光量子和血卟啉的放疗增敏作用与表皮生长因子关系的研究

本文采用放射免疫技术检测了充氧及充氧并用光量子或血卟啉和光量子与血卟啉联合治疗后进行局部放射治疗皮下Ｗ２５６移植瘤大鼠的血浆、瘤组织和颌下腺组织内表皮生长因子（ＥＧＦ）的含量。结果表明,与单纯充氧后放射治疗组大鼠比较：（１）光量子治疗组、血卟啉治疗组和光量子与血啉卟联合治疗组大鼠血浆ＥＧＦ含量显著升高（Ｐ〈０．０５）;（２）光量子治疗组、血卟啉治疗组和光量子与血卟啉联合治疗组大鼠组织与颌下腺中ＥＧ     

大鼠体内视网膜神经节细胞透向因子（RGNTF）及其受体的免疫组织化学定位

本文用ＲＧＮＴＦ单克隆抗体及抗独特型单克隆抗体的免疫组织化学反应,对ＲＧＮＴＦ及其受体在大鼠体仙的分布进行了研究。结果显示,大鼠的肾脏、肾上腺、下颌下腺、胃底腺,以及睾丸丸的生精细胞对ＲＧＮＴＦ均呈现强阳性免疫反应,并对ＲＧＮＴＦ抗独特型单克隆抗体也呈现阳性免疫反应,表明ＲＧＮＴＦ及其受体有较广泛的分布,这种情况与神经生长因子（ＮＧＦ）及睫状节神经诱向（营养）因子（ＣＮＴＦ）相类似。但是,ＲＧＮＴ     

用ELISA法检测2.5S鼠神经生长因子

鼠颌下腺提纯的２５ＳＮＧＦ免疫家兔,获得兔抗ＮＧＦ抗体,研制出鼠２５ＳＮＧＦＥＬＩＳＡ检测试剂盒,该试剂盒灵敏度小于１ｎｇ／ｍｌ,在６７０～０８４ｎｇ／ｍｌ范围内,线性良好,ｒ＝０９９。与大鼠、小鼠及人血浆无非特异反应,在大鼠血浆中,ＮＧＦ样品回收率在９１％～１０７％之间,变异系数小于１０％（ｎ＝４）。结果表明：本试剂盒操作简便,灵敏度高,特异性强,适合药代动力学研究及生产过程中的ＮＧＦ检测。     

大鼠运动性肥大心脏心肌血管内皮生长因子及其基因表达 …

目的和方法：血管内皮生长因子（ｖａｓｃｕｌａｒｅｎｄｏｔｈｅｌｉａｌｇｒｏｗｔｈＶＥＧＦ）是新近确定的一种特异作用血管内皮细胞的活性肽。最近发现正常心肌细胞可表达ＶＥＧＦ高血压肥大心脏恼肌ＶＥＧＦ及其因表达增强,但对运动性心肌肥大时的变化尚不清楚,本实验采用免疫组分和分子杂交方法,对游泳运动１０周大鼠稳定期肥大心脏心肌ＶＥＧＦ及其基因表达进行了研究,结果：ＷｉｓｔａｒＫｙｏｔｏ（ＷＫＹ）大鼠,自发     

雌激素拮抗剂对胎盘EGF受体及其基因表达的影响

中期孕鼠在他莫昔芬作用下,其颌下腺,血清中ＥＧＦ含量下降,胎盘中ＥＧＦ受体结合位点数下降以及它的ｍＲＮＡ表达受到抑制,再次证实了他莫昔芬抑制雌激素诱导ＥＧＦ受体ｍＲＮＡ的表达。从而使ＥＧＦ受体结合位点数减少,因此,他莫昔芬对孕鼠胚胎生长发育有不可忽视的影响。     

雌激素拮抗剂对胎盘EGF受体及其基因表达的影响

中期孕鼠在他莫昔芬作用下，其颌下腺，血清中ＥＧＦ含量下降，胎盘中ＥＧＦ受体结合位点数下降以及它的ｍＲＮＡ表达受到抑制，再次证实了他莫昔芬抑制雌激素诱导ＥＧＦ受体ｍＲＮＡ的表达，从而使ＥＧＦ受体结合位点数减少，因素，他莫昔芬对孕鼠胚胎生长发育有不可忽视的影响。     

大鼠体内视网膜神经节细胞诱向因子(RGNTF)及其受体的免疫组织化学定位

本文用ＲＧＮＴＦ单克隆抗体及抗独特型单克隆抗体的免疫组织化学反应,对ＲＧＮＴＦ及其受体在 大鼠体内的分布进行了研究．结果显示,大鼠的肾脏、肾上腺、下颌下腺、胃底腺,以及睾丸的生精细胞对 ＲＧＮＴＩＦ均呈现强阳性免疫反应,并对ＲＧＮＴＦ抗独特型单克隆抗体也呈现阳性免疫反应,表明 ＲＧＮＴＦ及其受体有较广泛的分布,这种情况与神经生长因子（ＮＧＦ）及睫状节神经诱向（营养）因子 （ＣＮＴＦ）相类似．但是,ＲＧＮＴＦ及其受体的分布特点和ＮＧＦ、ＣＮＴＦ的分布是不完全相同的,提示作者 分离的ＲＧＮＴＦ与ＮＧＦ和ＣＮＴＦ不是同源物。这样肾上腺皮质、下颌下腺的浆液腺泡及导管上皮细胞、 胃底腺上皮细胞和生精细胞不仅能够产生ＲＧＮＴＦ,也能合成ＲＧＮＴＦ受体。因此,它们对ＲＧＮＴＦ可能 有自分泌的功能,ＲＧＮＴＦ对这些细胞可能有自身调节的效应。     

小牛类表皮生长因子活性肽（c－EGF）的分离纯化及性质

本文报道小牛颌下腺通过酸抽提、ＣＭ５２、ＤＥ５２柱层析、ＳｅｐｈａｄｅｘＧ７５凝胶过滤及ＨＰＬＣ等步,分离纯化到一个分子量为６ｋＤ,等电点为４．６的小肽。该小肽类似人重组表皮生长因子（ｒｈ—ＥＧＦ）的生物活性,具有刺激ＮＲＫ细胞的增殖及刺激新生小鼠的睁眼、萌牙,并具有增加Ａ４３１细胞膜蛋白质磷酸化的功能。氨基酸组成缺少苯丙氨酸及苏氨酸残基。我们命名它为小牛类ＥＧＦ样活性肽（ｃａｌｆＥＧＦ－ｌｉｋｅａｃｔｉｖｅｐｅｐｔｉｄｅ,简称ｃ－ＥＧＦ）。     

大鼠和小鼠睾丸表皮生长因子表达的免疫组织化学定位观察

为了了解大鼠和小鼠睾丸是否产生ＥＧＦ及其细胞定位,本实验用ＥＧＦ单克隆抗体对大鼠和小鼠睾丸进行了免疫细胞化学定位研究,结果显示：（１）出生后,大鼠和小鼠睾丸即开始产生ＥＧＦ,分泌活动主要位于睾丸间质细胞。（２）至性成熟期,少数精原细胞、精母细胞及个别圆形精子细胞和管周肌样细胞也产生ＥＧＦ,使生精小管尤其是血睾屏障管腔小室侧的ＥＧＦ分泌增加。（３）在本实验中,睾丸支持细胞未见明显ＥＧＦ阳性染色。结果表明,大鼠和小鼠睾丸是可以产生ＥＧＦ的,间质细胞是其主要的ＥＧＦ分泌细胞。进入性成熟期后,少数精原细胞、精母细胞及个别圆形精子细胞和管周肌样细胞也产生ＥＧＦ。大鼠和小鼠睾丸在发育过程中ＥＧＦ分泌量呈上升趋势,至性成熟期达分泌高峰     

神经生长因子在6—OHDA化学性去交感神经中的保护作用

本实验用６－ＯＨＤＡ造成成年小白鼠颌下腺化学性去交感神经,观察了神经生长因子对该神经的保护作用。６－ＯＨＤＡ处理后２４小时腺体内去甲肾上腺素（ＮＥ）含量降至正常水平的２％以下。若在６－ＯＨＤＡ处理同时开始多次给予神经生长因子（ＮＧＦ）,则ＮＥ残留量明显提高。减小６－ＯＨＤＡ剂量到１０ｍｇ／ｋｇ,ＮＥ残留量增加,同时ＮＧＦ的作用亦较用６－ＯＨＤＡ１５ｍｇ／ｋｇ时列为显著。若提前２４小时给予ＮＧＦ,尽     

Immunoreactivities for epidermal growth factor (EGF) and for EGF receptors in rats with gastric ulcers

Summary The present study was aimed at assessing whether epidermal growth factor (EGF) and its receptors are present in the gastric mucosa during the healing of gastric ulcers. Immunohistochemical, immunochemical and functional studies were performed in rats after induction of ulcers in the oxyntic mucosa. Controls, which included non-operated and sham-operated animals, displayed only rare cells in the bottom of the oxyntic glands showing EGF-like immunoreactivity. Within one day after ulcer induction, a markedly increased number of chief cells in undamaged mucosa showed intense staining. Concomitantly, there was an increased immunoreactivity for EGF receptors in the mucous neck cells. Maximal immunostaining for both compounds was observed at 3 days after ulcer induction; augmented staining was still demonstrable after 3 weeks. RIA revealed significantly increased EGF concentration in the oxyntic mucosa three days after ulcer induction, and at this stage stimulated gastric acid secretion, measured in a parallel group of chronic fistula rats, indicated significant inhibition. The transient increases in EGF-like and EGF receptor immunoreactivities may stimulate gland cell proliferation. The local release of EGF-like substances may also serve to reduce gastric acidity and thereby promote ulcer healing.     

Reduction of EGF is associated with the delay of ulcer healing by cigarette smoking

Cigarette smoking is associated with peptic ulcer diseases. Smokers have lower levels of salivary epidermal growth factor (EGF) than nonsmokers. We investigated whether reduction of EGF is involved in the delay of gastric ulcer healing by cigarette smoking. Rats with acetic acid-induced ulcers were exposed to cigarette smoke (0, 2, or 4% vol/vol) 1 day after ulcer induction. EGF level was elevated 1 day after ulcer induction in salivary glands and serum, and 4 days after ulcer induction in the gastric mucosa. However, cigarette smoke depressed these beneficial effects and EGF mRNA expression in salivary glands and gastric mucosa. Cigarette smoke delayed gastric ulcer healing and reduced cell proliferation, angiogenesis, and mucus synthesis. Exogenous EGF (10 and 20 microg/kg i.v.) before smoke exposure reversed the adverse effects of cigarette smoke, whereas vascular endothelial growth factor level and nitric oxide synthase activity were unaffected. It is concluded that the detrimental effect of cigarette smoke on ulcer healing is a consequence of reduction of angiogenesis, cell proliferation, and mucus secretion through the depressive action on EGF biosynthesis and its mRNA expression in salivary glands and gastric mucosa.     

Role of capsaicin sensory nerves and EGF in the healing of gastric ulcer in rats

Accumulating evidence indicates that capsaicin sensitive afferent fibers play a pivotal role not only in gastroprotection but also in ulcer healing. Denervation of capsaicin sensitive afferent fibers exerts an adverse action on these effects. However, whether such an action is mediated through a depression on epidermal growth factor (EGF) is undefined. In this study, the effects of denervation of sensory neurons with capsaicin (100 mg/kg, s.c.) on acetic acid-induced chronic gastric ulcers and their relationship with the EGF expression in salivary glands, serum and gastric mucosa were investigated. Capsaicin significantly increased ulcer size, decreased gastric mucosal cell proliferation at the ulcer margin, angiogenesis in the granulation tissue and also gastric mucus content. Ulcer induction by itself dramatically elevated EGF levels in salivary glands and serum on day 1 and 4, and also in the gastric mucosa on day 4. However, capsaicin completely abolished these effects. It is concluded that stimulation of EGF expression in salivary glands and serum may be one of the mechanisms by which capsaicin sensitive nerves contribute to the gastroprotective and ulcer healing actions in the stomach.     

Bacterial colonization and healing of gastric ulcers: the effects of epidermal growth factor

Experimental gastric ulcers are rapidly colonized by various bacteria, resulting in significantly impaired healing. Epidermal growth factor (EGF) is capable of preventing bacterial colonization of the healthy intestinal mucosa. In this study, we examined the possibility that EGF accelerates gastric ulcer healing by reducing bacterial colonization of the ulcer. Gastric ulcers were induced by serosal application of acetic acid. The effect of daily administration of EGF on ulcer healing and bacterial colonization was assessed and compared with the effect of daily treatment with broad-spectrum antibiotics. EGF administration reduced colonization levels and accelerated ulcer healing as effectively as the antibiotic treatment. EGF was without effect on acid secretion or neutrophil infiltration into the ulcer. Bacterial growth was not inhibited in the presence of EGF in vitro. These results demonstrate that EGF reduces bacterial colonization during an established infection of a compromised mucosal surface. This effect may contribute to the ability of EGF to accelerate gastric ulcer healing. This effect is acid independent and not due to an anti-inflammatory effect or to direct bactericidal actions.     

Solcoseryl in prevention of stress-induced gastric lesions and healing of chronic ulcers

Solcoseryl, a deproteinized extract of calf blood, protects the gastric mucosa against various topical irritants and enhances the healing of chronic gastric ulcerations but the mechanisms of these effects have been little studied. This study was designed to elucidate the active principle in Solcoseryl and to determine the role of prostaglandins (PG) and polyamines in the antiulcer properties of this agent. Using both, the radioimmunoassay and radioreceptor assay, EGF-like material was detected in Solcoseryl preparation. Solcoseryl given s.c. prevented the formation of stress-induced gastric lesions and this was accompanied by an increase in the generation of PGE2 in the gastric mucosa. Similar effects were obtained with EGF. Pretreatment with indomethacin, to suppress mucosal generation of prostaglandins (PG), greatly augmented stress-induced gastric ulcerations and antagonized the protection exerted by both Solcoseryl and EGF. Solcoseryl, like EGF, enhanced the healing of chronic gastro-duodenal ulcerations. This effect was abolished by the pretreatment with difluoromethylornithine, an inhibitor of ornithine decarboxylase, the key enzyme in the biosynthesis of polyamines. The healing effects of Solcoseryl and EGF was also reduced by prednisolone which decreased the angiogenesis in the granulation tissue in the ulcer area. These results indicate that Solcoseryl 1. contains EGF-like material, 2. displays the protective and ulcer healing effects similar to those of EGF and involving both PG and polyamines and 3. acts via similar mechanism as does EGF.     

Involvement of heat shock proteins in the healing of acetic acid-induced gastric ulcers in rats.

The present study examined the expression of 73-kDa of heat shock cognate protein (HSC70), 72-kDa of heat shock protein (HSP70) and 47-kDa of HSP (HSP47) observed in the ulcer healing process in rats. Gastric ulcers were induced by a luminal application of acetic acid in male Donryu rats. During the ulcer healing process, the expression of HSPs in the ulcerated tissue was determined. A high level of HSC70 expression was observed both in the normal mucosa and ulcerated tissue, but the level did not change upon ulceration and ulcer healing. While HSP70 and HSP47 were markedly expressed in the ulcer base during ulceration, and decreased with ulcer healing. HSP70 expression in the ulcer margin was gradually increased with ulcer healing. Omeprazole accelerated the healing of gastric ulcers with strong inhibition of gastric acid secretion, while indomethactin delayed in ulcer healing despite slight inhibition of gastric acid secretion. Omperazole enhanced the expression of HSP70 both in the ulcer margin and base, but it reduced HSP47 expression in the ulcer base Indomethacin markedly enhanced HSP47 expression only in the ulcer base. In conclusion, the expression of HSP70 and HSP47 is changed during ulcer healing. Furthermore, it was suggested that the enhanced expression of HSP70 is involved in acceleration of ulcer healing, but overexpression of HSP47 is involved in delayed ulcer healing.     

Serum and Gastric Luminal Epidermal Growth Factor in Helicobacter Pylori—Associated Gastritis and Peptic Ulcer Disease

Background Helicobacter pylori is the cause of chronic (type B) gastritis, duodenal ulceration (DU), and gastric ulceration (GU). Smoking is associated with delayed ulcer healing. Epidermal growth factor (EGF) is produced in the salivary and Brunner's glands of the upper gastrointestinal tract, inhibits gastri acid secretion, and is a powerful mitogen. Materials and Methods. We sought to determine gastric luminal EGF (GL-EGF) in smokers and patients with Hp-associated DU and the effect of Hp eradication. Our aim was to determine GL-EGF in patients with GU and the effect of ulcer healing and to measure serum EGF in patients with Hp gastritis with or without DU disease. Results. GL-EGF was reduced in smokers compared to control (p= .008). Subjects with HP gastritis had reduced GL-EGF compared to controls (p= .0002). There was no difference in GL-EGF between Hp-positive subjects who had DU and those with chronic gastritis alone. Eradication of Hp from those patients with DU had no effect on the low levels of GL-EGF. There was no difference between GL-EGF in Hp gastritis alone and in Hp-associated active GU. GL-EGF fell after ulcer healing (p= .04), a difference confirmed by analysis of paired samples from patients before and after ulcer healing (p= .03). There was no difference in serum EGF between controls and subjects with Hp infection. There was no difference in serum EGF in subjects with DU-associated and non-ulcer-associated gastritis. Conclusions. Subjects with Hp gastritis, or those who smoke, had low concentrations of GL-EGF regardless of whether DU was present. Eradication of Hp did not return the concentrations of GL-EGF to normal in DU subjects. Individuals with Hp gastritis and inactive GU had low levels of GL-EGF compared to non-ulcer Hp infection. The relative increase in GL-EGF that occurred with ulceration of the gastric mucosa may have resulted from the development of an ulcer-associated cell lineage. Serum EGF did not play a role in the pathogenesis of Hp gastritis or of associated DU ulcer disease.     

RAPID HEALING OF PEPTIC ULCERS IN PATIENTS RECEIVING FRESH CABBAGE JUICE

Thirteen patients with peptic ulcer were treated with fresh cabbage juice, which, experiments have indicated, contains an antipeptic ulcer factor. This factor (vitamin U) prevents the development of histamin-induced peptic ulcers in guinea pigs.The average crater healing time for seven of these patients who had duodenal ulcer was only 10.4 days, while the average time as reported in the literature, in 62 patients treated by standard therapy, was 37 days.The average crater healing time for six patients with gastric ulcer treated with cabbage juice was only 7.3 days, compared with 42 days, as reported in the literature, for six patients treated by standard therapy.The rapid healing of peptic ulcers observed radiologically and gastroscopically in 13 patients treated with fresh cabbage juice indicates that the anti-peptic ulcer dietary factor may play an important role in the genesis of peptic ulcer in man.     

Antacid talcid activates in gastric mucosa genes encoding for EGF and its receptor. The molecular basis for its ulcer healing action.

In previous studies [Gut 35 (1994) 896-904], we demonstrated that antacid talcid (TAL) accelerates gastric ulcer healing and provides better quality of mucosal restoration within the scar than the omeprazole (OME). However, the mechanisms of TAL-induced ulcer healing are not clear. Since growth factors promote cell proliferation, re-epithelization, angiogenesis and ulcer healing, we studied whether TAL and/or OME affect expression of epidermal growth factor (EGF) and its receptors (EGF-R) in both normal and ulcerated gastric mucosae. Rats with or without acetic acid-induced gastric ulcers (n = 64) received i.g. twice daily 1 mL of either: A) placebo (PLA); B) TAL 100 mg; or C) OME 50 mg x kg(-1) for 14 d. Studies of gastric specimens: 1) ulcer size; 2) quantitative histology; 3) expression of EGF mRNAs was determined by RT/PCR; 4) gastric sections were immunostained with antibodies against EGF and its receptors. In non-ulcerated gastric mucosa of placebo or omeprazole treated group, EGF expression was minimal, while EGF-R was localized to few cells in the mucosal proliferative zone. Gastric ulceration triggered overexpression of EGF and its receptor in epithelial cells of the ulcer margin and scar. In ulcerated gastric mucosa TAL treatment significantly enhanced (versus PLA and omeprazole) expression of EGF and EGF-R. OME treatment reduced expression of EGF in ulcerated mucosa by 55 +/- 2% (P < 0.01). It is concluded that: 1) treatment with TAL activates genes for EGF and its receptor in normal and ulcerated gastric mucosae; 2) since EGF promotes growth of epithelial cells and their proliferation and migration, the above actions of TAL provide the mechanism for its ulcer healing action and improved (versus OME) quality of mucosal restoration.     

Role of nuclear factor-kappaB in gastric ulcer healing in rats

We investigated the role of nuclear factor-kappaB (NF-kappaB) in gastric ulcer healing in rats. NF-kappaB was activated in ulcerated tissue but not in normal mucosa, and the level of the activation was decreased with ulcer healing. NF-kappaB activation was observed in fibroblasts, monocytes/macrophages, and neutrophils. Treatment of gastric fibroblasts, isolated from the ulcer base, with interleukin-1beta activated NF-kappaB and the subsequently induced cyclooxygenase-2 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) mRNA expression. Inhibition of activated NF-kappaB action resulted in suppression of both their mRNA expression and increases in PGE(2) and CINC-1 levels induced by interleukin-1beta. Persistent prevention of NF-kappaB activation caused an impairment of ulcer healing in rats. Gene expression of interleukin-1beta, CINC-1, cyclooxygenase-2, and inducible nitric oxide synthase in ulcerated tissue had been inhibited before the delay in ulcer healing became manifest. The increased levels of cyclooxygenase-2 protein and PGE(2) production were also reduced. These results demonstrate that NF-kappaB, activated in ulcerated tissue, might upregulate the expression of healing-promoting factors responsible for gastric ulcer healing in rats.