人胎胰腺GnRH免疫反应细胞

目的：探讨促性腺激素释的激素(GnRH)免疫反应细胞在人胎胰腺的存在部位和数量变化。方法：用免疫组织化学SABC法，对37例第10-32w人胎胰腺内的GnRH-IR细胞进行观察，并用体视方法分析其数量变化。结果：人胎胰腺GnRH-IR细胞出现于第13w，其数密度随胎龄增加而增大；分布于胰岛及外分泌部的腺泡上皮、导管上皮细胞间。位于胰岛的GnRH-IR细胞呈圆形、卵圆形或多边形。位于腺泡上皮细胞间的GnRH-IR细胞多为锥体形，外分泌部的GnRH-IR细胞均为开放型细胞。结论：胰腺GnRH-IR细胞于胚胎第13w出现，广泛存在于内、外分泌部，其数量随胎龄增加而增加。     

Complete absence of bile and pancreatic ducts in a newborn: a new entity of congenital anomaly in hepato-pancreatic development

We examined a newborn who had no bile and pancreatic ducts. Hydrops was evident after 29 weeks of gestation and she died shortly after birth, weighing 1,368 g. One of her siblings had died of hydrops at about six months of gestation, and there were two more miscarriages of unknown cause. At autopsy on the newborn, the liver had an abnormally round shape and the pancreas was not in the normal position. There was an ectopic small pancreas with normally developed islets. Histological analysis revealed the complete absence of extra- and intra-hepatic bile and pancreatic ducts. Immunostaining of these tissues showed no positive bile duct marker staining using epithelial membrane antigen and cytokeratin 19 in the liver. Albumin and -fetoprotein staining was positive in the liver, and insulin and glucagon staining was positive in the remaining islets. Thus, this case is characterized by complete absence of bile and pancreatic ducts. These findings suggest the existence of a gene linked to the development of bile and pancreatic ducts.     

Chronic pancreatitis as a predisposing factor in the development of pancreatic cancer. Histological and histochemical studies

The frequency of hyperplasia, squamous metaplasia and dysplasia were examined in glandular tissue from 20 pancreatic specimens resected due to chronic inflammation. Hyperplasia of the epithelium of large pancreatic ducts with formation of papillomatous outgrowths was present in 6 cases. Epithelial hyperplasia of small ducts occurred in 10 cases. Dysplasia and squamous metaplasia of the epithelium of ducts, hypertrophy, hyperplasia and dysplasia of acinar cells were found in 7 cases. In 10 pancreatic specimens hypertrophy and hyperplasia of cells of the islets of Langerhans were noted. Increased histochemical reactions to dehydrogenases and proteinic thiol groups were present in epithelial cells which demonstrated hypertrophy, hyperplasia, metaplasia or dysplasia. Diminution of the PAS reaction to neutral glycoproteins and intensification of the reaction to acid glycoproteins were also noted in the ductal epithelium. The results obtained suggest that chronic inflammation of the pancreas should be clinically regarded as predisposing to the development of pancreatic cancer.     

Simultaneous alpha-1-antitrypsin accumulation in liver and pancreas

Inclusions positive for periodic acid-Schiff, resistant to diastase, and immunoreactive to alpha-1-antitrypsin (AAT) were found in hepatocytes and pancreatic islet cells of a patient with clinical and pathologic features of AAT deficiency. Alpha-1-antitrypsin was detected in all pancreatic islets, and AAT-positive cells were observed in the excretory pancreatic ducts. These findings suggest that the pancreas synthesizes AAT and possibly serves as a "storage" place in AAT deficiency. Intercalated cells in the excretory pancreatic ducts may be an additional source of AAT.     

Keratinocyte growth factor induces pancreatic ductal epithelial proliferation.

Keratinocyte growth factor (KGF) causes a proliferation of pancreatic ductal epithelial cells in adult rats after daily systemic administration for 1 to 2 weeks. Even before the proliferation of intralobular ducts is histologically evident, KGF also induces proliferating cell nuclear antigen expression within the ductal epithelium of intercalated, intralobular, and interlobular ducts. KGF also causes incorporation of 5-bromodeoxyuridine in ductal epithelial cells. Epithelial cell proliferation is histologically most prominent at the level of the intralobular ducts adjacent to and within the islets of Langerhans. Pancreatic ductal proliferation is not histologically apparent in rats sacrificed 7 to 10 days after the cessation of KGF administration. The pancreatic hormones insulin, glucagon, somatostatin, and pancreatic polypeptide are normally distributed within islets that demonstrate intrainsular ductal proliferation. The proliferating ductal epithelium does not show endocrine differentiation as evidenced by the lack of immunoreactivity for pancreatic hormones. KGF is a potent in vivo mitogen for pancreatic ductal epithelial cells.     

Carcinoembryonic antigen, alpha 1-antitrypsin, and alpha-fetoprotein in the pancreas of patients with cystic fibrosis

The ductular accumulation of "abnormal mucus" is the key histologic feature in cystic fibrosis. This material is periodic acid-Schiff positive and diastase resistant, suggesting that it is glycoprotein in nature. We used the avidin-biotin-peroxidase method to identify this material using antibodies to the serum glycoproteins carcinoembryonic antigen, alpha 1-antitrypsin, and alpha-fetoprotein on paraffin sections of pancreas obtained from a total of 21 patients: 9 with cystic fibrosis, 5 with chronic pancreatitis, and 7 controls. The control patients had normal pancreatic histologic findings, no alpha 1-antitrypsin or alpha-fetoprotein was demonstrated, and only the ductular epithelium reacted weakly for carcinoembryonic antigen. The pancreas in pancreatitis showed fibrosis, acinar atrophy, and ectasia of the ducts that contained only a small amount of periodic acid-Schiff-positive material. This material reacted weakly for carcinoembryonic antigen and alpha 1-antitrypsin. The appearance of the pancreas in cystic fibrosis was similar to that in chronic pancreatitis. However, the ducts contained a greater amount of periodic acid-Schiff-positive material, mostly in the form of globules that reacted strongly for carcinoembryonic antigen and alpha 1-antitrypsin and weakly for alpha-fetoprotein, as did the ductular epithelium. This study shows that the periodic acid-Schiff-positive material in cystic fibrosis contains at least the three serum glycoproteins and that the accumulation may represent a possible defect in cellular synthesis, assembly, or transport of glycoproteins in the ducts.     

Formation of pancreatic duct epithelium from bone marrow during neonatal development

Recent reports suggest that bone marrow-derived cells engraft and differentiate into pancreatic tissue at very low frequency after pancreatic injury. All such studies have used adult recipients. The aim of our studies was to investigate the potential of bone marrow to contribute to the exocrine and endocrine components of the pancreas during the normal rapid growth of the organ that occurs during the neonatal period. Five to ten million bone marrow cells from adult, male, transgenic, green fluorescent protein (GFP) mice were injected into neonatal nonobese diabetic/severely compromised immunodeficient/beta2microglobulin-null mice 24 hours after birth. Two months after bone marrow transplantation, pancreas tissue was analyzed with fluorescence immunohistochemistry and fluorescence in situ hybridization (FISH). Co-staining of GFP, with anticytokeratin antibody, and with FISH for the presence of donor Y chromosome indicated that up to 40% of ducts (median 4.6%) contained epithelial cells derived from donor bone marrow. In some of these donor-derived ducts, there were clusters of large and small ducts, all comprised of GFP+ epithelium, suggesting that whole branching structures were derived from donor bone marrow. In addition, rare cells that coexpressed GFP and insulin were found within islets. Unlike pancreatic damage models, no bone marrow-derived vascular endothelial cells were found. In contrast to the neonatal recipients, bone marrow transplanted into adult mice rarely generated ductal epithelium or islet cells (p<.05 difference between adult and neonate transplants). These findings demonstrate the existence in bone marrow of pluripotent stem cells or epithelial precursors that can migrate to the pancreas and differentiate into complex organ-specific structures during the neonatal period.     

Identification of human glandular kallikrein in the beta cell of the pancreas.

To determine the cellular localization of glandular kallikrein in the human pancreas, immunohistochemical studies were performed with a monospecific antibody against the antigenically identical urinary kallikrein (urokallikrein). The localization of glandular pancreatic kallikrein to the beta cells of the islets was the same as that of insulin in normal human pancreas and in two islet-cell tumors. When beta cells were lacking in islet-cell tumors or in the pancreas of a patient with juvenile-onset diabetes, kallikrein antigen was not detectable. Anti-urokallikrein absorbed with purified urinary or pancreatic kallikrein no longer identified a pancreatic antigen, whereas absorption with insulin had no effect. The beta-cell localization of human pancreatic kallikrein, an endopeptidase that, in concert with carboxypeptidase B, converts bovine proinsulin to a polypeptide with the electrophoretic mobility of insulin, suggests that pancreatic kallikrein may be involved in the physiologic activation of proinsulin.     

Distribution of somatostatin in pancreatic ductal adenocarcinoma remodels the normal pattern of the protein during foetal pancreatic development: an immunohistochemical analysis

AIM: To determine the immunoreactivity of somatostatin during the development of the human fetal pancreas and pancreatic ductal adenocarcinoma, given that, somatostatin-positive cells were demonstrated either into its embryonic anlage or into pancreatic cancer. METHODS: Tissue sections from 15 pancreatic fetal specimens, and an equal number of ductal adenocarcinoma specimens were assessed. RESULTS: The density of positive cells in the primitive exocrine ductal epithelium and endocrine epithelium was significantly different from the relevant density in the neoplastic pancreatic tissue of mixed (ductal-endocrine) and pure ductal type (P1=0.021 P2=0.001, P3<0.0001, P4=0.003 respectively). The above values were estimated from the 8th to 10th week. There was no significant difference in the density of positive cells in the mantle zone of the islets from the 13th to the 24th week, and the neoplastic tissue of mixed (P5=0.16) and pure ductal type (P6=0.65). CONCLUSION: The immunostaining for somatostatin identifies a subgroup of pancreatic ductal adenocarcinomas with a neuroendocrine component, (initially considered as pure ductal tumors), and mixed ductal and neuroendocrine tumors. This pattern of expression in neoplasms recapitulates the normal pattern during the embryonal development of the organ, raising the question of therapeutic efficacy of somatostatin and analogues as monotherapy in pancreatic cancer management.     

Development of colonic and pancreatic endocrine tumours in mice expressing a glucagon-SV40 T antigen transgene

We report the histological, immunohistochemical and ultrastructural changes in mice containing a chimeric glucagon-simian virus 40 T antigen (SV40Tag) gene. Transgene expression was detected in endocrine cells of pancreas, small and large intestine. Hyperplasia of glucagon-containing cells developed in pancreas and large bowel by gestational day 19. In large bowel, hyperplastic cells increased in number postnatally and invasive carcinomas were identified at 4 weeks; several animals had lymph node metastases. In contrast, no pathology was detected in the small bowel in any of the transgenic mice. Colonic tumours expressed SV40Tag, proglucagon-derived peptides and peptide YY (PYY); scattered cells contained cholecystokinin or glycoprotein hormone -subunit. Somatostatin or serotonin was also detected in some tumours. By electron microscopy, the colonic tumours retained features of endocrine differentiation, but secretory granules were smaller than those of non-tumorous intestinal glucagon-producing L cells. In postnatal pancreas, atypical cells containing SV40Tag and glucagon were initially clustered at the periphery of islets; this atypical hyperplasia progressed to neoplasia by 11–12 weeks. Some neoplastic pancreatic cells contained glucagon, PYY or vasoactive intestinal peptide immunopositivity, but most were negative for all peptides; they contained immunoreactivity for tyrosine hydroxylase and by electron microscopy, pancreatic tumour cells had neuronal features. Pancreatic polypeptide was not detected in the non-tumorous islets of transgenic animals. This line of transgenic mice provides a model for the analysis of endocrine tumour progression in the gut and pancreas.     

胰岛淀粉样多肽在大鼠胰腺内分布的免疫组织化学研究

用免疫组织化学ＡＢＣ法，研究了胰岛淀粉样多肽（ＩＡＰＰ）在大鼠胰腺内的分布，并用免疫组织化学双标记法，在邻片上观察了ＩＡＰＰ与生长抑素（ＳＳ）和胰岛素（ＩＮＳ）的共存关系。结果显示，大鼠胰岛内绝大多数细胞都呈ＩＡＰＰ阳性免疫反应，在胰腺外分泌部的腺泡之间和导管上皮内也散在分布有ＩＡＰＰ免疫反应细胞。多数ＩＡＰＰ免疫反应细胞同时显示ＩＮＳ免疫反应，胰岛内少数ＩＡＰＰ阳性细胞也呈ＳＳ免疫反应。表明ＩＡ     

Heterotopic pancreas of the stomach. Histogenesis and immunohistochemistry.

Ordinary histological investigation has suggested that heterotopic pancreas of the stomach may have two types of histogenesis; one is development from immigrated fetal pancreas tissue, and the other is development from primitive gastric mucosal epithelium following penetration into the submucosa with subsequent erroneous differentiation into pancreas tissue. It is suspected that type-I lesions include the majority of cases caused by immigration from fetal pancreas, and that some type-II cases arise through erroneous differentiation of primitive gastric mucosal epithelium. With regard to immunohistochemical findings, cells positive for pancreatic polypeptide and amylase were much more numerous in the acini of type-I cases compared with type-II cases. Positive cells were found not infrequently in the acini of type-II cases after staining for pancreatic polypeptide, insulin, glucagon, somatostatin, serotonin, and gastrin. On the other hand, a small number of cells in islets were not infrequently positive for alpha 1-antitrypsin, alpha 1-antichymotrypsin, and amylase. It is considered that in the heterotopic pancreas, ductal cells have the potential to differentiate into acinar cells and islet cells, as is the cases in the orthotopic pancreas.     

Localization of expression of human beta defensin-1 in the pancreas and kidney

Defensins are antimicrobial peptides which play a key role in innate immunity. High levels of human beta defensin-1 (hBD-1) have previously been detected in the kidney and pancreas, but the cell-specific location of hBD-1 mRNA has not been determined. The expression of hBD-1 mRNA has been examined in fetal and adult pancreas and kidney by mRNA in situ hybridization. In fetal pancreas, hBD-1 expression was detected in the developing acini and in adult pancreas in the acini, but not in the pancreatic ducts. In both fetal and adult kidney, hBD-1 expression was detected in the collecting ducts and in the loops of Henle in adult kidney. Expression of hBD-1 mRNA in the pancreas and kidney from early development and in the acini of the adult pancreas, rather than in the pancreatic ducts, may indicate that in these tissues, hBD-1 fulfils physiological functions in addition to host defence. © 1998 John Wiley & Sons, Ltd.     

胰抑素在人,猪和豚鼠胰腺分布的免疫组织化学研究

胰抑素(pancreastatin,PS)是一种具有抑制胰岛分泌作用的新肽。本研究用ABC免疫染色法,在Bouin液固定的常规石蜡切片上,研究了胰抑素在豚鼠,猪和人胰腺内的定位和分布,并用相邻切片双标记法,观察了它与胰岛素的共存关系。结果发现,在人胰腺胰抑素样免疫反应(PLI)细胞主要分布于胰岛的周边部。在猪和豚鼠,大部分胰岛细胞呈阳性胰抑素样免疫反应。用相邻薄切片免疫染色技术证明,猪和豚鼠的PLI细胞主要是B细胞。在3个种属胰腺外分泌部的导管和腺泡等处,也均见有PLI细胞分布,在豚鼠胰腺尤为多见。本文对胰抑素在3个种属胰腺不同分布方式的意义进行了讨论。     

胰组织结构提示多肽胰岛素的正常转运经淋巴而非门脉途径

目的　探讨胰岛多肽激素释放形式和细胞外正常转运途径的结构基础。方法　对大鼠和人胰尾部组织进行了光镜 (LM )和透射电镜 (TEM)观察。结果　胰组织主要由腺泡构成的腺小叶和分隔腺小叶的结缔组织所组成。胰腺的导管、血管和淋巴管 ,有髓和无髓神经纤维 ,均穿行于胰结缔组织内。在胰岛周围的结缔组织间隙内也可见到完整的膜包分泌颗粒 (2 0 0～ 5 0 0nm)。胰腺的毛细血管为窗孔 (5 0nm)型。结论　胰组织结构特点提示 :胰岛多肽激素的释放形式 ,可能是连同颗粒膜的整体释放而非传统认为的胞吐分泌 ;释放入胰组织液中的多态胰岛素或分泌颗粒 ,更易进入淋巴而非门脉血液     

Histogenesis of uterus in human fetuses

Introduction

The histological changes during the development of the human uterus throughout the fetal period exhibit varying cellular patterns in the lining epithelium. The present study documents these progressive changes during fetal uterine maturation.

Temporal restriction of pancreatic branching competence during embryogenesis is mirrored in differentiating embryonic stem cells

To develop methods for the generation of insulin-producing β-cells for the treatment of diabetes, we have used GFP-tagged embryonic stem cells (ESCs) to elucidate the process of pancreas development. Using the reporter Pdx1(GFP/w) ESC line, we have previously described a serum-free differentiation protocol in which Pdx1-GFP(+) cells formed GFP bright (GFP(br)) epithelial buds that resembled those present in the developing mouse pancreas. In this study we extend these findings to demonstrate that these cells can undergo a process of branching morphogenesis, similar to that seen during pancreatic development of the mid-gestation embryo. These partially disaggregated embryoid bodies containing GFP(br) buds initially form epithelial ring-like structures when cultured in Matrigel. After several days in culture, these rings undergo a process of proliferation and form a ramified network of epithelial branches. Comparative analysis of explanted dissociated pancreatic buds from E13.5 Pdx1(GFP/w) embryos and ESC-derived GFP(br) buds reveal a similar process of proliferation and branching, with both embryonic Pdx1(GFP/w) branching pancreatic epithelium and ESC-derived GFP(br) branching organoids expressing markers representing epithelial (EpCAM and E-Cadherin), ductal (Mucin1), exocrine (Amylase and Carboxypeptidase 1A), and endocrine cell types (Glucagon and Somatostatin). ESC-derived branching structures also expressed a suite of genes indicative of ongoing pancreatic differentiation, paralleling gene expression within similar structures derived from the E13.5 fetal pancreas. In summary, differentiating mouse ESCs can generate pancreatic material that has significant similarity to the fetal pancreatic anlagen, providing an in vitro platform for investigating the cellular and molecular mechanisms underpinning pancreatic development.     

Heterotopic Pancreas of the Stomach

Ordinary histological investigation has suggested that heterotopic pancreas of the stomach may have two types of histogenesis; one is development from immigrated fetal pancreas tissue, and the other is development from primitive gastric mucosal epithelium following penetration into the submucosa with subsequent erroneous differentiation into pancreas tissue. It is suspected that type I lesions include the majority of cases caused by immigration from fetal pancreas, and that some type II cases arise through erroneous differentiation of primitive gastric mucosal epithelium. With regard to immunohistochemical findings, cells positive for pancreatic polypeptide and amylase were much more numerous in the acini of type I cases compared with type II cases. Positive cells were found not infrequently in the acini of type II cases after staining for pancreatic polypeptide, insulin, glucagon, somatostatin, serotonin, and gastrin. On the other hand, a small number of cells in islets were not infrequently positive for α ₁–antitrypsin, α ₁,-antichimotrypsin, and amylase. It is considered that in the heterotopic pancreas, ductal cells have the potential to differentiate into acinar cells and islet cells, as is the cases in the orthotopic pancreas. Acta Pathol Jpn 42 : 249 254, 1992.