The role of nitric oxide (NO) in 5-HT-induced relaxations of the guinea-pig stomach

Summary In a previous study we showed that the relaxations induced after vagal stimulation of the guinea-pig stomach are mediated via nitric oxide (NO) or a NO-related substance. Intra-arterial injection (i.a.) of 5-hydroxytryptamine (5-HT) also induced relaxations in the guinea-pig stomach. Since it has been shown that in the guinea-pig colon 5-HT-induced relaxations are mediated via NO the aim of this study was to establish whether NO is involved in the 5-HT-induced relaxations in the guinea-pig stomach. Intra-arterial injection of 5-HT induced dose-dependent relaxations of the stomach. Since atropine and - and -adrenoceptor blocking agents did not influence the relaxation and since tetrodotoxin (TTX) blocked the relaxations, this effect is mediated via NANC-neurons. Administration of a NO-synthase-inhibitor N^G-nitro-l-arginine (L-NNA) concentration-dependently reduced the 5-HT-induced relaxations. Haemoglobin (a NO-scavanger) did not affect the relaxations to 5-HT, while addition of methylene blue, an inhibitor of soluble guanylate cyclase, reduced the relaxations by 50%. Addition of an opioid receptor agonist (loperamide), a 5-HT₁ antagonist (methiothepin or metergoline) or a 5-HT₄ receptor agonist (cisapride) or-antagonist (tropisetron in micromolar concentrations) inhibited the 5-HT-induced relaxations. Neither the 5-HT₄ receptor agonist renzapride, nor the novel 5-HT₄ receptor antagonist SDZ 205-557, affected the relaxations to 5-HT. These data indicate that 5-HT-induced relaxations of the guinea-pig stomach are mediated via NANC-inhibitory nerves on which inhibitory opioid-receptors are present. The use of selective agonists and antagonists indicates that 5-HT does not act via 5-HT₂, 5-HT₃ or 5-HT₄ receptors. 5-HT may act via 5-HT₁ receptors but the subtype involved, if any, has not yet been identified. The inhibitory neurotransmitter which is involved is NO or a NO-related substance. Correspondence to A. L. Meulemans at the above address     

胃癌细胞肿瘤坏死因子受体的研究

目的　探讨人胃癌细胞肿瘤坏死因子受体 ( TNFR)的数目与胃癌细胞分化程度以及与肿瘤坏死因子突变体 ( TNF- m)细胞毒效应之间的关系。方法　以12 5I- TNF- m为配体 ,用放射配体结合分析法 ,检测了高、中、低不同分化程度的体外培养胃癌细胞 ( MKN2 8、SGC790 1、MKN4 5)的 TNFR,同时用 MTT比色法研究了 TNF- m对三株胃癌细胞的细胞毒效应。结果　三株胃癌细胞 TNFR数目分别为每细胞 9.8× 10 -12 nmol、5.6× 10 -12 nmol、3.2× 10 -12 nmol,三者之间比较 ,TNFR数目差异有显著性 ( P<0 .0 5)。解离常数基本一致 ,同一温度时三株胃癌细胞 TNF- m的内化率几乎相等 ,且呈温度依赖关系。TNFR的半衰期大约为 90分钟 ,胞膜与胞浆 TNFR数目之比约为 1∶ 2 ,TNF- m对三株胃癌细胞的最大杀伤率分别为 86%、60 %、34 % ,差异有显著性 ( P<0 .0 5) ,且 39℃时的杀伤率高于37℃时的杀伤率。结论　胃癌细胞表面 TNFR数目与胃癌分化程度相关。 TNF- m的细胞毒效应与TNF数目及 TNF- m的内化量有关。     

The effect of TGFβ1 on murine tumor growth following direct intratumoral injection of plasmid DNA

In order to investigate TGFβ1 gene expression and its effect on murine tumor growth following direct intratumoral injection of naked plasmid DNA encoding human TGFβ1, LM₃ murine lung adenocarcinoma cells were inoculated subcutaneously to T₇₃₉ mice and grew to tumor nodules in 2 weeks. Multiple direct intratumoral injection of plasmid DNA, PMAMneo- TGFβ1, were given and compared with saline or vector plasmid administration groups. The growth of tumor was observed till the 8th week when the mice were killed for Northern blot analysis and histopathological study of tumoral tissue. The results showed that the growth of tumor was boosted in the TGFβ1 gene treated mice as compared with the control groups, whereas there was no significant difference in the metastatic behavior. Northern blot showed efficient expression of TGFβ1 mRNA in the treated group. The present study indicated that TGFβ1 may stimulate tumor growthin vivo through certain mechanisms. And direct intra-tumoral injection of nude plasmid DNA may be a promising gene transfer strategyin vivo. This work was supported by the National Natural Science Foundation of China (No. 39370761).     

乳腺良恶性病变中纤维连接蛋白的分布

目的观察乳腺良恶性病变中纤维连接蛋白（ＦＮ）的分布,探讨它与乳腺癌分化、浸润、转移的关系。方法应用免疫组织化学方法,对乳腺良恶性病变纤维连接蛋白进行半定量研究。结果乳腺癌及淋巴结转移细胞ＦＮ呈强阳性表达,而基膜ＦＮ及间质ＦＮ普遍减少甚至缺乏。结论细胞ＦＮ可能是乳腺癌的一个标记物,间质ＦＮ及基膜ＦＮ减少有利于乳腺癌浸润、转移。     

MR imaging of the male pelvis

Prostate and urinary bladder cancer are the most frequently encountered malignancies of the urinary tract. Appropriate use of the different imaging techniques is crucial for accurate assessment of prognosis and for the development of appropriate treatment planning. Especially determination of local tumor extension and detection of nodal or bone metastases is extremely important. In this regard MR imaging is the most promising imaging technique. Therefore, in this review its role in staging these malignancies is evaluated and compared with clinical staging, and other imaging techniques. Finally, future developments, such as new sequences, new contrast agents, the role of surface coils and MR-guided biopsy, are considered. Also, the preferred radiological approach is discussed.     

MR imaging of the chest: Mediastinum and chest wall

This review presents the options and limitations of MRI in non-vascular diseases of the mediastinum and the chest wall. In numerous thoracic pathologies, MRI is a useful supplement to spiral CT. This imaging procedure also allows a contrast-media-free differentiation of solid tumors and vascular lesions (e. g., aortic aneurysms). The advantages of MRI over CT are particularly useful when multiplanar tumor imaging is required prior to surgery to establish the exact spatial relationship between tumor and the other mediastinal structures. Primary indications for MRI in diseases of the mediastinum and chest wall are therefore: (a) tumors of the posterior mediastinum for determining their position in relation to the neural foramina and the spinal canal; (b) chest wall tumors; (c) preoperative multiplanar imaging of primary mediastinal tumors; and (d) contraindications against CT exams with iodine contrast media.     

Field stimulation-induced responses of circular smooth muscle from guinea-pig stomach

Summary Field stimulation of circular smooth muscle of guinea-pig stomach from the regions of the cardia and fundus caused contraction responses at low stimulation frequencies (0.25–1 Hz) with relaxation at higher frequencies (1–10 Hz), whilst tissues of the body and antrum responded with contraction throughout the frequency range. Atropine (10^–9–10^–8 M) antagonised the contraction responses of all tissues, with relaxation developing at higher concentrations (except for antral tissue). In contrast, metoclopramide (10^–8–10^–6 M) caused modest (cardia, fundus) or marked (body, antrum) enhancement of contractions to field stimulation, whilst domperidone (10^–8–10^–7 M), haloperidol (10^–8–10^–6 M), prazosin, propranolol and methysergide (10^–8–10^–6 M) failed to modify the contraction responses. However, whilst yohimbine and guanethidine failed to modify the contractions of the cardia, fundus and body tissues, those of the antral preparations were antagonised by nanomolar concentrations of yohimbine and by guanethidine (10^–6–5×10^–5 M). To optimise the relaxation responses for study, atropine was included in the physiological solution. Relaxation to field stimulation of preparations from the body and cardia, but not the fundus, was antagonised by reserpine pretreatment (5 mg/kg i.p., 24h), addition of guanethidine (10^–5–10^–4 M), phentolamine, prazosin or propranolol (10^–7–10^–6 M) (the effects of prazosin and propranolol being additive). Higher concentrations of haloperidol and domperidone antagonised the relaxation responses of the body preparations only. Metoclopramide, yohimbine and methysergide (10^–8–10^–6 M) were ineffective. Thus, it is concluded that the contractile effects of the 4 stomach areas to field stimulation reflects a major cholinergic involvement, with an additional ₂-adrenoceptor contractile component in antral tissue. Relaxation responses of cardia and body tissue involve ₂- and -adrenoceptors plus a further, unidentified, non-adrenergic component; the latter represents the total relaxation response of the fundic preparation.     

论吴鞠通治疳学术思想

吴鞠通《温病条辨·解儿难》对疳疾的论治文短义深,所提治疳九妙法蕴藏着深奥的学术思想。本文从脾胃学说、升降出入学说、营卫学说等方面进行了阐发,以期能发掘其学术渊薮,指导学术研究及临床实践。     

Apomorphine contracts and relaxes circular smooth muscle of guinea-pig stomach via action on adrenoceptor mechanisms

Summary Nanomolar concentrations of apomorphine caused contractions of the circular smooth muscle from the body region of the guinea-pig stomach, the response showing rapid tachyphylaxis. These contractions were antagonised by yohimbine but not by prazosin, haloperidol, propranolol or methysergide. Higher concentrations of apomorphine caused concentration-related relaxations of the stomach body which were not subject to tachyphylaxis. These were antagonised by propranolol but not by prazosin, yohimbine or haloperidol. Dopamine-induced contractions of the circular smooth muscle from the stomach body were antagonised by apomorphine in nanomolar concentration; acetylcholine-induced contractions and isoprenaline-, dopamine- and phenylephrine-induced relaxations were unaffected by apomorphine. Thus, it is concluded that the contraction of circular smooth muscle from the stomach body to apomorphine is mediated via an adrenoceptor with characteristics of the ₂-type, and that a partial agonist-antagonists action prevents subsequent contractile responses to apomorphine and dopamine. Relaxation caused only at higher concentrations of apomorphine is mediated via an adrenoceptor with characteristics of the -type.     

Benzamide action at α2-adrenoceptors modifies catecholamine-induced contraction and relaxation of circular smooth muscle from guinea-pig stomach

Summary Dopamine was shown to act on the circular smooth muscle of the stomach body to cause contraction at a yohimbine-sensitive site (₂) and a relaxation at a prazosin-sensitive site (₁). Metoclopramide and tiapride failed to modify either response, failed to antagonise a relaxation to phenylephrine at 1(₁ sites in the same tissue, and failed to modify the contractions caused by dopamine and phenylephrine at an ₂-adrenoceptor site in the pyloric sphincter. However, (+)- and (–)-sultopride and (+)-sulpiride antagonised the dopamine-induced contractions of the stomach body indicating an ₂-antagonist action. An ability to attenuate the relaxation of this tissue may reflect a displacement of the contraction curve to the right rather than an ₂-antagonist action since the response to phenylephrine was not antagonised either in this tissue or in the pyloric sphincter. Within the central nervous system the (–)-enantiomers of sultopride and sulpiride have a highly selective dopamine receptor blocking action. This cotrasts with the present findings in the stomach musculature of a non-stereospecific antagonism at ₂-type adrenoceptors.