Antibody-dependent neutrophil-mediated parasite killing in non-lethal rodent malaria

The effects of administrating recombinant human granulocyte colony-stimulating factor (rhG-CSF) and passively transferring immune serum on infection with an attenuated variant of Plasmodium berghei XAT (Pb XAT), in severe combined immunodeficiency (SCID) mice were examined. In immune competent (C.B-17) mice, the attenuated parasite infection was inevitably self-resolving and degenerating forms inside erythrocytes appeared, coinciding with the drop in parasitaemia, whereas SCID mice were unable to control parasite growth and all the mice died. Continuous administration with rhG-CSF caused neutrophilic granulocytosis in both SCID and C.B-17 mice. The effect of rhG-CSF on the infection in C.B-17 mice was to suppress the course of the parasitaemia at an early phase whereas it had no effect in SCID mice. When immune serum was transferred on the day of infection, the prepatent period was prolonged two days in both SCID and C.B-17 mice. When administration with rhG-CSF was combined with transfer of immune serum, SCID mice showed four days delay in patency and degenerating parasites were seen during the course of parasitaemia, although the infection was ultimately fatal. C.B-17 mice similarly treated showed a seven day delay in the onset of the patent parasitaemia which was of a lesser magnitude and shorter in duration compared with control mice. On the other hand, when C.B-17 mice were splenectomized three weeks before infection and then treated with rhG-CSF and immune serum, no degenerating parasites were seen during the infection and all mice died with high parasitaemias. These results show that antibody-dependent neutrophil-mediated parasite killing may occur in the spleen of mice infected with P. berghei XAT.     

小儿白血病瘤细胞P—糖蛋白测定方法及应用

本文介绍免疫组化法检测小儿白血病瘤细胞（Ｐ－ｇｐ）。检测３０例小儿白血病细胞膜Ｐ－ｇｐ，观察其原发耐药性。３０例中有８例ｐ－ｇｐ阳性，总阳性率２６．６７％，其中ＡＮＬＬ单项阳性率３３．３３％，ＡＬＬ为２０％。本组病例耐约性最高的是ＣＭＬ，其次是ＡＮＬＬ，ＡＬＬ组最低。同时发现ＭＤＲ阳性者复发率高，ＭＤＲ阴性者复发率低，多因素分析表明ＭＤＥＲ对初诊白血病患者预后及抗癌药物选择有重要意义。目的临床评价ＭＤＲ采用检测ｍｄｒ１ｍＲＮＡ或Ｆ－ｇｐ，本文认为采用简便、快速的免疫组化法检测Ｐ－ｇｐ在临床上具有较大的实用价值。     

Effects of substance P on the spontaneous binding of Salmonella minnesota R345 (Rb) to human peripheral blood lymphocytes

The effects of substance P (SP) on Salmonella minnesota R345 (Rb) binding to human peripheral blood lymphocytes (PBL) were evaluated. Two parameters of bacterial cytoadherence were considered, namely the binding lymphocytes (BL) and the number of bound-bacteria/lymphocyte (BB). The results showed that SP inhibits both BL and BB in a significant manner. Furthermore, distribution of Salmonella binding to CD4+ and CD8+ lymphocytes was studied following SP pretreatment of lymphoid cells. This neuropeptide is able to hamper the bacterial cytoadherence to both T-cell subpopulations and, in particular, the inhibitory effect on the T-suppressor/cytotoxic subset was more pronounced. These findings are discussed in terms of SP intervention in the mechanism of host protection against invading microorganisms.     

Differential effects of substance P on serotonin-modulated spinal nociceptive reflexes

Recent immunohistochemical studies indicate the presence of a bulbospinal substance P (SP) system, as well as a bulbospinal serotonin (5-HT) system, involved in spinal pain transmission. Although electrophysiological studies indicate that SP may modulate the effects of 5-HT on post-synaptic spinal nociceptive neurons, the functional relationship between SP and 5-HT on “pain behavior” remains obscure. To bridge this gap between mechanism and behavior, the purpose of the present study was to determine specific postsynaptic behavioral effects of SP and 5-HT on local spinal nociceptive reflexes in spinally transected animals. Administration of the 5-HT agonists 5-methoxydi-methyltryptamine (5-MeODMT) (0, 0.5, 1.5, 2.0 mg/kg) and quipazine (0, 5, 10, 20 mg/kg) 2 days after transection significantly expanded the receptive field (RF) areas of three spinal reflexes, as previously reported. Intrathecal administration of SP alone (0, 0.25, 2.5, 7.5 ng) also resulted in hyperalgesia, indicated by a significant expansion of the RF areas of all three nociceptive reflexes. However, administration of SP, in animals pretreated with 5-HT agonists, decreased the 5-HT-induced expansion of RF size. Therefore, SP had opposite effects on spinal nociceptive reflexes depending on whether or not the animal was pretreated with 5-HT agonists, i.e., hyperalgesia in the absence of 5-HT agonists, and analgesia in the presence of 5-HT agonists. The two effects of SP on local spinal reflexes may be related to the anatomical organization of the two spinal SP systems: 1) SP released from primary afferents facilitates nociceptive reflexes, and 2) SP associated with the descending bulbospinal system interacts with the descending bulbospinal 5-HT system and inhibits nociceptive reflexes. The present results help explain contradictory literature regarding the effect of SP on spinal nociceptive reflexes.     

P16MTS1、P27KIP1基因在胆管癌组织中的表达研究

目的：探讨P16^MIS1,P27^KIP1基因与胆管癌临床病理的关系。方法：采用免疫组化方法，检测48例胆管癌和8例伴慢性炎症的胆管壁组织中P16^MIS1,P27^KIP1蛋白表达情况。结果：（1）胆管癌中P16^MIS1,P27^KIP1阳性表达率分别为47．9％和35．4％，而伴炎症的胆管组织阳性表达率为100％和87．5％；（2）P16^MIS1,P27KIP1蛋白表达与胆管癌的分化程度，有无淋巴结或远处转移以及临床分期呈显著相关性。结论：P16^MIS1,P27^KIP1多基因表达异常可能与胆管癌的发生发展有关，是衡量胆管癌预后的有用指标。     

罗格列酮对多囊肾囊肿衬里上皮细胞p38促分裂原活化蛋白激酶信号通路的影响

Objective To investigate the effect of rosiglitazone on p38 mitogen-activated protein kinase (p38MAPK) pathway in polycystic kidney cyst-lining epithelial cells. Methods The cyst-lining epithelial cells (PKD cells) from human polycystic kidney were treated with rosiglitazone (10 μmol/L), peroxisome proliferator-activated receptor-γ (PPARγ) inhibitor GW9662 (10 μmol/L), rosiglitazone (10 μmol/L) +GW9662 (10 μmol/L), p38MAPK specific inhibitor SB203580 (10 μmol/L), SB203580 (10 μmol/L)+ rosiglitazone(10 μmol/L) for 2 hours followed by epidermal growth factor (EGF) stimulation. Protein expressions of p38, phuspho-p38 (p-p38) and proliferating cell nuclear antigen (PCNA) were detected by Western blot. p38 mRNA was examined by RT-PCR. Expression of c-fos and c-jun was observed by immunocytochemistry. Results (1) EGF markedly up-regulated the expressions of p38, p-p38, PCNA, c-fos anti c-jun compared with control group (P<0.01). (2) Compared with EGF treated group, rosiglitazone significantly reduced p38 activation and mRNA expression (P<0.01, respectively). Rosiglitazone, rosiglitazone+SB203580 could significantly down-regulated p-p38, PCNA, c-fos and c-jun expression (P<0.01, respectively) with no significant difference between these two groups. (3) GW9662 partially reversed the reduction effect of rosiglitazone. Conclusions Rosiglitazone can inhibit proliferation of autosomal dominant polycystic kidney disease cyst-lining epithelial cells partially through down-regulating p38 activation and reducing c-fos, c-jun and PCNA expression. The above effect of rosiglitazone is in part PPARγ-independcnt.     

氯喹敏感与抗性株恶性疟原虫对青蒿琥酯、克林霉素及其联用的体外敏感性

目的 为了解氯喹敏感和抗性株恶性疟原虫对青蒿琥酯、克林霉素及其二联用的敏感性。方法 运用Rieckmann体外微量法测定原虫对药物的敏感性。结果 氯喹敏感株恶性疟原虫对青蒿琥酯、克林霉素及青／克联用的ID50分别为2.8、3784.7及6.4/2046.6nmol/L；抗性株原虫对上述药物的ID50分别为8.1、1652.1及2.35/1409.4nmol/L。结论 抗氯喹恶性疟原虫对克林霉素无交叉抗性。青蒿琥酯与克林霉素联用在体外测定中，其抗疟作用对抗性株明显优于敏感株。     

Ki67、P53及微血管密度在大肠肿瘤中的表达

目的 研究Ki67、P53及微血管密度(microvessel density,MVD)在大肠肿瘤中的表达,探讨其与大肠肿瘤癌变的关系及作为早期癌变生物学标志物的可能性。方法 采用免疫组化技术分别测定正常大肠黏膜、大肠息肉及大肠癌组织标本中Ki67、P53及MVD值,共80例,分析其变化规律及相关性。结果 在正常黏膜、大肠息肉、大肠癌组中的Ki67标记指数逐渐增高(分别为11.00±10.70、39.64±17.70、52.96±26.40),组间比较差异显著(P=0.0001)。正常黏膜组P53蛋白均为阴性,大肠癌组P53蛋白表达的阳性率明显高于息肉组(P=0.0001)。Ki67、P53蛋白表达与性别、年龄、病程、病变部位、大小、大肠癌的病理类型、Dukes分期均无相关性。正常黏膜、大肠息肉、大肠癌组的MVD值(14.80±5.10、19.70±7.84、36.56±20.40)逐渐上升,3组差别显著(P=0.0001)。大肠癌中Dukes C、D期的MVD值(40.56±3.49)明显高于A、B期(29.50±2.45)(P=0.016)。Ki67与P53在各种组织中的表达呈正相关(r=0.5149,P=0.015)。联合检测Ki67及P53鉴别大肠良恶性病变的敏感度(70.37％)低于单侧Ki67(96.30％),但特异度(94.34％)明显增高。结论 Ki67标记指数可反映细胞增殖状态,指数高的大肠腺瘤易发生癌变。MVD值高的大肠癌易发生转移,MVD可作为判断大肠癌预后的参考指     

肝癌患者血清P-选择素测定及临床意义

目的：研究肝癌患血清P-selection(P-sel)在肝癌复发和转移中的作用。方法：采用ELISA法分别测定原发性肝癌患和对照组血清P-选择素的含量，同时测定AFP含量。结果：肝癌患P-sel含量显高于正常人，且与AFP含量呈线性正相关，术后2周浓度降低；P-sel含量以Ⅰ、Ⅲ和Ⅳ期肝癌患显高于Ⅰ期患；且大肝癌患显高于小肝癌患，有癌栓组、有肝内转移组明显高于无癌栓组和无转移组。结论：P-选择素测定在原发性肝癌的诊断和检测术后复发方面有重要价值，联合检测AFP和sP-sel可提高诊断敏感性。     

Illness-induced hyperalgesia is mediated by spinal neuropeptides and excitatory amino acids

The spinal cord dorsal horn contains neural mechanisms which can greatly facilitate pain. We have recently shown that ‘illness’-inducing agents, such as intraperitoneally administered lipopolysaccharide (LPS; bacterial endotoxin), can produce prolonged hyperalgesia. This hyperalgesic state is mediated at the level of the spinal cord via activation of the NMDA-nitric oxide cascade. However, prolonged neuronal depolarization is required before such a cascade can occur. The present series of experiments were aimed at identifying spinal neurotransmitters which might be responsible for creating such a depolarized state. These studies show that LPS hyperalgesia is mediated at the level of the spinal cord by substance P, cholecystokinin and excitatory amino acids acting at non-NMDA sites. No apparent role for serotonin or kappa opiate receptors was found.