ObjectiveTo explore the relationship between the -2548 G/A functional polymorphism in the 5′ promoter region of the leptin gene and gallstones. Methods The -2548 G/A polymorphisms of leptin gene were determined by polymerase chain reactionrestriction fragment length polymorphism technology (PCRRFLP) in 118 patients with cholesterol gallstones and 53 normal control subjects. Then the allele and genotype distribution were studied. Results The distribution of leptin2458 G/A in two groups was statistically significantly different: the genotype frequency of AA+GA of patients in gallstone group was higher than that in control group (χ2=4.251, P=0.039). AA+AG genotype had 2.813 times greater risk for gallstone disease compared with GG genotype (OR=2.813, 95% CI=1.020-7.757). Allele frequency distribution in the two groups was different: the allele frequency of A of patients in gallstone group was higher than that in control group (χ2=5.791, P=0.016). The risk of gallstone disease in the A alleles carriers was 1.777 times as higher as the carriers of G alleles (OR=1.777, 95% CI=1.110-2.844). ConclusionThe -2548 G/A polymorphism in the 5′ promoter region of leptin gene is significantly correlated with the gallstones. The A alleles of leptin may be a genetic factor which contributes to individual susceptibility for gallstone, while the G alleles of leptin may be a genetic factor that prevents people from gallstone.
Objective To explore the expression of tumor necrosis factor (TNF) mRNA, TNF and TNFR in the gallbladder mucosa which developed from hyperplasia, dysplasia to carcinoma, and to further discuss the relationship between TNF and pathogenesis of gallbladder carcinoma. Methods In situ hybridization and immunohistochemistry were used to determine TNF mRNA, TNF protein and TNFR protein expression in hyperplasia, dysplasia and carcinoma of gallbladder. Results ①No one of 20 cases of gallbladder hyperplasia was found to express TNF mRNA, while 4 of 20 (20%) cases of dysplasia and 18 of 20 (90%) cases of carcinoma were found to express TNF mRNA (P＜0.05). ②For the expression of TNF mRNA in mononuclear cells (MNC), positive staining was found in 15% of gallbladder hyperplasia, 85% of dysplasia and 90% of carcinoma, respectively (P＜0.05). The cell numbers of positive staining MNC were 4.85±1.50, 6.00±2.71 and 9.33±3.07, respectively (P＜0.05). ③In gallbladder carcinoma, the cell number of carcinoma and MNC with positive TNF mRNA expression was correlated with clinical stage (P＜0.05). The higher the clinical stage, the more the positive staining cell numbers. The positive staining cell numbers of carcinoma in stage Ⅰ-Ⅲ and Ⅳ-Ⅴ were 9.13±4.39 and 14.80±4.02, respectively (P＜0.01), and the positive staining cell numbers of MNC were 7.13±2.53 and 11.10±2.23, respectively (P＜0.05). ④The cell numbers of carcinoma and MNC with TNF mRNA expression increased with tumor size. In tumors with diameter over 2 cm and less than 2 cm, the positive staining cell numbers of carcinoma were 14.00±4.20 and 8.83±4.96, respectively (P＜0.05), and that of MNC were 10.50±2.54 and 7.00±2.83, respectively (P＜0.05). ⑤The region of TNF protein expression was similar to that of TNF mRNA, but TNF protein expression was more frequent and wider than that of TNF mRNA. ⑥The tumor necrosis factor receptor was expressed in tumoral vascular endothelial cells and MNC in all cases of carcinoma, but was negatively stained in mucosa epithelial cells and tumor cells of all cases. ⑦There was positive linear correlation in TNF mRNA between tumor cell and MNC (r=0.687, P＜0.01), same as that in TNF protein expression (r=0.742, P＜0.01); and there was positive linear correlation in tumor cell between TNF mRNA and TNF protein expression (r=0.847, P＜0.01), same as that in MNC (r=0.643, P＜0.01). Conclusion The TNF mRNA and TNF protein expression are increasing during the development of gallbladder mucosa epithelial from hyperplasia, dysplasia to carcinoma, and increasing with tumor stage. It suggests that TNF may contribute to carcinogenesis of gallbladder carcinoma induced by gallstone, and related to the progression of gallbladder carcinoma.
ObjectiveTo study the relationship between cholecystectomy and Helicobacter pylori （Hp） infection. MethodsOne hundred and eleven patients with cholecystolithiasis were chosen as the investigation group, while 577 patients with upper digestive tract symptoms without cholecystolithiasis as the control group. All the patients took the 13C breath test to determine whether they were infected by Hp. All the patients with Hp infection continued eradical therapy for Hp infection for one course after cholecystectomy and were followed up on outpatient basis. ResultsThe infection rate in the investigation group was 45.9%, while 27.4% in the control group. During the 3 to 6 months of followup for the patients undergoing eradical therapy for Hp infection, we found no patient complaining of epigastric pain, malaise, belching and nausea. ConclusionThe infection rate of Hp in patients with cholecystolithiasis is high, Hp may be one of the factors causing “postcholecystectomy syndrome”. Eradical therapy for Hp after cholecystectomy will help improve the effects of operation.
Objective To probe into disorder of plasma lipids and apolipoproteins in patients with gallstone,and their position and function in formation of gallstone. MethodsConcentration of plasma lipids and apolipoproteins in 94 healthy subjects and 161 patients with gallstones was investigated. ResultsThe gallstone group had a higher serum mean concentration of TG,Apo CⅡ,Apo CⅢ, and had a lower serum mean concentration of TC，HDLc，HDL2c，HDL3c and LDLc as compared with the control group (P＜0.01 or P＜0.05). Conclusion Higher serum mean concentration of TG，Apo CⅡ，Apo CⅢ, and lower serum mean concentration of TC, HDLc, HDL2c, HDL3c and LDLc, are characteristic of lipids metabolism and important cause of formation of gallstone.
Objective To discuss the relationship between motilin, vasoactive intestinal peptide and the gallstone formation. Methods The level of motilin, vasoactive intestinal peptide in plasma, bile and gallbladder tissue of 48 cases of chololithiasis before operation and the first, third, seventh day after cholecystectomy were mesured by radioimmunoassay. Results The level of motilin in plasma was markedly increased in patients with chololithiasis before cholecystectomy and the first day after cholecystectomy. The level of motilin, vasoactive intestinal peptide in bile and gallbladder tissue were significantly increased in patients and motilin was positively correlated with vasoactive intestinal peptide in the gallbladder tissue. Conclusion Motilin, vasoactive intestinal peptide might affect the gallstone formation by affecting the motility of gallbladder.
Objective To study the effects of glucose and lipid metabolism on gallstone formation. Methods Twenty five patients with gallstones and 25 normal volunteer controls were studied from January to April in 1998. The patients were well matched the control with sex and age (1∶1). In the study, Body Mass Index (BMI) and Waist-to-Hip circumference ratio (W/H) were measured. Blood glucose, glucosylated hemoglobin (HbA1C), insulin, C peptide and all parameters of lipids were detected at fasting state. The glucose,insulin, C peptide were detected again at 2-hour after taking 75g glucose orally.Results The result showed there was no difference on BMI and W/H between the patients and controls. HbA1C、mean fasting and 2hour glucose concentration were not in significantly different between the two groups (Pgt;0.05, Pgt;0.2, Pgt;0.1 respectively). There were 10 patients with abnormal glucose metabolism (7 with NIDDM, 3 with IGT), but only 4 controls were abnoumal (one with NIDDM, three with IGT). The difference was significant (Plt;0.05). Furthermore, the mean fasting and 2hour insulin concentration of gallstone group was higher than that of the control (Plt;0.02, Plt;0.05). And the gallstone group had a higher fasting C peptide concentration than control (Plt;0.05). There was no statistical difference on the parameters of plasma lipid between the tow groups. Conclusion The study suggests that diabetes mellious and hyperinsulinemia acted as an important role on gallstone formation.
To study bacterial changes of bile, to detect relationship between formation of core of gallstones and bacterial infection. Floras of bacteria in bile were studied in patients with gallstones by using aerobic, anaerobic and Lforms (X, Y,L) culturing system.Results: Bacterial growth positive was found in 88 of 98 patients in which single bacterial growth accounted for 54 cases, multiple growth 34 including type X 83, type L 23 and type Y 5. The results show that some alteration of bacteria flora exists during biliary infection and S. Liguefaoiens and E. Coli are the most frequent bacteria present. Formation of the core of gallstone might be related with bacterial infection.
To investigate the origin and releasing relation of motilin (MTL), vasoactive intestinal peptide (VIP) and somatostatin (SS) in guinea pig bile as well as its effects during gallstone formation. Guinea pig were divided into three groups: control group (50 animals), on normal diet; lithogenic group (70 animals), fed with lowprotein low fat; and recovering group (50 animals), fed with lowprotein low fat and recovering normal food after the experiment of gallstone formation. MTL, VIP and SS in the bile gallbladder tissue and portal vein plasma of the normal control group were measured with radioimmunoassay. Meanwhile the changes of the gut peptides in the bile and the bile components from different groups were also compared. Results: In control group the levels of MTL, VIP and SS in the bile were higher than those in the plasma, but, obviously lower than those in the tissues, the concentration relationship between in the bile and in the tissue was a positive correlation. In contrast to the control group, MTL concentration decreased but VIP and SS increased in the bile of the lithogenic group, the physicochemical nature of the bile also became lithogenic. In the recovering group the bile also became lithogenic, but, the concentration of those peptides and the nature of the bile all got normal. Conclusion: MTL, VIP and SS in guinea pig bile originate mainly form the gallbladder wall tissues. Food components affect the levels of the gut peptides in bile, which promote the bile lithogenic changes and gallstone formation.
To study the mechanism of cholesterol gallstone formation, rabbit models were induced by feeding with high cholesterol diet. Bile acids were tested with bi-wavelengh thin layer scan and low density lipoprotein receptor activity of hepatocytes binding to 125I-LDL were tested with radio immunoassay in different feeding phases as 1,2,3 and 4-week groups, as well as the control group. The results showed that cholesterol gallstones in 2,3 and 4-week groups were induced in respectively. The contents of glucocholic acid (GCA) in bile were decreased significantly (vs control group, Ｐ＜0.05). The Bmax values of LDL receptor of hepatocytes binding to 125I-LDL were decreased significantly (Ｐ＜0.05). Kd values of those gradually increased (Ｐ＜0.05). These suggest that the decreased activity of LDL receptor of hepatocytes would reduce the synthesis of GCA, thus resulting in the formation of cholesterol gallstones.
Using radioimmunoassay (RIA) and immunohistochemical LASB technique, the level of serum estradiol (E2), testosterone (T), progesterone (P), estrogen receptors (ER) and progesterone receptors (PR) in 30 male patients with gallstones were detected. The results showed that the level of serum P, E2/T and PR was higher. This suggests that the metabolic disorder of gonadal hormones play an important role in gallstone formation.