in the PPI model has been shown to correlate highly with the antipsychotic potency of a number of neuroleptics. As previously reported, clozapine (1–5.6 mg/kg) significantly reduced apomorphine-induced PPI deficits. The three D₄-selective compounds, CP-293,019 (5.6–17.8 mg/kg), U-101,387 (3–30 mg/kg) and L-745,870 (1–10 mg/kg), also significantly blocked the losses in PPI produced by apomorphine. Taken together, these results suggest that dopamine receptor antagonists with selectivity for the D₄ dopamine receptor subtype may be effective in the treatment of schizophrenia, while being less likely to produce dyskinesias associated with D₂ receptor antagonists. Received: 13 May 1997/Final version: 15 July 1997     

Effects of estrogen on the excitability of neurons projecting from the noradrenergic A1 region to the preoptic and anterior hypothalamic area

Estradiol benzoate administered to ovariectomized female rats significantly elevated the mean spontaneous firing rate and frequency of successful antidromic propagation into the somatodendritic spike and significantly reduced the strength of post-stimulus inhibition in presumed A1 noradrenergic neurons projecting directly to the preoptic and anterior hypothalamic area. The occurrence of both antidromic spikes and post-stimulus inhibition of the majority of these neurons was completely abolished by the injection of 6-hydroxydopamine but not by 5, 7-dihydroxytryptamine directly into the medial forebrain bundle.     

Metabotropic Glutamate Receptors in the Rat Nucleus Accumbens

The effects of glutamate metabotropic receptors (mGluRs) on excitatory transmission in the nucleus accumbens were investigated using electrophysiological techniques in rat nucleus accumbens slices. The broad-spectrum mGluR agonist (1S,3 R )-1-aminocyclopentyl-1,3-dicarboxylate, the mGluR group 2 selective agonists (S)-4-carboxy-3-hydroxyphenylglycine, (1S,3S)-ACPD) and (2S,1'S,2'S)-2-(2'-carboxycyclopropyl)glycine (L-CCG1), and the mGluR group 3 specific agonist L-2-amino-4-phosphonobutyrate (L-AP4) all reversibly inhibited evoked excitatory synaptic responses. The specific group 1 mGluR agonist (R,S)-3,5-dihydroxyphenylglycine [(R,S)-DHPG] did not depress transmission. Dose-response curves showed that the rank order of agonist potencies was: L-CCGI > L-AP4 > (1 S,3S)-ACPD. Group 2 and 3 mGluRs inhibited transmission via a presynaptic mechanism, as they increased paired-pulse facilitation, decreased the frequency of miniature excitatory postsynaptic currents and had no effect on their amplitude. The mGluRs did not inhibit transmitter release by reducing voltage-dependent Ca²⁺ currents through N- or P-type Ca²⁺ channels, as inhibition persisted in the presence of a-conotoxin-GVIA or Aga-IVA. The depression induced by mGluRs was not affected by specific antagonists of dopamine D1, GABA-B or adenosine A1 receptors, indicating direct effects. Finally, (13,s)-DHPG specifically blocked the postsynaptic afterhyperpolarization current (I_ahp). Our results represent the first direct demonstration of functional mGluRs in the nucleus accumbens of the rat.     

胎盘多肽对肿瘤细胞生长抑制作用研究

目的　探讨胎盘多肽 (PPs)对小鼠肿瘤细胞体内、外生长的影响。方法　染料排斥试验及肿瘤细胞体内种植实验。结果　PPs在体外对肿瘤细胞无明显的直接杀伤作用 (P >0 0 5 ) ,但体内肿瘤种植实验中给药组H2 2 腹水瘤小鼠生命延长率为 70 % ,S180 实体瘤生长抑制率为 6 5 % ,与对照组相比实验组荷瘤小鼠生存时间有显著差异 (P <0 0 1 )且肿瘤的形成也有明显的抑制作用 (P <0 0 1 )。结论　PPs在体内有明显的抑瘤作用