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Beta cells AND hyperplasia

Francesco Catanzariti, Lucilla Servi, Andrea Fabiani, Alessandra Filosa, Gabriele Mammana
INTRODUCTION: Testicular cancer is one of the most frequent in young men and its incidence is increasing in recent years because of incidental finding during routine ultrasound exams. Adenomatous hyperplasia of the rete testis is one of the benign and rare pathological types incidentally detected and very few cases are described in the literature. CASE REPORT: A 40 years old man come to our attention for a balanoposthitis without testicular pain. During andrological examination we performed palpation of the testes and we noticed a palpable nodule of hard consistency in the left testicle...
October 5, 2016: Archivio Italiano di Urologia, Andrologia
Rei Nagahara, Masayuki Kimura, Megu Itahashi, Go Sugahara, Masashi Kawashima, Hirotada Murayama, Toshinori Yoshida, Makoto Shibutani
Two solitary and minute tumors of 1 and 1.5 mm diameter were identified by microscopy in the left fourth mammary gland of a 13-year-old female Labrador Retriever dog, in addition to multiple mammary gland tumors. The former tumors were well circumscribed and were composed of small-to-large polyhedral neoplastic oncocytes with finely granular eosinophilic cytoplasm, and were arranged in solid nests separated by fine fibrovascular septa. Scattered lumina of variable sizes containing eosinophilic secretory material were evident...
November 2016: Journal of Veterinary Diagnostic Investigation
D A Maschio, R B Oliveira, M R Santos, C P F Carvalho, H C L Barbosa-Sampaio, C B Collares-Buzato
The Wnt/β-catenin signaling pathway, also known as the canonical Wnt pathway, plays a role in cell proliferation and differentiation in several tissues/organs. It has been recently described in humans a relationship between type 2 diabetes (T2DM) and mutation in the gene encoding the transcription factor TCF7L2 associated to the Wnt/β-catenin pathway. In the present study, we demonstrated that hyperplastic pancreatic islets from prediabetic mice fed a high-fat diet (HFD) for 60 d displayed nuclear translocation of active β-catenin associated with significant increases in protein content and gene expression of β-catenin as well as of cyclins D1, D2 and c-Myc (target genes of the Wnt pathway) but not of Tcf7l2 (the transcription factor)...
September 30, 2016: Biochemical and Biophysical Research Communications
Thomas G K Breuer, Laura Borker, Daniel R Quast, Andrea Tannapfel, Wolfgang E Schmidt, Waldemar Uhl, Juris J Meier
INTRODUCTION: Gastrin has been shown to promote beta-cell proliferation in rodents, but its effects in adult humans are largely unclear. Proton pump inhibitors (PPIs) lead to endogenous hypergastrinaemia, and improved glucose control during PPI therapy has been reported in patients with diabetes. Therefore, we addressed whether PPI treatment is associated with improved glucose homoeostasis, islet cell hyperplasia or increased new beta-cell formation in humans. PATIENTS AND METHODS: Pancreatic tissue specimens from 60 patients with and 33 patients without previous PPI therapy were examined...
November 2016: European Journal of Endocrinology
Sabela Diaz-Castroverde, Almudena Gómez-Hernández, Silvia Fernández, Gema García-Gómez, Marianna Di Scala, Gloria González-Aseguinolaza, Elisa Fernández-Millán, Águeda González-Rodríguez, María García-Bravo, Pierre Chambon, Carmen Álvarez, Liliana Perdomo, Nuria Beneit, Oscar Escribano, Manuel Benito
Type 2 diabetes mellitus is a complex metabolic disease and its pathogenesis involves abnormalities in both peripheral insulin action and insulin secretion. Previous in vitro data showed that insulin receptor isoform A, but not B, favours basal glucose uptake through its specific association with endogenous GLUT1/2 in murine hepatocytes and beta cells. With this background, we hypothesized that hepatic expression of insulin receptor isoform A in a mouse model of type 2 diabetes could potentially increase the glucose uptake of these cells decreasing the hyperglycaemia and therefore ameliorating the diabetic phenotype...
August 24, 2016: Disease Models & Mechanisms
Tina L Samuels, Justin Yan, Pawjai Khampang, Alexander MacKinnon, Wenzhou Hong, Nikki Johnston, Joseph E Kerschner
OBJECTIVE: Toll-like receptor signaling activated by bacterial otitis media pathogens in the middle ear has been shown to play a key role in OM susceptibility, pathogenesis and recovery. Recent studies implicate microRNA 146 (miR-146) in regulation of inflammation via negative feedback of toll-like receptor signaling (TLR) in a wide variety of tissues, however its involvement in otitis media is unknown. METHODS: Human middle ear epithelial cells were stimulated with proinflammatory cytokines, interleukin 1 beta or tumor necrosis factor alpha, for two to twenty-four hours...
September 2016: International Journal of Pediatric Otorhinolaryngology
Manar A Nader, Nariman Gameil, Rania R Abdelaziz, Khaled R Zalata, Amal Osman, Mohamed M Zedan, Nermin Abo-Elkheir, Abeer Abdalla Elsiddig, Magdy Zedan
AIM OF THE STUDY: The current investigation was taken to scrutinize the action of tranilast on the airway remodeling in chronic asthma in mice. MATERIALS AND METHODS: Intraperitoneal injection of ovalbumin was applied to mice for sensitization and subsequent inhalation of 1% ovalbumin three times week for 10 weeks for challenge. Beclomethasone or tranilast were given daily for the 10 week challenge period. At the end of the study, lung weight index, total collagen content, bronchoalveolar lavage level of total and differential cell counts, interleukin-13, in addition to lung tissue nitrate/nitrite and transforming growth beta-1 were measured...
August 2016: Experimental Lung Research
Eric Seidel, Ute I Scholl
The adrenal cortex is a major site of steroid hormone production. Two hormones are of particular importance: aldosterone, which is produced in the zona glomerulosa in response to volume depletion and hyperkalemia, and cortisol, which is produced in the zona fasciculata in response to stress. In both cases, acute stimulation leads to increased hormone production, and chronic stimulation causes hyperplasia of the respective zone. Aldosterone- and cortisol-producing adenomas (APAs and CPAs) are benign tumors of the adrenal cortex that cause excess hormone production, leading to primary aldosteronism and Cushing's syndrome, respectively...
2016: Frontiers in Endocrinology
Mai Abdel Mouti, Christopher Dee, Sarah E Coupland, Adam F L Hurlstone
Mutations affecting Gαq proteins are pervasive in uveal melanoma (UM), suggesting they 'drive' UM pathogenesis. The ERK1/2-MAPK pathway is critical for cutaneous melanoma development and consequently an important therapeutic target. Defining the contribution of ERK1/2-MAPK signalling to UM development has been hampered by the lack of an informative animal model that spontaneously develops UM. Towards this end, we engineered transgenic zebrafish to express oncogenic GNAQQ209P in the melanocyte lineage. This resulted in hyperplasia of uveal melanocytes, but with no evidence of malignant progression, nor perturbation of skin melanocytes...
May 6, 2016: Oncotarget
Pier Andrea Nicolosi, Enrico Tombetti, Norma Maugeri, Patrizia Rovere-Querini, Silvia Brunelli, Angelo A Manfredi
Fibrosis of the skin and of internal organs, autoimmunity, and vascular inflammation are hallmarks of Systemic Sclerosis (SSc). The injury and activation of endothelial cells, with hyperplasia of the intima and eventual obliteration of the vascular lumen, are early features of SSc. Reduced capillary blood flow coupled with deficient angiogenesis leads to chronic hypoxia and tissue ischemia, enforcing a positive feed-forward loop sustaining vascular remodelling, further exacerbated by extracellular matrix accumulation due to fibrosis...
2016: Stem Cells International
Verena Schwetz, Karl Horvath, Patrizia Kump, Carolin Lackner, Aurel Perren, Flavio Forrer, Thomas R Pieber, Gerlies Treiber, Harald Sourij, Julia K Mader
Nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. Diagnosis is often challenging and therapeutic options are scarce.In 2009, a 46-year-old female patient presented with recurrent severe hypoglycemia and immediate recovery after glucose ingestion. Although 72-h-fasting test was positive, various imaging technologies (sonography, computed tomography, somatostatin receptor scintigraphy, dopamine receptor positron emission tomography [DOPA-PET]) were negative. Endoscopic ultrasound revealed a lesion in the pancreatic corpus, whereas selective arterial calcium stimulation test, portal venous sampling and GLP-1-receptor scintigraphy were indicative of a lesion in the pancreatic tail, which was surgically removed...
April 2016: Medicine (Baltimore)
Wenjie Wang, Judong Luo, Wenjiong Sheng, Jiao Xue, Ming Li, Jiang Ji, Pengfei Liu, Xueguang Zhang, Jianping Cao, Shuyu Zhang
PURPOSE: To investigate the molecular changes underlying the pathogenesis of radiation-induced skin fibrosis. METHODS AND MATERIALS: Rat skin was irradiated to 30 or 45 Gy with an electron beam. Protein expression in fibrotic rat skin and adjacent normal tissues was quantified by label-free protein quantitation. Human skin cells HaCaT and WS-1 were treated by x-ray irradiation, and the proteasome activity was determined with a fluorescent probe. The effect of proteasome inhibitors on Transforming growth factor Beta (TGF-B) signaling was measured by Western blot and immunofluorescence...
June 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Li Chen, Jiaolong Wang, Glen Mouser, Yan Chun Li, Geno Marcovici
Androgenetic alopecia (AGA) affects approximately 70% of men and 40% of women in an age-dependent manner and is partially mediated by androgen hormones. Benign prostatic hyperplasia (BPH) similarly affects 50% of the male population, rising by 10% each decade. Finasteride inhibits 5-alpha reductase (5AR) and is used to treat both disorders, despite offering limited clinical benefits accompanied by significant adverse side effects. Building on our previous work demonstrating the efficacy of naturally derived 5AR inhibitors (such as stigmasterol and beta sitosterol), we hypothesize that targeting 5AR as well as inflammatory pathways may yield improved efficacy in AGA and BPH...
June 2016: Phytotherapy Research: PTR
Miriam Mints, Muhammad Mushtaq, Natalia Iurchenko, Larysa Kovalevska, Maria C Stip, Daria Budnikova, Sonia Andersson, Ludmila Polischuk, Lubov Buchynska, Elena Kashuba
Endometrial cancer (EC) is one of the most frequent causes of cancer death among women in developed countries. Histopathological diagnosis and imaging techniques for EC are limited, thus new prognostic markers are needed to offer patients the best treatment and follow-up.In the present paper we showed that the level of mitochondrial ribosomal protein MRPS18-2 (S18-2) increased in EC compared with the normal endometrium and hyperplasia, based on a study of 42 patient biopsies. Importantly, high expression of free E2F1 in EC correlates well with high S18-2 expression...
April 19, 2016: Oncotarget
Liisa Sjöblom, Outi Saramäki, Matti Annala, Katri Leinonen, Janika Nättinen, Teemu Tolonen, Tiina Wahlfors, Matti Nykter, G Steven Bova, Johanna Schleutker, Teuvo L J Tammela, Hans Lilja, Tapio Visakorpi
Microseminoprotein-beta (MSMB, MSMB) is an abundant secretory protein contributed by the prostate, and is implicated as a prostate cancer (PC) biomarker based on observations of its lower expression in cancerous cells compared with benign prostate epithelium. However, as the current literature on MSMB is inconsistent, we assessed the expression of MSMB at the protein and mRNA levels in a comprehensive set of different clinical stages of PC. Immunohistochemistry using monoclonal and polyclonal antibodies against MSMB was used to study protein expression in tissue specimens representing prostatectomies (n = 261) and in diagnostic needle biopsies from patients treated with androgen deprivation therapy (ADT) (n = 100), and in locally recurrent castration-resistant PC (CRPC) (n = 105) and CRPC metastases (n = 113)...
2016: PloS One
Pierre-Yves Jean-Charles, Lisheng Zhang, Jiao-Hui Wu, Sang-Oh Han, Leigh Brian, Neil J Freedman, Sudha K Shenoy
Toll-like receptor 4 (TLR4) promotes vascular inflammatory disorders such as neointimal hyperplasia and atherosclerosis. TLR4 triggers NFκB signaling through the ubiquitin ligase TRAF6 (tumor necrosis factor receptor-associated factor 6). TRAF6 activity can be impeded by deubiquitinating enzymes like ubiquitin-specific protease 20 (USP20), which can reverse TRAF6 autoubiquitination, and by association with the multifunctional adaptor protein β-arrestin2. Although β-arrestin2 effects on TRAF6 suggest an anti-inflammatory role, physiologic β-arrestin2 promotes inflammation in atherosclerosis and neointimal hyperplasia...
April 1, 2016: Journal of Biological Chemistry
Miki Nishio, Keishi Sugimachi, Hiroki Goto, Jia Wang, Takumi Morikawa, Yosuke Miyachi, Yusuke Takano, Hiroki Hikasa, Tohru Itoh, Satoshi O Suzuki, Hiroki Kurihara, Shinichi Aishima, Andrew Leask, Takehiko Sasaki, Toru Nakano, Hiroshi Nishina, Yuji Nishikawa, Yoshitaka Sekido, Kazuwa Nakao, Kazuo Shin-Ya, Koshi Mimori, Akira Suzuki
Mps One Binder Kinase Activator (MOB)1A/1B are core components of the Hippo pathway that coactivate large tumor suppressor homolog (LATS) kinases. Mob1a/1b double deficiency in mouse liver (LMob1DKO) results in hyperplasia of oval cells and immature cholangiocytes accompanied by inflammatory cell infiltration and fibrosis. More than half of mutant mice die within 3 wk of birth. All survivors eventually develop liver cancers, particularly combined hepatocellular and cholangiocarcinomas (cHC-CCs) and intrahepatic cholangiocellular carcinomas (ICCs), and die by age 60 wk...
January 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
Kristýna Němejcová, Ivana Tichá, Petra Kleiblová, Michaela Bártů, David Cibula, Kateřina Jirsová, Pavel Dundr
Hepatocyte nuclear factor 1-beta (HNF-1-beta) is a transcription factor involved in cancerogenesis of various tumors, including endometrioid carcinoma. We performed comprehensive analysis of HNF-1-beta in lesions of the endometrium, including protein expression and genetic and epigenetic changes. Expression of HNF-1-beta was analyzed immunohistochemically in 320 cases including both tumor and non-tumor endometrial lesions. Promoter methylation and genetic variants were evaluated, using bisulphite and direct sequencing, in 30 (18 fresh frozen, 12 FFPE tumors) endometrioid carcinomas (ECs) and 15 ovarian clear cell carcinomas (OCCCs) as a control group...
July 2016: Pathology Oncology Research: POR
Houari Abdesselem, Aisha Madani, Ahmad Hani, Muna Al-Noubi, Neha Goswami, Hisham Ben Hamidane, Anja M Billing, Jennifer Pasquier, Michael S Bonkowski, Najeeb Halabi, Rajaa Dalloul, Mohamed Z Sheriff, Nasrin Mesaeli, Mohamed ElRayess, David A Sinclair, Johannes Graumann, Nayef A Mazloum
The expansion of fat mass in the obese state is due to increased adipocyte hypertrophy and hyperplasia. The molecular mechanism that drives adipocyte hyperplasia remains unknown. The NAD(+)-dependent protein deacetylase sirtuin 1 (SIRT1), a key regulator of mammalian metabolism, maintains proper metabolic functions in many tissues, counteracting obesity. Here we report that differentiated adipocytes are hyperplastic when SIRT1 is knocked down stably in mouse 3T3-L1 preadipocytes. This phenotype is associated with dysregulated adipocyte metabolism and enhanced inflammation...
January 29, 2016: Journal of Biological Chemistry
Fong Cheng Pan, Marcela Brissova, Alvin C Powers, Samuel Pfaff, Christopher V E Wright
Homozygous Mnx1 mutation causes permanent neonatal diabetes in humans, but via unknown mechanisms. Our systematic and longitudinal analysis of Mnx1 function during murine pancreas organogenesis and into the adult uncovered novel stage-specific roles for Mnx1 in endocrine lineage allocation and β-cell fate maintenance. Inactivation in the endocrine-progenitor stage shows that Mnx1 promotes β-cell while suppressing δ-cell differentiation programs, and is crucial for postnatal β-cell fate maintenance. Inactivating Mnx1 in embryonic β-cells (Mnx1(Δbeta)) caused β-to-δ-like cell transdifferentiation, which was delayed until postnatal stages...
November 1, 2015: Development
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