Study of gastric carcinomas with special reference to intestinal metaplasia.

An attempt was made to classify 61 cases of gastric carcinomas according to Lauren's classification from the period January 1992-December 1993. All the gastrectomy specimens resected for carcinoma of stomach were included in the study. Of 61 cases, 57 were classifiable according to Lauren's criteria. 38 (62.3%) were of intestinal type and 19 (31.1%) were of diffuse type. 4 cases could not be classified into either group. There were significant correlation of type III intestinal metaplasia with intestinal type gastric carcinoma.     

Small early gastric cancer with special reference to macrophage infiltration.

The authors investigate the tumor-infiltrating cells in small early gastric cancer (EGC) (<10 mm) and describe the ultrastructural features and interactions of macrophages with tumor cells and other inflammatory cells. Sections from 20 small EGCs were stained by immunohistochemical methods for CD20, UCHL1, CD4, CD8, and CD68 (electron microscopic examination was used in 6 of the 20). In all of the tumors, CD68-positive macrophages accounted for most tumor-infiltrating cells, with UCHL1-positive T lymphocytes, eosinophils, and neutrophils being the next most frequent. We found only a few CD20-positive B lymphocytes. Electron microscopic analysis revealed macrophages with many phagocytic vesicles, cellular debris, and apoptotic bodies. These morphologic data show that macrophages are actively phagocytic. The tumor cells in contact with macrophages showed no cytopathic changes. These data do not support a macrophage-mediated cancer lysis like the ones reported in some systems in vitro. Contacts among macrophages and other inflammatory cells formed a recurrent ultrastructural hallmark and suggest a communication among varying inflammatory cell types during the precocious host response to gastric neoplasia.     

Peripheral glucagon-like peptide-1 (GLP-1) and satiation

Peripheral GLP-1 is produced by post-translational processing of pro-glucagon in enteroendocrine L-cells and is released in response to luminal nutrient (primarily carbohydrate and fat) stimulation. GLP-1 is well known for its potent insulinotropic and gluco-regulatory effects. GLP-1 receptors (GLP-1R) are expressed in the periphery and in several brain areas that are implicated in the control of eating. Both central and peripheral administration of GLP-1 have been shown to reduce food intake. Unresolved, however, is whether these effects reflect functions of endogenous GLP-1. Data collected in our laboratory indicate that in chow-fed rats: 1) Remotely controlled, intra-meal intravenous (IV) or intraperitoneal (IP) GLP-1 infusions selectively reduce meal size; 2) hindbrain GLP-1R activation is involved in the eating-inhibitory effect of IV infused GLP-1, whereas intact abdominal vagal afferents are necessary for the eating-inhibitory effect of IP, but not IV, infused GLP-1; 3) GLP-1 degradation in the liver prevents a systemic increase in endogenous GLP-1 during normal chow meals in rats; and 4) peripheral or hindbrain GLP-1R antagonism by exendin-9 does not affect spontaneous eating. Also, although our data indicate that peripheral GLP-1 can act in two different sites to inhibit eating, they argue against a role of systemic increases in endogenous GLP-1 in satiation in chow-fed rats. Therefore, further studies should examine whether a local paracrine action of GLP-1 in the intestine or and endocrine action in the hepatic-portal area is physiologically relevant for satiation.     

Pepsinogen A polymorphism in gastric mucosa and urine, with special reference to patients with gastric cancer

Electrophoretic pepsinogen A patterns were determined in gastric fundic mucosa biopsies from 601 patients with various gastric disorders and 25 healthy volunteers. Pepsinogen A patterns with an intense fraction 5 appeared to be associated with gastric cancer and premalignant changes of the stomach (p less than 10(-9)). In 60 individuals pepsinogen A patterns were determined in normal mucosa from different parts of the stomach. No differences were found between these patterns. In 29 out of 59 gastric cancer patients pepsinogen A could be demonstrated in the macroscopically malignant tissue. In two cases a different pattern compared with uninvolved fundic mucosa was observed. During a follow up study, major changes in the pepsinogen A pattern were observed in 7 out of 56 patients. In 8.6% of the examined patients urinary pepsinogen A patterns differed considerably as compared with the pattern observed in the gastric fundus. The results suggest that the highly significant association between intense Pg5 (the product of the D gene) and gastric cancer or its precursors may be caused by genetic as well as non-genetic factors.     

The relationship of gastrointestinal endocrine cells to gastric epithelial changes with special reference to gastric cancer.

Using advanced gastric adenocarcinoma and carcinoid as human material and gastric adenocarcinoma in rats induced by MNNG and in mice by localized X-irradiation of the stomach as experimental material, a pathological study was made on the relationship of gastric endocrine cells to gastric cancer. The results of the present study suggest that most of the endocrine cells in the cancer tissue are derived from the differentiation of cancer cells. Therefore, the following three may be given as the aformentioned relationship, that is, 1) carcinoid of endocrine cell origin, 2) endocrine cell carcinoma showing undifferentiated adenocarcinoma, and 3) endocrine cell cloning developed from the differentiation of cancer cell of adenocarcinoma. There is the possibility that most of 2) are of 3) origin and thus 2) and 3) should be discriminated from 1), having a functioning tumor in rare cases. The significance of reactive hyperplasia of endocrine cells in the non-metaplastic mucosa of the stomach around cancer and atypical epithelium is not yet determined, but that of EC cell seems at least to be related with the development of intestinal metaplasia in the gastric mucosa.     

胰高血糖素样肽-1及其类似物对心血管系统的影响

心血管病变是糖尿病常见的并发症,胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)作为一种肠促胰素,不仅具有葡萄糖浓度依赖性降糖作用、促进胰腺β细胞增生和修复、改善胰岛素抵抗,而且还可减轻体质量、调节脂质代谢、改善心血管危险因素。研究表明GLP-1可直接作用于血管内皮细胞和心肌细胞,对心血管系统可能具有保护效应。     

Thymoquinone activates imidazoline receptor to enhance glucagon-like peptide-1 secretion in diabetic rats

IntroductionThymoquinone (TQ) is one of the principal bioactive ingredients proven to exhibit anti-diabetic effects. Recently, glucagon-like peptide-1 (GLP-1) has been found to be involved in antidiabetic effects in rats. The aim of this study was to evaluate the mediation of GLP-1 in the antidiabetic effect of TQ and to understand the possible mechanisms.Material and methodsNCI-H716 cells and CHO-K1 cells were used to investigate the effects of TQ on GLP-1 secretion in vitro. In type 1 diabetic rats, the changes in plasma glucose and GLP-1 levels were evaluated with TQ treatment.ResultsThe direct effect of TQ on imidazoline receptors (I-Rs) was identified in CHO-K1 cells overexpressing I-Rs. Additionally, in the intestinal NCI-H716 cells that may secrete GLP-1, TQ treatment enhanced GLP-1 secretion in a dose-dependent manner. However, these effects of TQ were reduced by ablation of I-Rs with siRNA in NCI-H716 cells. Moreover, these effects were inhibited by BU224, the imidazoline I2 receptor (I-2R) antagonist. In diabetic rats, TQ increased plasma GLP-1 levels, which were inhibited by BU-224 treatment. Functionally, TQ-attenuated hyperglycemia is also evidenced through GLP-1 using pharmacological manipulations.ConclusionsThis report demonstrates that TQ may promote GLP-1 secretion through I-R activation to reduce hyperglycemia in type-1 diabetic rats.     

胎盘胰高血糖素样肽-1水平与胎儿出生体重关系的研究

目的探讨胎盘胰高血糖素样肽-1(GLP-1)水平与胎儿出生体重的关系。方法采用免疫组织化学SABC法检测30例分娩正常出生体重儿组(AGA组)、28例高出生体重儿组(LGA组)及28例低出生体重儿组(SGA组)胎盘组织中GLP-1的表达水平。结果①LGA组胎盘组织中GLP-1的表达水平低于AGA组,差异有统计学意义(P<0.05)。SGA组胎盘组织中GLP-1的表达水平高于AGA组,差异有统计学意义(P<0.05)。②胎盘组织中GLP-1的表达水平与胎儿出生体重呈负相关(r=-0.454,P<0.05)。结论胎盘组织中GLP-1表达水平的变化可能在胎儿出生体重的调节中起重要作用。     

Mucin histochemistry of pancreatic duct cell carcinoma, with special reference to organoid differentiation simulating gastric pyloric mucosa.

The present study was undertaken to explore mucins produced in normal, metaplastic, and hyperplastic ductal epithelia as well as in carcinoma tissues of the pancreas, and used a battery of histochemical techniques. Thirty-five cases of ordinary pancreatic duct cell carcinoma and nine cases of duct cell carcinoma, which fulfilled the clinical criteria of "mucin-producing carcinoma of the pancreas," were examined. The results indicated that all lesions of mucinous metaplasia with or without papillary hyperplasia as well as atypical hyperplasia characteristically had gastric mucins and showed organoid differentiation simulating the gastric pyloric mucosa, but never stained for 8-O-acetyl-N-acetylneuraminic acid, which is a histochemical marker of the large intestine. Ordinary duct cell carcinoma also contained gastric mucins and small intestinal mucins and showed organoid differentiation, but rarely had 8-O-acetyl-N-acetylneuraminic acid. Mucin-producing carcinomas were classified into two groups: the ordinary duct cell carcinoma group and a group that showed marked atrophy and extensive fibrosis of the parenchyma, a lack of organoid differentiation and gastric mucins, and an abundance of large and small intestinal mucins. These results suggest that gastrointestinal mucins are useful markers to detect cancer-related lesions and cancers of the pancreas.     

Distribution of glucagon-like peptide-1 immunoreactivity in the hypothalamic paraventricular and supraoptic nuclei

Glucagon-like peptide-1 (GLP-1) plays a role in modulating neuroendocrine and autonomic function. The hypothalamic paraventricular nucleus (PVN) contains aggregations of GLP-1 fibers and expresses GLP-1 receptors, making it a likely site of action for GLP-1 signaling. The current study was designed to establish domains of GLP-1 action, focusing on axosomatic appositions on different neuroendocrine and autonomic cell populations in the PVN. The data indicate abundant GLP-1-immunoreactive terminal appositions on corticotropin-releasing hormone neurons in the medial parvocellular PVN. GLP-1 positive boutons can also be observed in apposition to oxytocinergic neurons and on retrogradely labeled pre-autonomic neurons projecting to the region of the nucleus of the solitary tract. In contrast, there were very few vasopressinergic neurons with GLP-1 appositions. Overall, the data indicate that the central GLP-1 system preferentially targets neurons in hypophysiotrophic zones of the PVN, consistent with excitatory actions of GLP-1 on adrenocorticotropin release. GLP-1 is also in position to influence oxytocin secretion and control outflow to brainstem cardiovascular relays.     

胰高糖素样肽-1基因荧光真核表达载体的构建及鉴定

胰高糖素样肽-1（glucagon-like peptide-1,GLP-1）是近年来人们广泛关注的治疗糖尿病的最有前景的候选药物。pEYFP-N1是一系列绿色荧光蛋白（green fluorescent protein,GFP）的衍生蛋白之一,本实验构建了绿色荧光蛋白融合GLP-1基因的表达载体。该载体为糖尿病的进一步研究奠定了实验基础。