WorldWideScience

Sample records for acinar cells pathologic

  1. Acinar Cell Cyst adenoma (Acinar Cystic Transformation) of the Pancreas: the Radiologic-Pathologic Features

    Gumus, Mehmet; Algin, Oktay; Gundogdu, Haldun [Ataturk Training and Research Hospital, Ankara (Turkmenistan); Ugras, Serdar [Selcuk University, Selcuklu Medical Faculty, Konya (Turkmenistan)

    2011-02-15

    Acinar cystic transformation of the pancreas is also known as acinar cell cystadenoma (ACC), and this is an extremely rare benign lesion that was first described in April 2002. We report here on a case of a previously asymptomatic patient with pancreatic ACC and this was diagnosed by computed tomography (CT) and magnetic resonance imaging (MRI). To the best of our knowledge, there is no previous report concerning the CT or MRI features of ACC in the medical literature. We present here the CT, MRI and pathological findings of pancreatic ACC

  2. Acinar Cell Cystadenoma (Acinar Cystic Transformation) of the Pancreas: the Radiologic-Pathologic Features

    Gumus, Mehmet; Ugras, Serdar; Algin, Oktay; Gundogdu, Haldun

    2011-01-01

    Acinar cystic transformation of the pancreas is also known as acinar cell cystadenoma (ACC), and this is an extremely rare benign lesion that was first described in April 2002. We report here on a case of a previously asymptomatic patient with pancreatic ACC and this was diagnosed by computed tomography (CT) and magnetic resonance imaging (MRI). To the best of our knowledge, there is no previous report concerning the CT or MRI features of ACC in the medical literature. We present here the CT,...

  3. Alteration of chaperonin60 and pancreatic enzyme in pancreatic acinar cell under pathological condition

    Li, Yong-Yu; Bendayan, Moise

    2005-01-01

    AIM: To investigate the changes of chaperonin60 (Cpn60) and pancreatic enzymes in pancreatic acinar cells, and to explore their roles in the development of experimental diabetes and acute pancreatitis (AP).

  4. Acinar Cell Carcinoma of the Pancreas

    Hua Li; Qiang Li

    2008-01-01

    Acinar cell carcinoma of the pancreas is a rare tumor which is defined as a carcinoma that exhibits pancreatic enzyme production by neoplastic cells. This review includes re-cent developments in our understanding of the epidemiology and pathogenesis of ACC, imaging and pathological diagnosis and ap-proaches to treatment with reference to the literature.

  5. Papillocystic Variant of Acinar Cell Pancreatic Carcinoma

    Jasim Radhi

    2010-01-01

    Full Text Available Acinar cell pancreatic carcinoma is a rare solid malignant neoplasm. Recent review of the literature showed occasional cases with papillary or papillocystic growth patterns, ranging from 2 to 5 cm in diameter. We report a large 10 cm pancreatic tumor with papillocystic pathology features involving the pancreatic head. The growth pattern of these tumors could be mistaken for intraductal papillary mucinous tumors or other pancreatic cystic neoplasms.

  6. Ca2+ signaling in pancreatic acinar cells: physiology and pathophysiology

    O.H. Petersen

    2009-01-01

    Full Text Available The pancreatic acinar cell is a classical model for studies of secretion and signal transduction mechanisms. Because of the extensive endoplasmic reticulum and the large granular compartment, it has been possible - by direct measurements - to obtain considerable insights into intracellular Ca2+ handling under both normal and pathological conditions. Recent studies have also revealed important characteristics of stimulus-secretion coupling mechanisms in isolated human pancreatic acinar cells. The acinar cells are potentially dangerous because of the high intra-granular concentration of proteases, which become inappropriately activated in the human disease acute pancreatitis. This disease is due to toxic Ca2+ signals generated by excessive liberation of Ca2+ from both the endoplasmic reticulum and the secretory granules.

  7. Inflammatory role of the acinar cells during acute pancreatitis

    Isabel; De; Dios

    2010-01-01

    Pancreatic acinar cells are secretory cells whose main function is to synthesize, store and f inally release digestive enzymes into the duodenum. However, in response to noxious stimuli, acinar cells behave like real inflammatory cells because of their ability to activate signalling transduction pathways involved in the expression of inflammatory mediators. Mediated by the kinase cascade, activation of Nuclear factor-κB, Activating factor-1 and Signal transducers and activators of transcription transcription factors has been demonstrated in acinar cells, resulting in overexpression of inflammatory genes. In turn, kinase activity is down-regulated by protein phosphatases and the f inal balance between kinase and phosphatase activity will determine the capability of the acinar cells to produce inflammatory factors. The kinase/ phosphatase pair is a redox-sensitive system in which kinase activation overwhelms phosphatase activity under oxidant conditions. Thus, the oxidative stress developed within acinar cells at early stages of acute pancreatitis triggers the activation of signalling pathways involved in the up-regulation of cytokines, chemokines and adhesion molecules. In this way, acinar cells trigger the release of the f irst inflammatory signals which can mediate the activation and recruitment of circulating inflammatorycells into the injured pancreas. Accordingly, the role of acinar cells as promoters of the inflammatory response in acute pancreatitis may be considered. This concept leads to amplifying the focus from leukocyte to acinar cells themselves, to explain the local inflammation in early pancreatitis.

  8. TGF-β1 promotes acinar to ductal metaplasia of human pancreatic acinar cells.

    Liu, Jun; Akanuma, Naoki; Liu, Chengyang; Naji, Ali; Halff, Glenn A; Washburn, William K; Sun, Luzhe; Wang, Pei

    2016-01-01

    Animal studies suggest that pancreatitis-induced acinar-to-ductal metaplasia (ADM) is a key event for pancreatic ductal adenocarcinoma (PDAC) initiation. However, there has not been an adequate system to explore the mechanisms of human ADM induction. We have developed a flow cytometry-based, high resolution lineage tracing method and 3D culture system to analyse ADM in human cells. In this system, well-known mouse ADM inducers did not promote ADM in human cells. In contrast, TGF-β1 efficiently converted human acinar cells to duct-like cells (AD) in a SMAD-dependent manner, highlighting fundamental differences between the species. Functionally, AD cells gained transient proliferative capacity. Furthermore, oncogenic KRAS did not induce acinar cell proliferation, but did sustain the proliferation of AD cells, suggesting that oncogenic KRAS requires ADM-associated-changes to promote PDAC initiation. This ADM model provides a novel platform to explore the mechanisms involved in the development of human pancreatic diseases. PMID:27485764

  9. Effects of Benzodiazepines on Acinar and Myoepithelial Cells

    Mattioli, Tatiana M. F.; Alanis, Luciana R. A.; Sapelli, Silvana da Silva; de Lima, Antonio A. S.; de Noronha, Lucia; Rosa, Edvaldo A. R.; Althobaiti, Yusuf S.; Almalki, Atiah H.; Sari, Youssef; Ignacio, Sergio A.; Johann, Aline C. B. R.; Gregio, Ana M. T.

    2016-01-01

    Background: Benzodiazepines (BZDs), the most commonly prescribed psychotropic drugs with anxiolytic action, may cause hyposalivation. It has been previously shown that BZDs can cause hypertrophy and decrease the acini cell number. In this study, we investigated the effects of BZDs and pilocarpine on rat parotid glands, specifically on acinar, ductal, and myoepithelial cells. Methods: Ninety male Wistar rats were divided into nine groups. Control groups received a saline solution for 30 days (C30) and 60 days (C60), and pilocarpine (PILO) for 60 days. Experimental groups received lorazepam (L30) and midazolam (M30) for 30 days. Another group (LS60 or MS60) received lorazepam or midazolam for 30 days, respectively, and saline for additional 30 days. Finally, other groups (LP60 or MP60) received either lorazepam or midazolam for 30 days, respectively, and pilocarpine for additional 30 days. The expression of calponin in myoepithelial cells and the proliferating cell nuclear antigen (PCNA) in acinar and ductal cells were evaluated. Results: Animals treated with lorazepam showed an increase in the number of positive staining cells for calponin as compared to control animals (p < 0.05). Midazolam administered with pilocarpine (MP60) induced an increase in the proliferation of acinar and ductal cells and a decrease in the positive staining cells for calponin as compared to midazolam administered with saline (MS60). Conclusion: We found that myoepithelial cells might be more sensitive to the effects of BZD than acinar and ductal cells in rat parotid glands.

  10. Regulating effects of arsenic trioxide on cell death pathways and inflammatory reactions of pancreatic acinar cells in rats

    XUE Dong-bo; ZHANG Wei-hui; YUN Xiao-guang; SONG Chun; ZHENG Biao; SHI Xing-ye; WANG Hai-yang

    2007-01-01

    Background It is accepted that inflammatory cytokines play a key role in the development of acute pancreatitis, so blocking the initiation of inflammatory reactions may alleviate pathological changes of acute pancreatitis. We studied the regulatory effect of arsenic trioxide (As2O3) on apoptosis and oncosis of pancreatic acinar cells in vitro and in vivo and its therapeutic effect on acute pancreatitis.Methods Pancreatic acinar cells were isolated by collagenase digestion method. Apoptosis and oncosis of isolated pancreatic acinar cells were detected with Hoechst 33258+PI or Annexin V+PI double fluorescent staining. Amylase and lactate dehydrogenase release were measured. Acute pancreatitis was induced in Wistar rats by intraperitoneal injections of caerulein, and apoptosis was detected with terminal dUTP nick-end labeling method. Tumor necorsis factor α (TNF-α) mRNA, myeloperoxidase, nuclear factor-κB and histological grading of pancreatic damage were measured.Results There was an increased apoptosis but a decreased oncosis of pancreatic acinar cell after the treatment with As2O3. The levels of lactate dehydrogenase and amylase release were markedly decreased in As2O3 treated group.Myeloperoxidase content, TNF-α mRNA level, nuclear factor-κB activation and pathological score in As2O3 treated group were significantly lower than in the untreated group.Conclusions As2O3 can induce apoptosis and reduce oncosis of pancreatic acinar cell, thus resulting in reduced release of endocellular enzyme of acinar cells, reduced inflammatory cell infiltration and decreased the production of inflammatory cytokines, so that the outcome of alleviated pathological changes was finally achieved.

  11. ANF and exocrine pancreas: ultrastructural autoradiographic localization in acinar cells

    Atrial natriuretic factor (ANF) binding sites have been recently demonstrated to be present in exocrine pancreas by an in vitro autoradiographic approach. An autoradiographic study was carried out to identify the exocrine cells containing ANF binding sites and to monitor the fate of 125I-labeled ANF in acinar cells after removal of pancreas at specific time intervals (1-30 min) after intravenous administration. At the light microscopic level, silver grains were found over acinar and centroacinar cells. Concomitant injection of an excess of unlabeled ANF inhibited the binding of labeled peptide by approximately 60%. At the electron microscopic level, the time-course study in acinar cells has revealed that of the cell compartments examined, plasma membrane, Golgi apparatus, mitochondria, and zymogen granules, the nucleus had distinct labeling patterns. Plasma membrane was maximally labeled 1 and 2 min after injection with 125I-ANF. Golgi apparatus was significantly labeled from 2 to 30 min after injection, mitochondria from 1 to 30 min after injection, zymogen granules at 1 and 15 min, and the nucleus only at 30 min. The lysosomal compartment was not labeled during the 30-min observation period. These results suggest that after binding to the plasma membrane, ANF is rapidly internalized and distributed to the intracellular organelles as a function of time. Labeling of the zymogen granules suggests that they may bind ANF and that the atrial peptide may be secreted by acinar cells. The significance of association of radioactivity with mitochondria and nuclei remains to be elucidated but may represent intracellular sites of action of ANF complementary to those on plasma membranes

  12. Nicotine as a mitogenic stimulus for pancreatic acinar cell proliferation

    Parimal Chowdhury; Kodetthoor B Udupa

    2006-01-01

    Cell proliferation is an important process in life for growth of normal and cancer cells. The signal transduction pathways activated during this process are strictly regulated. This editorial focuses on the role of nicotine,a mitogen, in the induction of signaling pathways resulting in proliferation of pancreatic tumor cells and compares these events with those in normal acinar cells isolated from the rat pancreas. The data shows striking similarities between these two cellular systems.In addition, the editorial reviews very recent literature of the contribution of MAPK signaling in cell lines associated with human diseases. A prospective cellular model of nicotine induced activation of MAPK cascade is presented.

  13. Recurrent Pancreatitis Due to a Cystic Pancreatic Tumor: A Rare Presentation of Acinar Cell Carcinoma

    Raimondo M; Krishna M; Nguyen J; Scolapio J; Aqel B

    2004-01-01

    CONTEXT: Acinar cell carcinoma is an uncommon malignancy of the pancreas. It has characteristic histomorphology, immunohistochemistry profile, and clinicopathological behavior. CASE REPORT: We report a rare case of recurrent pancreatitis secondary to acinar cell carcinoma of the pancreas. We describe the endoscopic ultrasound characteristic, treatment and the surgical outcome. CONCLUSIONS: Acinar cell carcinoma should be considered in the differential diagnosis of cystic pancreatic tumors pre...

  14. Recurrent Pancreatitis Due to a Cystic Pancreatic Tumor: A Rare Presentation of Acinar Cell Carcinoma

    Raimondo M

    2004-05-01

    Full Text Available CONTEXT: Acinar cell carcinoma is an uncommon malignancy of the pancreas. It has characteristic histomorphology, immunohistochemistry profile, and clinicopathological behavior. CASE REPORT: We report a rare case of recurrent pancreatitis secondary to acinar cell carcinoma of the pancreas. We describe the endoscopic ultrasound characteristic, treatment and the surgical outcome. CONCLUSIONS: Acinar cell carcinoma should be considered in the differential diagnosis of cystic pancreatic tumors presenting with recurrent pancreatitis.

  15. Functional somatostatin receptors on a rat pancreatic acinar cell line

    Somatostatin receptors from a rat pancreatic acinar cell line, AR4-2J, were characterized biochemically, structurally, and functionally. Binding of 125I-[Tyr11]Somatostatin to AR4-2J cells was saturable, exhibiting a single class of high-affinity binding sites with a maximal binding capacity of 258 ± 20 fmol/106 cells. Somatostatin receptor structure was analyzed by covalently cross-linking 125I-[Tyr11]somatostatin to its plasma membrane receptors. Gel electrophoresis and autoradiography of cross-linked proteins revealed a peptide containing the somatostatin receptor. Somatostatin inhibited vasoactive intestinal peptide (VIP)-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation in a dose-dependent manner. The concentration of somatostatin that caused half-maximal inhibition of cAMP formation was close to the receptor affinity for somatostatin. Pertussis toxin pretreatment of AR4-2J cells prevented somatostatin inhibition of VIP-stimulated cAMP formation as well as somatostatin binding. The authors conclude that AR4-2J cells exhibit functional somatostatin receptors that retain both specificity and affinity of the pancreatic acinar cell somatostatin receptors and act via the pertussis toxin-sensitive guanine nucleotide-binding protein Ni to inhibit adenylate cyclase

  16. Nitric oxide-induced signalling in rat lacrimal acinar cells

    Looms, Dagnia Karen; Tritsaris, K.; Dissing, S.

    2002-01-01

    using the fluorescent NO indicator 4,5-diaminofluorescein (DAF-2). We initiated investigations by adding NO from an external source by means of the NO-donor, S-nitroso-N-acetyl-penicillamine (SNAP). Cellular concentrations of cyclic guanosine 5'-phosphate (cGMP) ([cGMP]) were measured by...... radioimmunoassay (RIA), and we found that SNAP induced a fast increase in the [cGMP], amounting to 350% of the [cGMP] in resting cells. Moreover, addition of SNAP and elevating [cGMP] in fura-2 loaded lacrimal acinar cells, resulted in a cGMP-dependent protein kinase-mediated release of Ca2+ from intracellular......-adrenergic stimulation and not by a rise in [Ca2+]i alone.   We show that in rat lacrimal acinar cells, NO and cGMP induce Ca2+ release from intracellular stores via G kinase activation. However, the changes in [Ca2+]i are relatively small, suggesting that this pathway plays a modulatory role in Ca2+ signalling, thus...

  17. Effects of hypothyroidism on the ultrastructure of rat pancreatic acinar cells: a stereological analysis

    Blanco-Molina, A.; González-Reyes, J. A.; Torre-Cisneros, J; López-Miranda, J.; Nicolás, M.; Pérez-Jiménez, F.

    1991-01-01

    The morphological and stereological characteristics of the exocrine pancreas subcellular organelles from healthy and thyroidectomized rats have been studied. The acinar tissue from hypothyroid rats showed an interstitial edema and evidence of degenerative processes. Stereological parameters of zymogen granules were significantly reduced in thyroidectomized rats. The hypothyroidism induced degenerative changes in the pancreatic acinar cells as well as a decr...

  18. KRAS Mutations in Canine and Feline Pancreatic Acinar Cell Carcinoma.

    Crozier, C; Wood, G A; Foster, R A; Stasi, S; Liu, J H W; Bartlett, J M S; Coomber, B L; Sabine, V S

    2016-07-01

    Companion animals may serve as valuable models for studying human cancers. Although KRAS is the most commonly mutated gene in human ductal pancreatic cancers (57%), with mutations frequently occurring at codons 12, 13 and 61, human pancreatic acinar cell carcinomas (ACCs) lack activating KRAS mutations. In the present study, 32 pancreatic ACC samples obtained from 14 dogs and 18 cats, including seven metastases, were analyzed for six common activating KRAS mutations located in codons 12 (n = 5) and 13 (n = 1) using Sequenom MassARRAY. No KRAS mutations were found, suggesting that, similar to human pancreatic ACC, KRAS mutations do not play a critical role in feline or canine pancreatic ACC. Due to the similarity of the clinical disease in dogs and cats to that of man, this study confirms that companion animals offer potential as a suitable model for investigating this rare subtype of pancreatic carcinoma. PMID:27290644

  19. Acinar Cell Carcinoma of the Pancreas: A Possible Role of S-1 as Chemotherapy for Acinar Cell Carcinoma. A Case Report

    Tameyoshi Yamamoto

    2012-01-01

    Full Text Available Context Acinar cell carcinoma of the pancreas is a rare malignancy, accounting for 1-2% of pancreatic exocrine malignancies. This rarity makes it difficult to standardize a protocol of treatment for acinar cell carcinoma. Case report A 71-year-old male without any particular past history was referred to our institute with abdominal distention and mild liver dysfunction. Computed tomography (CT revealed a cystic lesion with a diameter of 3.5 cm, which originated from the neck of pancreas and had solid nodules inside. Several nodules were demonstrated surrounding the cystic tumor. Laparotomy and histological study demonstrated peritoneal dissemination of acinar cell carcinoma. The patient was treated with S-1 monotherapy (80 mg/m2 for four weeks with a two-week interval as one cycle. After one cycle of S-1 monotherapy, CT demonstrated remarkable shrinkage of the main tumor and disappearance of the nodules on the peritoneum. The patient underwent a radical distal pancreatectomy. The patient was then treated with 16 cycles of S-1 monotherapy after the radical pancreatectomy and remains without any recurrence of the disease two years later. Conclusion Initially inoperable acinar cell carcinoma was treated by monotherapy using S-1, resulting in curative operation and two years disease free survival post operation. S-1 might be more effective on acinar cell carcinoma, rather than gemcitabine

  20. Regeneration of parotid acinar cells after high radiation doses. A morphological study in rat

    The acute and late effects of fractionated irradiation on rat parotid gland acinar cells were studied by light and electron microscopy. At 10 days after the last irradiation session (6 Gy or 9 Gy daily during five consecutive days) no effects were seen. At 180 days, minor loss of acini was detectable after a total dose of 30 Gy. After 45 Gy a massive acinar loss was seen at that time; the number of acini had diminished and minor duct-like structures and scattered amounts of fibrous stroma dominated the slides. The remaining acini were disorganized and usually larger compared with the control side and to non-irradiated animals. The acinar cells appeared larger than in the controls. The custs were better preserved but the intercalated ducts often seemed to be larger than normal. We suggest that this phenomenon indicates a remaining capacity of the parotid gland to regenerate acinar cells even after high radiation doses. (orig.)

  1. Analysis and Optimization of Nutritional Set-up for Murine Pancreatic Acinar Cells.

    Kurup S

    2002-01-01

    Full Text Available CONTEXT: Pancreatic acinar cell cultivation poses a serious problem due to limitations in the in vitro survival time despite variations of dissociation protocols, culture media and nutrient supplements. OBJECTIVE: To establish a long term culture of murine pancreatic acinar cells which retain their viability, monolayer formation and responsiveness to secretagogues. In order to investigate the mechanism of the short-life of acinar cells studied in vitro, we studied their survival under the influence of different supplements on nutrient media. INTERVENTIONS: Dissociated pancreatic acini were prepared from BALB/c mice pancreata by collagenase digestion supplemented with bovine serum albumin fraction V and soybean trypsin inhibitor. A nutrient set-up was designed for their long term survival in vitro. RESULTS: It was observed that mouse pancreatic acinar cells dissociated in presence of bovine serum albumin fraction V and soybean trypsin inhibitor result in 95% viability. Further cultivation of these acinar cells in Waymouth's MB 752/1 medium supplemented with 10% fetal calf serum (v/v, soybean trypsin inhibitor, bovine serum albumin, dexamethasone, and epidermal growth factor results in their survival for more than 6 days in culture with 85% viability, retention of the secretagogue responsiveness and formation of a monolayer without any extracellular matrix coating. CONCLUSIONS: Our study clearly demonstrates that the addition of soybean trypsin inhibitor to culture medium reduces zymogen granule fragility and acinar cell death, thus increasing their viability for sufficiently long periods. The present study offers an excellent, in vitro model for the investigation of exocrine dysfunction in response to acinar cell injury.

  2. A computer-based automated algorithm for assessing acinar cell loss after experimental pancreatitis.

    John F Eisses

    Full Text Available The change in exocrine mass is an important parameter to follow in experimental models of pancreatic injury and regeneration. However, at present, the quantitative assessment of exocrine content by histology is tedious and operator-dependent, requiring manual assessment of acinar area on serial pancreatic sections. In this study, we utilized a novel computer-generated learning algorithm to construct an accurate and rapid method of quantifying acinar content. The algorithm works by learning differences in pixel characteristics from input examples provided by human experts. HE-stained pancreatic sections were obtained in mice recovering from a 2-day, hourly caerulein hyperstimulation model of experimental pancreatitis. For training data, a pathologist carefully outlined discrete regions of acinar and non-acinar tissue in 21 sections at various stages of pancreatic injury and recovery (termed the "ground truth". After the expert defined the ground truth, the computer was able to develop a prediction rule that was then applied to a unique set of high-resolution images in order to validate the process. For baseline, non-injured pancreatic sections, the software demonstrated close agreement with the ground truth in identifying baseline acinar tissue area with only a difference of 1% ± 0.05% (p = 0.21. Within regions of injured tissue, the software reported a difference of 2.5% ± 0.04% in acinar area compared with the pathologist (p = 0.47. Surprisingly, on detailed morphological examination, the discrepancy was primarily because the software outlined acini and excluded inter-acinar and luminal white space with greater precision. The findings suggest that the software will be of great potential benefit to both clinicians and researchers in quantifying pancreatic acinar cell flux in the injured and recovering pancreas.

  3. A resected case of symptomatic acinar cell cystadenoma of the pancreas displacing the main pancreatic duct.

    Tanaka, Haruyoshi; Hatsuno, Tsuyoshi; Kinoshita, Mitsuru; Hasegawa, Kazuya; Ishihara, Hiromasa; Takano, Nao; Shimoyama, Satofumi; Nakayama, Hiroshi; Kataoka, Masato; Ichihara, Shu; Kanda, Mitsuro; Kodera, Yasuhiro; Kondo, Ken

    2016-12-01

    Acinar cell cystadenoma (ACA) of the pancreas has been newly recognized as an entity by the World Health Organization (WHO) definition (2010), and its pathogenesis has not been known adequately because of the rarity. Here, we report a case of a 22-year-old female who had been followed up for a cystic lesion at the tail of the pancreas pointed out by a screening computed tomography (CT) scan 7 years ago. The tumor grew in size from 3.3 to 5.1 cm in diameter for 6 years (0.3 cm per year). Particularly, it rapidly grew up to 6.3 cm in the latest 3 months in concurrence with the emergence of epigastralgia. A contrasted CT scan revealed the irregularly formed, multilocular cystic tumor having thin septum and calcification. The intratumoral magnetic resonance imaging intensity in the T1 and T2 weighted images were low and high, respectively. No communications between the tumor and the main pancreatic duct (MPD) were found, but the tumor displaced the MPD. She underwent surgical resection because the tumor was growing, turned symptomatic, and it seemed difficult to be diagnosed correctly until totally biopsied. Spleen-preserved distal pancreatectomy was performed. It was pathologically diagnosed as ACA; the cyst was lined by cells with normal acinar differentiation; cuboidal cells with round, basally oriented nuclei and eosinophilic granules in its apical cytoplasm. The abdominal pain has disappeared, and no recurrences have been found during a 5-year follow-up. Clinicians are recommended to consider an ACA as one of differential diagnoses of cystic tumors of the pancreas to provide appropriate diagnostics and therapeutics. PMID:27108123

  4. THE CHANGES OF PANCREATIC ACINAR CELL FUNCTION IN ACUTE NECROTIZING PANCREATITIS OF RATS

    余枭; 韩天权; 汤耀卿; 雷若庆; 夏宗勤

    2000-01-01

    Objective To evaluate the changes of pancreatic acinar cell functions in the rats with acute necrotizing pancreatitis (ANP). Methods Seventy SD rats were randomized into two groups: experimental group (n=35) and control group (n=35). To prepare the experimental model, the retrograde injection of 5% sodium taurocholate into the pancreatic duct was used for inducing ANP. Radioactive tracing by L- 3H-phenylalanine and autoradiography were performed for scoring the differences of changes of amino acid uptake, enzyme-protein synthesis and output from acinar cells in rats between both groups. Results No changes were observed in amino acid uptake and enzyme-protein synthesis in rats with dotted and haemorrhagic necrotizing foci as compared with control group. However, accumulated zymogen granules in the interstitial of acinar cells were seen in the experimental group. Conclusion It indicates that in experimental ANP rats, the functions of acinar cells in both amino acid uptake and protein synthesis were essentially normal, but the pathway of enzyme output was affected into ectopic secretion through the bottom or lateral cellular membrane of pancreatic acinar cell.

  5. Preparation of Pancreatic Acinar Cells for the Purpose of Calcium Imaging, Cell Injury Measurements, and Adenoviral Infection

    Orabi, Abrahim I.; Muili, Kamaldeen A.; Wang, Dong; Jin, Shunqian; Perides, George; Husain, Sohail Z.

    2013-01-01

    The pancreatic acinar cell is the main parenchymal cell of the exocrine pancreas and plays a primary role in the secretion of pancreatic enzymes into the pancreatic duct. It is also the site for the initiation of pancreatitis. Here we describe how acinar cells are isolated from whole pancreas tissue and intracellular calcium signals are measured. In addition, we describe the techniques of transfecting these cells with adenoviral constructs, and subsequently measuring the leakage of lactate de...

  6. Pancreatic acinar cells-derived cyclophilin A promotes pancreatic damage by activating NF-κB pathway in experimental pancreatitis

    Yu, Ge [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Wan, Rong [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Hu, Yanling [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Ni, Jianbo [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Yin, Guojian; Xing, Miao [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Shen, Jie [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Tang, Maochun [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Chen, Congying [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Fan, Yuting; Xiao, Wenqin; Zhao, Yan [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Wang, Xingpeng, E-mail: wangxingpeng@hotmail.com [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); and others

    2014-01-31

    Highlights: • CypA is upregulated in experimental pancreatitis. • CCK induces expression and release of CypA in acinar cell in vitro. • rCypA aggravates CCK-induced acinar cell death and inflammatory cytokine production. • rCypA activates the NF-κB pathway in acinar cells in vitro. - Abstract: Inflammation triggered by necrotic acinar cells contributes to the pathophysiology of acute pancreatitis (AP), but its precise mechanism remains unclear. Recent studies have shown that Cyclophilin A (CypA) released from necrotic cells is involved in the pathogenesis of several inflammatory diseases. We therefore investigated the role of CypA in experimental AP induced by administration of sodium taurocholate (STC). CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. In vitro, it was released from damaged acinar cells by cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced acinar cell necrosis, promoted nuclear factor (NF)-κB p65 activation, and increased cytokine production. In conclusion, CypA promotes pancreatic damage by upregulating expression of inflammatory cytokines of acinar cells via the NF-κB pathway.

  7. Pancreatic acinar cells-derived cyclophilin A promotes pancreatic damage by activating NF-κB pathway in experimental pancreatitis

    Highlights: • CypA is upregulated in experimental pancreatitis. • CCK induces expression and release of CypA in acinar cell in vitro. • rCypA aggravates CCK-induced acinar cell death and inflammatory cytokine production. • rCypA activates the NF-κB pathway in acinar cells in vitro. - Abstract: Inflammation triggered by necrotic acinar cells contributes to the pathophysiology of acute pancreatitis (AP), but its precise mechanism remains unclear. Recent studies have shown that Cyclophilin A (CypA) released from necrotic cells is involved in the pathogenesis of several inflammatory diseases. We therefore investigated the role of CypA in experimental AP induced by administration of sodium taurocholate (STC). CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. In vitro, it was released from damaged acinar cells by cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced acinar cell necrosis, promoted nuclear factor (NF)-κB p65 activation, and increased cytokine production. In conclusion, CypA promotes pancreatic damage by upregulating expression of inflammatory cytokines of acinar cells via the NF-κB pathway

  8. Effect of Taurine on Acinar Cell Apoptosis and Pancreatic Fibrosis in Dibutyltin Dichloride-induced Chronic Pancreatitis

    Sawa,Kiminari

    2012-08-01

    Full Text Available The relationship between pancreatic fibrosis and apoptosis of pancreatic acinar cells has not been fully elucidated. We reported that taurine had an anti-fibrotic effect in a dibutyltin dichloride (DBTC-chronic pancreatitis model. However, the effect of taurine on apoptosis of pancreatic acinar cells is still unclear. Therefore, we examined apoptosis in DBTC-chronic pancreatitis and in the AR42J pancreatic acinar cell line with/without taurine. Pancreatic fibrosis was induced by a single administration of DBTC. Rats were fed a taurine-containing diet or a normal diet and were sacrificed at day 5. The AR42J pancreatic acinar cell line was incubated with/without DBTC with taurine chloramines. Apoptosis was determined by using terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL assay. The expression of Bad and Bcl-2 proteins in the AR42J cells lysates was detected by Western blot analysis. The apoptotic index of pancreatic acinar cells in DBTC-administered rats was significantly increased. Taurine treatment inhibited pancreatic fibrosis and apoptosis of acinar cells induced by DBTC. The number of TUNEL-positive cells in the AR42J pancreatic acinar cell lines was significantly increased by the addition of DBTC. Incubation with taurine chloramines ameliorated these changes. In conclusion, taurine inhibits apoptosis of pancreatic acinar cells and pancreatitis in experimental chronic pancreatitis.

  9. Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia

    Liou, Geou-Yarh; Döppler, Heike; Braun, Ursula B.; Panayiotou, Richard; Scotti Buzhardt, Michele; Radisky, Derek C.; Crawford, Howard C.; Fields, Alan P.; Murray, Nicole R.; Wang, Q. Jane; Leitges, Michael; Storz, Peter

    2015-02-01

    The transdifferentiation of pancreatic acinar cells to a ductal phenotype (acinar-to-ductal metaplasia, ADM) occurs after injury or inflammation of the pancreas and is a reversible process. However, in the presence of activating Kras mutations or persistent epidermal growth factor receptor (EGF-R) signalling, cells that underwent ADM can progress to pancreatic intraepithelial neoplasia (PanIN) and eventually pancreatic cancer. In transgenic animal models, ADM and PanINs are initiated by high-affinity ligands for EGF-R or activating Kras mutations, but the underlying signalling mechanisms are not well understood. Here, using a conditional knockout approach, we show that protein kinase D1 (PKD1) is sufficient to drive the reprogramming process to a ductal phenotype and progression to PanINs. Moreover, using 3D explant culture of primary pancreatic acinar cells, we show that PKD1 acts downstream of TGFα and Kras, to mediate formation of ductal structures through activation of the Notch pathway.

  10. Acinar cell ultrastructure after taurine treatment in rat acute necrotizing pancreatitis

    To evaluate the organelle-based changes in acinar cells in experimental acute necrotizing pancreatitis (ANP) after taurine treatment and the association of electron microscopic findings with histopathalogical changes and oxidative stress markers. The study was performed in February 2005at Gulhane School of Medicine and Hacettepe University, Turkey. Forty-five rats were divided into 3 groups. Acute necrotizing pancreatitis was induced in groups II and III. Groups I and II were treated with saline and Group III with taurine 1000mg/kg/day, i.p, for 48 hours. Histopathological and ultrastructural examinations were determined using one-way analysis of variance and Kruskal-Wallis tests. Histopathologic findings improved significantly after taurine treatment. Degree of injury in rough and smooth endoplasmic reticulums, Golgi apparatus, mitochondria and nucleus of acinar cells also decreased with taurine in correlation with biochemical and histological results. Taurine improves acinar cell organelle structure, and ultrastructural recovery in ANP reflects histological improvement. (author)

  11. Acinar phenotype is preserved in human exocrine pancreas cells cultured at low temperature: implications for lineage-tracing of β-cell neogenesis.

    Mfopou, Josué K; Houbracken, Isabelle; Wauters, Elke; Mathijs, Iris; Song, Imane; Himpe, Eddy; Baldan, Jonathan; Heimberg, Harry; Bouwens, Luc

    2016-06-01

    The regenerative medicine field is expanding with great successes in laboratory and preclinical settings. Pancreatic acinar cells in diabetic mice were recently converted into β-cells by treatment with ciliary neurotrophic factor (CNTF) and epidermal growth factor (EGF). This suggests that human acinar cells might become a cornerstone for diabetes cell therapy in the future, if they can also be converted into glucose-responsive insulin-producing cells. Presently, studying pancreatic acinar cell biology in vitro is limited by their high plasticity, as they rapidly lose their phenotype and spontaneously transdifferentiate to a duct-like phenotype in culture. We questioned whether human pancreatic acinar cell phenotype could be preserved in vitro by physico-chemical manipulations and whether this could be valuable in the study of β-cell neogenesis. We found that culture at low temperature (4°C) resulted in the maintenance of morphological and molecular acinar cell characteristics. Specifically, chilled acinar cells did not form the spherical clusters observed in controls (culture at 37°C), and they maintained high levels of acinar-specific transcripts and proteins. Five-day chilled acinar cells still transdifferentiated into duct-like cells upon transfer to 37°C. Moreover, adenoviral-mediated gene transfer evidenced an active Amylase promoter in the 7-day chilled acinar cells, and transduction performed in chilled conditions improved acinar cell labelling. Together, our findings indicate the maintenance of human pancreatic acinar cell phenotype at low temperature and the possibility to efficiently label acinar cells, which opens new perspectives for the study of human acinar-to-β-cell transdifferentiation. PMID:26987985

  12. Transgenic Expression of a Single Transcription Factor Pdx1 Induces Transdifferentiation of Pancreatic Acinar Cells to Endocrine Cells in Adult Mice.

    Miyazaki, Satsuki; Tashiro, Fumi; Miyazaki, Jun-Ichi

    2016-01-01

    A promising approach to new diabetes therapies is to generate β cells from other differentiated pancreatic cells in vivo. Because the acinar cells represent the most abundant cell type in the pancreas, an attractive possibility is to reprogram acinar cells into β cells. The transcription factor Pdx1 (Pancreas/duodenum homeobox protein 1) is essential for pancreatic development and cell lineage determination. Our objective is to examine whether exogenous expression of Pdx1 in acinar cells of adult mice might induce reprogramming of acinar cells into β cells. We established a transgenic mouse line in which Pdx1 and EGFP (enhanced green fluorescent protein) could be inducibly expressed in the acinar cells. After induction of Pdx1, we followed the acinar cells for their expression of exocrine and endocrine markers using cell-lineage tracing with EGFP. The acinar cell-specific expression of Pdx1 in adult mice reprogrammed the acinar cells as endocrine precursor cells, which migrated into the pancreatic islets and differentiated into insulin-, somatostatin-, or PP (pancreatic polypeptide)-producing endocrine cells, but not into glucagon-producing cells. When the mice undergoing such pancreatic reprogramming were treated with streptozotocin (STZ), the newly generated insulin-producing cells were able to ameliorate STZ-induced diabetes. This paradigm of in vivo reprogramming indicates that acinar cells hold promise as a source for new islet cells in regenerative therapies for diabetes. PMID:27526291

  13. Transgenic Expression of a Single Transcription Factor Pdx1 Induces Transdifferentiation of Pancreatic Acinar Cells to Endocrine Cells in Adult Mice

    Miyazaki, Satsuki; Tashiro, Fumi; Miyazaki, Jun-ichi

    2016-01-01

    A promising approach to new diabetes therapies is to generate β cells from other differentiated pancreatic cells in vivo. Because the acinar cells represent the most abundant cell type in the pancreas, an attractive possibility is to reprogram acinar cells into β cells. The transcription factor Pdx1 (Pancreas/duodenum homeobox protein 1) is essential for pancreatic development and cell lineage determination. Our objective is to examine whether exogenous expression of Pdx1 in acinar cells of adult mice might induce reprogramming of acinar cells into β cells. We established a transgenic mouse line in which Pdx1 and EGFP (enhanced green fluorescent protein) could be inducibly expressed in the acinar cells. After induction of Pdx1, we followed the acinar cells for their expression of exocrine and endocrine markers using cell-lineage tracing with EGFP. The acinar cell-specific expression of Pdx1 in adult mice reprogrammed the acinar cells as endocrine precursor cells, which migrated into the pancreatic islets and differentiated into insulin-, somatostatin-, or PP (pancreatic polypeptide)-producing endocrine cells, but not into glucagon-producing cells. When the mice undergoing such pancreatic reprogramming were treated with streptozotocin (STZ), the newly generated insulin-producing cells were able to ameliorate STZ-induced diabetes. This paradigm of in vivo reprogramming indicates that acinar cells hold promise as a source for new islet cells in regenerative therapies for diabetes. PMID:27526291

  14. Transdifferentiation of human amniotic epithelial cells into acinar cells using a double-chamber system.

    Huang, Gui-Lin; Zhang, Ni-Ni; Wang, Jun-Sheng; Yao, Li; Zhao, Yu-Jie; Wang, Yu-Ying

    2012-08-01

    This study investigated the transdifferentiation of stem cells from human amnion tissue into functional acinar cells (ACs) using a co-culture system. Human amniotic epithelial cells (hAECs) were isolated from amnion tissue by mechanical mincing and enzymatic digestion. After primary culture, the phenotype of the cells was identified by flow cytometry (FCM) and immunocytochemical staining. hAECs were co-cultured with submandibular gland acinar cells of SD rats using a double-chamber system. The expression of α-amylase was determined by immunocytochemical method and fluorescent real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) after induction for 1 and 2 weeks, respectively. Digestion with trypsin is an effective method for isolating hAECs from amnion tissue. These cells were positive for CD29 and CK19 and weakly positive for CD44 and α-amylase. Within 2 weeks, α-amylase in hAECs increased with induction time. The expression of α-amylase in hAECs was increased 3.38-fold after co-culturing for 1 week. This ratio increased to 6.6-fold, and these cells were positive for mucins, after co-culturing for 2 weeks. hAECs possess the potential to differentiate into ACs in vitro. They might be a stem cell resource for clinical applications of cell replacement therapy in salivary gland dysfunction diseases. PMID:22800093

  15. Polyethylenimine-mediated expression of transgenes in the acinar cells of rats salivary glands in vivo

    Sramkova, Monika; Parente, Laura; Wigand, Timothy; Aye, Myo-Pale'; Shitara, Akiko; Weigert, Roberto

    2015-01-01

    Non viral-mediated transfection of plasmid DNA provides a fast and reliable way to express various transgenes in selected cell populations in live animals. Here, we show an improvement of a previously published method that is based on injecting plasmid DNA into the ductal system of the salivary glands in live rats. Specifically, using complexes between plasmid DNA and polyethyleneimine (PEI) we show that the expression of the transgenes is directed selectively to the salivary acinar cells. PE...

  16. Salivary gland acinar cells regenerate functional glandular structures in modified hydrogels

    Pradhan, Swati

    Xerostomia, a condition resulting from irradiation of the head and neck, affects over 40,000 cancer patients each year in the United States. Direct radiation damage of the acinar cells that secrete fluid and protein results in salivary gland hypofunction. Present medical management for xerostomia for patients treated for upper respiratory cancer is largely ineffective. Patients who have survived their terminal diagnosis are often left with a diminished quality of life and are unable to enjoy the simple pleasures of eating and drinking. This project aims to ultimately reduce human suffering by developing a functional implantable artificial salivary gland. The goal was to create an extracellular matrix (ECM) modified hyaluronic acid (HA) based hydrogel culture system that allows for the growth and differentiation of salivary acinar cells into functional acini-like structures capable of secreting large amounts of protein and fluid unidirectionally and to ultimately engineer a functional artificial salivary gland that can be implanted into an animal model. A tissue collection protocol was established and salivary gland tissue was obtained from patients undergoing head and neck surgery. The tissue specimen was assessed by histology and immunohistochemistry to establish the phenotype of normal salivary gland cells including the native basement membranes. Hematoxylin and eosin staining confirmed normal glandular tissue structures including intercalated ducts, striated ducts and acini. alpha-Amylase and periodic acid schiff stain, used for structures with a high proportion of carbohydrate macromolecules, preferentially stained acinar cells in the tissue. Intercalated and striated duct structures were identified using cytokeratins 19 and 7 staining. Myoepithelial cells positive for cytokeratin 14 were found wrapped around the serous and mucous acini. Tight junction components including ZO-1 and E-cadherin were present between both ductal and acinar cells. Ductal and acinar

  17. Intracellular mediators of Na+-K+ pump activity in guinea pig pancreatic acinar cells

    The involvement of Ca2+ and cyclic nucleotides in neurohormonal regulation of Na+-K+-ATPase (Na+-K+ pump) activity in guinea pig pancreatic acinar cells was investigated. Changes in Na+-K+ pump activity elicited by secretagogues were assessed by [3H]ouabain binding and by ouabain-sensitive 86Rb+ uptake. Carbachol (CCh) and cholecystokinin octapeptide (CCK-8) each stimulated both ouabain-sensitive 86Rb+ uptake and equilibrium binding of [3H]ouabain by approximately 60%. Secretin increased both indicators of Na+-K+ pump activity by approximately 40% as did forskolin, 8-bromo- and dibutyryl cAMP, theophylline, and isobutylmethylxanthine. Incubation of acinar cells in Ca2+-free HEPES-buffered Ringer (HR) with 0.5 mM EGTA reduced the stimulatory effects of CCh and CCK-8 by up to 90% but caused only a small reduction in the effects of secretin, forskolin, and cAMP analogues. In addition, CCh, CCK-8, secretin, and forskolin each stimulated ouabain-insensitive 86Rb+ uptake by acinar cells. The increase elicited by CCh and CCK-8 was greatly reduced in the absence of extracellular Ca2+, while that caused by the latter two agents was not substantially altered. The effects of secretagogues on free Ca2+ levels in pancreatic acinar cells also were investigated with quin-2, a fluorescent Ca2+ chelator. Basal intracellular Ca2+ concentration ([Ca2+]i) was 161 nM in resting cells and increased to 713 and 803 nM within 15 s after addition of 100 microM CCh or 10 nM CCK-8, respectively

  18. Quantitative description of a teleost exocrine pancreas. Ultrastructural morphometric study of nonstimulated acinar cells.

    Stipp, A C; Ferri, S; Sesso, A

    1984-01-01

    The quantitative analysis of exocrine pancreas was fulfilled in teleost fish ( Pimelodus maculatus). The volume fraction occupied by acinar cells, blood vessels and ducts has been assessed by point-counting volumetry in 0.25 micron araldite sections. Measurements of the diameters of the transections of acinar cells nuclei and nucleolus allowed the assessment of the mean nuclear and nucleolar volume according to the method of Bach (1963). With these data, the cytoplasm nuclei and nucleolus volume was calculated in cubic micrometers. Morphometric ultrastructural data was obtained by applying over the electronmicrophotographs (X 21,000) a test system of 84 segments regularly spaced one from another (Weibel 1966). The results obtained was analysed and compared to the mammalian. PMID:6721199

  19. Modelling the transition from simple to complex Ca2+ oscillations in pancreatic acinar cells

    Neeraj Manhas; James Sneyd; K R Pardasani

    2014-06-01

    A mathematical model is proposed which systematically investigates complex calcium oscillations in pancreatic acinar cells. This model is based on calcium-induced calcium release via inositol trisphosphate receptors (IPR) and ryanodine receptors (RyR) and includes calcium modulation of inositol (1,4,5) trisphosphate (IP3) levels through feedback regulation of degradation and production. In our model, the apical and the basal regions are separated by a region containing mitochondria, which is capable of restricting Ca2+ responses to the apical region. We were able to reproduce the observed oscillatory patterns, from baseline spikes to sinusoidal oscillations. The model predicts that calcium-dependent production and degradation of IP3 is a key mechanism for complex calcium oscillations in pancreatic acinar cells. A partial bifurcation analysis is performed which explores the dynamic behaviour of the model in both apical and basal regions.

  20. Constitutive IKK2 activation in acinar cells is sufficient to induce pancreatitis in vivo

    Baumann, Bernd; Wagner, Martin; Aleksic, Tamara; von Wichert, Götz; Weber, Christoph K.; Adler, Guido; Wirth, Thomas

    2007-01-01

    Activation of the inhibitor of NF-κB kinase/NF-κB (IKK/NF-κB) system and expression of proinflammatory mediators are major events in acute pancreatitis. However, the in vivo consequences of IKK activation on the onset and progression of acute pancreatitis remain unclear. Therefore, we modulated IKK activity conditionally in pancreatic acinar cells. Transgenic mice expressing the reverse tetracycline-responsive transactivator (rtTA) gene under the control of the rat elastase promoter were gene...

  1. Organelle selection determines agonist-specific Ca2+ signals in pancreatic acinar and beta cells

    Yamasaki, M.; Masgrau, R.; Morgan, A. J.; Churchill, G. C.; Patel, S.; Ashcroft, S. J. H.; Galione, A

    2004-01-01

    How different extracellular stimuli can evoke different spatiotemporal Ca2+ signals is uncertain. We have elucidated a novel paradigm whereby different agonists use different Ca2+-storing organelles ("organelle seleetion") to evoke unique responses. Some agonists select the endoplasmic reticulum (ER), and others select lysosome-related (acidic) organelles, evoking spatial Ca2+ responses that mirror the organellar distribution. In pancreatic acinar cells, acetylcholine and bombesin exclusively...

  2. The role of protein synthesis and digestive enzymes in acinar cell injury

    Logsdon, Craig D.; Ji, Baoan

    2013-01-01

    The exocrine pancreas is the organ with the highest level of protein synthesis in the adult—each day the pancreas produces litres of fluid filled with enzymes that are capable of breaking down nearly all organic substances. For optimal health, the pancreas must produce sufficient enzymes of the right character to match the dietary intake. Disruption of normal pancreatic function occurs primarily as a result of dysfunction of the acinar cells that produce these digestive enzymes, and can lead ...

  3. Functional role of MicroRNA-19b in acinar cell necrosis in acute necrotizing pancreatitis.

    Hu, Ming-Xing; Zhang, Hong-Wei; Fu, Qiang; Qin, Tao; Liu, Chuan-Jiang; Wang, Yu-Zhu; Tang, Qiang; Chen, Yu-Xin

    2016-04-01

    The expression of microRNA-19b (miR-19b) in acute necrotizing pancreatitis (ANP) and its functional role in acinar cell necrosis of SD rats were investigated. Twelve SD rats were divided into two groups randomly, including control group and ANP group. The rat ANP models were established by intraperitoneal injection of L-arginine (2400 mg/kg body weight), and equal volume of 0.9% NaCl was injected in the control group. MiRNA chip assay was performed to examine the expression of miRNAs in the pancreas in two different groups. Besides, to further explore the role of miR-19b in ANP in vitro, taurolithocholic acid 3-sulfate disodium salt (TLC-S) (200 μmol/L) was administrated to treat the rat pancreatic acinar cell line, AR42J, for establishing the ANP cells model. The quantitative real-time PCR (qRT-PCR) was adopted to measure the miR-19b expression. Moreover, the mimic miRNA, miRNA antisense oligonucleotide (AMO) and control vector were used to transfect AR42J cells, the expression of miR-19b was confirmed by qRT-PCR and the necrotizing rate of AR42J cells was detected with AO/EB method. The expression of miR-19b was significantly higher in ANP group than in control group as displayed by the miRNA chip assay. Furthermore, after inducing necrosis of AR42J cells in vitro, the expression of miR-19b was significantly increased by 2.51±0.14 times in comparison with the control group. As revealed by qRT-PCR assay, the expression of miR-19b was 5.94±0.95 times higher in the mimic miRNA group than in the control vector group, companied with an obviously increased acinar cell necrotizing rate (50.3%±1.5% vs. 39.6%±2.3%, P0.05). The expression of miR-19b was significantly induced in ANP. In addition, up-regulation of miR-19b could promote the necrosis of pancreatic acinar cells and miR-19b deficiency could decrease the rate of pancreatic acinar cell necrosis. PMID:27072966

  4. Phorbol esters and A23187 regulate Na+=K+-pump activity in pancreatic acinar cells

    To clarify the subcellular mechanisms that mediate stimulation of Na+-K+-pump activity in pancreatic acinar cells by cholinergic agonists, the authors examined the effects of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) and the Ca2+ ionophore A23187 on [3H]ouabain binding to dispersed guinea pig pancreatic acinar cells under conditions in which binding reflects the average rate of pump cycling. The phorbol ester more than doubled Na+-K+-pump activity as did the diacylglycerol analogue, 1-oleoyl-2-acetolyl-sn-3-glycerol. A23187 increased pump activity by a maximum of 31% at 0.3 μM but was progressively inhibitory at higher concentrations. The stimulatory effects of TPA and A23187 were additive, although either secretagogue elicited a less than additive response when added together with a maximally effective concentration of the cholinergic agonist, carbachol. Removal of extracellular Ca2+ had little effect on the pump response to TPA and did not reduce the maximal effect of A23187 but abolished the inhibitory effect seen at high ionophore concentrations in Ca2+-containing medium. These results indicate that both Ca2+ and protein kinase c are involved in regulating Na+-K+-pump activity in the pancreatic acinar cell

  5. Inactivation of TGFβ receptor II signalling in pancreatic epithelial cells promotes acinar cell proliferation, acinar-to-ductal metaplasia and fibrosis during pancreatitis.

    Grabliauskaite, Kamile; Saponara, Enrica; Reding, Theresia; Bombardo, Marta; Seleznik, Gitta M; Malagola, Ermanno; Zabel, Anja; Faso, Carmen; Sonda, Sabrina; Graf, Rolf

    2016-02-01

    Determining signalling pathways that regulate pancreatic regeneration following pancreatitis is critical for implementing therapeutic interventions. In this study we elucidated the molecular mechanisms underlying the effects of transforming growth factor-β (TGFβ) in pancreatic epithelial cells during tissue regeneration. To this end, we conditionally inactivated TGFβ receptor II (TGFβ-RII) using a Cre-LoxP system under the control of pancreas transcription factor 1a (PTF1a) promoter, specific for the pancreatic epithelium, and evaluated the molecular and cellular changes in a mouse model of cerulein-induced pancreatitis. We show that TGFβ-RII signalling does not mediate the initial acinar cell damage observed at the onset of pancreatitis. However, TGFβ-RII signalling not only restricts acinar cell replication during the regenerative phase of the disease but also limits ADM formation in vivo and in vitro in a cell-autonomous manner. Analyses of molecular mechanisms underlying the observed phenotype revealed that TGFβ-RII signalling stimulates the expression of cyclin-dependent kinase inhibitors and intersects with the EGFR signalling axis. Finally, TGFβ-RII ablation in epithelial cells resulted in increased infiltration of inflammatory cells in the early phases of pancreatitis and increased activation of pancreatic stellate cells in the later stages of pancreatitis, thus highlighting a TGFβ-based crosstalk between epithelial and stromal cells regulating the development of pancreatic inflammation and fibrosis. Collectively, our data not only contribute to clarifying the cellular processes governing pancreatic tissue regeneration, but also emphasize the conserved role of TGFβ as a tumour suppressor, both in the regenerative process following pancreatitis and in the initial phases of pancreatic cancer. PMID:26510396

  6. Genetic deletion of Rab27B in pancreatic acinar cells affects granules size and has inhibitory effects on amylase secretion.

    Hou, Yanan; Ernst, Stephen A; Lentz, Stephen I; Williams, John A

    2016-03-18

    Small G protein Rab27B is expressed in various secretory cell types and plays a role in mediating secretion. In pancreatic acinar cells, Rab27B was found to be expressed on the zymogen granule membrane and by overexpression to regulate the secretion of zymogen granules. However, the effect of Rab27B deletion on the physiology of pancreatic acinar cells is unknown. In the current study, we utilized the Rab27B KO mouse model to better understand the role of Rab27B in the secretion of pancreatic acinar cells. Our data show that Rab27B deficiency had no obvious effects on the expression of major digestive enzymes and other closely related proteins, e.g. similar small G proteins, such as Rab3D and Rab27A, and putative downstream effectors. The overall morphology of acinar cells was not changed in the knockout pancreas. However, the size of zymogen granules was decreased in KO acinar cells, suggesting a role of Rab27B in regulating the maturation of secretory granules. The secretion of digestive enzymes was moderately decreased in KO acini, compared with the WT control. These data indicate that Rab27B is involved at a different steps of zymogen granule maturation and secretion, which is distinct from that of Rab3D. PMID:26845357

  7. The econobiology of pancreatic acinar cells granule inventory and the stealthy nano-machine behind it.

    Hammel, Ilan; Meilijson, Isaac

    2016-03-01

    The pancreatic gland secretes most of the enzymes and many other macromolecules needed for food digestion in the gastrointestinal tract. These molecules play an important role in digestion, host defense and lubrication. The secretion of pancreatic proteins ensures the availability of the correct mix of proteins when needed. This review describes model systems available for the study of the econobiology of secretory granule content. The secretory pancreatic molecules are stored in large dense-core secretory granules that may undergo either constitutive or evoked secretion, and constitute the granule inventory of the cell. It is proposed that the Golgi complex functions as a distribution center for secretory proteins in pancreatic acinar cells, packing the newly formed secretory molecules into maturing secretory granules, also known functionally as condensing vacuoles. Mathematical modelling brings forward a process underlying granule inventory maintenance at various physiological states of condensation and aggregation by homotypic fusion. These models suggest unique but simple mechanisms accountable for inventory buildup and size, as well as for the distribution of secretory molecules into different secretory pathways in pancreatic acinar cells. PMID:26702787

  8. Secretory pathways in animal cells: with emphasis on pancreatic acinar cells.

    Beaudoin, A R; Grondin, G

    1991-01-01

    Studies over the past three decades have clearly established the existence of at least two distinct pathways for the intracellular transport and release of secretory proteins by animal cells. These have been identified as the regulated and constitutive pathways. Many observations have indicated that in certain cells, such as those of the exocrine pancreas and parotid glands at least, these pathways coexist in the same cells. Although the general scheme of protein transport within these pathways is well established, many fundamental aspects of intracellular transport remain to be unraveled. How are proteins transported through the endoplasmic reticulum? How are the transitional vesicles formed and what are the underlying mechanisms involved in their fusion with the cis-Golgi cisterna? Even the general mode of transfer through the Golgi stack is debated: Is there a diffusion through the stack by flow through intercisternal tubules and openings or is there a vesicle transfer system where membrane quanta hop from one cisterna to the other? What is the fate of secretory proteins in the trans-Golgi area and by what mechanisms is a fraction of newly synthesized molecules of a given secretory protein released spontaneously while the majority of such nascent molecules are diverted into a secretory granule compartment? In this review, we have examined these and other aspects of intracellular transport of secretory proteins using pancreatic acinar cells as our reference model and we present some evidence to support the existence of a paragranular pathway of secretion associated with secretory granule maturation. PMID:1993938

  9. Aquaporin expression and cell volume regulation in the SV40 immortalized rat submandibular acinar cell line.

    Hansen, Ann-Kristin; Galtung, Hilde Kanli

    2007-03-01

    The amount of aquaporins present and the cellular ability to perform regulatory volume changes are likely to be important for fluid secretions from exocrine glands. In this work these phenomena were studied in an SV40 immortalized rat submandibular acinar cell line. The regulatory cell volume characteristics have not previously been determined in these cells. Cell volume regulation following hyposmotic exposure and aquaporin induction was examined with Coulter counter methodology, radioactive efflux studies, fura-2 fluorescence, and polymerase chain reaction and Western blot techniques. Cell volume regulation was inhibited by the K(+) channel antagonists quinine and BaCl(2) and the Cl(-) channel blocker 5-nitro-2-(3-phenypropylamino)benzoic acid. A concomitant increase in cellular (3)H-taurine release and Ca(2+) concentration was also observed. Chelation of both intra- and extracellular Ca(2+) with EGTA and the Ca(2+) ionophore A23187 did not, however, affect cell volume regulation. Aquaporin 5 (AQP5) mRNA and protein levels were upregulated in hyperosmotic conditions and downregulated upon return to isosmotic solutions, but were reduced by the mitogen-activated ERK-activating kinase (MEK) inhibitor U0126. A 24-h MEK inhibition also diminished hyposmotically induced cell swelling and cell volume regulation. In conclusion, it was determined that regulatory volume changes in this immortalized cell line are due to KCl and taurine efflux. In conditions that increased AQP5 levels, the cells showed a faster cell swelling and a more complete volume recovery following hyposmotic exposure. This response could be overturned by MEK inhibition. PMID:17021794

  10. Whole exome sequencing reveals recurrent mutations in BRCA2 and FAT genes in acinar cell carcinomas of the pancreas

    Toru Furukawa; Hitomi Sakamoto; Shoko Takeuchi; Mitra Ameri; Yuko Kuboki; Toshiyuki Yamamoto; Takashi Hatori; Masakazu Yamamoto; Masanori Sugiyama; Nobuyuki Ohike; Hiroshi Yamaguchi; Michio Shimizu; Noriyuki Shibata; Kyoko Shimizu; Keiko Shiratori

    2015-01-01

    Acinar cell carcinoma of the pancreas is a rare tumor with a poor prognosis. Compared to pancreatic ductal adenocarcinoma, its molecular features are poorly known. We studied a total of 11 acinar cell carcinomas, including 3 by exome and 4 by target sequencing. Exome sequencing revealed 65 nonsynonymous mutations and 22 indels with a mutation rate of 3.4 mutations/Mb per tumor, on average. By accounting for not only somatic but also germline mutations with loss of the wild-type allele, we ide...

  11. Immunocytochemical localization of the [3H]estradiol-binding protein in rat pancreatic acinar cells

    Significant amounts of an estradiol-binding protein (EBP) are present in pancreatic acinar cells. This protein differs from the one found in female reproductive tissues and secondary sex organs (which is commonly referred to as estrogen receptor). EBP has now been purified from rat pancreas and was used as an antigen to induce polyclonal antibodies in rabbits. The antiserum obtained was purified initially by ammonium sulfate fractionation and then still further by interaction with a protein fraction from pancreas that was devoid of estradiol-binding activity. The latter procedure was used to precipitate nonspecific immunoglobulin Gs. Western blot analysis demonstrated that the anti-EBP antibody reacted specifically with a doublet of protein bands having mol wt of 64K and 66K. When this purified antibody was used as an immunocytochemical probe in conjunction with protein-A-gold, acinar cells were labeled on the surface of the endoplasmic reticulum, on the plasma membrane, and in mitochondria. This specific labeling pattern was not observed when preimmune serum was used. No labeling was observed over the nucleus, Golgi apparatus, or zymogen granules with purified anti-EBP antibodies. The unexpected distribution of EBP in both the endoplasmic reticulum and mitochondria is discussed

  12. Curative resection of a primarily unresectable acinar cell carcinoma of the pancreas after chemotherapy

    Dobrowolski Frank

    2009-02-01

    Full Text Available Abstract Background Acinar cell carcinoma (ACC represents only 1–2% of pancreatic cancers and is a very rare malignancy. At the time of diagnosis only 50% of the tumors appear to be resectable. Reliable data for an effective adjuvant or neoadjuvant treatment are not available. Case presentation A 65-year old male presented with obstructive jaundice and non-specific upper abdominal pain. MRI-imaging showed a tumor within the head of the pancreas concomitant with Serum-Lipase and CA19-9. During ERCP, a stent was placed. Endosonographic fine needle biopsy confirmed an acinar cell carcinoma. Laparotomy presented an locally advanced tumor with venous infiltration that was consequently deemed unresectable. The patient was treated with five cycles of 5-FU monotherapy with palliative intention. Chemotherapy was well tolerated, and no severe complications were observed. Twelve months later, the patient was in stable condition, and CT-scanning showed an obvious reduction in the size of the tumor. During further operative exploration, a PPPD with resection of the portal vein was performed. Histopathological examination gave evidence of a diffuse necrotic ACC-tumor, all resection margins were found to be negative. Eighteen months later, the patient showed no signs of recurrent disease. Conclusion ACC responded well to 5-FU monochemotherapy. Therefore, neoadjuvant chemotherapy could be an option to reduce a primarily unresectable ACC to a point where curative resection can be achieved.

  13. Cathepsin B Activity Initiates Apoptosis via Digestive Protease Activation in Pancreatic Acinar Cells and Experimental Pancreatitis.

    Sendler, Matthias; Maertin, Sandrina; John, Daniel; Persike, Maria; Weiss, F Ulrich; Krüger, Burkhard; Wartmann, Thomas; Wagh, Preshit; Halangk, Walter; Schaschke, Norbert; Mayerle, Julia; Lerch, Markus M

    2016-07-01

    Pancreatitis is associated with premature activation of digestive proteases in the pancreas. The lysosomal hydrolase cathepsin B (CTSB) is a known activator of trypsinogen, and its deletion reduces disease severity in experimental pancreatitis. Here we studied the activation mechanism and subcellular compartment in which CTSB regulates protease activation and cellular injury. Cholecystokinin (CCK) increased the activity of CTSB, cathepsin L, trypsin, chymotrypsin, and caspase 3 in vivo and in vitro and induced redistribution of CTSB to a secretory vesicle-enriched fraction. Neither CTSB protein nor activity redistributed to the cytosol, where the CTSB inhibitors cystatin-B/C were abundantly present. Deletion of CTSB reduced and deletion of cathepsin L increased intracellular trypsin activation. CTSB deletion also abolished CCK-induced caspase 3 activation, apoptosis-inducing factor, as well as X-linked inhibitor of apoptosis protein degradation, but these depended on trypsinogen activation via CTSB. Raising the vesicular pH, but not trypsin inhibition, reduced CTSB activity. Trypsin inhibition did not affect apoptosis in hepatocytes. Deletion of CTSB affected apoptotic but not necrotic acinar cell death. In summary, CTSB in pancreatitis undergoes activation in a secretory, vesicular, and acidic compartment where it activates trypsinogen. Its deletion or inhibition regulates acinar cell apoptosis but not necrosis in two models of pancreatitis. Caspase 3-mediated apoptosis depends on intravesicular trypsinogen activation induced by CTSB, not CTSB activity directly, and this mechanism is pancreas-specific. PMID:27226576

  14. Primary alveolar capillary dysplasia (acinar dysplasia) and surfactant protein B deficiency: a clinical, radiological and pathological study

    Hugosson, Claes O.; Khoumais, Nuha [King Faisal Specialist Hospital and Research Centre, Department of Radiology MBC 28, Riyadh (Saudi Arabia); Salama, Husam M.; Kattan, Abdul H. [King Faisal Specialist Hospital and Research Centre, Department of Paediatrics, Riyadh (Saudi Arabia); Al-Dayel, Fouad [King Faisal Specialist Hospital and Research Centre, Department of Pathology, Riyadh (Saudi Arabia)

    2005-03-01

    Full-term infants with severe and prolonged respiratory distress represent a diagnostic challenge. Plain radiographic findings may be nonspecific or similar to classic surfactant deficiency disease for infants with surfactant protein B deficiency and acinar dysplasia. Objectives: To describe the similar clinical-radiolgical patterns of two rare neonatal conditions. Six newborn babies with severe respiratory distress at birth demonstrated clinical and radiographically prolonged and progressive diffuse pulmonary opacification. All infants demonstrated hyperinflation of the lungs. The diffuse hazy opacification, which varied from mild (n=3) to moderate (n=3), progressed to severe diffuse opacification preceding death, which occurred at 12-36 days of life. Open lung biopsy confirmed the diagnosis of primary alveolar acinar dysplasia (AD) in four infants and surfactant protein B deficiency (SPBD) in two infants. In full-term babies with unexplained progressive respiratory distress from birth and progress of radiological changes, both AD and SPBD should be considered. (orig.)

  15. Primary alveolar capillary dysplasia (acinar dysplasia) and surfactant protein B deficiency: a clinical, radiological and pathological study

    Full-term infants with severe and prolonged respiratory distress represent a diagnostic challenge. Plain radiographic findings may be nonspecific or similar to classic surfactant deficiency disease for infants with surfactant protein B deficiency and acinar dysplasia. Objectives: To describe the similar clinical-radiological patterns of two rare neonatal conditions. Six newborn babies with severe respiratory distress at birth demonstrated clinical and radiographically prolonged and progressive diffuse pulmonary opacification. All infants demonstrated hyperinflation of the lungs. The diffuse hazy opacification, which varied from mild (n=3) to moderate (n=3), progressed to severe diffuse opacification preceding death, which occurred at 12-36 days of life. Open lung biopsy confirmed the diagnosis of primary alveolar acinar dysplasia (AD) in four infants and surfactant protein B deficiency (SPBD) in two infants. In full-term babies with unexplained progressive respiratory distress from birth and progress of radiological changes, both AD and SPBD should be considered. (orig.)

  16. Glucagon-like peptide-1 receptor is present in pancreatic acinar cells and regulates amylase secretion through cAMP.

    Hou, Yanan; Ernst, Stephen A; Heidenreich, Kaeli; Williams, John A

    2016-01-01

    Glucagon-like peptide-1 (GLP-1) is a glucoincretin hormone that can act through its receptor (GLP-1R) on pancreatic β-cells and increase insulin secretion and production. GLP-1R agonists are used clinically to treat type 2 diabetes. GLP-1 may also regulate the exocrine pancreas at multiple levels, including inhibition through the central nervous system, stimulation indirectly through insulin, and stimulation directly on acinar cells. However, it has been unclear whether GLP-1R is present in pancreatic acini and what physiological functions these receptors regulate. In the current study we utilized GLP-1R knockout (KO) mice to study the role of GLP-1R in acinar cells. RNA expression of GLP-1R was detected in acutely isolated pancreatic acini. Acinar cell morphology and expression of digestive enzymes were not affected by loss of GLP-1R. GLP-1 induced amylase secretion in wild-type (WT) acini. In GLP-1R KO mice, this effect was abolished, whereas vasoactive intestinal peptide-induced amylase release in KO acini showed a pattern similar to that in WT acini. GLP-1 stimulated cAMP production and increased protein kinase A-mediated protein phosphorylation in WT acini, and these effects were absent in KO acini. These data show that GLP-1R is present in pancreatic acinar cells and that GLP-1 can regulate secretion through its receptor and cAMP signaling pathway. PMID:26542397

  17. A systems biology approach identifies a regulatory network in parotid acinar cell terminal differentiation.

    Melissa A Metzler

    Full Text Available The transcription factor networks that drive parotid salivary gland progenitor cells to terminally differentiate, remain largely unknown and are vital to understanding the regeneration process.A systems biology approach was taken to measure mRNA and microRNA expression in vivo across acinar cell terminal differentiation in the rat parotid salivary gland. Laser capture microdissection (LCM was used to specifically isolate acinar cell RNA at times spanning the month-long period of parotid differentiation.Clustering of microarray measurements suggests that expression occurs in four stages. mRNA expression patterns suggest a novel role for Pparg which is transiently increased during mid postnatal differentiation in concert with several target gene mRNAs. 79 microRNAs are significantly differentially expressed across time. Profiles of statistically significant changes of mRNA expression, combined with reciprocal correlations of microRNAs and their target mRNAs, suggest a putative network involving Klf4, a differentiation inhibiting transcription factor, which decreases as several targeting microRNAs increase late in differentiation. The network suggests a molecular switch (involving Prdm1, Sox11, Pax5, miR-200a, and miR-30a progressively decreases repression of Xbp1 gene transcription, in concert with decreased translational repression by miR-214. The transcription factor Xbp1 mRNA is initially low, increases progressively, and may be maintained by a positive feedback loop with Atf6. Transfection studies show that Xbp1 activates the Mist1 promoter [corrected]. In addition, Xbp1 and Mist1 each activate the parotid secretory protein (Psp gene, which encodes an abundant salivary protein, and is a marker of terminal differentiation.This study identifies novel expression patterns of Pparg, Klf4, and Sox11 during parotid acinar cell differentiation, as well as numerous differentially expressed microRNAs. Network analysis identifies a novel stemness arm, a

  18. β-catenin is selectively required for the expansion and regeneration of mature pancreatic acinar cells in mice

    Matthew D. Keefe

    2012-07-01

    The size of the pancreas is determined by intrinsic factors, such as the number of progenitor cells, and by extrinsic signals that control the fate and proliferation of those progenitors. Both the exocrine and endocrine compartments of the pancreas undergo dramatic expansion after birth and are capable of at least partial regeneration following injury. Whether the expansion of these lineages relies on similar mechanisms is unknown. Although we have shown that the Wnt signaling component β-catenin is selectively required in mouse embryos for the generation of exocrine acinar cells, this protein has been ascribed various functions in the postnatal pancreas, including proliferation and regeneration of islet as well as acinar cells. To address whether β-catenin remains important for the maintenance and expansion of mature acinar cells, we have established a system to follow the behavior and fate of β-catenin-deficient cells during postnatal growth and regeneration in mice. We find that β-catenin is continuously required for the establishment and maintenance of acinar cell mass, extending from embryonic specification through juvenile and adult self-renewal and regeneration. This requirement is not shared with islet cells, which proliferate and function normally in the absence of β-catenin. These results make distinct predictions for the relative role of Wnt–β-catenin signaling in the etiology of human endocrine and exocrine disease. We suggest that loss of Wnt–β-catenin activity is unlikely to drive islet dysfunction, as occurs in type 2 diabetes, but that β-catenin is likely to promote human acinar cell proliferation following injury, and might therefore contribute to the resolution of acute or chronic pancreatitis.

  19. Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca2+ oscillations in mouse pancreatic acinar cells

    Huang, Zebing; Wang, Haiyan; Wang, Jingke; Zhao, Mengqin; Sun, Nana; Sun, Fangfang; Shen, Jianxin; Zhang, Haiying; Xia, Kunkun; Chen, Dejie; Gao, Ming; Hammer, Ronald P.; Liu, Qingrong; Xi, Zhengxiong; Fan, Xuegong; Wu, Jie

    2016-01-01

    Emerging evidence demonstrates that the blockade of intracellular Ca2+ signals may protect pancreatic acinar cells against Ca2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB2Rs modulate intracellular Ca2+ signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca2+ oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB2Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca2+ oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca2+ oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca2+ oscillations and L-arginine-induced enhancement of Ca2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis. PMID:27432473

  20. Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca(2+) oscillations in mouse pancreatic acinar cells.

    Huang, Zebing; Wang, Haiyan; Wang, Jingke; Zhao, Mengqin; Sun, Nana; Sun, Fangfang; Shen, Jianxin; Zhang, Haiying; Xia, Kunkun; Chen, Dejie; Gao, Ming; Hammer, Ronald P; Liu, Qingrong; Xi, Zhengxiong; Fan, Xuegong; Wu, Jie

    2016-01-01

    Emerging evidence demonstrates that the blockade of intracellular Ca(2+) signals may protect pancreatic acinar cells against Ca(2+) overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB2Rs modulate intracellular Ca(2+) signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca(2+) oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB2Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca(2+) oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca(2+) oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca(2+) oscillations and L-arginine-induced enhancement of Ca(2+) signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis. PMID:27432473

  1. Prolonged Survival in a Patient with a Pancreatic Acinar Cell Carcinoma.

    Ploquin, Anne; Baldini, Capucine; Vuagnat, Perrine; Makhloufi, Samira; Desauw, Christophe; Hebbar, Mohamed

    2015-01-01

    Pancreatic acinar cell carcinoma (ACC) is a rare entity. Herein we present the case of a 50-year-old male patient with an unlimited mass on the pancreatic corpus and tail with peripancreatic effusion and multiple metastases in the liver and spleen. A liver biopsy showed a pancreatic ACC. The patient received 9 cycles of gemcitabine plus oxaliplatin (GEMOX regimen), which had to be stopped because of a persistent grade 2 neuropathy. A CT scan showed complete response after 14 years. At the age of 61 years, a localized prostatic cancer was diagnosed, treated by prostatectomy. The patient carried a BRCA2 mutation. None of the precedent case reports describe a chemosensibility to the GEMOX regimen. In spite of the lack of study in these patients, chemotherapy with oxaliplatin seems to be the most effective. Long survival can be expected. PMID:26600777

  2. The Acinar Cage: Basement Membranes Determine Molecule Exchange and Mechanical Stability of Human Breast Cell Acini.

    Aljona Gaiko-Shcherbak

    Full Text Available The biophysical properties of the basement membrane that surrounds human breast glands are poorly understood, but are thought to be decisive for normal organ function and malignancy. Here, we characterize the breast gland basement membrane with a focus on molecule permeation and mechanical stability, both crucial for organ function. We used well-established and nature-mimicking MCF10A acini as 3D cell model for human breast glands, with ether low- or highly-developed basement membrane scaffolds. Semi-quantitative dextran tracer (3 to 40 kDa experiments allowed us to investigate the basement membrane scaffold as a molecule diffusion barrier in human breast acini in vitro. We demonstrated that molecule permeation correlated positively with macromolecule size and intriguingly also with basement membrane development state, revealing a pore size of at least 9 nm. Notably, an intact collagen IV mesh proved to be essential for this permeation function. Furthermore, we performed ultra-sensitive atomic force microscopy to quantify the response of native breast acini and of decellularized basement membrane shells against mechanical indentation. We found a clear correlation between increasing acinar force resistance and basement membrane formation stage. Most important native acini with highly-developed basement membranes as well as cell-free basement membrane shells could both withstand physiologically relevant loads (≤ 20 nN without loss of structural integrity. In contrast, low-developed basement membranes were significantly softer and more fragile. In conclusion, our study emphasizes the key role of the basement membrane as conductor of acinar molecule influx and mechanical stability of human breast glands, which are fundamental for normal organ function.

  3. Effect of ionizing radiation on acinar morphogenesis of human prostatic epithelial cells under three-dimensional culture conditions.

    Wang, T; X, S Ma; Kong, D; Yi, H; Wang, X; Liang, B; Xu, H; He, M; Jia, L; Qased, A B; Yang, Y; Liu, X

    2012-01-01

    Homeostasis is maintained by the interplay of multiple factors that directly or indirectly regulate cell proliferation and cell death. Complex multiple interactions between cells and the extracellular matrix occur during acinar morphogenesis and changes in these might indicate carcinogenesis of cells from a normal to a malignant, invasive phenotype. In this study, the human prostatic epithelial cell line RWPE-1 was cultured under three-dimensional (3-D) culture conditions, and the effect of ionizing radiation on acinar morphogenesis and its association with autophagy were discussed. The results illustrated that formation of specific spheroid (acinar) structures was detectable under 3-D culture conditions. Radiation induced the disruption of acini in different cell models using either gene overexpression (Akt) or gene knock-down (Beclin 1 and ATG7). Introduction of Akt not only accelerated the growth of cells (i.e., caused the cells to manifest elongating and microspike-like structures that are obviously different from structures seen in wild-type RWPE-1 cells under two-dimensional conditions), but also changed their morphological characteristics under 3-D culture conditions. Knock-down of autophagy-related genes (Beclin 1 and ATG7) increased the radiosensitivity of cells under 3-D culture conditions, and cells died of non-apoptotic death after radiation. The results suggested that ionizing radiation may change the cell phenotype and the formation of acini. Additionally even the autophagy mechanism may play a role in these processes. PMID:22296497

  4. Competence of failed endocrine progenitors to give rise to acinar but not ductal cells is restricted to early pancreas development

    Beucher, Anthony; Martín, Mercè; Spenle, Caroline; Poulet, Martine; Collin, Caitlin; Gradwohl, Gérard

    2011-01-01

    During mouse pancreas development, the transient expression of Neurogenin3 (Neurog3) in uncommitted pancreas progenitors is required to determine endocrine destiny. However it has been reported that Neurog3-expressing cells can eventually adopt acinar or ductal fates and that Neurog3 levels were important to secure the islet destiny. It is not known whether the competence of Neurog3-induced cells to give rise to non-endocrine lineages is an intrinsic property of these progenitors or depends o...

  5. Rab27A Is Present in Mouse Pancreatic Acinar Cells and Is Required for Digestive Enzyme Secretion.

    Yanan Hou

    Full Text Available The small G-protein Rab27A has been shown to regulate the intracellular trafficking of secretory granules in various cell types. However, the presence, subcellular localization and functional impact of Rab27A on digestive enzyme secretion by mouse pancreatic acinar cells are poorly understood. Ashen mice, which lack the expression of Rab27A due to a spontaneous mutation, were used to investigate the function of Rab27A in pancreatic acinar cells. Isolated pancreatic acini were prepared from wild-type or ashen mouse pancreas by collagenase digestion, and CCK- or carbachol-induced amylase secretion was measured. Secretion occurring through the major-regulated secretory pathway, which is characterized by zymogen granules secretion, was visualized by Dextran-Texas Red labeling of exocytotic granules. The minor-regulated secretory pathway, which operates through the endosomal/lysosomal pathway, was characterized by luminal cell surface labeling of lysosomal associated membrane protein 1 (LAMP1. Compared to wild-type, expression of Rab27B was slightly increased in ashen mouse acini, while Rab3D and digestive enzymes (amylase, lipase, chymotrypsin and elastase were not affected. Localization of Rab27B, Rab3D and amylase by immunofluorescence was similar in both wild-type and ashen acinar cells. The GTP-bound states of Rab27B and Rab3D in wild-type and ashen mouse acini also remained similar in amount. In contrast, acini from ashen mice showed decreased amylase release induced by CCK- or carbachol. Rab27A deficiency reduced the apical cell surface labeling of LAMP1, but did not affect that of Dextran-Texas Red incorporation into the fusion pockets at luminal surface. These results show that Rab27A is present in mouse pancreatic acinar cells and mainly regulates secretion through the minor-regulated pathway.

  6. Ca²⁺ signaling and regulation of fluid secretion in salivary gland acinar cells.

    Ambudkar, Indu S

    2014-06-01

    Neurotransmitter stimulation of plasma membrane receptors stimulates salivary gland fluid secretion via a complex process that is determined by coordinated temporal and spatial regulation of several Ca(2+) signaling processes as well as ion flux systems. Studies over the past four decades have demonstrated that Ca(2+) is a critical factor in the control of salivary gland function. Importantly, critical components of this process have now been identified, including plasma membrane receptors, calcium channels, and regulatory proteins. The key event in activation of fluid secretion is an increase in intracellular [Ca(2+)] ([Ca(2+)]i) triggered by IP3-induced release of Ca(2+) from ER via the IP3R. This increase regulates the ion fluxes required to drive vectorial fluid secretion. IP3Rs determine the site of initiation and the pattern of [Ca(2+)]i signal in the cell. However, Ca(2+) entry into the cell is required to sustain the elevation of [Ca(2+)]i and fluid secretion. This Ca(2+) influx pathway, store-operated calcium influx pathway (SOCE), has been studied in great detail and the regulatory mechanisms as well as key molecular components have now been identified. Orai1, TRPC1, and STIM1 are critical components of SOCE and among these, Ca(2+) entry via TRPC1 is a major determinant of fluid secretion. The receptor-evoked Ca(2+) signal in salivary gland acinar cells is unique in that it starts at the apical pole and then rapidly increases across the cell. The basis for the polarized Ca(2+) signal can be ascribed to the polarized arrangement of the Ca(2+) channels, transporters, and signaling proteins. Distinct localization of these proteins in the cell suggests compartmentalization of Ca(2+) signals during regulation of fluid secretion. This chapter will discuss new concepts and findings regarding the polarization and control of Ca(2+) signals in the regulation of fluid secretion. PMID:24646566

  7. 99mTc-pertechnetate uptake in parotid acinar cells by the Na+/K+/Cl- co-transport system.

    Helman, J; Turner, R J; Fox, P C; Baum, B.J.

    1987-01-01

    99mTc-Pertechnetate (99mTcO4-) has widespread clinical use in the diagnosis and evaluation of dysfunctions in many different tissues. However, despite the broad clinical application of this radionuclide, very little is known about the mechanism by which 99mTcO4- enters a cell. We report evidence here that 99mTcO4- shares the Na+/K+/Cl- co-transport system localized to the basolateral membrane of rat parotid acinar cells. 99mTcO4- uptake by these cells was quite rapid (t1/2 approximately 30 s)...

  8. Atp2c2 Is Transcribed From a Unique Transcriptional Start Site in Mouse Pancreatic Acinar Cells.

    Fenech, Melissa A; Sullivan, Caitlin M; Ferreira, Lucimar T; Mehmood, Rashid; MacDonald, William A; Stathopulos, Peter B; Pin, Christopher L

    2016-12-01

    Proper regulation of cytosolic Ca(2+) is critical for pancreatic acinar cell function. Disruptions in normal Ca(2+) concentrations affect numerous cellular functions and are associated with pancreatitis. Membrane pumps and channels regulate cytosolic Ca(2+) homeostasis by promoting rapid Ca(2+) movement. Determining how expression of Ca(2+) modulators is regulated and the cellular alterations that occur upon changes in expression can provide insight into initiating events of pancreatitis. The goal of this study was to delineate the gene structure and regulation of a novel pancreas-specific isoform for Secretory Pathway Ca(2+) ATPase 2 (termed SPCA2C), which is encoded from the Atp2c2 gene. Using Next Generation Sequencing of RNA (RNA-seq), chromatin immunoprecipitation for epigenetic modifications and promoter-reporter assays, a novel transcriptional start site was identified that promotes expression of a transcript containing the last four exons of the Atp2c2 gene (Atp2c2c). This region was enriched for epigenetic marks and pancreatic transcription factors that promote gene activation. Promoter activity for regions upstream of the ATG codon in Atp2c2's 24th exon was observed in vitro but not in in vivo. Translation from this ATG encodes a protein aligned with the carboxy terminal of SPCA2. Functional analysis in HEK 293A cells indicates a unique role for SPCA2C in increasing cytosolic Ca(2+) . RNA analysis indicates that the decreased Atp2c2c expression observed early in experimental pancreatitis reflects a global molecular response of acinar cells to reduce cytosolic Ca(2+) levels. Combined, these results suggest SPCA2C affects Ca(2+) homeostasis in pancreatic acinar cells in a unique fashion relative to other Ca(2+) ATPases. J. Cell. Physiol. 231: 2768-2778, 2016. © 2016 Wiley Periodicals, Inc. PMID:27017909

  9. Hydrogen sulfide: a novel gaseous signaling molecule and intracellular Ca2+ regulator in rat parotid acinar cells.

    Moustafa, Amira; Habara, Yoshiaki

    2015-10-01

    In addition to nitric oxide (NO), hydrogen sulfide (H2S) is recognized as a crucial gaseous messenger that exerts many biological actions in various tissues. An attempt was made to assess the roles and underlying mechanisms of both gases in isolated rat parotid acinar cells. Ductal cells and some acinar cells were found to express NO and H2S synthases. Cevimeline, a muscarinic receptor agonist upregulated endothelial NO synthase in parotid tissue. NO and H2S donors increased the intracellular Ca(2+) concentration ([Ca(2+)]i). This was not affected by inhibitors of phospholipase C and inositol 1,4,5-trisphosphate receptors, but was decreased by blockers of ryanodine receptors (RyRs), soluble guanylyl cyclase, and protein kinase G. The H2S donor evoked NO production, which was decreased by blockade of NO synthases or phosphoinositide 3-kinase or by hypotaurine, an H2S scavenger. The H2S donor-induced [Ca(2+)]i increase was diminished by a NO scavenger or the NO synthases blocker. These results suggest that NO and H2S play important roles in regulating [Ca(2+)]i via soluble guanylyl cyclase-cGMP-protein kinase G-RyRs, but not via inositol 1,4,5-trisphosphate receptors. The effect of H2S may be partially through NO produced via phosphoinositide 3-kinase-Akt-endothelial NO synthase. It was concluded that both gases regulate [Ca(2+)]i in a synergistic way, mainly via RyRs in rat parotid acinar cells. PMID:26224578

  10. Gramicidin-perforated Patch Recording Revealed the Oscillatory Nature of Secretory Cl− Movements in Salivary Acinar Cells

    Sugita, Makoto; Hirono, Chikara; Shiba, Yoshiki

    2004-01-01

    Elevations of cytoplasmic free calcium concentrations ([Ca2+]i) evoked by cholinergic agonists stimulate isotonic fluid secretion in salivary acinar cells. This process is driven by the apical exit of Cl− through Ca2+-activated Cl− channels, while Cl− enters the cytoplasm against its electrochemical gradient via a loop diuretic-sensitive Na+-K+-2Cl− cotransporter (NKCC) and/or parallel operations of Cl−-HCO3 − and Na+-H+ exchangers, located in the basolateral membrane. To characterize the con...

  11. Postnatal Pancreas of Mice Contains Tripotent Progenitors Capable of Giving Rise to Duct, Acinar, and Endocrine Cells In Vitro.

    Ghazalli, Nadiah; Mahdavi, Alborz; Feng, Tao; Jin, Liang; Kozlowski, Mark T; Hsu, Jasper; Riggs, Arthur D; Tirrell, David A; Ku, H Teresa

    2015-09-01

    Postnatal pancreas is a potential source for progenitor cells to generate endocrine β-cells for treating type 1 diabetes. However, it remains unclear whether young (1-week-old) pancreas harbors multipotent progenitors capable of differentiating into duct, acinar, and endocrine cells. Laminin is an extracellular matrix (ECM) protein important for β-cells' survival and function. We established an artificial extracellular matrix (aECM) protein that contains the functional IKVAV (Ile-Lys-Val-Ala-Val) sequence derived from laminin (designated aECM-lam). Whether IKVAV is necessary for endocrine differentiation in vitro is unknown. To answer these questions, we cultured single cells from 1-week-old pancreas in semi-solid media supplemented with aECM-lam, aECM-scr (which contains a scrambled sequence instead of IKVAV), or Matrigel. We found that colonies were generated in all materials. Individual colonies were examined by microfluidic reverse transcription-polymerase chain reaction, immunostaining, and electron microscopy analyses. The majority of the colonies expressed markers for endocrine, acinar, and ductal lineages, demonstrating tri-lineage potential of individual colony-forming progenitors. Colonies grown in aECM-lam expressed higher levels of endocrine markers Insulin1, Insulin2, and Glucagon compared with those grown in aECM-scr and Matrigel, indicating that the IKVAV sequence enhances endocrine differentiation. In contrast, Matrigel was inhibitory for endocrine gene expression. Colonies grown in aECM-lam displayed the hallmarks of functional β-cells: mature insulin granules and glucose-stimulated insulin secretion. Colony-forming progenitors were enriched in the CD133(high) fraction and among 230 micro-manipulated single CD133(high) cells, four gave rise to colonies that expressed tri-lineage markers. We conclude that young postnatal pancreas contains multipotent progenitor cells and that aECM-lam promotes differentiation of β-like cells in vitro. PMID

  12. Involvement of M3 Cholinergic Receptor Signal Transduction Pathway in Regulation of the Expression of Chemokine MOB-1, MCP-1 Genes in Pancreatic Acinar Cells

    郑海; 陈道达; 张景輝; 田原

    2004-01-01

    Whether M3 cholinergic receptor signal transduction pathway is involved in regulation of the activation of NF-κB and the expression of chemokine MOB-1, MCP-1genes in pancreatic acinar cells was investigated. Rat pancreatic acinar cells were isolated, cultured and treated with carbachol, atropine and PDTC in vitro. The MOB-1 and MCP-1 mRNA expression was detected by using RT-PCR. The activation of NF-κB was monitored by using electrophoretic mobility shift assay.The results showed that as compared with control group, M3 cholinergic receptor agonist (103mol/L, 104-4ol/L carbachol) could induce a concentration-dependent and time-dependent increase in the expression of MOB-1, MCP-1 mRNA in pancreatic acinar cells. After treatment with 10 -3mol/L carbachol for 2 h, the expression of MOB-1, MCP-1 mRNA was strongest. The activity of NF-κB in pancreatic acinar cells was significantly increased (P<0.01) after treated with M3 cholinergic receptor agonist (10-3 mol/L carbachol) in vitro for 30 min. Either M3 cholinergic receptor antagonist (10-5 mol/L atropine) or NF-κB inhibitor (10-2 mol/L PDTC) could obviously inhibit the activation of NF-κB and the chemokine MOB-1, MCP-1 mRNA expression induced by carbachol (P <0.05). This inhibitory effect was significantly increased by atropine plus PDTC (P<0.01). The results of these studies indicated that M3 cholinergic receptor signal transduction pathway was likely involved in regulation of the expression of chemokine MOB-1 and MCP-1genes in pancreatic acinar cells in vitro through the activation of NF-κB.

  13. Adenovirus-mediated hAQP1 expression in irradiated mouse salivary glands causes recovery of saliva secretion by enhancing acinar cell volume decrease.

    Teos, L Y; Zheng, C-Y; Liu, X; Swaim, W D; Goldsmith, C M; Cotrim, A P; Baum, B J; Ambudkar, I S

    2016-07-01

    Head and neck irradiation (IR) during cancer treatment causes by-stander effects on the salivary glands leading to irreversible loss of saliva secretion. The mechanism underlying loss of fluid secretion is not understood and no adequate therapy is currently available. Delivery of an adenoviral vector encoding human aquaporin-1 (hAQP1) into the salivary glands of human subjects and animal models with radiation-induced salivary hypofunction leads to significant recovery of saliva secretion and symptomatic relief in subjects. To elucidate the mechanism underlying loss of salivary secretion and the basis for AdhAQP1-dependent recovery of salivary gland function we assessed submandibular gland function in control mice and mice 2 and 8 months after treatment with a single 15-Gy dose of IR (delivered to the salivary gland region). Salivary secretion and neurotransmitter-stimulated changes in acinar cell volume, an in vitro read-out for fluid secretion, were monitored. Consistent with the sustained 60% loss of fluid secretion following IR, a carbachol (CCh)-induced decrease in acinar cell volume from the glands of mice post IR was transient and attenuated as compared with that in cells from non-IR age-matched mice. The hAQP1 expression in non-IR mice induced no significant effect on salivary fluid secretion or CCh-stimulated cell volume changes, except in acinar cells from 8-month group where the initial rate of cell shrinkage was increased. Importantly, the expression of hAQP1 in the glands of mice post IR induced recovery of salivary fluid secretion and a volume decrease in acinar cells to levels similar to those in cells from non-IR mice. The initial rates of CCh-stimulated cell volume reduction in acinar cells from hAQP1-expressing glands post IR were similar to those from control cells. Altogether, the data suggest that expression of hAQP1 increases the water permeability of acinar cells, which underlies the recovery of fluid secretion in the salivary glands

  14. Pancreatic panniculitis in a patient with pancreatic-type acinar cell carcinoma of the liver – case report and review of literature

    Zundler, Sebastian; Erber, Ramona; Agaimy, Abbas; Hartmann, Arndt; Kiesewetter, Franklin; Strobel, Deike; Neurath, Markus F; Wildner, Dane

    2016-01-01

    Background Pancreatic panniculitis is a rare condition, which has only been described in relation with pancreatic diseases up to now. It is characterized by necrotizing subcutaneous inflammation and is thought to be triggered by adipocyte necrosis due to systemic release of pancreatic enzymes with consecutive infiltration of neutrophils. We present the first case of a patient with pancreatic panniculitis caused by pancreatic-type primary acinar cell carcinoma (ACC) of the liver and without un...

  15. The natural history of pancreatic acinar cell cystadenoma: Is resection better than surveillance? An update to a case report from 2010

    Darcy, David G.; Dominique Jan

    2016-01-01

    Cystic lesions of the pancreas are a rare entity, and few reports have described their natural history in children. A previously published report described a 9-year-old boy with an acinar cell cystadenoma, discovered during a laparoscopic appendectomy. Initially asymptomatic and followed by serial MRI, this patient presented to our institution several years later with chronic obstructive symptoms that required surgical intervention. Planning for resection included multidisciplinary input from...

  16. E-cadherin-negative acinar cell carcinoma of the pancreas: report of a case showing a solid pseudopapillary growth pattern.

    Tajima, Shogo; Waki, Michihiko; Azuma, Masaki; Koda, Kenji; Ohata, Akihiko

    2016-09-01

    E-cadherin expression patterns in acinar cell carcinomas (ACCs) of the pancreas have not been well documented. Herein, we present a hitherto undescribed case of E-cadherin-negative ACC with a solid pseudopapillary growth pattern in a 65-year-old man. We used an antibody against the extracellular domain of E-cadherin. As a further unusual status in ACC, faint β-catenin expression was observed in the cytoplasm of carcinoma cells. Morphological distinction from a solid pseudopapillary neoplasm (SPN) of the pancreas might be problematic in such a case, because of their similarities concerned with the growth pattern and E-cadherin negativity. Without nuclear accumulation of β-catenin, a diagnosis of SPN was almost excluded. Immunoreactivity for trypsin and BCL10 made an accurate diagnosis of ACC to this case. The tumor recurred 10 months post-surgery as rapidly enlarging masses in the liver, presumably indicating the aggressiveness of the E-cadherin-negative phenotype among ACCs. PMID:25600280

  17. Early events of secretory granule formation in the rat parotid acinar cell under the influence of isoproterenol. An ultrastructural and lectin cytochemical study

    F D’Amico

    2009-12-01

    Full Text Available The events involved in the maturation process of acinar secretory granules of rat parotid gland were investigated ultrastructurally and cytochemically by using a battery of four lectins [Triticum vulgaris agglutinin (WGA, Ulex europaeus agglutinin I (UEA-I, Glycine max agglutinin (SBA, Arachys hypogaea agglutinin (PNA]. In order to facilitate the study, parotid glands were chronically stimulated with isoproterenol to induce secretion. Specimens were embedded in the Lowicryl K4M resin. The trans-Golgi network (TGN derived secretory granules, which we refer to as immature secretory granules, were found to be intermediate structures in the biogenesis process of the secretory granules in the rat parotid acinar cell. These early structures do not seem to be the immediate precursor of the mature secretory granules: in fact, a subsequent interaction process between these early immature granule forms and TGN elements seems to occur, leading, finally, to the mature granules. These findings could explain the origin of the polymorphic subpopulations of the secretory granules in the normal acinar cells of the rat parotid gland. The lectin staining patterns were characteristic of each lectin. Immature and mature secretory gran- ules were labelled with WGA, SBA, PNA, and lightly with UEA-I. Cis and intermediate cisternae of the Golgi apparatus were labelled with WGA, and trans cisternae with WGA and SBA.

  18. Transdifferentiation of mouse adipose-derived stromal cells into acinar cells of the submandibular gland using a co-culture system

    Lee, Jingu; Park, Sangkyu; Roh, Sangho, E-mail: sangho@snu.ac.kr

    2015-05-15

    A loss of salivary gland function often occurs after radiation therapy in head and neck tumors, though secretion of saliva by the salivary glands is essential for the health and maintenance of the oral environment. Transplantation of salivary acinar cells (ACs), in part, may overcome the side effects of therapy. Here we directly differentiated mouse adipose-derived stromal cells (ADSCs) into ACs using a co-culture system. Multipotent ADSCs can be easily collected from stromal vascular fractions of adipose tissues. The isolated ADSCs showed positive expression of markers such as integrin beta-1 (CD29), cell surface glycoprotein (CD44), endoglin (CD105), and Nanog. The cells were able to differentiate into adipocytes, osteoblasts, and neural-like cells after 14 days in culture. ADSCs at passage 2 were co-cultured with mouse ACs in AC culture medium using the double-chamber (co-culture system) to avoid mixing the cell types. The ADSCs in this co-culture system expressed markers of ACs, such as α-amylases and aquaporin5, in both mRNA and protein. ADSCs cultured in AC-conditioned medium also expressed AC markers. Cellular proliferation and senescence analyses demonstrated that cells in the co-culture group showed lower senescence and a higher proliferation rate than the AC-conditioned medium group at Days 14 and 21. The results above imply direct conversion of ADSCs into ACs under the co-culture system; therefore, ADSCs may be a stem cell source for the therapy for salivary gland damage. - Highlights: • ADSCs could transdifferentiate into acinar cells (ACs) using ACs co-culture (CCA). • Transdifferentiated ADSCs expressed ACs markers such as α-amylase and aquaporin5. • High proliferation and low senescence were presented in CCA at Day 14. • Transdifferentiation of ADSCs into ACs using CCA may be an appropriate method for cell-based therapy.

  19. Transdifferentiation of mouse adipose-derived stromal cells into acinar cells of the submandibular gland using a co-culture system

    A loss of salivary gland function often occurs after radiation therapy in head and neck tumors, though secretion of saliva by the salivary glands is essential for the health and maintenance of the oral environment. Transplantation of salivary acinar cells (ACs), in part, may overcome the side effects of therapy. Here we directly differentiated mouse adipose-derived stromal cells (ADSCs) into ACs using a co-culture system. Multipotent ADSCs can be easily collected from stromal vascular fractions of adipose tissues. The isolated ADSCs showed positive expression of markers such as integrin beta-1 (CD29), cell surface glycoprotein (CD44), endoglin (CD105), and Nanog. The cells were able to differentiate into adipocytes, osteoblasts, and neural-like cells after 14 days in culture. ADSCs at passage 2 were co-cultured with mouse ACs in AC culture medium using the double-chamber (co-culture system) to avoid mixing the cell types. The ADSCs in this co-culture system expressed markers of ACs, such as α-amylases and aquaporin5, in both mRNA and protein. ADSCs cultured in AC-conditioned medium also expressed AC markers. Cellular proliferation and senescence analyses demonstrated that cells in the co-culture group showed lower senescence and a higher proliferation rate than the AC-conditioned medium group at Days 14 and 21. The results above imply direct conversion of ADSCs into ACs under the co-culture system; therefore, ADSCs may be a stem cell source for the therapy for salivary gland damage. - Highlights: • ADSCs could transdifferentiate into acinar cells (ACs) using ACs co-culture (CCA). • Transdifferentiated ADSCs expressed ACs markers such as α-amylase and aquaporin5. • High proliferation and low senescence were presented in CCA at Day 14. • Transdifferentiation of ADSCs into ACs using CCA may be an appropriate method for cell-based therapy

  20. Ionizing irradiation induces apoptotic damage of salivary gland acinar cells via NADPH oxidase 1-dependent superoxide generation

    Reactive oxygen species (ROS) have important roles in various physiological processes. Recently, several novel homologues of the phagocytic NADPH oxidase have been discovered and this protein family is now designated as the Nox family. We investigated the involvement of Nox family proteins in ionizing irradiation-induced ROS generation and impairment in immortalized salivary gland acinar cells (NS-SV-AC), which are radiosensitive, and immortalized ductal cells (NS-SV-DC), which are radioresistant. Nox1-mRNA was upregulated by γ-ray irradiation in NS-SV-AC, and the ROS level in NS-SV-AC was increased to approximately threefold of the control level after 10 Gy irradiation. The increase of ROS level in NS-SV-AC was suppressed by Nox1-siRNA-transfection. In parallel with the suppression of ROS generation and Nox1-mRNA expression by Nox1-siRNA, ionizing irradiation-induced apoptosis was strongly decreased in Nox1-siRNA-transfected NS-SV-AC. There were no large differences in total SOD or catalase activities between NS-SV-AC and NS-SV-DC although the post-irradiation ROS level in NS-SV-AC was higher than that in NS-SV-DC. In conclusion, these results indicate that Nox1 plays a crucial role in irradiation-induced ROS generation and ROS-associated impairment of salivary gland cells and that Nox1 gene may be targeted for preservation of the salivary gland function from radiation-induced impairment

  1. Damage to pancreatic acinar cells and preservation of islets of Langerhans in a rat model of acute pancreatitis induced by Karwinskia humboldtiana (buckthorn).

    Carcano-Diaz, Katya; Garcia-Garcia, Aracely; Segoviano-Ramirez, Juan Carlos; Rodriguez-Rocha, Humberto; Loera-Arias, Maria de Jesus; Garcia-Juarez, Jaime

    2016-09-01

    Karwinskia humboldtiana (Kh) is a poisonous plant that grows in some regions of the American continent. Consuming large amounts of Kh fruit results in acute intoxication leading to respiratory failure, culminating in death within days. There is evidence of histological damage to the lungs, liver, and kidneys following accidental and experimental Kh intoxication. To date, the microscopic effect of Kh consumption on the pancreas has not been described. We examined the early effects of Kh fruit on pancreatic tissue at different stages of acute intoxication in the Wistar rat. We found progressive damage confined to the exocrine pancreas, starting with a reduction in the number of zymogen granules, loss of acinar architecture, the presence of autophagy-like vesicles, apoptosis and inflammatory infiltrate. The pancreatic pathology culminated in damaged acini characterized by necrosis and edema, with a complete loss of lobular architecture. Interestingly, the morphology of the islets of Langerhans was conserved throughout our evaluations. Taken together, our results indicate the damage induced by a high dose of Kh fruit in the Wistar rat is consistent with an early acute necrotizing pancreatitis that exclusively affects the exocrine pancreas. Therefore, this system might be useful as an animal model to study the treatment of pancreatic diseases. More importantly, as the islets of Langerhans were preserved, the active compounds of Kh fruit could be utilized for the treatment of acinar pancreatic cancer. Further studies might provide insight into the severity of acute Kh intoxication in humans and influence the design of treatments for pancreatic diseases and acinar pancreatic cancer. PMID:26877198

  2. Zinc induces necrosis on rat pancreatic acinar AR42J cells

    Complete text of publication follows. Zinc is one of the essential metals, but high amounts of zinc induce several kinds of tissue damage. In those tissues, pancreatic exocrine cells are very sensitive to zinc, but the cause is still unclear. When 600 μM of zinc was added to AR42J cells, necrosis, but not apoptosis, quickly occurred. Zinc and sodium ions did not increase in the cytosol of AR42J cells even if 600 μM of zinc was added. However, calcium ion immediately increased in the cytosol after the addition of zinc and decreased quickly. Then, cytosol calcium content gradually increased again in a time-dependent manner. When 1.5 mM of calcium was added to the medium, the effect of 600 μM of zinc disappeared. On the contrary, rat pancreatic insulinoma cell line, RIN cells, did not increase cytosolic calcium concentration from zinc and necrosis was not induced by zinc. It is thought that zinc induces necrosis on AR42J cells by the increase of cytosolic calcium concentration, and the increase of extracellular calcium content inhibits the action of zinc that stimulates calcium transportation.

  3. Autophagy in pancreatic acinar cells in caerulein-treated mice: immunolocalization of related proteins and their potential as markers of pancreatitis.

    Zhang, Leshuai; Zhang, Jun; Shea, Katherine; Xu, Lin; Tobin, Grainne; Knapton, Alan; Sharron, Stewart; Rouse, Rodney

    2014-01-01

    Drug-induced pancreatitis (DIP) is an underdiagnosed condition that lacks sensitive and specific biomarkers. To better understand the mechanisms of DIP and to identify potential tissue biomarkers, we studied experimental pancreatitis induced in male C57BL/6 mice by intraperitoneal injection of caerulein (10 or 50 μg/kg) at 1-hr intervals for a total of 7 injections. Pancreata from caerulein-treated mice exhibited consistent acinar cell autophagy and apoptosis with infrequent necrosis. Kinetic assays for serum amylase and lipase also showed a dose-dependent increase. Terminal deoxynucleotidyl transferase-mediated biotin-dNTP nick labeling (TUNEL) detected dose-dependent acinar cell apoptosis. By light microscopy, autophagy was characterized by the formation of autophagosomes and autolysosomes (ALs) within the cytoplasm of acinar cells. Immunohistochemical studies with specific antibodies for proteins related to autophagy and pancreatic stress were conducted to evaluate these proteins as potential biomarkers of pancreatitis. Western blots were used to confirm immunohistochemical results using pancreatic lysates from control and treated animals. Autophagy was identified as a contributing process in caerulein-induced pancreatitis and proteins previously associated with autophagy were upregulated following caerulein treatment. Autophagosomes and ALs were found to be a common pathway, in which cathepsins, lysosome-associated membrane protein 2, vacuole membrane protein 1, microtubule-associated protein 1 light chain 3 (LC3), autophagy-related protein 9, Beclin1, and pancreatitis-associated proteins were simultaneously involved in response to caerulein stimulus. Regenerating islet-derived 3 gamma (Reg3γ), a pancreatic acute response protein, was dose-dependently induced in caerulein-treated mice and colocalized with the autophagosomal marker, LC3. This finding supports Reg3γ as a candidate biomarker for pancreatic injury. PMID:23640381

  4. Quantitative characterization of the protein contents of the exocrine pancreatic acinar cell by soft x-ray microscopy and advanced digital imaging methods

    Loo Jr., Billy W.

    2000-06-09

    The study of the exocrine pancreatic acinar cell has been central to the development of models of many cellular processes, especially of protein transport and secretion. Traditional methods used to examine this system have provided a wealth of qualitative information from which mechanistic models have been inferred. However they have lacked the ability to make quantitative measurements, particularly of the distribution of protein in the cell, information critical for grounding of models in terms of magnitude and relative significance. This dissertation describes the development and application of new tools that were used to measure the protein content of the major intracellular compartments in the acinar cell, particularly the zymogen granule. Soft x-ray microscopy permits image formation with high resolution and contrast determined by the underlying protein content of tissue rather than staining avidity. A sample preparation method compatible with x-ray microscopy was developed and its properties evaluated. Automatic computerized methods were developed to acquire, calibrate, and analyze large volumes of x-ray microscopic images of exocrine pancreatic tissue sections. Statistics were compiled on the protein density of several organelles, and on the protein density, size, and spatial distribution of tens of thousands of zymogen granules. The results of these measurements, and how they compare to predictions of different models of protein transport, are discussed.

  5. Fractionated irradiation and late changes in rat parotid gland: effects on the number of acinar cells, potassium efflux, and amylase secretion

    The authors used different in vitro secretory models and quantitative morphological characterization of rat parotid gland following fractionated unilateral irradiation to one gland on a 5-day fraction schedule with 6 MV photons (total dose 30, 35, 40 and 45 Gy) or a two-fractions regimen in 5 days with total dose of 24 and 32 Gy. The contralateral shielded gland served as control, and parallel analyses of irradiated and control glands were performed 180 days following the last irradiation. The relative noradrenaline stimulated electrolyte secretion (86rubidium tracer for potassium) was decreased in the irradiated compared with control glands. The noradrenaline-stimulated exocytotic amylase release was not significantly affected by irradiation, but the gland content of amylase was decreased dose-dependently. The quantitative morphological analysis revealed a dose-dependent decline in the number of acinar cells; the other parenchymal cells were unaffected by irradiation compared with controls. (author)

  6. Slug inhibits pancreatic cancer initiation by blocking Kras-induced acinar-ductal metaplasia

    Kazumi Ebine; Chow, Christina R.; DeCant, Brian T.; Hattaway, Holly Z.; Grippo, Paul J.; Krishan Kumar; Munshi, Hidayatullah G.

    2016-01-01

    Cells in the pancreas that have undergone acinar-ductal metaplasia (ADM) can transform into premalignant cells that can eventually become cancerous. Although the epithelial-mesenchymal transition regulator Snail (Snai1) can cooperate with Kras in acinar cells to enhance ADM development, the contribution of Snail-related protein Slug (Snai2) to ADM development is not known. Thus, transgenic mice expressing Slug and Kras in acinar cells were generated. Surprisingly, Slug attenuated Kras-induced...

  7. The effect of irradiation on the intracellular transportation of the parotid gland acinar cells in the mouse. Localization of monosaccharides studied by electron microscopic autoradiography

    Matsunaga, Hajime (Nippon Dental Univ., Tokyo (Japan))

    1994-06-01

    The present study was designed to investigate the effects of radiation on the ability to ingest monosaccharides and intracellular transportation in the parotid gland in mice. The submandibular regions, including the parotid gland, was exposed to 10 Gy of X-rays. Three days after irradiation, the localization of reducing silver grains in organelles was determined, using electron microscopic autoradiography with H-3 labeled galactosamine, glucosamine, fucose, and mannose. In the non-irradiated group, the proportion of reducing silver grains in the acinar cells began to increase 15 min after administration of monosaccharides, reached a peak at 180 min, and thereafter decreased. Similar findings were observed in the irradiated group, although the values were lower than the non-irradiated group. The proportion of reducing silver grains in the endoplasmic reticulum reached a peak at 15 min in both the non-irradiated and irradiated groups, and gradually decreased until 120 min. Thereafter, it became almost constant and low, but the proportion in the irradiated group was slightly higher than in the non-irradiated group. The proportion of reducing silver grains in the Golgi apparatus was maximum at 60 min in the non-irradiated group, and gradually decreased until 360 min. A similar tendency was seen in the irradiated group, although its variation was not so marked as in the non-irradiated group. The proportion of reducing silver grains in the condensing vacuoles was maximum at 120 min, and thereafter, it decreased; the decrease was only slight in the irradiated group. The proportion of reducing silver grains in secretory granules increased with time in both the non-irradiated and irradiated groups, although this was only slight in the irradiated group, and reached a peak at 360 min. Transportation of monosaccharides in an acinar cell was found to be delayed by irradiation. (N.K.).

  8. The effect of irradiation on the intracellular transportation of the parotid gland acinar cells in the mouse. Localization of monosaccharides studied by electron microscopic autoradiography

    The present study was designed to investigate the effects of radiation on the ability to ingest monosaccharides and intracellular transportation in the parotid gland in mice. The submandibular regions, including the parotid gland, was exposed to 10 Gy of X-rays. Three days after irradiation, the localization of reducing silver grains in organelles was determined, using electron microscopic autoradiography with H-3 labeled galactosamine, glucosamine, fucose, and mannose. In the non-irradiated group, the proportion of reducing silver grains in the acinar cells began to increase 15 min after administration of monosaccharides, reached a peak at 180 min, and thereafter decreased. Similar findings were observed in the irradiated group, although the values were lower than the non-irradiated group. The proportion of reducing silver grains in the endoplasmic reticulum reached a peak at 15 min in both the non-irradiated and irradiated groups, and gradually decreased until 120 min. Thereafter, it became almost constant and low, but the proportion in the irradiated group was slightly higher than in the non-irradiated group. The proportion of reducing silver grains in the Golgi apparatus was maximum at 60 min in the non-irradiated group, and gradually decreased until 360 min. A similar tendency was seen in the irradiated group, although its variation was not so marked as in the non-irradiated group. The proportion of reducing silver grains in the condensing vacuoles was maximum at 120 min, and thereafter, it decreased; the decrease was only slight in the irradiated group. The proportion of reducing silver grains in secretory granules increased with time in both the non-irradiated and irradiated groups, although this was only slight in the irradiated group, and reached a peak at 360 min. Transportation of monosaccharides in an acinar cell was found to be delayed by irradiation. (N.K.)

  9. CELL THERAPY OF HEART PATHOLOGIES

    Lukash, L.

    2008-01-01

    The review article is devoted to cellular cardiomyoplasty as a novel technology of treatment of cardiac insufficiency. The experiments on animals and the first clinical trials have shown the possibility to improve the contractile function of diseased heart after transplantation of different types of donor cells: cardiomyocytes, bone marrow enriched by hematopoietic stem cells and mesenchymal stem cells. The problems of cellular cardiomyoplasty are discussed.

  10. Adult pancreatic acinar cells give rise to ducts but not endocrine cells in response to growth factor signaling

    Blaine, Stacy A.; Ray, Kevin C.; Anunobi, Reginald; Gannon, Maureen A.; Washington, Mary K.; Means, Anna L.

    2010-01-01

    Studies in both humans and rodents have found that insulin+ cells appear within or near ducts of the adult pancreas, particularly following damage or disease, suggesting that these insulin+ cells arise de novo from ductal epithelium. We have found that insulin+ cells are continuous with duct cells in the epithelium that makes up the hyperplastic ducts of both chronic pancreatitis and pancreatic cancer in humans. Therefore, we tested the hypothesis that both hyperplastic ductal cells and their...

  11. Knockdown of GRP78 promotes apoptosis in pancreatic acinar cells and attenuates the severity of cerulein and LPS induced pancreatic inflammation.

    Yong Liu

    Full Text Available Acute pancreatitis (AP is a potentially lethal disease characterized by inflammation and parenchymal cell death; also, the severity of AP correlates directly with necrosis and inversely with apoptosis. However, mechanisms of regulating cell death in AP remain unclear. The endoplasmic reticulum (ER chaperone protein GRP78 has anti-apoptotic properties, in addition to modulating ER stress responses. This study used RNA interference (RNAi approach to investigate the potential role of GRP78 in regulating apoptosis during AP. In vitro models of AP were successfully developed by treating AR42J cells with cerulein or cerulein plus lipoplysaccharide (LPS. There was more pancreatic inflammation and less apoptosis with the cerulein plus LPS treatment. Furthermore, knockdown of GRP78 expression markedly promoted apoptosis and reduced necrosis in pancreatic acinar cells. This was accomplished by enhancing the activation of caspases and inhibiting the activity of X-linked inhibitor of apoptosis protein (XIAP, as well as a receptor interacting protein kinase-1(RIPK1, which is a key mediator of necrosis. This attenuated the severity of pancreatic inflammation, especially after cerulein plus LPS treatment. In conclusion, these findings indicate that GRP78 plays an anti-apoptotic role in regulating the cell death response during AP. Therefore, GRP78 is a potential therapeutic target for AP.

  12. Pancreatic ductal bicarbonate secretion: challenge of the acinar acid load

    Peter eHegyi

    2011-07-01

    Full Text Available Acinar and ductal cells of the exocrine pancreas form a close functional unit. Although most studies contain data either on acinar or ductal cells, an increasing number of evidence highlights the importance of the pancreatic acinar-ductal functional unit. One of the best examples for this functional unit is the regulation of luminal pH by both cell types. Protons co-released during exocytosis from acini cause significant acidosis, whereas, bicarbonate secreted by ductal cells cause alkalization in the lumen. This suggests that the first and probably one of the most important role of bicarbonate secretion by pancreatic ductal cells is not only to neutralize the acid chyme entering into the duodenum from the stomach, but to neutralize acidic content secreted by acinar cells. To accomplish this role, it is more than likely that ductal cells have physiological sensing mechanisms which would allow them to regulate luminal pH. To date, four different classes of acid-sensing ion channels have been identified in the gastrointestinal tract (transient receptor potential ion channels, two-pore domain potassium channel, ionotropic purinoceptor and acid-sensing ion channel, however, none of these have been studied in pancreatic ductal cells. In this mini-review, we summarize our current knowledge of these channels and urge scientists to characterize ductal acid-sensing mechanisms and also to investigate the challenge of the acinar acid load on ductal cells.

  13. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation

    Sara Calafate

    2015-05-01

    Full Text Available Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer’s disease (AD. Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology.

  14. Serotonin promotes acinar dedifferentiation following pancreatitis-induced regeneration in the adult pancreas.

    Saponara, Enrica; Grabliauskaite, Kamile; Bombardo, Marta; Buzzi, Raphael; Silva, Alberto B; Malagola, Ermanno; Tian, Yinghua; Hehl, Adrian B; Schraner, Elisabeth M; Seleznik, Gitta M; Zabel, Anja; Reding, Theresia; Sonda, Sabrina; Graf, Rolf

    2015-12-01

    The exocrine pancreas exhibits a distinctive capacity for tissue regeneration and renewal following injury. This regenerative ability has important implications for a variety of disorders, including pancreatitis and pancreatic cancer, diseases associated with high morbidity and mortality. Thus, understanding its underlying mechanisms may help in developing therapeutic interventions. Serotonin has been recognized as a potent mitogen for a variety of cells and tissues. Here we investigated whether serotonin exerts a mitogenic effect in pancreatic acinar cells in three regenerative models, inflammatory tissue injury following pancreatitis, tissue loss following partial pancreatectomy, and thyroid hormone-stimulated acinar proliferation. Genetic and pharmacological techniques were used to modulate serotonin levels in vivo. Acinar dedifferentiation and cell cycle progression during the regenerative phase were investigated over the course of 2 weeks. By comparing acinar proliferation in the different murine models of regeneration, we found that serotonin did not affect the clonal regeneration of mature acinar cells. Serotonin was, however, required for acinar dedifferentiation following inflammation-mediated tissue injury. Specifically, lack of serotonin resulted in delayed up-regulation of progenitor genes and delayed the formation of acinar-to-ductal metaplasia and defective acinar cell proliferation. We identified serotonin-dependent acinar secretion as a key step in progenitor-based regeneration, as it promoted acinar cell dedifferentiation and the recruitment of type 2 macrophages. Finally, we identified a regulatory Hes1-Ptfa axis in the uninjured adult pancreas, activated by zymogen secretion. Our findings indicated that serotonin plays a critical role in the regeneration of the adult pancreas following pancreatitis by promoting the dedifferentiation of acinar cells. PMID:26235267

  15. Pancreatic Acinar Cells Employ miRNAs as Mediators of Intercellular Communication to Participate in the Regulation of Pancreatitis-Associated Macrophage Activation.

    Zhao, Yong; Wang, Hao; Lu, Ming; Qiao, Xin; Sun, Bei; Zhang, Weihui; Xue, Dongbo

    2016-01-01

    Macrophage activation plays an important role in the inflammatory response in acute pancreatitis. In the present study, the activation of AR42J pancreatic acinar cells was induced by taurolithocholate treatment. The results showed that the culture medium from the activated AR42J cells significantly enhanced NFκB activation in the macrophages compared to that without taurolithocholate treatment. Additionally, the precipitates obtained from ultracentrifugation of the culture media that were rich in exosomes were markedly more potent in activating macrophages compared with the supernatant fraction lacking exosomes. The results indicated that the mediators carried by the exosomes played important roles in macrophage activation. Exosomal miRNAs were extracted and examined using microarrays. A total of 115 differentially expressed miRNAs were identified, and 30 showed upregulated expression, while 85 displayed downregulated expression. Target genes of the differentially expressed miRNAs were predicted using TargetScan, MiRanda, and PicTar software programs. The putative target genes were subjected to KEGG functional analysis. The functions of the target genes were primarily enriched in MAPK pathways. Specifically, the target genes regulated macrophage activation through the TRAF6-TAB2-TAK1-NIK/IKK-NFκB pathway. As the mediators of signal transduction, miRNAs and their predicted target mRNAs regulate every step in the MAPK pathway. PMID:27546996

  16. The p21-activated kinase, PAK2, is important in the activation of numerous pancreatic acinar cell signaling cascades and in the onset of early pancreatitis events.

    Nuche-Berenguer, Bernardo; Ramos-Álvarez, Irene; Jensen, R T

    2016-06-01

    In a recent study we explored Group-1-p21-activated kinases (GP.1-PAKs) in rat pancreatic acini. Only PAK2 was present; it was activated by gastrointestinal-hormones/neurotransmitters and growth factors in a PKC-, Src- and small-GTPase-mediated manner. PAK2 was required for enzyme-secretion and ERK/1-2-activation. In the present study we examined PAK2's role in CCK and TPA-activation of important distal signaling cascades mediating their physiological/pathophysiological effects and analyzed its role in pathophysiological processes important in early pancreatitis. In rat pancreatic acini, PAK2-inhibition by the specific, GP.1.PAK-inhibitor, IPA-3-suppressed cholecystokinin (CCK)/TPA-stimulated activation of focal-adhesion kinases and mitogen-activated protein-kinases. PAK2-inhibition reversed the dual stimulatory/inhibitory effect of CCK/TPA on the PI3K/Akt/GSK-3β pathway. However, its inhibition did not affect PKC activation. PAK2-inhibition protected acini from CCK-induced ROS-generation; caspase/trypsin-activation, important in early pancreatitis; as well as from cell-necrosis. Furthermore, PAK2-inhibition reduced proteolytic-activation of PAK-2p34, which is involved in programmed-cell-death. To ensure that the study did not only rely in the specificity of IPA-3 as a PAK inhibitor, we used two other approaches for PAK inhibition, FRAX597 a ATP-competitive-GP.1-PAKs-inhibitor and infection with a PAK2-dominant negative(DN)-Advirus. Those two approaches confirmed the results obtained with IPA-3. This study demonstrates that PAK2 is important in mediating CCK's effect on the activation of signaling-pathways known to mediate its physiological/pathophysiological responses including several cellular processes linked to the onset of pancreatitis. Our results suggest that PAK2 could be a new, important therapeutic target to consider for the treatment of diseases involving deregulation of pancreatic acinar cells. PMID:26912410

  17. Nonenzymatic cryogenic isolation of therapeutic cells: novel approach for enzyme-free isolation of pancreatic islets using in situ cryopreservation of islets and concurrent selective freeze destruction of acinar tissue.

    Taylor, Michael J; Baicu, Simona C

    2014-01-01

    Cell-based therapies, which all involve processes for procurement and reimplantation of living cells, currently rely upon expensive, inconsistent, and even toxic enzyme digestion processes. A prime example is the preparation of isolated pancreatic islets for the treatment of type 1 diabetes by transplantation. To avoid the inherent pitfalls of these enzymatic methods, we have conceptualized an alternative approach based on the hypothesis that cryobiological techniques can be used for differential freeze destruction of the pancreas (Px) to release islets that are selectively cryopreserved in situ. Pancreata were procured from juvenile pigs using approved procedures. The concept of cryoisolation is based on differential processing of the pancreas in five stages: 1) infiltrating islets in situ preferentially with a cryoprotectant (CPA) cocktail via antegrade perfusion of the major arteries; 2) retrograde ductal infusion of water to distend the acinar; 3) freezing the entire Px solid to dithizone for identification of intact islets and with Syto 13/PI for fluorescence viability testing and glucose-stimulated insulin release assessment. As predicted, the cryoisolate contained small fragments of residual tissue comprising an amorphous mass of acinar tissue with largely intact and viable (>90%) embedded islets. Islets were typically larger (range 50-500 µm diameter) than their counterparts isolated from juvenile pigs using conventional enzyme digestion techniques. Functionally, the islets from replicate cryoisolates responded to a glucose challenge with a mean stimulation index = 3.3 ± 0.7. An enzyme-free method of islet isolation relying on in situ cryopreservation of islets with simultaneous freeze destruction of acinar tissue is feasible and proposed as a new and novel method that avoids the problems associated with conventional collagenase digestion methods. PMID:23992741

  18. Congenital acinar dysplasia. Case Report

    Pulmonary hypoplasia (PH) is a rare cause of pulmonary insufficiency , and had a significant rate of morbidity and mortality among affected infants. In most cases ,pulmonary hypoplasia is secondry to underlying abnormalities . These may include space occupying lesions as infants with cogential diaphragmatic hernia; malformation of chest wall resulting in a small thorcacic cavity; severe and prolonged olygohydramnios; and neuromuscular disorders, which prevent normal fetal chest expansion.All lead to poor lung development. Primary PH as a result of cogenital acinar dysplasia is exceedingly rare and is diagnosed by exclusionof all known etiologies of secondary PH. (author)

  19. Small renal cell carcinoma: CT and pathologic correlation

    Objective: To analyze the correlation of CT and pathological manifestation of small renal cell carcinoma (SRCC). Methods: Thirty-six SRCC were all diagnosed by surgical pathology. On CT, attenuation value and the amount of enhancement were observed; on pathology, tumor cell characteristics, cell arrangement, the stage and grade of the tumor et al were observed. Results: 31 tumors were iso- or hypo-attenuation on CT and clear cell tumors were dominant in 28 cases; 5 cases were hyper-attenuation and 2 of them were granular cell carcinoma. After the contrast enhancement, 31 tumors were enhanced more than 40 HU. 27 of them were solid which had abundant sinusoid vessels; Enhancement in 29 cases was heterogeneous, and on pathology, hemorrhage and necrosis were found in 27 of them. Conclusion: The CT findings of SRCC were correlated with tumor cell characteristic and architecture

  20. Pathological Consequence of Misguided Dendritic Cell Differentiation in Histiocytic Diseases

    Berres, Marie-Luise; Allen, Carl E.; Merad, Miriam

    2013-01-01

    Histiocytic disorders represent a group of complex pathologies characterized by the accumulation of histiocytes, an old term for tissue-resident macrophages and dendritic cells. Langerhans cell histiocytosis is the most frequent of histiocytosis in humans and has been thought to arise from the abnormal accumulation of epidermal dendritic cells called Langerhans cells. In this chapter, we discuss the origin and differentiation of Langerhans cells and dendritic cells and present accumulated evi...

  1. FDG PET imaging of Ela1-myc mice reveals major biological differences between pancreatic acinar and ductal tumours

    The aim was to evaluate FDG PET imaging in Ela1-myc mice, a pancreatic cancer model resulting in the development of tumours with either acinar or mixed acinar-ductal phenotype. Transversal and longitudinal FDG PET studies were conducted; selected tissue samples were subjected to autoradiography and ex vivo organ counting. Glucose transporter and hexokinase mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR); Glut2 expression was analysed by immunohistochemistry. Transversal studies showed that mixed acinar-ductal tumours could be identified by FDG PET several weeks before they could be detected by hand palpation. Longitudinal studies revealed that ductal - but not acinar - tumours could be detected by FDG PET. Autoradiographic analysis confirmed that tumour areas with ductal differentiation incorporated more FDG than areas displaying acinar differentiation. Ex vivo radioactivity measurements showed that tumours of solely acinar phenotype incorporated more FDG than pancreata of non-transgenic littermates despite the fact that they did not yield positive PET images. To gain insight into the biological basis of the differential FDG uptake, glucose transporter and hexokinase transcript expression was studied in microdissected tumour areas enriched for acinar or ductal cells and validated using cell-specific markers. Glut2 and hexokinase I and II mRNA levels were up to 20-fold higher in ductal than in acinar tumours. Besides, Glut2 protein overexpression was found in ductal neoplastic cells but not in the surrounding stroma. In Ela1-myc mice, ductal tumours incorporate significantly more FDG than acinar tumours. This difference likely results from differential expression of Glut2 and hexokinases. These findings reveal previously unreported biological differences between acinar and ductal pancreatic tumours. (orig.)

  2. FDG PET imaging of Ela1-myc mice reveals major biological differences between pancreatic acinar and ductal tumours

    Abasolo, Ibane [Institut Municipal d' Investigacio Medica-Hospital del Mar, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Universitat Pompeu Fabra, Parc de Recerca Biomedica de Barcelona, Departament de Ciencies Experimentals i de la Salut, Barcelona (Spain); Institut d' Alta Tecnologia - CRC, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Pujal, Judit; Navarro, Pilar [Institut Municipal d' Investigacio Medica-Hospital del Mar, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Rabanal, Rosa M.; Serafin, Anna [Universitat Autonoma de Barcelona, Departament de Medicina i Cirurgia Animals, Barcelona (Spain); Millan, Olga [Institut d' Alta Tecnologia - CRC, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Real, Francisco X. [Institut Municipal d' Investigacio Medica-Hospital del Mar, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Universitat Pompeu Fabra, Parc de Recerca Biomedica de Barcelona, Departament de Ciencies Experimentals i de la Salut, Barcelona (Spain); Programa de Patologia Molecular, Centro Nacional de Investigaciones Oncologicas, Madrid (Spain)

    2009-07-15

    The aim was to evaluate FDG PET imaging in Ela1-myc mice, a pancreatic cancer model resulting in the development of tumours with either acinar or mixed acinar-ductal phenotype. Transversal and longitudinal FDG PET studies were conducted; selected tissue samples were subjected to autoradiography and ex vivo organ counting. Glucose transporter and hexokinase mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR); Glut2 expression was analysed by immunohistochemistry. Transversal studies showed that mixed acinar-ductal tumours could be identified by FDG PET several weeks before they could be detected by hand palpation. Longitudinal studies revealed that ductal - but not acinar - tumours could be detected by FDG PET. Autoradiographic analysis confirmed that tumour areas with ductal differentiation incorporated more FDG than areas displaying acinar differentiation. Ex vivo radioactivity measurements showed that tumours of solely acinar phenotype incorporated more FDG than pancreata of non-transgenic littermates despite the fact that they did not yield positive PET images. To gain insight into the biological basis of the differential FDG uptake, glucose transporter and hexokinase transcript expression was studied in microdissected tumour areas enriched for acinar or ductal cells and validated using cell-specific markers. Glut2 and hexokinase I and II mRNA levels were up to 20-fold higher in ductal than in acinar tumours. Besides, Glut2 protein overexpression was found in ductal neoplastic cells but not in the surrounding stroma. In Ela1-myc mice, ductal tumours incorporate significantly more FDG than acinar tumours. This difference likely results from differential expression of Glut2 and hexokinases. These findings reveal previously unreported biological differences between acinar and ductal pancreatic tumours. (orig.)

  3. Pathological modifications of plant stem cell destiny

    In higher plants, the shoot apex contains undifferentiated stem cells that give rise to various tissues and organs. The fate of these stem cells determines the pattern of plant growth as well as reproduction; and such fate is genetically preprogrammed. We found that a bacterial infection can derai...

  4. [Molecular pathology of plasma cell neoplasms].

    Fend, F

    2010-10-01

    Plasma cell myeloma (PCM) and related immunosecretory disorders are a group of B-cell proliferations with a wide clinical and prognostic spectrum, characterized by the production of monoclonal immunoglobulin by immortalized plasma cells. Recent years have seen an explosion in knowledge on the genetic basis and biology of these diseases, followed by improved clinical risk stratification and the introduction of novel therapeutic concepts, such as treatment with proteasome inhibitors or immunomodulatory substances. PCM is a common malignancy, accounting for approximately 10% of all hematological neoplasms. There is good evidence to support a multistep transformation process in plasma cell neoplasms, which corresponds to clinically discernible disease stages. Monoclonal gammopathy of unknown significance is a common asymptomatic precursor lesion for PCM which carries an approximately 1% annual risk for progression. Terminal disease stages are characterized by increasing genetic complexity and independence from bone marrow stromal cells and show a rapidly increasing tumour load with severe clinical symptoms. Modern diagnostics of plasma cell neoplasms require inclusion of clinical, morphological, immunophenotypical and cytogenetic features to allow for individual risk assessment and therapy planning. PMID:20852863

  5. Cell Biology and Pathology of Podocytes

    Greka, Anna; Mundel, Peter

    2013-01-01

    As an integral member of the filtration barrier in the kidney glomerulus, the podocyte is in a unique geographical position: It is exposed to chemical signals from the urinary space (Bowman’s capsule), it receives and transmits chemical and mechanical signals to/from the glomerular basement membrane upon which it elaborates, and it receives chemical and mechanical signals from the vascular space with which it also communicates. As with every cell, the ability of the podocyte to receive signals from the surrounding environment and to translate them to the intracellular milieu is dependent largely on molecules residing on the cell membrane. These molecules are the first-line soldiers in the ongoing battle to sense the environment, to respond to friendly signals, and to defend against injurious foes. In this review, we take a membrane biologist’s view of the podocyte, examining the many membrane receptors, channels, and other signaling molecules that have been implicated in podocyte biology. Although we attempt to be comprehensive, our goal is not to capture every membrane-mediated pathway but rather to emphasize that this approach may be fruitful in understanding the podocyte and its unique properties. PMID:22054238

  6. Monoclonal Antibody 16D10 to the C-Terminal Domain of the Feto-Acinar Pancreatic Protein Binds to Membrane of Human Pancreatic Tumoral SOJ-6 Cells and Inhibits the Growth of Tumor Xenografts

    Laurence Panicot-Dubois

    2004-11-01

    Full Text Available Feto-acinar pancreatic protein (FAPP characterized by mAbJ28 reactivity is a specific component associated with ontogenesis and behaves as an oncodevelopment-associated antigen. We attempted to determine whether pancreatic tumoral SOJ-6 cells are expressed at their surface FAPP antigens and to examine if specific antibodies directed against these FAPP epitopes could decrease the growth of pancreatic tumors in a mice model. For this purpose, we used specific antibodies against either the whole FAPP, the O-glycosylated C-terminal domain, or the N-terminal domain of the protein. Our results indicate that SOJ-6 cells expressed at their surface a 32-kDa peptide corresponding to the C-terminal domain of the FAPP. Furthermore, we show, by using endoproteinase Lys-C or geldanamycin, a drug able to impair the FAPP secretion, that this 32-kDa peptide expressed on the SOJ-6 cell surface comes from the degradation of the FAPP. Finally, an in vivo prospective study using a preventative tumor model in nude mice indicates that targeting this peptide by the use of mAb16D10 inhibits the growth of SOJ-6 xenografts. The specificity of mAb16D10 for pancreatic tumors and the possibility to obtain recombinant structures of mucin-like peptides recognized by mAb16D10 and mAbJ28 are promising tools in immunologic approaches to cure pancreatic cancers.

  7. Sphingolipid mediators in cardiovascular cell biology and pathology.

    Levade, T; Augé, N; Veldman, R J; Cuvillier, O; Nègre-Salvayre, A; Salvayre, R

    2001-11-23

    Sphingolipids have emerged as a new class of lipid mediators. In response to various extracellular stimuli, sphingolipid turnover can be stimulated in vascular cells and cardiac myocytes. Subsequent generation of sphingolipid molecules such as ceramide, sphingosine, and sphingosine-1-phosphate, is followed by regulation of ion fluxes and activation of various signaling pathways leading to smooth muscle cell proliferation, endothelial cell differentiation or apoptotic cell death, cell contraction, retraction, or migration. The importance of sphingolipids in cardiovascular signaling is illustrated by recent observations implicating them in physiological processes such as vasculogenesis as well as in frequent pathological conditions, including atherosclerosis and its complications. PMID:11717151

  8. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation

    Sara Calafate; Arjan Buist; Katarzyna Miskiewicz; Vinoy Vijayan; Guy Daneels; Bart de Strooper; Joris de Wit; Patrik Verstreken; Diederik Moechars

    2015-01-01

    Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer’s disease (AD). Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close dista...

  9. Mixed acinar-neuroendocrine-ductal carcinoma of the pancreas: a tale of three lineages.

    Anderson, Mark J; Kwong, Christina A; Atieh, Mohammed; Pappas, Sam G

    2016-01-01

    Most pancreatic cancers arise from a single cell type, although mixed pancreatic carcinomas represent a rare exception. The rarity of these aggressive malignancies and the limitations of fine-needle aspiration (FNA) pose significant barriers to diagnosis and appropriate management. We report a case of a 54-year-old man presenting with abdominal pain, jaundice and a hypodense lesion within the uncinate process on CT. FNA suggested poorly differentiated adenocarcinoma, which was subsequently resected via pancreaticoduodenectomy. Pathological analysis yielded diagnosis of invasive mixed acinar-neuroendocrine-ductal pancreatic carcinoma. Given the rare and deadly nature of these tumours, clinicians must be aware of their pathophysiology and do practice with a high degree of clinical suspicion, when appropriate. Surgical resection and thorough pathological analysis with immunohistochemical staining and electron microscopy remain the standards of care for mixed pancreatic tumours without gross evidence of metastasis. Diligent characterisation of the presentation and histological findings associated with these neoplasms should continue in order to promote optimal diagnostic and therapeutic strategies. PMID:27257019

  10. T1 relaxation in renal cell carcinoma with pathologic correlation

    Renal cell carcinoma, unlike most tumors, can have a shorter T1 on MR imaging than its host tissue. The author compared the signal intensity of renal tumor and normal renal tissue on T1 images obtained using contrast agents. A short T1 signal was seen in 16 of 23 cases of clear cells and/or hemorrhage. In six of eight cases with a long T1 signal, necrosis was found on gross pathologic examination. In four of five cases of isointense signal an unusual pathology was found; one of the five patients was in end-stage renal failure. Fat-containing clear cells and hemorrhage produce a short T1 signal, whereas necrosis produces a long T1 signal

  11. Effects of a diet high in fish oil (MaxEPA) on the formation of micronucleated erythrocytes in blood and on the number of atypical acinar cell foci Induced in rat pancreas by azaserine.

    Appel, Marko J; Woutersen, Ruud A

    2003-01-01

    The present study was performed to investigate the influence of fish oil on the genotoxic effects of azaserine, using the formation of micronucleated erythrocytes as a measure for the degree of initiating potency and the number and size of putative preneoplastic pancreatic atypical acinar cell foci (AACF) as a measure for the actual number of initiated cells. Male Wistar rats were treated twice i.p. with 30 mg azaserine per kg body weight to induce AACF. During the initiation/early promotion phase the rats were maintained on diets containing 5 wt% vegetable oil (safflower and high-oleic sunflower oil), 25 wt% vegetable oil, 25 wt% fat (15% vegetable oil + 10 wt% fish oil), or 25 wt% fat (5% vegetable oil + 20 wt% fish oil), respectively. One day after carcinogen treatment, the numbers of micronucleated polychromatic erythrocytes were determined in blood smears obtained from 10 animals per group. Each high-fat diet resulted in higher percentages of micronucleated polychromatic erythrocytes than the low-fat diet. Dietary fish oil did not significantly influence the number of micronucleated cells. Two weeks after carcinogen treatment, the diets containing fish oil were replaced by the diet containing 25% vegetable oil, and the animals were further maintained for about 14 wk. Pancreatic tissue slides were microscopically evaluated for the number and size of AACF. Dietary fish oil caused an increase in the number and size of AACF, although a clear dose-effect relationship was absent. It was concluded that a high level of dietary fish oil, when given during the induction/early promotion phase, enhances azaserine-induced pancreatic carcinogenesis in rats. PMID:14769538

  12. Genes and pathology of non-small cell lung carcinoma.

    Sakashita, Shingo; Sakashita, Mai; Sound Tsao, Ming

    2014-02-01

    While histopathology has traditionally been the cornerstone of treatment decisions in the management of lung cancer patients, the complexity and heterogeneity of histological classification has had a limited impact in the routine practice of oncology. This has changed dramatically in the last few years, owing to discoveries of genomic aberrations and results of clinical trials of novel and targeted therapies. These discoveries have resulted in a new way of classifying non-small cell lung cancer (NSCLC), based on the occurrence of putative or proven driver and targetable genomic changes. The rapidity by which the landscape of mutation and genomic changes is being identified also has led to a new paradigm and approaches to pathological diagnosis of NSCLC. In this context, international consortia have proposed new classifications of lung adenocarcinoma and guidelines for molecular testing in lung cancer and have provided concrete recommendations on new ways to practice lung cancer pathology. PMID:24565579

  13. Confocal Raman microscopy of pathologic cells in cerebrospinal fluid

    In this work, the spatial localization of leucocytes, bacteria, and erythrocytes in the crystal pattern of a dried droplet of cerebrospinal fluid (CSF) is established. Characteristic lines are detected and identified in the Raman spectrum of the CSF that point to the presence of pathologic cells therein and can be used in a timely way to diagnose meningitis, the spectroscopic sample preparation procedure being simple enough. A dry CSF sample retains its characteristic spectral features for no less than three days, which is important for its safe keeping and transportation, and also for the computer processing of its spectra. (letter)

  14. Acinar autolysis and mucous extravasation in human sublingual glands: a microscopic postmortem study

    Luciana Reis AZEVEDO-ALANIS

    2015-10-01

    Full Text Available Although some morphological investigations on aged human sublingual glands (HSG found eventual phenomena identified as autolysis and mucous extravasation, the exact meaning of these findings has not been elucidated.Objective The aim of this work is to investigate whether acinar autolysis and mucous extravasation are related to the aging process in human sublingual glands. We also speculate if autolytic changes may assist forensic pathologists in determining time of death.Material and Methods 186 cadavers’ glands were allocated to age groups: I (0–30 years; II (31–60, and III (61–90. Time and mode of death were also recorded. Acinar autolysis and mucous extravasation were classified as present or absent. Ultrastructural analysis was performed using transmission electron microscopy (TEM. Data were compared using Mann-Whitney U, Spearman’s correlation coefficient, Kruskal-Wallis, and Dunn tests (p<0.05.Results There was correlation between age and acinar autolysis (r=0.38; p=0.0001. However, there was no correlation between autolysis and time of death. No differences were observed between genders. TEM showed mucous and serous cells presenting nuclear and membrane alterations and mucous cells were more susceptible to autolysis.Conclusion Acinar autolysis occurred in all age groups and increased with age while mucous extravasation was rarely found. Both findings are independent. Autolysis degrees in HSG could not be used to determine time of death.

  15. Stem cell applications for pathologies of the urinary bladder

    2015-01-01

    New stem cell based therapies are undergoing intenseresearch and are widely investigated in clinical fieldsincluding the urinary system. The urinary bladderperforms critical complex functions that rely on its highlycoordinated anatomical composition and multiplex ofregulatory mechanisms. Bladder pathologies resulting insevere dysfunction are common clinical encounter andoften cause significant impairment of patient's quality oflife. Current surgical and medical interventions to correcturinary dysfunction or to replace an absent or defectivebladder are sub-optimal and are associated with notablecomplications. As a result, stem cell based therapiesfor the urinary bladder are hoped to offer new venuesthat could make up for limitations of existing therapies.In this article, we review research efforts that describethe use of different types of stem cells in bladderreconstruction, urinary incontinence and retentiondisorders. In particular, stress urinary incontinence hasbeen a popular target for stem cell based therapiesin reported clinical trials. Furthermore, we discuss therelevance of the cancer stem cell hypothesis to thedevelopment of bladder cancer. A key subject thatshould not be overlooked is the safety and quality ofstem cell based therapies introduced to human subjectseither in a research or a clinical context.

  16. p21(WAF1) (/Cip1) limits senescence and acinar-to-ductal metaplasia formation during pancreatitis.

    Grabliauskaite, Kamile; Hehl, Adrian B; Seleznik, Gitta M; Saponara, Enrica; Schlesinger, Kathryn; Zuellig, Richard A; Dittmann, Anja; Bain, Martha; Reding, Theresia; Sonda, Sabrina; Graf, Rolf

    2015-02-01

    Trans-differentiation of pancreatic acinar cells into ductal-like lesions, a process defined as acinar-to-ductal metaplasia (ADM), is observed in the course of organ regeneration following pancreatitis. In addition, ADM is found in association with pre-malignant PanIN lesions and correlates with an increased risk of pancreatic adenocarcinoma (PDAC). Human PDAC samples show down-regulation of p21(WAF1) (/Cip1) , a key regulator of cell cycle and cell differentiation. Here we investigated whether p21 down-regulation is implicated in controlling the early events of acinar cell trans-differentiation and ADM formation. p21-mediated regulation of ADM formation and regression was analysed in vivo during the course of cerulein-induced pancreatitis, using wild-type (WT) and p21-deficient (p21(-/-) ) mice. Biochemical and immunohistochemical methods were used to evaluate disease progression over 2 weeks of the disease and during a recovery phase. We found that p21 was strongly up-regulated in WT acinar cells during pancreatitis, while it was absent in ADM areas, suggesting that p21 down-regulation is associated with ADM formation. In support of this hypothesis, p21(-/-) mice showed a significant increase in number and size of metaplasia. In addition, p21 over-expression in acinar cells reduced ADM formation in vitro, suggesting that the protein regulates the metaplastic transition in a cell-autonomous manner. p21(-/-) mice displayed increased expression and relocalization of β-catenin both during pancreatitis and in the subsequent recovery phase. Finally, loss of p21 was accompanied by increased DNA damage and development of senescence. Our findings are consistent with a gate-keeper role of p21 in acinar cells to limit senescence activation and ADM formation during pancreatic regeneration. PMID:25212177

  17. Induction of C-FOS, C-MYC and P53 by β-adrenergic receptor (β-AR) stimulation of rat parotid acinar cells (RPAC)

    Treatment of rats with the β-agonist isoproterenol (ISO) results in dramatically increased parotid gland protein synthesis, processing and cell proliferation. The authors have shown that in RPAC in vitro, β-AR stimulation has similar effect on protein synthesis and processing. Proto-oncogenes have been implicated in growth regulation, differentiation and in mediating some extracellular stimulated events at the level of gene expression. To understand the regulation of cellular events after β-AR stimulation, the expression of c-fos, c-myc and p53 was investigated. RPAC were incubated with or without 10-5M ISO for 15, 30, 60 min. mRNA was isolated from cells and hybridization analysis was performed on nitrocellulose paper-transferred mRNA using 32P-labeled DNA probes. At early time points, the levels of c-fos gene activation in ISO-treated and control cells were comparable. After 60 min of ISO treatment, a sharp 20-30 fold induction of c-fos expression occurred. Similar increases in c-myc and p53 gene expression were observed after 60 min of ISO treatment. The authors data indicate that early effects of β-AR stimulation of RPAC include induction of c-fos, c-myc and p53 gene expression as well as enhanced protein synthesis and processing

  18. Hypoxic vasoconstriction of partial muscular intra-acinar pulmonary arteries in murine precision cut lung slices

    Goldenberg Anna

    2006-06-01

    Full Text Available Abstract Background Acute alveolar hypoxia causes pulmonary vasoconstriction (HPV which serves to match lung perfusion to ventilation. The underlying mechanisms are not fully resolved yet. The major vascular segment contributing to HPV, the intra-acinar artery, is mostly located in that part of the lung that cannot be selectively reached by the presently available techniques, e.g. hemodynamic studies of isolated perfused lungs, recordings from dissected proximal arterial segments or analysis of subpleural vessels. The aim of the present study was to establish a model which allows the investigation of HPV and its underlying mechanisms in small intra-acinar arteries. Methods Intra-acinar arteries of the mouse lung were studied in 200 μm thick precision-cut lung slices (PCLS. The organisation of the muscle coat of these vessels was characterized by α-smooth muscle actin immunohistochemistry. Basic features of intra-acinar HPV were characterized, and then the impact of reactive oxygen species (ROS scavengers, inhibitors of the respiratory chain and Krebs cycle metabolites was analysed. Results Intra-acinar arteries are equipped with a discontinuous spiral of α-smooth muscle actin-immunoreactive cells. They exhibit a monophasic HPV (medium gassed with 1% O2 that started to fade after 40 min and was lost after 80 min. This HPV, but not vasoconstriction induced by the thromboxane analogue U46619, was effectively blocked by nitro blue tetrazolium and diphenyleniodonium, indicating the involvement of ROS and flavoproteins. Inhibition of mitochondrial complexes II (3-nitropropionic acid, thenoyltrifluoroacetone and III (antimycin A specifically interfered with HPV, whereas blockade of complex IV (sodium azide unspecifically inhibited both HPV and U46619-induced constriction. Succinate blocked HPV whereas fumarate had minor effects on vasoconstriction. Conclusion This study establishes the first model for investigation of basic characteristics of HPV

  19. 姜黄素对长期摄入酒精和不同量蛋白质的大鼠胰腺腺泡细胞损伤的保护作用研究%Effects of Curcumin on Pancreatic Acinar Cell Injury in Rats with Long-term Alcohol Intake and Different Amount of Protein

    周旭春

    2011-01-01

    目的:研究姜黄素对长期摄入酒精和不同量蛋白质的大鼠胰腺腺泡细胞损伤的保护作用.方法:实验分为5组,即正常对照(正常饲养)、高蛋白、低蛋白、高蛋白+姜黄素、低蛋白+姜黄素(以25%酒精代替饮水自由饮用,高、低蛋白质占总热量供给的32%、6%,喂饲6个月)组.在光镜和电镜下观察大鼠胰腺腺泡细胞结构变化,用比色法检测胰腺组织匀浆淀粉酶和脂肪酶的含量,TUNEL法检测腺泡细胞凋亡情况,免疫组化检测胰腺组织切片中环氧化酶-2(COX-2)的变化.结果:与高、低蛋白组比较,高、低蛋白+姜黄素组大鼠胰腺腺泡细胞髓样结构减少,线粒体肿胀减轻;淀粉酶和脂肪酶含量均显著升高(P<0.05);胰腺腺泡细胞凋亡显著减少(P<0.05);COX-2的表达降低.结论:姜黄素可预防摄入酒精联合过高或过低蛋白质的大鼠胰腺腺泡细胞损伤,延缓酒精性胰腺损伤的进程.%OBJECTIVE: To investigate the protective effects of curcumin on pancreatic acinar cell injury in rats with long-term alcohol intake and protein consumption. METHODS: Wistar rats were divided into 5 groups, I.e. Normal control group (the group fed with normal feed) ,high protein group, low protein group, high protein+curcumin group, low protein+curcumin group (those groups fed with diet containing 25% ethanol instead of drinking water for 6 months). High and low protein accounted for 32% and 6 % of total heat quantity. The structure change of pancreatic acinar cell was observed under light microscope and electron microscope. The contents of amylase and lipase in pancreatic tissue homogenate were determined by colorimetry. Apoptosis and expression of cyclooxygenase-2(COX-2) in acinar cell were detected by TUNEL and immunohistochemical staining, respectively. RESULTS: Compared with no application of curcumin, myelin figure and enlarged mitochondria were reduced in curcumin treatment groups. Lipase and amylase

  20. A Microfluidic Model of Biomimetically Breathing Pulmonary Acinar Airways.

    Fishler, Rami; Sznitman, Josué

    2016-01-01

    Quantifying respiratory flow characteristics in the pulmonary acinar depths and how they influence inhaled aerosol transport is critical towards optimizing drug inhalation techniques as well as predicting deposition patterns of potentially toxic airborne particles in the pulmonary alveoli. Here, soft-lithography techniques are used to fabricate complex acinar-like airway structures at the truthful anatomical length-scales that reproduce physiological acinar flow phenomena in an optically accessible system. The microfluidic device features 5 generations of bifurcating alveolated ducts with periodically expanding and contracting walls. Wall actuation is achieved by altering the pressure inside water-filled chambers surrounding the thin PDMS acinar channel walls both from the sides and the top of the device. In contrast to common multilayer microfluidic devices, where the stacking of several PDMS molds is required, a simple method is presented to fabricate the top chamber by embedding the barrel section of a syringe into the PDMS mold. This novel microfluidic setup delivers physiological breathing motions which in turn give rise to characteristic acinar air-flows. In the current study, micro particle image velocimetry (µPIV) with liquid suspended particles was used to quantify such air flows based on hydrodynamic similarity matching. The good agreement between µPIV results and expected acinar flow phenomena suggest that the microfluidic platform may serve in the near future as an attractive in vitro tool to investigate directly airborne representative particle transport and deposition in the acinar regions of the lungs. PMID:27214269

  1. Epiplakin deficiency aggravates murine caerulein-induced acute pancreatitis and favors the formation of acinar keratin granules.

    Karl L Wögenstein

    Full Text Available Epiplakin, a member of the plakin protein family, is exclusively expressed in epithelial tissues and was shown to bind to keratins. Epiplakin-deficient (EPPK-/- mice showed no obvious spontaneous phenotype, however, EPPK-/- keratinocytes displayed faster keratin network breakdown in response to stress. The role of epiplakin in pancreas, a tissue with abundant keratin expression, was not yet known. We analyzed epiplakin's expression in healthy and inflamed pancreatic tissue and compared wild-type and EPPK-/- mice during caerulein-induced acute pancreatitis. We found that epiplakin was expressed primarily in ductal cells of the pancreas and colocalized with apicolateral keratin bundles in murine pancreatic acinar cells. Epiplakin's diffuse subcellular localization in keratin filament-free acini of K8-deficient mice indicated that its filament-associated localization in acinar cells completely depends on its binding partner keratin. During acute pancreatitis, epiplakin was upregulated in acinar cells and its redistribution closely paralleled keratin reorganization. EPPK-/- mice suffered from aggravated pancreatitis but showed no obvious regeneration phenotype. At the most severe stage of the disease, EPPK-/- acinar cells displayed more keratin aggregates than those of wild-type mice. Our data propose epiplakin to be a protective protein during acute pancreatitis, and that its loss causes impaired disease-associated keratin reorganization.

  2. Metabolic Profile of Pancreatic Acinar and Islet Tissue in Culture

    Suszynski, Thomas M; Mueller, Kathryn; Gruessner, Angelika C.; Papas, Klearchos K.

    2014-01-01

    The amount and condition of exocrine impurities may affect the quality of islet preparations especially during culture. In this study, the objective was to determine the oxygen demandand viability of islet and acinar tissue post-isolation and whether they change disproportionately while in culture. We compare the OCR normalized to DNA (OCR/DNA, a measure of fractional viability in units nmol/min/mg DNA), and percent change in OCR and DNA recoveries between adult porcine islet and acinar tissu...

  3. Inhibition of proliferation by PERK regulates mammary acinar morphogenesis and tumor formation.

    Sharon J Sequeira

    Full Text Available Endoplasmic reticulum (ER stress signaling can be mediated by the ER kinase PERK, which phosphorylates its substrate eIF2alpha. This in turn, results in translational repression and the activation of downstream programs that can limit cell growth through cell cycle arrest and/or apoptosis. These responses can also be initiated by perturbations in cell adhesion. Thus, we hypothesized that adhesion-dependent regulation of PERK signaling might determine cell fate. We tested this hypothesis in a model of mammary acini development, a morphogenetic process regulated in part by adhesion signaling. Here we report a novel role for PERK in limiting MCF10A mammary epithelial cell proliferation during acinar morphogenesis in 3D Matrigel culture as well as in preventing mammary tumor formation in vivo. We show that loss of adhesion to a suitable substratum induces PERK-dependent phosphorylation of eIF2alpha and selective upregulation of ATF4 and GADD153. Further, inhibition of endogenous PERK signaling during acinar morphogenesis, using two dominant-negative PERK mutants (PERK-DeltaC or PERK-K618A, does not affect apoptosis but results instead in hyper-proliferative and enlarged lumen-filled acini, devoid of proper architecture. This phenotype correlated with an adhesion-dependent increase in translation initiation, Ki67 staining and upregulation of Laminin-5, ErbB1 and ErbB2 expression. More importantly, the MCF10A cells expressing PERKDeltaC, but not a vector control, were tumorigenic in vivo upon orthotopic implantation in denuded mouse mammary fat pads. Our results reveal that the PERK pathway is responsive to adhesion-regulated signals and that it is essential for proper acinar morphogenesis and in preventing mammary tumor formation. The possibility that deficiencies in PERK signaling could lead to hyperproliferation of the mammary epithelium and increase the likelihood of tumor formation, is of significance to the understanding of breast cancer.

  4. Bone marrow-derived cells are differentially involved in pathological and physiological retinal angiogenesis in mice

    Purpose: Bone marrow-derived cells have been shown to play roles in angiogenesis. Although these cells have been shown to promote angiogenesis, it is not yet clear whether these cells affect all types of angiogenesis. This study investigated the involvement of bone marrow-derived cells in pathological and physiological angiogenesis in the murine retina. Materials and methods: The oxygen-induced retinopathy (OIR) model was used as a retinal angiogenesis model in newborn mice. To block the influence of bone marrow-derived cells, the mice were irradiated with a 4-Gy dose of radiation from a 137Cs source. Irradiation was performed in four different conditions with radio dense 2-cm thick lead disks; (1) H group, the head were covered with these discs to protect the eyes from radiation; (2) A group, all of the body was covered with these discs; (3) N group, mice were completely unshielded; (4) C group, mice were put in the irradiator but were not irradiated. On P17, the retinal areas showing pathological and physiological retinal angiogenesis were measured and compared to the retinas of nonirradiated mice. Results: Although irradiation induced leukocyte depletion, it did not affect the number of other cell types or body weight. Retinal nonperfusion areas were significantly larger in irradiated mice than in control mice (P < 0.05), indicating that physiological angiogenesis was impaired. However, the formation of tuft-like angiogenesis processes was more prominent in the irradiated mice (P < 0.05), indicating that pathological angiogenesis was intact. Conclusions: Bone marrow-derived cells seem to be differentially involved in the formation of physiological and pathological retinal vessels. Pathological angiogenesis in the murine retina does not require functional bone marrow-derived cells, but these cells are important for the formation of physiological vessels. Our results add a new insight into the pathology of retinal angiogenesis and bolster the hypothesis that bone

  5. Multi-slice spiral CT and pathological correlation of renal cell carcinoma

    Objective: To analyze relationship between characteristics on multi-slice spiral CT (MSCT) and pathology of renal cell carcinoma. Methods: Multi-slice spiral CT and surgical pathological results on 32 cases of renal cell carcinoma were retrospectively analyzed. Results: Of the 32 cases, 28 were pathologically diagnosed as clear cell carcinoma, with tumor contrast enhancement similar to the normal cortex in the renal cortical phase (146-175HU), slight contrast washout in the renal parenchyma phase and significant contrast washout from the tumor in the pyelographic phase. Granular cell carcinoma in 4 patients showed no or mild contrast enhancement (38- 55HU) in all three phase. The overall diagnostic accordance rate was 100%, with preoperative staging accordance rate of 96.42%. Conclusion: The triple-phase contrast-enhanced MSCT is useful in predicting the tumor cell type and staging of renal cell carcinoma. (authors)

  6. PTD-NBD polypeptide down-regulates expression of NF-κB p65 in inflammatory pancreatic acinar cell injury in rats%PTD-NBD多肽对大鼠胰腺腺泡细胞炎症损伤中NF-κB表达的影响

    谢文瑞; 杨元生; 杨新魁; 陈垦; 陈婧华; 崔淑兰; 王晖

    2013-01-01

    To examine the effect of PTD-NBD polypeptide on the expression of nuclear factor κB (NF-κB) p65 in inflammatory pancreatic acinar cell injury in rats.METHODS:Rat pancreatic acinar cells were isolated,cultured,and divided into a normal control group,an acute pancreatitis (AP) group and a PTD-NBD polypeptides group.An in vitro model of AP was induced by treating rat pancreatic acinar cells with lipopolysaccharide (10 mg/L).Cell morphological changes were observed,and the contents of amylase,superoxide dismutase (SOD) and IL-1β in culture medium were tested.Expression of NF-κB p65 mRNA and protein in cells was detected by RT-PCR and Western blot 6 and 12 h after modeling,respectively.RESULTS:Compared to the control group,pancreatic acinar cell swelling and death were increased (6 h:8.9 ± 0.34 vs 1.1 ± 0.13; 12 h:9.4 ± 0.26 vs 1.2 ± 0.15,both P < 0.05),the contents of amylase (6 h:2135.8 ± 347.2 vs 873.5 ± 91.6; 12 h:3299.6 ± 217.7 vs 917.7 ± 101.9,both P < 0.05) and IL-1β (6 h:84.9 ± 15.7 vs 39.3 ± 7.9; 12 h:95.6 ± 17.1 vs 38.9 ± 5.2,both P < 0.05) were increased and the contents of SOD were decreased in culture medium (6 h:116.3 ± 30.3 vs 176.2 ± 21.6; 12h:101.5 ± 25.6 vs 173.6 ± 27.9,P < 0.05),and the expression of NF-kB p65 in pancreatic acinar ceils was increased (P < 0.05) in the AP group at 6 and 12 h after modeling.Compared to the AP group,pancreatic acinar cell swelling and death were lessened (6 h:6.8 ± 0.23 vs 8.9 ± 0.34; 12 h:7.5 ± 0.19 vs 9.4 ± 0.26,both P < 0.05),the contents of SOD were raised (6 h:137.6 ± 27.4 vs 116.3 ± 30.3; 12 h:144.3 ± 23.6 vs 101.5 ± 25.6,both P < 0.05)and the contents of amylase (6 h:1951.5 ± 211.7 vs 2135.8 ± 347.2; 12 h:1761.3 ± 231.5 vs 3299.6 ± 217.7,both P < 0.05) and IL-1β (6 h:66.8 ± 11.6 vs 84.9 ± 15.7; 12 h:54.8 ± 21.2 vs 95.6 ± 17.1,both P < 0.05) were decreased in culture medium,and the expression of NF-κB p65 mRNA and protein was down-regulated in the PAT

  7. Cytotoxic effect of desoxycholic acid on pancreatic acinar cells and its influence on the activity of nuclear transcription factors%脱氧胆酸对胰腺腺泡细胞的损伤及核转录因子活性的影响

    张桂信; 陈海龙; 曹传海; 林小洋; 张利; 纪军; 王永鹏

    2011-01-01

    目的 观察脱氧胆酸(DCA)对AR42J胰腺腺泡细胞的损伤作用并探讨其对核转录因子(TF)活性的影响。方法 应用噻唑蓝(MTT)比色法检测DCA作用下细胞存活率改变,流式细胞术AV/PI双染法检测细胞的凋亡/坏死率。细胞经0.4mmoL/L DCA分别作用15 min、30 min、4h后收集培液上清,收集细胞并提取细胞质和细胞核蛋白,分别检测培液上清和胞质淀粉酶的活性,利用Luminex检测细胞核TF的DNA结合活性。结果 DCA对AR42J胰腺腺泡细胞的损伤作用呈浓度和时间依赖性,对细胞质内和培液中的淀粉酶水平无明显影响。在检测的40种TF活性变化中,DCA诱导ATF2、AR33、STAT5、NFAT、FKHR和NKX-2.5这6种TF活性明显升高,而RUNX/AML、NF-Y、MEF2和E2F1这4种TF活性则明显下降,其余30种TF活性无明显变化。结论 DCA对腺泡细胞的损伤作用主要表现为凋亡和坏死,对细胞内酶的合成和分泌功能没有明显影响。DCA诱导细胞核TF活性的变化,可能是其诱导细胞损伤的分子生物学基础。%Objective To study the cytotoxic effect of desoxycholic acid (DCA) on pancreatic acinar cells AR42J, its impact on the synthesis and secretion function of amylase, and the influence on the activity of nuclear transcription factor (TF). MethodsThe cytotoxic effect of DCS was detected in rat AR42J cells by using methyl thiazol tetrazolium (MTT) assay. The rate of apoptosis or necrosis was determined by flow cytometry. After the cells were incubated with DCA (0. 4 mmol/L) for 15 min, 30 min, or 4 h, the medium was collected to detect the activity of amylase. The cytoplamic protein was extracted to detect the activity of amylase, and nuclear protein was extracted to detect the DNA binding activity of 40 TFs by Luminex. Results DCA exerted cytotoxic effects on AR42J cells in a time-and dose-dependent manner, and induced cell apoptosis and necrosis. DCA had no significant influence on the amylase synthesis and secretion

  8. Immune regulation of epithelial cell function: Implications for GI pathologies

    The mammalian immune system is a complex and dynamic network that recognizes, responds, and adapts to numerous foreign and self molecules. CD4+ T cells orchestrate adaptive immune responses, and upon stimulation by antigen, naive CD4+ T cells proliferate and differentiate into various T cell subsets...

  9. MR imaging of renal cell carcinoma. Associations among signal intensity, tumor enhancement, and pathologic findings

    The purpose of this study was to compare the MR characteristics of renal cell carcinomas against histologic findings and to assess the correlations among signal intensity, tumor enhancement, and pathologic findings. Fifty-four patients (56 lesions) were examined by MR imaging and then underwent partial or radical nephrectomy. The pathologic diagnosis of all lesions was renal cell carcinoma. All MR examinations were performed as dynamic studies using the same 1.5-T scanner. MR characteristics were compared against pathologic findings after resection, and the correlations among signal intensity, tumor enhancement, and pathologic findings were then assessed. A significant correlation was observed between tumor grade and tumor enhancement, with G3 lesions tending to show little enhancement. Regardless of the histologic classification, G3 tumors were found to contain highly heterotypic cancer cells and very few vessels by histopathologic examination. No significant correlations were noted between the other MR characteristics and pathologic findings. Renal cell carcinomas showing little enhancement tend to be highly malignant lesions based on the pathologic findings. Special consideration is required for these tumors with regard to the selection of surgical intervention and follow-up observation. (author)

  10. Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology

    Buonocore, Sofia; Ahern, Philip P.; Uhlig, Holm H; Ivanov, Ivaylo I.; Dan R. Littman; Maloy, Kevin J.; Powrie, Fiona

    2010-01-01

    The key role of IL-23 in the pathogenesis of autoimmune and chronic inflammatory disorders is supported by the identification of IL-23R susceptibility alleles associated with IBD, psoriasis and ankylosing spondylitis. IL-23 driven inflammation has primarily been linked to the actions of Th17 cells 1 . Somewhat overlooked, IL-23 also has inflammatory effects on innate immune cells 2 and can drive T cell- independent colitis. However the downstream cellular and molecular pathways involved in th...

  11. The Pathology of T Cells in Systemic Lupus Erythematosus

    Anselm Mak

    2014-01-01

    Full Text Available Systemic lupus erythematosus (SLE is characterized by the production of a wide array of autoantibodies. Thus, the condition was traditionally classified as a “B-cell disease”. Compelling evidence has however shown that without the assistance of the helper T lymphocytes, it is indeed difficult for the “helpless” B cells to become functional enough to trigger SLE-related inflammation. T cells have been recognized to be crucial in the pathogenicity of SLE through their capabilities to communicate with and offer enormous help to B cells for driving autoantibody production. Recently, a number of phenotypic and functional alterations which increase the propensity to trigger lupus-related inflammation have been identified in lupus T cells. Here, potential mechanisms involving alterations in T-cell receptor expressions, postreceptor downstream signalling, epigenetics, and oxidative stress which favour activation of lupus T cells will be discussed. Additionally, how regulatory CD4+, CD8+, and γδ T cells tune down lupus-related inflammation will be highlighted. Lastly, while currently available outcomes of clinical trials evaluating therapeutic agents which manipulate the T cells such as calcineurin inhibitors indicate that they are at least as efficacious and safe as conventional immunosuppressants in treating lupus glomerulonephritis, larger clinical trials are undoubtedly required to validate these as-yet favourable findings.

  12. Complete pathological resolution of pulmonary Langerhans cell histiocytosis

    Ninaber, Maarten; Dik, Hans; Peters, Elke

    2014-01-01

    Cigarette smoking is a major risk factor for pulmonary Langerhans cell histiocytosis (pLCH) and lung cancer. Resolution of pLCH may occur spontaneously, after smoking cessation or other interventions. However, despite clinicoradiological resolution, residual pulmonary Langerhans cells may be present and may lead to recurrent disease. We report the first case of pLCH with a complete histological resolution.

  13. Pathological and radiological correlation in an autopsy case of combined pulmonary fibrosis and emphysema

    Karata, Hiroki; Tanaka, Tomonori; Egashira, Ryoko; Tabata, Kazuhiro; Otani, Kyoko; Hayashi, Ryuji; Hori, Takashi; FUKUOKA, JUNYA

    2015-01-01

    We report an educational autopsy case of combined pulmonary fibrosis and emphysema. Radiological patterns of the upper lung were considered as mostly emphysema, but pathological observation revealed significant interstitial fibrosis of usual interstitial pneumonia as a major pathology. The patient eventually developed acute exacerbation of background interstitial pneumonia. Careful radiological and pathological correlation of the current case indicates that regions with distal acinar emphysem...

  14. Comparison of prefrontal cell pathology between depression and alcohol dependence

    Miguel-Hidalgo, José J.; Rajkowska, Grazyna

    2003-01-01

    Chronic alcohol abuse is often co-morbid with depression symptoms and in many cases it appears to induce major depressive disorder. Structural and functional neuroimaging has provided evidence supporting some degree of neuropathological convergence of alcoholism and mood disorders. In order to understand the cellular neuropathology of alcohol dependence and mood disorders, postmortem morphometric studies have tested the possibility of alterations in the number and size of cells in the prefron...

  15. An overview of renal cell cancer: Pathology and genetics

    Moch, Holger

    2012-01-01

    Renal cell carcinoma is a group of malignancies arising from the epithelium of the renal tubules. The pattern of somatic mutations in kidney tumors has been extensively investigated. In the current 2004 WHO classification, the molecular background of a renal tumor has become, in addition to histopathology, a major criterion for tumor classification. The goal of this review is to discuss morphology and genetics of adult renal epithelial cancer included in the 2004 WHO classification and to men...

  16. Langerhans' cell histiocytosis: pathology, imaging and treatment of skeletal involvement

    Langerhans' cell histiocytosis (LCH) is manifested in a variety of ways, the most common being the eosinophilic granuloma, a localized, often solitary bone lesion that occurs predominantly in the pediatric age group. The hallmark of LCH is the proliferation and accumulation of a specific histiocyte: the Langerhans' cell. In bone this may cause pain and adjacent soft-tissue swelling, but some lesions are asymptomatic. LCH can involve any bone, but most lesions occur in the skull (especially the calvarium and temporal bones), the pelvis, spine, mandible, ribs, and tubular bones. Imaging diagnosis of the disease in bone is first based on the plain radiographic appearance, which is usually a central destructive, aggressive-looking lesion. In the skull, the lesions develop in the diploic space, are lytic, and their edges may be beveled, scalloped or confluent (geographic), or show a ''button sequestrum.'' Vertebral body involvement usually causes collapse, resulting in vertebra plana. With significant recent improvements in the quality of gamma cameras, imaging techniques, and in studying children, bone scintigraphy at diagnosis and on follow-up usually reveals the sites of active disease, especially when the involvement is polyostotic. CT and MR imaging are very useful in providing detailed cross-sectional anatomic detail of the involved bone, including the bone marrow and the adjacent soft tissues. CT is better suited for demonstrating bone detail and MR imaging for bone marrow and soft-tissue involvement. (orig.)

  17. [Experimental pancreatitis of ductal origin. Anatomo-pathologic and ultrastructural study].

    Testas, P; Bitker, M O; Lautard, M; Vieillefond, A; Fabre, F

    1982-12-01

    The injection of bile under low pressure led in 21 dogs out of 30 to a process of acute pancreatitis and to the reproduction of the different histopathological types of pancreatitis seen in man. This represents a weighty argument in favour of the concept of oedematous pancreatitis, interstitial pancreatitis with sometimes major cytosteatonecrosis and necrosing pancreatitis as different manifestations of the same disease, which is not universally accepted. Our research has once again emphasized the fact that the interstitial phenomena and in particular fatty necrosis precede parenchymatous necrosis. Morphological studies were used to attempt to define the link between fat necrosis and acinar necrosis. Light microscopy showed that there was no topographic evidence of direct involvement of the acinar cell in contact with fat necrosis. By contrast, ultrastructural studies revealed initial involvement of the basal pole of the acinar cell. This would emphasize the responsibility of interstitial phenomena in the maintenance, if not the induction, of acinar necrosis. It cannot be excluded that fat necrosis could indirectly, via the liberation of factors carried by oedema, play a role in these phenomena of acinar necrosis. In addition, it was noted that the apical poles of the acinar cells did not seem to be damaged, the acinar lumina were dilated and there was loss of the intercellular junctions. This would hence indicate the possible passage into the interstitium of a toxic substance (bile salts, enzymes liberated in excess) coming directly from the acinar lumina. PMID:7161318

  18. Mice Engrafted With Human Fetal Thymic Tissue And Hematopoietic Stem Cells Develop Pathology Resembling Chronic GVHD

    Lockridge, Jennifer L.; Ying ZHOU; Becker, Yusof A.; Ma, Shidong; Kenney, Shannon C.; Hematti, Peiman; Capitini, Christian M.; Burlingham, William J.; Gendron-Fitzpatrick, Annette; Gumperz, Jenny E.

    2013-01-01

    Chronic Graft versus Host Disease (cGVHD) is a significant roadblock to long-term hematopoeitic stem cell (HSC) transplantation success. Effective treatments for cGVHD have been difficult to develop, in part because of a paucity of animal models that recapitulate the multi-organ pathologies observed in clinical cGVHD. Here we present an analysis of the pathology that occurs in immunodeficient mice engrafted with human fetal HSCs and implanted with fragments of human fetal thymus and liver. St...

  19. A diagnostic dilemma in breast pathology – benign fibroadenoma with multinucleated stromal giant cells

    Tobbia Igdam

    2008-08-01

    Full Text Available Abstract Fibroadenomas are common benign breast tumours that display a characteristic pathological morphology, although several epithelial and stromal variations exist. A very rare histological finding is the presence of multinucleated giant cells throughout the stroma of a benign fibroadenoma. Cells of this type, which are more commonly found incidentally within the interlobular stroma of breast tissue, are benign and should not be mistaken for malignant cells on microscopic examination. Unfortunately a lack of awareness of this pathological entity can lead to diagnostic confusion amongst pathologists resulting in the multinucleate giant cells being mistaken for highly mitotic cells and consequently the fibroadenoma being mistaken for a malignant lesion. This may have serious implications for the subsequent management of the patient. The presence of this unusual cell type in the stroma does not alter the prognosis of otherwise benign lesion. We encountered two such cases at our institution in a six month period recently. We present their histories along with relevant radiological, microscopic and immunohistochemical features, followed by a discussion of this unusual pathological entity.

  20. Peri-ampullary mixed acinar-endocrine carcinoma

    Ayman Walid Soubra

    2011-05-01

    Full Text Available Mixed acinar-endocrine carcinomas (MAEC are rare tumors of the pancreas. We present the case of a patient with peri-ampullary tumor that presented with painless jaundice and after investigation was found to have MAEC. He underwent pancreaticoduodunectomy with tumor free margins and negative lymph nodes. The patient presented with local recurrence and liver metastasis after 1 year and is on chemotherapy with stable lesions 30 months after the diagnosis.

  1. Physiological and pathological role of local and immigrating colonic stem cells

    Ferenc Sipos; Gábor Valcz; Béla Molnár

    2012-01-01

    The latest avenue of research is revealing the existence of and role for the colonic stem cells in the physiological renewal of the mucosa and in pathological circumstances where they have both positive and negative effects. In the case of human colon, different levels of stem cell compartments exist. First, the crypt epithelial stem cells, which have a role in the normal crypt epithelial cell dynamics and in colorectal carcinogenesis. Close to the crypts, the second layer of stem cells can be found; the local subepithelial stem cell niche, including the pericryptic subepithelial myofibroblasts that regulate the epithelial cell differentiation and have a crucial role in cancer progression and chronic inflammation-related fibrosis. The third level of stem cell compartment is the immigrating bone-marrow-derived stem cells, which have an important role in wound healing after severe mucosal inflammation, but are also involved in cancer invasion. This paper focuses on stem cell biology in the context of physiological and pathological processes in the human colon.

  2. Biopsy-verified bronchiolitis obliterans and other noninfectious lung pathologies after allogeneic hematopoietic stem cell transplantation.

    Uhlving, Hilde Hylland; Andersen, Claus B; Christensen, Ib Jarle; Gormsen, Magdalena; Pedersen, Karen Damgaard; Buchvald, Frederik; Heilmann, Carsten; Nielsen, Kim Gjerum; Mortensen, Jann; Moser, Claus; Sengeløv, Henrik; Müller, Klaus Gottlob

    2015-03-01

    Bronchiolitis obliterans (BO) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). Lung biopsy is the gold standard for diagnosis. This study describes the course of BO and assesses the congruity between biopsy-verified BO and a modified version of the National Institutes of Health's consensus criteria for BO syndrome (BOS) based exclusively on noninvasive measures. We included 44 patients transplanted between 2000 and 2010 who underwent lung biopsy for suspected BO. Of those, 23 were diagnosed with BO and 21 presented other noninfectious pulmonary pathologies, such as cryptogenic organizing pneumonia, diffuse alveolar damage, interstitial pneumonia, and nonspecific interstitial fibrosis. Compared with patients with other noninfectious pulmonary pathologies, BO patients had significantly lower values of forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity, and maximal mid-expiratory flow throughout follow-up, but there was no difference in the change in pulmonary function from the time of lung biopsy. The BO diagnosis was not associated with poorer overall survival. Fifty-two percent of patients with biopsy-verified BO and 24% of patients with other noninfectious pulmonary pathology fulfilled the BOS criteria. Pathological BO diagnosis was not superior to BOS criteria in predicting decrease in pulmonary function beyond the time of biopsy. A lung biopsy may provide a characterization of pathological patterns that can extend our knowledge on the pathophysiology of HSCT-related lung diseases. PMID:25498923

  3. Plasmacytoid Transitional Cell Carcinoma of Bladder: A Clinico-pathological Study and Review of Literatures

    FENG Xiaoli; ZHANG Hongtu; SUN Yuntian; LIU Xiuyun

    2006-01-01

    Objective: To study the pathologic features of plasmacytoid transitional cell carcinoma of the bladder, and to analyze the diagnostic features, criteria for differential diagnosis and the clinical significance of the tumor. Methods: Two cases of bladder plasmacytoid transitional cell carcinoma were studied. Routine paraffin sections with HE staining, Pap smear and immunohistochemistry by S-P method were observed under a light microscope. Pathological and clinical data were analyzed by comparison with early reported cases in literatures. Results: A characteristic feature of this tumor was of deep invasion in the lamina propria and/or muscularis propria, in addition to the component of carcinoma in situ in the mucosa, when tumors were diagnosed. The histological pattern and cytological features showed similarity to a plasmacytoid tumor. The tumor cells were strongly positive for AE1/AE3, CEA and CK18. The prognosis appeared to be worse than ordinary transitional cell carcinoma. Conclusion: The plasmacytoid transitional cell carcinoma of bladder is rare but has typical pathological, immunohistological and clinical features. Pathologists should be aware of this kind of primary tumor of bladder.

  4. Cancer Stem Cells in Primary Liver Cancers: Pathological Concepts and Imaging Findings

    There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth. Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes. Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations. In this article, we reviewed the recent concepts of CSCs in the development of primary liver cancers, focusing on their pathological and radiological findings. Awareness of the pathological concepts and imaging findings of primary liver cancers with features of CSCs is critical for accurate diagnosis, prediction of outcome, and appropriate treatment options for patients

  5. Cancer Stem Cells in Primary Liver Cancers: Pathological Concepts and Imaging Findings

    Joo, Ijin [Department of Radiology, Seoul National University Hospital, Seoul 110-744 (Korea, Republic of); Kim, Haeryoung [Department of Pathology, Seoul National University Bundang Hospital, Seongnam 463-707 (Korea, Republic of); Lee, Jeong Min [Department of Radiology, Seoul National University Hospital, Seoul 110-744 (Korea, Republic of)

    2015-11-01

    There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth. Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes. Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations. In this article, we reviewed the recent concepts of CSCs in the development of primary liver cancers, focusing on their pathological and radiological findings. Awareness of the pathological concepts and imaging findings of primary liver cancers with features of CSCs is critical for accurate diagnosis, prediction of outcome, and appropriate treatment options for patients.

  6. Development and function of protective and pathologic memory CD4 T cells

    Megan KL Macleod

    2015-09-01

    Full Text Available IImmunological memory is one of the defining features of the adaptive immune system. As key orchestrators and mediators of immunity, CD4 T cells are central to the vast majority of adaptive immune responses. Generated following an immune response, memory CD4 T cells retain pertinent information about their activation environment enabling them to make rapid effector responses upon reactivation. These responses can either benefit the host by hastening the control of pathogens or cause damaging immunopathology. Here, we will discuss the diversity of the memory CD4 T cell pool, the signals that influence the transition of activated T cells into that pool, and highlight how activation requirements differ between naïve and memory CD4 T cells. A greater understanding of these factors has the potential to aid the design of more effective vaccines and to improve regulation of pathologic CD4 T cells, such as in the context of autoimmunity and allergy.

  7. A46, a Benzothiophene Derived Compound, Suppresses Jak2-Mediated Pathologic Cell Growth

    Majumder, Anurima; Magis, Andrew T.; Park, Sung O.; Figueroa, Nicholas C.; Baskin, Rebekah; Kirabo, Annet; Robert W Allan; Zhao, Zhizhuang Joe; Bisht, Kirpal S.; Keserű, György M.; Sayeski, Peter P.

    2011-01-01

    Hyperkinetic Jak2 tyrosine kinase signaling has been implicated in several hematological disorders including the myeloproliferative neoplasms (MPNs). Effective Jak2 inhibitors can thus have significant therapeutic potential. Here, using structure based virtual screening, we identified a benzothiophene derived Jak2 inhibitor named A46. We hypothesized that this compound would inhibit Jak2-V617F mediated pathologic cell growth. To test this, A46 was analyzed for its ability to i) inhibit recomb...

  8. Blockade of pathological retinal ganglion cell hyperactivity improves optogenetically evoked light responses in rd1 mice

    John Martin Barrett; Patrick Degenaar

    2015-01-01

    Retinitis pigmentosa (RP) is a progressive retinal dystrophy that causes visual impairment and eventual blindness. Retinal prostheses are the best currently available vision-restoring treatment for RP, but only restore crude vision. One possible contributing factor to the poor quality of vision achieved with prosthetic devices is the pathological retinal ganglion cell (RGC) hyperactivity that occurs in photoreceptor dystrophic disorders. Gap junction blockade with meclofenamic acid (MFA) was ...

  9. Pathologic bladder microenvironment attenuates smooth muscle differentiation of skin derived precursor cells: implications for tissue regeneration.

    Cornelia Tolg

    Full Text Available Smooth muscle cell containing organs (bladder, heart, blood vessels are damaged by a variety of pathological conditions necessitating surgery or organ replacement. Currently, regeneration of contractile tissues is hampered by lack of functional smooth muscle cells. Multipotent skin derived progenitor cells (SKPs can easily be isolated from adult skin and can be differentiated in vitro into contractile smooth muscle cells by exposure to FBS. Here we demonstrate an inhibitory effect of a pathologic contractile organ microenvironment on smooth muscle cell differentiation of SKPs. In vivo, urinary bladder strain induces microenvironmental changes leading to de-differentiation of fully differentiated bladder smooth muscle cells. Co-culture of SKPs with organoids isolated from ex vivo stretched bladders or exposure of SKPs to diffusible factors released by stretched bladders (e.g. bFGF suppresses expression of smooth muscle markers (alpha SMactin, calponin, myocardin, myosin heavy chain as demonstrated by qPCR and immunofluorescent staining. Rapamycin, an inhibitor of mTOR signalling, previously observed to prevent bladder strain induced de-differentiation of fully differentiated smooth muscle cells in vitro, inhibits FBS-induced smooth muscle cell differentiation of undifferentiated SKPs. These results suggest that intended precursor cell differentiation may be paradoxically suppressed by the disease context for which regeneration may be required. Organ-specific microenvironment contexts, particularly prevailing disease, may play a significant role in modulating or attenuating an intended stem cell phenotypic fate, possibly explaining the variable and inefficient differentiation of stem cell constructs in in vivo settings. These observations must be considered in drafting any regeneration strategies.

  10. Nonredundant Functions of αβ and γδ T Cells in Acrolein-Induced Pulmonary Pathology

    Borchers, Michael T.; Wesselkamper, Scott C.; Eppert, Bryan L.; Motz, Gregory T.; Sartor, Maureen A; Tomlinson, Craig R.; Medvedovic, Mario; Tichelaar, Jay W.

    2008-01-01

    Acrolein exposure represents a significant human health hazard. Repeated acrolein exposure causes the accumulation of monocytes/macrophages and lymphocytes, mucous cell metaplasia, and epithelial injury. Currently, the mechanisms that control these events are unclear, and the relative contribution of T-cell subsets to pulmonary pathologies following repeated exposures to irritants is unknown. To examine whether lymphocyte subpopulations regulate inflammation and epithelial cell pathology, we ...

  11. Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer

    Youn, Je-in; Kumar, Vinit; Collazo, Michelle; Nefedova, Yulia; Condamine, Thomas; Cheng, Pingyan; Villagra, Alejandro; Antonia, Scott; McCaffrey, Judith C.; Fishman, Mayer; Sarnaik, Amod; Horna, Pedro; Sotomayor, Eduardo; Gabrilovich, Dmitry I.

    2013-01-01

    Two major populations of myeloid-derived suppressor cells (MDSC), monocytic MDSC (M-MDSC) and polymorphonuclear MDSC (PMN-MDSC) regulate immune responses in cancer and other pathologic conditions. Under physiologic conditions, Ly6ChiLy6G− inflammatory monocytes, which are the normal counterpart of M-MDSC, differentiate into macrophages and dendritic cells (DCs). PMN-MDSC is the predominant group of MDSC that accumulates in cancer. Here we show that a large proportion of M-MDSC in tumor-bearin...

  12. Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology

    Montes de Oca, Marcela; Kumar, Rajiv; de Labastida Rivera, Fabian; Amante, Fiona H; Sheel, Meru; Faleiro, Rebecca J.; Bunn, Patrick T.; Best, Shannon E.; Beattie, Lynette; Ng, Susanna S.; Edwards, Chelsea L.; Muller, Werner; Cretney, Erika; Nutt, Stephen L.; Smyth, Mark J.; Haque, Ashraful; Hill, Geoffrey R.; Sundar, Shyam; Kallies, Axel; Engwerda, Christian R.

    2016-01-01

    Tumor necrosis factor (TNF) is critical for controlling many intracellular infections, but can also contribute to inflammation. It can promote the destruction of important cell populations and trigger dramatic tissue remodeling following establishment of chronic disease. Therefore, a better understanding of TNF regulation is needed to allow pathogen control without causing or exacerbating disease. IL-10 is an important regulatory cytokine with broad activities, including the suppression of inflammation. IL-10 is produced by different immune cells; however, its regulation and function appears to be cell-specific and context-dependent. Recently, IL-10 produced by Th1 (Tr1) cells was shown to protect host tissues from inflammation induced following infection. Here, we identify a novel pathway of TNF regulation by IL-10 from Tr1 cells during parasitic infection. We report elevated Blimp-1 mRNA levels in CD4+ T cells from visceral leishmaniasis (VL) patients, and demonstrate IL-12 was essential for Blimp-1 expression and Tr1 cell development in experimental VL. Critically, we show Blimp-1-dependent IL-10 production by Tr1 cells prevents tissue damage caused by IFNγ-dependent TNF production. Therefore, we identify Blimp-1-dependent IL-10 produced by Tr1 cells as a key regulator of TNF-mediated pathology and identify Tr1 cells as potential therapeutic tools to control inflammation. PMID:26765224

  13. Choroidal mast cells in retinal pathology: a potential target for intervention.

    Bousquet, Elodie; Zhao, Min; Thillaye-Goldenberg, Brigitte; Lorena, Viera; Castaneda, Beatriz; Naud, Marie Christine; Bergin, Ciara; Besson-Lescure, Bernadette; Behar-Cohen, Francine; de Kozak, Yvonne

    2015-08-01

    Mast cells are important in the initiation of ocular inflammation, but the consequences of mast cell degranulation on ocular pathology remain uncharacterized. We induced mast cell degranulation by local subconjunctival injection of compound 48/80. Initial degranulation of mast cells was observed in the choroid 15 minutes after the injection and increased up to 3 hours after injection. Clinical signs of anterior segment inflammation paralleled mast cell degranulation. With the use of optical coherence tomography, dilation of choroidal vessels and serous retinal detachments (SRDs) were observed and confirmed by histology. Subconjunctival injection of disodium cromoglycate significantly reduced the rate of SRDs, demonstrating the involvement of mast cell degranulation in posterior segment disorders. The infiltration of polymorphonuclear and macrophage cells was associated with increased ocular media concentrations of tumor necrosis factor-α, CXCL1, IL-6, IL-5, chemokine ligand 2, and IL-1β. Analysis of the amounts of vascular endothelial growth factor and IL-18 showed an opposite evolution of vascular endothelial growth factor compared with IL-18 concentrations, suggesting that they regulate each other's production. These findings suggest that the local degranulation of ocular mast cells provoked acute ocular inflammation, dilation, increased vascular permeability of choroidal vessels, and SRDs. The involvement of mast cells in retinal diseases should be further investigated. The pharmacologic inhibition of mast cell degranulation may be a potential target for intervention. PMID:26166807

  14. Extracellular Membrane Vesicles as Vehicles for Brain Cell-to-Cell Interactions in Physiological as well as Pathological Conditions

    Gabriella Schiera

    2015-01-01

    Full Text Available Extracellular vesicles are involved in a great variety of physiological events occurring in the nervous system, such as cross talk among neurons and glial cells in synapse development and function, integrated neuronal plasticity, neuronal-glial metabolic exchanges, and synthesis and dynamic renewal of myelin. Many of these EV-mediated processes depend on the exchange of proteins, mRNAs, and noncoding RNAs, including miRNAs, which occurs among glial and neuronal cells. In addition, production and exchange of EVs can be modified under pathological conditions, such as brain cancer and neurodegeneration. Like other cancer cells, brain tumours can use EVs to secrete factors, which allow escaping from immune surveillance, and to transfer molecules into the surrounding cells, thus transforming their phenotype. Moreover, EVs can function as a way to discard material dangerous to cancer cells, such as differentiation-inducing proteins, and even drugs. Intriguingly, EVs seem to be also involved in spreading through the brain of aggregated proteins, such as prions and aggregated tau protein. Finally, EVs can carry useful biomarkers for the early diagnosis of diseases. Herein we summarize possible roles of EVs in brain physiological functions and discuss their involvement in the horizontal spreading, from cell to cell, of both cancer and neurodegenerative pathologies.

  15. Clinical and surgical-pathological staging in early non-small cell lung cancer

    Ioannis Koukis

    2013-12-01

    Full Text Available Staging is of the utmost importance in the evaluation of a patient with non-small cell lung cancer (NSCLC because it defines the actual extent of the disease. Accurate staging allows multidisciplinary oncology teams to plan the best surgical or medical treatment and to predict patient prognosis. Based on the recommendation of the International Association for the Study of Lung Cancer (IASLC, a tumor, node, and metastases (TNM staging system is currently used for NSCLC. Clinical staging (c-TNM is achieved via non-invasive modalities such as examination of case history, clinical assessment and radiological tests. Pathological staging (p-TNM is based on histological examination of tissue specimens obtained with the aid of invasive techniques, either non-surgical or during the intervention. This review is a critical evaluation of the roles of current pre-operative staging modalities, both invasive and non-invasive. In particular, it focuses on new techniques and their role in providing accurate confirmation of patient TNM status. It also evaluates the surgical-pathological staging modalities used to obtain the true-pathological staging for NSCLC.

  16. Regulatory T cells delay disease progression in Alzheimer-like pathology.

    Dansokho, Cira; Ait Ahmed, Dylla; Aid, Saba; Toly-Ndour, Cécile; Chaigneau, Thomas; Calle, Vanessa; Cagnard, Nicolas; Holzenberger, Martin; Piaggio, Eliane; Aucouturier, Pierre; Dorothée, Guillaume

    2016-04-01

    Recent studies highlight the implication of innate and adaptive immunity in the pathophysiology of Alzheimer's disease, and foster immunotherapy as a promising strategy for its treatment. Vaccines targeting amyloid-β peptide provided encouraging results in mouse models, but severe side effects attributed to T cell responses in the first clinical trial AN1792 underlined the need for better understanding adaptive immunity in Alzheimer's disease. We previously showed that regulatory T cells critically control amyloid-β-specific CD4(+)T cell responses in both physiological and pathological settings. Here, we analysed the impact of regulatory T cells on spontaneous disease progression in a murine model of Alzheimer's disease. Early transient depletion of regulatory T cells accelerated the onset of cognitive deficits in APPPS1 mice, without altering amyloid-β deposition. Earlier cognitive impairment correlated with reduced recruitment of microglia towards amyloid deposits and altered disease-related gene expression profile. Conversely, amplification of regulatory T cells through peripheral low-dose IL-2 treatment increased numbers of plaque-associated microglia, and restored cognitive functions in APPPS1 mice. These data suggest that regulatory T cells play a beneficial role in the pathophysiology of Alzheimer's disease, by slowing disease progression and modulating microglial response to amyloid-β deposition. Our study highlights the therapeutic potential of repurposed IL-2 for innovative immunotherapy based on modulation of regulatory T cells in Alzheimer's disease. PMID:26912648

  17. Endothelial precursor cell-based therapy to target the pathologic angiogenesis and compensate tumor hypoxia.

    Collet, Guillaume; Szade, Krzysztof; Nowak, Witold; Klimkiewicz, Krzysztof; El Hafny-Rahbi, Bouchra; Szczepanek, Karol; Sugiyama, Daisuke; Weglarczyk, Kazimierz; Foucault-Collet, Alexandra; Guichard, Alan; Mazan, Andrzej; Nadim, Mahdi; Fasani, Fabienne; Lamerant-Fayel, Nathalie; Grillon, Catherine; Petoud, Stéphane; Beloeil, Jean-Claude; Jozkowicz, Alicja; Dulak, Jozef; Kieda, Claudine

    2016-01-28

    Hypoxia-inducing pathologies as cancer develop pathologic and inefficient angiogenesis which rules tumor facilitating microenvironment, a key target for therapy. As such, the putative ability of endothelial precursor cells (EPCs) to specifically home to hypoxic sites of neovascularization prompted to design optimized, site-specific, cell-mediated, drug-/gene-targeting approach. Thus, EPC lines were established from aorta-gonad-mesonephros (AGM) of murine 10.5 dpc and 11.5 dpc embryo when endothelial repertoire is completed. Lines representing early endothelial differentiation steps were selected: MAgEC10.5 and MagEC11.5. Distinct in maturation, they differently express VEGF receptors, VE-cadherin and chemokine/receptors. MAgEC11.5, more differentiated than MAgEC 10.5, displayed faster angiogenesis in vitro, different response to hypoxia and chemokines. Both MAgEC lines cooperated to tube-like formation with mature endothelial cells and invaded tumor spheroids through a vasculogenesis-like process. In vivo, both MAgEC-formed vessels established blood flow. Intravenously injected, both MAgECs invaded Matrigel(TM)-plugs and targeted tumors. Here we show that EPCs (MAgEC11.5) target tumor angiogenesis and allow local overexpression of hypoxia-driven soluble VEGF-receptor2 enabling drastic tumor growth reduction. We propose that such EPCs, able to target tumor angiogenesis, could act as therapeutic gene vehicles to inhibit tumor growth by vessel normalization resulting from tumor hypoxia alleviation. PMID:26577811

  18. Renal pathology in hematopoietic cell transplant recipients: a contemporary biopsy, nephrectomy, and autopsy series.

    Brinkerhoff, Brian T; Houghton, Donald C; Troxell, Megan L

    2016-06-01

    Renal injury in hematopoietic cell transplant recipients may be related to a combination of factors including chemotherapy, radiation, infection, immunosuppressive agents, ischemia, and graft-versus-host disease, and can involve glomerular, tubulointerstitial, and vascular structures. We reviewed renal pathology from 67 patients at a single institution (2009-2014), including 14 patients with biopsy for clinical dysfunction, 6 patients with surgical kidney resection for other causes, and 47 autopsy patients. Kidney specimens frequently contained multiple histopathologic abnormalities. Thrombotic microangiopathy, membranous nephropathy, minimal change disease, and focal segmental glomerulosclerosis were the most common glomerular findings. Pathologies not previously reported in the hematopoietic cell transplant setting included collapsing glomerulopathy, antiglomerular basement membrane disease, fibrillary glomerulonephritis, and in the case of two surgical resections distinctive cellular segmental glomerular lesions that defied classification. Kidney specimens frequently demonstrated acute tubular injury, interstitial fibrosis, arteriolar hyaline, and arteriosclerosis. Other kidney findings at autopsy included leukemia and amyloid (both recurrent), diabetic nephropathy, bacterial infection, fungal invasion, and silver deposition along glomerular and tubular basement membranes. Also in the autopsy cohort, C4d immunohistochemistry demonstrated unexpected membranous nephropathy in two patients, yet C4d also colocalized with arteriolar hyaline. This retrospective hematopoietic cell transplant cohort illustrates multifaceted renal injury in patients with renal dysfunction, as well as in patients without clinically recognized kidney injury. PMID:27015134

  19. Bioluminescence imaging of β cells and intrahepatic insulin gene activity under normal and pathological conditions.

    Tokio Katsumata

    Full Text Available In diabetes research, bioluminescence imaging (BLI has been applied in studies of β-cell impairment, development, and islet transplantation. To develop a mouse model that enables noninvasive imaging of β cells, we generated a bacterial artificial chromosome (BAC transgenic mouse in which a mouse 200-kbp genomic fragment comprising the insulin I gene drives luciferase expression (Ins1-luc BAC transgenic mouse. BLI of mice was performed using the IVIS Spectrum system after intraperitoneal injection of luciferin, and the bioluminescence signal from the pancreatic region analyzed. When compared with MIP-Luc-VU mice [FVB/N-Tg(Ins1-lucVUPwrs/J] expressing luciferase under the control of the 9.2-kbp mouse insulin I promoter (MIP, the bioluminescence emission from Ins1-luc BAC transgenic mice was enhanced approximately 4-fold. Streptozotocin-treated Ins1-luc BAC transgenic mice developed severe diabetes concomitant with a sharp decline in the BLI signal intensity in the pancreas. Conversely, mice fed a high-fat diet for 8 weeks showed an increase in the signal, reflecting a decrease or increase in the β-cell mass. Although the bioluminescence intensity of the islets correlated well with the number of isolated islets in vitro, the intensity obtained from a living mouse in vivo did not necessarily reflect an absolute quantification of the β-cell mass under pathological conditions. On the other hand, adenovirus-mediated gene transduction of β-cell-related transcription factors in Ins1-luc BAC transgenic mice generated luminescence from the hepatic region for more than 1 week. These results demonstrate that BLI in Ins1-luc BAC transgenic mice provides a noninvasive method of imaging islet β cells and extrapancreatic activity of the insulin gene in the liver under normal and pathological conditions.

  20. LABILE IRON IN CELLS AND BODY FLUIDS . Physiology, Pathology and Pharmacology

    Zvi Ioav Cabantchik

    2014-03-01

    Full Text Available In living systems iron appears predominantly associated with proteins, but can also be detected in forms referred as labile iron, which denotes the combined redox properties of iron and its amenability to exchange between ligands, including chelators. The labile cell iron (LCI composition varies with metal concentration and substances with chelating groups but also with pH and the redox potential. Although physiologically in the lower µM range, LCI plays a key role in cell iron economy as cross-roads of metabolic pathways. LCI levels are continually regulated by an iron-responsive machinery that balances iron uptake versus deposition into ferritin. However, LCI rises aberrantly in some cell types due to faulty cell utilization pathways or infiltration by pathological iron forms that are found in hemosiderotic plasma. As LCI attains pathological levels, it can catalyze reactive O species (ROS formation that, at particular threshold, can surpass cellular anti-oxidant capacities and seriously damage its constituents. While in normal plasma and interstitial fluids, virtually all iron is securely carried by circulating transferrin (that renders iron essentially non-labile, in systemic iron overload (IO, the total plasma iron binding capacity is often surpassed by a massive iron influx from hyperabsorptive gut or from erythrocyte overburdened spleen and/or liver. As plasma transferrin approaches iron saturation, labile plasma iron (LPI emerges in forms that can infiltrate cells by unregulated routes and raise LCI to toxic levels. Despite the limited knowledge available on LPI speciation in different types and degrees of iron overload, LPI measurements can be and are in fact used for identifying systemic IO and for initiating/adjusting chelation regimens to attain full-day LPI protection. A recent application of labile iron assay is the detection of labile components in iv iron formulations per se as well as in plasma (LPI following parenteral iron

  1. Ouabain at pathological concentrations might induce damage in human vascular endothelial cells

    Yan-ping REN; Ruo-wen HUANG; Zhuo-ren L(U)

    2006-01-01

    Aim: To examine the time- and dose-dependent effects of ouabain on human umbilical vein endothelial cells (HUVEC) in vivo, and the changes in aortic endothelium and the different expression levels of Kv4.2 in vitro. Methods: The proliferation of HUVEC and cell death were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, the incorporation of [3H]TdR,trypan blue staining, and lactate dehydrogenase (LDH) release. The response of endothelial cells to ouabain was explored with a complementary DNA microarray and a candidate gene was found. "Ouabain-sensitive" hypertensive rats were established by chronic administration of ouabain. Changes in the aortic endothelium were observed by electron microscopy, and the expression level of Ky4.2 in different animals was studied by using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Results: Ouabain stimulated the proliferation of HUVEC at physiological concentrations (0.3-0.9 nmol/L). Ouabain at pathological concentrations (0.9-1.8 nmol/L) inhibited proliferation and induced cell death, mRNA profile analysis indicated that 340 genes were differentially expressed after ouabain treatment: 145 were upregulated, of which 6 were upregulated significantly, including KCND2 (encoding the potassium voltagegated channel shal-related subfamily member 2). The upregulated genes were mainly related to cell metabolism and transcription. In ouabain-sensitive hypertensive rats, the aortic endothelium was damaged and Kv4.2 (coded by KCND2)was over-expressed. Conclusion: The physiological role of ouabain in HUVEC might involve the control of growth and metabolism. Ouabain at pathological concentrations might affect the structure and function of the vascular endothelium by modification of expression of the KCND2 gene, and participate vascular remodeling in hypertension.

  2. F-18-FDG positron emission tomography findings correlate pathological proliferative activity of oral squamous cell carcinoma

    It is still controversial whether fluorodeoxyglucose (FDG) uptake is correlated with cellular proliferation and prognosis of oral squamous cell carcinoma (OSC). In this study, we performed positron emission tomography (PET) study and immunohistochemical analysis to elucidate the relationship between FDG uptake and expression of cellular proliferative markers and pathological prognostic markers in patients with OSC. FDG PET and immunohistochemical staining have been carried out in sixteen patients with OSC. Tumor uptake of FDG was expressed with standardized uptake value (SUV). The expression of Ki-67, Topoisomerase IIα (Topo IIα), p53, and p63 in cancer cells was quantitatively assessed with positivity of the immunohistochemical staining. SUV was compared with the results of immunohistochemical analysis. FDG PET study revealed that SUV ranged from 3.6 to 22.1 with average of 10.4. Average positive rate of Ki-67, Topo IIα, p53, and p63 was 68.9%, 58.9%, 72.0%, and 65.2%, respectively. Pearson product-moment correlation coefficient analysis revealed that SUV was significantly correlated with Ki-67 (r=0.616, p=0.01), Topo IIα (r=0.677, p=0.004), p53 (r=0.613, p=0.01), and p63 (r=0.710, p=0.002), respectively. The present preliminary study indicated that FDG uptake was closely correlated with pathological cellular proliferative and prognostic markers in patients with OSC. (author)

  3. Correlation between apparent diffusion coefficient value and pathological grading in pT1b clear cell renal cell carcinoma

    Objective: To evaluate the correlation of ADC values on 3.0 T MR with the pathological grades in pT1b clear cell renal cell carcinoma (CCRCC). Methods: Conventional MR images, ADC values and Fuhrman pathological grading of pT1b CCRCC were performed in 30 patients. Grade Ⅰ and Ⅱ were defined as low-grade group; grade Ⅲ and Ⅳ were defined as high-grade group. The differences of ADC values among four different pathologic grades were compared with a one-way analysis of variance. The comparison of ADC values of two different grade groups was performed with t test, and the ROC curve was performed to evaluate the diagnostic efficacy of ADC value. Correlation between pathological grading and ADC values was assessed with Spearman rank correlation analysis. Results: (1) The mean ADC value of grading Ⅰ (10 patients), Ⅱ (8 patients), Ⅲ (7 patients), Ⅳ (5 patients) was (0.94 ± 0.11) ×10-3 mm2/s, (0.82 ±0.13) × 10-3 mm2/s,(0.68 ±0.09) × 10-3 mm2/s, (0.59 ±0.03) × 10-3 mm2/s, respectively. Significant differences of ADC values among the four grades were present (F=16.422, P=0.000). (2) The mean ADC value of the low-grade group was significantly higher than that of the high-grade group (t=5.738, P=0.000). Sensitivity and specificity of diagnosing the low-grade group was 88.9% and 83.3% respectively. There was a negative correlation between pathological grading and ADC value (r=-0.807, P<0.05). Conclusions: The ADC values of pT1b CCRCC have close correlation with pathological grading. They can be used to predict the degree of tumor malignancy preoperatively and guide surgical planning. (authors)

  4. Columnar cell lesions of the canine mammary gland: pathological features and immunophenotypic analysis

    Cassali Geovanni D

    2010-02-01

    Full Text Available Abstract Background It has been suggested that columnar cell lesions indicate an alteration of the human mammary gland involved in the development of breast cancer. They have not previously been described in canine mammary gland. The aim of this paper is describe the morphologic spectrum of columnar cell lesions in canine mammary gland specimens and their association with other breast lesions. Methods A total of 126 lesions were subjected to a comprehensive morphological review based upon the human breast classification system for columnar cell lesions. The presence of preinvasive (epithelial hyperplasia and in situ carcinoma and invasive lesions was determined and immunophenotypic analysis (estrogen receptor (ER, progesterone receptor (PgR, high molecular weight cytokeratin (34βE-12, E-cadherin, Ki-67, HER-2 and P53 was perfomed. Results Columnar cell lesions were identified in 67 (53.1% of the 126 canine mammary glands with intraepithelial alterations. They were observed in the terminal duct lobular units and characterized at dilated acini may be lined by several layers of columnar epithelial cells with elongated nuclei. Of the columnar cell lesions identified, 41 (61.2% were without and 26 (38.8% with atypia. Association with ductal hyperplasia was observed in 45/67 (67.1%. Sixty (89.5% of the columnar cell lesions coexisted with neoplastic lesions (20 in situ carcinomas, 19 invasive carcinomas and 21 benign tumors. The columnar cells were ER, PgR and E-cadherin positive but negative for cytokeratin 34βE-12, HER-2 and P53. The proliferation rate as measured by Ki-67 appeared higher in the lesions analyzed than in normal TDLUs. Conclusions Columnar cell lesions in canine mammary gland are pathologically and immunophenotypically similar to those in human breast. This may suggest that dogs are a suitable model for the comparative study of noninvasive breast lesions.

  5. Columnar cell lesions of the canine mammary gland: pathological features and immunophenotypic analysis

    It has been suggested that columnar cell lesions indicate an alteration of the human mammary gland involved in the development of breast cancer. They have not previously been described in canine mammary gland. The aim of this paper is describe the morphologic spectrum of columnar cell lesions in canine mammary gland specimens and their association with other breast lesions. A total of 126 lesions were subjected to a comprehensive morphological review based upon the human breast classification system for columnar cell lesions. The presence of preinvasive (epithelial hyperplasia and in situ carcinoma) and invasive lesions was determined and immunophenotypic analysis (estrogen receptor (ER), progesterone receptor (PgR), high molecular weight cytokeratin (34βE-12), E-cadherin, Ki-67, HER-2 and P53) was perfomed. Columnar cell lesions were identified in 67 (53.1%) of the 126 canine mammary glands with intraepithelial alterations. They were observed in the terminal duct lobular units and characterized at dilated acini may be lined by several layers of columnar epithelial cells with elongated nuclei. Of the columnar cell lesions identified, 41 (61.2%) were without and 26 (38.8%) with atypia. Association with ductal hyperplasia was observed in 45/67 (67.1%). Sixty (89.5%) of the columnar cell lesions coexisted with neoplastic lesions (20 in situ carcinomas, 19 invasive carcinomas and 21 benign tumors). The columnar cells were ER, PgR and E-cadherin positive but negative for cytokeratin 34βE-12, HER-2 and P53. The proliferation rate as measured by Ki-67 appeared higher in the lesions analyzed than in normal TDLUs. Columnar cell lesions in canine mammary gland are pathologically and immunophenotypically similar to those in human breast. This may suggest that dogs are a suitable model for the comparative study of noninvasive breast lesions

  6. The Number of Pathologically Positive Lymph Nodes and Pathological Tumor Depth Predicts Prognosis in Patients With Poorly Differentiated Squamous Cell Carcinoma of the Oral Cavity

    Purpose: The objective of this retrospective study was twofold: (1) to investigate prognostic factors for clinical outcomes in patients with poorly differentiated oral cavity squamous cell carcinoma and (2) to identify specific prognostic subgroups that may help to guide treatment decisions. Methods and Materials: We examined 102 patients with poorly differentiated oral cavity squamous cell carcinoma. All patients were followed for at least 24 months after surgery or until death. The 5-year rates of local control, neck control, distant metastasis, disease-free, disease-specific, and overall survival served as main outcome measures. Results: The 5-year rates were as follows: local control (79%), neck control (64%), distant metastases (27%), disease-free survival (48%), disease-specific survival (52%), and overall survival (42%). Multivariable analysis showed that the number of pathologically positive nodes (≥4 vs. ≤3) was a significant predictor of neck control, distant metastasis, and disease-free, disease-specific, and overall survival rates. In addition, the presence of tumor depth of ≥11 mm (vs. <11 mm) was a significant predictor of distant metastasis, disease-specific survival, and overall survival rates. The combination of the two predictors (26.5%, 27/102) was independently associated with poorer neck control (p = 0.0319), distant metastasis (p < 0.0001), and disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall survival (p < 0.0001) rates. Conclusions: In patients with poorly differentiated oral cavity squamous cell carcinoma, the presence of at least 4 pathologically positive lymph nodes and of a pathological tumor depth ≥11 mm identifies a subset of subjects with poor clinical outcomes. Patients carrying both risk factors are suitable candidates for the development of novel therapeutic approaches.

  7. Central nervous system lesions in adult T-cell leukaemia: MRI and pathology

    Adult T-cell leukaemia (ATL) is a T-cell lymphoid neoplasm caused by human T-cell leukaemia virus type I (HTLV-I). Radiological findings in central nervous system (CNS) involvement have not been well characterised. We reviewed the MRI of 18 patients with ATL who developed new neurological symptoms or signs, and pathology specimens from a 53-year-old woman who died of ATL. MRI findings were divided into three categories: definite, probable, and other abnormal. Definite and probable findings were defined as ATL-related. The characteristic findings were multiple parenchymal masses with or without contrast enhancement adjacent to cerebrospinal fluid (CSF) spaced and the deep grey matter of both cerebral hemispheres, plus leptomeningeal lesion. One patient had both cerebral and spinal cord lesions. Other abnormal findings in eight patients included one case of leukoencephalopathy caused by methotrexate. The histology findings consisted of clusters of tumour cells along perivascular spaces, and scattered infiltration of the parenchyma, with nests of tumour cells. Leptomeningeal infiltration by tumour spread into the parenchyma and secondary degeneration of the neuronal tracts was observed. MRI was useful for detecting CNS invasion by ATL and differentiating it from other abnormalities. The MRI findings seemed to correlate well with the histological changes. (orig.)

  8. Central nervous system lesions in adult T-cell leukaemia: MRI and pathology

    Kitajima, M.; Korogi, Y.; Shigematsu, Y.; Liang, L.; Takahashi, M. [Department of Radiology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Matsuoka, M. [Second Division of Internal Medicine, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Yamamoto, T. [Department of Pathology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Jhono, M. [Department of Dermatology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Eto, K. [The National Institute for Minamata Disease, Minamata (Japan)

    2002-07-01

    Adult T-cell leukaemia (ATL) is a T-cell lymphoid neoplasm caused by human T-cell leukaemia virus type I (HTLV-I). Radiological findings in central nervous system (CNS) involvement have not been well characterised. We reviewed the MRI of 18 patients with ATL who developed new neurological symptoms or signs, and pathology specimens from a 53-year-old woman who died of ATL. MRI findings were divided into three categories: definite, probable, and other abnormal. Definite and probable findings were defined as ATL-related. The characteristic findings were multiple parenchymal masses with or without contrast enhancement adjacent to cerebrospinal fluid (CSF) spaced and the deep grey matter of both cerebral hemispheres, plus leptomeningeal lesion. One patient had both cerebral and spinal cord lesions. Other abnormal findings in eight patients included one case of leukoencephalopathy caused by methotrexate. The histology findings consisted of clusters of tumour cells along perivascular spaces, and scattered infiltration of the parenchyma, with nests of tumour cells. Leptomeningeal infiltration by tumour spread into the parenchyma and secondary degeneration of the neuronal tracts was observed. MRI was useful for detecting CNS invasion by ATL and differentiating it from other abnormalities. The MRI findings seemed to correlate well with the histological changes. (orig.)

  9. Vinpocetine suppresses pathological vascular remodeling by inhibiting vascular smooth muscle cell proliferation and migration.

    Cai, Yujun; Knight, Walter E; Guo, Shujie; Li, Jian-Dong; Knight, Peter A; Yan, Chen

    2012-11-01

    Abnormal vascular smooth muscle cell (SMC) activation is associated with various vascular disorders such as atherosclerosis, in-stent restenosis, vein graft disease, and transplantation-associated vasculopathy. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. However, its role in pathological vascular remodeling remains unexplored. Herein, we show that systemic administration of vinpocetine significantly reduced neointimal formation in carotid arteries after ligation injury. Vinpocetine also markedly decreased spontaneous remodeling of human saphenous vein explants in ex vivo culture. In cultured SMCs, vinpocetine dose-dependently suppressed cell proliferation and caused G1-phase cell cycle arrest, which is associated with a decrease in cyclin D1 and an increase in p27Kip1 levels. In addition, vinpocetine dose-dependently inhibited platelet-derived growth factor (PDGF)-stimulated SMC migration as determined by the two-dimensional migration assays and three-dimensional aortic medial explant invasive assay. Moreover, vinpocetine significantly reduced PDGF-induced type I collagen and fibronectin expression. It is noteworthy that PDGF-stimulated phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), but not protein kinase B, was specifically inhibited by vinpocetine. Vinpocetine powerfully attenuated intracellular reactive oxidative species (ROS) production, which largely mediates the inhibitory effects of vinpocetine on ERK1/2 activation and SMC growth. Taken together, our results reveal a novel function of vinpocetine in attenuating neointimal hyperplasia and pathological vascular remodeling, at least partially through suppressing ROS production and ERK1/2 activation in SMCs. Given the safety profile of vinpocetine, this study provides insight into the therapeutic potential of vinpocetine in proliferative vascular disorders. PMID:22915768

  10. Ultrasonographic Pattern of Testicular Metastasis of Clear Cell Renal Cell Carcinoma with Pathological Correlation

    Libert, Florent; Cabri-Wiltzer, Mathieu; Dardenne, Emmanuel; Draguet, Anne-Philippe; Puttemans, Thierry

    2016-01-01

    Two cases of testicular metastases of a clear cell renal cell carcinoma sharing a very similar ultrasonographic pattern are reported. The observed pattern – masses containing multiple tiny cyst-like areas – is very similar to that of a previously described ovarian metastasis of clear cell renal parenchymal tumor and can be explained by histopathologic features. Despite the small number of cases, this ultrasonographic pattern of testicular mass may be specific for metastasis of clear cell rena...

  11. Pathological and clinical correlates of FOXP3+ cells in renal allografts during acute rejection.

    Veronese, F; Rotman, S; Smith, R N; Pelle, T D; Farrell, M L; Kawai, T; Benedict Cosimi, A; Colvin, R B

    2007-04-01

    The localization and significance of regulatory T cells (Treg) in allograft rejection is of considerable clinical and immunological interest. We analyzed 80 human renal transplant biopsies (including seven donor biopsies) with a double immunohistochemical marker for the Treg transcription factor FOXP3, combined with a second marker for CD4 or CD8. Quantitative FOXP3 cell counts were performed and analyzed for clinical and pathologic correlates. FOXP3(+) cells were present in the interstitium in acute cellular rejection (ACR) type I and II, at a greater density than in acute humoral rejection or CNI toxicity (p attraction or generation at that site. Considering only patients with ACR, a higher density of FOXP3(+) correlated with HLA class II match (p = 0.03), but paradoxically with worse graft survival. We conclude that infiltration of FOXP3(+) cells occurs in ACR to a greater degree than in humoral rejection, however, within the ACR group, no beneficial effect on outcome was evident. Tregs concentrate in tubules, probably contributing to FOXP3 mRNA in urine; the significance and pathogenesis of 'Treg tubulitis' remains to be determined. PMID:17286616

  12. [A pathologic study of adenohypophyseal growth hormone cells in the rabbit after severe burn].

    Wu, J

    1989-06-01

    The growth hormone(GH), produced by the growth hormone cell in pars distalis of the adenohypophysis, acts on the sugar, protein and fat metabolism in various degrees. After trauma, the GH has relations with the energy supply, the maintenance of nitrogen balance, the tissue repair and the body resistance. However, pathological study on the GH cell after burn injury is rare in the literature so far. The purpose of the present investigation is to take a dynamic observation on the ultrastructural changes of the rabbit GH cell after napalm burn within one week. 46 male rabbits were used and divided into two groups, napalm burn group (N = 36) and control group (N = 10). The former is inflicted with 3rd degree burn covering 30% TBSA. The animals of former group were sacrificed at 3, 6, 12, 24, 48, 72, 96, 120, 168 hours postburn respectively. Using the light and electron microscopy and stereological method, the results revealed that: (1) the synthesis activity in GH cell was enhanced, the process of secretion was rapid, and the rate of granule maturation was increased; (2) the nude GH granules were found both in the sinusoids and the endothelial cells; (3) the newly formed mitochondria may be originated from the Golgi complex, and the newly formed Golgi complex from the reutilization of the plasma membrane components; (4) some endothelial cells manifested degeneration, and the others showed in active condition; (5) under the light microscopy, the distribution of the lower tint-phil GH cells had its regional-characteristics. PMID:2509038

  13. Biopsy-verified bronchiolitis obliterans and other noninfectious lung pathologies after allogeneic hematopoietic stem cell transplantation

    Uhlving, Hilde Hylland; Andersen, Claus B; Christensen, Ib Jarle;

    2015-01-01

    Bronchiolitis obliterans (BO) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). Lung biopsy is the gold standard for diagnosis. This study describes the course of BO and assesses the congruity between biopsy-verified BO and a modified version of the National...... Institutes of Health's consensus criteria for BO syndrome (BOS) based exclusively on noninvasive measures. We included 44 patients transplanted between 2000 and 2010 who underwent lung biopsy for suspected BO. Of those, 23 were diagnosed with BO and 21 presented other noninfectious pulmonary pathologies...... vital capacity, and maximal mid-expiratory flow throughout follow-up, but there was no difference in the change in pulmonary function from the time of lung biopsy. The BO diagnosis was not associated with poorer overall survival. Fifty-two percent of patients with biopsy-verified BO and 24% of patients...

  14. Reversal of pathology in CHMP2B-mediated frontotemporal dementia patient cells using RNA interference

    Nielsen, Troels Tolstrup; Mizielinska, Sarah; Hasholt, Lis; Isaacs, Adrian M; Nielsen, Jørgen E

    2012-01-01

    BACKGROUND: Frontotemporal dementia is the second most common form of young-onset dementia after Alzheimer's disease, and several genetic forms of frontotemporal dementia are known. A rare genetic variant is caused by a point mutation in the CHMP2B gene. CHMP2B is a component of the ESCRT...... and that the knockdown causes reversal of the abnormal endosomal phenotype observed in patient fibroblasts. CONCLUSIONS: This is the first description of a treatment that reverses the cellular pathology caused by mutant CHMP2B and suggests that RNA interference might be a feasible therapeutic strategy....... Furthermore, it provides the first proof of a direct link between the disease-causing mutation and the cellular phenotype in cells originating from CHMP2B mutation patients. Copyright © 2012 John Wiley & Sons, Ltd....

  15. Loss of the BRCA1-interacting helicase BRIP1 results in abnormal mammary acinar morphogenesis.

    Kazuhiro Daino

    Full Text Available BRIP1 is a DNA helicase that directly interacts with the C-terminal BRCT repeat of the breast cancer susceptibility protein BRCA1 and plays an important role in BRCA1-dependent DNA repair and DNA damage-induced checkpoint control. Recent studies implicate BRIP1 as a moderate/low-penetrance breast cancer susceptibility gene. However, the phenotypic effects of BRIP1 dysfunction and its role in breast cancer tumorigenesis remain unclear. To explore the function of BRIP1 in acinar morphogenesis of mammary epithelial cells, we generated BRIP1-knockdown MCF-10A cells by short hairpin RNA (shRNA-mediated RNA interference and examined its effect in a three-dimensional culture model. Genome-wide gene expression profiling by microarray and quantitative RT-PCR were performed to identify alterations in gene expression in BRIP1-knockdown cells compared with control cells. The microarray data were further investigated using the pathway analysis and Gene Set Enrichment Analysis (GSEA for pathway identification. BRIP1 knockdown in non-malignant MCF-10A mammary epithelial cells by RNA interference induced neoplastic-like changes such as abnormal cell adhesion, increased cell proliferation, large and irregular-shaped acini, invasive growth, and defective lumen formation. Differentially expressed genes, including MCAM, COL8A1, WIPF1, RICH2, PCSK5, GAS1, SATB1, and ELF3, in BRIP1-knockdown cells compared with control cells were categorized into several functional groups, such as cell adhesion, polarity, growth, signal transduction, and developmental process. Signaling-pathway analyses showed dysregulation of multiple cellular signaling pathways, involving LPA receptor, Myc, Wnt, PI3K, PTEN as well as DNA damage response, in BRIP1-knockdown cells. Loss of BRIP1 thus disrupts normal mammary morphogenesis and causes neoplastic-like changes, possibly via dysregulating multiple cellular signaling pathways functioning in the normal development of mammary glands.

  16. Activation of cannabinoid receptor 2 reduces inflammation in acute experimental pancreatitis via intra-acinar activation of p38 and MK2-dependent mechanisms.

    Michler, Thomas; Storr, Martin; Kramer, Johannes; Ochs, Stefanie; Malo, Antje; Reu, Simone; Göke, Burkhard; Schäfer, Claus

    2013-01-15

    The endocannabinoid system has been shown to mediate beneficial effects on gastrointestinal inflammation via cannabinoid receptors 1 (CB(1)) and 2 (CB(2)). These receptors have also been reported to activate the MAP kinases p38 and c-Jun NH(2)-terminal kinase (JNK), which are involved in early acinar events leading to acute pancreatitis and induction of proinflammatory cytokines. Our aim was to examine the role of cannabinoid receptor activation in an experimental model of acute pancreatitis and the potential involvement of MAP kinases. Cerulein pancreatitis was induced in wild-type, CB(1)-/-, and MK2-/- mice pretreated with selective cannabinoid receptor agonists or antagonists. Severity of pancreatitis was determined by serum amylase and IL-6 levels, intracellular activation of pancreatic trypsinogen, lung myeloperoxidase activity, pancreatic edema, and histological examinations. Pancreatic lysates were investigated by Western blotting using phospho-specific antibodies against p38 and JNK. Quantitative PCR data, Western blotting experiments, and immunohistochemistry clearly show that CB(1) and CB(2) are expressed in mouse pancreatic acini. During acute pancreatitis, an upregulation especially of CB(2) on apoptotic cells occurred. The unselective CB(1)/CB(2) agonist HU210 ameliorated pancreatitis in wild-type and CB(1)-/- mice, indicating that this effect is mediated by CB(2). Furthermore, blockade of CB(2), not CB(1), with selective antagonists engraved pathology. Stimulation with a selective CB(2) agonist attenuated acute pancreatitis and an increased activation of p38 was observed in the acini. With use of MK2-/- mice, it could be demonstrated that this attenuation is dependent on MK2. Hence, using the MK2-/- mouse model we reveal a novel CB(2)-activated and MAP kinase-dependent pathway that modulates cytokine expression and reduces pancreatic injury and affiliated complications. PMID:23139224

  17. Adrenoceptor-activated nitric oxide synthesis in salivary acinar cells

    Looms, Dagnia; Dissing, Steen; Tritsaris, Katerina;

    2000-01-01

    and [Ca2+]i. It was found that a simple correlation between the rise in [Ca2+]i and the rate of NO production following NE stimulation does not exist, and studies in which [Ca2+]i was elevated by means of the Ca 2+ ionophore, ionomycin, further established that even a very large rise in [Ca2+]i did...

  18. TXNDC5, a Newly Discovered Disulfide Isomerase with a Key Role in Cell Physiology and Pathology

    Elena Horna-Terrón

    2014-12-01

    Full Text Available Thioredoxin domain-containing 5 (TXNDC5 is a member of the protein disulfide isomerase family, acting as a chaperone of endoplasmic reticulum under not fully characterized conditions As a result, TXNDC5 interacts with many cell proteins, contributing to their proper folding and correct formation of disulfide bonds through its thioredoxin domains. Moreover, it can also work as an electron transfer reaction, recovering the functional isoform of other protein disulfide isomerases, replacing reduced glutathione in its role. Finally, it also acts as a cellular adapter, interacting with the N-terminal domain of adiponectin receptor. As can be inferred from all these functions, TXNDC5 plays an important role in cell physiology; therefore, dysregulation of its expression is associated with oxidative stress, cell ageing and a large range of pathologies such as arthritis, cancer, diabetes, neurodegenerative diseases, vitiligo and virus infections. Its implication in all these important diseases has made TXNDC5 a susceptible biomarker or even a potential pharmacological target.

  19. Prognostic biomarker study in pathologically staged N1 non-small cell lung cancer

    Purpose: The prognostic influence of 6 biomarkers correlated to histologic subtypes of non-small cell lung cancer (NSCLC) on loco-regional control, overall survival, disease-free survival (DFS), and distant disease control (DDC) rates, all measured at 5 years, were examined. Materials and Methods: Cell blocks from the primary tumors of 137 patients with pathologically staged N1 NSCLC at MDACC were analyzed by 6-biomarker status correlated to histological subtypes and their outcomes. Results: The ranges of biomarker values were as follows: apoptotic index, 0.2-2.8%; mitotic index, 0-1.8%; the proportion of cells in S+G2M, 3-36%; p53 status, 0-100%; Ki-67, 0-9.3%; DNA index, 1.0-2.74. Subtypes of 137 cases from the postoperative pathology specimen showed that 74 patients had squamous carcinoma and 63 patients had adenocarcinoma. Mean and median lengths of follow-up were 4.21 years and 2.43 years, respectively. Patients with squamous cell carcinoma (SCC) had a better 5-year survival (p = 0.006), DFS (pp = 0.002) than patients with adenocarcinoma (AC). Among patients with AC, the DNA index was a significant predictor of 5-year DFS (p = 0.02), DDC rate (p = 0.04), and local-regional control (p < 0.05). Higher apoptosis (p 0.03) and mitosis indices (p = 0.03) were also univariate predictors of increased distant disease among patients with AC. Multivariate analysis of patients with AC revealed that the DNA index and Ki-67 were the only significant independent predictors of distant metastasis (p < 0.04 and p < 0.02, respectively) and DFS (p < 0.04 for both). Among patients with SCC, univariate analysis showed that S+G2M proportion (p < 0.05) and Ki-67 levels (p < 0.02) were significant predictors for local-regional control; for SC, multivariate analysis showed that only mitosis was a significant predictor in this case for overall survival (p < 0.04). Conclusion: Spontaneous apoptotic index and Ki-67 were significantly higher in SC than in AC. Patients with SC had less

  20. Adrenomedullin promotes differentiation of oligodendrocyte precursor cells into myelin-basic-protein expressing oligodendrocytes under pathological conditions in vitro

    Takakuni Maki; Yoko Takahashi; Nobukazu Miyamoto; Liang, Anna C.; Masafumi Ihara; Eng H Lo; Ken Arai

    2015-01-01

    Oligodendrocytes, which are the main cell type in cerebral white matter, are generated from their precursor cells (oligodendrocyte precursor cells: OPCs). However, the differentiation from OPCs to oligodendrocytes is disturbed under stressed conditions. Therefore, drugs that can improve oligodendrocyte regeneration may be effective for white matter-related diseases. Here we show that a vasoactive peptide adrenomedullin (AM) promotes the in vitro differentiation of OPCs under pathological cond...

  1. Mixed acinar-endocrine carcinoma of pancreas: a case report and brief review of the literature

    Liu Z

    2015-07-01

    Full Text Available Zhenzhen Liu,1,2 Chengyong Dong,1,2 Chengye Wang,1,2 Qinlong Liu,1 Deguang Sun,1 Liming Wang1 1Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, 2Dalian Medical University, Dalian, Liaoning Province, People’s Republic of China Abstract: Mixed acinar-endocrine carcinoma (MAEC of the pancreas is a rare entity. We present a 65-year-old Chinese female who was admitted with jaundice and nagging epigastric pain with intermittent diarrhea for 1 month. She eventually underwent abdominal magnetic resonance imaging, which showed an 8×6 cm mass in the head of the pancreas and showed two abnormal lesions in the liver simultaneously. MAEC of the pancreas with synchronous hepatic metastasis was confirmed with immunohistochemistry after Whipple operation and hepatic partial resection of the lesions. Postoperative recovery of this patient was uneventful, and no evidence of recurrence or metastasis was observed after 12 months of follow-up. MAEC of pancreas is thought to be extremely rare and lack of typical clinical symptoms. The prognosis is poor overall, but early detection with complete resection may be beneficial to patients. Keywords: acinar cell carcinoma, neuroendocrine carcinoma of pancreas, neuroendocrine carcinoma, pancreatic neoplasms

  2. Fluorescence imaging to localize head and neck squamous cell carcinoma for enhanced pathological assessment.

    Warram, Jason M; de Boer, Esther; van Dam, Gooitzen M; Moore, Lindsay S; Bevans, Stephanie L; Walsh, Erika M; Young, Erik S; Carroll, William R; Stevens, Todd M; Rosenthal, Eben L

    2016-04-01

    Accurately identifying close or positive margins in real-time permits re-excision during surgical procedures. Intraoperative assessment of margins via gross examination and frozen section is a widely used tool to assist the surgeon in achieving complete resection. While this methodology permits diagnosis of freshly resected tissue, the process is fraught with misinterpretation and sampling errors. During fluorescence-guided surgery, an exogenous fluorescent agent specific for the target disease is imaged in order to navigate the surgical excision. As this technique quickly advances into the clinic, we hypothesize that the disease-specific fluorescence inherently contained within the resected tissues can be used to guide histopathological assessment. To evaluate the feasibility of fluorescence-guided pathology, we evaluated head and neck squamous cell carcinoma tumour specimens and margins resected from animals and patients after systemic injection of cetuximab-IRDye800CW. In a preclinical model of luciferase-positive tumour resection using bioluminescence as the gold standard, fluorescence assessment determined by closed-field fluorescence imaging of fresh resected margins accurately predicted the presence of disease in 33/39 positive margins yielding an overall sensitivity of 85%, specificity of 95%, positive predictive value (PPV) of 94%, and a negative predictive value (NPV) of 87%, which was superior to both surgical assessment (54%, 61%, 57%, and 58%) and pathological assessment (49%, 95%, 91%, and 66%), respectively. When the power of the technique was evaluated using human-derived tumour tissues, as little as 0.5mg (1mm(3)) of tumour tissue was identified (tumour-to-background-ratio:5.2). When the sensitivity/specificity of fluorescence-guided pathology was determined using traditional histological assessment as the gold standard in human tissues obtained during fluorescence-guided surgery, the technique was highly accurate with a sensitivity of 91

  3. Blockade of pathological retinal ganglion cell hyperactivity improves optogenetically evoked light responses in rd1 mice

    John Martin Barrett

    2015-08-01

    Full Text Available Retinitis pigmentosa (RP is a progressive retinal dystrophy that causes visual impairment and eventual blindness. Retinal prostheses are the best currently available vision-restoring treatment for RP, but only restore crude vision. One possible contributing factor to the poor quality of vision achieved with prosthetic devices is the pathological retinal ganglion cell (RGC hyperactivity that occurs in photoreceptor dystrophic disorders. Gap junction blockade with meclofenamic acid (MFA was recently shown to diminish RGC hyperactivity and improve the signal-to-noise ratio (SNR of RGC responses to light flashes and electrical stimulation in the rd10 mouse model of RP. We sought to extend these results to spatiotemporally patterned optogenetic stimulation in the faster-degenerating rd1 model and compare the effectiveness of a number of drugs known to disrupt rd1 hyperactivity.We crossed rd1 mice with a transgenic mouse line expressing the light-sensitive cation channel channelrhodopsin2 (ChR2 in RGCs, allowing them to be stimulated directly using high-intensity blue light. We used 60-channel ITO multielectrode arrays to record ChR2-mediated RGC responses from wholemount, ex-vivo retinas to full-field and patterned stimuli before and after application of MFA, 18-ß-glycyrrhetinic acid (18BGA, another gap junction blocker or flupirtine (Flu, a Kv7 potassium channel opener. All three drugs decreased spontaneous RGC firing, but 18BGA and Flu also decreased the sensitivity of RGCs to optogenetic stimulation. Nevertheless, all three drugs improved the SNR of ChR2-mediated responses. MFA also made it easier to discern motion direction of a moving bar from RGC population responses.Our results support the hypothesis that reduction of pathological RGC spontaneous activity characteristic in retinal degenerative disorders may improve the quality of visual responses in retinal prostheses and they provide insights into how best to achieve this for optogenetic

  4. Blockade of pathological retinal ganglion cell hyperactivity improves optogenetically evoked light responses in rd1 mice.

    Barrett, John M; Degenaar, Patrick; Sernagor, Evelyne

    2015-01-01

    Retinitis pigmentosa (RP) is a progressive retinal dystrophy that causes visual impairment and eventual blindness. Retinal prostheses are the best currently available vision-restoring treatment for RP, but only restore crude vision. One possible contributing factor to the poor quality of vision achieved with prosthetic devices is the pathological retinal ganglion cell (RGC) hyperactivity that occurs in photoreceptor dystrophic disorders. Gap junction blockade with meclofenamic acid (MFA) was recently shown to diminish RGC hyperactivity and improve the signal-to-noise ratio (SNR) of RGC responses to light flashes and electrical stimulation in the rd10 mouse model of RP. We sought to extend these results to spatiotemporally patterned optogenetic stimulation in the faster-degenerating rd1 model and compare the effectiveness of a number of drugs known to disrupt rd1 hyperactivity. We crossed rd1 mice with a transgenic mouse line expressing the light-sensitive cation channel channelrhodopsin2 (ChR2) in RGCs, allowing them to be stimulated directly using high-intensity blue light. We used 60-channel ITO multielectrode arrays to record ChR2-mediated RGC responses from wholemount, ex-vivo retinas to full-field and patterned stimuli before and after application of MFA, 18-β-glycyrrhetinic acid (18BGA, another gap junction blocker) or flupirtine (Flu, a Kv7 potassium channel opener). All three drugs decreased spontaneous RGC firing, but 18BGA and Flu also decreased the sensitivity of RGCs to optogenetic stimulation. Nevertheless, all three drugs improved the SNR of ChR2-mediated responses. MFA also made it easier to discern motion direction of a moving bar from RGC population responses. Our results support the hypothesis that reduction of pathological RGC spontaneous activity characteristic in retinal degenerative disorders may improve the quality of visual responses in retinal prostheses and they provide insights into how best to achieve this for optogenetic prostheses

  5. Gastrointestinal B-cell lymphomas: From understanding B-cell physiology to classification and molecular pathology.

    Sagaert, Xavier; Tousseyn, Thomas; Yantiss, Rhonda K

    2012-12-15

    The gut is the most common extranodal site where lymphomas arise. Although all histological lymphoma types may develop in the gut, small and large B-cell lymphomas predominate. The sometimes unexpected finding of a lymphoid lesion in an endoscopic biopsy of the gut may challenge both the clinician (who is not always familiar with lymphoma pathogenesis) and the pathologist (who will often be hampered in his/her diagnostic skill by the limited amount of available tissue). Moreover, the past 2 decades have spawned an avalanche of new data that encompasses both the function of the reactive B-cell as well as the pathogenic pathways that lead to its neoplastic counterpart, the B-cell lymphoma. Therefore, this review aims to offer clinicians an overview of B-cell lymphomas in the gut, and their pertinent molecular features that have led to new insights regarding lymphomagenesis. It addresses the question as how to incorporate all presently available information on normal and neoplastic B-cell differentiation, and how this knowledge can be applied in daily clinical practice (e.g., diagnostic tools, prognostic biomarkers or therapeutic targets) to optimalise the managment of this heterogeneous group of neoplasms. PMID:23443141

  6. Predicting non-small cell lung cancer prognosis by fully automated microscopic pathology image features

    Yu, Kun-Hsing; Zhang, Ce; Berry, Gerald J.; Altman, Russ B.; Ré, Christopher; Rubin, Daniel L.; Snyder, Michael

    2016-01-01

    Lung cancer is the most prevalent cancer worldwide, and histopathological assessment is indispensable for its diagnosis. However, human evaluation of pathology slides cannot accurately predict patients' prognoses. In this study, we obtain 2,186 haematoxylin and eosin stained histopathology whole-slide images of lung adenocarcinoma and squamous cell carcinoma patients from The Cancer Genome Atlas (TCGA), and 294 additional images from Stanford Tissue Microarray (TMA) Database. We extract 9,879 quantitative image features and use regularized machine-learning methods to select the top features and to distinguish shorter-term survivors from longer-term survivors with stage I adenocarcinoma (P<0.003) or squamous cell carcinoma (P=0.023) in the TCGA data set. We validate the survival prediction framework with the TMA cohort (P<0.036 for both tumour types). Our results suggest that automatically derived image features can predict the prognosis of lung cancer patients and thereby contribute to precision oncology. Our methods are extensible to histopathology images of other organs. PMID:27527408

  7. Correlation between metabolic tumor volume and pathologic tumor volume in squamous cell carcinoma of the oral cavity

    Purpose: To explore the relationship between pathologic tumor volume and volume estimated from different tumor segmentation techniques on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in oral cavity cancer. Materials and methods: Twenty-three patients with squamous cell carcinoma of the oral tongue had PET–CT scans before definitive surgery. Pathologic tumor volume was estimated from surgical specimens. Metabolic tumor volume (MTV) was defined from PET–CT scans as the volume of tumor above a given SUV threshold. Multiple SUV thresholds were explored including absolute SUV thresholds, relative SUV thresholds, and gradient-based techniques. Results: Multiple MTV’s were associated with pathologic tumor volume; however the correlation was poor (R2 range 0.29–0.58). The ideal SUV threshold, defined as the SUV that generates an MTV equal to pathologic tumor volume, was independently associated with maximum SUV (p = 0.0005) and tumor grade (p = 0.024). MTV defined as a function of maximum SUV and tumor grade improved the prediction of pathologic tumor volume (R2 = 0.63). Conclusions: Common SUV thresholds fail to predict pathologic tumor volume in head and neck cancer. The optimal technique that allows for integration of PET–CT with radiation treatment planning remains to be defined. Future investigation should incorporate biomarkers such as tumor grade into definitions of MTV.

  8. Synchronous clear cell renal cell carcinoma and multilocular cystic renal cell neoplasia of low malignant potential: A clinico-pathologic and molecular study.

    Raspollini, Maria Rosaria; Castiglione, Francesca; Cheng, Liang; Montironi, Rodolfo; Lopez-Beltran, Antonio

    2016-05-01

    We report a rare case of synchronous clear cell renal cell carcinoma and multilocular cystic renal cell neoplasia of low malignant potential in the same kidney. The tumors were seen incidentally in a 45-year-old man. Pathologic study revealed that the former tumor was nucleolar grade 2, and the multilocular cystic renal cell neoplasia of low malignant potential was nucleolar grade 1. At immunohistochemistry, the clear cells in both tumors were positive for CD10 and CA IX. Interestingly, these uncommon synchronous tumors showed a different KRAS/NRAS mutation analysis that was characterized by KRAS mutation at codon p.G12C in the clear cell renal cell carcinoma, while this mutation was not present in the case of multilocular cystic renal cell neoplasia of low malignant potential. NRAS mutation was not seen in any of the tumors. PMID:26874573

  9. Pathologic characteristics of resected squamous cell carcinoma of the trachea: prognostic factors based on an analysis of 59 cases.

    Honings, J.; Gaissert, H.A.; Ruangchira-Urai, R.; Wain, J.C.; Wright, C.D.; Mathisen, D.J.; Mark, E.J.

    2009-01-01

    While squamous cell carcinoma (SCC) is the most common tracheal malignancy, few reports describe the pathologic considerations that may guide intraoperative decisions and prognostic assessment. We reviewed 59 tracheal SCC treated between 1985 and 2008 by segmental resection of the trachea, including

  10. Gastrointestinal B-cell lymphomas: From understanding B-cell physiology to classification and molecular pathology

    2012-01-01

    The gut is the most common extranodal site where lymphomas arise. Although all histological lymphoma types may develop in the gut, small and large B-cell lymphomas predominate. The sometimes unexpected finding of a lymphoid lesion in an endoscopic biopsy of the gut may challenge both the clinician (who is not always familiar with lymphoma pathogenesis) and the pathologist (who will often be hampered in his/her diagnostic skill by the limited amount of available tissue). Moreover, the past 2 d...

  11. Oxyphil Cell Parathyroid Adenomas Causing Primary Hyperparathyroidism: a Clinico-Pathological Correlation.

    Howson, Pamela; Kruijff, Schelto; Aniss, Ahmad; Pennington, Thomas; Gill, Anthony J; Dodds, Tristan; Delbridge, Leigh W; Sidhu, Stan B; Sywak, Mark S

    2015-09-01

    Oxyphil cell parathyroid adenomas (OPA) are considered to be an uncommon cause of primary hyperparathyroidism (PHPT), and were historically thought to be clinically silent. It has been our clinical impression that these adenomas present more often than previously thought and may manifest a more severe form of primary hyperparathyroidism than classical adenoma. The aim of this study was to describe the incidence and clinical presentation of OPA. An observational case-control study was undertaken. The study group comprised patients undergoing parathyroidectomy for PHPT where the final pathology confirmed OPA. The controls were made up of an age- and sex-matched group of patients having parathyroidectomy in the same time period where the final pathology confirmed a classical or non-oxyphil adenoma. OPA were defined as parathyroid tumours containing >75% oxyphilic cells. The OPA cases were obtained by reviewing all histopathology slides over an 11-year period (2002-12) where the reports contained the words 'oxyphil' or 'oxyphilic' parathyroid adenomas. These were then reviewed by two independent pathologists to confirm a diagnosis of OPA. The primary outcome measures were preoperative serum calcium and parathyroid hormone (PTH) levels. Secondary outcome measures were symptoms at presentation, accuracy of preoperative localization studies, parathyroid gland weight following surgery, and type of surgery undertaken. In the period 2002-2012, 2739 patients underwent surgery for PHPT. Following pathological review, 91 cases were confirmed as being OPA and formed the study group. A control group (n = 91) from the same period was selected following matching on the basis of age at presentation and sex. OPA were associated with higher preoperative serum calcium (10.84 versus 10.48 mg/dL, p < 0.001) and parathyroid hormone (139 versus 64 ng/L, p < 0.001). At presentation, a lower proportion of OPA cases had asymptomatic disease (15 versus 29%, p = 0.03). There was

  12. Pathological evaluation of ganglion cells in biopsies from upper side of the dentate line in patients with perianal problems

    Marjan Joudi

    2014-07-01

    Full Text Available Introduction: Constipation is one of the most common complaints of individuals, which may present with complication like hemorrhoid and fissure. Hirschsprung is a disease presenting with chronic constipation and its diagnosis may be delayed until adulthood. It is diagnosed by biopsies from anorectal transitional zone. This study aimed to evaluate the association between Hirschsprung and anorectal problems. Method: Sixty three patients with anorectal problems who underwent surgery enrolled in this study. Some consecutive biopsies were obtained from anal canal at 2, 4 and 6 cm above the dentate line. Biopsies were assessed for ganglion cells changes. Patients' data and biopsies results were analyzed with SPSS version18. Results: Out of 63 patients 29 (46 % patients were female and 34 (54 % were male with the mean of 32.65 ± 13.73 years. Fifty six (73 % patients complained from constipation with the mean time of 57.65 ± 45.21 months. Aganglionic zone were reported in six patients with the mean length of 43.33 mm. There was not any relation between anal ganglion cells pathology and constipation (p=0.363, but there was a significant relation between duration of constipation and pathologic changes (p=0.001. The ratio of constipation duration to age was related to anal ganglion cell pathology (p=0.001. Hemorrhoid degree was also affected anal ganglion cells pathology (p=0.037. Conclusion: The relation between Hirschsprung's disease and anorectal problems in adults were significant. The pathologic findings were more presented in younger patients, and those with longer history of constipation and lower degree hemorrhoids. Key words: Anal ganglion cells, Hemorrhoids, Constipation  

  13. Quantitative & qualitative analysis of endothelial cells of donor cornea before & after penetrating keratoplasty in different pathological conditions

    Aruna K.R. Gupta

    2016-01-01

    Full Text Available Background & objectives: Endothelial cells of the donor cornea are known to be affected quantitatively and qualitatively in different pathological conditions after penetrating keratoplasty (PK and this has direct effect on the clarity of vision obtained after PK. This study was undertaken to analyze the qualitative and quantitative changes in donor endothelial cells before and after PK in different pathological conditions. Methods: A prospective investigational analysis of 100 consecutive donor corneas used for penetrating keratoplasty between June 2006 and June 2008, was conducted. The patients were evaluated on the first day, at the end of first week, first month, third and six months and one year. Results: A decrease was observed in endothelial cell count in all pathological conditions. After one year of follow up the loss was 33.1 per cent in corneal opacity, 45.9 per cent in acute infective keratitis (AIK, 58.5 per cent in regrafts, 28.5 per cent in pseudophakic bullous keratopathy (PBK, 37 per cent in descemetocele, 27 per cent in keratoconus and 35.5 per cent in aphakic bullous keratopathy (ABK cases. Interpretation & conclusions: The endothelial cell loss was highest in regraft cases which was significant (P<0.05, while the least endothelial cell loss was seen in keratoconus cases. The cell loss was associated with increase in coefficient of variation (CV, i.e. polymegathism and pleomorphism. Inspite of this polymegathism and pleomorphism, the clarity of the graft was maintained.

  14. Quantitative & qualitative analysis of endothelial cells of donor cornea before & after penetrating keratoplasty in different pathological conditions

    Gupta, Aruna K.R.; Gupta, Roopam K.R.

    2016-01-01

    Background & objectives: Endothelial cells of the donor cornea are known to be affected quantitatively and qualitatively in different pathological conditions after penetrating keratoplasty (PK) and this has direct effect on the clarity of vision obtained after PK. This study was undertaken to analyze the qualitative and quantitative changes in donor endothelial cells before and after PK in different pathological conditions. Methods: A prospective investigational analysis of 100 consecutive donor corneas used for penetrating keratoplasty between June 2006 and June 2008, was conducted. The patients were evaluated on the first day, at the end of first week, first month, third and six months and one year. Results: A decrease was observed in endothelial cell count in all pathological conditions. After one year of follow up the loss was 33.1 per cent in corneal opacity, 45.9 per cent in acute infective keratitis (AIK), 58.5 per cent in regrafts, 28.5 per cent in pseudophakic bullous keratopathy (PBK), 37 per cent in descemetocele, 27 per cent in keratoconus and 35.5 per cent in aphakic bullous keratopathy (ABK) cases. Interpretation & conclusions: The endothelial cell loss was highest in regraft cases which was significant (P<0.05), while the least endothelial cell loss was seen in keratoconus cases. The cell loss was associated with increase in coefficient of variation (CV), i.e. polymegathism and pleomorphism. Inspite of this polymegathism and pleomorphism, the clarity of the graft was maintained. PMID:27121519

  15. Clear cell chondrosarcoma: radiographic, computed tomographic, and magnetic resonance findings in 34 patients with pathologic correlation

    Collins, Mark S.; Koyama, Takashi; Swee, Ronald G.; Inwards, Carrie Y. [Department of Radiology, Mayo Clinic, 200 First Street SW, MN 55905, Rochester (United States)

    2003-12-01

    To describe the radiographic features of clear cell chondrosarcoma (CCCS), including the computed tomographic (CT) and magnetic resonance (MR) findings, and to correlate them with the histopathologic findings. A retrospective review was carried out of 72 patients with histopathologically confirmed CCCS. Imaging studies were available for 34 patients: conventional radiographs (n=28), CT scans (n=14), and MR images (n=15). Radiographic studies were reviewed by three radiologists who rendered a consensus opinion; the studies were correlated with the histopathologic findings. Of the 34 patients with imaging studies, 30 were male and 4 were female (mean age 38.6 years; range 11-74 years). Twenty-two lesions were in long bones (15, proximal femur; 1, distal femur; 1, proximal tibia; 5, proximal humerus) and 11 were in flat bones (5, vertebra; 4, rib; 1, scapula; 1, innominate). One lesion occurred in the tarsal navicular bone. Typically, long bone lesions were located in the epimetaphysis (19/22) and were lucent with a well-defined sclerotic margin and no cortical destruction or periosteal new bone formation. More than one-third of the long bone lesions contained matrix mineralization with a characteristic chondroid appearance. Pathologic fractures were present in six long bone lesions (4, humerus; 2, femur). Lesions in the proximal humerus were more likely to have indistinct margins (4/5) and extend into the diaphysis. Flat bone lesions were typically lytic and expansile and occasionally demonstrated areas of cortical disruption. Typically, matrix mineralization, when present, was amorphous. MR imaging, when available, was superior to conventional radiographs for demonstrating the intramedullary extent of a lesion as well as soft tissue extension. CT images better delineated the presence of cortical destruction and the character of matrix mineralization patterns. CCCS lesions were typically low signal intensity on T1-weighted images and moderately or significantly

  16. Clear cell chondrosarcoma: radiographic, computed tomographic, and magnetic resonance findings in 34 patients with pathologic correlation

    To describe the radiographic features of clear cell chondrosarcoma (CCCS), including the computed tomographic (CT) and magnetic resonance (MR) findings, and to correlate them with the histopathologic findings. A retrospective review was carried out of 72 patients with histopathologically confirmed CCCS. Imaging studies were available for 34 patients: conventional radiographs (n=28), CT scans (n=14), and MR images (n=15). Radiographic studies were reviewed by three radiologists who rendered a consensus opinion; the studies were correlated with the histopathologic findings. Of the 34 patients with imaging studies, 30 were male and 4 were female (mean age 38.6 years; range 11-74 years). Twenty-two lesions were in long bones (15, proximal femur; 1, distal femur; 1, proximal tibia; 5, proximal humerus) and 11 were in flat bones (5, vertebra; 4, rib; 1, scapula; 1, innominate). One lesion occurred in the tarsal navicular bone. Typically, long bone lesions were located in the epimetaphysis (19/22) and were lucent with a well-defined sclerotic margin and no cortical destruction or periosteal new bone formation. More than one-third of the long bone lesions contained matrix mineralization with a characteristic chondroid appearance. Pathologic fractures were present in six long bone lesions (4, humerus; 2, femur). Lesions in the proximal humerus were more likely to have indistinct margins (4/5) and extend into the diaphysis. Flat bone lesions were typically lytic and expansile and occasionally demonstrated areas of cortical disruption. Typically, matrix mineralization, when present, was amorphous. MR imaging, when available, was superior to conventional radiographs for demonstrating the intramedullary extent of a lesion as well as soft tissue extension. CT images better delineated the presence of cortical destruction and the character of matrix mineralization patterns. CCCS lesions were typically low signal intensity on T1-weighted images and moderately or significantly

  17. Renal cell carcinoma of clear type: correlation of CT features with tumor size, architectural patterns, and pathologic staging

    The purpose of this study was to report the CT findings of renal cell carcinoma of clear type (RCCCT) and to determine if there are characteristic morphologic features in RCCCT with respect to tumor size, architectural patterns, and pathologic stage. The CT scans of 35 patients with RCCCT were reviewed retrospectively. The CT findings (tumor size, attenuation patterns, presence of calcifications, encapsulation, margins of neoplasms, venous involvement by neoplasms) were correlated with tumor size, architectural patterns, and pathologic staging. Of the 35 neoplasms, 28 (80 %) were solid, 4 (11 %) were papillary, and 3 (9 %) were cystic. Complete encapsulation was more frequent in lower pathologic stages (40 % in stages 1 and 2 vs 0 % in stages 3 and 4; p < 0.05). Venous involvement was less frequent with completely encapsulated neoplasms (0 of 10, 0 %) than with incompletely or nonencapsulated neoplasms (8 of 25, 32 %; p < 0.05). Encapsulated RCCCT are more likely to have lower pathologic stage. Nonencapsulated neoplasms are more likely to have a higher pathologic stage. (orig.). With 4 figs., 3 tabs

  18. Effect of bone marrow derived mesenchymal stem cells on lung pathology and inflammation in ovalbumin-induced asthma in mouse

    Maryam Mohammadian

    2016-01-01

    Full Text Available Objective(s:Bone marrow-derived mesenchymal stem cells (BMSCs have attracted significant interest to treat asthma and its complication. In this study, the effects of BMSCs on lung pathology and inflammation in an ovalbumin-induced asthma model in mouse were examined. Materials and Methods:BALB/c mice were divided into three groups: control group (animals were not sensitized, asthma group (animals were sensitized by ovalbumin, asthma+BMSC group (animals were sensitized by ovalbumin and treated with BMSCs. BMSCs were isolated and characterized and then labeled with Bromodeoxyuridine (BrdU. After that the cells transferred into asthmatic mice. Histopathological changes of the airways, BMSCs migration and total and differential white blood cell (WBC count in bronchoalveolar lavage (BAL fluid were evaluated. Results:A large number of BrdU-BMSCs were found in the lungs of mice treated with BMSCs. The histopathological changes, BAL total WBC counts and the percentage of neutrophils and eosinophils were increased in asthma group compared to the control group. Treatment with BMSCs significantly decreased airway pathological indices, inflammatory cell infiltration, and also goblet cell hyperplasia. Conclusion:The results of this study revealed that BMSCs therapy significantly suppressed the lung pathology and inflammation in the ovalbumin induced asthma model in mouse.

  19. A review of novel optical imaging strategies of the stroke pathology and stem cell therapy in stroke

    Markus eAswendt

    2014-08-01

    Full Text Available Transplanted stem cells can induce and enhance functional recovery in experimental stroke. Invasive analysis has been extensively used to provide detailed cellular and molecular characterization of the stroke pathology and engrafted stem cells. But post mortem analysis is not appropriate to reveal the time scale of the dynamic interplay between the cell graft, the ischemic lesion and the endogenous repair mechanisms. This review describes non-invasive imaging techniques which have been developed to provide complementary in vivo information. Recent advances were made in analyzing simultaneously different aspects of the cell graft (e.g. number of cells, viability state and cell fate, the ischemic lesion (e.g. blood brain barrier consistency, hypoxic and necrotic areas and the neuronal and vascular network. We focus on optical methods, which permit simple animal preparation, repetitive experimental conditions, relatively medium-cost instrumentation and are performed under mild anesthesia, thus nearly under physiological conditions. A selection of recent examples of optical intrinsic imaging, fluorescence imaging (FLI and bioluminescence imaging (BLI to characterize the stroke pathology and engrafted stem cells are discussed. Special attention is paid to novel optimal reporter genes/probes for genetic labeling and tracking of stem cells and appropriate transgenic animal models. Requirements, advantages and limitations of these imaging platforms are critically discussed and placed into the context of other non-invasive techniques, e.g. magnetic resonance imaging (MRI and positron emission tomography (PET, which can be joined with optical imaging in multimodal approaches.

  20. Balancing immune protection and immune pathology by CD8+ T cell responses to influenza infection

    Susu eDuan

    2016-02-01

    Full Text Available Influenza A virus (IAV is a significant human pathogen causing annual epidemics and periodic pandemics. CD8+ cytotoxic T lymphocyte (CTL-mediated immunity contributes to clearance of virus-infected cells; CTL immunity targeting the conserved internal proteins of IAVs is a key protection mechanism when neutralizing antibodies are absent during heterosubtypic IAV infection. However, CTL infiltration into the airways, their cytotoxicity, and the effects of produced pro-inflammatory cytokines can cause severe lung tissue injury, thereby contributing to immunopathology. Studies have discovered complicated and exquisite stimulatory and inhibitory mechanisms that regulate CTL magnitude and effector activities during IAV infection. Here, we review the state of knowledge on the roles of IAV-specific CTLs in immune protection and immunopathology during IAV infection in animal models, highlighting the key findings of various requirements and constraints regulating the balance of immune protection and pathology involved in CTL immunity. We also discuss the evidence of cross-reactive CTL immunity as a positive correlate of cross-subtype protection during secondary IAV infection in both animal and human studies. We argue that the effects of CTL immunity on protection and immunopathology depend on multiple layers of host and viral factors, including complex host mechanisms to regulate CTL magnitude and effector activity, the pathogenic nature of the IAV, the innate response milieu, and the host historical immune context of influenza infection. Future efforts are needed to further understand these key host and viral factors, especially to differentiate those that constrain optimally effective CTL anti-viral immunity from those necessary to restrain CTL-mediated nonspecific immunopathology in the various contexts of IAV infection, in order to develop better vaccination and therapeutic strategies for modifying protective CTL immunity.

  1. Experimental evidence of age-related adaptive changes in human acinar airways.

    Quirk, James D; Sukstanskii, Alexander L; Woods, Jason C; Lutey, Barbara A; Conradi, Mark S; Gierada, David S; Yusen, Roger D; Castro, Mario; Yablonskiy, Dmitriy A

    2016-01-15

    The progressive decline of lung function with aging is associated with changes in lung structure at all levels, from conducting airways to acinar airways (alveolar ducts and sacs). While information on conducting airways is becoming available from computed tomography, in vivo information on the acinar airways is not conventionally available, even though acini occupy 95% of lung volume and serve as major gas exchange units of the lung. The objectives of this study are to measure morphometric parameters of lung acinar airways in living adult humans over a broad range of ages by using an innovative MRI-based technique, in vivo lung morphometry with hyperpolarized (3)He gas, and to determine the influence of age-related differences in acinar airway morphometry on lung function. Pulmonary function tests and MRI with hyperpolarized (3)He gas were performed on 24 healthy nonsmokers aged 19-71 years. The most significant age-related difference across this population was a 27% loss of alveolar depth, h, leading to a 46% increased acinar airway lumen radius, hence, decreased resistance to acinar air transport. Importantly, the data show a negative correlation between h and the pulmonary function measures forced expiratory volume in 1 s and forced vital capacity. In vivo lung morphometry provides unique information on age-related changes in lung microstructure and their influence on lung function. We hypothesize that the observed reduction of alveolar depth in subjects with advanced aging represents a remodeling process that might be a compensatory mechanism, without which the pulmonary functional decline due to other biological factors with advancing age would be significantly larger. PMID:26542518

  2. NKG2D Mediates NK Cell Hyperresponsiveness and Influenza-Induced Pathologies in a Mouse Model of COPD

    Wortham, Brian W.; Eppert, Bryan L.; Motz, Greg T.; Flury, Jennifer L.; Orozco-Levi, Mauricio; Hoebe, Kasper; Panos, Ralph J.; Maxfield, Melissa; Glasser, Stephan W.; Senft, Albert P; Raulet, David H.; Borchers, Michael T.

    2012-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by peribronchial and perivascular inflammation and largely irreversible airflow obstruction. Acute disease exacerbations, due frequently to viral infections, lead to enhanced disease symptoms and contribute to long-term progression of COPD pathology. Previously, we demonstrated that NK cells from cigarette smoke (CS)-exposed mice exhibit enhanced effector functions in response to stimulating cytokines or toll-like receptor ligands....

  3. Relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma

    Cheng-De; Wang; Xin-Rong; Wang; Chao-Yang; Wang; Yi-Jun; Tang; Ming-Wen; Hao

    2015-01-01

    Objective:To study the relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma.Methods:A total of 297 patients from July 2009 to May 2013 were chosen as objects.EGFR gene mutation were detected with fluorescence quantitative PCR.Relevance of EGFR gene mutation with clinical and pathological features was analyzed,and the prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was compared.Results:In 297 patients.136(45.79%) showed EGFR gene mutation.EGFR gene mutation had no significant relevance with age.gender,smoking history,family history of cancer and clinical stage(P>0.05);there was significant relevance between EGFR gene mutation and blood type,pathologic types,differentiation and diameter of cancer(P<0.05).The difference between prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was statistical significance(P<0.05).Conclusions:EGFR gene mutation has significant relevance with pathological features,the prognosis of EGFRmutant-paticnts is better than that of EGFR- wide type-patients.

  4. Endotoxin-induced basal respiration alterations of renal HK-2 cells: A sign of pathologic metabolism down-regulation

    Quoilin, C., E-mail: cquoilin@ulg.ac.be [Laboratory of Biomedical Spectroscopy, Department of Physics, University of Liege, 4000 Liege (Belgium); Mouithys-Mickalad, A. [Center of Oxygen Research and Development, Department of Chemistry, University of Liege, 4000 Liege (Belgium); Duranteau, J. [Department of Anaesthesia and Surgical ICU, CHU Bicetre, University Paris XI Sud, 94275 Le Kremlin Bicetre (France); Gallez, B. [Biomedical Magnetic Resonance Group, Louvain Drug Research Institute, Universite catholique de Louvain, 1200 Brussels (Belgium); Hoebeke, M. [Laboratory of Biomedical Spectroscopy, Department of Physics, University of Liege, 4000 Liege (Belgium)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer A HK-2 cells model of inflammation-induced acute kidney injury. Black-Right-Pointing-Pointer Two oximetry methods: high resolution respirometry and ESR spectroscopy. Black-Right-Pointing-Pointer Oxygen consumption rates of renal cells decrease when treated with LPS. Black-Right-Pointing-Pointer Cells do not recover normal respiration when the LPS treatment is removed. Black-Right-Pointing-Pointer This basal respiration alteration is a sign of pathologic metabolism down-regulation. -- Abstract: To study the mechanism of oxygen regulation in inflammation-induced acute kidney injury, we investigate the effects of a bacterial endotoxin (lipopolysaccharide, LPS) on the basal respiration of proximal tubular epithelial cells (HK-2) both by high-resolution respirometry and electron spin resonance spectroscopy. These two complementary methods have shown that HK-2 cells exhibit a decreased oxygen consumption rate when treated with LPS. Surprisingly, this cellular respiration alteration persists even after the stress factor was removed. We suggested that this irreversible decrease in renal oxygen consumption after LPS challenge is related to a pathologic metabolic down-regulation such as a lack of oxygen utilization by cells.

  5. Endotoxin-induced basal respiration alterations of renal HK-2 cells: A sign of pathologic metabolism down-regulation

    Highlights: ► A HK-2 cells model of inflammation-induced acute kidney injury. ► Two oximetry methods: high resolution respirometry and ESR spectroscopy. ► Oxygen consumption rates of renal cells decrease when treated with LPS. ► Cells do not recover normal respiration when the LPS treatment is removed. ► This basal respiration alteration is a sign of pathologic metabolism down-regulation. -- Abstract: To study the mechanism of oxygen regulation in inflammation-induced acute kidney injury, we investigate the effects of a bacterial endotoxin (lipopolysaccharide, LPS) on the basal respiration of proximal tubular epithelial cells (HK-2) both by high-resolution respirometry and electron spin resonance spectroscopy. These two complementary methods have shown that HK-2 cells exhibit a decreased oxygen consumption rate when treated with LPS. Surprisingly, this cellular respiration alteration persists even after the stress factor was removed. We suggested that this irreversible decrease in renal oxygen consumption after LPS challenge is related to a pathologic metabolic down-regulation such as a lack of oxygen utilization by cells.

  6. Bronchopulmonary dysplasia: understanding of the underlying pathological mechanisms

    Daniela Fanni

    2014-06-01

    Full Text Available Bronchopulmonary dysplasia (BPD is a chronic lung disease occurring in preterm infants, typically before 28 weeks of gestational age, characterized by a prolonged need for supplemental oxygen or positive pressure ventilation. The normal stages of lung development and their relation to the timing of preterm birth is strategic in order to understand the pathogenesis of BPD. In embryonic and pseudoglandular stages the lungs arise from the anterior foregut as a bud where the branching morphogenesis generate a tree-like network of airways. The canalicular stage is characterized by increasing proliferation of distal lung epithelial cells and rapid expansion of the intra-acinar capillaries. The complexity of the airways increases, secondary crests begin to form and full maturation of the alveolus occurs during the saccular and the alveolar stages. Mesechyme components, expecially elastin and myofibroblast, display a major role in normal lung development. BPD is thought to result after an acute insult to the neonatal lung following therapy with oxygen supplementation and mechanical ventilation. Chorioamnionitis, infections and genetic susceptibly are hypothesized to contribute to the injury that affect the normal human lung development. Abnormalities in the mesenchyme were consistently seen in association with inhibition of alveolarization. The pathological features that characterize BPD are complex and differ according with the disease progression. Alveolar simplification, interstitial fibrosis, septal thickness, large airways, smooth muscle hypertrophy, fetal artery persistance and decrease in the arterial number can be histologically observed. In conclusion, in order to reach a complete clinical-pathological diagnosis, the correlation of the pathological features with the fundamental steps of lung morphogenesis and a strict dialogue between the neonatologist and the perinatal pathologist are required. Given these conditions, in our experience, a

  7. DEAR1 is a dominant regulator of acinar morphogenesis and an independent predictor of local recurrence-free survival in early-onset breast cancer.

    Steven T Lott

    2009-05-01

    Full Text Available BACKGROUND: Breast cancer in young women tends to have a natural history of aggressive disease for which rates of recurrence are higher than in breast cancers detected later in life. Little is known about the genetic pathways that underlie early-onset breast cancer. Here we report the discovery of DEAR1 (ductal epithelium-associated RING Chromosome 1, a novel gene encoding a member of the TRIM (tripartite motif subfamily of RING finger proteins, and provide evidence for its role as a dominant regulator of acinar morphogenesis in the mammary gland and as an independent predictor of local recurrence-free survival in early-onset breast cancer. METHODS AND FINDINGS: Suppression subtractive hybridization identified DEAR1 as a novel gene mapping to a region of high-frequency loss of heterozygosity (LOH in a number of histologically diverse human cancers within Chromosome 1p35.1. In the breast epithelium, DEAR1 expression is limited to the ductal and glandular epithelium and is down-regulated in transition to ductal carcinoma in situ (DCIS, an early histologic stage in breast tumorigenesis. DEAR1 missense mutations and homozygous deletion (HD were discovered in breast cancer cell lines and tumor samples. Introduction of the DEAR1 wild type and not the missense mutant alleles to complement a mutation in a breast cancer cell line, derived from a 36-year-old female with invasive breast cancer, initiated acinar morphogenesis in three-dimensional (3D basement membrane culture and restored tissue architecture reminiscent of normal acinar structures in the mammary gland in vivo. Stable knockdown of DEAR1 in immortalized human mammary epithelial cells (HMECs recapitulated the growth in 3D culture of breast cancer cell lines containing mutated DEAR1, in that shDEAR1 clones demonstrated disruption of tissue architecture, loss of apical basal polarity, diffuse apoptosis, and failure of lumen formation. Furthermore, immunohistochemical staining of a tissue

  8. A pathological study of the salivary glands of rabid dogs in the Philippines.

    Boonsriroj, Hassadin; Manalo, Daria Llenaresas; Kimitsuki, Kazunori; Shimatsu, Taichi; Shiwa, Nozomi; Shinozaki, Harumi; Takahashi, Yurika; Tanaka, Naoto; Inoue, Satoshi; Park, Chun-Ho

    2016-01-01

    Rabies is a zoonotic disease caused by the rabies virus. While the salivary glands are important as exit and propagation sites for the rabies virus, the mechanisms of rabies excretion remain unclear. Here, we investigated the histopathology of the salivary glands of rabid dogs and analyzed the mechanism of excretion into the oral cavity. Mandibular and parotid glands of 22 rabid dogs and three control dogs were used. Mild to moderate non-suppurative sialadenitis was observed in the mandibular glands of 19 of the 22 dogs, characterized by loss of acinar epithelium and infiltration by lymphoplasmacytic cells. Viral antigens were detected in the mucous acinar epithelium, ganglion neurons and myoepithelium. Acinar epithelium and lymphocytes were positive for anti-caspase-3 antibodies and TUNEL staining. In contrast, no notable findings were observed in the ductal epithelial cells and serous demilune. In the parotid gland, the acinar cells, myoepithelium and ductal epithelium all tested negative. These findings confirmed the path through which the rabies virus descends along the facial nerve after proliferation in the brain to reach the ganglion neurons of the mandibular gland, subsequently traveling to the acinar epithelium via the salivary gland myoepithelium. Furthermore, the observation that nerve endings passing through the myoepithelium were absent from the ductal system suggested that viral proliferation and cytotoxicity could not occur there, ensuring that secretions containing the virus are efficiently excreted into the oral cavity. PMID:26278996

  9. Pathological stage after neoadjuvant chemoradiation and esophagectomy superiorly predicts survival in patients with esophageal squamous cell carcinoma

    Background and purpose: To assess the usefulness of pathological stage according to the 7th edition of the Union for International Cancer Control–American Joint Committee on Cancer (UICC–AJCC) as a prognostic tool in patients undergoing neoadjuvant chemoradiation followed by esophagectomy (trimodality therapy, TMT) for locally advanced esophageal squamous cell carcinoma. Material and methods: One hundred twenty-five eligible patients completing TMT were enrolled for analysis. The clinical (cTNM7) and pathological (ypTNM7) stage groups of their tumors were prospectively classified, and re-grouped by the 6th edition (ypTNM6). Survival was analyzed using the Kaplan–Meier method. The Cox proportional hazard model and the Akaike information criterion (AIC) were used to compare the performance of staging systems. Results: With a median follow-up of 24.6 months, 54 patients (43.2%) died. Forty patients (32%) achieved pathological complete remission (pCR). The median survival was 31.8 months. On multivariate analysis, ypTNM7 (but not pCR or pN) was the only independent factor affecting overall survival (p < 0.001). The ypTNM7 was superior to cTNM7 or ypTNM6 in predicting both overall and recurrence-free survival after TMT based on AIC values and Cox proportional hazard model analysis. Conclusions: In patients with locally advanced esophageal squamous cell carcinoma undergoing TMT, ypTNM7 is the best predictor of survival

  10. The pattern of fibrosis in the acinar zone 3 areas in early alcoholic liver disease

    Junge, Jette; Horn, T; Vyberg, M;

    1991-01-01

    The degree of fibrosis and the pattern of collagen distribution in the acinar zone 3, as well as the thickness of the terminal hepatic vein walls (THV) were analyzed in 48 consecutive liver needle biopsies from 48 alcoholics with preserved liver architecture. The fibrosis occurred to more or less...

  11. Ectrodactyly and Lethal Pulmonary Acinar Dysplasia Associated with Homozygous FGFR2 Mutations Identified by Exome Sequencing.

    Barnett, Christopher P; Nataren, Nathalie J; Klingler-Hoffmann, Manuela; Schwarz, Quenten; Chong, Chan-Eng; Lee, Young K; Bruno, Damien L; Lipsett, Jill; McPhee, Andrew J; Schreiber, Andreas W; Feng, Jinghua; Hahn, Christopher N; Scott, Hamish S

    2016-09-01

    Ectrodactyly/split hand-foot malformation is genetically heterogeneous with more than 100 syndromic associations. Acinar dysplasia is a rare congenital lung lesion of unknown etiology, which is frequently lethal postnatally. To date, there have been no reports of combinations of these two phenotypes. Here, we present an infant from a consanguineous union with both ectrodactyly and autopsy confirmed acinar dysplasia. SNP array and whole-exome sequencing analyses of the affected infant identified a novel homozygous Fibroblast Growth Factor Receptor 2 (FGFR2) missense mutation (p.R255Q) in the IgIII domain (D3). Expression studies of Fgfr2 in development show localization to the affected limbs and organs. Molecular modeling and genetic and functional assays support that this mutation is at least a partial loss-of-function mutation, and contributes to ectrodactyly and acinar dysplasia only in homozygosity, unlike previously reported heterozygous activating FGFR2 mutations that cause Crouzon, Apert, and Pfeiffer syndromes. This is the first report of mutations in a human disease with ectrodactyly with pulmonary acinar dysplasia and, as such, homozygous loss-of-function FGFR2 mutations represent a unique syndrome. PMID:27323706

  12. Geometrical influence of pulmonary acinar models on respiratory flows and particle deposition

    Hofemeier, Philipp; Sznitman, Josue

    2012-11-01

    Due to experimental challenges in assessing respiratory flows in the deep regions of the lungs, computational simulations are typically sought to quantify inhaled aerosol transport and deposition in the acinus. Most commonly, simulations are performed using generic geometries of alveoli, including spheres, toroids and polyhedra to mimic the acinar region. However, local respiratory flows and ensuing particle trajectories are anticipated to be highly influenced by the specific geometrical structures chosen. To date, geometrical influences have not yet been thoroughly quantified. Knowing beforehand how geometries affect acinar flows and particle transport is critical in translating simulated data to predictions of aerosol deposition in real lungs. Here, we conduct a systematic investigation on a number of generic acinar models. Simulations are conducted for simple alveolated airways featuring a selection of geometries. Deposition patterns and efficiencies are quantified both for massless particles, highlighting details of the local flow, and micron-scale aerosols. This latter group of particles represents an important class of inhaled aerosols known to reach and deposit in the acinus. Our work emphasizes the subtleties of acinar geometry in determining the fate of inhaled aerosols.

  13. In Vivo Detection of Acinar Microstructural Changes in Early Emphysema with 3He Lung Morphometry

    Quirk, James D.; Lutey, Barbara A.; Gierada, David S.; Woods, Jason C.; Senior, Robert M.; Lefrak, Stephen S.; Sukstanskii, Alexander L; Conradi, Mark S; Yablonskiy, Dmitriy A.

    2011-01-01

    In vivo helium 3 lung morphometry has greater sensitivity to early emphysematous changes than does low-dose CT or traditional pulmonary function testing (PFT), and this modality can be used to detect significant changes in acinar airway geometry, even in individuals with clinically normal PFT results.

  14. Inhibitory effect of human telomerase antisense oligodeoxyribonucleotides on the growth of gastric cancer cell lines in variant tumor pathological subtype

    Jing Ye; Yun-Lin Wu; Shu Zhang; Zi Chen; Li-Xia Guo; Ruo-Yu Zhou; Hong Xie

    2005-01-01

    AIM: To investigate the inhibitory effect of specialized human telomerase antisense oligodeoxyribonucleotides on the growth of well (MKN-28), moderately (SGC-7901)and poorly (MKN-45) differentiated gastric cancer cell lines under specific conditions and its inhibition mechanism,and to observe the correlation between the growth inhibition ratio and the tumor pathologic subtype of gastric cancer cells.METHODS: Telomerase activity in three gastric cancer cell lines of variant tumor pathologic subtype was determined by modified TRAP assay before and after the specialized human telomerase antisense oligodeoxyribonucleotides were dealt with under specific conditions. Effect of antisense oligomer under specific conditions of the growth and viability of gastric cancer cell lines was explored by using trypan blue dye exclusion assay, and cell apoptosis was detected by cell morphology observation, flow cytometry and TUNEL assay.RESULTS: Telomerase activity was detected in well,moderately and poorly differentiated gastric cancer cell lines (the quantification expression of telomerase activity was 43.7TPG, 56.5TPG, 76.7TPG, respectively).Telomerase activity was controlled to 30.2TPG, 36.3TPG and 35.2TPG for MKN-28, SGC-7901 and MKN-45 cell lines respectively after treatment with human telomerase antisense oligomers at the concentration of 5 μmol/L, and was entirely inhibited at 10 μmol/L, against the template region of telomerase RNA component, whereas no inhibition effect was detected in missense oligomers (P<0.05). After treatment with antisense oligomers at different concentrations under specific conditions for 96 h, significant growth inhibition effects were found in MKN-45 and SGC-7901gastric cancer cell lines (the inhibition ratio was 40.89%and 71.28%), but not in MKN-28 cell lines (15.86%). The ratio of inactive SGC-7901 cells increased according to the prolongation of treatment from 48 to 96 h. Missense oligomers could not lead to the same effect (P<0

  15. Ultrastructural changes in aster yellows phytoplasma affected Limonium sinuatum Mill. plants II. Pathology of cortex parenchyma cells

    Anna Rudzińska-Langwald

    2014-02-01

    Full Text Available In Limonium sinuatum Mill, plants with severe symptoms of aster yellows infection phytoplasmas were present not only in the phloem but also in some cortex parenchymas cells. These parenchyma cells were situated at some distance from the conducting bundles. The phytoplasmas were observed directly in parenchyma cells cytoplasm. The number of phytoplasmas present in each selected cell varies. The cells with a small number of phytoplasmas show little pathological changes compared with the unaffected cells of the same zone of the stem as well with the cells of healthy plants. The cells filled with a number of phytoplasmas had their protoplast very much changed. The vacuole was reduced and in the cytoplasm a reduction of the number of ribosomes was noted and regions of homogenous structure appeared. Mitochondria were moved in the direction of the tonoplast and plasma membrane. Compared to the cells unaffected by phytoplasma, the mitochondria were smaller and had an enlarged cristae internal space. The chloroplasts from affected cells had a very significant reduction in size and the tylacoids system had disappeared. The role of these changes for creating phytoplasma friendly enviroment is discused.

  16. Pathological Mobilization and Activities of Dendritic Cells in Tumor-Bearing Hosts: Challenges and Opportunities for Immunotherapy of Cancer

    Tesone, Amelia J.; Svoronos, Nikolaos; Allegrezza, Michael J.; Conejo-Garcia, Jose R.

    2013-01-01

    A common characteristic of solid tumors is the pathological recruitment of immunosuppressive myeloid cells, which in certain tumors includes dendritic cells (DCs). DCs are of particular interest in the field of cancer immunotherapy because they induce potent and highly specific anti-tumor immune responses, particularly in the early phase of tumorigenesis. However, as tumors progress, these cells can be transformed into regulatory cells that contribute to an immunosuppressive microenvironment favoring tumor growth. Therefore, controlling DC phenotype has the potential to elicit effective anti-tumor responses while simultaneously weakening the tumor’s ability to protect itself from immune attack. This review focuses on the dual nature of DCs in the tumor microenvironment, the regulation of DC phenotype, and the prospect of modifying DCs in situ as a novel immunotherapeutic approach. PMID:24339824

  17. Characterization of T cell clones from chagasic patients: predominance of CD8 surface phenotype in clones from patients with pathology

    Washington R. Cuna

    1995-08-01

    Full Text Available Human Chagas' disease, caused by the protozoan Trypanosoma cruzi, is associated with pathological processes whose mechanisms are not known. To address this question, T cell lines were developed from chronic chagasic patients peripheral blood mononuclear cells (PBMC and cloned. These T cell clones (TCC were analyzed phenotypically with monoclonal antibodies by the use of a fluorescence microscope. The surface phenotype of the TCC from the asymptomatic patient were predominantly CD4 positive (86%. On the contrary, the surface phenotype CD8 was predominant in the TCC from the patients suffering from cardiomegaly with right bundle branch block (83%, bradycardia with megacolon (75 % and bradycardia (75%. Future studies will be developed in order to identify the antigens eliciting these T cell subpopulations.

  18. Mechanical behavior of pathological and normal red blood cells in microvascular flow based on modified level-set method

    Zhang, XiWen; Ma, FangChao; Hao, PengFei; Yao, ZhaoHui

    2016-01-01

    The research of the motion and deformation of the RBCs is important to reveal the mechanism of blood diseases. A numerical method has been developed with level set formulation for elastic membrane immersed in incompressible fluid. The numerical model satisfies mass and energy conservation without the leaking problems in classical Immersed Boundary Method (IBM), at the same time, computing grid we used can be much smaller than the general literatures. The motion and deformation of a red blood cell (including pathological & normal status) in microvascular flow are simulated. It is found that the Reynolds number and membrane's stiffness play an important role in the transmutation and oscillation of the elastic membrane. The normal biconcave shape of the RBC is propitious to create high deformation than other pathological shapes. With reduced viscosity of the interior fluid both the velocity of the blood and the deformability of the cell reduced. With increased viscosity of the plasma both the velocity of the blood and the deformability of the cell reduced. The tank treading of the RBC membrane is observed at low enough viscosity contrast in shear flow. The tank tread fixed inclination angle of the cell depends on the shear ratio and viscosity contrast, which can be compared with the experimental observation well.

  19. An Important Method in the Investigation of Vascular Pathologies: Endothelial Cell Culture

    Yusufhan Yazır

    2012-12-01

    Full Text Available Endothelial cells line the interior surface of blood vessels and form an interface between circulating blood in the lumen and the rest of the vessel wall. Endothelial cells are involved in many aspects of vascular biology, including barrier function, vasoconstriction, coagulation and inflamation. The endothelial cells in different organs have different functions and surface phenotype. These cells express prostoglandin-I2, platelet activating factor, collagen, endothelin-1, laminin, fibronectin and growth factors including platelet derived growth factor, fibroblast growth factor. İn the cell culture, cells can be isolated, maintened and proliferate in the laboratory conditions. The techniques of the cell culture have allowed scientists to use the cells in vitro for experimental studies, such as the production of vaccine, antibody and enzime, drug research, cell-cell interactions. Human umbilical vein endothelial cell is a good source for endothelial cell, because it is cheaper, easy to find and has the basic features of the normal endothelial cells.

  20. Use of induced pluripotent stem cell derived neurons engineered to express BDNF for modulation of stressor related pathology.

    Hymie Anisman

    2014-10-01

    Full Text Available Combined cell and gene-based therapeutic strategies offer potential in the treatment of neurodegenerative and psychiatric conditions that have been associated with structural brain disturbances. In the present investigation, we used a novel virus-free re-programming method to generate induced pluripotent stem cells (iPSCs, and then subsequently transformed these cells into neural cells which over-expressed brain derived neurotrophic factor (BDNF. Importantly, the infusion of iPSC derived neural cells (as a cell replacement and gene delivery tool and BDNF (as a protective factor influenced neuronal outcomes Specifically, intracerebroventricular transplantation of iPSC-derived neural progenitors that over-expressed BDNF reversed the impact of immune (lipopolysaccharide and chronic stressor challenges upon subventricular zone adult neurogenesis and the iPSC-derived neural progenitor cells alone blunted the stressor induced corticosterone response. Moreover, our findings also indicate that mature dopamine producing neurons can also be generated using iPSC procedures and these cells appeared to be viable when infused in vivo. Taken together, these data could have important implications for using gene-plus-cell replacement methods to modulate stressor related pathology.

  1. 18-F fluorodeoxyglucose uptake in positron emission tomography as a pathological grade predictor for renal clear cell carcinomas

    To evaluate the usefulness of Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18-F FDG-PET/CT) in the prediction of Fuhrman pathological grades of renal clear cell carcinoma (cRCC). This retrospective study was approved by our institutional review board, and written informed consent was waived. Thirty-one patients with pathologically proven cRCC underwent 18-F FDG-PET/CT for tumour staging. Maximum standardized uptake value of cRCC (tumour SUVmax) and mean SUV of the liver and spleen (liver and spleen SUVmean) were measured by two independent observers. Tumour SUVmax, tumour-to-liver SUV ratio, and tumour-to-spleen SUV ratio were correlated with the pathological grades. Logistic analysis demonstrated that only the tumour-to-liver SUV ratio was a significant parameter for differentiating high-grade (Fuhrman grades 3 and 4) tumours from low-grade (Fuhrman grades 1 and 2) tumours (P = 0.007 and 0.010 for observers 1 and 2, respectively). Sensitivity, specificity, and positive and negative predictive values for detecting tumours of Fuhrman grades 3 and 4 were 64, 100, 100, and 77 %, respectively, for observer 1, and 79, 88, 85, and 83 %, respectively, for observer 2. The tumour-to-liver SUV ratio with 18-F FDG-PET/CT appeared to be a valuable imaging biomarker in the prediction of high-grade cRCC. (orig.)

  2. 18-F fluorodeoxyglucose uptake in positron emission tomography as a pathological grade predictor for renal clear cell carcinomas

    Noda, Yoshifumi; Goshima, Satoshi; Kondo, Hiroshi; Watanabe, Haruo; Kawada, Hiroshi; Kawai, Nobuyuki; Tanahashi, Yukichi [Gifu University Hospital, Department of Radiology, Gifu (Japan); Kanematsu, Masayuki [Gifu University Hospital, Department of Radiology, Gifu (Japan); Gifu University Hospital, Department of Radiology Services, Gifu (Japan); Suzui, Natsuko [Gifu University Hospital, Department of Pathology, Gifu (Japan); Hirose, Yoshinobu [Osaka Medical College, Department of Pathology, Osaka (Japan); Matsunaga, Kengo [Kizawa Memorial Hospital, Department of Pathology, Minokamo (Japan); Nishibori, Hironori [Kizawa Memorial Hospital, Department of Radiology, Minokamo (Japan); Bae, Kyongtae T. [University of Pittsburgh Medical Center, Department of Radiology, Pittsburgh, PA (United States)

    2015-10-15

    To evaluate the usefulness of Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18-F FDG-PET/CT) in the prediction of Fuhrman pathological grades of renal clear cell carcinoma (cRCC). This retrospective study was approved by our institutional review board, and written informed consent was waived. Thirty-one patients with pathologically proven cRCC underwent 18-F FDG-PET/CT for tumour staging. Maximum standardized uptake value of cRCC (tumour SUV{sub max}) and mean SUV of the liver and spleen (liver and spleen SUV{sub mean}) were measured by two independent observers. Tumour SUV{sub max}, tumour-to-liver SUV ratio, and tumour-to-spleen SUV ratio were correlated with the pathological grades. Logistic analysis demonstrated that only the tumour-to-liver SUV ratio was a significant parameter for differentiating high-grade (Fuhrman grades 3 and 4) tumours from low-grade (Fuhrman grades 1 and 2) tumours (P = 0.007 and 0.010 for observers 1 and 2, respectively). Sensitivity, specificity, and positive and negative predictive values for detecting tumours of Fuhrman grades 3 and 4 were 64, 100, 100, and 77 %, respectively, for observer 1, and 79, 88, 85, and 83 %, respectively, for observer 2. The tumour-to-liver SUV ratio with 18-F FDG-PET/CT appeared to be a valuable imaging biomarker in the prediction of high-grade cRCC. (orig.)

  3. Use of induced pluripotent stem cell derived neurons engineered to express BDNF for modulation of stressor related pathology.

    Liu, Gele; Rustom, Nazneen; Litteljohn, Darcy; Bobyn, Jessica; Rudyk, Chris; Anisman, Hymie; Hayley, Shawn

    2014-01-01

    Combined cell and gene-based therapeutic strategies offer potential in the treatment of neurodegenerative and psychiatric conditions that have been associated with structural brain disturbances. In the present investigation, we used a novel virus-free re-programming method to generate induced pluripotent stem cells (iPSCs), and then subsequently transformed these cells into neural cells which over-expressed brain derived neurotrophic factor (BDNF). Importantly, the infusion of iPSC derived neural cells (as a cell replacement and gene delivery tool) and BDNF (as a protective factor) influenced neuronal outcomes. Specifically, intracerebroventricular transplantation of iPSC-derived neural progenitors that over-expressed BDNF reversed the impact of immune (lipopolysaccharide) and chronic stressor challenges upon subventricular zone adult neurogenesis, and the iPSC-derived neural progenitor cells alone blunted the stressor-induced corticosterone response. Moreover, our findings indicate that mature dopamine producing neurons can be generated using iPSC procedures and appear to be viable when infused in vivo. Taken together, these data could have important implications for using gene-plus-cell replacement methods to modulate stressor related pathology. PMID:25352778

  4. α-Synuclein vaccination modulates regulatory T cell activation and microglia in the absence of brain pathology

    Christiansen, Josefine R; Olesen, Mads N; Otzen, Daniel E; Romero-Ramos, Marina; Sanchez-Guajardo, Vanesa

    2016-01-01

    have studied the changes induced by vaccination with α-synuclein in the CD4 T cell pool and its impact on brain microglia to understand the immune mechanisms behind successful vaccination strategies in Parkinson's disease animal models. METHODS: Mice were immunized with WT or nitrated α-synuclein at a......BACKGROUND: Passive and active immunization with α-synuclein has been shown to be neuroprotective in animal models of Parkinson's disease. We have previously shown that vaccination with α-synuclein, long before α-synuclein-induced brain pathology, prevents striatal degeneration by inducing...... regulatory T cell infiltration in parenchyma and antibody deposition on α-synuclein overexpressing neurons. However, the effect of peripheral α-synuclein on the immune system is unknown, as are the mechanistic changes induced in the CD4 T cell population during successful neuroprotective animal studies. We...

  5. Quantitation and renewal of alveolar and bronchiolar cell populations of rat lungs. Changes during some pathological processes

    The various cells of alveolar and bronchiolar tissues of rat lungs were studied qualitatively and quantitatively. In physiological conditions, the renewal rate of the cell populations is low and the frequency of the various cell types is constant. This stability, especially at the level of the alveolar tissue, was also found during the latency period and the development of radiation-induced lung cancers. A particular cellular population was demonstrated: marginated leukocyte pool at the level of the pulmonary circulation. This pool was different both qualitatively and quantitatively from the leukocytes of the systemic circulation and, in physiological conditions, behaved as a cellular reservoir of monocytes chiefly re-distributed according to the body needs. In pathological conditions, its fast migration contributed to the defence of the alveolar medium. A quantitative study of the renewal of alveolar macrophages showed that under 1 p. cent of the marginated leukocyte pool is used daily to keep up this population. This fraction undergoes a maturation stage by cellular division within the endoalveolar medium. In some pathological conditions, this division can be completely inhibited

  6. Adrenomedullin promotes differentiation of oligodendrocyte precursor cells into myelin-basic-protein expressing oligodendrocytes under pathological conditions in vitro

    Takakuni Maki

    2015-07-01

    Full Text Available Oligodendrocytes, which are the main cell type in cerebral white matter, are generated from their precursor cells (oligodendrocyte precursor cells: OPCs. However, the differentiation from OPCs to oligodendrocytes is disturbed under stressed conditions. Therefore, drugs that can improve oligodendrocyte regeneration may be effective for white matter-related diseases. Here we show that a vasoactive peptide adrenomedullin (AM promotes the in vitro differentiation of OPCs under pathological conditions. Primary OPCs were prepared from neonatal rat brains, and differentiated into myelin-basic-protein expressing oligodendrocytes over time. This in vitro OPC differentiation was inhibited by prolonged chemical hypoxic stress induced by non-lethal CoCl2 treatment. However, AM promoted the OPC differentiation under the hypoxic stress conditions, and the AM receptor antagonist AM22–52 canceled the AM-induced OPC differentiation. In addition, AM treatment increased the phosphorylation level of Akt in OPC cultures, and correspondingly, the PI3K/Akt inhibitor LY294002 blocked the AM-induced OPC differentiation. Taken together, AM treatment rescued OPC maturation under pathological conditions via an AM-receptor-PI3K/Akt pathway. Oligodendrocytes play critical roles in white matter by forming myelin sheath. Therefore, AM signaling may be a promising therapeutic target to boost oligodendrocyte regeneration in CNS disorders.

  7. Adrenomedullin promotes differentiation of oligodendrocyte precursor cells into myelin-basic-protein expressing oligodendrocytes under pathological conditions in vitro.

    Maki, Takakuni; Takahashi, Yoko; Miyamoto, Nobukazu; Liang, Anna C; Ihara, Masafumi; Lo, Eng H; Arai, Ken

    2015-07-01

    Oligodendrocytes, which are the main cell type in cerebral white matter, are generated from their precursor cells (oligodendrocyte precursor cells: OPCs). However, the differentiation from OPCs to oligodendrocytes is disturbed under stressed conditions. Therefore, drugs that can improve oligodendrocyte regeneration may be effective for white matter-related diseases. Here we show that a vasoactive peptide adrenomedullin (AM) promotes the in vitro differentiation of OPCs under pathological conditions. Primary OPCs were prepared from neonatal rat brains, and differentiated into myelin-basic-protein expressing oligodendrocytes over time. This in vitro OPC differentiation was inhibited by prolonged chemical hypoxic stress induced by non-lethal CoCl(2) treatment. However, AM promoted the OPC differentiation under the hypoxic stress conditions, and the AM receptor antagonist AM(22-52) canceled the AM-induced OPC differentiation. In addition, AM treatment increased the phosphorylation level of Akt in OPC cultures, and correspondingly, the PI3K/Akt inhibitor LY294002 blocked the AM-induced OPC differentiation. Taken together, AM treatment rescued OPC maturation under pathological conditions via an AM-receptor-PI3K/Akt pathway. Oligodendrocytes play critical roles in white matter by forming myelin sheath. Therefore, AM signaling may be a promising therapeutic target to boost oligodendrocyte regeneration in CNS disorders. PMID:26002630

  8. Efficient Assessment of Developmental, Surgical and Pathological Lymphangiogenesis Using a Lymphatic Reporter Mouse and Its Embryonic Stem Cells

    Jung, Wonhyuek; Seong, Young Jin; Park, Eunkyung; Bramos, Athanasios; Kim, Kyu Eui; Lee, Sunju; Daghlian, George; Seo, Jung In; Choi, Inho; Choi, In-Seon; Koh, Chester J.; Kobielak, Agnieszka; Ying, Qi-Long; Johnson, Maxwell; Gardner, Daniel; Wong, Alex K.; Choi, Dongwon; Hong, Young-Kwon

    2016-01-01

    Several lymphatic reporter mouse lines have recently been developed to significantly improve imaging of lymphatic vessels. Nonetheless, the usage of direct visualization of lymphatic vessels has not been fully explored and documented. Here, we characterized a new Prox1-tdTomato transgenic lymphatic reporter mouse line, and demonstrated how this animal tool enables the researchers to efficiently assess developmental, surgical and pathological lymphangiogenesis by direct visualization of lymphatic vessels. Moreover, we have derived embryonic stem cells from this reporter line, and successfully differentiated them into lymphatic vessels in vivo. In conclusion, these experimental tools and techniques will help advance lymphatic research. PMID:27280889

  9. Epidermal stem cells - role in normal, wounded and pathological psoriatic and cancer skin

    Kamstrup, M.; Faurschou, A.; Gniadecki, R.;

    2008-01-01

    In this review we focus on epidermal stem cells in the normal regeneration of the skin as well as in wounded and psoriatic skin. Furthermore, we discuss current data supporting the idea of cancer stem cells in the pathogenesis of skin carcinoma and malignant melanoma. Epidermal stem cells present...... stem cells or transit amplifying cells constitute a primary pathogenetic factor in the epidermal hyperproliferation seen in psoriasis. In cutaneous malignancies mounting evidence supports a stem cell origin in skin carcinoma and malignant melanoma and a possible existence of cancer stem cells...

  10. Endoplasmic reticulum redox state is not perturbed by pharmacological or pathological endoplasmic reticulum stress in live pancreatic β-cells.

    Irmgard Schuiki

    Full Text Available Accumulation of unfolded, misfolded and aggregated proteins in the endoplasmic reticulum (ER causes ER stress. ER stress can result from physiological situations such as acute increases in secretory protein biosynthesis or pathological conditions that perturb ER homeostasis such as alterations in the ER redox state. Here we monitored ER redox together with transcriptional output of the Unfolded Protein Response (UPR in INS-1 insulinoma cells stably expressing eroGFP (ER-redox-sensor and mCherry protein driven by a GRP78 promoter (UPR-sensor. Live cell imaging, flow cytometry and biochemical characterization were used to examine these parameters in response to various conditions known to induce ER stress. As expected, treatment of the cells with the reducing agent dithiothreitol caused a decrease in the oxidation state of the ER accompanied by an increase in XBP-1 splicing. Unexpectedly however, other treatments including tunicamycin, thapsigargin, DL-homocysteine, elevated free fatty acids or high glucose had essentially no influence on the ER redox state, despite inducing ER stress. Comparable results were obtained with dispersed rat islet cells expressing eroGFP. Thus, unlike in yeast cells, ER stress in pancreatic β-cells is not associated with a more reducing ER environment.

  11. Clinico-pathological correlation of micronuclei in oral squamous cell carcinoma by exfoliative cytology

    Palve Devendra

    2008-01-01

    Full Text Available Oral squamous cell carcinoma accounts for 90% to 95% of all oral malignancies. Though its diagnosis seldom presents difficulty, it is the cancer staging and histopathological grading that are important to prognostication; and micronuclei are good prognostic indicators. Micronucleus frequencies in oral exfoliated cells stained with papanicolaou stain were counted and correlated with the histopathological grades and clinical stages of squamous cell carcinoma patients. They were also compared with healthy control subjects. Micronuclei (MN frequencies were found higher in squamous cell carcinoma patients than in control subjects. MN frequencies were also found to be raised with increasing histological grades of squamous cell carcinoma.

  12. Pathological clavicular fracture as ifrst presentation of renal cell carcinoma:a case report and literature review

    Yan Kong; Jin Wang; Huan Li; Peng Guo; Jian-Fa Xu; He-Lin Feng

    2015-01-01

    Renal cell carcinoma (RCC) accounts for approximately 3%of all cancer cases. RCCs usually metastasize to the lungs, bones, liver, or brain. Only<1%of patients with bone metastases manifested clavicular RCC metastases. hTus, clavicular metastasis as the initial presentation of RCC is extremely rare. We report a patient with RCC metastasis to the letf clavicle, which was ifrst presented with pain caused by a pathological fracture. Magnetic resonance image revealed a renal tumor, and technetium-99m–methylene diphosphonate bone scintigraphy showed multiple osseous metastases. The patient eventually underwent surgery to remove the lateral end of the letf clavicle and right kidney. Histopathology revealed renal tumor and clear cell carcinoma in the clavicle. Finally, we review 17 cases of clavicular metastases originating from different malignancies.

  13. Solitary pulmonary metastases from renal cell carcinoma. Comparison of high-resolution CT with pathological findings

    The aim of this study was to examine the radiographic features of solitary pulmonary metastases from renal cell carcinoma by comparing high-resolution CT (HRCT) findings with histopathological observations. Three thoracic radiologists retrospectively reviewed HRCT findings from eight patients who underwent surgery on the basis of the diagnosis of solitary pulmonary metastatic renal cell carcinoma. The histopathological diagnoses for six of these eight lesions were metastases from clear cell carcinoma of the kidney, one case was a metastasis from papillary renal cell carcinoma, and the remaining case was a metastasis from a poorly differentiated carcinoma including predominantly spindle cells, papillary cells, and clear cells. The HRCT findings of all cases of clear cell carcinoma showed solid nodular lesions without ground-glass attenuation (GGA). The HRCT findings for one case of papillary renal cell carcinoma showed a lobulated nodule with a small amount of GGA in an area in the periphery and an air bronchogram. The HRCT findings of the remaining case of poorly differentiated carcinoma showed an ill-defined nodule with a GGA area and pleural indentations. In brief, solitary pulmonary metastases from renal cell carcinoma may present as a smoothly marginated nodule, lobulated nodule, or a nodule with peripheral GGA. (author)

  14. Pathological Analysis of Cell Differentiation in Cholesterol Granulomas Experimentally Induced in Mice

    Sakai, Kenzo; Nakano, Keisuke; Matsuda, Saeka; Tsujigiwa, Hidetsugu; Ochiai, Takanaga; Shoumura, Masahito; Osuga, Naoto; Hasegawa, Hiromasa; Kawakami, Toshiyuki

    2016-01-01

    In this study, cholesterin was implanted in the subcutaneous tissue in mice to induce the formation of cholesterol granuloma. Histological examination was carried out to determine the type and source of cells. The tissue surrounding the embedded cholesterin was examined histologically within the period of 6 months. Cell differentiation in cholesterol granulomas was investigated using ddY mice and GFP bone marrow transplanted mice. Cholesterin was embedded in mice subcutaneously and histopathological examination was carried out in a period of 6 months. Results showed that at 2 weeks, cholesterin was replaced partly by granulation tissues. The majority of cells in the granulation tissues were macrophages and foreign body giant cells and the center consists of small amount of fibroblasts, collagen fibers and capillaries. At 3 months, more granulation tissue was observed compared to 2 weeks. Similar cells were observed, however, there were more fibroblasts, collagen bundles and capillaries present compared to 2 weeks. At 6 months, the cholesterin was mostly substituted by fibrous tissues consisting mainly of fibroblasts and collagen fibers with some macrophages and foreign body giant cells. Specifically, the outer part of the tissue consists of fibroblasts, collagen bundles and capillaries and the inner portion is filled with collagen bundles. Immunohistochemistry revealed that macrophages and foreign body giant cells were positive to GFP and CD68 although the fibroblasts and capillaries in the outer portion of cholesterol granulomas were GFP negative. Some spindle shape fibroblasts were also GFP positive. Immunofluorescent double staining revealed that cells lining the blood vessels were both positive to GFP and CD31 indicating that those were endothelial cells and were actually derived from the transplanted bone marrow cells. The results suggest that macrophages, foreign body giant cells as well as fibroblasts and capillary endothelial cells are bone marrow derived

  15. Stem cells and the pancreas: from discovery to clinical approach

    Angelica Dessì

    2016-02-01

    Full Text Available The existence of stem cells within the adult pancreas is supported by the ability of this organ to regenerate its endocrine component in various conditions such as pregnancy and following partial pancreatectomy. Several studies have shown that progenitor or adult stem cells may reside within the pancreas and particularly in the pancreatic ducts, including acinar cells and islets of Langerhans. The discovery of human pluripotent stem cells in the pancreas, and the possibility of development of strategies for generating these, represented a turning point for the therapeutic interventions of type 1 diabetes.Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

  16. Evidence from human and animal studies: Pathological roles of CD8+ T cells in autoimmune peripheral neuropathies

    Mu eYang

    2015-10-01

    Full Text Available Autoimmune peripheral neuropathies such as Guillain Barre Syndrome (GBS and chronic inflammatory demyelinating polyneuropathy (CIDP affect millions of people worldwide. Despite significant advances in understanding the pathology, the molecular and cellular mechanisms of immune-mediated neuropathies remain elusive. T lymphocytes definitely play an important role in disease pathogenesis and CD4+ T cells have been the main area of research for decades. This is partly due to the fact that the most frequent animal model to study autoimmune peripheral neuropathy is experimental allergic neuritis (EAN. As it is induced commonly by immunization with peripheral nerve proteins, EAN is driven mainly by CD4+ T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicate that CD8+ T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8+ T cells in autoimmune peripheral neuropathy. We also discuss the findings from our most recent studies using a transgenic mouse line (L31 mice in which the T cell co-stimulator molecule B7.2 (CD86 is constitutively expressed in antigen presenting cells of the nervous tissues. L31 mice spontaneously develop peripheral neuropathy, and CD8+ T cells are found accumulating in peripheral nerves of symptomatic animals. Interestingly, depletion of CD4+ T cells accelerates disease onset and increases disease prevalence. Finally, we point out some unanswered questions for future research to dissect the critical roles of CD8+ T cells in autoimmune peripheral neuropathies.

  17. Evidence from Human and Animal Studies: Pathological Roles of CD8+ T Cells in Autoimmune Peripheral Neuropathies

    Yang, Mu; Peyret, Corentin; Shi, Xiang Qun; Siron, Nicolas; Jang, Jeong Ho; Wu, Sonia; Fournier, Sylvie; Zhang, Ji

    2015-01-01

    Autoimmune peripheral neuropathies such as Guillain-Barre Syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) affect millions of people worldwide. Despite significant advances in understanding the pathology, the molecular and cellular mechanisms of immune-mediated neuropathies remain elusive. T lymphocytes definitely play an important role in disease pathogenesis and CD4+ T cells have been the main area of research for decades. This is partly due to the fact that the most frequent animal model to study autoimmune peripheral neuropathy is experimental allergic neuritis (EAN). As it is induced commonly by immunization with peripheral nerve proteins, EAN is driven mainly by CD4+ T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicates that CD8+ T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8+ T cells in autoimmune peripheral neuropathies. We also discuss the findings from our most recent studies using a transgenic mouse line (L31 mice) in which the T cell co-stimulator molecule B7.2 (CD86) is constitutively expressed in antigen presenting cells of the nervous tissues. L31 mice spontaneously develop peripheral neuropathy, and CD8+ T cells are found accumulating in peripheral nerves of symptomatic animals. Interestingly, depletion of CD4+ T cells accelerates disease onset and increases disease prevalence. Finally, we point out some unanswered questions for future research to dissect the critical roles of CD8+ T cells in autoimmune peripheral neuropathies. PMID:26528293

  18. Clinico-pathological correlation of micronuclei in oral squamous cell carcinoma by exfoliative cytology

    Palve Devendra; Tupkari Jagdish

    2008-01-01

    Oral squamous cell carcinoma accounts for 90% to 95% of all oral malignancies. Though its diagnosis seldom presents difficulty, it is the cancer staging and histopathological grading that are important to prognostication; and micronuclei are good prognostic indicators. Micronucleus frequencies in oral exfoliated cells stained with papanicolaou stain were counted and correlated with the histopathological grades and clinical stages of squamous cell carcinoma patients. They were al...

  19. Concurrent sickle cell anemia and alpha-thalassemia. Effect on pathological properties of sickle erythrocytes.

    Embury, S H; Clark, M R; Monroy, G; Mohandas, N

    1984-01-01

    The concurrence of sickle cell anemia and alpha-thalassemia results in less severe hemolytic anemia apparently as a result of reduced intraerythrocytic concentration of hemoglobin S and its retarded polymerization. We have evaluated the effect of alpha-globin gene number on several interrelated properties of sickle erythrocytes (RBC) that are expected to correlate with the hemolytic and rheologic consequences of sickle cell disease. The irreversibly sickled cell number, proportion of very den...

  20. Dynamic simulation of red blood cell metabolism and its application to the analysis of a pathological condition

    Kinoshita Ayako

    2005-05-01

    Full Text Available Abstract Background Cell simulation, which aims to predict the complex and dynamic behavior of living cells, is becoming a valuable tool. In silico models of human red blood cell (RBC metabolism have been developed by several laboratories. An RBC model using the E-Cell simulation system has been developed. This prototype model consists of three major metabolic pathways, namely, the glycolytic pathway, the pentose phosphate pathway and the nucleotide metabolic pathway. Like the previous model by Joshi and Palsson, it also models physical effects such as osmotic balance. This model was used here to reconstruct the pathology arising from hereditary glucose-6-phosphate dehydrogenase (G6PD deficiency, which is the most common deficiency in human RBC. Results Since the prototype model could not reproduce the state of G6PD deficiency, the model was modified to include a pathway for de novo glutathione synthesis and a glutathione disulfide (GSSG export system. The de novo glutathione (GSH synthesis pathway was found to compensate partially for the lowered GSH concentrations resulting from G6PD deficiency, with the result that GSSG could be maintained at a very low concentration due to the active export system. Conclusion The results of the simulation were consistent with the estimated situation of real G6PD-deficient cells. These results suggest that the de novo glutathione synthesis pathway and the GSSG export system play an important role in alleviating the consequences of G6PD deficiency.

  1. Acinus-on-a-chip: a microfluidic platform for pulmonary acinar flows

    Fishler, Rami; Mulligan, Molly; Sznitman, Josue; Sznitman Biofluids Team

    2013-11-01

    Convective respiratory flows in the pulmonary acinus and their influence on the fate of inhaled particles are typically studied using computational fluid dynamics (CFD) or scaled-up experimental models. However, current experiments generally capture only flow dynamics, without inhaled particle dynamics, due to difficulties in simultaneously matching flow and particle dynamics. In an effort to overcome these limitations, we have designed a novel microfluidic device mimicking acinar flow conditions directly at the physiological scale. The model features an anatomically-inspired acinar geometry with five dichotomously branching airway generations lined with periodically expanding and contracting alveoli. Using micro-particle image velocimetry (PIV), we reveal experimentally a gradual transition of alveolar flow patterns along the acinar tree from recirculating to radial streamlines, in support of previous predictions from CFD simulations. We demonstrate the applicability of the device for studying the mechanisms of particle deposition in the pulmonary acinus by mapping deposition sites of airborne fluorescent micro-particles (0.1-1 μm) and visualizing trajectories of airborne incense particles inside the system.

  2. Coupling of guanine nucleotide inhibitory protein to somatostatin receptors on pancreatic acinar membranes

    Guanine nucleotides and pertussis toxin were used to investigate whether somatostatin receptors interact with the guanine nucleotide inhibitory protein (NI) on pancreatic acinar membranes in the rat. Guanine nucleotides reduced 125I-[Tyr1]somatostatin binding to acinar membranes up to 80%, with rank order of potency being 5'-guanylyl imidodiphosphate [Gpp(NH)p]>GTP>TDP>GMP. Scatchard analysis revealed that the decrease in somatostatin binding caused by Gpp(NH)p was due to the decrease in the maximum binding capacity without a significant change in the binding affinity. The inhibitory effect of Gpp(NH)p was partially abolished in the absence of Mg2+. When pancreatic acini were treated with 1 μg/ml pertussis toxin for 4 h, subsequent 125I-[Tyr1]somatostatin binding to acinar membranes was reduced. Pertussis toxin treatment also abolished the inhibitory effect of somatostatin on vasoactive intestinal peptide-stimulated increase in cellular content of adenosine 3',5'-cyclic monophosphate (cAMP) in the acini. The present results suggest that 1) somatostatin probably functions in the pancreas to regulate adenylate cyclase enzyme system via Ni, 2) the extent of modification of Ni is correlated with the ability of somatostatin to inhibit cAMP accumulation in acini, and 3) guanine nucleotides also inhibit somatostatin binding to its receptor

  3. Video-Assisted Thoracic Surgery (VATS) Lobectomy for Pathologic Stage I Non-Small Cell Lung Cancer: A Comparative Study with Thoracotomy Lobectomy

    Park, Joon Suk; Kim, Kwhanmien; Choi, Min Suk; Chang, Sung Wook; Han, Woo-sik

    2011-01-01

    Background Surgical treatment of stage I non-small cell lung cancer (NSCLC) can be performed either by thoracotomy or by employing video-assisted thoracic surgery (VATS). The aim of this study was to evaluate the feasibility of VATS lobectomy for pathologic stage I NSCLC. Material and Methods Between December 2003 and December 2007, 529 patients with pathologic stage I NSCLC underwent lobectomies (373 thoracotomy, 156 VATS). Patients in both groups were selected after being matched by age, ge...

  4. Pathologic and Protective Roles for Microglial Subsets and Bone Marrow- and Blood-Derived Myeloid Cells in Central Nervous System Inflammation

    Wlodarczyk, Agnieszka; Cédile, Oriane; Jensen, Kirstine Nolling;

    2015-01-01

    Inflammation is a series of processes designed for eventual clearance of pathogens and repair of damaged tissue. In the context of autoimmune recognition, inflammatory processes are usually considered to be pathological. This is also true for inflammatory responses in the central nervous system...... (CNS). However, as in other tissues, neuroinflammation can have beneficial as well as pathological outcomes. The complex role of encephalitogenic T cells in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE) may derive from heterogeneity of the myeloid cells with...... three populations of myeloid cells: CD11c(+) microglia, CD11c(-) microglia, and CD11c(+) blood-derived cells in terms of their pathological versus protective functions in the CNS of mice with EAE. Our data show that CNS-resident microglia include functionally distinct subsets that can be distinguished...

  5. Pathological study of breast cancer by method postneaadyuvancia RCB (residual tumor burden) associated with cell proliferation index report preliminary data

    Full text: Introduction: The evaluation of residual disease increases prognostic information postneaadyuvancia and obtained by the study of pathological response. Using method index residual tumor burden (RCB)developed at M D Anderson where from morphological parameters (Size of the tumor bed, residual percentage of invasive carcinoma, carcinoma in situ percentage residual metastatic nodes number and size of largest metastasis)the index is calculated. Proliferation index represents an independent predictor of response to particular drugs. A high rate of cell proliferation after chemotherapy is linked with a poor survival We compared the results of both indices Material and Methods: We applied method residual tumor burden index (RCB)in 30 patients operated breast carcinoma after neoadjuvant therapy. Documentation was performed digital macroscopic bed residual tumor, printing and bulk sampling mapping performed on serially reading sheets histological double-blind by two pathologists using graphical illustrations of the percentage of cellularity neoplastic. The application of the formula classified as: RCB 0, complete pathological response (Rpc), RCB I, minimal residual disease, moderate residual disease RCB II, III RBC extensive disease residual. We immunohistochemical proliferation index (PI)with K i 67 in 14 cases (RCB II and III) with double-blinded histological evaluation by performing a percentage of stained nuclei in the greater staining sector thereof and with a cutoff of 14% of stained nuclei. Results: The size of the residual tumor bed was between 4x3mm and 110x60mm. Percentages cellularity invasive component between 0 and 86%, carcinoma in situ between 0 and 30 %. RCB case 0, RCB I a case, RCB RCB II and III seventeen cases eleven cases. Proliferation index was between 1% to 90 %, greater than 14 % in 29% of III and 21% RCB RCB II. Less than 14% was seen in 29% of RCB II and 7% RCB III In six cases there was variation in the rate of pre and post neoadjuvant

  6. Dendritic cell biology in human cytomegalovirus infection and the clinical consequences for host immunity and pathology

    Gredmark-Russ, Sara; Söderberg-Nauclér, Cecilia

    2012-01-01

    Human cytomegalovirus (HCMV), a member of the herpesvirus family, establishes life-long persistence and latency after primary infection and can be reactivated later in life. In immunosuppressed patients, it is an important pathogen that can cause severe disease. HCMV is also thought to play a causative role in inflammatory diseases and cancer. The virus can infect different immune cells, including dendritic cells (DCs) and can take advantage of host immune functions to avoid immune recognitio...

  7. Feline cutaneous neuroendocrine carcinoma (Merkel cell tumour): clinical and pathological findings.

    Bagnasco, Giorgio; Properzi, Roberto; Porto, Roberto; Nardini, Vincenzo; Poli, Alessandro; Abramo, Francesca

    2003-04-01

    A case of a feline Merkel cell tumour is described. An 8-year-old, female cat developed a round, alopecic, reddish mass on the nose. Wide excisional surgery was performed with cartilage resection. Histologically the mass was composed of solid islands of mostly basophilic densely packed cells with a scant cytoplasm, which was suggestive of a neuroendocrine origin. Results of immunohistochemical studies using antibodies against neurone-specific enolase, chromogranin, synaptophysin and pan-cytokeratin allowed classification of the lesion as a Merkel cell tumour. Ultrastructurally, dense core granules were identified in the cytoplasm. In a 2-year follow-up no relapses or metastases were observed. The clinical course recorded is in contrast with the malignant nature of a Merkel cell tumour recently described in a cat and of the human Merkel cell tumour, but is similar to the course of the canine Merkel cell tumour which is often benign. Early diagnosis along with the use of wide surgical excision might be considered an important factor in preventing relapse of this tumour. PMID:12662269

  8. Clear cell carcinoma, not otherwise specified/hyalinising clear cell carcinoma of the salivary gland: The current nomenclature, clinical/pathological characteristics and management.

    Daniele, Luca; Nikolarakos, Dimitrios; Keenan, Jonathon; Schaefer, Nathan; Lam, Alfred King-Yin

    2016-06-01

    Clear cell carcinoma, not otherwise specified (NOS)/hyalinising clear cell carcinoma (HCCC) is a rare entity in salivary gland tumour. The aim of the research is to review the current concepts and characteristics of this carcinoma. The clinical and pathological data of the disease obtained from literature and two original cases were analysed. Overall, 152 cases were reviewed up to the year 2014. The carcinomas were noted often in woman, in the seventh decade of life, located in oral cavity and as early-stages cancers. On pathological examination, they were characterized by tumour cells having clear cell morphology with hyalinised stroma. Immunohistochemical studies revealed that the carcinoma is positive for cytokeratin and negative for myoepithelial differentiation. EWSR1-ATF1 fusion is specific for the carcinoma. Also, 9% of the reported cases had local nodal metastasis, with 6 cases demonstrating distant metastases at presentation. On follow-up, 22% of patients had recurrent or with persistent diseases after surgery. The time for the first recurrence could be as long as 24 years. Risk factors for recurrence include advanced stage at diagnosis and metastases at presentation. To conclude, HCCC is a low grade malignancy but have the potential for local metastases, recurrence, distant metastases and cancer-related death. PMID:27150676

  9. Pathological gambling

    ... to a gambling habit. Stressful situations can worsen gambling problems. ... to avoid letting other people know about their problem. The American Psychiatric Association defines pathological gambling as having five or more of the following ...

  10. Intracellular lipid in papillary renal cell carcinoma (pRCC): T2 weighted (T2W) MRI and pathologic correlation

    Schieda, Nicola; Van der Pol, Christian B.; Moosavi, Bardia; McInnes, Matthew D.F. [The Ottawa Hospital, The University of Ottawa, Department of Medical Imaging, Ottawa, Ontario (Canada); Mai, Kien T.; Flood, Trevor A. [The Ottawa Hospital, The University of Ottawa, Department of Anatomical Pathology, Ottawa, Ontario (Canada)

    2015-07-15

    To evaluate if pRCCs demonstrate intracellular lipid (i-lipid) at chemical-shift (CS) MRI, and assess T2W-MRI and pathologic characteristics. Sixty-two patients with a pRCC diagnosis underwent MRI over 11 years (IRB-approved). Two radiologists independently assessed for presence of i-lipid on CS-MRI and homogeneity on T2W-MRI. Inter-observer agreement was assessed via an intraclass correlation and results were compared using the Chi-square test. Discordant cases were reviewed to establish consensus. T2W SI-ratios (SI.tumor/SI.kidney) and CS-SI index were compared using independent t-tests and Spearman correlation. Two pathologists re-evaluated the histopathology. Nine of the 62 pRCCs (14.5 %) demonstrated i-lipid; agreement was moderate (ICC = 0.63). Pathology review depicted clear cells in four tumours and foamy histiocytes in five tumours. 25.8-35.4 % (ICC = 0.65) of tumours were homogeneous on T2W-MRI. No pRCC with i-lipid was considered homogeneous (p = 0.01-0.04). Overall, T2W SI-ratio and CS-SI index were 0.89 (±0.29) and -3.63 % (-7.27 to 11.42). pRCC with i-lipid had significantly higher T2W SI-ratio (p = 0.003). There was a correlation between the CS-SI index and T2W SI-ratio, (r = 0.44, p < 0.001). Intracellular lipid is uncommonly detected in pRCCs due to clear cell changes and foamy histiocytes. These tumours are associated with heterogeneously-increased SI in T2W-MRI. (orig.)

  11. Intracellular lipid in papillary renal cell carcinoma (pRCC): T2 weighted (T2W) MRI and pathologic correlation

    To evaluate if pRCCs demonstrate intracellular lipid (i-lipid) at chemical-shift (CS) MRI, and assess T2W-MRI and pathologic characteristics. Sixty-two patients with a pRCC diagnosis underwent MRI over 11 years (IRB-approved). Two radiologists independently assessed for presence of i-lipid on CS-MRI and homogeneity on T2W-MRI. Inter-observer agreement was assessed via an intraclass correlation and results were compared using the Chi-square test. Discordant cases were reviewed to establish consensus. T2W SI-ratios (SI.tumor/SI.kidney) and CS-SI index were compared using independent t-tests and Spearman correlation. Two pathologists re-evaluated the histopathology. Nine of the 62 pRCCs (14.5 %) demonstrated i-lipid; agreement was moderate (ICC = 0.63). Pathology review depicted clear cells in four tumours and foamy histiocytes in five tumours. 25.8-35.4 % (ICC = 0.65) of tumours were homogeneous on T2W-MRI. No pRCC with i-lipid was considered homogeneous (p = 0.01-0.04). Overall, T2W SI-ratio and CS-SI index were 0.89 (±0.29) and -3.63 % (-7.27 to 11.42). pRCC with i-lipid had significantly higher T2W SI-ratio (p = 0.003). There was a correlation between the CS-SI index and T2W SI-ratio, (r = 0.44, p < 0.001). Intracellular lipid is uncommonly detected in pRCCs due to clear cell changes and foamy histiocytes. These tumours are associated with heterogeneously-increased SI in T2W-MRI. (orig.)

  12. Physiological, pathological, and engineered cell identity reprogramming in the central nervous system.

    Smith, Derek K; Wang, Lei-Lei; Zhang, Chun-Li

    2016-07-01

    Multipotent neural stem cells persist in restricted regions of the adult mammalian central nervous system. These proliferative cells differentiate into diverse neuron subtypes to maintain neural homeostasis. This endogenous process can be reprogrammed as a compensatory response to physiological cues, traumatic injury, and neurodegeneration. In addition to innate neurogenesis, recent research has demonstrated that new neurons can be engineered via cell identity reprogramming in non-neurogenic regions of the adult central nervous system. A comprehensive understanding of these reprogramming mechanisms will be essential to the development of therapeutic neural regeneration strategies that aim to improve functional recovery after injury and neurodegeneration. WIREs Dev Biol 2016, 5:499-517. doi: 10.1002/wdev.234 For further resources related to this article, please visit the WIREs website. PMID:27258392

  13. Pathologic effects of fractionated fast neutrons or photons on the pancreas, pylorus and duodenum of dogs

    Thirty-nine adult male Beagles received either fast neutron or photon irradiation to the right thorax to determine the relative biological effectiveness (RBE) of fast neutrons on normal pulmonary tissue. The right anterior abdomen was included in the field of radiation. Twenty-four dogs (six/group) received fast neutrons with an average energy of 15 MeV to total doses of 1000, 1500, 2250 or 3375 rad in four fractions per week for six weeks. Fifteen dogs received 3000, 4500, or 6750 rad of photons (five/group) in an identical fractionation pattern. All neutron irradiated dogs receiving 3375 and 2250 rad and one receiving 1500 rad developed clinical signs of pancreatic, hepatic and gastrointestinal disturbances. The liver enzymes of these dogs became elevated and they died or were euthanized in extremis 47-367 days after irradiation. Only one 6750 rad photon dog developed similar signs and died 708 days post-irradiation. Five neutron and 10 photon exposed dogs died of other causes. Neutron-induced lesions in the stomach and duodenum included hemorrhages, erosions, ulcerations and fibrosis. Ulcers perforated the GI tract of five dogs. Pancreatic lesions included degranulation and necrosis of acinar cells, fibrosis and atrophy. Islet cells were not obviously damaged. All lesions were associated with degenerative and occlusive vascular changes. The RBE of fast neutrons, assessed by clinical signs, gross and microscopic pathology, is approximately 3-4.5 for pancreas and about 4.5 for pylorus and duodenum

  14. MicroRNAs in the pathology of B-Cell Chronic Lymphocytic Leukemia

    In chronic lymphocytic leukemia (B-CLL), aberrations along the p53 axis lead to decreased overall survival and therapy resistance. Recent studies identified miR-34a as a major downstream target of p53. We monitored the expression of miR-34a during disease development in a murine B-CLL model. miR-34a was upregulated >20-fold during the leukemic but not during the preleukemic phase. In the human system, B-CLL cells also had 4.6-fold higher miR-34a expression as compared to B-cells of healthy controls. In B-CLL cells of patients with p53 aberrations miR-34a expression was consistently low. The broad distribution of miR-34a levels in p53 wild-type individuals prompted us to study the correlation between SNP309 in the intronic promoter of MDM2 and miR-34a expression. B-CLL cells of patients with the SNP309 GG genotype had significantly lower miR-34a expression levels as compared to patients with the TT genotype (P =0.002). Low miR-34a levels were able to predict shorter time to treatment (P = 0.003) and were associated with an abbreviated lymphocyte doubling time. Further, overexpression of miR-34a in primary B-CLL cells induced apoptosis. These findings suggest miR-34a as a possible therapeutic avenue and a sensitive indicator of the activity of the p53 axis in B-CLL. (author)

  15. Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies

    S. Salvioli

    2007-01-01

    Full Text Available Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.

  16. Giant cells glioblastoma: case report and pathological analysis from this uncommon subtype of glioma

    Telmo A.B. Belsuzarri

    2015-03-01

    Full Text Available Glioblastoma multiforme (GBM is the most common glial tumor of the brain system; nevertheless, the giant cell (GC subtype is uncommon. Recent reviews report for an incidence of 1% in adults and 3% in children. The GCs usually have a better prognosis than GBM and also an increasing long-term survival rate. It is known that the diagnosis of this tumor is due to its histological findings and patterns, such as the unusual increased number of giant cells. Unfortunately, due to its rarity, the immunohistochemical and cytogenetical analysis of this tumor is not well known. Some authors also suggest that there are few subtypes of GCs and their patterns of aggressiveness could be due to cytogenetical markers. It is recognized that maximum safe resection treatment and adjuvant radiotherapy can improve survival rate (5-13 months similar to GBM patients.

  17. Clinical-Pathological Parameters as Prognostic Indicators in Oral Squamous Cell

    Raimundo Fernandes de ARAÚJO JÚNIOR

    2006-08-01

    Full Text Available Objective: To correlate the TNM classification and histological scores of malignancy, and these parameters with the prognosis in 38 cases of squamous cell carcinoma oral. Method: The cases were selected from the files of "Dr. Luiz Antônio" Cancer Hospital, Natal, RN, Brazil. After analysis of the patients' records, the data concerning TNM classification and prognosis (in a 5-year-follow-up were obtained. All cases were classified according to the histological malignancy grading system proposed by Bryne (1998. Results: There was correlation between histological scores of malignancy and prognosis and TNM classification with prognosis. Conclusion: It was concluded that TNM classification and histological malignancy grading are important prognostic indicators the squamous cell carcinoma oral.

  18. Geometric characterization of red blood cells. Differentiation of normal and pathologic samples

    Javier Rodríguez; Catalina Correa; Signed Prieto; Benjamín Ospino; Pedro Bernal; Liliana Ortiz; Ángela Munévar

    2008-01-01

    the irregularity of abstract and natural objectswith the fractal dimension. Fractal calculationshave been applied to the structures of the humanbody and to quantifications in physiology fromthe theory of dynamic systems.Material and Methods. The fractal dimensionswere calculated, the number of occupationspaces in the space border of box counting andthe area of two red blood cells groups, 7 normalones, group A, and 7 abnormal, group B, comingfrom patient and of bags for transfusion, werecalcul...

  19. Evaluation of Mast Cell Activation Syndromes: Impact of Pathology and Immunohistology

    Horny, H.-P.; Sotlar, K; Valent, P

    2012-01-01

    Mast cell activation syndromes (MCAS) are clinically defined disease states with a largely unknown morphological background. Since mastocytosis may be associated with MCAS, it is crucial in every patient to document or exclude mastocytosis by appropriate histological, molecular, and serological investigations of tissues/organs that are commonly involved in mastocytosis like skin, mucosa of the gastrointestinal tract and bone marrow. Accordingly, histopathological investigation including immun...

  20. Clinical and surgical-pathological staging in early non-small cell lung cancer

    Ioannis Koukis; Ioannis Gkiozos; Ioannis Ntanos; Elias Kainis; Konstantinos N. Syrigos

    2013-01-01

    Staging is of the utmost importance in the evaluation of a patient with non-small cell lung cancer (NSCLC) because it defines the actual extent of the disease. Accurate staging allows multidisciplinary oncology teams to plan the best surgical or medical treatment and to predict patient prognosis. Based on the recommendation of the International Association for the Study of Lung Cancer (IASLC), a tumor, node, and metastases (TNM) staging system is currently used for NSCLC. Clinical staging (c-...

  1. Systemic immunotherapy delays photoreceptor cell loss and prevents vascular pathology in Royal College of Surgeons rats

    Adamus, Grazyna; Wang, Shaomei; Kyger, Madison; Worley, Aneta; Lu, Bin; Burrows, Gregory G.

    2012-01-01

    Purpose Degenerative retinopathies, including retinitis pigmentosa, age-related retinal degeneration, autoimmune retinopathy, and related diseases affect millions of people around the world. Currently, there is no effective treatment for most of those diseases. We investigated systemic recombinant T-cell receptor ligand (RTL) immunotherapy for preventing retinal degeneration and vascular damage in the Royal College of Surgeons (RCS) rat model of retinal degeneration. Methods RCS rats were tre...

  2. Sox17 regulates insulin secretion in the normal and pathologic mouse β cell.

    Diva Jonatan

    Full Text Available SOX17 is a key transcriptional regulator that can act by regulating other transcription factors including HNF1β and FOXA2, which are known to regulate postnatal β cell function. Given this, we investigated the role of SOX17 in the developing and postnatal pancreas and found a novel role for SOX17 in regulating insulin secretion. Deletion of the Sox17 gene in the pancreas (Sox17-paLOF had no observable impact on pancreas development. However, Sox17-paLOF mice had higher islet proinsulin protein content, abnormal trafficking of proinsulin, and dilated secretory organelles suggesting that Sox17-paLOF adult mice are prediabetic. Consistant with this, Sox17-paLOF mice were more susceptible to aged-related and high fat diet-induced hyperglycemia and diabetes. Overexpression of Sox17 in mature β cells using Ins2-rtTA driver mice resulted in precocious secretion of proinsulin. Transcriptionally, SOX17 appears to broadly regulate secretory networks since a 24-hour pulse of SOX17 expression resulted in global transcriptional changes in factors that regulate hormone transport and secretion. Lastly, transient SOX17 overexpression was able to reverse the insulin secretory defects observed in MODY4 animals and restored euglycemia. Together, these data demonstrate a critical new role for SOX17 in regulating insulin trafficking and secretion and that modulation of Sox17-regulated pathways might be used therapeutically to improve cell function in the context of diabetes.

  3. Geometric characterization of red blood cells. Differentiation of normal and pathologic samples

    Javier Rodríguez

    2008-12-01

    Full Text Available the irregularity of abstract and natural objectswith the fractal dimension. Fractal calculationshave been applied to the structures of the humanbody and to quantifications in physiology fromthe theory of dynamic systems.Material and Methods. The fractal dimensionswere calculated, the number of occupationspaces in the space border of box counting andthe area of two red blood cells groups, 7 normalones, group A, and 7 abnormal, group B, comingfrom patient and of bags for transfusion, werecalculated using the method of box counting anda software developed for such effect. The obtainedmeasures were compared, looking for differencesbetween normal and abnormal red blood cells,with the purpose of differentiating samples.Results. The abnormality characterizes by anumber of squares of occupation of the fractalspace greater or equal to 180; values of areasbetween 25.117 and 33.548 correspond to normality.In case that the evaluation according tothe number of pictures is of normality, must beconfirmed with the value of the area applied toadjacent red blood cells within the sample, thatin case of having values by outside establishedand/or the greater or equal spaces to 180, theysuggest abnormality of the sample.Conclusions. The developed methodology iseffective to differentiate the red globules alterationsand probably useful in the analysis of bagsof transfusion for clinical use.

  4. Sox17 Regulates Insulin Secretion in the Normal and Pathologic Mouse β Cell

    Jonatan, Diva; Spence, Jason R.; Method, Anna M.; Kofron, Matthew; Sinagoga, Katie; Haataja, Leena; Arvan, Peter; Deutsch, Gail H.; Wells, James M.

    2014-01-01

    SOX17 is a key transcriptional regulator that can act by regulating other transcription factors including HNF1β and FOXA2, which are known to regulate postnatal β cell function. Given this, we investigated the role of SOX17 in the developing and postnatal pancreas and found a novel role for SOX17 in regulating insulin secretion. Deletion of the Sox17 gene in the pancreas (Sox17-paLOF) had no observable impact on pancreas development. However, Sox17-paLOF mice had higher islet proinsulin prote...

  5. Whirler Mutant Hair Cells Have Less Severe Pathology than Shaker 2 or Double Mutants

    Mustapha, Mirna; Lisa A. Beyer; Izumikawa, Masahiko; Swiderski, Donald L.; Dolan, David F.; Raphael, Yehoash; Camper, Sally A.

    2007-01-01

    MYOSIN XV is a motor protein that interacts with the PDZ domain-containing protein WHIRLIN and transports WHIRLIN to the tips of the stereocilia. Shaker 2 (sh2) mice have a mutation in the motor domain of MYOSIN XV and exhibit congenital deafness and circling behavior, probably because of abnormally short stereocilia. Whirler (wi) mice have a similar phenotype caused by a deletion in the third PDZ domain of WHIRLIN. We compared the morphology of Whrnwi/wi and Myo15sh2/sh2 sensory hair cells a...

  6. Pro-angiogenic Hematopoietic Progenitor Cells and Endothelial Colony Forming Cells in Pathological Angiogenesis of Bronchial and Pulmonary Circulation

    Duong, Heng; Erzurum, Serpil; Asosingh, Kewal

    2011-01-01

    Dysregulation of angiogenesis is a common feature of many disease processes. Vascular remodeling is believed to depend on the participation of endothelial progenitor cells, but the identification of endothelial progenitors in postnatal neovascularization remains elusive. Current understanding posits a role for circulating pro-angiogenic hematopoietic cells, which interact with local endothelial cells to establish an environment that favors angiogenesis in physiologic and pathophysiologic resp...

  7. Neural Stem Cell Gene Therapy Ameliorates Pathology and Function in a Mouse Model of Globoid Cell Leukodystrophy

    Neri, Margherita; Ricca, Alessandra; di Girolamo, Ilaria; Alcala'-Franco, Beatriz; Cavazzin, Chiara; Orlacchio, Aldo; Martino, Sabata; Naldini, Luigi; Gritti, Angela

    2011-01-01

    Murine neural stem cells (mNSCs), either naive or genetically modified to express supranormal levels of β-galactocerebrosidase (GALC), were transplanted into the brain of Twitcher mice, a murine model of globoid cell leukodystrophy, a severe sphingolipidosis. Cells engrafted long-term into the host cytoarchitecture, producing functional GALC. Levels of enzyme activity in brain and spinal cord tissues were enhanced when GALC-overexpressing NSC were used. Enzymatic correction correlated with re...

  8. Oral squamous cell carcinoma: clinicopathological features from 346 cases from a single Oral Pathology service during an 8-year period

    Fabio Ramoa Pires

    2013-09-01

    Full Text Available Epidemiological data from oral squamous cell carcinoma (OSCC is mostly derived from North American, European and East Asian populations. OBJECTIVE: The aim of this study was to report the demographic and clinicopathological features from OSCC diagnosed in an Oral Pathology service in southeastern Brazil in an 8-year period. MATERIAL AND METHODS: All OSCC diagnosed from 2005 to 2012 were reviewed, including histological analysis of all hematoxylin and eosin stained slides and review of all demographic and clinical information from the laboratory records. RESULTS: A total of 346 OSCC was retrieved and males represented 67% of the sample. Mean age of the patients was 62.3 years-old and females were affected a decade older than males (p<0.001. Mean time of complaint with the tumors was 10 months and site distribution showed that the border of the tongue (37%, alveolar mucosa/gingiva (20% and floor of mouth/ventral tongue (19% were the most common affected sites. Mean size of the tumors was 3.4 cm, with no differences for males and females (p=0.091 and males reported both tobacco and alcohol consumption more frequently than females. Histological grade of the tumors revealed that 27%, 40% and 21% of the tumors were, respectively, classified as well-, moderately- and poorly-differentiated OSCC, 26 cases (7.5% were microinvasive OSCC and 17 cases were OSCC variants. OSCC in males mostly affected the border of tongue, floor of mouth/ventral tongue and alveolar mucosa/gingival, while they were more frequent on the border of tongue, alveolar mucosa/gingival and buccal mucosa/buccal sulcus in females (p=0.004. CONCLUSIONS: The present data reflect the epidemiological characteristics of OSCC diagnosed in a public Oral Pathology laboratory in southeastern Brazil and have highlighted several differences in clinicopathological features when comparing male and female OSCC-affected patients.

  9. Clinico-pathological study on non-squamous cell carcinomas of the oral cavity and oropharynx

    We reviewed 22 cases of non-squamous cell carcinoma (NSCC) of the oral cavity and oropharynx that were treated at the Kurume University Hospital between 1976 and 2005. Two percent of the oral carcinomas and 5% of the oropharyngeal carcinomas were NSCCs. The 5-year and 10-year survival rates of NSCC in the oropharynx were 90%. There was no statistically significant difference in survival rate between squamous cell carcinoma (SCC) and NSCC (p=0.06). The 5-year and 10-year survival rates of NSCC in the oral cavity were 75% and 37%, respectively. There was no statistically significant difference in the survival rate between SCC and NSCC. Survival results well correlated with clinical stages. A significant difference between Stage I, II and III versus Stage IV was found (p=0.04). In contrast, no significant relationship was found between survival and histologic type, or between survival and treatment. Patients with adenoid cystic carcinoma of Grade III, peri-neural invasion or vessel invasion, are recommended to receive adjuvant therapy. (author)

  10. Pathological Role of Tonsillar B Cells in IgA Nephropathy

    Yusuke Suzuki

    2011-01-01

    Full Text Available Although impaired immune regulation along the mucosa-bone marrow axis has been postulated to play an important role, the pathogenesis of IgA nephropathy (IgAN is unknown; thus, no disease-specific therapy for this disease exists. The therapeutic efficacy of tonsillectomy or tonsillectomy in combination with steroid pulse therapy for IgAN has been discussed. Although randomized control trials for these therapies are ongoing in Japan, the scientific rationale for these therapies remains obscure. It is now widely accepted that abnormally glycosylated IgA1 and its related immune complex (IC are probably key molecules for the pathogenesis, and are thus considered possible noninvasive biomarkers for this disease. Emerging evidence indicates that B cells in mucosal infections, particularly in tonsillitis, may produce the nephritogenic IgA. In this paper, we briefly summarize characteristics of the nephritogenic IgA/IgA IC, responsible B cells, and underlying mechanisms. This clinical and experimental information may provide important clues for a therapeutic rationale.

  11. Langerhans' cell histiocytosis: pathology, imaging and treatment of skeletal involvement

    Azouz, E. Michel [University of Miami, Pediatric Radiology Section, Department of Radiology, Miami, FL (United States); Saigal, Gaurav [McGill University, Department of Medical Imaging, Quebec (Canada); Rodriguez, Maria M. [University of Miami, Department of Pathology, Miami, FL (United States); Podda, Antonello [University of Miami, Division of Pediatric Hematology/Oncology, Miami, FL (United States)

    2005-02-01

    Langerhans' cell histiocytosis (LCH) is manifested in a variety of ways, the most common being the eosinophilic granuloma, a localized, often solitary bone lesion that occurs predominantly in the pediatric age group. The hallmark of LCH is the proliferation and accumulation of a specific histiocyte: the Langerhans' cell. In bone this may cause pain and adjacent soft-tissue swelling, but some lesions are asymptomatic. LCH can involve any bone, but most lesions occur in the skull (especially the calvarium and temporal bones), the pelvis, spine, mandible, ribs, and tubular bones. Imaging diagnosis of the disease in bone is first based on the plain radiographic appearance, which is usually a central destructive, aggressive-looking lesion. In the skull, the lesions develop in the diploic space, are lytic, and their edges may be beveled, scalloped or confluent (geographic), or show a ''button sequestrum.'' Vertebral body involvement usually causes collapse, resulting in vertebra plana. With significant recent improvements in the quality of gamma cameras, imaging techniques, and in studying children, bone scintigraphy at diagnosis and on follow-up usually reveals the sites of active disease, especially when the involvement is polyostotic. CT and MR imaging are very useful in providing detailed cross-sectional anatomic detail of the involved bone, including the bone marrow and the adjacent soft tissues. CT is better suited for demonstrating bone detail and MR imaging for bone marrow and soft-tissue involvement. (orig.)

  12. Risk factors of brain metastases in completely resected pathological stage IIIA-N2 non-small cell lung cancer

    Ding Xiao

    2012-07-01

    Full Text Available Abstract Background Brain metastases (BM is one of the most common failures of locally advanced non-small cell lung cancer (LA-NSCLC after combined-modality therapy. The outcome of trials on prophylactic cranial irradiation (PCI has prompted us to identify the highest-risk subset most likely to benefit from PCI. Focusing on patients with completely resected pathological stage IIIA-N2 (pIIIA-N2 NSCLC, we aimed to assess risk factors of BM and to define the highest-risk subset. Methods Between 2003 and 2005, the records of 217 consecutive patients with pIIIA-N2 NSCLC in our institution were reviewed. The cumulative incidence of BM was estimated using the Kaplan–Meier method, and differences between the groups were analyzed using log-rank test. Multivariate Cox regression analysis was applied to assess risk factors of BM. Results Fifty-three (24.4 % patients developed BM at some point during their clinical course. On multivariate analysis, non-squamous cell cancer (relative risk [RR]: 4.13, 95 % CI: 1.86–9.19; P = 0.001 and the ratio of metastatic to examined nodes or lymph node ratio (LNR ≥ 30 % (RR: 3.33, 95 % CI: 1.79–6.18; P = 0.000 were found to be associated with an increased risk of BM. In patients with non-squamous cell cancer and LNR ≥ 30 %, the 5-year actuarial risk of BM was 57.3 %. Conclusions In NSCLC, patients with completely resected pIIIA-N2 non-squamous cell cancer and LNR ≥ 30 % are at the highest risk for BM, and are most likely to benefit from PCI. Further studies are warranted to investigate the effect of PCI on this subset of patients.

  13. Risk factors of brain metastases in completely resected pathological stage IIIA-N2 non-small cell lung cancer

    Brain metastases (BM) is one of the most common failures of locally advanced non-small cell lung cancer (LA-NSCLC) after combined-modality therapy. The outcome of trials on prophylactic cranial irradiation (PCI) has prompted us to identify the highest-risk subset most likely to benefit from PCI. Focusing on patients with completely resected pathological stage IIIA-N2 (pIIIA-N2) NSCLC, we aimed to assess risk factors of BM and to define the highest-risk subset. Between 2003 and 2005, the records of 217 consecutive patients with pIIIA-N2 NSCLC in our institution were reviewed. The cumulative incidence of BM was estimated using the Kaplan–Meier method, and differences between the groups were analyzed using log-rank test. Multivariate Cox regression analysis was applied to assess risk factors of BM. Fifty-three (24.4 %) patients developed BM at some point during their clinical course. On multivariate analysis, non-squamous cell cancer (relative risk [RR]: 4.13, 95 % CI: 1.86–9.19; P = 0.001) and the ratio of metastatic to examined nodes or lymph node ratio (LNR) ≥ 30 % (RR: 3.33, 95 % CI: 1.79–6.18; P = 0.000) were found to be associated with an increased risk of BM. In patients with non-squamous cell cancer and LNR ≥ 30 %, the 5-year actuarial risk of BM was 57.3 %. In NSCLC, patients with completely resected pIIIA-N2 non-squamous cell cancer and LNR ≥ 30 % are at the highest risk for BM, and are most likely to benefit from PCI. Further studies are warranted to investigate the effect of PCI on this subset of patients

  14. Diffuse large B-Cell lymphoma: a clinico- pathologic and prognostic study on 1470 biopsy specimens

    Sadighi S

    2009-11-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Diffuse large B Cell lymphoma (DLBCL is the most common subtype of non-Hogkin lymphoma (NHL. We performed a retrospective study of patients with de novo DLBCL treated in the Medical Oncology department of Cancer Institute of Iran, Tehran to assess the clinicopathologic and immunohistochemistry correlation and prognosis of the patients. "n"nMethods: World Health Organization (WHO classification was used to reexamine 1470 biopsy specimens related to the years 1985-2006. After excluding five cases of T Cell large cell lymphoma, 50 Patients diagnosed as DLBCL. "n"nResults: Median age of the patients was 45.5(20-85 years: 60% were male and 30% had primary extranodal disease. The most common extranodal sites were bone, gastrointestinal tract and Head and neck areas. The most common stages were stage II (32%, stage III (32%, stage IV (20% and stage I (16% retrospectively and 33% had B-symptoms. All of The Patients received chemotherapy (83% CHOP regimen and 46% treated by radiotherapy after chemotherapy. With a mean follow up time of 32 months, median survival time was 34 (95% CI 24-40 months. Prognostic factors for survival were tumor stage, B-symptoms and early relapse (less than 6 months."n"nConclusions: Our

  15. Digital pathology

    Sucaet, Yves

    2014-01-01

    Digital pathology has experienced exponential growth, in terms of its technology and applications, since its inception just over a decade ago. Though it has yet to be approved for primary diagnostics, its values as a teaching tool, facilitator of second opinions and quality assurance reviews and research are becoming, if not already, undeniable. It also offers the hope of providing pathology consultant and educational services to under-served areas, including regions of the world that could not possibly sustain this level of services otherwise. And this is just the beginning, as its adoption b

  16. Roads Less Traveled: Sexual Dimorphism and Mast Cell Contributions to Migraine Pathology

    Loewendorf, Andrea I.; Matynia, Anna; Saribekyan, Hakob; Gross, Noah; Csete, Marie; Harrington, Mike

    2016-01-01

    Migraine is a common, little understood, and debilitating disease. It is much more prominent in women than in men (~2/3 are women) but the reasons for female preponderance are not clear. Migraineurs frequently experience severe comorbidities, such as allergies, depression, irritable bowel syndrome, and others; many of the comorbidities are more common in females. Current treatments for migraine are not gender specific, and rarely are migraine and its comorbidities considered and treated by the same specialist. Thus, migraine treatments represent a huge unmet medical need, which will only be addressed with greater understanding of its underlying pathophysiology. We discuss the current knowledge about sex differences in migraine and its comorbidities, and focus on the potential role of mast cells (MCs) in both. Sex-based differences in pain recognition and drug responses, fluid balance, and the blood–brain barrier are recognized but their impact on migraine is not well studied. Furthermore, MCs are well recognized for their prominent role in allergies but much less is known about their contributions to pain pathways in general and migraine specifically. MC-neuron bidirectional communication uniquely positions these cells as potential initiators and/or perpetuators of pain. MCs can secrete nociceptor sensitizing and activating agents, such as serotonin, prostaglandins, histamine, and proteolytic enzymes that can also activate the pain-mediating transient receptor potential vanilloid channels. MCs express receptors for both estrogen and progesterone that induce degranulation upon binding. Furthermore, environmental estrogens, such as Bisphenol A, activate MCs in preclinical models but their impact on pain pathways or migraine is understudied. We hope that this discussion will encourage scientists and physicians alike to bridge the knowledge gaps linking sex, MCs, and migraine to develop better, more comprehensive treatments for migraine patients. PMID:27148260

  17. Roads Less Traveled: Sexual Dimorphism and Mast Cell Contributions to Migraine Pathology.

    Loewendorf, Andrea I; Matynia, Anna; Saribekyan, Hakob; Gross, Noah; Csete, Marie; Harrington, Mike

    2016-01-01

    Migraine is a common, little understood, and debilitating disease. It is much more prominent in women than in men (~2/3 are women) but the reasons for female preponderance are not clear. Migraineurs frequently experience severe comorbidities, such as allergies, depression, irritable bowel syndrome, and others; many of the comorbidities are more common in females. Current treatments for migraine are not gender specific, and rarely are migraine and its comorbidities considered and treated by the same specialist. Thus, migraine treatments represent a huge unmet medical need, which will only be addressed with greater understanding of its underlying pathophysiology. We discuss the current knowledge about sex differences in migraine and its comorbidities, and focus on the potential role of mast cells (MCs) in both. Sex-based differences in pain recognition and drug responses, fluid balance, and the blood-brain barrier are recognized but their impact on migraine is not well studied. Furthermore, MCs are well recognized for their prominent role in allergies but much less is known about their contributions to pain pathways in general and migraine specifically. MC-neuron bidirectional communication uniquely positions these cells as potential initiators and/or perpetuators of pain. MCs can secrete nociceptor sensitizing and activating agents, such as serotonin, prostaglandins, histamine, and proteolytic enzymes that can also activate the pain-mediating transient receptor potential vanilloid channels. MCs express receptors for both estrogen and progesterone that induce degranulation upon binding. Furthermore, environmental estrogens, such as Bisphenol A, activate MCs in preclinical models but their impact on pain pathways or migraine is understudied. We hope that this discussion will encourage scientists and physicians alike to bridge the knowledge gaps linking sex, MCs, and migraine to develop better, more comprehensive treatments for migraine patients. PMID:27148260

  18. Molecular Pathways Regulating Macrovascular Pathology and Vascular Smooth Muscle Cells Phenotype in Type 2 Diabetes

    Sara Casella

    2015-10-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a disease reaching a pandemic proportion in developed countries and a major risk factor for almost all cardiovascular diseases and their adverse clinical manifestations. T2DM leads to several macrovascular and microvascular alterations that influence the progression of cardiovascular diseases. Vascular smooth muscle cells (VSMCs are fundamental players in macrovascular alterations of T2DM patients. VSMCs display phenotypic and functional alterations that reflect an altered intracellular biomolecular scenario of great vessels of T2DM patients. Hyperglycemia itself and through intraparietal accumulation of advanced glycation-end products (AGEs activate different pathways, in particular nuclear factor-κB and MAPKs, while insulin and insulin growth-factor receptors (IGFR are implicated in the activation of Akt and extracellular-signal-regulated kinases (ERK 1/2. Nuclear factor-κB is also responsible of increased susceptibility of VSMCs to pro-apoptotic stimuli. Down-regulation of insulin growth-factor 1 receptors (IGFR-1R activity in diabetic vessels also influences negatively miR-133a levels, so increasing apoptotic susceptibility of VSMCs. Alterations of those bimolecular pathways and related genes associate to the prevalence of a synthetic phenotype of VSMCs induces extracellular matrix alterations of great vessels. A better knowledge of those biomolecular pathways and related genes in VSMCs will help to understand the mechanisms leading to macrovascular alterations in T2DM patients and to suggest new targeted therapies.

  19. Various ocular MR imaging in a mouse implanted with a new cell line of retinoblastoma and the correlation with the pathology: preliminary study

    We wanted to show various MR and correlated pathologic images of retinoblastoma in nude mouse with a new human retinoblastoma cell line (SNUOT-Rb1), which was inoculated into the intravitreous cavity. The established cell line was inoculated into the intravitreous cavity of 36 eyeballs of 18 mice and the transplanted retinoblastoma was examined for 3 months. The T1-weighted (T1WI), T2-weighted (T2WI), and contrast enhanced (Gd-DTPA) T1-weighted images were obtained with using a small loop coil. After scanning, the mice's eyeballs were extracted and the hematoxylin and eosin stained specimens were examined with a microscope. We compared the MR imagings with pathologic findings and evaluated the character of the tumors. The innoculated cells in the eyeballs of the mice grew into retinoblastoma (23/36, 64%). The eyeballs with retinoblastoma protruded externally and showed focal hemorrhage. Most tumors showed iso-signal intensity on TIWI (13/23, 57%), high signal intensity on T2WI (17/23, 74%), and good enhancement (21/23, 91%) with contrast. Almost all of the tumors (n = 21) were located in the retina and three extraretinal tumors were confirmed by pathology. Involvement of the optic nerve was suspected on MRI and this was confirmed by pathology in 6 cases and 5 cases, respectively. We could demonstrate various MR imagings of transplanted retinoblastoma by using the new tumor cell line in vivo

  20. Various ocular MR imaging in a mouse implanted with a new cell line of retinoblastoma and the correlation with the pathology: preliminary study

    Kim, Dong Hun; Kim, Il Joong; Yang, Jae Han; Byun, Joo Nam; Lee, Bong Jae [Chosun University, College of Medicine, Gwangju (Korea, Republic of); Kim, Jeong Hun; Yu, Young Suk [Seoul National University, College of Medicine, Seoul (Korea, Republic of)

    2007-05-15

    We wanted to show various MR and correlated pathologic images of retinoblastoma in nude mouse with a new human retinoblastoma cell line (SNUOT-Rb1), which was inoculated into the intravitreous cavity. The established cell line was inoculated into the intravitreous cavity of 36 eyeballs of 18 mice and the transplanted retinoblastoma was examined for 3 months. The T1-weighted (T1WI), T2-weighted (T2WI), and contrast enhanced (Gd-DTPA) T1-weighted images were obtained with using a small loop coil. After scanning, the mice's eyeballs were extracted and the hematoxylin and eosin stained specimens were examined with a microscope. We compared the MR imagings with pathologic findings and evaluated the character of the tumors. The innoculated cells in the eyeballs of the mice grew into retinoblastoma (23/36, 64%). The eyeballs with retinoblastoma protruded externally and showed focal hemorrhage. Most tumors showed iso-signal intensity on TIWI (13/23, 57%), high signal intensity on T2WI (17/23, 74%), and good enhancement (21/23, 91%) with contrast. Almost all of the tumors (n = 21) were located in the retina and three extraretinal tumors were confirmed by pathology. Involvement of the optic nerve was suspected on MRI and this was confirmed by pathology in 6 cases and 5 cases, respectively. We could demonstrate various MR imagings of transplanted retinoblastoma by using the new tumor cell line in vivo.

  1. Pretreatment Primary Tumor SUVmax Measured by FDG-PET and Pathologic Tumor Depth Predict for Poor Outcomes in Patients With Oral Cavity Squamous Cell Carcinoma and Pathologically Positive Lymph Nodes

    Purpose: The pathologic tumor depth is an independent prognosticator for local control (LC) and survival in patients with oral cavity squamous cell carcinoma (OSCC). We sought to investigate the prognostic value of the preoperative maximal standardized uptake value (SUVmax) at the primary tumor in OSCC patients with pathologically positive lymph nodes. Methods and Materials: A total of 109 OSCC patients with pathologically positive lymph nodes were investigated. All patients underwent 2-deoxy-2[(18)F]fluoro-D-glucose-positron emission tomography within 2 weeks before surgery and neck dissection. All patients were followed for ≥24 months after surgery or until death. The optimal cutoff value for the primary tumor SUVmax was selected according to the 5-year LC rate. Independent prognosticators were identified by Cox regression analysis. Results: The median follow-up for all patients was 26 months (39 months for surviving patients). A cutoff SUVmax of 19.3 provided the greatest prognostic information for the 5-year LC rate (55% vs. 88%, p = 0.0135). A tumor depth ≥12 mm appeared to be the most appropriate cutoff for predicting the 5-year LC rate (76% vs. 95%, p = 0.0075). A scoring system using the primary tumor SUVmax and tumor depth was formulated to define distinct prognostic groups. Patients with both a SUVmax of ≥19.3 and tumor depth of ≥12 mm (n = 8) had significantly poorer 5-year LC, 5-year disease-free, 5-year disease-specific, and 5-year overall survival rates compared with the other patient groups. Conclusion: The combination of the primary tumor SUVmax (≥19.3) and pathologic tumor depth (≥12 mm) identified a subgroup of OSCC patients at greatest risk of poor LC and death

  2. Impact of FDG-PET/CT on Radiotherapy Volume Delineation in Non-Small-Cell Lung Cancer and Correlation of Imaging Stage With Pathologic Findings

    Purpose: Fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) is more accurate than CT in determining the extent of non-small-cell lung cancer. We performed a study to evaluate the impact of FDG-PET/CT on the radiotherapy volume delineation compared with CT without using any mathematical algorithm and to correlate the findings with the pathologic examination findings. Methods and Materials: A total of 32 patients with proven non-small-cell lung cancer, pathologic specimens from the mediastinum and lung primary, and pretreatment chest CT and FDG-PET/CT scans were studied. For each patient, two data sets of theoretical gross tumor volumes were contoured. One set was determined using the chest CT only, and the second, done separately, was based on the co-registered FDG-PET/CT data. The disease stage of each patient was determined using the TNM staging system for three data sets: the CT scan only, FDG-PET/CT scan, and pathologic findings. Results: Pathologic examination altered the CT-determined stage in 22 (69%) of 32 patients and the PET-determined stage in 16 (50%) of 32 patients. The most significant alterations were related to the N stage. PET altered the TNM stage in 15 (44%) of 32 patients compared with CT alone, but only 7 of these 15 alterations were confirmed by the pathologic findings. With respect to contouring the tumor volume for radiotherapy, PET altered the contour in 18 (56%) of 32 cases compared with CT alone. Conclusion: The contour of the tumor volume of non-small-cell lung cancer patients with co-registered FDG-PET/CT resulted in >50% alterations compared with CT targeting, findings similar to those of other publications. However, the significance of this change is unknown. Furthermore, pathologic examination showed that PET is not always accurate and histologic examination should be obtained to confirm the findings of PET whenever possible

  3. Inhibition of pancreatic acinar mitochondrial thiamin pyrophosphate uptake by the cigarette smoke component 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

    Srinivasan, Padmanabhan; Thrower, Edwin C; Gorelick, Fred S; Said, Hamid M

    2016-05-15

    Thiamin is essential for normal metabolism in pancreatic acinar cells (PAC) and is obtained from their microenvironment through specific plasma-membrane transporters, converted to thiamin pyrophosphate (TPP) in the cytoplasm, followed by uptake of TPP by mitochondria through the mitochondrial TPP (MTPP) transporter (MTPPT; product of SLC25A19 gene). TPP is essential for normal mitochondrial function. We examined the effect of long-term/chronic exposure of PAC in vitro (pancreatic acinar 266-6 cells) and in vivo (wild-type or transgenic mice carrying the SLC25A19 promoter) of the cigarette smoke toxin, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), on the MTPP uptake process. Our in vitro and in vivo findings demonstrate that NNK negatively affects MTPP uptake and reduced expression of MTPPT protein, MTPPT mRNA, and heterogenous nuclear RNA, as well as SLC25A19 promoter activity. The effect of NNK on Slc25a19 transcription was neither mediated by changes in expression of transcriptional factor NFY-1 (known to drive SLC25A19 transcription), nor due to changes in methylation profile of the Slc25a19 promoter. Rather, it appears to be due to changes in histone modifications that involve significant decreases in histone H3K4-trimethylation and H3K9-acetylation (activation markers). The effect of NNK on MTPPT function is mediated through the nonneuronal α7-nicotinic acetylcholine receptor (α7-nAChR), as indicated by both in vitro (using the nAChR antagonist mecamylamine) and in vivo (using an α7-nAchR(-/-) mouse model) studies. These findings demonstrate that chronic exposure of PAC to NNK negatively impacts PAC MTPP uptake. This effect appears to be exerted at the level of Slc25a19 transcription, involve epigenetic mechanism(s), and is mediated through the α7-nAchR. PMID:26999808

  4. Pineal Diffuse Large B-Cell Lymphoma Concomitant With Pituitary Prolactinoma: Possible Correlation Between 2 Distinguished Pathologies: A Case Report.

    Kim, Yeong-Jin; Kim, Hee Kyung; Yang, Deok-Hwan; Jung, Shin; Noh, Myung-Giun; Lee, Jae-Hyuk; Lee, Kyung-Hwa; Moon, Kyung-Sub

    2016-02-01

    This is the first reported case of pineal lymphoma with concomitant prolactin-producing pituitary adenoma.A 51-year-old male experienced worsening headaches accompanied by nausea, diplopia, and memory loss for 1 month. Cranial nerve examination revealed bilateral upward gaze limitation with convergence impairment, which is known as Parinaud syndrome. Magnetic resonance images revealed a mass in the pineal gland with a coexisting mass within the enlarged sella fossa. Hormone analysis revealed hyperprolactinemia. The pineal mass was removed without injuring the hypothalamus, brain stem, or any neighboring vessels. Pathology examination confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) involving the pineal gland. After further studies, the pineal lymphoma was determined to be a secondary tumor from a gastric primary tumor. The patient died 6 months after diagnosis due to systemic progression of DLBCL.Although the mechanistic link between hyperprolactinemia and lymphoma progression has not been clarified on a clinical basis, high prolactin levels may contribute to the rapid progression and therapeutic resistance of the lymphoma. PMID:26937937

  5. Pineal Diffuse Large B-Cell Lymphoma Concomitant With Pituitary Prolactinoma: Possible Correlation Between 2 Distinguished Pathologies

    Kim, Yeong-Jin; Kim, Hee Kyung; Yang, Deok-Hwan; Jung, Shin; Noh, Myung-Giun; Lee, Jae-Hyuk; Lee, Kyung-Hwa; Moon, Kyung-Sub

    2016-01-01

    Abstract This is the first reported case of pineal lymphoma with concomitant prolactin-producing pituitary adenoma. A 51-year-old male experienced worsening headaches accompanied by nausea, diplopia, and memory loss for 1 month. Cranial nerve examination revealed bilateral upward gaze limitation with convergence impairment, which is known as Parinaud syndrome. Magnetic resonance images revealed a mass in the pineal gland with a coexisting mass within the enlarged sella fossa. Hormone analysis revealed hyperprolactinemia. The pineal mass was removed without injuring the hypothalamus, brain stem, or any neighboring vessels. Pathology examination confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) involving the pineal gland. After further studies, the pineal lymphoma was determined to be a secondary tumor from a gastric primary tumor. The patient died 6 months after diagnosis due to systemic progression of DLBCL. Although the mechanistic link between hyperprolactinemia and lymphoma progression has not been clarified on a clinical basis, high prolactin levels may contribute to the rapid progression and therapeutic resistance of the lymphoma. PMID:26937937

  6. Acinar ventilation heterogeneity in COPD relates to diffusion capacity, resistance and reactance.

    Jarenbäck, Linnea; Ankerst, Jaro; Bjermer, Leif; Tufvesson, Ellen

    2016-01-01

    The aim of this study was to investigate heterogenic ventilation in the acinar (Sacin) and conductive (Scond) airways of patients with varying chronic obstructive pulmonary disease (COPD) severity and how these relates to advanced lung function parameters, primarily measured by impulse oscillometry (IOS). A secondary aim was to investigate the effects of a short acting beta2-agonist and a muscarinic antagonist on the heterogenic ventilation. Eleven never smoking controls, 12 smoking controls, and 57 COPD patients (7 GOLD 1, 25 GOLD 2, 14 GOLD 3 and 11 GOLD 4) performed flow-volume spirometry, IOS, body plethysmography, single breath carbon monoxide diffusion, and N2-multiple breath washout. Six smoking controls and 13 of the COPD patients also performed double reversibility test by using salbutamol and its combination with ipratropium. Sacin was significantly higher in GOLD 2-4 compared to never smoking controls and smoking controls, but showed similar levels in GOLD 3 and 4. A factor analysis identified 4 components consisting of; 1) IOS parameters, 2) volume parameters, 3) diffusion parameters, Sacin and some IOS parameters and 4) Scond with central obstruction/air trapping. Salbutamol and its combination with ipratropium had no effect on Sacin and Scond. Increased Sacin in COPD was strongly related to diffusion capacity and lung volumes, but also weakly to resistance and reactance, showing a link between ventilation heterogeneity in the acinar airways and parameters measured by IOS. PMID:26607879

  7. Restricted diffusion in a model acinar labyrinth by NMR: Theoretical and numerical results

    Grebenkov, D. S.; Guillot, G.; Sapoval, B.

    2007-01-01

    A branched geometrical structure of the mammal lungs is known to be crucial for rapid access of oxygen to blood. But an important pulmonary disease like emphysema results in partial destruction of the alveolar tissue and enlargement of the distal airspaces, which may reduce the total oxygen transfer. This effect has been intensively studied during the last decade by MRI of hyperpolarized gases like helium-3. The relation between geometry and signal attenuation remained obscure due to a lack of realistic geometrical model of the acinar morphology. In this paper, we use Monte Carlo simulations of restricted diffusion in a realistic model acinus to compute the signal attenuation in a diffusion-weighted NMR experiment. We demonstrate that this technique should be sensitive to destruction of the branched structure: partial removal of the interalveolar tissue creates loops in the tree-like acinar architecture that enhance diffusive motion and the consequent signal attenuation. The role of the local geometry and related practical applications are discussed.

  8. Early and late-onset acute GvHD following hematopoietic cell transplantation: CT features of gastrointestinal involvement with clinical and pathological correlation

    Objective: With the introduction of non-myeloablative hematopoietic cell transplantation, acute graft-versus-host-disease (GvHD) is frequently observed beyond the traditional 100 days cut-off. The aim of this study was to describe and compare CT features of gastrointestinal early and late-onset GvHD and to correlate findings with clinical and pathology grading. Subjects and methods: Abdominal CT scans were obtained in 20 patients with early and 15 with late-onset GvHD. Examinations were assessed for intestinal and extraintestinal abnormalities and findings compared between the two subgroups of GvHD. Distinct CT abnormalities as well as a CT-score integrating multiple pathologies were correlated with gut, clinical or pathology grading. Results: Frequent intestinal abnormalities included wall thickening, abnormal enhancement, and excessive fluid-filling (94%, 89%, and 94%). 86% of patients showed concomitant small and large bowel involvement. A discontinuous distribution was observed in 54%. Bile tract abnormality was the most common extra-intestinal finding (74%). The distribution of pathologies was equal between subgroups of early or late-onset disease. Wall thickening and mucosal attenuation in non-enhanced scans were significantly related to clinical and pathology scores (P ≤ 0.018). Number of abnormal segments, small bowel dilatation, engorgement of the vasa recta, mesenteric fat stranding and ascites were linked to clinical grading (P ≤ 0.019). A CT-score integrating multiple abnormalities was correlated to gut, overall clinical and pathology grading (r = 0.64, 0.57, 0.50). Conclusion: CT morphology of acute GvHD is independent of its time of onset and, thus, facilitates differential diagnosis of late-onset acute GvHD. Correlation of CT morphology with clinical and pathological grading is important in terms of prognosis and may help guiding the therapeutic approach.

  9. Expression of Yes-associated protein in non-small cell lung cancer and its relationship with clinical pathological factors

    SU Li-li; MA Wei-xia; YUAN Jian-feng; SHAO Yang; XIAO Wei; JIANG Shu-juan

    2012-01-01

    Background Yes-associated protein(YAP)plays an important role in signal transduction and gene transcription regulation in normal cells,with elevated and over-expressed YAP levels observed in various malignant tumors.The aim of this study was to investigate the expression of YAP in non-small cell lung cancer(NSCLC),and to study the possible relationship of YAP expression with the occurrence and development of NSCLC.Methods YAP expression was assessed in 40 cases of NSCLC tumor tissues by immunohistochemistry,and their protein and mRNA levels were evaluated through Western blotting and reverse transcription-polymerase chain reaction(PCR),respectively.Normal lung tissues obtained from the same patient were used as control.Statistical analysis was performed to correlate the YAP expression to clinical pathological factors,such as tumor type,stage and grade.Results YAP-positive expression was found in 28(70%)of the 40 cases of NSCLC,which included 10 cases of squamous cell carcinoma(25%),17 cases of adenocarcinoma(42.5%)and 1 case of squamous adenocarcinoma(2.5%).In the 28 YAP-positive cases,19 cases showed lymph node metastasis and were classified in TNM stage Ⅱ+Ⅲ(47.5%);the other nine cases showed no lymph node metastasis(22.5%)and were classified in the TNM stage Ⅰ.There was no relationship between YAP expression and patients'age,gender or tumor histological grades.However,YAP showed significant over expression in late period of T stage(P=0.012),TNM stage(P=0.039),and lymph node metastasis(P=0.013),respectively.Notably,YAP-positive expression was significantly higher in adenocarcinoma than that in squamous cell carcinoma(P=0.041).Conclusions Over-expression of YAP was associated with NSCLC,especially lung adenocarcinoma.The high YAP expression in late period of tumor stage and lymph node metastasis may indicate that YAP expression could be an early marker for NSCLC tumorigenesis.

  10. Combined gene/cell therapies provide long-term and pervasive rescue of multiple pathological symptoms in a murine model of globoid cell leukodystrophy.

    Ricca, Alessandra; Rufo, Nicole; Ungari, Silvia; Morena, Francesco; Martino, Sabata; Kulik, Wilem; Alberizzi, Valeria; Bolino, Alessandra; Bianchi, Francesca; Del Carro, Ubaldo; Biffi, Alessandra; Gritti, Angela

    2015-06-15

    Globoid cell leukodystrophy (GLD) is a lysosomal storage disease caused by deficient activity of β-galactocerebrosidase (GALC). The infantile forms manifest with rapid and progressive central and peripheral demyelination, which represent a major hurdle for any treatment approach. We demonstrate here that neonatal lentiviral vector-mediated intracerebral gene therapy (IC GT) or transplantation of GALC-overexpressing neural stem cells (NSC) synergize with bone marrow transplant (BMT) providing dramatic extension of lifespan and global clinical-pathological rescue in a relevant GLD murine model. We show that timely and long-lasting delivery of functional GALC in affected tissues ensured by the exclusive complementary mode of action of the treatments underlies the outstanding benefit. In particular, the contribution of neural stem cell transplantation and IC GT during the early asymptomatic stage of the disease is instrumental to enhance long-term advantage upon BMT. We clarify the input of central nervous system, peripheral nervous system and periphery to the disease, and the relative contribution of treatments to the final therapeutic outcome, with important implications for treatment strategies to be tried in human patients. This study gives proof-of-concept of efficacy, tolerability and clinical relevance of the combined gene/cell therapies proposed here, which may constitute a feasible and effective therapeutic opportunity for children affected by GLD. PMID:25749991

  11. Mouse Pancreas Tissue Slice Culture Facilitates Long-Term Studies of Exocrine and Endocrine Cell Physiology in situ

    Speier, Stephan; Marciniak, Anja; Selck, Claudia; Friedrich, Betty

    2013-01-01

    Studies on pancreatic cell physiology rely on the investigation of exocrine and endocrine cells in vitro. Particularly, in the case of the exocrine tissue these studies have suffered from a reduced functional viability of acinar cells in culture. As a result not only investigations on dispersed acinar cells and isolated acini were limited in their potential, but also prolonged studies on pancreatic exocrine and endocrine cells in an intact pancreatic tissue environment were unfeasible. To ove...

  12. Oral ulceration and bleeding associated with pancreatic enzyme supplementation in a German shepherd with pancreatic acinar atrophy

    Snead, Elisabeth

    2006-01-01

    A 20-month-old German shepherd with primary pancreatic acinar atrophy and exocrine pancreatic insufficiency that was treated with pancreatic enzyme supplementation, vitamin B12, and cimetidine developed oral bleeding. Following discontinuation of the cimetidine, increased preincubation of the enzymes with the food, and symptomatic therapy for the ulceration, the dog’s condition improved.

  13. Ki-67 as a prognostic marker in mantle cell lymphoma-consensus guidelines of the pathology panel of the European MCL Network

    Klapper, W.; Hoster, E.; Determann, O.;

    2009-01-01

    Mantle cell lymphoma (MCL) has a heterogeneous clinical course and is mainly an aggressive B cell non-Hodgkin lymphoma; however, there are some indolent cases The Ki-67 index, defined by the percentage of Ki-67-positive lymphoma cells on histopathological slides, has been shown to be a very...... powerful prognostic biomarker. The pathology panel of the European MCL Network evaluated methods to assess the Ki-67 index including stringent counting, digital image analysis, and estimation by eyeballing. Counting of 2 x 500 lymphoma cells is the gold standard to assess the Ki-67 index since this value.......37 for two methods of digital image analysis, respectively). Counting a reduced number of lymphoma cells (2 x 100 cells) showed high interobserver agreement (CCC = 0.74). Pitfalls of the Ki-67 index are discussed and guidelines and recommendations for assessing the Ki-67 index in MCL are given...

  14. Overexpression of the IGF-II/M6P receptor in mouse fibroblast cell lines differentially alters expression profiles of genes involved in Alzheimer's disease-related pathology.

    Yanlin Wang

    Full Text Available Alzheimer's disease (AD is the most common type of senile dementia affecting elderly people. The processing of amyloid precursor protein (APP leading to the generation of β-amyloid (Aβ peptide contributes to neurodegeneration and development of AD pathology. The endocytic trafficking pathway, which comprises of the endosomes and lysosomes, acts as an important site for Aβ generation, and endocytic dysfunction has been linked to increased Aβ production and loss of neurons in AD brains. Since insulin-like growth factor-II (IGF-II receptor plays a critical role in the transport of lysosomal enzymes from the trans-Golgi network to endosomes, it is likely that the receptor may have a role in regulating Aβ metabolism in AD pathology. However, very little is known on how altered levels of the IGF-II receptor can influence the expression/function of various molecules involved in AD pathology. To address this issue, we evaluated the expression profiles of 87 selected genes related to AD pathology in mouse fibroblast MS cells that are deficient in murine IGF-II receptor and corresponding MS9II cells overexpressing ∼ 500 times the human IGF-II receptors. Our results reveal that an elevation in IGF-II receptor levels alters the expression profiles of a number of genes including APP as well as enzymes regulating Aβ production, degradation and clearance mechanisms. Additionally, it influences the expression of various lysosomal enzymes and protein kinases that are involved in Aβ toxicity. IGF-II receptor overexpression also alters expression of several genes involved in intracellular signalling as well as cholesterol metabolism, which play a critical role in AD pathology. The altered gene profiles observed in this study closely match with the corresponding protein levels, with a few exceptions. These results, taken together, suggest that an elevation in IGF-II receptor levels can influence the expression profiles of transcripts as well as proteins

  15. Residual lymph node status is an independent prognostic factor in esophageal squamous cell Carcinoma with pathologic T0 after preoperative radiotherapy

    Wang, Qifeng; Shufei YU; Xiao, Zefen; Liu, Xiao; Zhang, Wencheng; Zhang, Xun; He, Jie; Kelin SUN; Xu, Ting; Feng, Qinfu; Zhou, Zongmei; Wang, Lvhua; Yin, Weibo

    2015-01-01

    Objective To evaluate the prognostic factors affecting survival in esophageal squamous cell Carcinoma (ESCC) patients with pathologic T0 (ypT0) underwent preoperative radiotherapy. Patients and methods Two hundred and ninety-six patients with ESCC who had received preoperative radiotherapy from 1980 to 2007 were retrospectively analyzed. One hundred patients were ypT0 after preoperative radiotherapy. Univariate and multivariate analyses were performed to evaluate the predictive impact of resi...

  16. Estrategias para la diferenciaci??n in vitro de c??lulas ES de rat??n a c??lulas acinares pancre??ticas

    Rovira Clusellas, Meritxell

    2007-01-01

    Las patolog??as m??s importantes del p??ncreas exocrino, como la pancreatitis cr??nica (PC) o el c??ncer de p??ncreas, representan un gran problema de salud p??blica en Europa. En la PC, el tejido acinar es substituido por complejos ductales. Adem??s, es dif??cil mantener el fenotipo diferenciado de las c??lulas acinares en cultivo ya que sufren una transdiferenciaci??n acinar-ductal.Las c??lulas madre embrionarias (ES) de rat??n han sido utilizadas en la ??ltima d??cada para generar in vitro...

  17. Pathological gambling.

    Hollander, E; Buchalter, A J; DeCaria, C M

    2000-09-01

    With increasing access to gambling facilities through casinos, the Internet, and other venues, PG is a rapidly emerging mental health concern. This impulse-control disorder tends to be comorbid with a wide range of other disorders and is reportedly associated with a high rate of suicide. For most gamblers, gambling is a form of entertainment, but for many individuals, the activity leads to far-reaching disruption of family and work. The personal and societal financial ramifications are severe, and many individuals with PG end up in the criminal justice system. An understanding of the neurobiology of PG is beginning to surface. 5-HT is linked to behavioral initiation and disinhibition, which are important in the onset of the gambling cycle and the difficulty in ceasing the behavior. Norepinephrine is associated with the arousal and risk taking in patients with PG. Dopamine is linked to positive and negative reward, the addictive component of this disorder. Effective treatment strategies for pathological gamblers are emerging. Potentially useful pharmacologic agents include SRIs (clomipramine and fluvoxamine), mood stabilizers for pathological gamblers with comorbid bipolar disorders (lithium), and naltrexone. Cognitive-behavioral psychotherapies offer promising results in the treatment of patients with this disorder. To devise prevention and early-intervention programs, research is needed to identify specific features of the individuals at risk for gambling problems. Education targeting vulnerable youth that show early signs of gambling behavior may be worthwhile and should be investigated further. Funding is necessary to support these endeavors, so perhaps a portion of tax revenues generated from the gambling industry should go toward specialized treatment facilities, educational efforts, and research into the neurobiology and treatment of PG. PMID:10986732

  18. Exosomes in liver pathology.

    Sato, Keisaku; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco

    2016-07-01

    Exosomes are small (∼100nm) membrane-bound extracellular vesicles released by various types of cells into biological fluids. They contain proteins, mRNAs and miRNAs as cargo. Different cell types can take up exosomes by endocytosis and the cargo contained within them can be transferred horizontally to these recipient cells. Exosomal proteins and miRNAs can be functional and regulate physiological cell events modifying the microenvironment in target cells, a key event of liver pathology. Exosome-mediated cell-cell communication can alter tumor growth, cell migration, antiviral infection and hepatocyte regeneration, indicating that exosomes have great potential for development as diagnostic or therapeutic tools. Analyses of circulating total or exosomal miRNAs have identified a large number of candidate miRNAs that are regulated in liver diseases, and the diagnostic testing using single or multiple miRNAs shows good sensitivity and specificity. Some candidate miRNAs have been identified to play an important role in various liver disorders. This review summarizes recent findings on the role of extracellular vesicles in liver diseases and their diagnostic and therapeutic potential, mainly focusing on exosomes but also includes microvesicles in liver pathology. PMID:26988731

  19. Long-term follow-up of post hematopoietic stem cell transplantation for Hurler syndrome: Clinical, biochemical, and pathological improvements

    Eriko Yasuda

    2015-03-01

    In conclusion, this long-term post-HSCT observation should shed light on a new aspect of therapeutic effect associated with skeletal pathology and GAG levels as a biomarker, indicating that HSCT is a primary choice at an early stage for not only CNS but also skeletal system in combination of appropriate surgical procedures.

  20. Microchimerism in Endocrine Pathology

    Rust, Daniel W.; Bianchi, Diana W.

    2009-01-01

    Chimerism in an individual refers to the coexistence of cells arising from two distinct organisms. It can arise iatrogenically via transplant or blood transfusion, and physiologically via twin to twin transfer, or from trafficking between mother and fetus during pregnancy. Many of the diseases associated with microchimerism affect the endocrine system (e.g., autoimmune thyroid disease and diabetes mellitus type 1). Microchimerism is relevant to endocrine pathology because (a) it is associated...

  1. Application of ADC measurement in characterization of renal cell carcinomas with different pathological types and grades by 3.0 T diffusion-weighted MRI

    Purpose: To test the feasibility of apparent diffusion coefficient (ADC) value obtained with 3.0 T diffusion-weighted imaging (DWI) in the characterization of renal cell carcinomas (RCC) with different pathological subtypes and grades. Materials and methods: A total of 137 patients who were diagnosed with RCC and underwent DWI were included in this study. The diagnosis was confirmed by pathological examination of surgical specimens. Images of DWI were obtained with b values of 0 and 800 s/mm2. The ADC values in the solid area of tumors and in the corresponding regions of contralateral normal renal parenchyma were measured and analyzed statistically. Results: The mean ADC value was significantly lower in RCC (1.381 ± 0.444 × 10−3 mm2/s) than in normal renal parenchyma (2.232 ± 0.221 × 10−3 mm2/s) (P < 0.001). The ADC value was also statistically different between clear cell RCC (CCRCC) and non-CCRCC, and between different grades of CCRCC except grade I vs II and grade III vs IV. Conclusion: ADC measurement on 3.0 T DWI provides useful information in diagnostic work-up of RCC in terms of differentiation of RCC and normal renal parenchyma, and characterization of RCC with different pathological subtypes and grades.

  2. Application of ADC measurement in characterization of renal cell carcinomas with different pathological types and grades by 3.0 T diffusion-weighted MRI

    Yu, Xiaoduo, E-mail: yxd98@yahoo.com.cn [Department of Diagnostic Radiology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (China); Lin, Meng, E-mail: linmeng77xp@yahoo.com.cn [Department of Diagnostic Radiology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (China); Ouyang, Han, E-mail: hbybj@sohu.com [Department of Diagnostic Radiology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (China); Zhou, Chunwu, E-mail: cjr.zhouchunwu@163.vip.com [Department of Diagnostic Radiology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (China); Zhang, Hongtu, E-mail: zhanghongtu1010@yahoo.com.cn [Department of Pathology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (China)

    2012-11-15

    Purpose: To test the feasibility of apparent diffusion coefficient (ADC) value obtained with 3.0 T diffusion-weighted imaging (DWI) in the characterization of renal cell carcinomas (RCC) with different pathological subtypes and grades. Materials and methods: A total of 137 patients who were diagnosed with RCC and underwent DWI were included in this study. The diagnosis was confirmed by pathological examination of surgical specimens. Images of DWI were obtained with b values of 0 and 800 s/mm{sup 2}. The ADC values in the solid area of tumors and in the corresponding regions of contralateral normal renal parenchyma were measured and analyzed statistically. Results: The mean ADC value was significantly lower in RCC (1.381 {+-} 0.444 Multiplication-Sign 10{sup -3} mm{sup 2}/s) than in normal renal parenchyma (2.232 {+-} 0.221 Multiplication-Sign 10{sup -3} mm{sup 2}/s) (P < 0.001). The ADC value was also statistically different between clear cell RCC (CCRCC) and non-CCRCC, and between different grades of CCRCC except grade I vs II and grade III vs IV. Conclusion: ADC measurement on 3.0 T DWI provides useful information in diagnostic work-up of RCC in terms of differentiation of RCC and normal renal parenchyma, and characterization of RCC with different pathological subtypes and grades.

  3. Calcium and adenosine triphosphate control of cellular pathology: asparaginase-induced pancreatitis elicited via protease-activated receptor 2.

    Peng, Shuang; Gerasimenko, Julia V; Tsugorka, Tatiana; Gryshchenko, Oleksiy; Samarasinghe, Sujith; Petersen, Ole H; Gerasimenko, Oleg V

    2016-08-01

    Exocytotic secretion of digestive enzymes from pancreatic acinar cells is elicited by physiological cytosolic Ca(2+) signals, occurring as repetitive short-lasting spikes largely confined to the secretory granule region, that stimulate mitochondrial adenosine triphosphate (ATP) production. By contrast, sustained global cytosolic Ca(2+) elevations decrease ATP levels and cause necrosis, leading to the disease acute pancreatitis (AP). Toxic Ca(2+) signals can be evoked by products of alcohol and fatty acids as well as bile acids. Here, we have investigated the mechanism by which l-asparaginase evokes AP. Asparaginase is an essential element in the successful treatment of acute lymphoblastic leukaemia, the most common type of cancer affecting children, but AP is a side-effect occurring in about 5-10% of cases. Like other pancreatitis-inducing agents, asparaginase evoked intracellular Ca(2+) release followed by Ca(2+) entry and also substantially reduced Ca(2+) extrusion because of decreased intracellular ATP levels. The toxic Ca(2+) signals caused extensive necrosis. The asparaginase-induced pathology depended on protease-activated receptor 2 and its inhibition prevented the toxic Ca(2+) signals and necrosis. We tested the effects of inhibiting the Ca(2+) release-activated Ca(2+) entry by the Ca(2+) channel inhibitor GSK-7975A. This markedly reduced asparaginase-induced Ca(2+) entry and also protected effectively against the development of necrosis.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377732

  4. Calcium and adenosine triphosphate control of cellular pathology: asparaginase-induced pancreatitis elicited via protease-activated receptor 2

    Peng, Shuang; Gerasimenko, Julia V.; Tsugorka, Tatiana; Gryshchenko, Oleksiy; Samarasinghe, Sujith; Gerasimenko, Oleg V.

    2016-01-01

    Exocytotic secretion of digestive enzymes from pancreatic acinar cells is elicited by physiological cytosolic Ca2+ signals, occurring as repetitive short-lasting spikes largely confined to the secretory granule region, that stimulate mitochondrial adenosine triphosphate (ATP) production. By contrast, sustained global cytosolic Ca2+ elevations decrease ATP levels and cause necrosis, leading to the disease acute pancreatitis (AP). Toxic Ca2+ signals can be evoked by products of alcohol and fatty acids as well as bile acids. Here, we have investigated the mechanism by which l-asparaginase evokes AP. Asparaginase is an essential element in the successful treatment of acute lymphoblastic leukaemia, the most common type of cancer affecting children, but AP is a side-effect occurring in about 5–10% of cases. Like other pancreatitis-inducing agents, asparaginase evoked intracellular Ca2+ release followed by Ca2+ entry and also substantially reduced Ca2+ extrusion because of decreased intracellular ATP levels. The toxic Ca2+ signals caused extensive necrosis. The asparaginase-induced pathology depended on protease-activated receptor 2 and its inhibition prevented the toxic Ca2+ signals and necrosis. We tested the effects of inhibiting the Ca2+ release-activated Ca2+ entry by the Ca2+ channel inhibitor GSK-7975A. This markedly reduced asparaginase-induced Ca2+ entry and also protected effectively against the development of necrosis. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377732

  5. Pathology Reports

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Lung Cancer Lymphoma Pancreatic Cancer ... edge of the material removed Negative, not involved, clear, or free ... as carcinoma, melanoma, and lymphoma Help diagnose and classify leukemias ...

  6. Diverse Physiological Roles of Calcitonin Gene-Related Peptide in Migraine Pathology: Modulation of Neuronal-Glial-Immune Cells to Promote Peripheral and Central Sensitization.

    Durham, Paul L

    2016-08-01

    The neuropeptide calcitonin gene-related peptide (CGRP) is implicated in the underlying pathology of migraine by promoting the development of a sensitized state of primary and secondary nociceptive neurons. The ability of CGRP to initiate and maintain peripheral and central sensitization is mediated by modulation of neuronal, glial, and immune cells in the trigeminal nociceptive signaling pathway. There is accumulating evidence to support a key role of CGRP in promoting cross excitation within the trigeminal ganglion that may help to explain the high co-morbidity of migraine with rhinosinusitis and temporomandibular joint disorder. In addition, there is emerging evidence that CGRP facilitates and sustains a hyperresponsive neuronal state in migraineurs mediated by reported risk factors such as stress and anxiety. In this review, the significant role of CGRP as a modulator of the trigeminal system will be discussed to provide a better understanding of the underlying pathology associated with the migraine phenotype. PMID:27334137

  7. Expression patterns of DLK1 and INSL3 identify stages of Leydig cell differentiation during normal development and in testicular pathologies, including testicular cancer and Klinefelter syndrome

    Lottrup, G; Nielsen, J E; Maroun, L L;

    2014-01-01

    STUDY QUESTION: What is the differentiation stage of human testicular interstitial cells, in particular Leydig cells (LC), within micronodules found in patients with infertility, testicular cancer and Klinefelter syndrome? SUMMARY ANSWER: The Leydig- and peritubular-cell populations in testes with......, are impaired in adult men with testicular pathologies including testis cancer and Klinefelter syndrome. STUDY FUNDING/COMPETING INTERESTS: This work was funded by Rigshospitalet's research funds, the Danish Cancer Society and Kirsten and Freddy Johansen's foundation. The authors have no conflicts of...... specimens and in 58 adult testis samples from patients with testicular germ cell tumours, including precursor carcinoma in situ (CIS), infertility or Klinefelter syndrome. PARTICIPANTS/MATERIALS, SETTING, METHODS: The expression patterns of DLK1, INSL3, chicken ovalbumin upstream promoter transcription...

  8. Parasite antigen-specific, IL-4-, TGFβ- and IL-1- dependent expansion of Th9 cells is associated with clinical pathology in human lymphatic filariasis

    Anuradha, Rajamanickam; George, Parakkal Jovvian; Hanna, Luke E.; Chandrasekaran, Vedachalam; Kumaran, Paul; Nutman, Thomas B.; Babu, Subash

    2013-01-01

    Th9 cells are a subset of CD4+ T cells, shown to be important in allergy, autoimmunity and anti-tumor responses. However, their role in human infectious diseases has not been explored in detail. We identified a population of IL-9 and IL-10 co-expressing cells (lacking IL-4 expression) in normal individuals that respond to antigenic and mitogenic stimulation but are distinct from IL-9+ Th2 cells. We also demonstrate that these Th9 cells exhibit antigen –specific expansion in a chronic helminth infection (lymphatic filariasis). Comparison of Th9 responses reveals that individuals with pathology associated with filarial infection exhibit significantly expanded frequencies of filarial antigen induced Th9 cells but not of IL9+Th2 cells in comparison to filarial-infected individuals without associated disease. Moreover, the per cell production of IL-9 is significantly higher in Th9 cells compared to IL9+Th2 cells, indicating that the Th9 cells are the predominant CD4+ T cell subset producing IL-9 in the context of human infection. This expansion was reflected in elevated antigen stimulated IL-9 cytokine levels in whole blood culture supernatants. Finally, the frequencies of Th9 cells correlated positively with the severity of lymphedema (and presumed inflammation) in filarial diseased individuals. This expansion of Th9 cells was dependent on IL-4, TGFβ and IL-1 in vitro. We have therefore a identified an important human CD4+ T cell subpopulation co – expressing IL-9 and IL-10 but not IL-4 that is whose expansion is associated with disease in chronic lymphatic filariasis and could potentially play an important role in the pathogenesis of other inflammatory disorders. PMID:23913964

  9. Matrix metalloproteinase activity and glycosaminoglycans in chronic venous disease: the linkage among cell biology, pathology and translational research

    Mannello, Ferdinando; Raffetto, Joseph D.

    2010-01-01

    Primary chronic venous disease (CVD) is an inflammatory pathology involving an erratic structural remodeling in the venous well leading to vascular incompetence and the development of varicose vein, characterized by altered collagen and elastin content. In the early steps of varicose vein formation is crucial the role of MMP/TIMP balance, implicated in both ECM and vascular degradation during inflammation processes in early and late stages of venous diseases. Although several pharmacological ...

  10. The epithelial cell adhesion molecule (Ep-CAM) as a morphoregulatory molecule is a tool in surgical pathology.

    Winter, M.J.; Nagtegaal, I.D.; Krieken, J.H.J.M. van; Litvinov, S.V.

    2003-01-01

    Cell adhesion receptors (CAMs) are actively involved in regulating various cell processes, including growth, differentiation, and cell death. Therefore, CAMs represent a large group of morphoregulating molecules, mediating cross-talk between cells and of cells with their environment. From this persp

  11. Peripheral nerve pathology, including aberrant Schwann cell differentiation, is ameliorated by doxycycline in a laminin-α2-deficient mouse model of congenital muscular dystrophy

    Homma, Sachiko; Beermann, Mary Lou; Miller, Jeffrey Boone

    2011-01-01

    The most common form of childhood congenital muscular dystrophy, Type 1A (MDC1A), is caused by mutations in the human LAMA2 gene that encodes the laminin-α2 subunit. In addition to skeletal muscle deficits, MDC1A patients typically show a loss of peripheral nerve function. To identify the mechanisms underlying this loss of nerve function, we have examined pathology and cell differentiation in sciatic nerves and ventral roots of the laminin-α2-deficient (Lama2−/−) mice, which are models for MD...

  12. Curriculum Guidelines for Pathology and Oral Pathology.

    Journal of Dental Education, 1985

    1985-01-01

    Guidelines for dental school pathology courses describe the interrelationships of general, systemic, and oral pathology; primary educational goals; prerequisites; a core curriculum outline and behavioral objectives for each type of pathology. Notes on sequencing, faculty, facilities, and occupational hazards are included. (MSE)

  13. 基底细胞癌的病理诊断分析及预后%Pathological Diagnosis and Prognostic of Basal Cell Carcinoma

    杜晓敏

    2015-01-01

    目的:探讨基底细胞癌的病理诊断分析及预后。方法整群选取2010年10月—2014年5月在该病理科进行基底细胞癌的病理诊断的74例患者作为研究对象,并对其病理资料进行回顾性分析。结果74例基底细胞癌患者中,眶周部23例,占31.1%,峡部5例,占6.8%,额部9例,占12.2%,颧骨部7例,占9.4%,鼻翼部19例,占25.6%,上唇部6例,占8.1%,下颌部3例,占4.1%,背部2例,占2.7%。镜下可见瘤细胞团块状或巢状排列,细胞核大小不一,排列密集紊乱,胞浆少淡染,瘤细胞巢周围裂隙形成,间质慢性炎细胞浸润。结论基底细胞癌是皮肤科最常见的恶性肿瘤之一,及早进行病理诊断和治疗,预后较好,可以明显的提高患者的生命质量。%Objective To investigate the pathological diagnosis and the prognosis of basal cell carcinoma. Methods 74 patients who underwent pathological diagnosis of basal cell carcinoma in our hospital from October 2010 to May 2014 in the Department of Pathology of our hospital were selected as the research object and their pathological data were retrospectively analyzed. Results In all the 74 patients, basal cell carcinoma in periorbital region was found in 23 cases, accounting for 31.1%; in isthmus in 5 cases, accounting for 6.8%; in forehead in 9 cases, accounting for 12.2%, in the zygomatic in 7 cases, accounting for 9.4%, in alae nasi in 19 cases, accounting for 25.6%, in upper lip in 6 cases, accounting for 8.1%, in lower jaw in 3 cases, accounting for 4.1% and in back in 2 cases, accounted for 2.7%. Under the microscope, the tumor cells, of which the nucleus of difference size were ar-ranged dense and irregular, and of which the scanty cytoplasm was slightly stained, distributed in the form of round or spindle and of nest. Interstitial chronic inflammatory cell infiltration was developed in the fracture around tumor cells. Conclusion Basal cell carcinoma is one of

  14. NKG2D mediates NK cell hyperresponsiveness and influenza-induced pathologies in a mouse model of chronic obstructive pulmonary disease.

    Wortham, Brian W; Eppert, Bryan L; Motz, Greg T; Flury, Jennifer L; Orozco-Levi, Mauricio; Hoebe, Kasper; Panos, Ralph J; Maxfield, Melissa; Glasser, Stephan W; Senft, Albert P; Raulet, David H; Borchers, Michael T

    2012-05-01

    Chronic obstructive pulmonary disease (COPD) is characterized by peribronchial and perivascular inflammation and largely irreversible airflow obstruction. Acute disease exacerbations, due frequently to viral infections, lead to enhanced disease symptoms and contribute to long-term progression of COPD pathology. Previously, we demonstrated that NK cells from cigarette smoke (CS)-exposed mice exhibit enhanced effector functions in response to stimulating cytokines or TLR ligands. In this article, we show that the activating receptor NKG2D is a key mediator for CS-stimulated NK cell hyperresponsiveness, because CS-exposed NKG2D-deficient mice (Klrk1(-/-)) did not exhibit enhanced effector functions as assessed by cytokine responsiveness. NK cell cytotoxicity against MHC class I-deficient targets was not affected in a COPD model. However, NK cells from CS-exposed mice exhibit greater cytotoxic activity toward cells that express the NKG2D ligand RAET1ε. We also demonstrate that NKG2D-deficient mice exhibit diminished airway damage and reduced inflammation in a model of viral COPD exacerbation, which do not affect viral clearance. Furthermore, adoptive transfer of NKG2D(+) NK cells into CS-exposed, influenza-infected NKG2D-deficient mice recapitulated the phenotypes observed in CS-exposed, influenza-infected wild-type mice. Our findings indicate that NKG2D stimulation during long-term CS exposure is a central pathway in the development of NK cell hyperresponsiveness and influenza-mediated exacerbations of COPD. PMID:22467655

  15. Hyper-active non-homologous end joining selects for synthetic lethality resistant and pathological Fanconi anemia hematopoietic stem and progenitor cells.

    Du, Wei; Amarachintha, Surya; Wilson, Andrew F; Pang, Qishen

    2016-01-01

    The prominent role of Fanconi anemia (FA) proteins involves homologous recombination (HR) repair. Poly[ADP-ribose] polymerase1 (PARP1) functions in multiple cellular processes including DNA repair and PARP inhibition is an emerging targeted therapy for cancer patients deficient in HR. Here we show that PARP1 activation in hematopoietic stem and progenitor cells (HSPCs) in response to genotoxic or oxidative stress attenuates HSPC exhaustion. Mechanistically, PARP1 controls the balance between HR and non-homologous end joining (NHEJ) in double strand break (DSB) repair by preventing excessive NHEJ. Disruption of the FA core complex skews PARP1 function in DSB repair and led to hyper-active NHEJ in Fanca(-/-) or Fancc(-/-) HSPCs. Re-expression of PARP1 rescues the hyper-active NHEJ phenotype in Brca1(-/-)Parp1(-/-) but less effective in Fanca(-/-)Parp1(-/-) cells. Inhibition of NHEJ prevents myeloid/erythroid pathologies associated with synthetic lethality. Our results suggest that hyper-active NHEJ may select for "synthetic lethality" resistant and pathological HSPCs. PMID:26916217

  16. Interferon Regulator Factor 8 (IRF8) Limits Ocular Pathology during HSV-1 Infection by Restraining the Activation and Expansion of CD8+ T Cells

    Yu, Cheng-Rong; He, Chang; Mahdi, Rashid M.; Chan, Chi-Chao; Wang, Hongsheng; Morse, Herbert C.; Egwuagu, Charles E.

    2016-01-01

    Interferon Regulatory Factor-8 (IRF8) is constitutively expressed in monocytes and B cell lineages and plays important roles in immunity to pathogens and cancer. Although IRF8 expression is induced in activated T cells, the functional relevance of IRF8 in T cell-mediated immunity is not well understood. In this study, we used mice with targeted deletion of Irf8 in T-cells (IRF8KO) to investigate the role of IRF8 in T cell-mediated responses during herpes simplex virus 1 (HSV-1) infection of the eye. In contrast to wild type mice, HSV-1-infected IRF8KO mice mounted a more robust anti-HSV-1 immune response, which included marked expansion of HSV-1-specific CD8+ T cells, increased infiltration of inflammatory cells into the cornea and trigeminal ganglia (TG) and enhanced elimination of virus within the trigeminal ganglion. However, the consequence of the enhanced immunological response was the development of ocular inflammation, limbitis, and neutrophilic infiltration into the cornea of HSV-1-infected IRF8KO mice. Surprisingly, we observed a marked increase in virus-specific memory precursor effector cells (MPEC) in IRF8KO mice, suggesting that IRF8 might play a role in regulating the differentiation of effector CD8+ T cells to the memory phenotype. Together, our data suggest that IRF8 might play a role in restraining excess lymphocyte proliferation. Thus, modulating IRF8 levels in T cells can be exploited therapeutically to prevent immune-mediated ocular pathology during autoimmune and infectious diseases of the eye. PMID:27171004

  17. Interferon Regulator Factor 8 (IRF8 Limits Ocular Pathology during HSV-1 Infection by Restraining the Activation and Expansion of CD8+ T Cells.

    Lin Sun

    Full Text Available Interferon Regulatory Factor-8 (IRF8 is constitutively expressed in monocytes and B cell lineages and plays important roles in immunity to pathogens and cancer. Although IRF8 expression is induced in activated T cells, the functional relevance of IRF8 in T cell-mediated immunity is not well understood. In this study, we used mice with targeted deletion of Irf8 in T-cells (IRF8KO to investigate the role of IRF8 in T cell-mediated responses during herpes simplex virus 1 (HSV-1 infection of the eye. In contrast to wild type mice, HSV-1-infected IRF8KO mice mounted a more robust anti-HSV-1 immune response, which included marked expansion of HSV-1-specific CD8+ T cells, increased infiltration of inflammatory cells into the cornea and trigeminal ganglia (TG and enhanced elimination of virus within the trigeminal ganglion. However, the consequence of the enhanced immunological response was the development of ocular inflammation, limbitis, and neutrophilic infiltration into the cornea of HSV-1-infected IRF8KO mice. Surprisingly, we observed a marked increase in virus-specific memory precursor effector cells (MPEC in IRF8KO mice, suggesting that IRF8 might play a role in regulating the differentiation of effector CD8+ T cells to the memory phenotype. Together, our data suggest that IRF8 might play a role in restraining excess lymphocyte proliferation. Thus, modulating IRF8 levels in T cells can be exploited therapeutically to prevent immune-mediated ocular pathology during autoimmune and infectious diseases of the eye.

  18. Preventing effect of L-type calcium channel blockade on electrophysiological alterations in dentate gyrus granule cells induced by entorhinal amyloid pathology.

    Hamid Gholami Pourbadie

    Full Text Available The entorhinal cortex (EC is one of the earliest affected brain regions in Alzheimer's disease (AD. EC-amyloid pathology induces synaptic failure in the dentate gyrus (DG with resultant behavioral impairment, but there is little known about its impact on neuronal properties in the DG. It is believed that calcium dyshomeostasis plays a pivotal role in the etiology of AD. Here, the effect of the EC amyloid pathogenesis on cellular properties of DG granule cells and also possible neuroprotective role of L-type calcium channel blockers (CCBs, nimodipine and isradipine, were investigated. The amyloid beta (Aβ 1-42 was injected bilaterally into the EC of male rats and one week later, electrophysiological properties of DG granule cells were assessed. Voltage clamp recording revealed appearance of giant sIPSC in combination with a decrease in sEPSC frequency which was partially reversed by CCBs in granule cells from Aβ treated rats. EC amyloid pathogenesis induced a significant reduction of input resistance (Rin accompanied by a profound decreased excitability in the DG granule cells. However, daily administration of CCBs, isradipine or nimodipine (i.c.v. for 6 days, almost preserved the normal excitability against Aβ. In conclusion, lower tendency to fire AP along with reduced Rin suggest that DG granule cells might undergo an alteration in the membrane ion channel activities which finally lead to the behavioral deficits observed in animal models and patients with early-stage Alzheimer's disease.

  19. The Danish Pathology Register

    Bjerregaard, Beth; Larsen, Ole B

    The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established.......The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established....

  20. Intracellular Trypsin Induces Pancreatic Acinar Cell Death but Not NF-κB Activation*

    JI, BAOAN; Gaiser, Sebastian; Chen, Xueqing; Ernst, Stephen A.; Logsdon, Craig D.

    2009-01-01

    Premature intracellular activation of the digestive enzyme trypsinogen is considered to be the initiating event in pancreatitis. However, the direct consequences of intracellular trypsin activity have not previously been examined. In the current study, a mutant trypsinogen (paired basic amino acid cleaving enzyme (PACE)-trypsinogen), which is activated intracellularly by the endogenous protease PACE, was developed. This new construct allowed for the first time direct examination of the effect...

  1. Lysosome associated membrane proteins maintain pancreatic acinar cell homeostasis : LAMP-2 deficient mice develop pancreatitis

    Mareninova, Olga A; Sendler, Matthias; Malla, Sudarshan Ravi; Yakubov, Iskandar; French, Samuel W; Tokhtaeva, Elmira; Vagin, Olga; Oorschot, Viola; Lüllmann-Rauch, Renate; Blanz, Judith; Dawson, David; Klumperman, Judith; Lerch, Markus M; Mayerle, Julia; Gukovsky, Ilya; Gukovskaya, Anna S

    2015-01-01

    BACKGROUND & AIMS: The pathogenic mechanism of pancreatitis is poorly understood. Recent evidence implicates defective autophagy in pancreatitis responses; however, the pathways mediating impaired autophagy in pancreas remain largely unknown. Here, we investigate the role of lysosome associated memb

  2. Prognostic value of 18F-fluorodeoxyglucose positron emission tomography, computed tomography and magnetic resonance imaging in oral cavity squamous cell carcinoma with pathologically positive neck lymph node

    To evaluate the prognostic value of preoperative neck lymph node (LN) assessment with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), computed tomography (CT), and magnetic resonance imaging (MRI) in oral cavity squamous cell carcinoma (OSCC) patients with pathologically positive LN. In total, 47 OSCC patients with pathologically positive LN were retrospectively reviewed with preoperative 18F-FDG PET and CT/MRI. All patients underwent surgical resection, neck dissection and postoperative adjuvant radiotherapy and/or chemotherapy between March 2002 and October 2010. Histologic correlation was performed for findings of 18F-FDG PET and CT/MRI. Thirty-six (76.6%) of 47 cases were correctly diagnosed with neck LN metastasis by 18F-FDG PET and 32 (68.1%) of 47 cases were correctly diagnosed by CT/MRI. Follow-up ranged from 20 to 114 months (median, 56 months). Clinically negative nodal status evaluated by 18F-FDG PET or CT/MRI revealed a trend toward better clinical outcomes in terms of overall survival, disease-free survival, local recurrence-free survival, regional nodal recurrence-free survival, and distant metastasis-free survival rates even though the trends were not statistically significant. However, there was no impact of neck node standardized uptake value (SUVmax) on clinical outcomes. Notably, SUVmax showed significant correlation with tumor size in LN (p 2 = 0.62). PET and CT/MRI status of LN also had significant correlation with the size of intranodal tumor deposit (p 2 = 0.37 and p 2 = 0.48, respectively). 18F-FDG PET and CT/MRI at the neck LNs might improve risk stratification in OSCC patients with pathologically positive neck LN in this study, even without significant prognostic value of SUVmax.

  3. Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial

    Background and purpose: To evaluate the benefits and the drawbacks of post-operative radiotherapy in completely resected Stage I (a and b) non-small cell lung cancer (NSCLC). Materials and methods: Patients with pathological Stages Ia and Ib NSCLC have been randomized into two groups: Group 1 (G1) received adjuvant radiotherapy, Group 0 (G0) the control group did not receive any adjuvant therapy. Local control, toxicity and survival have been evaluated. Results: Between July 1989 and June 1997, 104 patients with pathological stage I NSCLC have been enrolled in this study. Fifty-one patients were randomized to G1 and 53 to G0. Six patients have been excluded from the study due to incomplete follow-up data. Regarding local control, one patient in the G1 group had a local recurrence (2.2%) while in the G0 12 local recurrences have been observed (23%). Seventy-one percent of patients are disease-free at 5 years in G1 and 60% in G0 (P=0.039). Overall 5-year survival (Kaplan-Meier) showed a positive trend in the treated group: 67 versus 58% (P=0.048). Regarding toxicity in G1, six patients experienced a grade 1 acute toxicity. Radiological evidence of long-term lung toxicity, with no significant impairment of the respiratory function, has been detected in 18 of the 19 patients who have been diagnosed as having a post-radiation lung fibrosis. Conclusions: Adjuvant radiotherapy gave good results in terms of local control in patients with completely resected NSCLC with pathological Stage I. Overall 5-year survival and disease-free survival showed a promising trend. Treatment-related toxicity is acceptable

  4. Role of Ink4a/Arf Locus in Beta Cell Mass Expansion under Physiological and Pathological Conditions

    Elisabet Salas

    2014-01-01

    Full Text Available The ARF/INK4A (Cdkn2a locus includes the linked tumour suppressor genes p16INK4a and p14ARF (p19ARF in mice that trigger the antiproliferative activities of both RB and p53. With beta cell self-replication being the primary source for new beta cell generation in adult animals, the network by which beta cell replication could be increased to enhance beta cell mass and function is one of the approaches in diabetes research. In this review, we show a general view of the regulation points at transcriptional and posttranslational levels of Cdkn2a locus. We describe the molecular pathways and functions of Cdkn2a in beta cell cycle regulation. Given that aging reveals increased p16Ink4a levels in the pancreas that inhibit the proliferation of beta cells and decrease their ability to respond to injury, we show the state of the art about the role of this locus in beta cell senescence and diabetes development. Additionally, we focus on two approaches in beta cell regeneration strategies that rely on Cdkn2a locus negative regulation: long noncoding RNAs and betatrophin.

  5. Role of Ink4a/Arf Locus in Beta Cell Mass Expansion under Physiological and Pathological Conditions

    Salas, Elisabet; Rabhi, Nabil; Froguel, Philippe; Annicotte, Jean-Sébastien

    2014-01-01

    The ARF/INK4A (Cdkn2a) locus includes the linked tumour suppressor genes p16INK4a and p14ARF (p19ARF in mice) that trigger the antiproliferative activities of both RB and p53. With beta cell self-replication being the primary source for new beta cell generation in adult animals, the network by which beta cell replication could be increased to enhance beta cell mass and function is one of the approaches in diabetes research. In this review, we show a general view of the regulation points at transcriptional and posttranslational levels of Cdkn2a locus. We describe the molecular pathways and functions of Cdkn2a in beta cell cycle regulation. Given that aging reveals increased p16Ink4a levels in the pancreas that inhibit the proliferation of beta cells and decrease their ability to respond to injury, we show the state of the art about the role of this locus in beta cell senescence and diabetes development. Additionally, we focus on two approaches in beta cell regeneration strategies that rely on Cdkn2a locus negative regulation: long noncoding RNAs and betatrophin. PMID:24672805

  6. Biopsy follow-up in patients with isolated atypical small acinar proliferation (ASAP in prostate biopsy

    Luca Leone

    2014-12-01

    Full Text Available The incidence of prostate cancer (PCA was evaluated in 155 patients with isolated Atypical Small Acinar Proliferation (ASAP found on initial prostate biopsy, after a medium-term follow-up (40 months with at least one re-biopsy. Clinical and histological data were analysed. Cancer was detected in 81 of 155 (52.3%. The cancer detection rate was 71.6%, 91.3%, 97.5%, 100% at the 1st re-biopsy, 2nd, 3rd, and 4th rebiopsy respectively. At the uni- and multivariate analyses, prostate volume (≤ 30 cc, transition zone volume (≤ 10 cc, small core length at the initial biopsy (≤ 10 mm and few number of cores at initial biopsy (≤ 8 are predictive of cancer. Furthermore, tumour characteristics on the whole surgical specimens was assessed in 30 men: 13 of 30 (43 % had clinically relevant cancer (volume > 0.5 ml or/and Gleason score ≥ 7, or pT3. Most of relevant cancers were detected in the distal apex, anterior gland and midline. These anatomical sites could be under-sampled at the initial biopsy using the transrectal approach. Our data suggest that follow-up biopsy is recommended in all cases of isolated ASAP detected after biopsy using endfire transrectal probe. The re-biopsy strategy should increase the number of cores (or a saturation biopsy, focusing on area of ASAP in the initial biopsy, but also including the under-sampled areas (anterior gland, distal apex and midline to detect clinically relevant cancers.

  7. Pathologic assessment of myocardial cell necrosis and apoptosis after ischemia and reperfusion with molecular and morphological markers.

    Takashi, E; Ashraf, M

    2000-02-01

    The present work illustrates the critical subcellular changes in the rat heart after 10-30 min of left coronary artery (LCA) occlusion and 120 min of reperfusion with a combination of several staining techniques. Triphenyltetrazolium chloride (TTC) to detect non-injured myocytes, horseradish peroxidase (HRP) and terminal deoxynucleotide nick-end labeling (TUNEL) to detect necrotic and apoptotic cells were employed and electron microscopy (EM) was used to validate these changes. After 20 min of LCA occlusion, myocytes began to undergo necrosis whilst after 10 min occlusion, no myocyte underwent irreversible cell injury in the risk area. After 30 min of LCA occlusion and 120 min reperfusion, 36.3, 26.6 and 25% cells were normal, necrotic, and reversibly injured, respectively; the remaining 12.8% cells were apoptotic. Necrotic cells were strongly positive with HRP and negative for TTC and TUNEL. TUNEL-positive or apoptotic cells were slightly HRP-positive, indicating altered cell membrane permeability. Reversibly-injured myocytes were TTC-, HRP- and TUNEL-negative. These changes were more accurately defined in the 100- microm thick sections than in the traditional slices. It is concluded that: (1) TTC-staining of 100- microm thick sections is far superior and accurate for the detection of ischemic changes with shorter period of ischemia (10 min); (2) the combination of TTC-staining, HRP reaction and TUNEL method is excellent for demarcation of early ischemic changes; (3) TTC-negativity in ischemia less than 20 min does not indicate necrosis but only represents reversible changes; (4) the apoptosis is absent in early ischemia of 20 min with or without reperfusion at a time when sufficient ATP is present, and appears only after 30 min of coronary ligation and reperfusion; and (5) the apoptotic cells lose membrane integrity accompanied by decreased glycocalyx thickness and cell swelling as opposed to commonly known characteristics of apoptotic cells. PMID:10722798

  8. Cell model for efficient simulation of wave propagation in human ventricular tissue under normal and pathological conditions

    In this paper, we formulate a model for human ventricular cells that is efficient enough for whole organ arrhythmia simulations yet detailed enough to capture the effects of cell level processes such as current blocks and channelopathies. The model is obtained from our detailed human ventricular cell model by using mathematical techniques to reduce the number of variables from 19 to nine. We carefully compare our full and reduced model at the single cell, cable and 2D tissue level and show that the reduced model has a very similar behaviour. Importantly, the new model correctly produces the effects of current blocks and channelopathies on AP and spiral wave behaviour, processes at the core of current day arrhythmia research. The new model is well over four times more efficient than the full model. We conclude that the new model can be used for efficient simulations of the effects of current changes on arrhythmias in the human heart

  9. Study on the relationship between serum concentration of CYFRA21-1 and pathological staging in patients with non-small cell lung cancer

    Objective: To study the relationship between of serum concentrations of CYFRA21-1 and to pathological staging in patients with non-small cell lung cancer. Methods: Serum concentrations of CYFRA21-1 were determined with IRMA in 224 patients with non-small cell lung cancer. Results: The serum CYFRA21-1 levels in patients with non-small cell lung carcinoma increased gradually as the tumor size enlarged. Levels in patients of T2 and T3 stages were significantly higher than those in patients of T1 stage, but the difference between those in patients of T2 stage and T3 stage were not significant. The serum CYFRA21-1 levels also increased as the number of lymph nodes with metastasis increased. Differences of serum levels of CYFRA21-1 in patients of consecutive lymph node stages were all significant. Conclusion: Preoperative detection of the serum concentration of CYFRA21-1 in patient with non-small cell lung cancer has important clinical significance on the judgement of T, N stages. (authors)

  10. Glomerulonephritis associated with marginal zone B-cell lymphoma: clinical, pathological characteristics of renal injury and treatment (clinical cases

    B. T. Dzhumabaeva

    2015-12-01

    Full Text Available Glomerulonephritis associated with marginal zone B-cell lymphoma at the onset of disease is rarely diagnosed. In this article we reported two patient of the extranodal marginal zone B-cell lymphoma with kidney damage. The first patient with the extranodal marginal zone B-cell lymphoma involved the stomach, lymph nodes, bone marrow and associated with mesangioproliferative glomerulonephritis and renal failure. The second patient with the splenic form of marginal zone B-cell lymphoma associated with fibrillary glomerulonephritis and hepatitis C and involve the lymph nodes, liver, bone marrow, and synthesis monoclonal immunoglobulin (IgMκ, cryoglobulin type II. Glomerulonephritis of the both cases were established on the renal biopsies by the morphological investigation, immunofluorescence, and electron microscopy.Both patients received therapy with bendamustine and rituximab, which has resulted in complete remission for lymphatic tumors and improve of kidney function. Overall and event-free survival in the first case corresponds to 21 and 16 months, the second 29 and 20, respectively.These cases illustrates that the kidney may be initially involved by extranodal marginal zone B-cell lymphoma, and the need for expanded investigation of the possible dissemination. Combination of bendamustine and rituximab were effective and safety treatment in these cases.

  11. Macrophages in Langerhans cell histiocytosis are differentiated toward M2 phenotype: their possible involvement in pathological processes.

    Ohnishi, Koji; Komohara, Yoshihiro; Sakashita, Naomi; Iyama, Ken-Ichi; Murayama, Toshihiko; Takeya, Motohiro

    2010-01-01

    Although numerous macrophages are found in the lesions of Langerhans cell histiocytosis (LCH), their activation phenotypes and their roles in the disease process have not been clarified. Paraffin-embedded LCH samples were examined on immunohistochemistry and it was found that CD163 can be used to distinguish infiltrated macrophages from neoplastic Langerhans cells (LC). The number of CD163-positve macrophages was positively correlated with the number of multinucleated giant cells (MGC), indicating that most MGC are derived from infiltrated macrophages. A significant number of CD163-positive macrophages were positive for interleukin (IL)-10 and phospho-signal transducer and activator of transcription-3 (pSTAT3), an IL-10-induced signal transduction molecule. This indicates that these macrophages are polarized to anti-inflammatory macrophages of M2 phenotype. Tumor-derived macrophage-colony-stimulating factor (M-CSF) was considered to responsible for inducing M2 differentiation of infiltrated macrophages. The number of CD163-positive macrophages in different cases of LCH varied, and interestingly the density of CD163-positive macrophages was inversely correlated with the Ki-67-positivity of LC. Although the underlying mechanism is not fully elucidated, macrophage-derived IL-10 was considered to be involved in the suppression of tumor cell proliferation via activation of STAT3. PMID:20055949

  12. Pulmonary langerhans cell histiocytosis in adults: high-resolution CT - pathology comparisons and evolutional changes at CT

    Kim, Hyo Jin; Lee, Ho Yun; Kim, Tae Sung [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Lee, Kyung Soo [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Samsung Medical Center, Department of Radiology, Seoul (Korea, Republic of); Johkoh, Takeshi [Kinki Central Hospital of Mutual Aid Association of Public School Teachers, Department of Radiology, Hyoko (Japan); Tomiyama, Noriyuki [Osaka University Graduate School of Medicine, Department of Radiology, Osaka (Japan); Han, Joungho [Sungkyunkwan University School of Medicine, Department of Pathology, Samsung Medical Center, Seoul (Korea, Republic of)

    2011-07-15

    To compare high-resolution (HR) CT and histopathological findings and to evaluate serial CT findings in pulmonary Langerhans cell histiocytosis (PLCH). We reviewed CT of lung lesions in 27 adults (M:F = 20:7, mean age, 41 {+-} 12.3 years) with PLCH. After evaluating lung abnormalities including nodules, micronodules, thick-walled, thin-walled, and bizarre-shaped cysts and reticulation, observers compared CT findings obtained at lung biopsy sites with histopathological findings. The final CT was compared with the initial CT to determine disease extent changes. The most frequently observed patterns of lung abnormalities were micronodules (n = 24, 89%), thick-walled (n = 22, 82%), and thin-walled (n = 22, 82%) cysts. Even thin-walled and bizarre cysts harboured active inflammatory Langerhans cell sheets and eosinophils in their walls. In thin-walled cysts, we noted pericystic inflammatory cell infiltrations along the alveolar walls, as well as pericystic emphysema. Thin-walled or bizarre cysts demonstrated a tendency to coalesce with surrounding cysts via their cystic wall destruction. Fourteen (52%) patients showed improvement and nine (33%) showed progressing disease. More than half of patients with pulmonary PLCH show improvement at follow-up CT. Even thin-walled cysts harbour active inflammatory cells on histopathology and exhibit improvement at follow-up CT. (orig.)

  13. Pulmonary langerhans cell histiocytosis in adults: high-resolution CT - pathology comparisons and evolutional changes at CT

    To compare high-resolution (HR) CT and histopathological findings and to evaluate serial CT findings in pulmonary Langerhans cell histiocytosis (PLCH). We reviewed CT of lung lesions in 27 adults (M:F = 20:7, mean age, 41 ± 12.3 years) with PLCH. After evaluating lung abnormalities including nodules, micronodules, thick-walled, thin-walled, and bizarre-shaped cysts and reticulation, observers compared CT findings obtained at lung biopsy sites with histopathological findings. The final CT was compared with the initial CT to determine disease extent changes. The most frequently observed patterns of lung abnormalities were micronodules (n = 24, 89%), thick-walled (n = 22, 82%), and thin-walled (n = 22, 82%) cysts. Even thin-walled and bizarre cysts harboured active inflammatory Langerhans cell sheets and eosinophils in their walls. In thin-walled cysts, we noted pericystic inflammatory cell infiltrations along the alveolar walls, as well as pericystic emphysema. Thin-walled or bizarre cysts demonstrated a tendency to coalesce with surrounding cysts via their cystic wall destruction. Fourteen (52%) patients showed improvement and nine (33%) showed progressing disease. More than half of patients with pulmonary PLCH show improvement at follow-up CT. Even thin-walled cysts harbour active inflammatory cells on histopathology and exhibit improvement at follow-up CT. (orig.)

  14. Glycosylation of type II collagen is of major importance for T cell tolerance and pathology in collagen-induced arthritis

    Bäcklund, Johan; Treschow, Alexandra; Bockermann, Robert;

    2002-01-01

    Type II collagen (CII) is a candidate cartilage-specific autoantigen, which can become post-translationally modified by hydroxylation and glycosylation. T cell recognition of CII is essential for the development of murine collagen-induced arthritis (CIA) and also occurs in rheumatoid arthritis (RA...

  15. Synergistically increased ILC2 and Th9 cells in lung tissue jointly promote the pathological process of asthma in mice.

    Ying, Xinyu; Su, Zhaoliang; Bie, Qingli; Zhang, Pan; Yang, Huijian; Wu, Yumin; Xu, Yunyun; Wu, Jing; Zhang, Mengying; Wang, Shengjun; Xu, Huaxi

    2016-06-01

    In recent years, T helper (Th) 9 cells have been demonstrated to be key mediators in immune responses in asthmatic lungs, and innate lymphoid cells 2 (ILC2s) have been described as a novel type of innate immunocyte with the ability to enhance immunoglobulin E (IgE) production. However, the interaction between ILC2s and Th9 cells in the pulmonary system of a mouse model of asthma remains to be elucidated. In the present study, the response state of lung tissue with regards to Th9 and ILC2s in a mouse model of asthma was investigated by detecting Th9‑ and ILC2‑associated cytokine receptors. The present study also investigated the association between the expression levels of the cytokine receptors in lung tissue samples and the IgE levels in sera samples from mouse models of asthma. Results from the present study demonstrated that the frequency of ILC2s and Th9 cells was significantly increased in the lung tissue samples, indicating that a Th2-type immune response had occurred. In addition, high mRNA expression levels of RAR‑related orphan receptor α, interleukin 1 receptor‑like 1, transcription factor PU.1 and interleukin (IL)‑9 were observed. Furthermore, IL‑5Rα, IL‑13Rα2 and high‑affinity IgE receptor were increased in mouse models of asthma, and a positive association was observed between the expression levels of ILC2‑ or Th9‑associated receptors in tissue samples and IgE levels in the sera. This indicated that ILC2s and Th9 were in a state of polarization and may promote each other in the lung tissue of mouse models of asthma, and that the lung tissue was responding to the two types of cells via increased expression of receptors. PMID:27109139

  16. Matrix metalloproteinase-10 is a target of T and B cell responses that correlate with synovial pathology in patients with antibiotic-refractory Lyme arthritis.

    Crowley, Jameson T; Strle, Klemen; Drouin, Elise E; Pianta, Annalisa; Arvikar, Sheila L; Wang, Qi; Costello, Catherine E; Steere, Allen C

    2016-05-01

    Infection-induced autoimmunity is thought to be a contributing factor in antibiotic-refractory Lyme arthritis, but studies of autoimmunity have been hindered by difficulty in identifying relevant autoantigens. We developed a novel approach that begins with the identification of T cell epitopes in synovial tissue using tandem mass spectrometry. Herein, we identified an immunogenic HLA-DR-presented peptide (T cell epitope) derived from the source protein matrix metalloproteinase-10 (MMP-10) from the synovium of a patient with antibiotic-refractory arthritis. This finding provided a bridge for the identification of autoantibody responses to MMP-10, the "first autoimmune hit" in a subgroup of patients with erythema migrans, the initial skin lesion of the infection. Months later, after priming of the immune response to MMP-10 in early infection, a subset of patients with antibiotic-responsive or antibiotic-refractory arthritis had MMP-10 autoantibodies, but only patients with antibiotic-refractory arthritis had both T and B cell responses to the protein, providing evidence for a "second autoimmune hit". Further support for a biologically relevant autoimmune event was observed by the positive correlation of anti-MMP-10 autoantibodies with distinct synovial pathology. This experience demonstrates the power of new, discovery-based methods to identify relevant autoimmune responses in chronic inflammatory forms of arthritis. PMID:26922382

  17. Pathology of the region of the knee

    Aufdermaur, M.

    1981-09-01

    Radiological, clinical and pathologic-anatomical findings seen in four types of disorders of the region of the knee jointare described. An attempt is made to explain the clinical symptomatology on the basis of pathologic-anatomical findings. It is demonstrated that the histology of a giant cell neoplasm does not permit conclusions as to prognosis. Etiology and pathogenesis of villonodular synovitis and of chondrocalcinosis are unexplained. Pathologic-anatomical findings of chondromalacia patellae are those of early osteoarthrosis.

  18. Derivation of cochlear cells from pathological or isogenic human iPSCs for modeling hereditary hearing loss

    Czajkowski, Amandine; Grobarczyk, Benjamin; Hanon, Kevin; Lefebvre, Philippe; Delacroix, Laurence; Malgrange, Brigitte

    2016-01-01

    Alström Syndrome (AS) is a human autosomal recessive genetic disorder characterized by numerous clinical symptoms including deafness. AS is caused by mutations in the ALMS1 gene encoding for ALMS1 protein expressed at the basal body and implicated in ciliogenesis, cell cycle and proliferation (Jagger et al., 2011; Zulato et al., 2011 & Shenje et al., 2014). We are interesting in understanding the unknown mechanisms involving this protein in the genetic deafness of AS patients. To develop a m...

  19. Abnormal Calcium Handling Properties Underlie Familial Hypertrophic Cardiomyopathy Pathology in Patient-Specific Induced Pluripotent Stem Cells

    Lan, Feng; Lee, Andrew S.; Liang, Ping; Sanchez-Freire, Veronica; Nguyen, Patricia K; Wang, Li; Han, Leng; Yen, Michelle; Wang, Yongming; Sun, Ning; Abilez, Oscar J.; Hu, Shijun; Ebert, Antje D.; Navarrete, Enrique G.; Simmons, Chelsey S.

    2013-01-01

    Familial hypertrophic cardiomyopathy (HCM) is a prevalent hereditary cardiac disorder linked to arrhythmia and sudden cardiac death. While the causes of HCM have been identified as genetic mutations in the cardiac sarcomere, the pathways by which sarcomeric mutations engender myocyte hypertrophy and electrophysiological abnormalities are not understood. To elucidate the mechanisms underlying HCM development, we generated patient-specific induced pluripotent stem cell cardiomyocytes (iPSC-CMs)...

  20. Correlation of Radiographic and Pathologic Findings of Dermal Lymphatic Invasion in Head and Neck Squamous Cell Carcinoma

    Spector, Matthew E; Gallagher, K. Kelly; McHugh, Jonathan B; Mukherji, Suresh K.

    2011-01-01

    Head and neck squamous cell carcinoma (HNSCC) that involves the skin is able to invade the dermal lymphatic system. Currently there is no way to identify patients with dermal lymphatic invasion preoperatively. The purpose of this study is to determine if CT can predict dermal lymphatic invasion. Medical records, CT scans, and corresponding histopathologic slides were reviewed of HNSCC patients with skin resected as part of their treatment. Dermal lymphatic invasion was defined radiographicall...

  1. Updates of pathologic myopia.

    Ohno-Matsui, Kyoko; Lai, Timothy Y Y; Lai, Chi-Chun; Cheung, Chiu Ming Gemmy

    2016-05-01

    Complications from pathologic myopia are a major cause of visual impairment and blindness, especially in east Asia. The eyes with pathologic myopia may develop loss of the best-corrected vision due to various pathologies in the macula, peripheral retina and the optic nerve. Despite its importance, the definition of pathologic myopia has been inconsistent. The refractive error or axial length alone often does not adequately reflect the 'pathologic myopia'. Posterior staphyloma, which is a hallmark lesion of pathologic myopia, can occur also in non-highly myopic eyes. Recently a revised classification system for myopic maculopathy has been proposed to standardize the definition among epidemiological studies. In this META-PM (meta analyses of pathologic myopia) study classification, pathologic myopia was defined as the eyes having chorioretinal atrophy equal to or more severe than diffuse atrophy. In addition, the advent of new imaging technologies such as optical coherence tomography (OCT) and three dimensional magnetic resonance imaging (3D MRI) has enabled the detailed observation of various pathologies specific to pathologic myopia. New therapeutic approaches including intravitreal injections of anti-vascular endothelial growth factor agents and the advance of vitreoretinal surgeries have greatly improved the prognosis of patients with pathologic myopia. The purpose of this review article is to provide an update on topics related to the field of pathologic myopia, and to outline the remaining issues which need to be solved in the future. PMID:26769165

  2. Forms of pathologization

    Brinkmann, Svend

    before, perhaps due to the malaises of modernity. Instead, we have learned to think and talk about human problems in new ways, viz. ways that involve pathologization. Pathologization, however, is not a unitary phenomenon, and the presentation gives an overview of four types of pathologization, which are...

  3. Genetic aberrations in small B-cell lymphomas and leukemias: molecular pathology, clinical relevance and therapeutic targets.

    Bogusz, Agata M; Bagg, Adam

    2016-09-01

    Small B-cell lymphomas and leukemias (SBCLs) are a clinically, morphologically, immunophenotypically and genetically heterogeneous group of clonal lymphoid neoplasms, including entities such as chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL) and hairy cell leukemia (HCL). The pathogenesis of some of these lymphoid malignancies is characterized by distinct translocations, for example t(11;14) in the majority of cases of MCL and t(14;18) in most cases of FL, whereas other entities are associated with a variety of recurrent but nonspecific numeric chromosomal abnormalities, as exemplified by del(13q14), del(11q22), and +12 in CLL, and yet others such as LPL and HCL that lack recurrent or specific cytogenetic aberrations. The recent surge in next generation sequencing (NGS) technology has shed more light on the genetic landscape of SBCLs through characterization of numerous driver mutations including SF3B1 and NOTCH1 in CLL, ATM and CCND1 in MCL, KMT2D and EPHA7 in FL, MYD88 (L265P) in LPL, KLF2 and NOTCH2 in splenic MZL (SMZL) and BRAF (V600E) in HCL. The identification of distinct genetic lesions not only provides greater insight into the molecular pathogenesis of these disorders but also identifies potential valuable biomarkers for prognostic stratification, as well as specific targets for directed therapy. This review discusses the well-established and recently identified molecular lesions underlying the pathogenesis of SBCLs, highlights their clinical relevance and summarizes novel targeted therapies. PMID:27121112

  4. Residual lymph node status is an independent prognostic factor in esophageal squamous cell Carcinoma with pathologic T0 after preoperative radiotherapy

    To evaluate the prognostic factors affecting survival in esophageal squamous cell Carcinoma (ESCC) patients with pathologic T0 (ypT0) underwent preoperative radiotherapy. Two hundred and ninety-six patients with ESCC who had received preoperative radiotherapy from 1980 to 2007 were retrospectively analyzed. One hundred patients were ypT0 after preoperative radiotherapy. Univariate and multivariate analyses were performed to evaluate the predictive impact of residual lymph node status on overall survival (OS) and progression-free survival (PFS). Among the originally analyzed 296 patients, 100 (33.7 %) patients had ypT0, including 78 patients (78 %) with ypT0N0, and 22 patients (22 %) with ypT0N1. The 5-year OS of the total patients was 42.4 %. Patients with ypT0N0 have significant improved 5-year OS and PFS than ypT0N1 patients (OS: 50.7 % vs 13.6 %, P = 0.004; PFS: 49.6 % vs 13.6 %, P = 0.003). In multivariate analysis, residual lymph node status was also an independent prognostic factors for OS (HR: 0.406, 95 % CI: 0.240–0.686, P = 0.001) and PFS (HR: 0.427, 95 % CI: 0.248–0.734, P = 0.002). Our results indicate that patients with ypT0N0 after preoperative radiotherapy had significantly better OS and PFS than patients with ypT0N1 in ESCC. Residual nodal metastasis of ESCC patients with pathological complete response of the primary tumor after neoadjuvant radiotherapy does influence prognosis

  5. Pathological and radiological correlation in an autopsy case of combined pulmonary fibrosis and emphysema

    Karata H

    2015-07-01

    Full Text Available Hiroki Karata,1 Tomonori Tanaka,1 Ryoko Egashira,2 Kazuhiro Tabata,1 Kyoko Otani,3 Ryuji Hayashi,4 Takashi Hori,5 Junya Fukuoka1 1Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; 2Department of Radiology, Faculty of Medicine, Saga University, Saga, Japan; 3Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan; 4Department of Internal Medicine, University of Toyama, Faculty of Medicine, Toyama, Japan; 5Laboratory of Pathology, Toyama University Hospital, Toyama, Japan Abstract: We report an educational autopsy case of combined pulmonary fibrosis and emphysema. Radiological patterns of the upper lung were considered as mostly emphysema, but pathological observation revealed significant interstitial fibrosis of usual interstitial pneumonia as a major pathology. The patient eventually developed acute exacerbation of background interstitial pneumonia. Careful radiological and pathological correlation of the current case indicates that regions with distal acinar emphysema on computed tomography image may possess histologically marked dense fibrosis of lethal interstitial pneumonia. Keywords: interstitial pneumonia, CPFE, AEF, smoking, CT

  6. Illumination from light-emitting diodes (LEDs) disrupts pathological cytokines expression and activates relevant signal pathways in primary human retinal pigment epithelial cells.

    Shen, Ye; Xie, Chen; Gu, Yangshun; Li, Xiuyi; Tong, Jianping

    2016-04-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the aged people. The latest systemic review of epidemiological investigations revealed that excessive light exposure increases the risk of AMD. With the drastically increasing use of high-energy light-emitting diodes (LEDs) light in our domestic environment nowadays, it is supposed to pose a potential oxidative threat to ocular health. Retinal pigment epithelium (RPE) is the major ocular source of pathological cytokines, which regulate local inflammation and angiogenesis. We hypothesized that high-energy LED light might disrupt the pathological cytokine expression of retinal pigment epithelium (RPE), contributing to the pathogenesis of AMD. Primary human RPE cells were isolated from eyecups of normal eye donors and seeded into plate wells for growing to confluence. Two widely used multichromatic white light-emitting diodes (LEDs) with correlated color temperatures (CCTs) of 2954 and 7378 K were used in this experiment. The confluent primary RPE cells were under white LEDs light exposure until 24 h. VEGF-A, IL-6, IL-8 and MCP-1 proteins and mRNAs were measured using an ELISA kit and RT-PCR, respectively. Activation of mitogen-activated protein kinases (MAPKs), Akt, Janus kinase (JAK)2 and Nuclear factor (NF)-κB signal pathways after LEDs illumination were evaluated by western blotting analysis. The level of reactive oxygen species (ROS) using chloromethyl- 2',7'-dichlorodihydrofluorescein diacetate. Inhibitors of relevant signal pathways and anti-oxidants were added to the primary RPE cells before LEDs illumination to evaluate their biological functions. We found that 7378 K light, but not 2954 K upregulated the VEGF-A, IL-6, IL-8 and downregulated MCP-1 proteins and mRNAs levels in a time-dependent manner. In parallel, initial activation of MAPKs and NF-κB signal pathways were also observed after 7378 K light exposure. Mechanistically, antioxidants for eliminating reactive oxygen

  7. β-Cell regeneration through the transdifferentiation of pancreatic cells: Pancreatic progenitor cells in the pancreas.

    Kim, Hyo-Sup; Lee, Moon-Kyu

    2016-05-01

    Pancreatic progenitor cell research has been in the spotlight, as these cells have the potential to replace pancreatic β-cells for the treatment of type 1 and 2 diabetic patients with the absence or reduction of pancreatic β-cells. During the past few decades, the successful treatment of diabetes through transplantation of the whole pancreas or isolated islets has nearly been achieved. However, novel sources of pancreatic islets or insulin-producing cells are required to provide sufficient amounts of donor tissues. To overcome this limitation, the use of pancreatic progenitor cells is gaining more attention. In particular, pancreatic exocrine cells, such as duct epithelial cells and acinar cells, are attractive candidates for β-cell regeneration because of their differentiation potential and pancreatic lineage characteristics. It has been assumed that β-cell neogenesis from pancreatic progenitor cells could occur in pancreatic ducts in the postnatal stage. Several studies have shown that insulin-producing cells can arise in the duct tissue of the adult pancreas. Acinar cells also might have the potential to differentiate into insulin-producing cells. The present review summarizes recent progress in research on the transdifferentiation of pancreatic exocrine cells into insulin-producing cells, especially duct and acinar cells. PMID:27330712

  8. Proteome-wide analysis of SUMO2 targets in response to pathological DNA replication stress in human cells

    Bursomanno, Sara; Beli, Petra; Khan, Asif M;

    2015-01-01

    subfamily. SUMO2/3, in contrast to SUMO1, are predominantly involved in the cellular response to certain stresses, including heat shock. Substantial evidence from studies in yeast has shown that SUMOylation plays an important role in the regulation of DNA replication and repair. Here, we report a proteomic...... analysis of proteins modified by SUMO2 in response to DNA replication stress in S phase in human cells. We have identified a panel of 22 SUMO2 targets with increased SUMOylation during DNA replication stress, many of which play key functions within the DNA replication machinery and/or in the cellular...... response to DNA damage. Interestingly, POLD3 was found modified most significantly in response to a low dose aphidicolin treatment protocol that promotes common fragile site (CFS) breakage. POLD3 is the human ortholog of POL32 in budding yeast, and has been shown to act during break-induced recombinational...

  9. Early maturation and distinct tau pathology in induced pluripotent stem cell-derived neurons from patients with MAPT mutations.

    Iovino, Mariangela; Agathou, Sylvia; González-Rueda, Ana; Del Castillo Velasco-Herrera, Martin; Borroni, Barbara; Alberici, Antonella; Lynch, Timothy; O'Dowd, Sean; Geti, Imbisaat; Gaffney, Daniel; Vallier, Ludovic; Paulsen, Ole; Káradóttir, Ragnhildur Thóra; Spillantini, Maria Grazia

    2015-11-01

    Tauopathies, such as Alzheimer's disease, some cases of frontotemporal dementia, corticobasal degeneration and progressive supranuclear palsy, are characterized by aggregates of the microtubule-associated protein tau, which are linked to neuronal death and disease development and can be caused by mutations in the MAPT gene. Six tau isoforms are present in the adult human brain and they differ by the presence of 3(3R) or 4(4R) C-terminal repeats. Only the shortest 3R isoform is present in foetal brain. MAPT mutations found in human disease affect tau binding to microtubules or the 3R:4R isoform ratio by altering exon 10 splicing. We have differentiated neurons from induced pluripotent stem cells derived from fibroblasts of controls and patients with N279K and P301L MAPT mutations. Induced pluripotent stem cell-derived neurons recapitulate developmental tau expression, showing the adult brain tau isoforms after several months in culture. Both N279K and P301L neurons exhibit earlier electrophysiological maturation and altered mitochondrial transport compared to controls. Specifically, the N279K neurons show abnormally premature developmental 4R tau expression, including changes in the 3R:4R isoform ratio and AT100-hyperphosphorylated tau aggregates, while P301L neurons are characterized by contorted processes with varicosity-like structures, some containing both alpha-synuclein and 4R tau. The previously unreported faster maturation of MAPT mutant human neurons, the developmental expression of 4R tau and the morphological alterations may contribute to disease development. PMID:26220942

  10. CORRELATIONS AMONG EXPRESSION OF ANGIOPOIETIN-1 TO CLINICAL PATHOLOGICAL CHARACTERISTICS AN ANGIO- GENESIS IN ORAL SQUAMOUS CELL CARCINOMA

    LI Chao; CHEN Jian-chao; WANG Zhao-hui; ZHANG Bing; LI Bin; SONG Yu-feng

    2006-01-01

    Objective: To study the expression and the significance of Angiopoietin-1 (Ang-1) through observing the correlations among the expression of Ang-1 to clinicopathologic characteristics and microvessel density (MVD) in oral squamous cell carcinoma (OSCC). Methods: Expressions of Angiopoietin-1 and CD34 in 41 human OSCC tissues, 30 adjacent noncancerous oral tissues and 10 normal oral mucosas were detected by immunohistochemical SABC method. MCD was also assessed. Results: Of the 41 OSCC tissues, 41.46% (17/41) was Ang-1 positive. The expression of Ang-1 was significantly lower in OSCC than that in adjacent noncancerous oral tissues (P<0.05) and normal oral mucosa (P<0.05). The Ang-1 expression was significantly higher in high differentiated tumor than that in moderately differentiated tumor (P<0.05). The MVD was significantly higher in Ang-1-negative OSCC than in Ang-1-positive OSCC (P<0.01), and negatively correlated with the expression of Ang-1 (r=-0.32, P<0.05). Conclusion: Down-regulated expression of Ang-1 may play a crucial role in the development of OSCC. It negatively regulated the angiogenesis of tumor.

  11. Adult T-cell leukemia-lymphoma: a clinico-pathologic study of twenty-six patients from Martinique.

    Plumelle, Y; Pascaline, N; Nguyen, D; Panelatti, G; Jouannelle, A; Jouault, H; Imbert, M

    1993-01-01

    Twenty-six cases of adult T-cell leukemia/lymphoma (ATLL) were identified between 1983 and 1991 in Martinique (French West Indies). There were 14 men and 12 women, all of mixed racial descent and born in Martinique. Their ages ranged from 23 to 95 years. The main clinical and laboratory features at initial presentation were peripheral lymphadenopathy (22 cases), hepatomegaly (11 cases), splenomegaly (10 cases), cutaneous lesions (12 cases), hypercalcemia (16 cases), refractory infection by Strongyloides stercoralis (12 cases), and pre-existing autoimmune disorders (4 cases). All patients had absolute lymphocytosis with circulating pleomorphic abnormal lymphocytes. The prognosis was poor, with most patients (20 cases) surviving for less than 6 months. Although the overall clinicopathologic features of ATLL in this series are similar to those described in previous reports, we observed three additional points of interest: a high association with Strongyloides infection, an increased incidence of tropical spastic paresis/HTLV-1 associated myelopathy (TSP/HAM) among the relatives of the patients (5 cases), and the presence of prior collagen vascular diseases. PMID:8113152

  12. The role of Cajal cells in chronic prostatitis.

    Haki Yuksel, Ozgur; Urkmez, Ahmet; Verit, Ayhan

    2016-01-01

    Types of prostatitis can be defined as groups of syndromes in adult men associated with infectious and noninfectious causes characterized frequently by lower abdominal and perineal signs and diverse clinical symptoms and complications. Etiopathogenesis of chronic prostatitis is not well defined. Moreover, its treatment outcomes are not satisfactory. Presence of c-kit positive interstitial cells in human prostate is already known. It has been demonstrated that these cells can be pacemaker cells which trigger spontaneous slow-wave electrical activity in the prostate and can be responsible for the transport of glandular secretion from acinar cells into major and minor prostatic ducts and finally into urethra. In the light of all these data, when presence of a possible inflammatory pathology is thought to involve prostate that secretes and has a reservoir which drains its secretion (for prostate, prostatic urethra), two points are worth mentioning. Impairment of secretion mechanism and collection of secretion within the organ with reflux of the microbial material from its reservoir back into prostate gland. Both of these potential conditions can be explained by ductal neuromuscular mechanism, which induces secretion. We think that in this neuromuscular mechanism interstitial Cajal cells have an important role in chronic prostatitis. Our hypothesis is that curability of prostatitis is correlated with the number of Cajal cells not subjected to apoptosis. PMID:27377090

  13. Glucocerebrosidase 1 deficient Danio rerio mirror key pathological aspects of human Gaucher disease and provide evidence of early microglial activation preceding alpha-synuclein-independent neuronal cell death

    Keatinge, Marcus; Bui, Hai; Menke, Aswin; Chen, Yu-Chia; Sokol, Anna M.; Bai, Qing; Ellett, Felix; Da Costa, Marc; Burke, Derek; Gegg, Matthew; Trollope, Lisa; Payne, Thomas; McTighe, Aimee; Mortiboys, Heather; de Jager, Sarah; Nuthall, Hugh; Kuo, Ming-Shang; Fleming, Angeleen; Schapira, Anthony H.V.; Renshaw, Stephen A.; Highley, J. Robin; Chacinska, Agnieszka; Panula, Pertti; Burton, Edward A.; O'Neill, Michael J.; Bandmann, Oliver

    2015-01-01

    Autosomal recessively inherited glucocerebrosidase 1 (GBA1) mutations cause the lysosomal storage disorder Gaucher's disease (GD). Heterozygous GBA1 mutations (GBA1+/−) are the most common risk factor for Parkinson's disease (PD). Previous studies typically focused on the interaction between the reduction of glucocerebrosidase (enzymatic) activity in GBA1+/− carriers and alpha-synuclein-mediated neurotoxicity. However, it is unclear whether other mechanisms also contribute to the increased risk of PD in GBA1+/− carriers. The zebrafish genome does not contain alpha-synuclein (SNCA), thus providing a unique opportunity to study pathogenic mechanisms unrelated to alpha-synuclein toxicity. Here we describe a mutant zebrafish line created by TALEN genome editing carrying a 23 bp deletion in gba1 (gba1c.1276_1298del), the zebrafish orthologue of human GBA1. Marked sphingolipid accumulation was already detected at 5 days post-fertilization with accompanying microglial activation and early, sustained up-regulation of miR-155, a master regulator of inflammation. gba1c.1276_1298del mutant zebrafish developed a rapidly worsening phenotype from 8 weeks onwards with striking reduction in motor activity by 12 weeks. Histopathologically, we observed marked Gaucher cell invasion of the brain and other organs. Dopaminergic neuronal cell count was normal through development but reduced by >30% at 12 weeks in the presence of ubiquitin-positive, intra-neuronal inclusions. This gba1c.1276_1298del zebrafish line is the first viable vertebrate model sharing key pathological features of GD in both neuronal and non-neuronal tissue. Our study also provides evidence for early microglial activation prior to alpha-synuclein-independent neuronal cell death in GBA1 deficiency and suggests upregulation of miR-155 as a common denominator across different neurodegenerative disorders. PMID:26376862

  14. 基底细胞癌29例临床病理分析%Clinical and pathological analysis of 29 cases of basal cell carcinoma

    周红; 陈敏慧

    2012-01-01

    Objective: To study the clinical features of skin basal cell carcinoma. Methods: Data of 29 cases of basal cell carcinoma was analyzed. Results: The ratio of male and female in these patients was 1: 1. 23. Age ranged from 36 to 81, patients over 50 - years - old of 24 patients was 82.76%. The most common type of nodules was solid (16 cases 55. 17% ). Conclusion: This disease developed more in old person with long term sun exposure.Pathological examination in the correct diagnosis, treatment and prognosis plays an important role.%目的:探讨皮肤基底细胞癌(basal cell carcinoma.BCC)临床病理特点及诱发因素,提高对该病的诊断水平.方法:对29例基底细胞癌患者的临床病理资料进行综合分析.结果:本组患者中男性13例,女性16例,男女比例1:1.23,年龄36 -81岁,其中≥50岁24例(82.76%),农民居多,以结节型(实性)最多见(16例,55.17%).结论:基底细胞癌的发病以中老年为主,好发于头面部等暴晒部位,基底细胞癌的发生与慢性长期日光照射密切相关,病理检查对该病的正确诊断、治疗及预后判断起着重要作用.

  15. EXPRESSION OF P53 GENE IN ORAL SQUAMOUS CELL CARCINOMA AND ITS RELATION WITH CLINICAL AND PATHOLOGICAL PARAMETERS AND PROGNOSIS OF PATIENTS

    毛驰; 卢勇; 赖钦声; 夏雨和; 杨橙

    1995-01-01

    One hundred and eleven cases of cral squamous cell carcinoma (OSCC) were examined for overexpression of p53 protein by using immunchistochemical technique.Association between p53 protein overexpression and clinical and pathological parameters as well as prognosis of patients were also analyzed. p53 protein overexpression was commonly observed (69.4%) in OSCC and may be used as a marker of carcinogenesis of OSCC.The level of p53 protein overexpression is correlated with the lowet three and five-year survival rate of OSCC.The presence of absence of p53 overexpression was not correlated with sex,age,site of tumor,size of tumor,degree of differentiation,node status,and clinical stage in OSCC.Single factor COX proportinoal hazards regression model analysis indicated that there was no significant association between p53 overexpression and prognosis of OSCC,Multivariable COX model analysis failed to establish effective life function of risk rate function,These showed that all the parameters analyzed in this study as well as p53 overexpression were not significant and effective risk factors of prognosis for patients wich OSCC.

  16. Combined gene/cell therapies provide long-term and pervasive rescue of multiple pathological symptoms in a murine model of globoid cell leukodystrophy

    Ricca, Alessandra; Rufo, Nicole; Ungari, Silvia; Morena, Francesco; Martino, Sabata; Kulik, Wilem; Alberizzi, Valeria; Bolino, Alessandra; Bianchi, Francesca; del Carro, Ubaldo; Biffi, Alessandra; Gritti, Angela

    2015-01-01

    Globoid cell leukodystrophy (GLD) is a lysosomal storage disease caused by deficient activity of β-galactocerebrosidase (GALC). The infantile forms manifest with rapid and progressive central and peripheral demyelination, which represent a major hurdle for any treatment approach. We demonstrate here that neonatal lentiviral vector-mediated intracerebral gene therapy (IC GT) or transplantation of GALC-overexpressing neural stem cells (NSC) synergize with bone marrow transplant (BMT) providing ...

  17. Close association of centroacinar ductular and insular cells in the rat pancreas

    Leeson, Thomas S.; Leeson, Roland

    1986-01-01

    Close contacts between endocrine insular cells and exocrine acinar, centroacinar and ductular cells occur frequently in the rat pancreas as seen by both light and electron microscopy. lslets of Langerhans are surrounded incompletely by a thin connective tissue capsule or mantle but numerous exocrine-endocrine cell contacts occur at the periphery, which is irregular with considerable "intermingling" of the two cell types. Centroacinar ...

  18. Pathology informatics fellowship training: Focus on molecular pathology

    Diana Mandelker; Lee, Roy E.; Platt, Mia Y.; Gregory Riedlinger; Andrew Quinn; Luigi K F Rao; Klepeis, Veronica E.; Michael Mahowald; Lane, William J; Beckwith, Bruce A; Baron, Jason M.; David S McClintock; Kuo, Frank C.; Lebo, Matthew S.; Gilbertson, John R.

    2014-01-01

    Background: Pathology informatics is both emerging as a distinct subspecialty and simultaneously becoming deeply integrated within the breadth of pathology practice. As specialists, pathology informaticians need a broad skill set, including aptitude with information fundamentals, information systems, workflow and process, and governance and management. Currently, many of those seeking training in pathology informatics additionally choose training in a second subspecialty. Combining pathology ...

  19. Pathological Gambling in Parkinson's Disease

    Callesen, Mette Buhl; Linnet, Jakob; Thomsen, Kristine Rømer;

    Pathological Gambling in Parkinson’s Disease Mette Buhl Callesen, Jakob Linnet, Kristine Rømer Thomsen, Albert Gjedde, Arne Møller PET Center, Aarhus University Hospital and Center of Functionally Integrative Neuroscience, Aarhus University.   The neurotransmitter dopamine is central to many...... aspects of human functioning, e.g., reward, learning, and addiction, including Pathological Gambling (PG), and its loss is key to Parkinson’s Disease (PD). PD is a neurodegenrative disorder caused by progressive loss of dopamine-producing cells in the midbrain [1]. One type of treatment of PD symptoms...... are twofold, both driven by the main hypothesis that PD patients who develop PG secondary to treatment with dopamine agonists have a decreased sensitivity towards dopamine and hence an increased demand for dopamine. The neurophysiological subproject 1 uses PET imaging to determine changes of dopamine...

  20. Cell Line Derived Multi-Gene Predictor of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer: A Validation Study on US Oncology 02-103 Clinical Trial

    Shen Kui

    2012-11-01

    Full Text Available Abstract Background The purpose of this study is to assess the predictive accuracy of a multi-gene predictor of response to docetaxel, 5-fluorouracil, epirubicin and cyclophosphamide combination chemotherapy on gene expression data from patients who received these drugs as neoadjuvant treatment. Methods Tumor samples were obtained from patients with stage II-III breast cancer before starting neoadjuvant chemotherapy with four cycles of 5-fluorouracil/epirubicin/cyclophosphamide (FEC followed by four cycles of docetaxel/capecitabine (TX on US Oncology clinical trial 02-103. Most patients with HER-2-positive cancer also received trastuzumab (H. The chemotherapy predictor (TFEC-MGP was developed from publicly available gene expression data of 42 breast cancer cell-lines with corresponding in vitro chemotherapy sensitivity results for the four chemotherapy drugs. No predictor was developed for treatment with trastuzumab. The predictive performance of TFEC-MGP in distinguishing cases with pathologic complete response from those with residual disease was evaluated for the FEC/TX and FEC/TX plus H group separately. The area under the receiver-operating characteristic curve (AU-ROC was used as the metric of predictive performance. Genomic predictions were performed blinded to clinical outcome. Results The AU-ROC was 0.70 (95% CI: 0.57-0.82 for the FEC/TX group (n=66 and 0.43 (95% CI: 0.20-0.66 for the FEC/TX plus H group (n=25. Among the patients treated with FEC/TX, the AU-ROC was 0.69 (95% CI: 0.52-0.86 for estrogen receptor (ER-negative (n=28 and it was 0.59 (95% CI: 0.36-0.82 for ER-positive cancers (n=37. ER status was not reported for one patient. Conclusions Our results indicate that the cell line derived 291-probeset genomic predictor of response to FEC/TX combination chemotherapy shows good performance in a blinded validation study, particularly in ER-negative patients.

  1. A divide-and-conquer strategy in tumor sampling enhances detection of intratumor heterogeneity in routine pathology: A modeling approach in clear cell renal cell carcinoma

    Lopez, José I.; Cortes, Jesús M.

    2016-01-01

    Intratumor heterogeneity (ITH) is an inherent process in cancer development which follows for most of the cases a branched pattern of evolution, with different cell clones evolving independently in space and time across different areas of the same tumor. The determination of ITH (in both spatial and temporal domains) is nowadays critical to enhance patient treatment and prognosis. Clear cell renal cell carcinoma (CCRCC) provides a good example of ITH. Sometimes the tumor is too big to be totally analyzed for ITH detection and pathologists decide which parts must be sampled for the analysis. For such a purpose, pathologists follow internationally accepted protocols. In light of the latest findings, however, current sampling protocols seem to be insufficient for detecting ITH with significant reliability. The arrival of new targeted therapies, some of them providing promising alternatives to improve patient survival, pushes the pathologist to obtain a truly representative sampling of tumor diversity in routine practice. How large this sampling must be and how this must be performed are unanswered questions so far.  Here we present a very simple method for tumor sampling that enhances ITH detection without increasing costs. This method follows a divide-and-conquer (DAC) strategy, that is, rather than sampling a small number of large-size tumor-pieces as the routine protocol (RP) advises, we suggest sampling many small-size pieces along the tumor. We performed a computational modeling approach to show that the usefulness of the DAC strategy is twofold: first, we show that DAC outperforms RP with similar laboratory costs, and second, DAC is capable of performing similar to total tumor sampling (TTS) but, very remarkably, at a much lower cost. We thus provide new light to push forward a shift in the paradigm about how pathologists should sample tumors for achieving efficient ITH detection. PMID:27127618

  2. The expression of GST isoenzymes in acinar adenocarcinoma, intraepithelial neoplasia, and benign prostate tissue: correlation of clinical parameters with GST isoenzymes

    ŞİMŞEK, Gülçin; Serpil OĞUZTÜZÜN; GÜREŞCİ, Servet; KILIÇ, Murat

    2012-01-01

    This study investigated the immunohistochemical staining characteristics of glutathione-S-transferase (GST) alpha, pi, mu, and theta in prostatic acinar adenocarcinoma (PCA), prostatic intraepithelial neoplasia (PIN), and benign prostatic tissues from 19 patients. Relationships between GST isoenzyme expression in benign, PIN, and PCA tissue were examined by the Wilcoxon signed-rank test and clinicopathological data were examined by the Spearman correlation rank test. When the benign, PIN, and...

  3. Widespread cytoskeletal pathology characterizes corticobasal degeneration.

    Feany, M B; Dickson, D W

    1995-01-01

    Corticobasal degeneration (CBD) is a rare, progressive neurological disorder characterized by widespread neuronal and glial pathology. Using immunohistochemistry and laser confocal microscopy, we demonstrate that the nonamyloid cortical plaques of CBD are actually collections of abnormal tau in the distal processes of astrocytes. These glial cells express both vimentin and CD44, markers of astrocyte activation. Glial pathology also includes tau-positive cytoplasmic inclusions, here localized ...

  4. Podocyte Pathology and Nephropathy

    Sandra eMerscher

    2014-07-01

    Full Text Available Sphingolipids are components of the lipid rafts in plasma membranes, which are important for proper function of podocytes, a key element of the glomerular filtration barrier. Research revealed an essential role of sphingolipids and sphingolipid metabolites in glomerular disorders of genetic and non-genetic origin. The discovery that glucocerebrosides accumulate in Gaucher disease in glomerular cells and are associated with clinical proteinuria initiated intensive research into the function of other sphingolipids in glomerular disorders. The accumulation of sphingolipids in other genetic diseases including Tay-Sachs, Sandhoff, Fabry, hereditary inclusion body myopathy 2, Niemann-Pick and nephrotic syndrome of the Finnish type and its implications with respect to glomerular pathology will be discussed. Similarily, sphingolipid accumulation occurs in glomerular diseases of non-genetic origin including diabetic kidney disease (DKD, HIV-associated nephropathy, focal segmental glomerulosclerosis (FSGS and lupus nephritis. Sphingomyelin metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate have also gained tremendous interest. We recently described that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b is expressed in podocytes where it modulates acid sphingomyelinase (ASMase activity and acts as a master modulator of danger signaling. Decreased SMPDL3b expression in post-reperfusion kidney biopsies from transplant recipients with idiopathic FSGS correlates with the recurrence of proteinuria in patients and in experimental models of xenotransplantation. Increased SMPDL3b expression is associated with DKD. The consequences of differential SMPDL3b expression in podocytes in these diseases with respect to their pathogenesis will be discussed. Finally, the role of sphingolipids in the formation of lipid rafts in podocytes and their contribution to the maintenance of a functional slit diaphragm in the glomerulus will be discussed.

  5. Pathologic conditions in pregnancy

    Soma authors suggested that MR imaging could rapresent an effective diagnostic alternative in the study of pathologic conditions of mother and fetus during pregnancy. To verify the actual role of MR imaging, we examined 20 patients in the 2nd and 3rd trimester of gestation, after a preliminary US examination. Fifteen patients presented fetal or placental pathologies; in 4 patients the onset of the pathologic condition occurred during pregnancy; in 1 case of US diagnosis of fetal ascites, MR findings were nornal and the newborn was healty. As for placental pathologies, our series included a case of placental cyst, two hematomas between placenta and uterine wall, and two cases of partial placenta previa. As for fetal malformation, we evaluated a case of omphalocele, one of Prune-Belly syndrome, a case of femoral asimmetry, one of thanatophoric dwarfism, a case of thoracopagus twins with cardiovascular abnormalities, two fetal hydrocephali, and three cases of pyelo-ureteral stenosis. As for maternal pathologies during pregnancy, we observed a case of subserous uterine fibromyoma, one of of right hydronephrosis, one of protrusion of lumbar invertebral disk, and a large ovarian cyst. In our experience, MR imaging exhibited high sensitivity and a large field of view, which were both useful in the investigation of the different conditions occurring during pregnancy. In the evaluation of fetal and placental abnormalities, especially during the 3rd trimester, the diagnostic yieldof MR imaging suggested it as a complementary technique to US for the evaluation of fetal malformation and of intrauterine growth retardation

  6. Clinical and pathological analysis for seven cases of giant basal cell carcinoma%7例巨大基底细胞癌的临床与组织病理分析

    雷山川; 高敏娜; 朱堂友

    2013-01-01

    Objective To study the clinical and pathologic features for seven cases of giant basal cell carcinoma. Methods Retrospective analysis was conducted on the clinical and pathological data for 7 cases of giant basal cell carcinoma retrospectively. Results Long course of disease and high rate of metastasis as well as site of tissue damaged seriously showed in the cases. Conclusion Karly pathological diagnosis and operation treatment can reduce tissue damage and educe metastasis of tumor and postoperative recurrence as well as possibility of mortality.%目的 探讨巨大基底细胞癌临床与组织病理学特点.方法 回顾性分析比较7例巨大基底细胞癌临床与组织病理学资料.结果 巨大基底细胞癌临床上病程长、肿瘤转移率高、对发生部位的组织器官毁损严重,组织病理为多亚型改变的组织病理相.结论 早期组织病理学检查确诊及手术治疗是减少、减轻对组织、器官毁损的前提,同时也可降低肿瘤的转移率、手术复发率及死亡率.

  7. Complications of Pathologic Myopia.

    Cho, Bum-Joo; Shin, Joo Young; Yu, Hyeong Gon

    2016-01-01

    Pathologic myopia (PM) is one of the leading causes of visual impairment worldwide. The pathophysiology of PM is not fully understood, but the axial elongation of the eye followed by chorioretinal thinning is suggested as a key mechanism. Pathologic myopia may lead to many complications such as chorioretinal atrophy, foveoschisis, choroidal neovascularization, rhegmatogenous retinal detachment, cataract, and glaucoma. Some complications affect visual acuity significantly, showing poor visual prognosis. This article aims to review the types, pathophysiology, treatment, and visual outcome of the complications of PM. PMID:26649982

  8. Complexity and forensic pathology.

    Jones, Richard Martin

    2015-12-01

    It has become increasingly apparent that nonlinearity and complexity are the norm in human physiological systems, the relevance of which is informing an enhanced understanding of basic pathological processes such as inflammation, the host response to severe trauma, and critical illness. This article will explore how an understanding of nonlinear systems and complexity might inform the study of the pathophysiology of deaths of medicolegal interest, and how 'complexity thinking' might usefully be incorporated into modern forensic medicine and forensic pathology research, education and practice. PMID:26372537

  9. LOXL2 induces aberrant acinar morphogenesis via ErbB2 signaling

    J. Chang (Jufang); M.M. Nicolau (Monica); T.R. Cox (Thomas); D. Wetterskog (Daniel); J.W.M. Martens (John); H. E Barker (Holly); J.T. Erler (Janine)

    2013-01-01

    textabstractIntroduction: Lysyl oxidase-like 2 (LOXL2) is a matrix-remodeling enzyme that has been shown to play a key role in invasion and metastasis of breast carcinoma cells. However, very little is known about its role in normal tissue homeostasis. Here, we investigated the effects of LOXL2 expr

  10. Pathological Gambling: Psychiatric Models

    Westphal, James R.

    2008-01-01

    Three psychiatric conceptual models: addictive, obsessive-compulsive spectrum and mood spectrum disorder have been proposed for pathological gambling. The objectives of this paper are to (1) evaluate the evidence base from the most recent reviews of each model, (2) update the evidence through 2007 and (3) summarize the status of the evidence for…

  11. TC pathological Neck

    This presentation is about different imaging techniques such as ultrasound, CT, RNM, PET-CT. These techniques permit to detect head and neck tumors, breast and digestive pathologies as well as congenital diseases and glandular tumor in the thyroid, parathyroid, muscles, lymphatic, nerves and vessels

  12. Pathological Gambling Subtypes

    Vachon, David D.; Bagby, R. Michael

    2009-01-01

    Although pathological gambling (PG) is regarded in the 4th edition of the "Diagnostic and Statistical Manual of Mental Disorders" (American Psychiatric Association, 1994) as a unitary diagnostic construct, it is likely composed of distinct subtypes. In the current report, the authors used cluster analyses of personality traits with a…

  13. The Quest for Tissue Stem Cells in the Pancreas and Other Organs, and their Application in Beta-Cell Replacement

    Houbracken, Isabelle; Bouwens, Luc

    2010-01-01

    Adult stem cell research has drawn a lot of attention by many researchers, due to its medical hope of cell replacement or regenerative therapy for diabetes patients. Despite the many research efforts to date, there is no consensus on the existence of stem cells in adult pancreas. Genetic lineage tracing experiments have put into serious doubt whether β-cell neogenesis from stem/progenitor cells takes place postnatally. Different in vitro experiments have suggested centroacinar, ductal, acinar...

  14. Pathological tau disrupts ongoing network activity.

    Menkes-Caspi, Noa; Yamin, Hagar G; Kellner, Vered; Spires-Jones, Tara L; Cohen, Dana; Stern, Edward A

    2015-03-01

    Pathological tau leads to dementia and neurodegeneration in tauopathies, including Alzheimer's disease. It has been shown to disrupt cellular and synaptic functions, yet its effects on the function of the intact neocortical network remain unknown. Using in vivo intracellular and extracellular recordings, we measured ongoing activity of neocortical pyramidal cells during various arousal states in the rTg4510 mouse model of tauopathy, prior to significant cell death, when only a fraction of the neurons show pathological tau. In transgenic mice, membrane potential oscillations are slower during slow-wave sleep and under anesthesia. Intracellular recordings revealed that these changes are due to longer Down states and state transitions of membrane potentials. Firing rates of transgenic neurons are reduced, and firing patterns within Up states are altered, with longer latencies and inter-spike intervals. By changing the activity patterns of a subpopulation of affected neurons, pathological tau reduces the activity of the neocortical network. PMID:25704951

  15. Pathology informatics fellowship training: Focus on molecular pathology

    Diana Mandelker

    2014-01-01

    Full Text Available Background: Pathology informatics is both emerging as a distinct subspecialty and simultaneously becoming deeply integrated within the breadth of pathology practice. As specialists, pathology informaticians need a broad skill set, including aptitude with information fundamentals, information systems, workflow and process, and governance and management. Currently, many of those seeking training in pathology informatics additionally choose training in a second subspecialty. Combining pathology informatics training with molecular pathology is a natural extension, as molecular pathology is a subspecialty with high potential for application of modern biomedical informatics techniques. Methods and Results: Pathology informatics and molecular pathology fellows and faculty evaluated the current fellowship program′s core curriculum topics and subtopics for relevance to molecular pathology. By focusing on the overlap between the two disciplines, a structured curriculum consisting of didactics, operational rotations, and research projects was developed for those fellows interested in both pathology informatics and molecular pathology. Conclusions: The scope of molecular diagnostics is expanding dramatically as technology advances and our understanding of disease extends to the genetic level. Here, we highlight many of the informatics challenges facing molecular pathology today, and outline specific informatics principles necessary for the training of future molecular pathologists.

  16. Feline oral pathology

    Costa, S.; Pais, B.; Almeida, D.; Simões, J.; Mega, A. C.; Vala, Helena

    2013-01-01

    The main pathologies of the oral cavity are of utmost importance, not only by the number of exposed individuals, but also by the consequences which stems. With the development of this work, we intend to conduct a brief approach to the same, since, specifically affecting domestic felines. Feline Lymphoplasmatic Gingivostomatitis (GELF), the Feline Odontoclastic Reabsorption Lesions (LROF) Complex and gingivitis-stomatitis-pharyngitis, have been studied, some of which are considered an enigma i...

  17. Pathology of tropical appendicitis.

    S. C. Gupta; A. K. Gupta; Keswani, N. K.; Singh, P. A.; Tripathi, A.K.; Krishna, V.

    1989-01-01

    Over the past 25 years, 2921 appendicectomies were performed at this hospital. All were subjected to routine histopathological examination. In 95% of cases, histopathological examination did not add any further information but in 153 (5%) cases, clinically important pathological findings were detected for the first time. Seventy (2.3%) specimens showed typical evidence of tuberculosis. Parasitic infestation was detected in 75 (2.5%), including enterobiasis (1.4%), amoebiasis (0.5%), ascariasi...

  18. Estrategias para la diferenciación in vitro de células ES de ratón a células acinares pancreáticas

    Rovira Clusellas, Meritxell

    2007-01-01

    Las patologías más importantes del páncreas exocrino, como la pancreatitis crónica (PC) o el cáncer de páncreas, representan un gran problema de salud pública en Europa. En la PC, el tejido acinar es substituido por complejos ductales. Además, es difícil mantener el fenotipo diferenciado de las células acinares en cultivo ya que sufren una transdiferenciación acinar-ductal.Las células madre embrionarias (ES) de ratón han sido utilizadas en la última década para generar in vitro células comple...

  19. American Society for Clinical Pathology

    ... With the National Cancer Institute for Inaugural Global Pathology Conference March 2016 OneLab Memo ASCP Action Alert - ... 2016 Copyright © 2016 by American Society for Clinical Pathology. All Rights Reserved. Terms of Use About ASCP ...

  20. ERG gene rearrangements are common in prostatic small cell carcinomas

    Lotan, Tamara L.; Gupta, Nilesh S; Wang, Wenle; Toubaji, Antoun; Haffner, Michael C; Chaux, Alcides; Hicks, Jessica L.; Meeker, Alan K.; Bieberich, Charles J.; De Marzo, Angelo M.; Epstein, Jonathan I; Netto, George J.

    2011-01-01

    Small cell carcinoma of the prostate is a rare subtype with an aggressive clinical course. Despite the frequent occurrence of ERG gene rearrangements in acinar carcinoma, the incidence of these rearrangements in prostatic small cell carcinoma is unclear. In addition, molecular markers to distinguish prostatic small cell carcinomas from lung and bladder small cell carcinomas may be clinically useful. We examined the occurrence of ERG gene rearrangements by fluorescence in situ hybridization in...

  1. Pathological tau disrupts ongoing network activity

    Menkes-Caspi, Noa; Yamin, Hagar G; Kellner, Vered; Spires-Jones, Tara L; Cohen, Dana; Stern, Edward A.

    2015-01-01

    Pathological tau leads to dementia and neurodegeneration in tauopathies, including Alzheimer's disease. It has been shown to disrupt cellular and synaptic functions, yet its effects on the function of the intact neocortical network remain unknown. Using in vivo intracellular and extracellular recordings, we measured ongoing activity of neocortical pyramidal cells during various arousal states in the rTg4510 mouse model of tauopathy, prior to significant cell death, when only a fraction of the...

  2. Priorities in seed pathology research

    Nameth S.T.

    1998-01-01

    Seed pathology as a subdisipline of plant pathology is relatively new. Paul Neergard is considered the father of seed pathology. Recent developments in the area of seed pathology technology allow for more ecofriendly seed treatments and more reliable seed health testing. Due to economics and new interest in environmental issues, research into the viability of biological seed treatments is becoming more common. The use of sophisticated DNA amplification technologies allows for the detection of...

  3. Pathology Gross Photography: The Beginning of Digital Pathology.

    Rampy, B Alan; Glassy, Eric F

    2016-03-01

    The underutilized practice of photographing anatomic pathology specimens from surgical pathology and autopsies is an invaluable benefit to patients, clinicians, pathologists, and students. Photographic documentation of clinical specimens is essential for the effective practice of pathology. When considering what specimens to photograph, all grossly evident pathology, absent yet expected pathologic features, and gross-only specimens should be thoroughly documented. Specimen preparation prior to photography includes proper lighting and background, wiping surfaces of blood, removing material such as tubes or bandages, orienting the specimen in a logical fashion, framing the specimen to fill the screen, positioning of probes, and using the right-sized scale. PMID:26851666

  4. Recent advances in stem cell research for the treatment of diabetes

    Noguchi, Hirofumi

    2009-01-01

    The success achieved over the last decade with islet transplantation has intensified interest in treating diabetes, not only by cell transplantation, but also by stem cells. The formation of insulin-producing cells from pancreatic duct, acinar, and liver cells is an active area of investigation. Protocols for the in vitro differentiation of embryonic stem (ES) cells based on normal developmental processes, have generated insulin-producing cells, though at low efficiency and without full respo...

  5. Molecular pathology in real time.

    Ryška, Aleš

    2016-03-01

    With the development of sophisticated individualized therapeutic approaches, the role of pathology in classification of tumors is enormously increasing. The solely morphological characterization of neoplastic process is no more sufficient for qualified decision on optimal therapeutic approach. Thus, morphologic diagnosis must be supplemented by molecular analysis of the lesion with emphasis on the detection of status of certain markers used as predictive factors for targeted therapy. Both intrinsic and acquired types of intratumor heterogeneity have an impact at various moments of cancer diagnostics and therapy. The primary heterogeneity of neoplastic tissue represents a significant problem in patients, where only limited biopsy samples from the primary tumor are available for diagnosis, such as core needle biopsy specimens in breast cancer, transthoracic or endobronchial biopsies in lung cancer, or endoscopic biopsies in gastric cancer. Detection of predictive markers may be influenced by this heterogeneity, and the marker detection may be falsely negative or (less probably) falsely positive. In addition, as these markers are often detected in the tissue samples from primary tumor, the differences between molecular features of the primary lesion and its metastases may be responsible for failure of systemic therapy in patients with discordant phenotype between primary and metastatic disease. The fact of tumor heterogeneity must be taken into consideration already in establishing pathological diagnosis. One has to be aware that limited biopsy specimen must not always be fully representative of the entire tumor volume. To overcome these limitations, there does not exist one single simple solution. Examination of more tissue (preference of surgical resection specimens over biopsies, whenever possible), use of ultra-sensitive methods able to identify the minute subclones as a source of possible resistance to treatment, and detection of secondary molecular events from

  6. Molecular Pathology and Personalized Medicine: The Dawn of a New Era in Companion Diagnostics—Practical Considerations about Companion Diagnostics for Non-Small-Cell-Lung-Cancer

    Till Plönes

    2016-01-01

    Full Text Available Companion diagnostics (CDx have become a major tool in molecular pathology and assist in therapy decisions in an increasing number of various cancers. Particularly, the developments in lung cancer have been most impressing in the last decade and consequently lung cancer mutation testing and molecular profiling has become a major business of diagnostic laboratories. However, it has become difficult to decide which biomarkers are currently relevant for therapy decisions, as many of the new biomarkers are not yet approved as therapy targets, remain in the status of clinical studies, or still have not left the experimental phase. The current review is focussed on those markers that do have current therapy implications, practical implications arising from the respective companion diagnostics, and thus is focused on daily practice.

  7. GSK-3β-induced Tau pathology drives hippocampal neuronal cell death in Huntington's disease: involvement of astrocyte-neuron interactions.

    L'Episcopo, F; Drouin-Ouellet, J; Tirolo, C; Pulvirenti, A; Giugno, R; Testa, N; Caniglia, S; Serapide, M F; Cisbani, G; Barker, R A; Cicchetti, F; Marchetti, B

    2016-01-01

    Glycogen synthase kinase-3β (GSK-3β) has emerged as a critical factor in several pathways involved in hippocampal neuronal maintenance and function. In Huntington's disease (HD), there are early hippocampal deficits both in patients and transgenic mouse models, which prompted us to investigate whether disease-specific changes in GSK-3β expression may underlie these abnormalities. Thirty-three postmortem hippocampal samples from HD patients (neuropathological grades 2-4) and age- and sex-matched normal control cases were analyzed using real-time quantitative reverse transcription PCRs (qPCRs) and immunohistochemistry. In vitro and in vivo studies looking at hippocampal pathology and GSK-3β were also undertaken in transgenic R6/2 and wild-type mice. We identified a disease and stage-dependent upregulation of GSK-3β mRNA and protein levels in the HD hippocampus, with the active isoform pGSK-3β-Tyr(216) being strongly expressed in dentate gyrus (DG) neurons and astrocytes at a time when phosphorylation of Tau at the AT8 epitope was also present in these same neurons. This upregulation of pGSK-3β-Tyr(216) was also found in the R6/2 hippocampus in vivo and linked to the increased vulnerability of primary hippocampal neurons in vitro. In addition, the increased expression of GSK-3β in the astrocytes of R6/2 mice appeared to be the main driver of Tau phosphorylation and caspase3 activation-induced neuronal death, at least in part via an exacerbated production of major proinflammatory mediators. This stage-dependent overactivation of GSK-3β in HD-affected hippocampal neurons and astrocytes therefore points to GSK-3β as being a critical factor in the pathological development of this condition. As such, therapeutic targeting of this pathway may help ameliorate neuronal dysfunction in HD. PMID:27124580

  8. Pathological potential of astroglia

    Chvátal, Alexandr; Anděrová, Miroslava; Neprašová, Helena; Prajerová, Iva; Benešová, Jana; Butenko, Olena; Verkhratsky, Alexei

    2008-01-01

    Roč. 57, Suppl.3 (2008), S101-S110. ISSN 0862-8408 R&D Projects: GA ČR GA305/06/1316; GA ČR GA305/06/1464; GA ČR GA305/08/1384; GA ČR GA309/08/1381; GA MŠk(CZ) LC554 Grant ostatní: GA MŠk(CZ) 1M0538 Institutional research plan: CEZ:AV0Z50390512 Keywords : astrocyte * astrogliosis * brain pathology Subject RIV: FH - Neurology Impact factor: 1.653, year: 2008

  9. Marketing the pathology practice.

    Berkowitz, E N

    1995-07-01

    Effective marketing of the pathology practice is essential in the face of an increasingly competitive market. Successful marketing begins with a market-driven planning process. As opposed to the traditional planning process used in health care organizations, a market-driven approach is externally driven. Implementing a market-driven plan also requires recognition of the definition of the service. Each market to which pathologists direct their service defines the service differently. Recognition of these different service definitions and creation of a product to meet these needs could lead to competitive advantages in the marketplace. PMID:7625911

  10. Pathological α-synuclein distribution in subjects with coincident Alzheimer's and Lewy body pathology.

    Toledo, Jon B; Gopal, Pallavi; Raible, Kevin; Irwin, David J; Brettschneider, Johannes; Sedor, Samantha; Waits, Kayla; Boluda, Susana; Grossman, Murray; Van Deerlin, Vivianna M; Lee, Edward B; Arnold, Steven E; Duda, John E; Hurtig, Howard; Lee, Virginia M-Y; Adler, Charles H; Beach, Thomas G; Trojanowski, John Q

    2016-03-01

    We investigated the distribution patterns of Lewy body-related pathology (LRP) and the effect of coincident Alzheimer disease (AD) pathology using a data-driven clustering approach that identified groups with different LRP pathology distributions without any diagnostic or researcher's input in two cohorts including: Parkinson disease patients without (PD, n = 141) and with AD (PD-AD, n = 80), dementia with Lewy bodies subjects without AD (DLB, n = 13) and demented subjects with AD and LRP pathology (Dem-AD-LB, n = 308). The Dem-AD-LB group presented two LRP patterns, olfactory-amygdala and limbic LRP with negligible brainstem pathology, that were absent in the PD groups, which are not currently included in the DLB staging system and lacked extracranial LRP as opposed to the PD group. The Dem-AD-LB individuals showed relative preservation of substantia nigra cells and dopamine active transporter in putamen. PD cases with AD pathology showed increased LRP. The cluster with occipital LRP was associated with non-AD type dementia clinical diagnosis in the Dem-AD-LB group and a faster progression to dementia in the PD groups. We found that (1) LRP pathology in Dem-AD-LB shows a distribution that differs from PD, without significant brainstem or extracranial LRP in initial phases; (2) coincident AD pathology is associated with increased LRP in PD indicating an interaction; (3) LRP and coincident AD pathology independently predict progression to dementia in PD, and (4) evaluation of LRP needs to acknowledge different LRP spreading patterns and evaluate substantia nigra integrity in the neuropathological assessment and consider the implications of neuropathological heterogeneity for clinical and biomarker characterization. PMID:26721587

  11. On the representation of cells in bone marrow pathology by a scalar field: propagation through serial sections, co-localization and spatial interaction analysis

    Weis, Cleo-Aron; Grießmann, Benedict Walter; Scharff, Christoph; Detzner, Caecilia; Pfister, Eva; Marx, Alexander; Zöllner, Frank Gerrit

    2015-01-01

    Background Immunohistochemical analysis of cellular interactions in the bone marrow in situ is demanding, due to its heterogeneous cellular composition, the poor delineation and overlap of functional compartments and highly complex immunophenotypes of several cell populations (e.g. regulatory T-cells) that require immunohistochemical marker sets for unambiguous characterization. To overcome these difficulties, we herein present an approach to describe objects (e.g. cells, bone trabeculae) by ...

  12. Pathology of the vestibulocochlear nerve

    De Foer, Bert [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: bert.defoer@GZA.be; Kenis, Christoph [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: christophkenis@hotmail.com; Van Melkebeke, Deborah [Department of Neurology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: Deborah.vanmelkebeke@Ugent.be; Vercruysse, Jean-Philippe [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: jphver@yahoo.com; Somers, Thomas [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: Thomas.somers@GZA.be; Pouillon, Marc [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: marc.pouillon@GZA.be; Offeciers, Erwin [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: Erwin.offeciers@GZA.be; Casselman, Jan W. [Department of Radiology, AZ Sint-Jan AV Hospital, Ruddershove 10, Bruges (Belgium); Consultant Radiologist, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium); Academic Consultent, University of Ghent (Belgium)], E-mail: jan.casselman@azbrugge.be

    2010-05-15

    There is a large scala of pathology affecting the vestibulocochlear nerve. Magnetic resonance imaging is the method of choice for the investigation of pathology of the vestibulocochlear nerve. Congenital pathology mainly consists of agenesis or hypoplasia of the vestibulocochlear nerve. Tumoral pathology affecting the vestibulocochlear nerve is most frequently located in the internal auditory canal or cerebellopontine angle. Schwannoma of the vestibulocochlear nerve is the most frequently found tumoral lesion followed by meningeoma, arachnoid cyst and epidermoid cyst. The most frequently encountered pathologies as well as some more rare entities are discussed in this chapter.

  13. Tracking in anatomic pathology.

    Pantanowitz, Liron; Mackinnon, Alexander C; Sinard, John H

    2013-12-01

    Bar code-based tracking solutions, long present in clinical pathology laboratories, have recently made an appearance in anatomic pathology (AP) laboratories. Tracking of AP "assets" (specimens, blocks, slides) can enhance laboratory efficiency, promote patient safety, and improve patient care. Routing of excess clinical material into research laboratories and biorepositories are other avenues that can benefit from tracking of AP assets. Implementing tracking is not as simple as installing software and turning it on. Not all tracking solutions are alike. Careful analysis of laboratory workflow is needed before implementing tracking to assure that this solution will meet the needs of the laboratory. Such analysis will likely uncover practices that may need to be modified before a tracking system can be deployed. Costs that go beyond simply that of purchasing software will be incurred and need to be considered in the budgeting process. Finally, people, not technology, are the key to assuring quality. Tracking will require significant changes in workflow and an overall change in the culture of the laboratory. Preparation, training, buy-in, and accountability of the people involved are crucial to the success of this process. This article reviews the benefits, available technology, underlying principles, and implementation of tracking solutions for the AP and research laboratory. PMID:23634908

  14. Preoperative [18F]Fluorodeoxyglucose Positron Emission Tomography Standardized Uptake Value of Neck Lymph Nodes Predicts Neck Cancer Control and Survival Rates in Patients With Oral Cavity Squamous Cell Carcinoma and Pathologically Positive Lymph Nodes

    Purpose: Survival in oral cavity squamous cell carcinoma (OSCC) depends heavily on locoregional control. In this prospective study, we sought to investigate whether preoperative maximum standardized uptake value of the neck lymph nodes (SUVnodal-max) may predict prognosis in OSCC patients. Methods and Materials: A total of 120 OSCC patients with pathologically positive lymph nodes were investigated. All subjects underwent a [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scan within 2 weeks before radical surgery and neck dissection. All patients were followed up for at least 24 months after surgery or until death. Postoperative adjuvant therapy was performed in the presence of pathologic risk factors. Optimal cutoff values of SUVnodal-max were chosen based on 5-year disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). Independent prognosticators were identified by Cox regression analysis. Results: The median follow-up for surviving patients was 41 months. The optimal cutoff value for SUVnodal-max was 5.7. Multivariate analyses identified the following independent predictors of poor outcome: SUVnodal-max ≥5.7 for the 5-year neck cancer control rate, distant metastatic rate, DFS, DSS, and extracapsular spread (ECS) for the 5-year DSS and OS. Among ECS patients, the presence of a SUVnodal-max ≥5.7 identified patients with the worst prognosis. Conclusion: A SUVnodal-max of 5.7, either alone or in combination with ECS, is an independent prognosticator for 5-year neck cancer control and survival rates in OSCC patients with pathologically positive lymph nodes.

  15. Influence of Pathological Nodal Status and Maximal Standardized Uptake Value of the Primary Tumor and Regional Lymph Nodes on Treatment Plans in Patients With Advanced Oral Cavity Squamous Cell Carcinoma

    Purpose: A better understanding of the prognostic factors in oral cavity squamous cell carcinoma (OSCC) may optimize the therapeutic approach. In this study, we sought to investigate whether the combination of clinical information, pathologic results, and preoperative maximal standardized uptake value (SUVmax) at the primary tumor and regional lymph nodes might improve the prognostic stratification in this patient group. Methods and Materials: A total of 347 consecutive OSCC patients were investigated. All participants underwent fluorodeoxyglucose-positron emission tomography within 2 weeks before surgery and neck dissection. The duration of follow-up was at least 24 months in all surviving patients. The optimal cutoff values for SUVmax at the primary tumor (SUVtumor-max) and regional lymph nodes (SUVnodal-max) were selected according to the 5-year disease-free survival (DFS) rate. Independent prognosticators were identified by Cox regression analysis. Results: In multivariate analysis, a cutoff SUVtumor-max of 8.6, a cutoff SUVnodal-max of 5.7, and the presence of pathologic lymph node metastases were found to be significant prognosticators for the 5-year DFS. A scoring system using these three prognostic factors was formulated to define distinct prognostic groups. The 5-year rates for patients with a score between 0 and 3 were as follows: neck control, 94%, 86%, 77%, 59% (p < 0.0001); distant metastases, 1%, 7%, 22%, 47% (p < 0.0001); disease-specific survival, 93%, 85%, 61%, 36%, respectively (p < 0.0001). Conclusion: Based on the study findings, the combined evaluation of pathologic node status and SUVmax at the primary tumor and regional lymph nodes may improve prognostic stratification in OSCC patients.

  16. Myoepithelial cell carcinoma of the oral cavity: A case report and review of literature

    Yashwant Ingle

    2014-01-01

    Full Text Available Myoepithelial carcinoma (MC is a malignant salivary gland neoplasm whose tumor cells demonstrate cytologic differentiation toward myoepithelial cells and lack ductal or acinar differentiation. It is a relatively rare tumor and many a times remains undiagnosed because of histopathological heterogeneity. It represents about 0.4-0.6% of all salivary gland tumors and 1.2-1.5% of carcinomas. It occurs predominantly in the parotid gland with a mean age of presentation being 55 years (range 14-86 with no sex predilection. MC appears to be a low grade malignancy when arising in a pleomorphic adenoma, but tends to be more aggressive and has a higher metastatic potential when arising de novo. The clinical behavior of MC is variable and there are no pathologic features that correlate with patients′ outcome. Most tumors that display marked cytologic atypia, high mitotic activity and necrosis tend to behave aggressively. The current case is of a 42-year-old male with recurrent tumor mass in the mandibular right posterior region. The purpose of this article was to describe the clinicopathological and immunohistochemical features of intraoral MC and to discuss review of literature of this rare tumor.

  17. The Cyan Fluorescent Protein (CFP Transgenic Mouse as a Model for Imaging Pancreatic Exocrine Cells

    Hop S Tran Cao

    2009-03-01

    Full Text Available The use of fluorescent proteins for in vivo imaging has opened many new areas of research. Among the important advances in the field have been the development of transgenic mice expressing various fluorescent proteins. Objective To report whole-body and organ-specific fluorescence imaging to characterize the transgenic cyan fluorescent protein mouse. Design Mice were imaged using two devices. Brightfield images were obtained with the OV100 Small Animal Imaging System (Olympus Corp., Tokyo, Japan. Fluorescence imaging was performed under the cyan fluorescent protein filter using the iBox Small Animal Imaging System (UVP, Upland, CA, USA. Intervention All animals were sacrificed immediately before imaging. They were imaged before and throughout multiple steps of a complete necropsy. Harvested organs were also imaged with both devices. Selected organs were then frozen and processed for histology, fluorescence microscopy, and H&E staining. Fluorescence microscopy was performed with an Olympus IMT-2 inverted fluorescence microscope. Main outcome measure Determination of fluorescence intensity of different organs. Results Surprisingly, we found that there is differential enhancement of fluorescence among organs; most notably, the pancreas stands out from the rest of the gastrointestinal tract, displaying the strongest fluorescence of all organs in the mouse. Fluorescence microscopy demonstrated that the cyan fluorescent protein fluorescence resided in the acinar cells of the pancreas and not the islet cells. Conclusions The cyan fluorescent protein mouse should lead to a deeper understanding of pancreatic function and pathology, including cancer.

  18. [Cystic renal pathology].

    Rosi, P; Cesaroni, M; Bracarda, S; Rociola, W; Virgili, G

    1993-08-01

    Ultrasonography has a great interest in diagnosis of cystic kidney disorders for typical eco-pattern of this pathology. In this work we show the eco-pattern of the most common cystic kidney disorders. Particularly we examine simple cysts (typical, atypical, complicated), multicystic kidney dysplasia, autosomal recessive polycystic kidney disease (infantile) autosomal dominant polycystic kidney disease (adult age). The so-called neoplastic cysts (multiloculated cysts, multiloculated cysts nephroma, cystic nephroblastoma), medullar cysts (medullary sponge kidney, medullary cystic disease), parapyelic cysts, acquired cystic kidney disease in renal failure patients, parasitic cysts, epidermoid cysts. About this disorders we present the more typical and expressive ultrasonographic appearance and we define the role and the opportunity of diagnostic setting by echography, moreover ultrasonography allows us to make a differential diagnosis between cystic kidney disorders and other kidney disease. PMID:8353538

  19. 'Pathological Science'; is not Scientific Misconduct (nor is it pathological

    Henry H. Bauer

    2002-04-01

    Full Text Available 'Pathological' science implies scientific misconduct: it should not happen and the scientists concerned ought to know better. However, there are no clear and generally agreed definitions of pathological science or of scientific misconduct. The canonical exemplars of pathological science in chemistry (N-rays, polywater as well as the recent case of cold fusion in electrochemistry involved research practices not clearly distinguishable from those in (revolutionary science. The concept of 'pathological science' was put forth nearly half a century ago in a seminar and lacks justification in contemporary understanding of science studies (history, philosophy, and sociology of science. It is time to abandon the phrase.

  20. Outcome and pathologic classification of children and adolescents with mediastinal large B-cell lymphoma treated with FAB/LMB96 mature B-NHL therapy

    Gerrard, Mary; Waxman, Ian M.; Sposto, Richard; Auperin, Anne; Perkins, Sherrie L.; Goldman, Stanton; Harrison, Lauren; Pinkerton, Ross; McCarthy, Keith; Raphael, Martine; Patte, Catherine; Cairo, Mitchell S

    2013-01-01

    Mediastinal large B-cell lymphoma (MLBL) represents 2% of mature B-cell non-Hodgkin lymphoma in patients ≤ 18 years of age. We analyzed data from childhood and adolescent patients with stage III MLBL (n = 42) and non-MLBL DLBCL (n = 69) treated with Group B therapy in the French-American-British/Lymphome Malins de Burkitt (FAB/LMB) 96 study. MLBL patients had a male/female 26/16; median age, 15.7 years (range, 12.5-19.7); and LDH < 2 versus ≥ 2 × the upper limit of normal, 23:19. Six MLBL pat...

  1. [Diagnostic significance of pathologic synkinesis for detection of pyramidal pathology].

    Baliasnyĭ, M M

    1991-01-01

    Five types of pathological synkinesis (++blepharo-ocular, ++blepharo-facial, ++bucco-manual, ++digito-digital on the hands, ++pedo-digital) are described. They are of definite importance for revealing pyramidal pathology including its early stages as well as for objective evaluation and observation of the time-course of changes in the illness. PMID:1654715

  2. Clearance of pathological antibodies using biomimetic nanoparticles

    Copp, Jonathan A.; Fang, Ronnie H.; Luk, Brian T.; Hu, Che-Ming J.; Gao, Weiwei; Zhang, Kang; Zhang, Liangfang

    2014-01-01

    The selective depletion of disease-causing antibodies using nanoparticles offers a new model in the management of type II immune hypersensitivity reactions. The demonstration of pathophysiologically inspired nanoengineering serves as a valuable prototype for additional therapeutic improvements with the goal of minimizing therapy-related adverse effects. Through the use of cell membrane-cloaked nanoparticles, nanoscale decoys with strong affinity to pathological antibodies can be administered ...

  3. Protein folding pathology in domestic animals*

    Gruys, Erik

    2004-01-01

    Fibrillar proteins form structural elements of cells and the extracellular matrix. Pathological lesions of fibrillar microanatomical structures, or secondary fibrillar changes in globular proteins are well known. A special group concerns histologically amorphous deposits, amyloid. The major characteristics of amyloid are: apple green birefringence after Congo red staining of histological sections, and non-branching 7–10 nm thick fibrils on electron microscopy revealing a high content of cross...

  4. 牙龈腺泡细胞癌1例报告及文献复习%Clinical and pathological characteristics of acinic cell carcinoma of gingiva:A case report and review of literature

    朱王勇; 陶谦

    2014-01-01

    本文报告了1例发生于右上颌牙龈的腺泡细胞癌病例,并回顾相关文献,总结口腔颌面部异位腺泡细胞癌的临床及病理特点。口腔颌面部异位腺泡细胞癌生长缓慢,或有疼痛、神经麻木,治疗以手术为首选,复发和转移率不高,必要时辅以放化疗。%To summarize the clinical and pathological characteristics of heterotopic acinic cell carcinoma of oromaxillo-facial region.A case of acinic cell carcinoma of gingiva was reported and the relevant literatures were reviewed and analyzed.The heterotopic acinic cell carcinoma grows slowly.Clinical symptom is pain or numbness.Surgery is the main means of treatment.Radiotherapy or chemotherapy is added after operation if necessary.The recurrence rate is low and malignant transformation is rare.

  5. Rotator cuff pathology

    Fifteen volunteers and 73 patients with suspected rotator cuff lesions were examined at 0.5 T with T2*-weighted gradient-echo (GE) MR imaging (700/33/30 degrees) (oblique coronal and sagittal 3 mm thick, surface coil). Results were compared with those of arthrography (all cases), T1-weighted GE imaging (400/20/90 degrees) (35 cases), surgery (28 cases), and T2-weighted spin-echo (SE) images (2,000/60-120) (17 cases). GE images demonstrated all tears (complete, 32, partial, 12) and was superior to arthrography in determining site and size and in displaying muscles (critical point in surgical planning). In 20 cases without tears on arthrography, GE imaging demonstrated five cases of tendinitis, five cases of bursitis, and six probable intratendinous or superficial partial tears. T2*-weighted GE imaging was superior to T2-weighted SE and T1-weighted GE imaging, with higher fluid contrast and a low fat signal. Therefore, it might replace arthrography in the diagnosis and surgical approach to this pathology

  6. Molecular pathology of lymphoma

    Coupland, S E

    2012-01-01

    Ocular lymphomas can be divided into intraocular lymphomas and ocular adnexal lymphomas. The vitreoretinal lymphoma—usually a diffuse large B-cell lymphoma (DLBCL) of high-grade malignancy—is the most common lymphoid malignancy arising in the eye, while the extranodal marginal zone B-cell lymphoma (EMZL), an indolent often recurrent tumour, occurs most frequently in the ocular adnexal tissue. The two lymphoma subtypes differ significantly in their clinical presentation, subsequent course and ...

  7. Histopathology and immune histochemistry of red tattoo reactions. Interface dermatitis is the lead pathology, with increase in T-lymphocytes and Langerhans cells suggesting an allergic pathomechanism

    Høgsberg, T; Thomsen, B M; Serup, J

    2015-01-01

    BACKGROUND: The majority of tattoo reactions are affiliated to red pigmented areas and often suspected to be allergic in nature. A sizeable series of biopsies of such reactions has not previously been performed. The aim of this study was to type and grade epidermal and dermal changes in tattoo...... reactions to red/red nuances by microscopy and immunochemistry relevant for the assessment of a possible allergic pathomechanism. METHODS: Skin biopsies were taken from red tattoo reactions, graded by conventional microscopy and stained for T and B-lymphocytes, Langerhans cells, macrophages and tumour......-α was common. CONCLUSION: The predominant histological pattern of chronic tattoo reactions in red/red nuances is interface dermatitis. T-lymphocytes and Langerhans cells are increased suggesting an allergic pathomechanism. TNF-α may contribute to reactions. In many cases, overlapping reactive patterns...

  8. Immunogenetics and the Pathological Mechanisms of Human T-Cell Leukemia Virus Type 1- (HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP

    Mineki Saito

    2010-01-01

    Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 is a replication-competent human retrovirus associated with two distinct types of disease only in a minority of infected individuals: the malignancy known as adult T-cell leukemia (ATL and a chronic inflammatory central nervous system disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. Although the factors that cause these different manifestations of HTLV-1 infection are not fully understood, accumulating evidence suggests that complex virus-host interactions play an important role in determining the risk of HAM/TSP. This review focuses on the role of the immune response in controlling or limiting viral persistence in HAM/TSP patients, and the reason why some HTLV-1-infected people develop HAM/TSP whereas the majority remains asymptomatic carriers of the virus.

  9. PKC and neurofibromin in the molecular pathology of urinary bladder carcinoma:the effect of PKC inhibitors on carcinoma cell junctions, movement and death

    Aaltonen, V. (Vesa)

    2007-01-01

    Abstract This study examined the role of tumor suppressor neurofibromin and Protein kinase C (PKC) in urinary bladder cancer, and the effect of PKC inhibitors on cancer cell behaviour. Tumor suppressor protein neurofibromin is a product of the NF1 gene, a mutation of which causes the most common hereditary tumor syndrome, type 1 neurofibromatosis. NF1 gene mutations and changes in expression have been demonstrated in malignancies, unrelated to type 1 neurofibromatosis. The best known ...

  10. An update: improvements in imaging perfluorocarbon-mounted plant leaves with implications for studies of plant pathology, physiology, development and cell biology

    Littlejohn, George R.; Mansfield, Jessica C.; Christmas, Jacqueline T.; Witterick, Eleanor; Fricker, Mark D; Grant, Murray R.; Smirnoff, Nicholas; Everson, Richard M.; Moger, Julian; Love, John

    2014-01-01

    Plant leaves are optically complex, which makes them difficult to image by light microscopy. Careful sample preparation is therefore required to enable researchers to maximize the information gained from advances in fluorescent protein labeling, cell dyes and innovations in microscope technologies and techniques. We have previously shown that mounting leaves in the non-toxic, non-fluorescent perfluorocarbon (PFC), perfluorodecalin (PFD) enhances the optical properties of the leaf with minimal...

  11. The Impact of Alpha-Syntrophin Deletion on the Changes in Tissue Structure and Extracellular Diffusion Associated with Cell Swelling under Physiological and Pathological Conditions

    Dmytrenko, Lesia; Cicanič, Michal; Anděrová, Miroslava; Voříšek, Ivan; Ottersen, O. P.; Syková, Eva; Vargová, Lýdia

    2013-01-01

    Roč. 8, č. 7 (2013), e68044. E-ISSN 1932-6203 R&D Projects: GA ČR GA309/09/1597; GA ČR(CZ) GAP303/11/2378; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:68378041 Keywords : extracellular space * diffusion parameters * cell swelling Subject RIV: FH - Neurology Impact factor: 3.534, year: 2013

  12. 原发中枢神经系统弥漫大B细胞淋巴瘤临床病理观察%Clinical pathology observation of primary central nervous system diffuse large B cell lymphoma

    王永峰; 张红鸽; 高恒瑞

    2014-01-01

    Objective:To explore the clinical pathological features,diagnosis and differential diagnosis of primary central nervous system diffuse large B cell lymphoma.Methods:The clinical data,histological pathological morphology and immunohistochemical results of 12 patients with primary central nervous system diffuse large B cell lymphoma were retrospectively analyzed.Results:The average age of 12 patients was 53.2 years.Visible tumor cells showed diffuse invasive distribution under light microscope, there was no boundaries with brain tissue,tumor cells in certain areas aggregated around vessel with raglan sleeves structure. There were infiltration and destruction of vascular wall.Immunohistochemistry showed that 12 cases of CD20,CD79,PAX5 and BCL-6 were positive,Ki-67 proliferation index was 40%~90%;CD3,CD10,Mum-1,GFAP,S-100 and CKpn were all negative. Conclusion:The incidence rate of primary central nervous system diffuse large B cell lymphoma is low.It has no clinical specificity. Its malignancy degree is high.Correctly grasping the clinical pathological and immunohistochemical features have important significance to the diagnosis of the disease.%目的:探讨原发中枢神经系统弥漫大B细胞淋巴瘤临床病理特征、诊断与鉴别诊断。方法:回顾性分析12例原发中枢神经系统弥漫大B细胞淋巴瘤患者临床资料、组织学病理形态及免疫组化结果。结果:12例患者平均年龄53.2岁,光镜下可见肿瘤细胞呈弥漫浸润性分布,与脑组织无明显分界,某些区域肿瘤细胞聚集在血管周围,呈袖套样结构,浸润和破坏血管壁。免疫组化示12例CD20、CD79а、PAX5和BCL-6均弥漫阳性,Ki-67增殖指数40%~90%;CD3、CD10、Mum-1、GFAP、S-100和CKpn均阴性。结论:原发中枢神经系统弥漫大B细胞淋巴瘤发病率低,临床无特异性,恶性程度高,正确掌握临床病理与免疫组化特征对该病的诊断具有重要意义。

  13. Comparative pathology in bivalves: Aetiological agents and disease processes.

    Carella, F; Feist, S W; Bignell, J P; De Vico, G

    2015-10-01

    Comparative pathology as a scientific discipline studies animal diseases in relation to their aetiology, pathogenesis and prognosis. Among the main aspects of this discipline, regressive changes, host defense responses with pathological implications and progressive changes, represent the majority of the possible responses of cells and tissues to pathogens and exposure to chemicals. One of the most persistent issues in the field of invertebrate pathology is the variability in terminology and definition, which has led to confusion in scientific communication. The aim of this paper is to provide an overview of the pathological basis of bivalve disease (defensive, regressive and progressive phenomena) and contribute to the standardised terminology for bivalve molluscan disease in the context of comparative pathology. PMID:26215472

  14. Pathological changes in the liver after allogeneic bone marrow stromal cells transplantation via percutaneous needle injection in patients with acute liver injury

    Objective: To observe the histopathological changes in the liver after transplanting allogeneic bone marrow stromal cells (BMSCs) into liver of acute liver injury (ALI) via percutaneous needle injection. Methods: BMSCs were derived from bone marrow obtained from femoral and tibial bones of male albino rabbits BMSCs were separated, grown, and propagated in culture for 3 weeks 58 syngeneic male rabbits were reduced liver injury with D-galactosamine 24 hours later. 5 mL (about 2×107 cell/mL) BMSCs or D-hanks solution were percutaneously injected into livers of BMSCs group (n=24) and control group (D-hanks solution group, n=34) respectively. The rabbits were killed at different time points (1 week, 2 week, 4 week) Histopathological changes and degrees of necrosis in the hepatic tissues were assessed by two histopathologists blinded to treated group and each other's results. Results: The degree of liver necrosis was decreased and the proliferation of hepatocytes was significantly stimulated in the BMSCs group compared to the D-hanks group; the histopathological scores of the 2 groups were statistically significant (P<0.001). Conclusion: The transplantation of BMSCs have a significant anti-injurious ability. (authors)

  15. 肾脏黏液性管状和梭形细胞癌4例报告%Clinical and pathological characteristics of renal mucinous tubular and spindle cell carcinoma

    王俊生; 林云华; 商建峰; 勇强; 姜永光

    2011-01-01

    目的 探讨肾脏黏液性管状和梭形细胞癌的临床病理特征.方法 回顾分析4例肾脏黏液性管状和梭形细胞癌患者的临床资料.女性3例,男性1例;年龄35~56岁,平均41岁;左肾2例,右肾2例;肾上极3例,肾下极1例;肿瘤直径3.5~6.5cm,平均5.5cm;无明显临床症状及体征,均为体检发现.B超检查提示,2例肾囊实性占位,为良性肿瘤;2例为厚壁型肾囊肿.CT检查提示,3例肾囊实性占位,为良性肿瘤;1例为厚壁型肾囊肿.2例行MRI检查提示,肾脏囊实性占位,为良性肿瘤.结果 4例患者均予手术治疗,术中发现肿块与肾组织的界限清楚,易分离;肿块呈囊实性,囊壁厚薄均匀,组织致密且内壁光滑.术后病理组织学检查示:2例为低度恶性上皮细胞肿瘤,1例为恶性肿瘤(透明细胞癌不排除),另1例为肾脏黏液性管状和梭形细胞癌.结论 肾脏黏液性管状和梭形细胞癌是一种具有良性肿瘤生长特性的低度恶性倾向的肿瘤.%Objective To explore the clinical and pathological characteristics of renal mucinous tubular and spindle cell carcinoma. Methods Clinical data of 4 patients including 3 female and 1 male aged from 35 to 56 were analyzed retrospectively. Among the 4 cases, two tumors were in the left side and two in right. Three tumors located in the upper part of kidneys, one in the lower part. The size of tumors ranged from 3.5 to 6.5 cm. There was no obvious symptom or physical sign in all cases and the tumors were detected during healthy examination. In B type untrasonography, two patients showed cystsolid tumor and two showed thick-wall cyst of kidney. In CT scan, three patients showed cystsolid tumor and one showed thick-wall cyst of kidney. In MRI scan, two patients showed cystsolid tumor. All the imaging examinations indicated the lump was benign. Results There were clear boundaries between the tumors and normal kidney tissue and the lesions were easy to be separated

  16. Carcinosarcoma of the Ureter with a Small Cell Component: Report of a Rare Pathologic Entity and Potential for Diagnostic Error on Biopsy

    Kent Newsom

    2014-01-01

    Full Text Available Carcinosarcomas of the ureter are rare biphasic neoplasms, composed of both malignant epithelial (carcinomatous and malignant mesenchymal (sarcomatous components. Carcinosarcomas of the urinary tract are exceedingly rare. We report a unique case of a carcinosarcoma of the ureter with a chondrosarcoma and small cell tumor component arising in a 68-year-old male who presented with microscopic hematuria. CT intravenous pyelogram revealed right-sided hydroureter and hydronephrosis with thickening and narrowing of the right ureter. The patient underwent robot-assisted ureterectomy with bladder cuff excision and subsequent adjuvant chemotherapy. The patient is disease-free at 32 months after treatment. We provide a brief synoptic review of carcinosarcoma of the ureter and bladder with utilization of immunohistochemical (IHC stains and potential diagnostic pitfalls.

  17. An update: improvements in imaging perfluorocarbon-mounted plant leaves with implications for studies of plant pathology, physiology, development and cell biology.

    George R Littlejohn

    2014-04-01

    Full Text Available Plant leaves are optically complex, which makes them difficult to image by light microscopy. Careful sample preparation is therefore required to enable researchers to maximise the information gained from advances in fluorescent protein labelling, cell dyes and innovations in microscope technologies and techniques. We have previously shown that mounting leaves in the non-toxic, non-fluorescent perfluorocarbon (PFC, perfluorodecalin (PFD enhances the optical properties of the leaf with minimal impact on physiology. Here, we assess the use of the perfluorocarbons PFD, and perfluoroperhydrophenanthrene (PP11 for in vivo plant leaf imaging using 4 advanced modes of microscopy: laser scanning confocal microscopy (LSCM, Two-photon fluorescence (TPF microscopy, second harmonic generation (SHG microscopy and stimulated Raman scattering (SRS microscopy. For every mode of imaging tested, we observed an improved signal when leaves were mounted in PFD or in PP11, compared to mounting the samples in water. Using an image analysis technique based on autocorrelation to quantitatively assess LSCM image deterioration with depth, we show that PP11 outperformed PFD as a mounting medium by enabling the acquisition of clearer images deeper into the tissue. In addition, we show that SRS microscopy can be used to image perfluorocarbons directly in the mesophyll and thereby easily delimit the negative space within a leaf, which may have important implications for studies of leaf development. Direct comparison of on and off resonance SRS micrographs show that PFCs do not to form intracellular aggregates in live plants. We conclude that the application of PFCs as mounting media substantially increases advanced microscopy image quality of living mesophyll and leaf vascular bundle cells.

  18. Telocyte implications in human pathology: An overview.

    Ibba-Manneschi, Lidia; Rosa, Irene; Manetti, Mirko

    2016-07-01

    Telocytes are a recently described interstitial cell population widely distributed in the stromal compartment of many organs in vertebrates, including humans. Owing to their close spatial relationship with multiple cell types, telocytes are universally considered as 'connecting cells' mostly committed to intercellular signaling by converting the interstitium into an integrated system that drives organ development and contributes to the maintenance of local tissue homeostasis. Increasing evidence indicates that telocytes may cooperate with tissue-resident stem cells to foster organ repair and regeneration, and that telocyte damage and dysfunction may occur in several disorders. The goal of this review is to provide an overview of the most recent findings concerning the implication of telocytes in a variety of pathologic conditions in humans, including heart disease, chronic inflammation and multiorgan fibrosis. Based on recent promising experimental data, there is realistic hope that by targeting telocytes alone or in tandem with stem cells, we might be able to promote organ regeneration and/or prevent irreversible end-stage organ damage in different pathologies. PMID:26805444

  19. Digital pathology and anatomic pathology laboratory information system integration to support digital pathology sign-out

    Huazhang Guo

    2016-01-01

    Full Text Available Background: The adoption of digital pathology offers benefits over labor-intensive, time-consuming, and error-prone manual processes. However, because most workflow and laboratory transactions are centered around the anatomical pathology laboratory information system (APLIS, adoption of digital pathology ideally requires integration with the APLIS. A digital pathology system (DPS integrated with the APLIS was recently implemented at our institution for diagnostic use. We demonstrate how such integration supports digital workflow to sign-out anatomical pathology cases. Methods: Workflow begins when pathology cases get accessioned into the APLIS (CoPathPlus. Glass slides from these cases are then digitized (Omnyx VL120 scanner and automatically uploaded into the DPS (Omnyx; Integrated Digital Pathology (IDP software v.1.3. The APLIS transmits case data to the DPS via a publishing web service. The DPS associates scanned images with the correct case using barcode labels on slides and information received from the APLIS. When pathologists remotely open a case in the DPS, additional information (e.g. gross pathology details, prior cases gets retrieved from the APLIS through a query web service. Results: Following validation of this integration, pathologists at our institution have signed out more than 1000 surgical pathology cases in a production environment. Integration between the APLIS and DPS enabled pathologists to review digital slides while simultaneously having access to pertinent case metadata. The introduction of a digital workflow eliminated costly manual tasks involving matching of glass slides and avoided delays waiting for glass slides to be delivered. Conclusion: Integrating the DPS and APLIS were instrumental for successfully implementing a digital solution at our institution for pathology sign-out. The integration streamlined our digital sign-out workflow, diminished the potential for human error related to matching slides, and

  20. Brain venous pathologies: MRI findings

    Purpose: To describe MRI findings of the different brain venous pathologies. Material and Methods: Between January 2002 and March 2004, 18 patients were studied 10 males and 8 females between 6 and 63 years old; with different brain venous pathologies. In all cases brain MRI were performed including morphological sequences with and without gadolinium injection and angiographic venous sequences. Results: 10 venous occlusions were found, 6 venous angiomas, and 2 presented varices secondary to arteriovenous dural fistula. Conclusion: Brain venous pathologies can appear in many different clinical contexts, with different prognosis and treatment. In all the cases brain MRI was the best imaging study to disclose typical morphologic abnormalities. (author)

  1. 老年人皮肤基底细胞癌的临床与病理特征研究%Clinical and pathology characteristic of skin basal cell carcinoma in the aged

    倪通; 黄方; 吴波

    2012-01-01

    目的 研究老年人皮肤基底细胞癌的临床及病理特征,提高对本病的认识及诊治水平. 方法 对174例老年人皮肤基底细胞癌病例临床特征、组织病理、误诊情况、治疗方法及预后等进行综合分析. 结果 本组患者病程长,平均(5±1.8)年,无明显发病诱因.头面部好发56.32%,多为单发(92.53%).临床表现以结节溃疡型93例(17.57%)、色素型31例(41.89%)、浅表型17例(22.97%)多见;病理分型以混合型63例(36.21%)、结节型42例(24.14%),浅表型37例(21.26%)多见.误诊64例(占36.78%),以混合色素型误诊最多;手术治疗效果好,预后佳. 结论 老年人基底细胞癌好发于头面部,其临床表现和组织病理学特征明显,手术治疗预后良好.%Objective To research clinical and pathology characteristics of skin basal cell carcinoma in the aged to improve recognitions and diagnosis of this disease. Methods Clinical features, tissue pathology,diagnostic errors, therapies and prognosis of 174 aged cases who undered skin basal cell carcinoma were analyzed. Results The course of disease was long, and the average time was 5 ± 1. 8 years. The inducements of them were not obvious. The skin lesion was most commom on head and face, 56. 32% , was single. Clinical manifestation of nodule and ulcer 93(17. 57% ) , pigment 31(41.89%), superficial 17 (22. 97% ) were common. Pathologyformas of mixde type 63 (36. 21 % ) , nodular type 42 (24. 14% ) and superficial type 37(21. 26% ) were commom. Misdiagnosis rate was 36. 78 percent, most was mixed pig-mented type, surgical treatment was preety goog, patients have good prognosis. Conclusions Skin basal cell carcinoma in advanced age always occurred on head and face, clinical manifestation and pathology characteristic of it were variety. Surgical treatment have good prognosis.

  2. Pathology of Perineural Spread.

    Brown, Ian S

    2016-04-01

    The perineural space is a compartment located between the nerve axons, supporting cells and tissues, and the epineural fibrous sheath. Tumor cells invade this space in response to a complex interplay of trophic factors in the local microenviroment. This attraction of tumor cells to nerves is referred to as neurotropism. The perineural space provides a conduit for tumor spread beyond the primary site of tumor occurrence. Perineural tumor growth is of two types: perineural invasion, affecting small unnamed nerves; and perineural spread, affecting larger, named nerves and presenting with clinical symptoms related to the involved nerve. Both forms of perineural tumor growth represent an adverse prognostic feature and are an essential element of the histopathologic reporting of malignancies of the head and neck region. Perineural spread is associated with decreased overall survival. Endoneurial invasion frequently accompanies perineural spread. The epineurium is more resistant to invasion and represents an important barrier to tumor spread. Immunohistochemical stains such as broad-spectrum keratin can aid in defining the proximal extent of perineural tumor spread. PMID:27123388

  3. Microscopic Disease Extension in Three Dimensions for Non–Small-Cell Lung Cancer: Development of a Prediction Model Using Pathology-Validated Positron Emission Tomography and Computed Tomography Features

    Purpose: One major uncertainty in radiotherapy planning of non–small-cell lung cancer concerns the definition of the clinical target volume (CTV), meant to cover potential microscopic disease extension (MDE) around the macroscopically visible tumor. The primary aim of this study was to establish pretreatment risk factors for the presence of MDE. The secondary aim was to establish the impact of these factors on the accuracy of positron emission tomography (PET) and computed tomography (CT) to assess the total tumor-bearing region at pathologic examination (CTVpath). Methods and Materials: 34 patients with non–small-cell lung cancer who underwent CT and PET before lobectomy were included. Specimens were examined microscopically for MDE. The gross tumor volume (GTV) on CT and PET (GTVCT and GTVPET, respectively) was compared with the GTV and the CTV at pathologic examination, tissue deformations being taken into account. Using multivariate logistic regression, image-based risk factors for the presence of MDE were identified, and a prediction model was developed based on these factors. Results: MDE was found in 17 of 34 patients (50%). The MDE did not exceed 26 mm in 90% of patients. In multivariate analysis, two parameters (mean CT tumor density and GTVCT) were significantly associated with MDE. The area under the curve of the two-parameter prediction model was 0.86. Thirteen tumors (38%, 95% CI: 24–55%) were identified as low risk for MDE, being potential candidates for reduced-intensity therapy around the GTV. In the low-risk group, the effective diameter of the GTVCT/PET accurately represented the CTVpath. In the high-risk group, GTVCT/PET underestimated the CTVpath with, on average, 19.2 and 26.7 mm, respectively. Conclusions: CT features have potential to predict the presence of MDE. Tumors identified as low risk of MDE show lower rates of disease around the GTV than do high-risk tumors. Both CT and PET accurately visualize the CTVpath in low-risk tumors

  4. Molecular characterization of the PK-LR gene in pyruvate kinase deficient Spanish patients. Red Cell Pathology Group of the Spanish Society of Haematology (AEHH).

    Zarza, R; Alvarez, R; Pujades, A; Nomdedeu, B; Carrera, A; Estella, J; Remacha, A; Sánchez, J M; Morey, M; Cortes, T; Pérez Lungmus, G; Bureo, E; Vives Corrons, J L

    1998-11-01

    The PK-LR gene has been studied in 12 unrelated patients with red cell pyruvate kinase deficiency and hereditary nonspherocytic haemolytic anaemia (CNSHA). The entire codifying region of the R-type PK gene and the flanking intronic regions were analysed by single-stranded conformation polymorphism (SSCP) followed by direct sequencing of abnormal DNA. 10 different mutations were identified in 22/24 alleles at risk. Eight of these were missense mutations that caused the following single amino acid changes: G514C (172Glu-Gln), G1010A (337Arg-Gln), G1015C (339Asp-Gln), T1070C (357Ile-Thr), C1223T (408Thr-Ile), G1291A (431Ala-Thr), C1456T (486Arg-Trp) and G1595A (532Arg-Gln). Two were nonsense mutations: G721T (241Glu-Stop) and C1675T (559Arg-Stop). 7/22 alleles demonstrated the same C1456 --> T mutation. The study of the polymorphic site at nucleotide (nt) 1705 performed in all cases disclosed a 1705 C/C mutation in 10 and a 1705 A/C mutation in three. This is the first report on the presence of several different L-type PK gene mutations within Spanish population. Furthermore, from the PK gene mutations found, six were unique and not previously described (1015C, 1070C, 1223T, 1291A, 1595A and 1675T) and one (C1456T) seems to be predominant in Spain. Interestingly, no case with the 1529A mutation commonly found in Northern European populations was present here. PMID:9827908

  5. Experimental infection of commercial layers with wild or attenuated Salmonella Gallinarum mutant strains: anatomic pathology, total blood cell count and serum protein levels

    KO Garcia

    2013-06-01

    Full Text Available The aim of the present study was to comparatively evaluate hemogram, blood serum components and anatomopathologic alterations in commercial layers experimentally challenged with an attenuated vaccine candidate strain (SG∆cobS∆cbiA and other two pathogenic strains (SGDcobS and SGNalr of Gallinarum (SG. In total, 280 commercial layers were randomly divided into 4 groups (G1, G2, G3 and G4. At five days of age, birds from groups G1 received approximately 107 colony forming units (CFU of SGDcobS; meanwhile birds from group G2 and G3 received the same dose of SGNalr and SG∆cobS∆cbiA, respectively. Birds from G4 were not infected. At 24 hours before (DBI and 24 hours after (1 DAI, and three (3 DAI, five (5 DAI, seven (7 DAI ten (10 DAI, and fifteen (15 DAI days after the infection, 10 birds of each group were humanely killed and blood samples collected to hematological and serum tests. Samples of liver, spleen, thymus, bursa of Fabricius, kidney and heart were also collected for the histological examination. Birds inoculated with SGDcobS and SGNalr showed similar alterations in hemogram, blood serum components and anatomopathologic exams. On the other hand, the exams of birds inoculated with SG∆cobS∆cbiA strain were similar to those of the uninfected birds. However, changes could be noticed in levels of uric acid and cholesterol during the course of the infection of birds from G3. Decrease in levels of light IgG 3 DAI was also observed in birds from this group. Pyknosis in kidney cells was a microscopic alteration found in birds from G3. Further studies must be done to verify if these alterations will not interfere in the performance of the vaccinate birds with SG∆cobS∆cbiA strain.

  6. Value of clusterin expression in pathologic diagnosis and histogenesis of giant cell tumor of tendon sheath%腱鞘巨细胞瘤clusterin表达对病理诊断和组织发生的意义

    汤莉; 周隽; 蒋智铭; 张惠箴; 刘亮; 陈杰

    2012-01-01

    Objective Analyze the immunophenotype of the different cells in the various subtypes of giant cell tumor of tendon sheath (GCTS) and investigate the value of clusterin in pathological diagnosis and histogenesis of giant cell tumor of tendon sheath.Methods A total of 104 cases of GCTS from the surgical pathology files of Shanghai Jiaotong university affiliated the sixth people's hospital were identified.Immunohistochemistry (IHC) for clusterin,desmin,CD163,CD68,p63,p53,Ki-67 and CD35 was performed on all cases,using EnVision technique.Results All cases of GCTS were researched,including 44 cases of localized type ( L-GCTS ),32 cases of diffused type ( D-GCTS ),26 cases of pigmented villonodular synovitis (PVNS) and 2 cases of malignant type.There was a slight female predominance in all these subtypes,and the male to female ratio was about 38:66. L-GCTS usually occured within the small joints(90.9%,40/44),while D-GCTS,PVNS and M-GCTS commonly occured within the large weightbearing joints [68.8% (22/32),100% (26/26) and 2/2 respectively].Of 74 cases with follow-up,the recurrence rates of L-GCTS,D-GCTS,PVNS and M-GCTS respectively were 30.3% (10/33),30.4%(7/23),18.8% (3/16) and 2/2.The different subtypes of GCTS had the same cell components,including the large synovial-like mononuclear cells,the small histiocytoid cells,foamy histiocytes cells,inflammatory cells,fibroblasts and the osteoclast-like multinucleated giant cells.There were obvious differences among immunophenotype of the various cell components in GCTS:the large synovial-like mononuclear cells were strong positive for clusterin,partly positive for desmin and Ki-67,and negative for CD163. The small histiocytoid cells were strong positive for CD163 but negative for clusterin and desmin.The osteoclast-like multinucleated giant cells were strong positive for CD68 but negative for clusterin,CD163 and desmin.Normal synoviocytes were strong positive for clusterin,partly positive for desmin.The number of

  7. Digital photography in anatomical pathology

    Leong F; Leong A

    2004-01-01

    Digital imaging has made major inroads into the routine practice of anatomical pathology and replaces photographic prints and Kodachromes for reporting and conference purposes. More advanced systems coupled to computers allow greater versatility and speed of turnaround as well as lower costs of incorporating macroscopic and microscopic pictures into pathology reports and publications. Digital images allow transmission to remote sites via the Internet for consultation, quality assurance and ed...

  8. Development of pathology in Turkey

    Gökhan GEDİKOĞLU

    2007-05-01

    Full Text Available Autospy is an important tool for the development of pathology as a science. In western civilisation dissection of human body became widespread with Renaissance, in contrast in the Ottoman Empire first dissection was not performed until the 19th century. Mustafa Behçet Efendi, head physician of the Empire, was one of the Ottoman physician who suggested the importance of dissection in the medical education. The first dissection was however performed by Charles Ambroise Bernard, a foreign physician who had been invited to help establishing a new medical school; “Mekteb-i Tıbbiye-i Adliye-i Şâhâne”, in 1843. The first modern medical schools called “Tıphane” and “Cerrahhane-i Amire” which were founded in 1827, did not have pathology courses. Pathology courses began in “Mekteb-i Tıbbiye-i Adliyei Şâhâne”. Dr. Hamdi Suat (Aknar, educated in anatomic pathology in Germany, was the first pathologist who established the modern pathology in Turkey in “İstanbul Darülfünun” medical school. In 1933 “Darülfünün” was closed and İstanbul University was built and the “University Reform Commission” invited many scientists escaping from Nazi government to study in İstanbul University. Dr. Philipp Schwartz had an important role both in the invitation of these scientists and establishment of the pathology department in İstanbul University. Practical courses were increased, clinicopathologic courses were organized for the first time and a lot of autopsies were performed, as high as 1000 autopsy per year, by Dr. Philipp Schwartz. More progress has takes place in Turkey over the years since pathology was first established. Today Turkey has many pathology departments which keep up with the worldwide advances in the field.

  9. Pathological features and origin of primary pineal mixed germ cell tumors%原发性松果体区混合性生殖细胞肿瘤病理特点及其起源探讨

    肖罡; 方陆雄; 邱炳辉; 漆松涛

    2011-01-01

    目的 通过影像学表现、术中所见及病理成分探讨松果体区混合性生殖细胞肿瘤的起源.方法 回顾分析我院2000年1月致2010年9月间经术后病理证实的15例松果体区混合性生殖细胞肿瘤的术前影像学表现和病理标本.结果 影像学表现,12例存在钙化,10例含有囊变,5例含有脂质.矢状位类圆或类椭圆状6例,边缘均较光滑,不规则形状9例,边缘多突起;术中所见,所有肿瘤均位于大脑大静脉蛛网膜袖套包绕形成的松果体隐窝内;病理成分,13例含有生殖细胞成分,9例含有畸胎瘤成分,4例含有胚胎性癌成分,3例含有绒癌成分,7例含有卵黄囊瘤成分,3例含有横纹肌瘤成分.在7例标本边缘发现牛殖细胞瘤,10例患者生殖细胞瘤成分与其余成分相互穿插或被其它成分包绕.结论 松果体区混合性生殖细胞肿瘤起源于松果体周围残余生殖细胞,其极有可能来自单一的原始生殖细胞.%To investigate the origin of mixed germ cell tumors in the pineal region based on the image data,surgical findings and pathological examination of the tumor. Methods The preoperative CT and magnetic resonance imaging (MRI) findings and tumor specimens were retrospectively analyzed in 15 cases of pineal mixed germ cell tumors confirmed by postoperative histological examination between January 2000 and September 2010. Results Radiographic examination of the tumor revealed calcification in 12 cases, cystic changes in 10 cases, and the presence of lipid in 5 cases. On the anteroposterior images, the tumors appeared round or elliptic with smooth edge in 6 cases,and showed irregular shape with multiple processes on the edge in 9 cases. Surgical exploration found all the tumors located in the the suprapineal recess enclosed by the arachnoidal envelope of the Galen vein. Pathologically, 13 specimens contained germinoma component, 9 contained teratoma component, 4 had embryonic carcinoma component, 3 had

  10. 混合性生殖细胞瘤的64层螺旋CT诊断及病理表现%Diagnosis of mixed germ cell tumor by 64-slice spiral CT and pathological manifestations

    朱刚明; 谭琦碹; 钟胜; 李兆勇; 付东

    2011-01-01

    目的:探讨64层螺旋CT对混合性生殖细胞瘤的诊断价值.方法:回顾性分析7例经病理证实的混合性生殖细胞瘤的CT平扫及两期增强表现、病理标本及切片特征.结果:7例病灶3例位于卵巢,3例位于前纵隔.1例位于睾丸;其中3例边界清楚;各病灶密度不均匀,内见囊变、坏死区,1例可见脂肪及钙化:增强扫描静脉期较动脉期强化明显,均呈不均匀强化.病理结果2例卵黄囊瘤与成熟畸胎瘸混合型.2例卵黄囊瘤与未成熟畸胎瘤混合型.1例卵黄囊瘤、胚胎性癌、畸胎瘤混合型,1例绒癌与无性细胞癌混合型,1例精原细胞瘤、胚胎性癌、滋养细胞成分混合型.结论:64层螺旋CT对混合性生殖细胞瘤的诊断虽无特异性,但在一定程度上为肿瘤良恶性判断、临床分期提供十分重要的依据.%Objective:To investigate the diagnostic value of mixed germ cell tumor by 64 -slice spiral CT. Methods: The plain CT and two-phase enhanced CT scanning and pathological specimens of 7 cases of the tumor confirmed by pathology were retrospectively studied. Results: 3 cases were found in ovarian and 3 cases in anterior mediastinum and 1 case in testis. 3 lesions were clear boundary, with fat and calcification in 1 lesion. All the lesions were uneven density and the cystic or necrotic area could be found. Venous phase enhancement was significantly higher than other phase, showed inhomogc-neous enhance. Pathological findings: induded 2 cases of yolk sac tumor and mature teratoma mixed. 2 cases of yolk sac tumor and immature teratoma mixed, 1 case of yolk sac tumor embryonal carcinoma and teratoma mixed. 1 case of chorio-carcinoma and asexual cell carcinoma mixed, and 1 case of seminoma embryonal carcinoma and trophoblastic ingredients mixed. Conclusion: Although there is no specific by 64-slice spiral CT. To a certain degree.it can determine the benign or malignant tumor and give the important prop for clinical staging.

  11. Rap1 integrates tissue polarity, lumen formation, and tumorigenicpotential in human breast epithelial cells

    Itoh, Masahiko; Nelson, Celeste M.; Myers, Connie A.; Bissell,Mina J.

    2006-09-29

    Maintenance of apico-basal polarity in normal breast epithelial acini requires a balance between cell proliferation, cell death, and proper cell-cell and cell-extracellular matrix signaling. Aberrations in any of these processes can disrupt tissue architecture and initiate tumor formation. Here we show that the small GTPase Rap1 is a crucial element in organizing acinar structure and inducing lumen formation. Rap1 activity in malignant HMT-3522 T4-2 cells is appreciably higher than in S1 cells, their non-malignant counterparts. Expression of dominant-negative Rap1 resulted in phenotypic reversion of T4-2 cells, led to formation of acinar structures with correct apico-basal polarity, and dramatically reduced tumor incidence despite the persistence of genomic abnormalities. The resulting acini contained prominent central lumina not observed when other reverting agents were used. Conversely, expression of dominant-active Rap1 in T4-2 cells inhibited phenotypic reversion and led to increased invasiveness and tumorigenicity. Thus, Rap1 acts as a central regulator of breast architecture, with normal levels of activation instructing apical polarity during acinar morphogenesis, and increased activation inducing tumor formation and progression to malignancy.

  12. MRI and pathologic correlation of cardiac myxomas

    Objective: To investigate the MRI features of cardiac myxoma by correlated with its pathological findings. Methods: MRI features of 22 cases of pathologically confirmed cardiac myxomas were retrospectively reviewed. Results: Of 22 cases, 21 are solitary, 12 located in left atrium, 6 located in right atrium, 2 located in left ventricle and 1 located in fight ventricle. The other one occupied multiple chambers. MRI: 19 are heterogeneous and 3 are homogeneous. Cine-MRI: 18 attach to the endocardium with a pedunculated stalk and 4 are sessile and with a broad attachment. Thirteen cases had secondary valve insufficience or stenosis. Nine have compromised cardiac function. Nineteen cases demonstrated mild to moderate heterogeneous enhancement after Gd-DTPA administration and 3 case showed no enhancement. Four cases had gadolinium first-pass perfusion study and showed a slow and continuous increasing time-intensity, lower than normal myocardium. The pedicles and wall showed delay enhancement. Pathologic findings: 21 are oval and lobular configuration, 1 is grape-like. Ten cases had fresh hemorrhage and 5 had chronic hemorrhage. Fourteen had necrosis, 2 had cystic change and 4 had calcification. Blood vessels or inflammatory cells could be detected in 19 cases. Conclusions: MRI can evaluate the size, location, morphology, especially the vascularity, histologic features and cardiac function of cardiac myxomas. (authors)

  13. Automated cellular pathology in noninvasive confocal microscopy

    Ting, Monica; Krueger, James; Gareau, Daniel

    2014-03-01

    A computer algorithm was developed to automatically identify and count melanocytes and keratinocytes in 3D reflectance confocal microscopy (RCM) images of the skin. Computerized pathology increases our understanding and enables prevention of superficial spreading melanoma (SSM). Machine learning involved looking at the images to measure the size of cells through a 2-D Fourier transform and developing an appropriate mask with the erf() function to model the cells. Implementation involved processing the images to identify cells whose image segments provided the least difference when subtracted from the mask. With further simplification of the algorithm, the program may be directly implemented on the RCM images to indicate the presence of keratinocytes in seconds and to quantify the keratinocytes size in the en face plane as a function of depth. Using this system, the algorithm can identify any irregularities in maturation and differentiation of keratinocytes, thereby signaling the possible presence of cancer.

  14. CLINICO - PATHOLOGICAL STUDY OF CARCINOMA OF PENIS

    Sarada

    2015-05-01

    Full Text Available Carcinoma of penis is a tumor with devastating psycho sexual repercussions on the patient . It was reported from different parts of the world with wide variation in incidence . Several factors were considered as inducing agents for cancer of penis . A clinic - pathological study is undertaken to find the incidence , the probable causative factors and the possible treatment methods that can be adapted . Preputial hygiene seems to be an important factor in preventing carcinoma penis . All the cases were of squamous cell carcinoma . Patients are coming for treatment in advanced stage of disease due to lack of awareness about the condition , becoming ineligible for modern conservative surgeries .

  15. The Pathology of Acute Liver Failure.

    Lefkowitch, Jay H

    2016-05-01

    Acute liver failure (ALF) is a rare and severe liver disease that usually develops in 8 weeks or less in individuals without preexisting liver disease. Its chief causes worldwide are hepatitis virus infections (hepatitis A, B, and E) and drug hepatotoxicity (particularly intentional or unintentional acetaminophen toxicity). Massive hepatic necrosis is often seen in liver specimens in ALF and features marked loss of hepatocytes, variable degrees of inflammation, and a stereotypic proliferation of bile ductular structures (neocholangioles) derived from activated periportal hepatic progenitor cells. This paper reviews the liver pathology in ALF, including forms of zonal necrosis and their etiologies. PMID:27058243

  16. Mouse pancreas tissue slice culture facilitates long-term studies of exocrine and endocrine cell physiology in situ.

    Anja Marciniak

    Full Text Available Studies on pancreatic cell physiology rely on the investigation of exocrine and endocrine cells in vitro. Particularly, in the case of the exocrine tissue these studies have suffered from a reduced functional viability of acinar cells in culture. As a result not only investigations on dispersed acinar cells and isolated acini were limited in their potential, but also prolonged studies on pancreatic exocrine and endocrine cells in an intact pancreatic tissue environment were unfeasible. To overcome these limitations, we aimed to establish a pancreas tissue slice culture platform to allow long-term studies on exocrine and endocrine cells in the intact pancreatic environment. Mouse pancreas tissue slice morphology was assessed to determine optimal long-term culture settings for intact pancreatic tissue. Utilizing optimized culture conditions, cell specificity and function of exocrine acinar cells and endocrine beta cells were characterized over a culture period of 7 days. We found pancreas tissue slices cultured under optimized conditions to have intact tissue specific morphology for the entire culture period. Amylase positive intact acini were present at all time points of culture and acinar cells displayed a typical strong cell polarity. Amylase release from pancreas tissue slices decreased during culture, but maintained the characteristic bell-shaped dose-response curve to increasing caerulein concentrations and a ca. 4-fold maximal over basal release. Additionally, endocrine beta cell viability and function was well preserved until the end of the observation period. Our results show that the tissue slice culture platform provides unprecedented maintenance of pancreatic tissue specific morphology and function over a culture period for at least 4 days and in part even up to 1 week. This analytical advancement now allows mid -to long-term studies on the cell biology of pancreatic disorder pathogenesis and therapy in an intact surrounding in situ.

  17. [Pathology of the vitreomacular interface].

    Pop, Monica; Gheorghe, Alina

    2014-01-01

    Vitreous role in the pathophysiology of retinal diseases has increased importantly over the recent years. This was possible using Optical Coherence Tomography which reviewed the way the vitreoretinal interface should be looked at and defined and classified new pathologies such as Vitreoretinal Traction Syndrome. Vitreous is not an empty space but an important anatomical structure with role in ocular physiology. With age biochemical changes occur so that vitreous starts to liquefy. Once the vitreous is liquefied (sinchisis) it collapses and passes in the retrohialoid space (sineresis). In complete PVD besides sinchisis there is a weakness of the adherence between the posterior cortex and ILM with total detachment of posterior cortex. Abnormal adhesions are associated with incomplete PVD. The definition and understanting of vitreoretinal pathology is an active and continuous process, PVD being the trigger of a lot of retinal pathologies: epiretinal membrane, macular hole, tractional macular oedema, VMTS, myopic traction maculopathy, exacerbations of exudative ARMD. PMID:25300121

  18. Pathological study of 130 cases of nonalcoholic fatty liver disease based on NASH-CRN system

    ZHOU Guangde; ZHAO Jingmin; DING Xiaohui; PAN Deng; SUN Yanling; YANG Jianfa; ZHAO Yulai

    2007-01-01

    To summarize the pathological features of nonalcoholic liver disease(NAFLD)in China based on a histological scoring system for NAFLD designed by the Pathology Committee of NASH Clinical Research Network(NASHCRN),the specimens of liver needle biopsies from 130 patients with NAFLD were histopathologically analyzed by haematoxylin eosin,reticular fiber and Masson trichrome stain.Immunohistochemistry staining was used to exclude non-NAFLD cases combined with clinical data.Hepatic steatosis,lobular inflammation,hepatocytic ballooning and fibrosis were presented widespread in NAFLD liver tissues.Furthermore,macrovesicular steatosis predominantly located in acinar zone 3 was the main histologic feature of NAFLD and lobular inflammation was usually presented mildly.Hepatocyte ballooning was observed in 94.6% of all 130 cases.Mild perisinusoidal fibrosis and periportal fibrosis were often observed in stage 1 cases.According to the statistic analysis,hepatic steatosis was positively correlated with lobular inflammation,hepatocytic ballooning and fibrosis (r=0.587,0.488,0.374,respectively,all P value<0.01).The number of microgranulomas,lipogranulomas and apoptotic bodies increased following severity of steatosis,lobular inflammation and fibrosis.Meanwhile,the number of megamitochondria and glycogen nuclei was paralleveled to the degree of hepatocytic ballooning(P value all<0.01).We suggest that the role of portal inflammation should be emphasized besides hepatic steatosis,lobular inflammation,hepatocyte ballooning and fibrosis in diagnosis and evaluation of NAFLD.It needs to be further verified whether microgranulomas,lipogranulomas and apoptosis bodies could be used as histopathological markers of development of NAFLD.The number of megamitochondria is more frequently be found in NAFLD,while in alcoholic liver diseases was Mallory bodies.

  19. Pharmacological Treatments in Pathological Gambling

    Grant, Jon E; Odlaug, Brian Lawrence; Schreiber, Liana R N

    2012-01-01

    AIMS: Pathological gambling (PG) is a relatively common and often disabling psychiatric condition characterized by intrusive urges to engage in deleterious gambling behavior. Although common and financially devastating to individuals and families, there currently exist no formally approved...... pharmacotherapeutic interventions for this disorder. This review seeks to examine the history of medication treatments for PG. METHODS: A systematic review of the 18 double-blind, placebo-controlled pharmacotherapy studies conducted for the treatment of pathological gambling was conducted. Study outcome and the mean...

  20. Effects of hyperprolactinemia on toxicological parameters and proliferation of islet cells in male rats.

    Ose, Keiko; Miyata, Kaori; Yoshioka, Kaoru; Okuno, Yasuyoshi

    2009-04-01

    Prolactin has a wide variety of biological effects. Consequences of hyperprolactinemia on islet B cell proliferation as well as general toxicological parameters were here examined using anterior pituitary-grafted rats. Three or six anterior pituitary glands were implanted under single renal capsules of F344 male rats and left there for 13 weeks afterward. Clinical observation along with measurement of body weight and food consumption was conducted during the observation period, and subsequently hematology, blood biochemistry, gross pathology, organ weights and histopathology were examined. In addition, the proliferation rate of islet B cells was measured by a 5-bromo-2'-deoxy-uridine (BrdU) labeling technique. Serum prolactin concentrations at week 13 were 36, 70, 75 and 105 ng/ml in the sham-operated, 3-pituitary-grafted groups from male or female donors, and 6-pituitary-grafted group from male donors, respectively. Higher cholinesterase and total cholesterol values, lower trigriceride and leutenizing hormones (LH) values, and higher adrenal weights compared to those in the sham-operated group were apparent in the 3- and/or 6-pituitary-grafted groups. Also, the study revealed that mammary gland structure was transformed with change of differentiation from a male to a female acinar pattern. Furthermore a specific increase of islet cell proliferation rate was found, positively correlated with serum prolactin concentration. These findings suggest that elevation of serum prolactin level over 13 weeks induces islet cell proliferation and changes in toxicological parameters, including cholinesterase activity, elements of lipid metabolism and histopathology/morphology of the adrenals and mammary glands in male rats. PMID:19336972

  1. Polarization of Calcium Signaling and Fluid Secretion in Salivary Gland Cells

    Ambudkar, I.S.

    2012-01-01

    The secretion of fluid, electrolytes, and protein by exocrine gland acinar cells is a vectorial process that requires the coordinated regulation of multiple channel and transporter proteins, signaling components, as well as mechanisms involved in vesicular fusion and water transport. Most critical in this is the regulation of cytosolic free [Ca2+] ([Ca2+]i) in response to neurotransmitter stimulation. Control of [Ca2+]i increase in specific regions of the cell is the main determinant of fluid...

  2. Contemporary minimally invasive therapeutics in the management of tissue pathologies

    Jerjes, W

    2015-01-01

    The aim of this thesis was to investigate and evaluate the effect of photodynamic therapy (PDT) in the management of tissue pathologies as well as the advances in photodynamic applications. Firstly, 5-ALA-PDT and mTHPC-PDT were applied in the management of superficial tissue disease. This includes oral dysplasia (147 patients), early stage oral squamous cell carcinoma (38 patients), actinic keratosis (62 patients), basal cell carcinoma (148 patients) and cutaneous squamous cell carcinoma (22 ...

  3. Physiological and pathological cardiac hypertrophy.

    Shimizu, Ippei; Minamino, Tohru

    2016-08-01

    The heart must continuously pump blood to supply the body with oxygen and nutrients. To maintain the high energy consumption required by this role, the heart is equipped with multiple complex biological systems that allow adaptation to changes of systemic demand. The processes of growth (hypertrophy), angiogenesis, and metabolic plasticity are critically involved in maintenance of cardiac homeostasis. Cardiac hypertrophy is classified as physiological when it is associated with normal cardiac function or as pathological when associated with cardiac dysfunction. Physiological hypertrophy of the heart occurs in response to normal growth of children or during pregnancy, as well as in athletes. In contrast, pathological hypertrophy is induced by factors such as prolonged and abnormal hemodynamic stress, due to hypertension, myocardial infarction etc. Pathological hypertrophy is associated with fibrosis, capillary rarefaction, increased production of pro-inflammatory cytokines, and cellular dysfunction (impairment of signaling, suppression of autophagy, and abnormal cardiomyocyte/non-cardiomyocyte interactions), as well as undesirable epigenetic changes, with these complex responses leading to maladaptive cardiac remodeling and heart failure. This review describes the key molecules and cellular responses involved in physiological/pathological cardiac hypertrophy. PMID:27262674

  4. Learning Biology with Plant Pathology.

    Carroll, Juliet E.

    This monograph contains 10 plant pathology experiments that were written to correspond to portions of a biology curriculum. Each experiment is suitable to a biology topic and designed to encourage exploration of those biological concepts being taught. Experiments include: (1) The Symptoms and Signs of Disease; (2) Koch's Postulates; (3)…

  5. Telescoping phenomenon in pathological gambling

    Grant, Jon E; Odlaug, Brian Lawrence; Mooney, Marc E

    2012-01-01

    The course of pathological gambling (PG) in women has been described as having a later age of initiation but a shorter time to problematic gambling ("telescoped"). This study examined evidence for telescoping and its relationship with comorbidities. Seventy-one treatment-seeking individuals with PG...

  6. Chondroblastoma patella presenting as a pathological fracture

    Gudi Narayan

    2008-01-01

    Full Text Available A 24-year-old male presented with an inability to walk after a trivial fall. He had pain and mild swelling anterior to the right knee for the past one year. X-ray showed a transverse fracture of patella with a lytic lesion occupying most of the two halves of the patella. Fine needle aspiration cytology (FNAC of the lytic lesion revealed a few osteoclastic giant cells and occasional osteoblasts against a hemorrhagic background. Patellectomy was performed. Histology revealed trabecular bone admixed with proliferating chondroid tissue at places admixed with myxoid and fibrous tissue with focal areas of calcification suggestive of chondroblastoma. Focal areas showed osteoclastic giant cells with areas of hemorrhage. The purpose is to present a rare tumor occurring at an unusual site which presented as pathological fracture.

  7. Relação entre escore de Gleason e fatores prognósticos no adenocarcinoma acinar de próstata The relation between Gleason score and prognostic factors in acinar adenocarcinoma of prostate

    Eduardo Cambruzzi

    2010-02-01

    Full Text Available INTRODUÇÃO: O adenocarcinoma de próstata corresponde a uma das neoplasias malignas mais frequentes em homens, comprometendo principalmente da sexta a oitava décadas. Algumas características histopatológicas do tumor, como grau de diferenciação, invasão capsular e escore de Gleason, podem ser correlacionadas com o prognóstico da doença. OBJETIVOS: Estimar a associação entre o escore de Gleason e fatores prognósticos em casos de adenocarcinoma prostático. MATERIAL E MÉTODO: O estudo avaliou 118 espécimes de prostatectomia radical provenientes do Laboratório de Patologia da ULBRA entre 2003 e 2008. Em cada caso foram determinados os seguintes dados: idade, lateralidade, estadiamento, escore total e padrões primário e secundário de Gleason, grau de diferenciação, presença de invasão capsular, angiolinfática e perineural e extensão extraprostática. Foram usados os testes do qui-quadrado e o teste exato de Fischer para verificar a associação entre as variáveis, considerando um nível de significância menor que 5%. RESULTADOS: A idade média correspondeu a 63,86 anos. Observou-se a predominância do escore 6 de Gleason (55 casos - 46,61%, de bilateralidade (72 casos - 61,02% e do estádio T2c (57 casos - 48,31%. O escore de Gleason esteve associado a idade (0,001, lateralidade (p INTRODUCTION: The prostate adenocarcinoma corresponds to one of the most frequent malignant neoplasias affecting 60 to 80 year old men. Some histopathological characteristics of the tumor, such as degree of differentiation, capsular invasion and Gleason score, may be correlated with the prognosis of the disease. OBJECTIVES: To assess the association of Gleason score and prognostic factors in cases of prostatic adenocarcinoma. MATERIAL AND METHOD: The study evaluated one hundred and eighteen specimens of radical prostatectomy from the laboratory of pathology of ULBRA between 2003 and 2008. In each case, the following data were recorded: age

  8. A multifunctional 3D co-culture system for studies of mammary tissue morphogenesis and stem cell biology.

    Jonathan J Campbell

    Full Text Available Studies on the stem cell niche and the efficacy of cancer therapeutics require complex multicellular structures and interactions between different cell types and extracellular matrix (ECM in three dimensional (3D space. We have engineered a 3D in vitro model of mammary gland that encompasses a defined, porous collagen/hyaluronic acid (HA scaffold forming a physiologically relevant foundation for epithelial and adipocyte co-culture. Polarized ductal and acinar structures form within this scaffold recapitulating normal tissue morphology in the absence of reconstituted basement membrane (rBM hydrogel. Furthermore, organoid developmental outcome can be controlled by the ratio of collagen to HA, with a higher HA concentration favouring acinar morphological development. Importantly, this culture system recapitulates the stem cell niche as primary mammary stem cells form complex organoids, emphasising the utility of this approach for developmental and tumorigenic studies using genetically altered animals or human biopsy material, and for screening cancer therapeutics for personalised medicine.

  9. Role of mitochondria in parvovirus pathology.

    Jonna Nykky

    Full Text Available Proper functioning of the mitochondria is crucial for the survival of the cell. Viruses are able to interfere with mitochondrial functions as they infect the host cell. Parvoviruses are known to induce apoptosis in infected cells, but the role of the mitochondria in parvovirus induced cytopathy is only partially known. Here we demonstrate with confocal and electron microscopy that canine parvovirus (CPV associated with the mitochondrial outer membrane from the onset of infection. During viral entry a transient depolarization of the mitochondrial transmembrane potential and increase in ROS level was detected. Subsequently, mitochondrial homeostasis was normalized shortly, as detected by repolarization of the mitochondrial membrane and decrease of ROS. Indeed, activation of cell survival signalling through ERK1/2 cascade was observed early in CPV infected cells. At 12 hours post infection, concurrent with the expression of viral non-structural protein 1, damage to the mitochondrial structure and depolarization of its membrane were apparent. Results of this study provide additional insight of parvovirus pathology and also more general information of virus-mitochondria association.

  10. Quality in pathology laboratory practice.

    Weinstein, S

    1995-06-01

    Quality refers not only to analytical quality control, a traditional area of laboratory excellence, but to the entire science of quality management. As measures of quality, structural indicators refer to staffing and physical facilities, process indicators to the institutions operations and, perhaps most importantly, outcome indicators address the ultimate patient care uses that pathology information is put to. Comparison of performance to peer laboratories, external quality control, is a practical, if limited, yardstick of performance. Customer satisfaction and turn-around-time of tests are receiving more recent attention as quality measures. Blood banking, because of its inherently complex cycle from donor phlebotomy to product infusion, requires special considerations with regard to quality management. Reporting of anatomical pathology, where the only gold standard is a consensus of experts, also does not lend itself to classical numerical quality assessment. PMID:7670717

  11. Synovial pathology: Magnetic resonance study

    The synovial membrane lines the inner surface of the entire joint capsule of the so-called synovial, or diarthrosis, joints. It also constitutes the lining synovial bursa and tendon sheaths. It is lubricated at all these sites by the synovial fluid secreted by the membrane itself. The identification of this structure is bases on the correct knowledge of its anatomical locations. Synovial membrane pathology includes lesions produced by tumors, inflammation, degeneration and trauma. In this report, we classify them as benign (cysts, chondromatosis, pigmented villonodular synovitis, inflammatory synovitis and hemangioma) or malignant (synovial sarcoma and hemangiosarcoma). Magnetic resonance (MR) constitutes a useful and reliable method for diagnosis synovial lesions, providing a means of determining their origin and identifying distinctive features of some types. We present our experience in 12 cases of synovial pathology studied by MR over the past year, all of which were confirmed by histopathological study. 13 refs

  12. Radioisotope studies under pathologic conditions

    This article presents a general discussion on salivary pathology, before dealing with the various salivary gland diseases which can draw real advantage from radioisotope studies. Clinical problems related to the salivary glands first concern diffuse or focal glandular swelling. Focal swelling includes inflammatory or metastatic deposits in preauricular or submandibular lymph nodes, cysts, abscesses, foci of inflammation, benign and malignant neoplasms of the salivary glands themselves or of surrounding blood or lymph vessels, nerves, connective tissue, and oral mucosa. Primary tumors of the salivary glands are rare and usually benign. The combination of a systemic disease with dry mouth and dry eyes due to inflamed conjunctiva and cornea because of decreased fluid production, forms Sjogren syndrome. It may also cause diffuse glandular swelling. Chronic alcoholism, cirrhosis, diabetes mellitus, hyperlipoproteinemia, and malnutrition are other pathologic conditions sometimes associated with diffuse salivary gland swelling

  13. Diagnostic pathology in 2012: development of digital pathology in an open access journal

    Kayser Klaus

    2013-01-01

    Full Text Available Abstract Herein we describe and interpret the digital world of diagnostic surgical pathology, and take the in Pathology leading Open Access Journal Diagnostic Pathology as example. Virtual slide http://www.diagnosticpathology.diagnomx.eu/vs/1944221953867351

  14. Canine and feline oral pathology

    Costa, S.; Pais, B.; Almeida, D.; Simões, J.; Mega, A. C.; Vala, Helena

    2013-01-01

    The aim of this work was to present a brief review of the main conditions affecting the oral cavity of dogs and cats. In recent years there has been increased attention with regard to veterinary dentistry, being several and frequent the pathologies located in the oral cavity of our pets. These diseases mainly affect the teeth and the mucous membranes of the oral cavity, and may, in chronic cases, also affect vital organs. This condition could have different causes, including hereditary, conge...

  15. Insulin dysfunction and Tau pathology

    Emmanuel Planel

    2014-02-01

    Full Text Available The neuropathological hallmarks of Alzheimer's disease (AD include senile plaques of β-amyloid (Aβ peptides (a cleavage product of the Amyloid Precursor Protein, or APP and neurofibrillary tangles (NFT of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF. NFT pathology is important since it correlates with the degree of cognitive impairment in AD.Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99% is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease.Insulin dysfunction, manifested by diabetes mellitus (DM might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM and type 2 diabetes (T2DM are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment.Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting on Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia.

  16. Medical discourse in pathological anatomy.

    Moskalenko, R; Tatsenko, N; Romanyuk, A; Perelomova, O; Moskalenko, Yu

    2012-05-01

    The paper is devoted to the peculiarities of medical discourse in pathological anatomy as coherent speech and as a linguistic correlate of medical practice taking into account the analysis of its strategies and tactics. The purpose of the paper is to provide a multifaceted analysis of the speech strategies and tactics of pathological anatomy discourse and ways of their implementation. The main strategies of medical discourse in pathological anatomy are an anticipating strategy, a diagnosing strategy and an explaining one. The supporting strategies are pragmatic, conversational and a rhetorical one. The pragmatic strategy is implemented through contact establishing tactics, the conversational one - with the help of control tactics, the rhetorical one - with the help of attention correction tactics. The above mentioned tactics and strategies are used in the distinguishing of major, closely interrelated strategies: "the contact strategy" (to establish contact with a patient's relatives - phatic replicas of greeting and addressing) and "the strategy of explanation" (used in the practice of a pathologist for a detailed explanation of the reasons of a patient's death). The ethic aspect of speech conduct of a doctor-pathologist is analyzed. PMID:22870841

  17. Digital imaging in anatomic pathology.

    O'Brien, M J; Sotnikov, A V

    1996-10-01

    Advances in computer technology continue to bring new innovations to departments of anatomic pathology. This article briefly reviews the present status of digital optical imaging, and explores the directions that this technology may lead over the next several years. Technical requirements for digital microscopic and gross imaging, and the available options for image archival and retrieval are summarized. The advantages of digital images over conventional photography in the conference room, and the usefulness of digital imaging in the frozen section suite and gross room, as an adjunct to surgical signout and as a resource for training and education, are discussed. An approach to the future construction of digital histologic sections and the computer as microscope is described. The digital technologic applications that are now available as components of the surgical pathologist's workstation are enumerated. These include laboratory information systems, computerized voice recognition, and on-line or CD-based literature searching, texts and atlases and, in some departments, on-line image databases. The authors suggest that, in addition to these resources that are already available, tomorrow's surgical pathology workstation will include network-linked digital histologic databases, on-line software for image analysis and 3-D image enhancement, expert systems, and ultimately, advanced pattern recognition capabilities. In conclusion, the authors submit that digital optical imaging is likely to have a significant and positive impact on the future development of anatomic pathology. PMID:8853053

  18. Xanthogranulomatous Endometritis: An Unusual Pathological Entity Mimicking Endometrial Carcinoma

    Makkar, M; Gill, MK; Singh, DP

    2013-01-01

    Xanthogranulomatous endometritis is an unusual pathological entity mimicking endometrial carcinoma. This shows sheets of foamy histiocytes alongwith other inflammatory cells. We, hereby, report a case of 45 year multigravida female with irregular menstrual history, clinically diagnosed as carcinoma and histopathologically turned out as xanthogranulomatous endometritis. So, this condition should always be dealt with caution, and pathologists and clinicians should be aware of it.

  19. A Multifunctional 3D Co-Culture System for Studies of Mammary Tissue Morphogenesis and Stem Cell Biology

    Campbell, Jonathan J.; Davidenko, Natalia; Caffarel, Maria M.; Cameron, Ruth E.; Watson, Christine J

    2011-01-01

    Studies on the stem cell niche and the efficacy of cancer therapeutics require complex multicellular structures and interactions between different cell types and extracellular matrix (ECM) in three dimensional (3D) space. We have engineered a 3D in vitro model of mammary gland that encompasses a defined, porous collagen/hyaluronic acid (HA) scaffold forming a physiologically relevant foundation for epithelial and adipocyte co-culture. Polarized ductal and acinar structures form within this sc...

  20. Domoic Acid Toxicologic Pathology: A Review

    Olga M. Pulido

    2008-05-01

    Full Text Available Domoic acid was identified as the toxin responsible for an outbreak of human poisoning that occurred in Canada in 1987 following consumption of contaminated blue mussels [Mytilus edulis]. The poisoning was characterized by a constellation of clinical symptoms and signs. Among the most prominent features described was memory impairment which led to the name Amnesic Shellfish Poisoning [ASP]. Domoic acid is produced by certain marine organisms, such as the red alga Chondria armata and planktonic diatom of the genus Pseudo-nitzschia. Since 1987, monitoring programs have been successful in preventing other human incidents of ASP. However, there are documented cases of domoic acid intoxication in wild animals and outbreaks of coastal water contamination in many regions world-wide. Hence domoic acid continues to pose a global risk to the health and safety of humans and wildlife. Several mechanisms have been implicated as mediators for the effects of domoic acid. Of particular importance is the role played by glutamate receptors as mediators of excitatory neurotransmission and the demonstration of a wide distribution of these receptors outside the central nervous system, prompting the attention to other tissues as potential target sites. The aim of this document is to provide a comprehensive review of ASP, DOM induced pathology including ultrastructural changes associated to subchronic oral exposure, and discussion of key proposed mechanisms of cell/tissue injury involved in DOM induced brain pathology and considerations relevant to food safety and human health.

  1. Domoic acid toxicologic pathology: a review.

    Pulido, Olga M

    2008-01-01

    Domoic acid was identified as the toxin responsible for an outbreak of human poisoning that occurred in Canada in 1987 following consumption of contaminated blue mussels [Mytilus edulis]. The poisoning was characterized by a constellation of clinical symptoms and signs. Among the most prominent features described was memory impairment which led to the name Amnesic Shellfish Poisoning [ASP]. Domoic acid is produced by certain marine organisms, such as the red alga Chondria armata and planktonic diatom of the genus Pseudo-nitzschia. Since 1987, monitoring programs have been successful in preventing other human incidents of ASP. However, there are documented cases of domoic acid intoxication in wild animals and outbreaks of coastal water contamination in many regions world-wide. Hence domoic acid continues to pose a global risk to the health and safety of humans and wildlife. Several mechanisms have been implicated as mediators for the effects of domoic acid. Of particular importance is the role played by glutamate receptors as mediators of excitatory neurotransmission and the demonstration of a wide distribution of these receptors outside the central nervous system, prompting the attention to other tissues as potential target sites. The aim of this document is to provide a comprehensive review of ASP, DOM induced pathology including ultrastructural changes associated to subchronic oral exposure, and discussion of key proposed mechanisms of cell/tissue injury involved in DOM induced brain pathology and considerations relevant to food safety and human health. PMID:18728725

  2. Analysis on Features of Clinical Pathology in 13 Cases with Multilocular Cystic Renal Cell Carcinoma%13例多房性囊性肾细胞癌的临床病理特点分析

    马进; 宋新兰; 王路祎; 孙振柱

    2015-01-01

    目的:探讨多房性囊性肾细胞癌(MCRCC)的临床病理特点。方法收集13例MCRCC的资料,进行临床特点,形态学和免疫组织化学比较。结果13例患者中男性9例,女性4例,男女比例2.25:1。患病年龄26-68岁,平均年龄47.2岁。临床上多为偶然或体检发现,偶有腰痛症状。形态学检查:肿瘤最大径1.7-6cm,囊性或局灶实性,境界清楚,切面均呈多房性或蜂窝状,部分囊内含灰黄色或血性液体。镜下观察:囊腔大多衬覆单层肿瘤细胞,部分为多层,胞质透明、核小、未见明显核仁、Fuhrman核分级Ⅰ级,局灶囊内有小乳头结构。大多数病例中纤维间隔内可见与囊腔衬覆细胞类似的透明细胞团,多呈巢状。免疫组织化学染色:肿瘤细胞对免疫组化标记AE1/3,EMA,Vimetin均呈弥漫阳性表达,8例的CK7及10例的CD10肿瘤细胞呈阳性或局灶阳性,P504S有3例阳性或局灶阳性表达,CK20,CD117,CD163均呈阴性,Ki-67指数达1%-5%。P53中有11例阴性表达,2例有1%肿瘤细胞阳性表达。结论 MCRCC是一种少见的肾细胞癌组织学亚型,预后良好,免疫组化标记AE1/3,EMA,Vimetin,CK7,CK20,CD10等对其诊断及鉴别诊断有帮助。%Objective To investigate the clinicopathological features of multilocular cystic renal cell carcinoma (MCRCC), and to improve the clincopathological features of this disease. Methods 13 cases MCRCC data, clinical characteristics, pathological features and also immuniophenotype were collected. Results In 13 patients: 9 of them were males and 4 were females, the ratio is 2.25: 1. The prevalence o age was at a range of 26-68 years, mean age is 47.2 years. Mostly of them were found by incidental or only back pain symptoms occasionally. Morphological examination:maximum of tumors is at a range of 1.7-6cm. They were cystic or focal cystic solid, have a clear boundary. They showed as multilocular or honeycomb

  3. 骨髓干细胞移植后mdx鼠腓肠肌病理变化%Pathologic change in mdx mice gastrocnemius muscle after bone marrow stem cells transplantation

    卢锡林; 冯善伟; 姚晓黎; 张为西; 于美娟; 张成

    2008-01-01

    Objective To investigate the pathologic change in mdx mice gastrecnemius muscle after the bone marrow stem cells transplantation. Methods Twenty mdx mice (7 to 9 weeks old) preconditioned with 7 Gy γ-ray were divided into 4 groups and bone marrow stem ceils from C57 mice (6 to 8 weeks old) were injected intravenously into the mdx mice. Morphology and centrally nucleated fibers (CNF)were observed by HE stain and the rate of CNF was calculated 4 weeks ,8 weeks ,12 weeks and 16 weeks after transplantation respectively. Five C57 mice and 5 mdx mice were acted as positive and negative controls. Results The myocytes of normal C57 mice were polygon and uniform in size with nuclei localized in borderline. No inflammation was found in intraceilular substance. The myocytes of treated and untreated mdx mice were round in shape and various in size. The obvious abnormality was nucleus centralized. The rate of CNF in untreated mdx mice was highest, up to 70%. The rate of CNF decreased to 55%,50% and 44% at the 4th, 12th, 16th week after transplantation. Condusion CNF of mdx mice gastrecnemias muscle decreases gradually after bone marrow stem cells transplantation, which indicates that the bone marrow stem cells can participate in the repair and regeneration of the injured tissues permanently and constantly.%目的 研究骨髓干细胞移植后mdx鼠腓肠肌组织病理变化. 方法 7~9周龄mdx鼠20只平均分为4组,放射处理后移植1.2×107细胞/只同种异基因全骨髓干细胞,于移植后4、8、12及16周用HE染色观察腓肠肌组织细胞形态及核中心移位纤维(CNF).C57鼠和未治疗mdx鼠各5只作阳性和阴性对照. 结果 CS7鼠腓肠肌横切面可见肌细胞大小形态基本一致,无核中心移位现象.各细胞移植治疗组和阴性对照组mdx鼠均有大量的炎细胞浸润,核中心移位明显.未治疗mdx鼠CNF最高,约达70%;移植后4、12和16周,CNF分别为55%、50%和44%. 结论 骨髓干细胞移植后mdx鼠腓肠

  4. Pathological review of late cerebral radionecrosis

    Late cerebral radionecrosis may be considered to be a specific chronic inflammatory response, although it is unknown whether the initial damage by brain irradiation is to an endothelial cell or a glial cell. I discuss the pathological specificity of late cerebral radionecrosis by studying the published literature and a case that I experienced. In late cerebral radionecrosis, there are typical coagulation necrosis areas containing fibrinoid necrosis with occlusion of the lumina and poorly active inflammatory areas with many inflammatory ghost cells, focal perivascular lymphocytes, hyalinized vessels, and telangiectatic vascularization near and in the necrotic tissue, and more active inflammatory areas formed as a partial rim of the reactive zone by perivascular lymphocytes, much vascularization, and glial fibrillary acidic protein (GFAP)-positive astrocytes at the corticomedullary border adjacent to necrotic tissue in the white matter. It is difficult to believe that coagulation necrosis occurs without first disordering the vascular endothelial cells because fibrinoid necrosis is a main feature and a diffusely multiple lesion in late cerebral radionecrosis. Because various histological findings do develop, progress, and extend sporadically at different areas and times in the irradiated field of the brain for a long time after radiation, uncontrolled chronic inflammation containing various cytokine secretions may also play a key role in progression of this radionecrosis. Evaluation of the mechanism of the development/aggravation of late cerebral radionecrosis requires a further study for abnormal cytokine secretions and aberrant inflammatory reactions. (author)

  5. Extensive renovation the pathology of heritage building

    Rasmussen, Torben Valdbjørn

    2015-01-01

    The pathology of heritage buildings is often related to renovation initiatives typically initiated by implementing energy savings measures.......The pathology of heritage buildings is often related to renovation initiatives typically initiated by implementing energy savings measures....

  6. Extensive renovation the pathology of heritage buildings

    Rasmussen, Torben Valdbjørn

    2015-01-01

    The pathology of heritage buildings is often related to renovation initiatives typically initiated by implementing energy savings measures.......The pathology of heritage buildings is often related to renovation initiatives typically initiated by implementing energy savings measures....

  7. Personality dimensions and disorders in pathological gambling

    Odlaug, Brian Lawrence; Schreiber, Liana R N; Grant, Jon E

    2013-01-01

    This review presents the most current research in personality dimensions and disorders with respect to pathological gambling.......This review presents the most current research in personality dimensions and disorders with respect to pathological gambling....

  8. Metastatic non-small-cell lung cancer: consensus on pathology and molecular tests, first-line, second-line, and third-line therapy: 1st ESMO Consensus Conference in Lung Cancer; Lugano 2010

    Felip, E; Gridelli, C; Baas, P;

    2011-01-01

    The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21 and 22 May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics, medical oncology, surgical oncology and radiation oncology. Before the...

  9. Phytic acid as a potential treatment for Alzheimer's pathology: evidence from animal and in vitro models

    Thimmappa S. Anekonda; Wadsworth, Teri L.; Sabin, Robert; Frahler, Kate; Harris, Christopher; Petriko, Babett; Ralle, Martina; Woltjer, Randy; Joseph F. Quinn

    2011-01-01

    Alzheimer’s disease (AD) causes progressive age-dependent cortical and hippocampal dysfunctions leading to abnormal intellectual capacity and memory. We propose a novel protective treatment for AD pathology with phytic acid (inositol hexakisphosphate), a phytochemical found in food grains and a key signaling molecule in mammalian cells. We evaluated the protective and beneficial effects of phytic acid against amyloid beta pathology in MC65 cells and the Tg2576 mouse model. In MC65 cells, 48–7...

  10. Epicardial Fat: Physiological, Pathological, and Therapeutic Implications

    Salazar, Juan; Luzardo, Eliana; Mejías, José Carlos; Ferreira, Antonio; Rivas-Ríos, José Ramón; Bermúdez, Valmore

    2016-01-01

    Epicardial fat is closely related to blood supply vessels, both anatomically and functionally, which is why any change in this adipose tissue's behavior is considered a potential risk factor for cardiovascular disease development. When proinflammatory adipokines are released from the epicardial fat, this can lead to a decrease in insulin sensitivity, low adiponectin production, and an increased proliferation of vascular smooth muscle cells. These adipokines move from one compartment to another by either transcellular passing or diffusion, thus having the ability to regulate cardiac muscle activity, a phenomenon called vasocrine regulation. The participation of these adipokines generates a state of persistent vasoconstriction, increased stiffness, and weakening of the coronary wall, consequently contributing to the formation of atherosclerotic plaques. Therefore, epicardial adipose tissue thickening should be considered a risk factor in the development of cardiovascular disease, a potential therapeutic target for cardiovascular pathology and a molecular point of contact for “endocrine-cardiology.” PMID:27213076

  11. The sonographic findings of the scrotal pathology

    Clinical differentiation of the various pathological conditions affecting scrotal contents can be difficult. The superficial location of scrotum is suited for sonographic examination. March, 1984 to december, 1987 authors experienced 23 cases of the inflammatory and tumorous condition, which were confirmed by operation and clinical follow up. The results are as follows : 1. Sonographic examination is safe, noninvasive, and useful in screening test of scrotum. 2. Sonography is useful for the confirmation of complicated epididymitis. 3. In palpable mass cases, sonography can differentiate intratesticular and extratesticular lesions. 4. Sonography is useful for detection of primary tumor in clinically uncertain conditions. 5. In epididymitis, sonography shows enlargement and decreased echogenecity of epididymis, reactive hydrocele, and thickening of scrotal wall. 6. In testicular tumor : Seminoma shows hypoechoic solid mass lesion with enlargement. Embryonal cell carcinoma shows ill defined hypoechoic testicular enlargement. Rhabdomyosarcoma shows ill defined hypoechoic mass with central necrosis. Metastatic testicular tumor shows bilaterallity and ill defined abnormal echogenecity, more older age distribution

  12. Pathological Plasticity in Fragile X Syndrome

    Brandon S. Martin

    2012-01-01

    Full Text Available Deficits in neuronal plasticity are common hallmarks of many neurodevelopmental disorders. In the case of fragile-X syndrome (FXS, disruption in the function of a single gene, FMR1, results in a variety of neurological consequences directly related to problems with the development, maintenance, and capacity of plastic neuronal networks. In this paper, we discuss current research illustrating the mechanisms underlying plasticity deficits in FXS. These processes include synaptic, cell intrinsic, and homeostatic mechanisms both dependent on and independent of abnormal metabotropic glutamate receptor transmission. We place particular emphasis on how identified deficits may play a role in developmental critical periods to produce neuronal networks with permanently decreased capacity to dynamically respond to changes in activity central to learning, memory, and cognition in patients with FXS. Characterizing early developmental deficits in plasticity is fundamental to develop therapies that not only treat symptoms but also minimize the developmental pathology of the disease.

  13. 42 CFR 493.853 - Condition: Pathology.

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Pathology. 493.853 Section 493.853 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.853 Condition: Pathology. The specialty of pathology includes, for purposes...

  14. Stem Cell-Soluble Signals Enhance Multilumen Formation in SMG Cell Clusters.

    Maruyama, C L M; Leigh, N J; Nelson, J W; McCall, A D; Mellas, R E; Lei, P; Andreadis, S T; Baker, O J

    2015-11-01

    Saliva plays a major role in maintaining oral health. Patients with salivary hypofunction exhibit difficulty in chewing and swallowing foods, tooth decay, periodontal disease, and microbial infections. At this time, treatments for hyposalivation are limited to medications (e.g., muscarinic receptor agonists: pilocarpine and cevimeline) that induce saliva secretion from residual acinar cells as well as artificial salivary substitutes. Therefore, advancement of restorative treatments is necessary to improve the quality of life in these patients. Our previous studies indicated that salivary cells are able to form polarized 3-dimensional structures when grown on growth factor-reduced Matrigel. This basement membrane is rich in laminin-III (L1), which plays a critical role in salivary gland formation. Mitotically inactive feeder layers have been used previously to support the growth of many different cell types, as they provide factors necessary for cell growth and organization. The goal of this study was to improve salivary gland cell differentiation in primary cultures by using a combination of L1 and a feeder layer of human hair follicle-derived mesenchymal stem cells (hHF-MSCs). Our results indicated that the direct contact of mouse submandibular (mSMG) cell clusters and hHF-MSCs was not required for mSMG cells to form acinar and ductal structures. However, the hHF-MSC conditioned medium enhanced cell organization and multilumen formation, indicating that soluble signals secreted by hHF-MSCs play a role in promoting these features. PMID:26285810

  15. Iliopsoas: Pathology, Diagnosis, and Treatment.

    Anderson, Christian N

    2016-07-01

    Disorders of the iliopsoas can be a significant source of groin pain in the athletic population. Commonly described pathologic conditions include iliopsoas bursitis, tendonitis, impingement, and snapping. The first-line treatment for iliopsoas disorders is typically conservative, including activity modification, physical therapy, nonsteroidal anti-inflammatory drugs, and corticosteroid injections. Surgical treatment can be considered if the patient fails conservative measures and typically involves arthroscopic lengthening of the musculotendinous unit and treatment of concomitant intra-articular abnormality. Tendon release has been described: in the central compartment, in the peripheral compartment, and at the lesser trochanter, with similar outcomes observed between the techniques. PMID:27343394

  16. Blood-based biomarkers of microvascular pathology in Alzheimer's disease.

    Ewers, Michael

    2012-02-01

    Sporadic Alzheimer\\'s disease (AD) is a genetically complex and chronically progressive neurodegenerative disorder with molecular mechanisms and neuropathologies centering around the amyloidogenic pathway, hyperphosphorylation and aggregation of tau protein, and neurofibrillary degeneration. While cerebrovascular changes have not been traditionally considered to be a central part of AD pathology, a growing body of evidence demonstrates that they may, in fact, be a characteristic feature of the AD brain as well. In particular, microvascular abnormalities within the brain have been associated with pathological AD hallmarks and may precede neurodegeneration. In vivo assessment of microvascular pathology provides a promising approach to develop useful biological markers for early detection and pathological characterization of AD. This review focuses on established blood-based biological marker candidates of microvascular pathology in AD. These candidates include plasma concentration of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) that are increased in AD. Measures of endothelial vasodilatory function including endothelin (ET-1), adrenomedullin (ADM), and atrial natriuretic peptide (ANP), as well as sphingolipids are significantly altered in mild AD or during the predementia stage of mild cognitive impairment (MCI), suggesting sensitivity of these biomarkers for early detection and diagnosis. In conclusion, the emerging clinical diagnostic evidence for the value of blood-based microvascular biomarkers in AD is promising, however, still requires validation in phase II and III diagnostic trials. Moreover, it is still unclear whether the described protein dysbalances are early or downstream pathological events and how the detected systemic microvascular alterations relate to cerebrovascular and neuronal pathologies in the AD brain.

  17. Multidetector CT and MRI findings in periportal space pathologies

    Karcaaltincaba, Musturay [Department of Radiology, Hacettepe University School of Medicine, Ankara 06100 (Turkey)]. E-mail: musturayk@yahoo.com; Haliloglu, Mithat [Department of Radiology, Hacettepe University School of Medicine, Ankara 06100 (Turkey); Akpinar, Erhan [Department of Radiology, Hacettepe University School of Medicine, Ankara 06100 (Turkey); Akata, Deniz [Department of Radiology, Hacettepe University School of Medicine, Ankara 06100 (Turkey); Ozmen, Mustafa [Department of Radiology, Hacettepe University School of Medicine, Ankara 06100 (Turkey); Ariyurek, Macit [Department of Radiology, Hacettepe University School of Medicine, Ankara 06100 (Turkey); Akhan, Okan [Department of Radiology, Hacettepe University School of Medicine, Ankara 06100 (Turkey)

    2007-01-15

    Periportal region is an anatomic space around portal vein comprising hepatic artery, bile duct, nerves, lymphatics and a potential space. Periportal pathologies may involve any of these structures diffusely or focally with characteristic radiologic findings. Radiologic findings can be helpful in differential diagnosis of pathologies of periportal structures including periportal cavernomatous transformation, hepatic artery aneurysm, biliary diseases, neurofibromatosis, lymphoma, langerhans' cell histiocytosis, periportal fatty infiltration and other causes of periportal halo in adult and pediatric patients. Lobar/segmental intrahepatic involvement can be seen in neurofibromatosis, cavernomatous transformation, fatty infiltration and periportal edema. In this review, we discuss CT and MRI findings of periportal pathologies which can be in the form of diffuse or segmental/lobar involvement.

  18. Multidetector CT and MRI findings in periportal space pathologies

    Periportal region is an anatomic space around portal vein comprising hepatic artery, bile duct, nerves, lymphatics and a potential space. Periportal pathologies may involve any of these structures diffusely or focally with characteristic radiologic findings. Radiologic findings can be helpful in differential diagnosis of pathologies of periportal structures including periportal cavernomatous transformation, hepatic artery aneurysm, biliary diseases, neurofibromatosis, lymphoma, langerhans' cell histiocytosis, periportal fatty infiltration and other causes of periportal halo in adult and pediatric patients. Lobar/segmental intrahepatic involvement can be seen in neurofibromatosis, cavernomatous transformation, fatty infiltration and periportal edema. In this review, we discuss CT and MRI findings of periportal pathologies which can be in the form of diffuse or segmental/lobar involvement

  19. Formation of the tetraploid intermediate is associated with the development of cells with more than four centrioles in the elastase-simian virus 40 tumor antigen transgenic mouse model of pancreatic cancer.

    1991-01-01

    The development of pancreatic cancer in transgenic mice expressing the simian virus 40 tumor antigen placed under controlling regions of the elastase I gene is characterized by the sequential appearance of tetraploid and then multiple aneuploid cell populations. Pancreatic tissues from such transgenic mice were studied between 8 and 32 days of age. Virtually 100% of acinar cell nuclei had immunohistochemically detectable tumor antigen by 18 days. Tetraploid cells were demonstrated by DNA cont...

  20. Gastric schwannomas: radiological features with endoscopic and pathological correlation

    Hong, H.S. [Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seodaemoon-gu, Seoul (Korea, Republic of); Ha, H.K. [Department of Radiology, University of Ulsan College of Medicine, Songpa-gu, Seoul (Korea, Republic of)], E-mail: hkha@amc.seoul.kr; Won, H.J.; Byun, J.H.; Shin, Y.M.; Kim, A.Y.; Kim, P.N.; Lee, M.-G. [Department of Radiology, University of Ulsan College of Medicine, Songpa-gu, Seoul (Korea, Republic of); Lee, G.H. [Internal Medicine, University of Ulsan College of Medicine, Songpa-gu, Seoul (Korea, Republic of); Kim, M.J. [Pathology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul (Korea, Republic of)

    2008-05-15

    Aim: To describe the radiological, endoscopic, and pathological findings of gastric schwannomas in 16 patients. Materials and methods: The radiological, endoscopic, and pathological findings of 16 surgically proven cases of gastric schwannoma were retrospectively reviewed. All patients underwent computed tomography (CT) and four patients were evaluated with upper gastrointestinal series. Two radiologists reviewed the CT and upper gastrointestinal series images by consensus with regard to tumour size, contour, margin, and growth pattern, the presence or absence of ulcer, cystic change, and the CT enhancement pattern. Endoscopy was performed in eight of these 16 patients. Six patients underwent endoscopic ultrasonography. Pathological specimens were obtained from and reviewed in all 16 patients. Immunohistochemistry was performed for c-kit, CD34, smooth muscle actin, and S-100 protein. Results: On radiographic examination, gastric schwannomas appeared as submucosal tumours with the CT features of well-demarcated, homogeneous, and uncommonly ulcerated masses. Endoscopy with endoscopic ultrasonography demonstrated homogeneous, submucosal masses contiguous with the muscularis propria in all six examined cases. On pathological examination, gastric schwannomas appeared as well-circumscribed and homogeneous tumours in the muscularis propria and consisted microscopically of interlacing bundles of spindle cells. Strong positivity for S-100 protein was demonstrated in all 16 cases on immunohistochemistry. Conclusion: Gastric schwannomas appear as submucosal tumours of the stomach and have well-demarcated and homogeneous features on CT, endoscopic ultrasonography, and gross pathology. Immunohistochemistry consistently reveals positivity for S-100 protein in the tumours.

  1. Role of ROBO4 Signalling in Developmental and Pathological Angiogenesis

    Suresh Singh Yadav

    2014-01-01

    Full Text Available Transmembrane roundabout receptor family members (ROBO1–ROBO4 principally orchestrate the neuronal guidance mechanism of the nervous system. Secreted glycoprotein SLITs are the most appreciated ligands for ROBOs. Recently identified ROBO4 is the key mediator of SLIT-ROBO mediated developmental and pathological angiogenesis. Although SLIT2 has been shown to interact with ROBO4 as ligand, it remains an open question whether this protein is the physiologic partner of ROBO4. The purpose of this review is to summarise how reliable SLIT2 as ligand for ROBO4 is, if not what the other possible mechanisms demonstrated till date for ROBO4 mediated developmental and pathological angiogenesis are. We conclude that ROBO4 is expressed specially in vascular endothelial cells and maintains the vascular integrity via either SLIT2 dependent or SLIT2 independent manner. On the contrary, it promotes the pathological angiogenesis by involving different signalling arm(s/unknown ligand(s. This review explores the interactions SLIT2/ROBO1, SLIT2/ROBO1–ROBO4, ROBO1/ROBO4, and ROBO4/UNC5B which can be promising and potential therapeutic targets for developmental angiogenesis defects and pathological angiogenesis. Finally we have reviewed the ROBO4 signalling pathways and made an effort to elaborate the insight of this signalling as therapeutic target of pathological angiogenesis.

  2. Fibroadenomas: Sonographic-pathologic correlation

    To correlate sonographic appearance and histopathologic findings of fibroadenomas. Forty-one biopsy-proven fibroadenomas were retrospectively evaluate for sonographic-pathologic correlation. The fibroadenomas were histologically classified into sclerotic, myxoid, glandular and mixed type. The stromal cellularity and fibrosis were also classified into mild and severe. The internal echotexture and posterior acoustic enhancement of mass in ultrasonogram were correlated with histopathologic findings. The pathologic types of fibroadenomas were sclerotic in sixteen, myxoid in thirteen, and glandular or mixed in each of six cases. Most of the sclerotic type showed hypoechoic internal echotexture (68.8%) and myxoid and glandular types showed isoechoic internal echotexture (84.6%, 83.3% respectively). The hypoechoic masses showed 12 cases of mild (75.0%) and 4 cases of severe (25.0%) in cellularity and 3 cases of mild (18.7%) and 13 cases (81.3%) of sever degree in fibrosis. Most of the myxoid type (77%) showed posterior enhancement, and most of the sclerotic type (87.5%) did not show posterior enhancement on ultrasonogram. Posterior enhancement was absent in 22 cases, in which 4 cases (18.2%) showed mild and 18 cases (81.2%) showed severe degree of fibrosis. Sclerotic type with mild cellularity and severe fibrosis on histopathology showed hypoechogenicity on ultrasonogram; whereas myxoid and glandular types were predominantly isoechoic. Most of the myxoid type showed posterior enhancement. Sclerotic type with mild cellularity and severe fibrosis did not show posterior enhancement.

  3. Fibroadenomas: Sonographic-pathologic correlation

    Kim, Mi Sung; Choi, Hye Young; Kim, Eun Ah; Lee, Sun Wha; Sung, Soon Hee [Ewha Womans University, Seoul (Korea, Republic of)

    1999-09-15

    To correlate sonographic appearance and histopathologic findings of fibroadenomas. Forty-one biopsy-proven fibroadenomas were retrospectively evaluate for sonographic-pathologic correlation. The fibroadenomas were histologically classified into sclerotic, myxoid, glandular and mixed type. The stromal cellularity and fibrosis were also classified into mild and severe. The internal echotexture and posterior acoustic enhancement of mass in ultrasonogram were correlated with histopathologic findings. The pathologic types of fibroadenomas were sclerotic in sixteen, myxoid in thirteen, and glandular or mixed in each of six cases. Most of the sclerotic type showed hypoechoic internal echotexture (68.8%) and myxoid and glandular types showed isoechoic internal echotexture (84.6%, 83.3% respectively). The hypoechoic masses showed 12 cases of mild (75.0%) and 4 cases of severe (25.0%) in cellularity and 3 cases of mild (18.7%) and 13 cases (81.3%) of sever degree in fibrosis. Most of the myxoid type (77%) showed posterior enhancement, and most of the sclerotic type (87.5%) did not show posterior enhancement on ultrasonogram. Posterior enhancement was absent in 22 cases, in which 4 cases (18.2%) showed mild and 18 cases (81.2%) showed severe degree of fibrosis. Sclerotic type with mild cellularity and severe fibrosis on histopathology showed hypoechogenicity on ultrasonogram; whereas myxoid and glandular types were predominantly isoechoic. Most of the myxoid type showed posterior enhancement. Sclerotic type with mild cellularity and severe fibrosis did not show posterior enhancement.

  4. [Update of pathological diagnosis of pulmonary neuroendocrine tumor].

    Xiaodong, Teng; Ming, Zhao; Maode, Lai

    2016-05-25

    Pulmonary neuroendocrine tumors are common in pathological practice and its pathological classification and histological grading are not exactly the same as that of those in the digestive tract and pancreas. In 2015 edition of World Health Organization classification, pulmonary neuroendocrine tumors are classified as carcinoid tumors (including typical carcinoid and atypical carcinoid), small cell lung carcinoma, large cell neuroendocrine carcinoma, and precursor lesion diffuse idiopathic neuroendocrine cell hyperplasia; each category has distinctive morphological and immunohistochemical features. The morphologic features including growth patterns and cytological appearances are keys for the diagnosis of neuroendocrine tumor, and immunohistochemical findings are also critical for its diagnosis. Furthermore, the diagnostic criteria vary for different types of specimen. In this article, we present a concise review and summary of the update of clinicopathological characterizations of pulmonary neuroendocrine tumor, with an emphasis on its diagnostic criteria and differential diagnosis. PMID:27045239

  5. Secretory vesicles in live cells are not free-floating but tethered to filamentous structures: A study using photonic force microscopy

    It is well established that actin and microtubule cytoskeletal systems are involved in organelle transport and membrane trafficking in cells. This is also true for the transport of secretory vesicles in neuroendocrine cells and neurons. It was however unclear whether secretory vesicles remain free-floating, only to associate with such cytoskeletal systems when needing transport. This hypothesis was tested using live pancreatic acinar cells in physiological buffer solutions, using the photonic force microscope (PFM). When membrane-bound secretory vesicles (0.2-1.2 μm in diameter) in live pancreatic acinar cells were trapped at the laser focus of the PFM and pulled, they were all found tethered to filamentous structures. Mild exposure of cells to nocodazole and cytochalasin B, disrupts the tether. Immunoblot analysis of isolated secretory vesicles, further demonstrated the association of actin, myosin V, and kinesin. These studies demonstrate for the first time that secretory vesicles in live pancreatic acinar cells are tethered and not free-floating, suggesting that following vesicle biogenesis, they are placed on their own railroad track, ready to be transported to their final destination within the cell when required. This makes sense, since precision and regulation are the hallmarks of all cellular process, and therefore would hold true for the transport and localization of subcellular organelles such as secretory vesicles

  6. Inflammatory pseudotumor of the Lung : CT findings and pathologic correlation

    Kim, Hyun Sook; Jung, Gyoo Sik; Baek, Kyong Hee; Lee, Seung Ryong; Huh, Jin Do; Joh, Young Duk; Jang, Hee Kyong [Kosin Medican College, Pusan (Korea, Republic of)

    1998-01-01

    To define the CT findings of inflammatory pseudotumor of the lung, and determine pathologic correlation. In five cases, CT showed that irregular, spiculated nodules or masses contacted with the pleura: in one, a well-defined nodule contacted with the fissure : and in one, there was consolidation. On postcontrast CT images, all six cases showed enhancement, with a central, low-density component. In four cases, ground-glass opacity surrounding the lesion was identified, and in three focal pleural thickening adjacent to the lesion was noted. The predominant pathologic composition of the enhanced portions of the lesion, as seen on CT, was chronic inflammatory or spindle cells, and the angiogenesis of small vessels was also noted. Non-enhanced, central, low-density areas were accounted for by hemorrhaging, necrosis and the focal aggregation of acute and chronic inflammatory cells. Surrounding groud-glass opacity corresponded pathologically to organizing pneumonia, cellular infiltration along the alveolar wall, and alveolar collapse. The CT features of inflammatory pseudotumor of the lung were mainly peripheral, irregular, spiculated nodule or mass, with contrast-enhancement and a central low-density component , combined with surrounding ground-glass opacity. All these findings correlated well with pathologic findings. (author). 26 refs., 2 tabs., 4 figs.

  7. Inflammatory pseudotumor of the Lung : CT findings and pathologic correlation

    To define the CT findings of inflammatory pseudotumor of the lung, and determine pathologic correlation. In five cases, CT showed that irregular, spiculated nodules or masses contacted with the pleura: in one, a well-defined nodule contacted with the fissure : and in one, there was consolidation. On postcontrast CT images, all six cases showed enhancement, with a central, low-density component. In four cases, ground-glass opacity surrounding the lesion was identified, and in three focal pleural thickening adjacent to the lesion was noted. The predominant pathologic composition of the enhanced portions of the lesion, as seen on CT, was chronic inflammatory or spindle cells, and the angiogenesis of small vessels was also noted. Non-enhanced, central, low-density areas were accounted for by hemorrhaging, necrosis and the focal aggregation of acute and chronic inflammatory cells. Surrounding groud-glass opacity corresponded pathologically to organizing pneumonia, cellular infiltration along the alveolar wall, and alveolar collapse. The CT features of inflammatory pseudotumor of the lung were mainly peripheral, irregular, spiculated nodule or mass, with contrast-enhancement and a central low-density component , combined with surrounding ground-glass opacity. All these findings correlated well with pathologic findings. (author). 26 refs., 2 tabs., 4 figs

  8. Pathology of hepatic iron overload

    Yves Deugnier; Bruno Turlin

    2007-01-01

    Although progress in imaging and genetics allow for a noninvasive diagnosis of most cases of genetic iron overload, liver pathology remains often useful (1) to assess prognosis by grading fibrosis and seeking for associated lesions and (2) to guide the etiological diagnosis, especially when no molecular marker is available.Then, the type of liver siderosis (parenchymal, mesenchymal or mixed) and its distribution throughout the lobule and the liver are useful means for suggesting its etiology: HLA-linked hemochromatosis gene (HFE) hemochromatosis or other rare genetic hemochromatosis,nonhemochromatotic genetic iron overload (ferroportin disease, aceruloplasminemia), or iron overload secondary to excessive iron supply, inflammatory syndrome,noncirrhotic chronic liver diseases including dysmetabolic iron overload syndrome, cirrhosis, and blood disorders.

  9. Contemporary pharmacotherapy and iatrogenic pathology

    Trailović D.R.

    2005-01-01

    Full Text Available During the past few decades, the pharmaceutical industry has developed into a powerful human activity highly influencing modern medicine. Thousands of synthetic therapeuticals have been developed, and these formulations enabled the successful treatment of many diseases, some of which were considered incurable. An increase in drug consumption followed the development of the pharmaceutical industry and the introduction of synthetic drugs. The widespread use of new medicals enabled the collection of data confirming their effectiveness, but also more and more data concerning side and unwanted effects were reported. Frequent side/unwanted effect reports gave rise to development of iatrogenic pathology, a new branch of clinical pathology. The knowledge of the possible unwanted effects of drugs on macro organisms did not enable the effective withdrawal of such formulations from the market. At the beginning, the reports concerning unwanted effects were not verealed. Consequently some potentially harmful formulations were used for years without methodical analyses of their side/unwanted effects. Some potentially dangerous formulations are still on the market such as drugs containing ulcerogenic, hepatotoxic, nephrotoxic substances as well as those inducing bone marrow aplasia. The administration of these potentially dangerous formulations is understandable in the case of clear therapeutic indications allowing no alternatives. In these cases the risk of harmful side effects is greatly overwhelmed by the risk from the primary disease. Otherwise the administration of the potentially harmful drug is unjustified, especially if the indication is not a disease. Many potentially harmful drugs are formulated for use in healthy animals, recommended as growth, laying and milk stimulators, those allowing higher speed and strength in sport and racing horses, estrus inducers and suppressors. The misuse or maluse medication is highly present in sport horses daily

  10. Radiographic and Pathologic Manifestations of Uncommon and Rare Pulmonary Lesions.

    Pfeifer, Kyle; Mian, Ali; Adebowale, Adeniran; Alomari, Ahmed; Kalra, Vivek; Krejci, Elise; Shin, Myung Soo

    2016-05-01

    Pulmonary opacities/nodules are common findings on computed tomography examinations, which may represent an underlying infections or malignancy. However, not every pulmonary nodule or opacity represents malignancy or infection. We present a pictorial essay illustrating common as well as obscure noninfectious, nonmalignant pulmonary lesions. Lesions discussed include organizing pneumonia, Langerhans cell histiocytosis, pulmonary amyloidosis, hyalinizing granuloma, tumourlet (benign localized neuroendocrine cell proliferations), atypical alveolar hyperplasia, inflammatory myofibroblastic tumour, papillary alveolar adenoma, plasma cell granuloma, juvenile xanthogranuloma, and sclerosing hemangiomas. We discuss the clinical presentation, prevalence, radiographic clues, pathology, and diagnostic pitfalls of these rare lesions. PMID:26690551

  11. Differential induction and spread of tau pathology in young PS19 tau transgenic mice following intracerebral injections of pathological tau from Alzheimer's disease or corticobasal degeneration brains.

    Boluda, Susana; Iba, Michiyo; Zhang, Bin; Raible, Kevin M; Lee, Virginia M-Y; Trojanowski, John Q

    2015-02-01

    Filamentous tau pathologies are hallmark lesions of several neurodegenerative tauopathies including Alzheimer's disease (AD) and corticobasal degeneration (CBD) which show cell type-specific and topographically distinct tau inclusions. Growing evidence supports templated transmission of tauopathies through functionally interconnected neuroanatomical pathways suggesting that different self-propagating strains of pathological tau could account for the diverse manifestations of neurodegenerative tauopathies. Here, we describe the rapid and distinct cell type-specific spread of pathological tau following intracerebral injections of CBD or AD brain extracts enriched in pathological tau (designated CBD-Tau and AD-Tau, respectively) in young human mutant P301S tau transgenic (Tg) mice (line PS19) ~6-9 months before they show onset of mutant tau transgene-induced tau pathology. At 1 month post-injection of CBD-Tau, tau inclusions developed predominantly in oligodendrocytes of the fimbria and white matter near the injection sites with infrequent intraneuronal tau aggregates. In contrast, injections of AD-Tau in young PS19 mice induced tau pathology predominantly in neuronal perikarya with little or no oligodendrocyte involvement 1 month post-injection. With longer post-injection survival intervals of up to 6 months, CBD-Tau- and AD-Tau-induced tau pathology spread to different brain regions distant from the injection sites while maintaining the cell type-specific pattern noted above. Finally, CA3 neuron loss was detected 3 months post-injection of AD-Tau but not CBD-Tau. Thus, AD-Tau and CBD-Tau represent specific pathological tau strains that spread differentially and may underlie distinct clinical and pathological features of these two tauopathies. Hence, these strains could become targets to develop disease-modifying therapies for CBD and AD. PMID:25534024

  12. Slot Machine Response Frequency Predicts Pathological Gambling

    Linnet, Jakob; Rømer Thomsen, Kristine; Møller, Arne;

    2013-01-01

    Slot machines are among the most addictive forms of gambling, and pathological gambling slot machine players represent the largest group of treatment seekers, accounting for 35% to 93% of the population. Pathological gambling sufferers have significantly higher response frequency (games / time) on...... slot machines compared with non-problem gamblers, which may suggest increased reinforcement of the gambling behavior in pathological gambling. However, to date it is unknown whether or not the increased response frequency in pathological gambling is associated with symptom severity of the disorder....... This study tested the hypothesis that response frequency is associated with symptom severity in pathological gambling. We tested response frequency among twenty-two pathological gambling sufferers and twenty-one non-problem gamblers on a commercially available slot machine, and screened for...

  13. Heat shock protein 70 prevents secretagogue-induced cell injury in the pancreas by preventing intracellular trypsinogen activation

    Bhagat, Lakshmi; Singh, Vijay P.; Hietaranta, Antti J.; Agrawal, Sudhir; Steer, Michael L; Saluja, Ashok K

    2000-01-01

    Rodents given a supramaximally stimulating dose of cholecystokinin or its analogue cerulein develop acute pancreatitis with acinar cell injury, pancreatic inflammation, and intrapancreatic digestive enzyme (i.e., trypsinogen) activation. Prior thermal stress is associated with heat shock protein 70 (HSP70) expression and protection against cerulein-induced pancreatitis. However, thermal stress can also induce expression of other HSPs. The current studies were performed using an in vitro syste...

  14. Pathologic mitoses and pathology of mitosis in tumorigenesis

    RG Steinbeck

    2009-12-01

    Full Text Available The gist of my hypothesis (.. is a certain abnormal chromatin constitution. Each process, which brings about this chromatin constitution, would result in the origin of a malignant tumour. Certainly, I consider irregularities with mitosis as the normal mode of the origin of an incorrectly assembled nucleus. This statement by Boveri (1914 has considered earlier observations of asymmetric divisions in human cancers (Hansemann, 1890. The hypothesis is based on the understanding of mitosis as an equational bipartition of the hereditary substance (Flemming, 1879; Roux, 1883. Latest since it was known that genes are located on chromosomes (Sturtevant, 1913, their balanced transport in anaphase appeared as a condition of correct somatic proliferation. True mitoses guarantee the constancy of terminally differentiated tissues. Politzer (1934 has performed X-ray experiments to investigate abnormal karyokinesis with regard to anomalous chromatin condensation, chromosome breakage, spindle malformation, and failure in cytokinesis. On the basis of light microscopy, further significant progress in understanding the pathology of mitosis was not possible. Tumour cases with reduced chromosome numbers seduced to the idea that mitotic activity is rather under cytoplasmic than under nuclear control (Koller, 1947.

  15. Matrix metalloproteinases and their inhibitors in cardiovascular pathologies: current knowledge and clinical potential

    Johnson, Jason

    2014-01-01

    Jason Lee Johnson Laboratory of Cardiovascular Pathology, School of Clinical Sciences, University of Bristol, Bristol, UK Abstract: Matrix metalloproteinases (MMPs) constitute a family of endopeptidases that harbor matrix-degrading potential, but also modulate the proliferation, migration, and apoptosis of resident blood-vessel cells and recruited inflammatory cells. Accordingly, they are proposed to play a major regulatory role in numerous cardiovascular pathologies, including restenosis, a...

  16. Impaired decisional impulsivity in pathological videogamers

    Irvine, Michael A.; Worbe, Yulia; Bolton, Sorcha; Harrison, Neil A.; Bullmore, Edward T.; Voon, Valerie

    2013-01-01

    Abstract Background Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort. Methods Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling ...

  17. Spiritual Pathology: The Case of Adolf Hitler

    W. George Scarlett

    2012-04-01

    Full Text Available Hitler had a noble purpose (to save the world and a strong faith in the laws of Nature as he understood Nature. He was, then, a spiritual person, though his spirituality was pathological and destructive. Here, the example of Hitler, his faith, and his spiritual pathology is given to both understand spiritual pathology in general and, through contrast, to understand positive spiritual development.

  18. The Notion "Pathology" in Set Theory

    DePauli-Schimanovich, Werner

    2008-01-01

    When we study the paradoxes of set theory we find out that there are mainly 2 types: the pathologies and the antinomies. These 2 notions are made precise and compared with the somehow inductively definable concept "abnormal". (See my paper "Naive Axiomatic Mengenlehre for Experiments" in arXiv.) In the following 5 Patho Theses are discussed in order to formalize this notion of pathology. This allows us to define formally the property "Hereditary-non-Pathological" for well-formed formulas. Wit...

  19. On-Line Full Text Pathology Database

    Fink, Daniel; Clark, Anthony; Sideli, Robert

    1988-01-01

    A free text database for pathology reports has been developed using the BRS/SEARCH free text management software. All pathology reports are stored in the free text pathology database. Standardized section headings make any word searchable both by itself or within the context of a specific part of the report. The free text management software supplies a rich set of Boolean, positional, and relational operators. These operators make an iterative search strategy an effective method of searching ...

  20. Metastatic non-small-cell lung cancer: consensus on pathology and molecular tests, first-line, second-line, and third-line therapy: 1st ESMO Consensus Conference in Lung Cancer; Lugano 2010

    Felip, E; Gridelli, C; Baas, P; Rosell, R; Stahel, R; Sørensen, Jens Benn

    2011-01-01

    The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21 and 22 May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics, medical oncology, surgical oncology and radiation oncology. Before the...... treatment of first-line, and second-line/third-line therapy in metastatic NSCLC are reported in this article. The recommendations detailed here are based on an expert consensus after careful review of published data. All participants have approved this final update....