Augmentation of recombinant CH50 polypeptide on the function of macrophages of mice during chemotherapy

CH50 is a Cell I- Hep Ⅱ bifunctional-domain recombinant polypeptide of human fibronectin expressed in E. colilll. This polypeptide can inhibit theinvasion and metastasis of tumor cells 1'n the[2] andactivate the anti--tumor activity of macrophages[']. Ithas been reported that this polypeptide andchemotherapeutic agent have a synergistic inhibitoryeffect on the metastasis of tumors[4J. In this study,we further investigated the effect of CH50 on thefunction of macrophages of mice during chem…     

NANC transmitters in the female pig urethra–localization and modulation of release via α2-adrenoceptors and potassium channels

1. To investigate further the release, localization and identity of a non-nitrergic mediator of smooth muscle relaxation in the female pig urethra, we studied the effects of drugs acting at α₂-adrenoceptors or K⁺ channels, the effects of capsaicin and chemical sympathectomy, and the actions of several transmitter candidates.
2. Electrical field stimulation (EFS; frequencies above 12 Hz) of spontaneously contracted smooth muscle strips from the female pig urethra evoked long-lasting, frequency-dependent relaxations in the presence of prazosin, scopolamine, and N^G-nitro-L-arginine. Treatment with the selective α₂-adrenoceptor agonist UK-14 304 markedly reduced the relaxations evoked by EFS at all frequencies tested (16–30 Hz). The inhibitory effect of UK-14 304 was completely antagonized by the α₂-adrenoceptor antagonist rauwolscine. The muscarinic M₁ receptor antagonist, pirenzepine, or exogenously administered carbachol, did not have any effects on the electrically evoked relaxations.
3. Inhibition of high conductance Ca²⁺ activated K⁺ channels by iberiotoxin or charybdotoxin significantly enhanced the relaxations evoked by EFS at all frequencies. However, inhibition of voltage-sensitive K⁺ channels with 4-aminopyridine or dendrotoxin-1, treatment with the ATP-sensitive K⁺ channel blocker, glibenclamide, or treatment with the high and low conductance Ca²⁺ activated K⁺ channel blockers, tetraethylammonium chloride and apamin, had no effect on the relaxations evoked by EFS.
4. Electrically evoked relaxations were not affected by adrenergic denervation with 6-hydroxydopamine (6-OHDA) at any frequency. However, treatment with 6-OHDA abolished prazosin-sensitive electrically induced contractions, and a long-lasting relaxation was revealed. Treatment with capsaicin, believed to damage selectively a subpopulation of primary afferent fibres, did not affect basal tone or relaxations evoked by EFS.
5. Exogenously applied vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating peptide (PACAP)-27, PACAP-38, adenosine, ATP and 5-hydroxy-tryptamine caused relaxations of the urethral preparations, whereas prostaglandin E₂ and calcitonin gene-related peptide had no effects. VIP 10-28, α, β-methylene-ATP, reactive blue-2, suramin or indomethacin did not reduce the electrically-evoked relaxations at any frequency. However, the relaxations were slightly reduced by trypsin or α-chymotrypsin.
6. The present results suggest that the release of the unknown mediator in the female pig urethra can be modulated via α₂-adrenoceptors and high conductance Ca²⁺ activated K⁺ channels. Furthermore, the mediator does not appear to be localized to or released from adrenergic or capsaicin-sensitive sensory nerve-endings. The identity of the transmitter remains to be established.

     

Intracisternal injection of TRH antibody blocks gastric emptying stimulated by 2-deoxy-d-glucose in rats

We evaluated the effect of 2-deoxy-d-glucose (2-DG) on gastric emptying of a non nutrient solution in conscious rats using a Phenol red method. Intravenous injection of 2-deoxy-d-glucose dose-dependently increased the rate of gastric emptying. This stimulatory action of 2-DG was abolished by subdiaphragmatic vagotomy. Intracisternal injection of thyrotropin-releasing hormone (TRH) antibody blocked intracisternal TRH and intravenous 2-DG-induced enhancement of gastric empyting but not the stimulation of gastric emptying induced by intracisternal pancreatic polypeptide. The TRH antibody injected intraperitoneally had no effect. These results suggest that endogenous TRH in the brain is involved in vagal-dependent stimulation of gastric emptying by 2-DG.     

Inhibitory Effect of recombinant FN polypeptide CH50 on the metastasis and tumor growth

Immunotherapycouldremoveresidualtumorcellsbyenhancinganti-tumorfunc-tionofimmunesystemaftersurgicalre-movaloftumor.ltisatime-consumingtofullyactivateimmunece11sandformstrongcytotoxicityontumorcellsinvivo.ltisim-perativetofindawaytoactivateanti-tumoractivityofimmunecellsquick1yenoughinvivosothattheresidualtumorcellscouldbeattackedasearlyaspossible.CH5oisabifunctiona1-domainrecombinantpolypep-tidewhichcontainsCellIandHepIdo-mainsofhumanfibronectin(FN)andisabIetoexpressinE-coli[lj.Thispolypep-…     

三结构域重组纤连蛋白多肽在大肠杆菌中表达及其产物的纯化与鉴定

在大肠杆菌中表达了一种抗肿瘤转移多肽——人纤连蛋白（ＦＮ） 的ＣｅｌｌＩ－Ｈｅｐ Ⅱ－ＣｅｌｌⅡ三结构域重组多肽（ＣＨ８２）, 表达效率达２１％ 。在低温 （２２ ℃） 培养表达时, ＣＨ８２大部分为可溶性产物, 经ＤＥＡＥ－５２ 层析及Ｈｅｐａｒｉｎ－ａｇａｒｏｓｅ亲和层析可得到纯品; 在高温（３７ ℃） 培养表达时, ＣＨ８２ 主要以包涵体形式出现, 经尿素变性与复性处理后,可通过Ｈｅｐａｒｉｎ－ａｇａｒｏｓｅ 亲和层析得到纯品。所得纯品均具有结合肝素和结合细胞的功能, 且结合细胞的能力比双结构域ＦＮ更强, 表明两个结合细胞的功能结构域均有活性     

应用多中心合成技术合成人乙酰胆碱酯酶的抗原多肽

目的和方法利用多中心同步多肽合成技术合成人乙酸胆碱酯酶的574个抗原十肽,并且生物素化。结果电喷雾质谱支持合成肽的准确性。结论多中心合成技术可以快速、同步合成高纯度及序列正确的多肽,是研究蛋白质和肽的一种重要工具。     

Long-term enhancement of REM sleep by the pituitary adenylyl cyclase-activating polypeptide (PACAP) in the pontine reticular formation of the rat

In rats, rapid eye movement (REM) sleep can be elicited by microinjection of vasoactive intestinal polypeptide (VIP) into the oral pontine reticular nucleus (PnO). In the present study, we investigated whether this area could also be a REM-promoting target for a peptide closely related to VIP: the pituitary adenylyl cyclase-activating polypeptide (PACAP). When administered into the posterior part of the PnO, but not in nearby areas, of freely moving chronically implanted rats, PACAP-27 and PACAP-38 (0.3 and 3 pmol) induced a marked enhancement (60-85% over baseline) of REM sleep for 8 h that could be prevented by prior infusion of the antagonist PACAP-(6-27) (3 pmol) into the same site. Moreover, injections of PACAP into the centre of the posterior PnO resulted in REM sleep enhancement which could last for up to 11 consecutive days. Quantitative autoradiography using [125I]PACAP-27 revealed the presence in the PnO of specific binding sites with high affinity for PACAP-27 and PACAP-38 (IC50 = 2.4 and 3.2 nM, respectively), but very low affinity for VIP (IC50 > 1 microM). These data suggest that PACAP within the PnO may play a key role in REM sleep regulation, and provide evidence for long-term (several days) mechanisms involved in such a control. PAC1 receptors which have a much higher affinity for PACAP than for VIP might mediate this long-term action of PACAP on REM sleep.     

Serum tumor marker kinetics and the clinical course of patients with advanced breast cancer

Serum carcinoembryonic antigens (CEA), CA 15-3, and tissue polypeptide antigens (TPA) have been used in monitoring the clinical course of patients with breast cancer. However, recent reports have suggested that the serial levels of these markers during therapy do not always correlate with the response to therapy. To clarify the usefulness of the serial combination assay of these markers in monitoring the clinical course of patients during therapy, we investigated the relationship between the initial changes and the kinetic patterns of the markers after therapy and the objective responses. When an increase or decrease of over 20% in these markers is taken to be significant, then the initial changes in all three markers significantly correlated with the therapeutic responses (P<0.01). Five distinct kinetic patterns in the marker levels were observed. A paradoxical kinetic pattern of CEA and CA 15-3 levels — that is, an initial surge and subsequent drop — was seen in one-third of the responders. The TPA levels tended to exhibit a steady decline pattern in those responders. The sensitivity and specificity of the kinetic patterns to predict the clinical courses were significantly higher than those obtained from the analysis of initial changes. These findings thus suggest that adequate knowledge of the unique kinetics of each marker may help to make a more accurate prediction of the therapeutic responses.     

胆管结石乳头局部组织中血管活性肠肽和一氧化氮合酶表达的改变及意义

目的 探讨胆管结石患者乳头局部组织中血管活性肠肽(VIP)和一氧化氮合酶(NOS)表达的改变及意义。方法 选择68例进行逆行胰胆管造影和/或乳头括约肌切开术的胆管结石患者,采用内镜下活检乳头局部组织。常规石蜡包埋,连续切片,免疫组化SABC法检测VIP及NOS。对照组为门诊胃镜检查胃粘膜大致正常者。结果 结石组乳头粘膜内 VlP和NOS阳性产物与对照组相比较显著降低(P相似文献   

鹿茸口服液促进RNA和蛋白质合成作用的研究

目的：研究鹿茸口服液对青年及老年小鼠RNA和蛋白质合成的作用。方法：观察口服鹿茸口服液对小鼠肝RNA和蛋白质含量及^3H-Uridine和^3H-Leucine掺入的影响。结果：鹿茸口服液可明显增加老年小鼠肝RNA和蛋白质含量及[^3H]Uridine和[^3H]Leucine掺入RNA和蛋白质，作用明显强于青年小鼠。结论：鹿茸口服液对老年小鼠RNA和蛋白质合成有明显促进作用。