Cholera Toxin B-Mediated Targeting of Lipid Vesicles Containing Ganglioside GM1 to Mucosal Epithelial Cells

Purpose. To determine whether the non-toxic pentameric B subunit of Cholera toxin (CTB) binding to ganglioside GM1 on both the lipid vesicles and epithelial cells may provide a means to target lipid vesicles to mucosal cells expressing surface GM1. Methods. Sonicated lipid vesicles containing ganglioside GM1 were prepared. Inter-vesicle cross-linking due to pentameric CTB binding to these GM1 vesicles was determined with a sub-micron particle analyzer. Association of CTB to GM1 vesicles was analyzed with continuous sucrose gradient centrifugation. CTB-mediated binding of GM1 vesicles to human mucosal epithelial cells (Caco-2 and HT-29), mucous membranes of mouse trachea, and nasal tissues were detected with fluorescent labeled vesicles. Results. An increase in lipid particle size due to binding of CTB to lipid vesicles and inter-vesicles cross-linking was detected. At a 30-to-1 mole ratio of membrane-bound GMl-to-CTB, optimum increase in GM1 vesicle aggregation, was detected. Under such conditions, all the added CTB molecules were associated with GM1 vesicles. Time course analysis showed that inter-vesicles cross linking by CTB was detectable within 10 min. and reached a maximum value at 60 min. CTB associated GM1-vesicles bind to mucosal epithelial cells HT-29 and Caco-2 with similar affinity [K_d = 7.8 × 10^–4 M lipid (Caco-2) and 7.6 × 10^–4 M lipid (HT-29)]. GM1 mediated binding specificity was demonstrated by blocking with anti-GMl antibody and the insignificant degree of CTB-associated GM1 vesicle binding to GM1 deficient C6 cells. Conclusions. The CTB-mediated GM1 binding to multiple membrane surfaces provides selective localization of GM1 vesicles to GM1 expressing mucosal cells and tissues. The strategy may be useful in localizing drugs and proteins to gut and respiratory tract mucosa.     

Development of intestinal epithelial cell lines using a transgenic mouse

The epithelial cells of the colonic mucosa of the animal have proved impossible to culture using standard tissue culture techniques. Immortalization of adult colonic epithelial cells has been unsuccessful due to the lack of DNA synthesis in these cells once they are isolated from the tissue. Recently an unique transgenic mouse bearing a temperature sensitive mutant of the known immortalizing gene, SV40 large T has become available. The advantage of this mouse is that the SV40 large T gene is expressed in every cell. Active immortalizing protein is produced in each cell at the permissive temperature. We have used colonic mucosa from these mice to initiate cultures of epithelial cells from the colon of adult mice. The cells grow readily at the permissive temperature but die within 7 days at the non-permissive temperature. The methods used to develop these cultures are described.     

The Influence of a New Timing Strategy of Band Adjustment on the Vomiting Frequency and the Food Consumption of Obese Women Operated with Laparoscopic Adjustable Silicone Gastric Banding (LAP-BAND)

Objective: To evaluate the effects of a new timing strategy of band adjustment on the short-term outcome of obese women operated with adjustable silicone gastric banding. Subjects: The outcome of 30 women without binge-eating disorder operated with laparoscopic adjustable silicone gastric banding with a wider intraoperatory band calibration (LAP-BAND) was compared to that of 30 body mass index-matched women without binge-eating disorder previously operated with adjustable silicone gastric banding (ASGB) applied by laparotomy with the usual intraoperatory band calibration. The patients were evaluated 3, 6 and 12 months after surgery. Measurements: (1) weight loss; (2) total daily energy intake; (3) percent as liquid, soft or solid food; (4) vomiting frequency; (5) rate of postoperative percutaneous band adjustments; (6) rate of band-related complications. Results: Both the weight loss and the daily energy intake did not differ between patients with LAP-BAND and patients with ASGB. After surgery, the patients with LAP-BAND ate more solid food and less liquid food than the patients with ASGB. Vomiting frequency was higher in patients with ASGB than in patients with LAP-BAND. The total number of percutaneous band adjustments was higher in women with LAP-BAND than in women with ASGB. Band inflation because of weight stabilization was performed in six (20.0%) women with ASGB and in 19 (63.3%) women with LAP-BAND. Neostoma stenosis occurred in one women with ASGB, but in none of the women with LAP-BAND. One patient with LAP-BAND presented band slippage. Conclusions: The wider intraoperatory band calibration performed in patients with LAP-BAND did not reduce the short-term efficacy of adjustable silicone gastric banding. This new timing strategy of band adjustment required more postoperative percutaneous band inflations, but it improved the eating pattern of the patients (low vomiting frequency and high intake of solid food).     

乙酰胆硷和电刺激迷走神经对HC1引起的大鼠胃粘膜损伤的保护作用

本工作观察了乙酰胆硷(Ach)和电刺激迷走神经对0.6N HCl引起的胃粘膜出血性损伤的保护作用,发现皮下注射50μg/kg的氯化Ach和电刺激膈下迷走神经5min,可明显降低HCl引起的胃粘膜出血量,这一作用可被消炎痛及阿托品所阻断。提示这种保护作用是通过依赖于M-受体的内源性前列腺素。     

门脉高压性胃病患者的胃壁血气变化

作者观测了４３例门脉高压症患者股动脉血ＰＯ２、胃网膜有动静脉胃壁支血ＰＯ２、胃壁支静脉及肘静脉血ｐＨ、ＨＣＯ３－和胃网膜右静脉压力，其中２３例并有非出血期门脉高压性胃病。结果表明：①门脉高压症患者的股动脉血ＰＯ２低于对照组；②门脉高压症患者胃网膜右动静脉胃壁支血氧分压差低于对照组，胃网膜右静脉压力高于对照组，胃壁支静脉血ｐＨ和ＨＣＯ３－低于对照组和同组肘静脉血。并有门脉高压性胃病者这些变化更为显著。提示门脉高压性胃病的发病机制在于门脉系压力增高、胃粘膜下动静脉短路开放、胃粘膜缺血缺氧和胃壁局部酸中毒。     

Reduced Expression of nm23 Is Associated with Metastasis of Human Gastric Carcinomas

Reduced expression of nm23 gene is implicated in high metastatic potential In a variety of malignancies. To elucidate the role of nm23 in human gastric carcinomas, we examined loss of heterozygosity (LOH) of nm23 gene by Southern blotting, nm23 mRNA expression by Northern blotting and nm23 protein expression by Western blotting as well as immunohistochemistry in both primary and metastatic tumors. LOH of nm23 gene was found in 2 (8%) out of the 23 informative gastric carcinomas. Twenty-two (84%) out of the 26 cases expressed nm23 mRNA at higher levels in primary tumor tissue than in corresponding non-neoplastic mucosa. No obvious correlation was observed between clinico-pathological features and LOH of nm23 gene or nm23 mRNA expression. On the other hand, 52% of the gastric carcinomas showed reduction of nm23 immunoreactivity in the metastatic tumor of regional lymph nodes, as compared to the primary tumor. Interestingly, 71% of the gastric carcinomas showed weaker nm23 immunoreactivity in the liver metastasis than in the primary tumor. These results suggest that nm23 overexpression is linked with development of gastric carcinomas and the decrease in expression of nm23 participates in metastasis.     

Treatment of gingival lichen with free palatal grafts

BACKGROUND: Recalcitrant gingival erythematous lichen planus/lichenoid lesions comprise a considerable therapeutic problem. The objective of this study was to evaluate the therapeutic effect of grafting keratinized oral palatal mucosa to the sites of gingival lichen. METHODS: In 12 patients 20 grafts were transplanted to buccal gingival lesions. Mean age of the patients was 59.8 +/- 7.1 years (range 46-71 years). The mean observation time was 32 +/- 32.7 months (range 5-97 months). RESULTS: On a 4-point clinical grade scale (0-3), 12 (60%) transplants showed complete healing grade 3, six (30%) grade 2 and two (10%) grade 1. CONCLUSIONS: Using oral mucosal grafts from the palatal mucosa for the treatment of recalcitrant erythematous gingival lichen planus/lichenoid lesions seems to be a promising treatment modality.     

改良Millard法修复单侧重度完全性唇裂

目的：探讨一种修复重度完全性单侧唇裂的方法。方法：应用改良Mi11ard法与裂隙缘粘膜瓣联合应用修复单侧重度完全性唇裂，笔者自2000年始应用此法对单侧完全性重度唇裂的鼻槛修复及口、鼻瘘口封闭、鼻堤重建效果满意。21例患者创口均Ⅰ期愈合。所有病例经术后复查效果满意。结果：该组病例在唇裂修复的同期行口、鼻瘘口之完善封闭。结论：此方法适用于单侧重度完全性唇裂且齿槽骨裂隙较宽大者。     

Admission rates for peptic ulcer in the Trent Region, UK, 1972–2000: Changing pattern, a changing disease?

BACKGROUND AND AIM: Peptic ulcer disease is believed to be less common and less severe as a result of modern medical treatment. We therefore examined changes in the admission rates for patients with duodenal ulcer and gastric ulcer, both emergency (for haemorrhage, perforation or severe pain) and for elective surgery, before and since the introduction of the new advances in therapy. These admission indices reflect disease prevalence and severity. PATIENTS AND METHODS: We identified admission rates during 1972--2000 within the Trent Regional Health Authority, UK (population 4.7 million), from computerised patient information using diagnostic search codes ICD8-10 and expressed as rates per million resident population. Drug expenditure details were obtained from the Department of Health. RESULTS: Emergency admission rates as a whole changed little, a decline in the young being offset by an increase in the elderly. Haemorrhage was the most common reason (approximately 115 per million for duodenal ulcer and 87 for gastric ulcer) throughout [compared with perforation (80 and 21) and pain (90 and 68)]. In contrast, elective surgery has almost disappeared; this reduction began before the introduction of modern treatment. CONCLUSION: Emergency admission rates for duodenal and gastric ulcer for complications or severe pain have fluctuated over the last three decades but with little overall change. In contrast, elective surgery has declined dramatically, as a result of advances in treatment but also from changes in the natural history.     

OK-432增强人腹腔抗癌免疫功能的研究

目的　探讨腹腔内注射OK - 4 32增强腹腔免疫功能的机制。方法　选择非炎症和非肿瘤手术患者作为实验对象 ,实验组分别于手术前 72小时、4 8小时和 2 4小时腹腔内注射 4KE的OK - 4 32。开腹后采集腹腔内巨噬细胞 ,并用人胃癌MKN1细胞作为靶细胞对巨噬细胞的癌细胞毒性进行分析。同时采集大网膜 ,对大网膜乳斑的数量和面积进行了观察分析。结果　OK - 4 32显著增加了腹腔内巨噬细胞的数量 (P <0 .0 5 )、增强了巨噬细胞的吞噬活性和酶活性 (P <0 .0 5 )、增加了NO的分泌和巨噬细胞的癌细胞毒性 (P <0 .0 5 ) ,以及大网膜乳斑的数量和面积 (P <0 .0 5 )。结论　手术前腹腔内注射OK - 4 32可以作为预防癌细胞腹腔内种植转移的有效方法。