Differential DNA methylation status between breast carcinomatous and normal tissues

Breast cancer has been considered to be a multifactorial disease with a wide array of well-characterized gene mutations and chromosomal abnormalities. However, it is becoming evident that the onset or development of breast cancer also depends on epigenetic factors, although the mechanisms have not been fully elucidated. We performed a genome-wide analysis of DNA methylation of breast carcinomatous tissues and paired normal tissues to examine the differences in methylation between them. Methylation-specific polymerase chain reaction (MSP) was used to validate the hypermethylated genes screened out by DNA methylation microarray. We found that hypomethylation and hypermethylation occurred in 2753 and 1795 genes, respectively, in breast carcinomatous tissues. Meanwhile, gene ontology analysis and ingenuity pathway analysis revealed the function and pathway of several genes whose methylation status was altered in breast carcinomatous tissues. In addition, we investigated the promoter methylation status of four genes in breast carcinomatous tissue and paired normal tissues (n = 30) by MSP. Promoter hypermethylation of CRABP1, HOXB13, IFNGR2, and PIK3C3 was found in 37% (11/30), 23% (7/30), 17% (5/30), and 2% (2/30) of the carcinomas, respectively. Mutation of these four important genes was critical to many types of cancer. Our results suggest that DNA methylation mechanisms may be involved in regulating the occurrence and development of breast cancer.     

Purification and characterization of a pancreas cancer-associated antigen from normal colonic mucosa

Pancreas cancer-associated antigen (PCAAc) was extracted, isolated and purified from human normal colonic mucosa. Purified PCAAc from normal colonic mucosa was homogeneous, as determined by polyacrylamide disc gel electrophoresis. The PCAAc had a molecular weight of approximately 600 000 and consisted of 30% carbohydrate and 70% protein. It had an isoelectric point of 4.4, and migrated to the alpha 2-beta region on immunoelectrophoresis. It was apparently different from other known gastrointestinal mucus antigens. Antiserum against purified PCAAc did not react with normal human serum, pancreas, liver, spleen or lung, but did react with ascites fluid from a patient with pancreatic cancer. PCAAc appears to be a mucus antigen that is associated with pancreatic cancer.     

Characterization of gamma-glutamyltranspeptidase from human exocrine pancreatic carcinomas

Two different types of gamma-glutamyltranspeptidase (gamma-GTP) have been found in normal human pancreas following bromelain treatment. On the other hand, three human pancreatic ductal cell carcinomas have only a single type of gamma-GTP upon analysis with polyacrylamide gel electrophoresis, anion-exchange column chromatography and isoelectric focusing. Carcinoma gamma-GTPs were almost identical to one of the two types of normal pancreatic gamma-GTPs. The gamma-GTP from pancreatic carcinomas bound to anion-exchange column and was eluted at the same NaCl fractions as normal pancreatic gamma-GTP. The properties of pancreatic carcinoma-gamma-GTP, as assessed by binding to concanavalin A and lentil lectin affinity columns, were also similar to one of the two enzymes of normal pancreas. No apparent difference in isoelectric points was found between the carcinoma gamma-GTPs and one of the two normal pancreatic gamma-GTPs.     

Decrease in serum gamma-glutamyltranspeptidase following abstention from alcohol

When an alcoholic becomes abstinent, his serum 7-glutamyltranspeptidase decreases to normal in a few weeks according to an exponential law with a constant of 4.1 to 14.5 · 10^?2 days ^?1. It is thus valueless to establish 7-glutamyltranspeptidase reference values in a population in which all alcohol-drinking subjects have not been excluded.     

小型猪正常胰腺MRI表现

目的 探讨小型猪正常胰腺的MRI表现及其解剖学基础.方法 对8头健康小型猪行MR扫描,观察胰腺的形态、大小及信号强度.然后开腹观察所有猪的胰腺形态、位置和毗邻,同时术中探查胆总管和胰管的开口.术后处死2头,完整取出胰腺供解剖研究.结果 小型猪正常胰腺分左、中、右三叶,在MRI上均能清晰显示.整个胰腺T1加权像信号强度高于肝、脾,T2加权像信号强度低于肝、脾.MR胰胆管水成像未见胰管显影,但胆总管能清晰辨认.解剖发现胆总管开口在胃幽门稍下方的十二指肠上部,而胰管开口于胰右叶对应十二指肠内壁乳头.结论 小型猪正常胰腺MR成像显示良好;解剖上小型猪胰腺形态和胰胆管汇入方式与人类有所不同.     

Multimolecular forms of gamma-glutamyltranspeptidase

Seven % acrylamide gel electrophoresis, pH 8.9, followed by revelation in situ of enzymic activity allowed detection of multimolecular forms of serum gammaglutamyltranspeptidase. Five zones with enzymic activity were separated from normal adult sera, pregnant women's sera in the third month of pregnancy, and cord blood; a sixth band is inconstantly detected in this last. Additional enzymic fractions with slow migration were revealed from sera of patients with hepatobiliary diseases; however, serum gamma-glutamyltranspeptidase zymograms seem to have no diagnostic value in hepatobiliary diseases and in the detection of liver metastases.     

Characterization of human serum gamma-glutamyltranspeptidase

The contribution of proteolysis to leakage of gamma-glutamyltranspeptidase from the liver into the serum was examined by comparing the properties of human serum gamma-glutamyltranspeptidase with those of partially purified enzyme preparations solubilized from human liver with Triton X-100 and with papain. The Triton-solubilized enzyme was hydrophobic, whereas the papain-solubilized enzyme was hydrophilic. Serum gamma-glutamyltranspeptidase was found to be hydrophilic, since it could be extracted without addition of detergent after acetone treatment to remove bound cholate. The affinity of serum-gamma-glutamyltranspeptidase to concanavalin A-Sepharose was compared with those of the Triton-solubilized and papain-solubilized enzymes. All three enzymes were adsorbed to concanavalin A-Sepharose in 50 mmol/l imidazole buffer, pH 7.2. The serum enzyme and papain-solubilized enzyme were eluted with 100 mmol/l alpha-methylmannoside in 50 mmol/l imidazole buffer containing 1% Triton X-100. The molecular weights of the Triton-solubilized, papain-solubilized and serum-gamma-glutamyltranspeptidases were estimated as 98 000 +/- 2000, 90 000 +/- 2000 and 90 000 +/- 2000, respectively, by electrophoresis. These results show chemical similarities between the serum-gamma-glutamyltranspeptidase and papain-solubilized gamma-glutamyltranspeptidase.     

Correlation between estrogen receptor protein and carcinoembryonic antigen in normal and carcinomatous human breast tissue.

We determined estrogen receptor protein and carcinoembryonic antigen in cytosols prepared from 189 human breast carcinoma tissues, 85 benign or normal breast biopsies, and 101 tissue specimens metastatic from breast carcinoma. Carcinoembryonic antigen was observed in 70% of the primary carcinomatous tissues, 15% of the benign or normal specimens, and 51% of the metastases. Ninety-six of the 189 primary carcinomatous specimens with increased concentrations of carcinoembryonic antigen were also positive for estrogen receptor protein, whereas 67 of the 72 benign or normal biopsies with low concentrations of carcinoembryonic antigen were also negative for estrogen receptor protein. All five fenign specimens with positive estrogen receptor protein and normal carcinoembryonic antigen concentrations were from fibroadenomas. The concordance between estrogen receptor protein and carcinoembryonic antigen in the primary carcinomatous tissue was 66%, in metastatic carcinoma 51%, and in benign and normal tissue 85%.     

SD大鼠正常胰腺MRI表现

目的 观察SD大鼠正常胰腺MRI表现.方法 对9只健康SD大鼠行MR平扫及增强扫描,观察胰腺形态、分布、位置毗邻及信号特点.之后处死大鼠,观察其胰腺解剖及组织学表现.结果 共8只大鼠顺利完成MR扫描,1只因麻醉死亡.MRI显示胰腺位于胃、脾脏及左肾之间,分为胃叶、脾叶及十二指肠叶,汇合于胰腺结合部;脾叶信号强度＞十二指...     

CT观察与测量国人儿童正常胰腺

目的通过观察国人儿童正常胰腺CT图像,得到不同年龄段国人儿童胰腺不同部位径线CT测量值的参考范围,为判断儿童胰腺形态、大小异常提供依据。方法选取接受腹部CT增强扫描的无胰腺疾病及其他相关疾病儿童200例,按年龄分为婴儿期(<1岁)、幼儿期(1～2岁)、学龄前期(3～6岁)、学龄期(7～12岁)和青春期(13～16岁),测量每组胰头左右径、胰颈前后径和胰体前后径的最大径线长度,并进行统计学处理。结果胰头左右径、胰颈前后径和胰体前后径最大径线长度在婴儿期分别为(11.50±3.24)mm、(6.60±2.11)mm、(9.52±3.37)mm,幼儿期分别为(15.28±3.38)mm、(9.16±3.01)mm、(14.67±1.61)mm,学龄前期分别为(17.66±4.99)mm、(11.05±3.48)mm、(17.26±1.98)mm,学龄期分别为(18.87±4.06)mm、(12.04±4.25)mm、(19.83±3.91)mm,青春期分别为(21.71±7.60)mm、(15.76±1.82)mm、(22.93±4.37)mm;不同年龄期胰腺各部位的径线随着年龄的增加而增加差异有统计学意义(P<0.05);同年龄期不同胰腺部位间径线长度的差异有统计学意义(P<0.05)。结论本研究初步得到不同年龄段国人儿童胰腺径线的相关正常值,可作为检测儿童胰腺疾病发生、转归提供重要依据。     

Vagal influence on exocrine pancreas of alcohol-fed and of normal dogs

A histochemical study has indicated increased activity of acetylcholine in the pancreas of chronic alcoholic dogs, and we have recently reported decrease pancreatic responsiveness to cholinergic stimulation in such dogs. This prompted us to determine, in chronic alcoholic dogs, the net pancreatic response to stimulation mediated by cholinergic nerves. Therefore, the pancreatic response to vagal stimulation by intravenous 2-deoxy-d-glucose (2DG) infusion was examined in such dogs and in controls. After 2DG, 100 mg kg-1, significant and similar increases in protein output up to maximally 2.7 +/- 0.8 and 2.3 +/- 0.5 mg kg-1 (15 min)-1 were observed in control and alcohol-treated dogs. A significant rise in flow rate and HCO-3 output up to maximally 0.26 +/- 0.07 ml kg-1 (15 min)-1 and 43 +/- 13 mumol kg-1 (15 min)-1, respectively, occurred in the controls but was delayed in the alcoholics. The finding in alcoholic dogs of no change in protein response to 2DG is not in favour of a primary increase of vagally mediated pancreatic protein secretion. It could, however, be compatible with a primary increase in cholinergic receptor resistance due to alcohol and secondary adaptive increase in cholinergic activities, which when combined, would yield no net change of the cholinergically mediated protein response.     

Age-related morphology of the normal pancreas on computed tomography

Abdominal computed tomographic scans were performed on a group of 360 patients between the ages of 20 and 80 years. The anteroposterior diameter of the pancreatic head, body, and tail, the age-related ratio of vertebral body-pancreas diameter, and the external and internal contours of the organ were analyzed. The age-related changes in the pancreas were compared with known anatomical findings.     

The normal pancreas: acoustic characteristics and frequency of imaging.

This article reports the results of a study designed to evaluate both pancreatic echogenicity and success of visualizing recognizable pancreatic tissue. The acoustic characteristics of the normal pancreas were compared with those of the liver. Of 100 scans reviewed, 65 scans (65 percent) depicted recognizable pancreatic tissue. Two cases were discarded on the basis of hepatocellular disease, and one case was discarded because of hepatic metastases. Thirty-two cases demonstrated pancreatic echogenicity greater than that of the liver, and 30 cases demonstrated pancreatic echogenicity equivalent to that of the liver. We found no normal pancreas that displayed less echogenicity than the liver. A hypothesis is offered to explain the observed results.     

Dietary vitamin D is essential for normal insulin secretion from the perfused rat pancreas.

We have reported previously that arginine-induced insulin secretion was impaired in the vitamin D-deficient rat pancreas, and that it was improved by dietary vitamin D repletion (Norman, A. W., B. J. Frankel, A. M. Heldt, and G. M. Grodsky, 1980, Science [Wash. DC]. 209:823-825). In this study, we evaluate in the perfused rat pancreas system whether the effects of vitamin D and its metabolites on insulin secretion are direct in action on the pancreas and limited to the secretagogue arginine, or whether they are secondary to the hypocalcemia or reduced caloric and calcium intake associated with vitamin D deficiency. In an experiment where vitamin D-replete (+D) rats were pair-fed to D-deficient (-D) rats fed ad lib., the secretion of insulin in response to arginine infusion in the +D perfused rat pancreas was threefold higher than in the -D control. In a second experiment, the serum calcium level was elevated from the characteristic hypocalcemic level of -D rats (4.9 +/- 0.1 mg/dl) to a normal calcemic level (10.0 +/- 0.3 mg/dl) by feeding the rats a -D diet with dietary calcium levels ranging from 0.4 to 4%. In these -D rats, the pancreatic perfusion study with the secretagogue arginine showed a similar blunted insulin secretion response in all groups in spite of the significant differences of serum calcium levels. In a third experiment, insulin secretion in response to the separate administration of arginine (10 mM), glucose (16.9 mM), and tolbutamide (0.37 mM) was found to be significantly higher in pair-fed, normocalcemic +D rats than in -D rats with normal calcium levels. These results indicate that vitamin D or its metabolites are essential for normal insulin secretion and that the dietary intake of calcium and the resulting serum calcium levels play a lesser role than vitamin D availability in mediating insulin secretion.