Mineralocorticoid Receptor Deficiency in Macrophages Inhibits Neointimal Hyperplasia and Suppresses Macrophage Inflammation Through SGK1-AP1/NF-κB Pathways.

PubMed

Sun, Jian-Yong; Li, Chao; Shen, Zhu-Xia; Zhang, Wu-Chang; Ai, Tang-Jun; Du, Lin-Juan; Zhang, Yu-Yao; Yao, Gao-Feng; Liu, Yan; Sun, Shuyang; Naray-Fejes-Toth, Aniko; Fejes-Toth, Geza; Peng, Yong; Chen, Mao; Liu, Xiaojing; Tao, Jun; Zhou, Bin; Yu, Ying; Guo, Feifan; Du, Jie; Duan, Sheng-Zhong

2016-05-01

Restenosis after percutaneous coronary intervention remains to be a serious medical problem. Although mineralocorticoid receptor (MR) has been implicated as a potential target for treating restenosis, the cellular and molecular mechanisms are largely unknown. This study aims to explore the functions of macrophage MR in neointimal hyperplasia and to delineate the molecular mechanisms. Myeloid MR knockout (MMRKO) mice and controls were subjected to femoral artery injury. MMRKO reduced intima area and intima/media ratio, Ki67- and BrdU-positive vascular smooth muscle cells, expression of proinflammatory molecules, and macrophage accumulation in injured arteries. MMRKO macrophages migrated less in culture. MMRKO decreased Ki67- and BrdU-positive macrophages in injured arteries. MMRKO macrophages were less Ki67-positive in culture. Conditioned media from MMRKO macrophages induced less migration, Ki67 positivity, and proinflammatory gene expression of vascular smooth muscle cells. After lipopolysaccharide treatment, MMRKO macrophages had decreased p-cFos and p-cJun compared with control macrophages, suggesting suppressed activation of activator protein-1 (AP1). Nuclear factor-κB (NF-κB) pathway was also inhibited by MMRKO, manifested by decreased p-IκB kinase-β and p-IκBα, increased IκBα expression, decreased nuclear translocation of p65 and p50, as welll as decreased phosphorylation and expression of p65. Finally, overexpression of serum-and-glucocorticoid-inducible-kinase-1 (SGK1) attenuated the effects of MR deficiency in macrophages. Selective deletion of MR in myeloid cells limits macrophage accumulation and vascular inflammation and, therefore, inhibits neointimal hyperplasia and vascular remodeling. Mechanistically, MR deficiency suppresses migration and proliferation of macrophages and leads to less vascular smooth muscle cell activation. At the molecular level, MR deficiency suppresses macrophage inflammatory response via SGK1-AP1/NF-κB pathways. �

Conditional expression of the type 2 angiotensin II receptor in mesenchymal stem cells inhibits neointimal formation after arterial injury.

PubMed

Feng, Jian; Liu, Jian-Ping; Miao, Li; He, Guo-Xiang; Li, De; Wang, Hai-Dong; Jing, Tao

2014-10-01

Percutaneous coronary interventions (PCIs) are an effective treatment for obstructive coronary artery diseases. However, the procedure's success is limited by remodeling and formation of neointima. In the present study, we engineered rat mesenchymal stem cells (MSCs) to express type 2 angiotensin II receptor (AT2R) using a tetracycline-regulated system that can strictly regulate AT2R expression. We tested the ability of the modified MSCs to reduce neointima formation following arterial injury. We subjected rats to balloon injury, and reverse transcriptase polymerase chain reaction (RT-PCR) indicated no significant AT2R expression in normal rat arteries. Low expression of AT2R was observed at 28 days after balloon-induced injury. Interestingly, MSCs alone were unable to reduce neointimal hyperplasia after balloon-induced injury; after transplantation of modified MSCs, doxycycline treatment significantly upregulated neointimal AT2R expression and inhibited osteopontin mRNA expression, as well as neointimal formation. Taken together, these results suggest that transplantation of MSCs conditionally expressing AT2R could effectively suppress neointimal hyperplasia following balloon-induced injury. Therefore, MSCs with a doxycycline-controlled gene induction system may be useful for the management of arterial injury after PCI.

Tracking and Therapeutic Value of Human Adipose Tissue–derived Mesenchymal Stem Cell Transplantation in Reducing Venous Neointimal Hyperplasia Associated with Arteriovenous Fistula

PubMed Central

Yang, Binxia; Brahmbhatt, Akshaar; Nieves Torres, Evelyn; Thielen, Brian; McCall, Deborah L.; Engel, Sean; Bansal, Aditya; Pandey, Mukesh K.; Dietz, Allan B.; Leof, Edward B.; DeGrado, Timothy R.; Mukhopadhyay, Debabrata

2016-01-01

Purpose To determine if adventitial transplantation of human adipose tissue–derived mesenchymal stem cells (MSCs) to the outflow vein of B6.Cg-Foxn1nu/J mice with arteriovenous fistula (AVF) at the time of creation would reduce monocyte chemoattractant protein-1 (Mcp-1) gene expression and venous neointimal hyperplasia. The second aim was to track transplanted zirconium 89 (89Zr)–labeled MSCs serially with positron emission tomography (PET) for 21 days. Materials and Methods All animal experiments were performed according to protocols approved by the institutional animal care and use committee. Fifty B6.Cg-Foxn1nu/J mice were used to accomplish the study aims. Green fluorescent protein was used to stably label 2.5 × 105 MSCs, which were injected into the adventitia of the outflow vein at the time of AVF creation in the MSC group. Eleven mice died after AVF placement. Animals were sacrificed on day 7 after AVF placement for real-time polymerase chain reaction (n = 6 for MSC and control groups) and histomorphometric (n = 6 for MSC and control groups) analyses and on day 21 for histomorphometric analysis only (n = 6 for MSC and control groups). In a separate group of experiments (n = 3), animals with transplanted 89Zr-labeled MSCs were serially imaged with PET for 3 weeks. Multiple comparisons were performed with two-way analysis of variance, followed by the Student t test with post hoc Bonferroni correction. Results In vessels with transplanted MSCs compared with control vessels, there was a significant decrease in Mcp-1 gene expression (day 7: mean reduction, 62%; P = .029), with a significant increase in the mean lumen vessel area (day 7: mean increase, 176% [P = .013]; day 21: mean increase, 415% [P = .011]). Moreover, this was accompanied by a significant decrease in Ki-67 index (proliferation on day 7: mean reduction, 81% [P = .0003]; proliferation on day 21: mean reduction, 60%, [P = .016]). Prolonged retention of MSCs at the adventitia was evidenced by

Stent-based nitric oxide delivery reducing neointimal proliferation in a porcine carotid overstretch injury model.

PubMed

Hou, Dongming; Narciso, Hugh; Kamdar, Kirti; Zhang, Ping; Barclay, Bruce; March, Keith L

2005-01-01

The effects of nitric acid (NO) on vessel response to injury include the inhibition of platelet adhesion, platelet aggregation, leukocyte adhesion and smooth muscle cell proliferation. Releasing NO from a stent might reduce the clinical problem of restenosis. The present study was designed to examine whether an NO-eluting covered stent can prevent neointimal formation in a porcine carotid overstretch injury model. The interior of a self-expanding polytetrafluoroethylene (ePTFE)-covered aSpire stent was coated with silicone, which contained 23.6 microg or 54.5 microg sodium nitroprusside (SNP, NO-releasing compound). The stent was implanted into carotid artery. Six pigs were implanted with stents, one high-dose SNP and one uncoated control, following balloon overstretch injury of the carotid artery with a balloon-to-artery ratio of 1.3:1. No local or systemic toxicity was evidenced in the six pigs after carotid artery implantation with either low- or high-dose stents within a week. At day 28, the mean intimal thickness was 0.12 +/- 0.05 mm for NO-eluting stents and 0.43 +/- 0.09 mm for uncoated stents (p = 0.008). The mean neointimal area was reduced from 2.40 +/- 0.39 mm2 for control stents to 0.49 +/- 0.16 mm2 for NO-eluting stents (p < 0.0001), which resulted in a 24% reduction of angiographic vessel narrowing. The NO-eluting ePTFE-covered stent is feasible and effectively reduces in-stent neointimal hyperplasia at 28 days in a porcine carotid overstretch model.

Targeted nitric oxide delivery by supramolecular nanofibers for the prevention of restenosis after arterial injury

DOE PAGES

Bahnson, Edward S. M.; Kassam, Hussein A.; Moyer, Tyson J.; ...

2016-01-21

Cardiovascular interventions continue to fail as a result of arterial restenosis secondary to neointimal hyperplasia. Here we sought to develop and evaluate a systemically delivered nanostructure targeted to the site of arterial injury to prevent neointimal hyperplasia. Nanostructures were based on self-assembling biodegradable molecules known as peptide amphiphiles. The targeting motif was a collagen-binding peptide, and the therapeutic moiety was added by S-nitrosylation of cysteine residues. As a result, structure of the nanofibers was characterized by transmission electron microscopy and small-angle X-ray scattering. S-nitrosylation was confirmed by mass spectrometry, and nitric oxide (NO) release was assessed electrochemically and by chemiluminescentmore » detection. The balloon carotid artery injury model was performed on 10-week-old male Sprague-Dawley rats. Immediately after injury, nanofibers were administered systemically via tail vein injection. S-nitrosylated (S-nitrosyl [SNO])-targeted nanofibers significantly reduced neointimal hyperplasia 2 weeks and 7 months following balloon angioplasty, with no change in inflammation. This is the first time that an S-nitrosothiol (RSNO)-based therapeutic was shown to have targeted local effects after systemic administration. This approach, combining supramolecular nanostructures with a therapeutic NO-based payload and a targeting moiety, overcomes the limitations of delivering NO to a site of interest, avoiding undesirable systemic side effects. In conclusion, we successfully synthesized and characterized an RSNO-based therapy that when administered systemically, targets directly to the site of vascular injury. By integrating therapeutic and targeting chemistries, these targeted SNO nanofibers provided durable inhibition of neointimal hyperplasia in vivo and show great potential as a platform to treat cardiovascular diseases« less

Novel Role of Copper Transport Protein Antioxidant-1 in Neointimal Formation Following Vascular Injury

PubMed Central

Kohno, Takashi; Urao, Norifumi; Ashino, Takashi; Sudhahar, Varadarajan; McKinney, Ronald D.; Hamakubo, Takao; Iwanari, Hiroko; Ushio-Fukai, Masuko; Fukai, Tohru

2013-01-01

Objective Vascular smooth muscle cell (VSMC) migration is critically important for neointimal formation following vascular injury and atherosclerosis lesion formation. Copper (Cu) chelator inhibits neointimal formation, and we previously demonstrated that Cu transport protein Antioxidant-1 (Atox1) is involved in Cu-induced cell growth. However, role of Atox1 in VSMC migration and neointimal formation after vascular injury is unknown. Approach and Results Here we show that Atox1 expression is upregulated in injured vessel, and it is colocalized with the Cu transporter ATP7A, one of downstream targets of Atox1, mainly in neointimal VSMCs at day 14 after wire injury. Atox1−/− mice show inhibition of neointimal formation and extracellular matrix expansion, which is associated with a decreased VSMCs accumulation within neointima and lysyl oxidase activity. Mechanistically, in cultured VSMC, Atox1 depletion with siRNA inhibits platelet-derived growth factor (PDGF)-induced Cu-dependent VSMC migration by preventing translocation of ATP7A and small G protein Rac1 to the leading edge as well as Cu- and Rac1-dependent lamellipodia formation. Furthermore, Atox1−/− mice show decreased perivascular macrophage infiltration in wire-injured vessels as well as thioglycollate-induced peritoneal macrophage recruitment. Conclusions Atox1 is involved in neointimal formation after vascular injury through promoting VSMC migration and inflammatory cell recruitment in injured vessels. Thus, Atox1 is a potential therapeutic target for VSMC migration and inflammation-related vascular diseases. PMID:23349186

Novel role of copper transport protein antioxidant-1 in neointimal formation after vascular injury.

PubMed

Kohno, Takashi; Urao, Norifumi; Ashino, Takashi; Sudhahar, Varadarajan; McKinney, Ronald D; Hamakubo, Takao; Iwanari, Hiroko; Ushio-Fukai, Masuko; Fukai, Tohru

2013-04-01

Vascular smooth muscle cell (VSMC) migration is critically important for neointimal formation after vascular injury and atherosclerosis lesion formation. Copper (Cu) chelator inhibits neointimal formation, and we previously demonstrated that Cu transport protein antioxidant-1 (Atox1) is involved in Cu-induced cell growth. However, role of Atox1 in VSMC migration and neointimal formation after vascular injury is unknown. Here, we show that Atox1 expression is upregulated in injured vessel, and it is colocalized with the Cu transporter ATP7A, one of the downstream targets of Atox1, mainly in neointimal VSMCs at day 14 after wire injury. Atox1(-/-) mice show inhibition of neointimal formation and extracellular matrix expansion, which is associated with a decreased VSMCs accumulation within neointima and lysyl oxidase activity. Mechanistically, in cultured VSMC, Atox1 depletion with siRNA inhibits platelet-derived growth factor-induced Cu-dependent VSMC migration by preventing translocation of ATP7A and small G protein Rac1 to the leading edge, as well as Cu- and Rac1-dependent lamellipodia formation. Furthermore, Atox1(-/-) mice show decreased perivascular macrophage infiltration in wire-injured vessels, as well as thioglycollate-induced peritoneal macrophage recruitment. Atox1 is involved in neointimal formation after vascular injury through promoting VSMC migration and inflammatory cell recruitment in injured vessels. Thus, Atox1 is a potential therapeutic target for VSMC migration and inflammation-related vascular diseases.

Effect on Intimal Hyperplasia of Dexamethasone Released from Coated Metal Stents Compared with Non-Coated Stents in Canine Femoral Arteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strecker, Ernst-Peter; Gabelmann, Andreas; Boos, Irene

1998-11-15

Purpose: Polymer-coated, dexamethasone (DXM)-releasing stents were tested in order to assess the efficacy of DXM released locally for the prevention of stent restenosis due to intimal hyperplasia. Methods: Strecker stents coated with a biodegradable membrane containing DXM were implanted percutaneously into the femoral artery in 14 dogs. The contralateral artery received a conventional non-coated stent serving as control. The drugs are eluted by degradation of the carrier membrane. Follow-up intraarterial digital subtraction angiography (DSA) was obtained at 3, 6, 9, 12, and 24 weeks with subsequent autopsy. Specimens for gross and microscopic pathology were obtained and histomorphometry was performed. Results:more » Four of 14 DXM-coated stents showed thrombotic occlusion within the first 3 weeks; ten DXM-coated stents remained patent. At follow-up DSA, DXM-coated stents showed a significantly wider lumen than the non-coated stents. At morphometry there was less intimal hyperplasia over DXM-coated stents than over non-coated stents (p < 0.05). Conclusion: DXM-coated stents reduce neointimal hyperplasia in dogs when compared with non-coated stents.« less

In vivo evaluation of a fluorine-acryl-stylene-urethane-silicone antithrombogenic coating material copolymer for intravascular stents.

PubMed

Matsuhashi, T; Miyachi, H; Ishibashi, T; Sakamoto, K; Yamadera, A

1996-07-01

We evaluated the effectiveness of a fluorine-acryl-styrene-urethane-silicone (FASUS) copolymer as an antithrombogenic coating material for intravascular stents in dogs. FASUS copolymer-coated stents were placed in the right iliac veins, and uncoated 304 stainless steel stents were placed in the left iliac veins. We examined platelet deposition, microthrombus formation, and neointimal hyperplasia 4 weeks after stent placement by measuring the activity of 111In-labeled platelets, by using scanning electron microscopy, and by measuring neointimal thickness. Platelet deposition was significantly decreased on coated than on uncoated stents (p < .05). A less pronounced increase in red blood cell deposition was observed at the sites of the coated than uncoated stents (p < .05). Neointimal thickness 4 weeks after stent placement also was significantly less at the sites of the coated stents (0.27 +/- 0.08 mm versus 0.48 +/- 0.23 mm, p < .05). FASUS copolymer coating over the vascular stent is effective for preventing thrombus formation and neointimal hyperplasia.

Effects of ticagrelor on neointimal hyperplasia and endothelial function, compared with clopidogrel and prasugrel, in a porcine coronary stent restenosis model.

PubMed

Kim, Hyun Kuk; Jeong, Myung Ho; Lim, Kyung Seob; Kim, Jung Ha; Lim, Han Chul; Kim, Min Chul; Hong, Young Joon; Kim, Sung Soo; Park, Keun-Ho; Chang, Kyoung-Sig

2017-08-01

Several investigations have been conducted to evaluate the off-target effects of ticagrelor. The aim of the present study was to evaluate the off-target effects of ticagrelor such as neointimal formation and endothelial function after drug-eluting stent implantation in a porcine restenosis model. A total of 30 pigs were randomly allocated based on the following P2Y 12 inhibitor: (1) clopidogrel 300mg loading plus 75mg maintenance (n=10); (2) prasugrel 60mg loading plus 10mg maintenance (n=10); (3) ticagrelor 180mg loading plus 180mg maintenance (n=10). In each group, zotarolimus-eluting stents were implanted in the proximal portion of the left anterior descending artery and left circumflex artery. One month after stenting, the animals underwent follow-up angiography, endothelial function assessment, optical coherence tomography (OCT) and histopathological analysis. Regarding vasomotor responses to acetylcholine infusion, there were significant vasoconstrictions to maximal acetylcholine infusion in the clopidogrel and prasugrel group compared with those in the ticagrelor group. The mean neointimal area were significantly lower in the ticagrelor group (1.0±0.3 by OCT, 0.9±0.3 by histology), than in the clopidogrel (1.8±0.7, p=0.003, 1.6±0.8, p=0.030) and prasugrel (1.8±0.5, p=0.001, 1.5±0.5, p=0.019) groups. Percentages of moderate to dense peri-strut inflammatory cell infiltration were significantly lower in the ticagrelor group (9.0%) compared with the clopidogrel (17.3%, p<0.001) and prasugrel groups (15.7%, p=0.002). There were no significant differences in all findings between clopidogrel and prasugrel groups. Compared to clopidogrel and prasugrel, ticagrelor reduced neointimal formation, endothelial dysfunction, and peri-strut inflammation. Copyright © 2017 Elsevier B.V. All rights reserved.

Favorable effect of optimal lipid-lowering therapy on neointimal tissue characteristics after drug-eluting stent implantation: qualitative optical coherence tomographic analysis.

PubMed

Jang, Ji-Yong; Kim, Jung-Sun; Shin, Dong-Ho; Kim, Byeong-Keuk; Ko, Young-Guk; Choi, Donghoon; Jang, Yangsoo; Hong, Myeong-Ki

2015-10-01

Serial follow-up optical coherence tomography (OCT) was used to evaluate the effect of optimal lipid-lowering therapy on qualitative changes in neointimal tissue characteristics after drug-eluting stent (DES) implantation. DES-treated patients (n = 218) who received statin therapy were examined with serial follow-up OCT. First and second follow-up OCT evaluations were performed approximately 6 and 18 months after the index procedure, respectively. Patients were divided into two groups, based on the level of low-density lipoprotein-cholesterol (LDL-C), which was measured at the second follow-up. The optimal lipid-lowering group (n = 121) had an LDL-C reduction of ≥50% or an LDL-C level ≤70 mg/dL, and the conventional group (n = 97). Neointimal characteristics were qualitatively categorized as homogeneous or non-homogeneous patterns using OCT. The non-homogeneous group included heterogeneous, layered, or neoatherosclerosis patterns. Qualitative changes in neointimal tissue characteristics between the first and second follow-up OCT examinations were assessed. Between the first and second follow-up OCT procedures, the neointimal cross-sectional area increased more substantially in the conventional group (0.4 mm(2) vs. 0.2 mm(2) in the optimal lipid-lowering group, p = 0.01). The neointimal pattern changed from homogeneous to non-homogeneous less often in the optimal lipid-lowering group (1.3%, 1/77, p < 0.001) than in the conventional group (15.3%, 11/72, p = 0.44). Optimal LDL-C reduction was an independent predictor for the prevention of neointimal pattern change from homogeneous to non-homogeneous (odds ratio: 0.05, 95% confidence interval: 0.01∼0.46, p = 0.008). Our findings suggest that an intensive reduction in LDL-C levels can prevent non-homogeneous changes in the neointima and increases in neointimal cross-sectional area compared with conventional LDL-C controls. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Central role of endogenous Toll-like receptor-2 activation in regulating inflammation, reactive oxygen species production, and subsequent neointimal formation after vascular injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shishido, Tetsuro; Nozaki, Naoki; Takahashi, Hiroki

2006-07-14

Background: It is now evident that inflammation after vascular injury has significant impact on the restenosis after revascularization procedures such as angioplasty, stenting, and bypass grafting. However, the mechanisms that regulate inflammation and repair after vascular injury are incompletely understood. Here, we report that vascular injury-mediated cytokine expression, reactive oxygen species (ROS) production, as well as subsequent neointimal formation requires Toll-like receptor-2 (TLR-2) mediated signaling pathway in vivo. Methods and results: Vascular injury was induced by cuff-placement around the femoral artery in non-transgenic littermates (NLC) and TLR-2 knockout (TLR-2KO) mice. After cuff-placement in NLC mice, expression of TLR-2 was significantlymore » increased in both smooth muscle medial layer and adventitia. Interestingly, we found that inflammatory genes expression such as tumor necrosis factor-{alpha}, interleukin-1{beta} (IL-1{beta}), IL-6, and monocyte chemoattractant protein-1 were markedly decreased in TLR-2KO mice compared with NLC mice. In addition, ROS production after vascular injury was attenuated in TLR-2KO mice compared with NLC mice. Since we observed the significant role of endogenous TLR-2 activation in regulating inflammatory responses and ROS production after vascular injury, we determined whether inhibition of endogenous TLR-2 activation can inhibit neointimal proliferation after vascular injury. Neointimal hyperplasia was markedly suppressed in TLR-2KO mice compared with WT mice at both 2 and 4 weeks after vascular injury. Conclusions: These findings suggested that endogenous TLR-2 activation might play a central role in the regulation of vascular inflammation as well as subsequent neointimal formation in injured vessels.« less

Deficiency of endothelial CXCR4 reduces reendothelialization and enhances neointimal hyperplasia after vascular injury in atherosclerosis-prone mice.

PubMed

Noels, Heidi; Zhou, Baixue; Tilstam, Pathricia V; Theelen, Wendy; Li, Xiaofeng; Pawig, Lukas; Schmitz, Corinna; Akhtar, Shamima; Simsekyilmaz, Sakine; Shagdarsuren, Erdenechimeg; Schober, Andreas; Adams, Ralf H; Bernhagen, Jürgen; Liehn, Elisa A; Döring, Yvonne; Weber, Christian

2014-06-01

The Cxcl12/Cxcr4 chemokine ligand/receptor axis mediates the mobilization of smooth muscle cell progenitors, driving injury-induced neointimal hyperplasia. This study aimed to investigate the role of endothelial Cxcr4 in neointima formation. β-Galactosidase staining using bone marrow x kinase (Bmx)-CreER(T2) reporter mice and double immunofluorescence revealed an efficient and endothelial-specific deletion of Cxcr4 in Bmx-CreER(T2+) compared with Bmx-CreER(T2-) Cxcr4-floxed apolipoprotein E-deficient (Apoe(-/-)) mice (referred to as Cxcr4(EC-KO)ApoE(-/-) and Cxcr4(EC-WT) ApoE(-/-), respectively). Endothelial Cxcr4 deficiency significantly increased wire injury-induced neointima formation in carotid arteries from Cxcr4(EC-KO)ApoE(-/-) mice. The lesions displayed a higher number of macrophages, whereas the smooth muscle cell and collagen content were reduced. This was associated with a significant reduction in reendothelialization and endothelial cell proliferation in injured Cxcr4(EC-KO)ApoE(-/-) carotids compared with Cxcr4(EC-WT)ApoE(-/-) controls. Furthermore, stimulation of human aortic endothelial cells with chemokine (C-X-C motif) ligand 12 (CXCL12) significantly enhanced their wound-healing capacity in an in vitro scratch assay, an effect that could be reversed with the CXCR4 antagonist AMD3100. Also, flow cytometric analysis showed a reduced mobilization of Sca1(+)Flk1(+)Cd31(+) and of Lin(-)Sca1(+) progenitors in Cxcr4(EC-KO) ApoE(-/-) mice after vascular injury, although Cxcr4 surface expression was unaltered. No differences could be detected in plasma concentrations of Cxcl12, vascular endothelial growth factor, sphingosine 1-phosphate, or Flt3 (fms-related tyrosine kinase 3) ligand, all cytokines with an established role in progenitor cell mobilization. Nonetheless, double immunofluorescence revealed a significant reduction in local endothelial Cxcl12 staining in injured carotids from Cxcr4(EC-KO)ApoE(-/-) mice. Endothelial Cxcr4 is crucial for

Neointimal patterns obtained by optical coherence tomography correlate with specific histological components and neointimal proliferation in a swine model of restenosis.

PubMed

Kim, Jung-Sun; Afari, Maxwell E; Ha, Jinyong; Tellez, Armando; Milewski, Krzysztof; Conditt, Gerard; Cheng, Yanping; Hua Yi, Geng; Kaluza, Greg L; Granada, Juan F

2014-03-01

Although optical coherence tomography (OCT) is capable to detect microscopic peri-strut changes that seem to be related to neointimal inhibition and healing, its ability to characterize these components is still limited. In this study, we aimed to compare different OCT morphological characteristics with different in-stent neointimal tissue types analysed by histology. A total of 69 stents (39 drug eluting and 30 bare metal stents) were implanted in coronary arteries of 27 swine. By OCT, neointimal type was classified as homogeneous, heterogeneous, or layered according to its pattern of backscatter and optical intensity. The resulting optical patterns were correlated with several histological findings [external elastic lamina (EEL) disruption, fibrin deposition, circumferential rim of peri-strut inflammatory cell infiltration, and fibrous connective deposition] in every single cross-section (CS) analysed. A total of 197 matched OCT and histological CS were analysed. The heterogeneous (0.44 ± 0.21 mm) and layered (0.65 ± 0.16 mm) patterns had a significantly higher degree of neointimal thickness compared with the homogeneous pattern (0.25 ± 0.16 mm, P < 0.001). Fibrous connective tissue deposition was more frequently present in the homogeneous pattern (71.6%, P < 0.001), whereas significant fibrin deposits were more commonly seen in the heterogeneous pattern (56.9%, P = 0.007). Peri-strut inflammation was less frequently found in the homogeneous pattern (19.8%, P < 0.001) in comparison with the layered (73.9%) or heterogeneous patterns (43.1%). The presence of EEL rupture was also more commonly seen in layered (73.9%) and heterogeneous (46.6%) patterns than in the homogeneous pattern (22.4%, P < 0.001). The optical characteristics of neointimal formation seen in OCT properly correlated with the presence of several histological findings involved in stent healing. The biological implications of these findings in clinical outcomes require further investigation.

Novel Paradigms for Dialysis Vascular Access: Downstream Vascular Biology–Is There a Final Common Pathway?

PubMed Central

2013-01-01

Summary Vascular access dysfunction is a major cause of morbidity and mortality in hemodialysis patients. The most common cause of vascular access dysfunction is venous stenosis from neointimal hyperplasia within the perianastomotic region of an arteriovenous fistula and at the graft-vein anastomosis of an arteriovenous graft. There have been few, if any, effective treatments for vascular access dysfunction because of the limited understanding of the pathophysiology of venous neointimal hyperplasia formation. This review will (1) describe the histopathologic features of hemodialysis access stenosis; (2) discuss novel concepts in the pathogenesis of neointimal hyperplasia development, focusing on downstream vascular biology; (3) highlight future novel therapies for treating downstream biology; and (4) discuss future research areas to improve our understanding of downstream biology and neointimal hyperplasia development. PMID:23990166

Automatic characterization of neointimal tissue by intravascular optical coherence tomography.

PubMed

Ughi, Giovanni J; Steigerwald, Kristin; Adriaenssens, Tom; Desmet, Walter; Guagliumi, Giulio; Joner, Michael; D'hooge, Jan

2014-02-01

Intravascular optical coherence tomography (IVOCT) is rapidly becoming the method of choice for assessing vessel healing after stent implantation due to its unique axial resolution <20  μm. The amount of neointimal coverage is an important parameter. In addition, the characterization of neointimal tissue maturity is also of importance for an accurate analysis, especially in the case of drug-eluting and bioresorbable stent devices. Previous studies indicated that well-organized mature neointimal tissue appears as a high-intensity, smooth, and homogeneous region in IVOCT images, while lower-intensity signal areas might correspond to immature tissue mainly composed of acellular material. A new method for automatic neointimal tissue characterization, based on statistical texture analysis and a supervised classification technique, is presented. Algorithm training and validation were obtained through the use of 53 IVOCT images supported by histology data from atherosclerotic New Zealand White rabbits. A pixel-wise classification accuracy of 87% and a two-dimensional region-based analysis accuracy of 92% (with sensitivity and specificity of 91% and 93%, respectively) were found, suggesting that a reliable automatic characterization of neointimal tissue was achieved. This may potentially expand the clinical value of IVOCT in assessing the completeness of stent healing and speed up the current analysis methodologies (which are, due to their time- and energy-consuming character, not suitable for application in large clinical trials and clinical practice), potentially allowing for a wider use of IVOCT technology.

Gingerol Inhibits Serum-Induced Vascular Smooth Muscle Cell Proliferation and Injury-Induced Neointimal Hyperplasia by Suppressing p38 MAPK Activation.

PubMed

Jain, Manish; Singh, Ankita; Singh, Vishal; Maurya, Preeti; Barthwal, Manoj Kumar

2016-03-01

Gingerol inhibits growth of cancerous cells; however, its role in vascular smooth muscle cell (VSMC) proliferation is not known. The present study investigated the effect of gingerol on VSMC proliferation in cell culture and during neointima formation after balloon injury. Rat VSMCs or carotid arteries were harvested at 15 minutes, 30 minutes, 1, 6, 12, and 24 hours of fetal bovine serum (FBS; 10%) stimulation or balloon injury, respectively. Gingerol prevented FBS (10%)-induced proliferation of VSMCs in a dose-dependent manner (50 μmol/L-400 μmol/L). The FBS-induced proliferating cell nuclear antigen (PCNA) upregulation and p27(Kip1) downregulation were also attenuated in gingerol (200 μmol/L) pretreated cells. Fetal bovine serum-induced p38 mitogen-activated protein kinase (MAPK) activation, PCNA upregulation, and p27(Kip1) downregulation were abrogated in gingerol (200 μmol/L) and p38 MAPK inhibitor (SB203580, 10 μmol/L) pretreated cells. Balloon injury induced time-dependent p38 MAPK activation in the carotid artery. Pretreatment with gingerol (200 μmol/L) significantly attenuated injury-induced p38 MAPK activation, PCNA upregulation, and p27(Kip1) downregulation. After 14 days of balloon injury, intimal thickening, neointimal proliferation, and endothelial dysfunction were significantly prevented in gingerol pretreated arteries. In isolated organ bath studies, gingerol (30 nmol/L-300 μmol/L) inhibited phenylephrine-induced contractions and induced dose-dependent relaxation of rat thoracic aortic rings in a partially endothelium-dependent manner. Gingerol prevented FBS-induced VSMC proliferation and balloon injury-induced neointima formation by regulating p38 MAPK. Vasodilator effect of gingerol observed in the thoracic aorta was partially endothelium dependent. Gingerol is thus proposed as an attractive agent for modulating VSMC proliferation, vascular reactivity, and progression of vascular proliferative diseases. © The Author(s) 2015.

Prevention of Bronchial Hyperplasia by EGFR Pathway Inhibitors in an Organotypic Culture Model

PubMed Central

Lee, Jangsoon; Ryu, Seung-Hee; Kang, Shin Myung; Chung, Wen-Cheng; Gold, Kathryn Ann; Kim, Edward S.; Hittelman, Walter N.; Hong, Waun Ki; Koo, Ja Seok

2011-01-01

Lung cancer is the leading cause of cancer-related mortality worldwide. Early detection or prevention strategies are urgently needed to increase survival. Hyperplasia is the first morphologic change that occurs in the bronchial epithelium during lung cancer development, followed by squamous metaplasia, dysplasia, carcinoma in situ, and invasive tumor. The current study was designed to determine the molecular mechanisms that control bronchial epithelium hyperplasia. Using primary normal human tracheobronchial epithelial (NHTBE) cells cultured using the 3-dimensional organotypic method, we found that the epidermal growth factor receptor (EGFR) ligands EGF, transforming growth factor-alpha, and amphiregulin induced hyperplasia, as determined by cell proliferation and multilayered epithelium formation. We also found that EGF induced increased cyclin D1 expression, which plays a critical role in bronchial hyperplasia; this overexpression was mediated by activating the mitogen-activated protein kinase pathway but not the phosphoinositide 3-kinase/Akt signaling pathway. Erlotinib, an EGFR tyrosine kinase inhibitor, and U0126, a MEK inhibitor, completely inhibited EGF-induced hyperplasia. Furthermore, a promoter analysis revealed that the activator protein-1 transcription factor regulates EGF-induced cyclin D1 overexpression. Activator protein-1 depletion using siRNA targeting its c-Jun component completely abrogated EGF-induced cyclin D1 expression. In conclusion, we demonstrated that bronchial hyperplasia can be modeled in vitro using primary NHTBE cells maintained in a 3-dimensional (3-D) organotypic culture. EGFR and MEK inhibitors completely blocked EGF-induced bronchial hyperplasia, suggesting that they have a chemopreventive role. PMID:21505178

Impact of vessel curvature on neointimal healing after stent implantation as assessed by optical coherence tomography.

PubMed

Fu, Yandong; Zhang, Shaotao; Du, Hongwei; Li, Lulu; Wang, Chao; Zheng, Gonghui; Wang, Yan; Dong, Hui; Jia, Haibo; Yu, Bo

2018-04-01

Previous studies have indicated that stent implantation could alter the vessel geometry, which may impact the neointimal healing process. Curvature is an important parameter for evaluating vessel geometry. The purpose of our study was to investigate the relationship between vessel curvature and neointimal healing after stent implantation. Fifty-nine patients with acute coronary syndrome (ACS) who underwent stent implantation were enrolled in the study. According to the post-percutaneous coronary intervention vessel curvature measured by quantitative coronary angiography, patients were divided into high (n = 30) and low (n = 29) curvature groups. Neointimal thickness and area together with the neointimal type were assessed by optical coherence tomography at a 6-month follow-up. Baseline clinical characteristics were comparable between the 2 groups. The vessel curvature at pre- and 6-month follow-up was significantly higher in the high curvature group than the low curvature group. At 6-month follow-up, neointimal thickness (0.22 [0.08-0.32] mm vs. 0.10 [0.07-0.16] mm, P = .043) and neointimal area (1.86 [0.66-2.66] vs. 0.82 [0.60-1.41] mm, P = .030) were significantly higher in the high curvature group than the low curvature group. In the high curvature group, the incidence of the heterogeneous neointimal type was higher than that in the low curvature group (50.00% vs. 17.20%, respectively, P = .004), whereas the frequency of the homogeneous neointimal type was lower (43.30% vs. 82.80%, respectively, P = .004) in the high curvature group than the low curvature group. Higher vessel curvature after stent implantation may potentially have an impact on the neointimal healing with a higher incidence of heterogeneous neointimal.

Experimental Evaluation of a New Tubular Coronary Stent (V-Flexª).

PubMed

Shun; Wang; Zhou; Verbeken; Ping; Szilard; Yanming; Jianhua; De Scheerder IK

1998-11-01

The safety, efficacy, angiographic and histological effects of a new 316 L, SS seamless stainless steel tubular stent (V-Flexª, Global Therapeutics, Broomfield, Colorado) was evaluated in a porcine coronary and peripheral artery model. Implantation in the right coronary artery was successful in all 16 pigs. Eight pigs were angiographically controlled after 6 weeks and then sacrificed for morphometric analysis. All stented coronary vessels were widely patent at this moment and morphometric analysis showed only a mild fibromuscular neointimal hyperplasia resulting in a neointimal hyperplasia of 1.15 +/- 0.38 mm2. The remaining 8 pigs were controlled and sacrificed at 12 weeks. At that time, all stented vessels were patent and neointimal hyperplasia was 1.22 +/- 0.34 mm2. Comparison with the Palmaz-Schatzª coronary stent (Cordis, Miami, Florida) in a porcine peripheral artery model demonstrated significantly less neointimal hyperplasia at 6 weeks (1.11 +/- 0.73 vs. 2.40 +/- 0.36, p = 0.001) and at 12 weeks (1.53 +/- 0.42 vs. 2.47 +/- 0.63, p = 0.003) for the V-Flex stent. In conclusion, V-Flex coronary stent implantation in a porcine coronary and peripheral arteries results in a high procedural success rate without subacute thrombotic occlusions, despite no further anticoagulation nor antiplatelet therapy. Six and 12 week histopathological and morphometric evaluation demonstrated only a mild fibromuscular neointimal hyperplasia. Comparison with the Palmaz-Schatz coronary stent in a peripheral artery model showed significantly less neointimal hyperplasia in the V-Flex stent.

Comparison of diamond-like carbon-coated nitinol stents with or without polyethylene glycol grafting and uncoated nitinol stents in a canine iliac artery model

PubMed Central

Kim, J H; Shin, J H; Shin, D H; Moon, M-W; Park, K; Kim, T-H; Shin, K M; Won, Y H; Han, D K; Lee, K-R

2011-01-01

Objective Neointimal hyperplasia is a major complication of endovascular stent placement with consequent in-stent restenosis or occlusion. Improvements in the biocompatibility of stent designs could reduce stent-associated thrombosis and in-stent restenosis. We hypothesised that the use of a diamond-like carbon (DLC)-coated nitinol stent or a polyethylene glycol (PEG)-DLC-coated nitinol stent could reduce the formation of neointimal hyperplasia, thereby improving stent patency with improved biocompatibility. Methods A total of 24 stents were implanted, under general anaesthesia, into the iliac arteries of six dogs (four stents in each dog) using the carotid artery approach. The experimental study dogs were divided into three groups: the uncoated nitinol stent group (n = 8), the DLC-nitinol stent group (n = 8) and the PEG-DLC-nitinol stent group (n = 8). Results The mean percentage of neointimal hyperplasia was significantly less in the DLC-nitinol stent group (26.7±7.6%) than in the nitinol stent group (40.0±20.3%) (p = 0.021). However, the mean percentage of neointimal hyperplasia was significantly greater in the PEG-DLC-nitinol stent group (58.7±24.7%) than in the nitinol stent group (40.0±20.3%) (p = 0.01). Conclusion Our findings indicate that DLC-coated nitinol stents might induce less neointimal hyperplasia than conventional nitinol stents following implantation in a canine iliac artery model; however, the DLC-coated nitinol stent surface when reformed with PEG induces more neointimal hyperplasia than either a conventional or DLC-coated nitinol stent. PMID:21325363

Exercise training prevents endometrial hyperplasia and biomarkers for endometrial cancer in rat model of type 1 diabetes.

PubMed

Al-Jarrah, Muhammed; Matalka, Ismail; Aseri, Hasan Al; Mohtaseb, Alia; Smirnova, Irina V; Novikova, Lesya; Stehno-Bittel, Lisa; Alkhateeb, Ahed

2010-10-11

Endometrial cancer is one of the most common types of gynecologic cancers. The ability of exercise to reduce the risk of endometrial cancer in women with type 2 diabetes has been established, but no studies have examined this link in type 1 diabetes.A randomized, controlled animal study was designed using a standard rat model of type 1 diabetes. The goal of this study was to investigate the ability of exercise to prevent increased levels of endometrial cancer biomarkers, estrogen receptor (ERα) and p16, and endometrial hyperplasia associated with diabetes. FORTY FEMALE RATS WERE RANDOMIZED INTO FOUR GROUPS: sedentary control, exercise control, sedentary or exercised diabetic. Diabetes was induced by alloxan injection. A 4-week treadmill training program was initiated with the development of diabetes. Endometrial tissues were evaluated for hyperplasia and ERα and p16 levels and subcellular localization using microscopy. Severe diabetes lead to hyperplasia in the endometrial tissue in 70% of sedentary diabetic rats. Exercise-trained diabetic rats and the non-diabetic rats displayed no hyperplasia. The expression of ERα increased significantly (p < 0.02) while the expression level of p16 decreased significantly (p < 0.04) in the diabetic sedentary group compared to the non-diabetic groups. Exercise training led to a reversal in the percentage of p16 and ERα positive cells in diabetic rats. Severe diabetes leads to hyperplasia of the endometrial tissue and increased ERα levels and decreased p16 levels in rats, which can be prevented with aerobic exercise. Diabetes; Estrogen receptor alpha; P16; Endometrial hyperplasia; Endometrial cancer; Exercise.

Small interfering RNA targeting nuclear factor kappa B to prevent vein graft stenosis in rat models.

PubMed

Meng, X B; Bi, X L; Zhao, H L; Feng, J B; Zhang, J P; Song, G M; Sun, W Y; Bi, Y W

2013-01-01

Intimal hyperplasia plays an important role in vein graft stenosis. Inflammatory injury, especially nuclear factor kappaB (NF-κB) gene activation, is highly involved in stenosis progression. We examined whether neointimal hyperplasia and vein graft stenosis could be inhibited by silencing the NF-κB gene with small interference RNA (siRNA). Sixty adult male Sprague-Dawley rats were randomly divided into a normal vein group, a vein graft group, a scrambled siRNA group, and an NF-κB siRNA group. We performed reverse interpositional grafting of the autologous external jugular vein to the abdominal aorta. Vein grafts were treated with liposome and gel complexes containing NF-κB siRNA or scrambled siRNA. The levels of monocyte chemoattractant protein -1, tumor necrosis factor-α, and NF-κB p65 in vessel tissues were evaluated after surgery for content of proliferating cell nuclear antigen (PCNA) and vascular wall thickness. NF-κB siRNA treated vein graft showed less neointimal formation and fewer positive PCNA cells (P < .05). In addition there were lower levels of, NF-κB p65 protein and of inflammatory mediators (P < .05) compared with the vein graft group. Our study suggested that siRNA transfection suppressed NF-κB expression, reduced inflammatory factors, lessened neointimal proliferation, and suppressed PCNA. Copyright © 2013 Elsevier Inc. All rights reserved.

A stent for co-delivering paclitaxel and nitric oxide from abluminal and luminal surfaces: Preparation, surface characterization, and in vitro drug release studies

NASA Astrophysics Data System (ADS)

Gallo, Annemarie; Mani, Gopinath

2013-08-01

Most drug-eluting stents currently available are coated with anti-proliferative drugs on both abluminal (toward blood vessel wall) and luminal (toward lumen) surfaces to prevent neointimal hyperplasia. While the abluminal delivery of anti-proliferative drugs is useful for controlling neointimal hyperplasia, the luminal delivery of such drugs impairs or prevents endothelialization which causes late stent thrombosis. This research is focused on developing a bidirectional dual drug-eluting stent to co-deliver an anti-proliferative agent (paclitaxel - PAT) and an endothelial cell promoting agent (nitric oxide - NO) from abluminal and luminal surfaces of the stent, respectively. Phosphonoacetic acid, a polymer-free drug delivery platform, was initially coated on the stents. Then, the PAT and NO donor drugs were co-coated on the abluminal and luminal stent surfaces, respectively. The co-coating of drugs was collectively confirmed by the surface characterization techniques such as Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), 3D optical surface profilometry, and contact angle goniometry. SEM showed that the integrity of the co-coating of drugs was maintained without delamination or cracks formation occurring during the stent expansion experiments. In vitro drug release studies showed that the PAT was released from the abluminal stent surfaces in a biphasic manner, which is an initial burst followed by a slow and sustained release. The NO was burst released from the luminal stent surfaces. Thus, this study demonstrated the co-delivery of PAT and NO from abluminal and luminal stent surfaces, respectively. The stent developed in this study has potential applications in inhibiting neointimal hyperplasia as well as encouraging luminal endothelialization to prevent late stent thrombosis.

Role of the Renin–Angiotensin System in the Pathogenesis of Intimal Hyperplasia: Therapeutic Potential for Prevention of Vein Graft Failure?

PubMed Central

Osgood, Michael J.; Harrison, David G.; Sexton, Kevin W.; Hocking, Kyle M.; Voskresensky, Igor V.; Komalavilas, Padmini; Cheung-Flynn, Joyce; Guzman, Raul J.; Brophy, Colleen M.

2014-01-01

The saphenous vein remains the most widely used conduit for peripheral and coronary revascularization despite a high rate of vein graft failure. The most common cause of vein graft failure is intimal hyperplasia. No agents have been proven to be successful for the prevention of intimal hyperplasia in human subjects. The rennin–angiotensin system is essential in the regulation of vascular tone and blood pressure in physiologic conditions. However, this system mediates cardiovascular remodeling in pathophysiologic states. Angiotensin II is becoming increasingly recognized as a potential mediator of intimal hyperplasia. Drugs modulating the renin–angiotensin system include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. These drugs are powerful inhibitors of atherosclerosis and cardiovascular remodeling, and they are first-line agents for management of several medical conditions based on class I evidence that they delay progression of cardiovascular disease and improve survival. Several experimental models have demonstrated that these agents are capable of inhibiting intimal hyperplasia. However, there are no data supporting their role in prevention of intimal hyperplasia in patients with vein grafts. This review summarizes the physiology of the rennin–angiotensin system, the role of angiotensin II in the pathogenesis of cardiovascular remodeling, the medical indications for these agents, and the experimental data supporting an important role of the rennin–angiotensin system in the pathogenesis of intimal hyperplasia. PMID:22445245

Current siRNA Targets in the Prevention and Treatment of Intimal Hyperplasia

PubMed Central

Pradhan-Nabzdyk, Leena; Huang, Chenyu; LoGerfo, Frank W.; Nabzdyk, Christoph S.

2014-01-01

Intimal hyperplasia (IH) is the leading cause of late vein and prosthetic bypass graft failure. Injury at the time of graft implantation leading to the activation of endothelial cells and dedifferentiation of vascular smooth muscle cells to a synthetic phenotype are known causes of IH. Prior attempts to develop therapy to mitigate these cellular changes to prevent IH and graft failure have failed. Small interfering RNA (siRNA) mediated targeted gene silencing is a promising tool to prevent IH. Several studies have been performed in this direction to target genes that are involved in IH. In this review we discuss siRNA targets that are being investigated for prevention and treatment of IH. PMID:25227753

Reduction of Intimal Hyperplasia with Re-188-labeled Stents in a Rabbit Model at 7 and 26 Weeks: An Experimental Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tepe, Gunnar, E-mail: gunnar.tepe@med.uni-tuebingen.de; Dietrich, Tobias; Grafen, Franziska

2005-06-15

The aim of this study was to analyze the feasibility of {sup 188}Re-labeled stents to reduce neointimal formation in a rabbit atherosclerosis model and to test the long-term effects at 7 and 26 weeks. Fifty-nine male New Zealand White rabbits were fed a 0.5% cholesterol diet for 4 weeks before balloon angioplasty and insertion of Palmaz stents in the infrarenal aorta. The animals were sacrificed 7 and 26 weeks after stent implantation. Control stents were compared with {sup 188}Re stents: (dose 1) 11.3 {+-} 1.8 MBq; (dose 2) 37.3 {+-} 4.2 MBq, and (dose 3) 80.1 {+-} 7.8 MBq. Eachmore » activity group consisted of a short-term (7 weeks) and a long-term group (26 weeks), resulting in a total of eight study groups. No thrombotic occlusion was observed. The neointimal formation in the control group was 2.11 [95% confidence interval (CI): 0.68-6.52] mm{sup 2} at 7 weeks and 2.10 (0.62-7.11) at 26 weeks. In the treatment groups, neointima reduction was detectable at 7 weeks [dose 1: 0.33 (0.09-1.22) mm{sup 2}; dose 2: 0.17 (0.05-0.57) mm{sup 2}; dose 3: 0.03 (0.01-0.13) mm{sup 2}]. After 26 weeks, a catch-up of neointimal formation in the radioactive groups was most obvious in the low-dose group [dose 1: 0.80 (0.28-2.29) mm{sup 2}; dose 2: 0.18([0.06-0.52) mm{sup 2}; dose 3: 0.50 (0.17-1.42) mm{sup 2}]. Compared to the long-term control group, neointimal reduction was still >60%. No induction of neointimal formation was observed at the edges of the stents. Radiation resulted in delayed re-endothelialization. {sup 188}Re stents were capable to reduce intimal hyperplasia and did not cause thrombosis. The edge effect, which was the major limitation of {sup 32}P stents, was not observed in {sup 188}Re stents.« less

Preventive effects of ACTICOA powder, a cocoa polyphenolic extract, on experimentally induced prostate hyperplasia in Wistar-Unilever rats.

PubMed

Bisson, Jean-François; Hidalgo, Sophie; Rozan, Pascale; Messaoudi, Michaël

2007-12-01

Plant extracts are useful in the management of benign prostatic hyperplasia (BPH). This study investigates whether ACTICOA (Barry Callebaut France, Louviers, France) powder (AP), a cocoa polyphenolic extract, could prevent prostate hyperplasia induced by testosterone propionate (TP) in rats. Male Wistar-Unilever rats were randomly divided in four groups of 12 rats: one negative control group receiving subcutaneous injections of corn oil and treated with vehicle and three groups injected subcutaneously with TP and treated with the vehicle (positive control) or AP at 24 (AP24) and 48 (AP48) mg/kg/day. Treatments were given orally and started 2 weeks before the induction of prostate hyperplasia. The influence of TP and AP on body weights and food and water consumption of rats was examined. On day 36, rats were sacrificed, and the prostates were removed, cleaned, and weighed. The prostate size ratio (prostate weight/rat body weight) was then calculated. TP significantly influenced the body weight gain of the rats and their food and water consumption, while AP at both doses tested reduced significantly these differences. TP significantly increased prostate size ratio (P < .001), and this induced increase was significantly inhibited in AP-treated rats in comparison with positive controls (P < .001) in a dose-dependent manner. We conclude that AP can prevent TP-induced prostate hyperplasia and therefore may be beneficial in the management of BPH.

Inhibition of vascular smooth muscle cell proliferation and migration in vitro and neointimal hyperplasia in vivo by adenoviral-mediated atrial natriuretic peptide delivery.

PubMed

Larifla, Laurent; Déprez, Isabelle; Pham, Isabelle; Rideau, Dominique; Louzier, Vanessa; Adam, Micheline; Eloit, Marc; Foucan, Lydia; Adnot, Serge; Teiger, Emmanuel

2012-07-01

Vascular smooth muscle cell (VSMC) proliferation and migration are important components of the remodeling process in atherosclerosis or following angioplasty. Atrial natriuretic peptide (ANP) inhibits the growth of VSMCs in vitro but this effect has not been proven in vivo. In the present study, we examined the effects of local overexpression of ANP following gene transfer on in vitro VSMC proliferation and migration and in vivo neointimal formation in a rat carotid artery model of vascular injury. ANP gene transfer was performed using a recombinant adenovirus containing the ANP cDNA controlled by the Rous sarcoma virus (RSV) long terminal repeat (Ad-RSV-ANP). A recombinant adenovirus expressing the RSV-controlled β-galactosidase gene (Ad-RSV-β-gal) was used as the control. Rat VSMC culture was used for in vitro studies. In the in vivo experiments, carotid arteries were analyzed after balloon injury and local infusion of the viral solution. VSMCs transfected by Ad-RSV-ANP produced a significant amount of ANP detected by immunoreactive assay and accumulated about 6.5 times more cGMP than the viral control. VSMC proliferation stimulated with 10% fetal calf serum was reduced by 31% and migration by 25%. Fourteen days after injury, neointimal formation and the intima/media ratio were reduced by 25% and 28%, respectively, in the Ad-RSV-ANP-treated group compared to the control group. The present study demonstrates the efficacy of recombinant adenovirus Ad-RSV-ANP with respect to inhibiting rat VSMC proliferation and migration. Our findings also provide evidence that ANP is implicated in the modulation of vascular remodeling following endothelial injury. Copyright © 2012 John Wiley & Sons, Ltd.

Neointimal Hyperplasia after Silverhawk Atherectomy versus Percutaneous Transluminal Angioplasty (PTA) in Femoropopliteal Stent Reobstructions: A Controlled, Randomized Pilot Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brodmann, Marianne, E-mail: marianne.brodmann@medunigraz.at; Rief, Peter; Froehlich, Harald

2013-02-15

Due to intimal hyperplasia instent reobstruction in the femoropopliteal arterial segment is still an unsolved problem. Different techniques have been discussed in case of reintervention to guarantee longlasting patency rate. We conducted a randomized, controlled, pilot trial comparing Silverhawk atherectomy with percutaneous transluminal angioplasty (PTA) in patients with a first instent reobstruction in the femoropopliteal arterial segment, to evaluate intima media thickness (IMT) within the treated segment, as a parameter of recurrence of intimal hyperplasia. In a total 19 patients were included: 9 patients in the atherectomy device and 10 patients in the PTA arm. IMT within the treated segmentmore » was statistically significantly elevated in all patients treated with the Silverhawk device versus the patients treated with PTA. The obvious differentiation in elevation of IMT in nonfavor for patients treated with the Silverhawk device started at month 2 (max IMT SH 0.178 mm vs. IMT PTA 0.1 mm, p = 0.001) with a spike at month 5 (max IMT SH 0.206 mm vs. IMT PTA 0.145 mm, p = 0.003) and a decline once again at month 6 (max IMT SH 0.177 mm vs. IMT PTA 0.121 mm, p = 0.02). The values for mean IMT performed the same way. Although Silverhawk atherectomy provides good results at first sight, in the midterm follow-up of treatment of first instent restenosis it did not perform better than PTA as it showed elevated reoccurrence of intimal media hyperplasia.« less

Neointimal hyperplasia after silverhawk atherectomy versus percutaneous transluminal angioplasty (PTA) in femoropopliteal stent reobstructions: a controlled, randomized pilot trial.

PubMed

Brodmann, Marianne; Rief, Peter; Froehlich, Harald; Dorr, Andreas; Gary, Thomas; Eller, Philipp; Hafner, Franz; Deutschmann, Hannes; Seinost, Gerald; Pilger, Ernst

2013-02-01

Due to intimal hyperplasia instent reobstruction in the femoropopliteal arterial segment is still an unsolved problem. Different techniques have been discussed in case of reintervention to guarantee longlasting patency rate. We conducted a randomized, controlled, pilot trial comparing Silverhawk atherectomy with percutaneous transluminal angioplasty (PTA) in patients with a first instent reobstruction in the femoropopliteal arterial segment, to evaluate intima media thickness (IMT) within the treated segment, as a parameter of recurrence of intimal hyperplasia. In a total 19 patients were included: 9 patients in the atherectomy device and 10 patients in the PTA arm. IMT within the treated segment was statistically significantly elevated in all patients treated with the Silverhawk device versus the patients treated with PTA. The obvious differentiation in elevation of IMT in nonfavor for patients treated with the Silverhawk device started at month 2 (max IMT SH 0.178 mm vs. IMT PTA 0.1 mm, p = 0.001) with a spike at month 5 (max IMT SH 0.206 mm vs. IMT PTA 0.145 mm, p = 0.003) and a decline once again at month 6 (max IMT SH 0.177 mm vs. IMT PTA 0.121 mm, p = 0.02). The values for mean IMT performed the same way. Although Silverhawk atherectomy provides good results at first sight, in the midterm follow-up of treatment of first instent restenosis it did not perform better than PTA as it showed elevated reoccurrence of intimal media hyperplasia.

Roscovitine attenuates intimal hyperplasia via inhibiting NF-κB and STAT3 activation induced by TNF-α in vascular smooth muscle cells.

PubMed

He, Ming; Wang, Chao; Sun, Jia-Huan; Liu, Yu; Wang, Hong; Zhao, Jing-Shan; Li, Yun-Feng; Chang, Hong; Hou, Jian-Ming; Song, Jun-Na; Li, Ai-Ying; Ji, En-Sheng

2017-08-01

Roscovitine is a selective CDK inhibitor originally designed as anti-cancer agent, which has also been shown to inhibit proliferation in vascular smooth muscle cells (VSMCs). However, its effect on vascular remodeling and its mechanism of action remain unknown. In our study, we created a new intimal hyperplasia model in male Sprague-Dawley rats by trypsin digestion method, which cause to vascular injury as well as the model of rat carotid balloon angioplasty. Roscovitine administration led to a significant reduction in neointimal formation and VSMCs proliferation after injury in rats. Western blot analysis revealed that, in response to vascular injury, TNF-α stimulation induced p65 and STAT3 phosphorylation and promoted translocation of these molecules into the nucleus. p65 can physically associate with STAT3 and bind to TNF-α-regulated target promoters, such as MCP-1 and ICAM-1, to initiate gene transcription. Roscovitine can interrupt activation of NF-κB and reduce expression of TNF-α-induced proinflammatory gene, thus inhibiting intimal hyperplasia. These findings provide a novel mechanism to explain the roscovitine-mediated inhibition of intimal hyperplasia induced by proinflammatory pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Selective endothelin A receptor antagonism with sitaxentan reduces neointimal lesion size in a mouse model of intraluminal injury

PubMed Central

Duthie, Karolina M; Hadoke, Patrick W F; Kirkby, Nicholas S; Miller, Eileen; Ivy, Jessica R; McShane, John F; Lim, Win Gel; Webb, David J

2015-01-01

Background and Purpose Endothelin (ET) receptor antagonism reduces neointimal lesion formation in animal models. This investigation addressed the hypothesis that the selective ETA receptor antagonist sitaxentan would be more effective than mixed ETA/B receptor antagonism at inhibiting neointimal proliferation in a mouse model of intraluminal injury. Experimental Approach Antagonism of ETA receptors by sitaxentan (1–100 nM) was assessed in femoral arteries isolated from adult, male C57Bl6 mice using isometric wire myography. Neointimal lesion development was induced by intraluminal injury in mice receiving sitaxentan (ETA antagonist; 15 mg·kg−1·day−1), A192621 (ETB antagonist; 30 mg·kg−1·day−1), the combination of both antagonists or vehicle. Treatment began 1 week before, and continued for 28 days after, surgery. Femoral arteries were then harvested for analysis of lesion size and composition. Key Results Sitaxentan produced a selective, concentration-dependent parallel rightward shift of ET-1-mediated contraction in isolated femoral arteries. Sitaxentan reduced neointimal lesion size, whereas ETB and combined ETA/B receptor antagonism did not. Macrophage and α-smooth muscle actin content were unaltered by ET receptor antagonism but sitaxentan reduced the amount of collagen in lesions. Conclusions and Implications These results suggest that ETA receptor antagonism would be more effective than combined ETA/ETB receptor antagonism at reducing neointimal lesion formation. PMID:25598351

Parathyroid hyperplasia

MedlinePlus

Enlarged parathyroid glands; Osteoporosis - parathyroid hyperplasia; Bone thinning - parathyroid hyperplasia; Osteopenia - parathyroid hyperplasia; High calcium level - parathyroid hyperplasia; Chronic kidney disease - parathyroid hyperplasia; ...

Enhanced effect of losartan and rosuvastatin on neointima hyperplasia.

PubMed

Yi, Inseon; Lee, Jung-Jin; Park, Jeong-Sook; Zhang, Wei Yun; Kim, In-Su; Kim, Yohan; Shin, Chang-Yong; Kim, Hyung Sik; Myung, Chang-Seon

2010-04-01

The beneficial effects of losartan and rosuvastatin on neointimal formation have been well characterized, but little is known about the combined treatment benefit of these two drugs. This study was designed to investigate the synergistic effect of losartan combined with rosuvastatin on the magnitude of protective action in vascular injury mediated by cuff-induced neointimal formation model in vivo. Losartan at 20 mg/kg or rosuvastatin at 40 mg/kg significantly decreased both the neointimal formation and BrdU-positive cells in neointima, indicating the inhibition of cell proliferation including a progress of DNA synthesis. The combination treatment used lower doses of losartan with rosuvastatin (10 + 20 & 5 + 10 mg/kg, respectively) that proved to be significant in decreasing the neointimal formation and BrdU incorporation. These results were comparable to the diminution attained with monotherapy of either drug in higher doses. Interaction index measured by isobolar method indicated drug synergism in these two combinations of both drugs at lower doses. Therefore, the administration of losartan and rosuvastatin in combination with low doses synergistically decreased in cuff-induced neointimal formation by reducing cell proliferation, suggesting that this drug synergism may be fully effective with, lower adverse effects, for the treatment of vascular remodeling such as restenosis.

A new polymer-free drug-eluting stent with nanocarriers eluting sirolimus from stent-plus-balloon compared with bare-metal stent and with biolimus A9 eluting stent in porcine coronary arteries.

PubMed

Takimura, Celso K; Galon, Micheli Z; Gutierrez, Paulo S; Sojitra, Prakash; Vyas, Ashwin; Doshi, Manish; Lemos, Pedro A

2015-04-01

Permanent polymers in first generation drug-eluting stent (DES) have been imputed to be a possible cause of persistent inflammation, remodeling, malapposition and late stent thrombosis. We aim to describe the in vivo experimental result of a new polymer-free DES eluting sirolimus from stent-plus-balloon (Focus np stent, Envision Scientific) compared with a bare-metal stent (BMS) (Amazonia CroCo, Minvasys) and with a biolimus A9 eluting stent (Biomatrix, Biosensors). In 10 juvenile pigs, 23 coronary stents were implanted in the coronary arteries (8 Amazonia CroCo, 8 Focus np, and 7 Biomatrix). At 28-day follow-up, optical coherence tomography (OCT) and histology were used to evaluate neointimal hyperplasia and healing response. According to OCT analysis, Focus np stents had a greater lumen area and less neointimal hyperplasia response than BMS and Biomatrix had. Histomorphometry results showed less neointimal hyperplasia in Focus np than in BMS. Histology showed a higher fibrin deposition in Biomatrix stent compared to Focus np and BMS. The new polymer-free DES with sirolimus eluted from stent-plus-balloon demonstrated safety and reduced neointimal proliferation compared with the BMS and Biomatrix stents at 28-day follow-up in this porcine coronary model. This new polymer-free DES is promising and warrants further clinical studies.

Connective tissue changes in a mouse model of vein graft disease.

PubMed

Schachner, T; Heiss, S; Mayr, T; Steger, C; Zipponi, D; Reisinger, P; Bonaros, N; Laufer, G; Bonatti, J

2008-04-01

The extracellular matrix plays an important physiological role in the architecture of the vascular wall. In arterialized vein grafts severe early changes, such as thrombosis and neointimal hyperplasia occur. Paclitaxel is in clinical use as antiproliferative coating of coronary stents. We aimed to investigate the early connective tissue changes in arterialized vein grafts and the influence of perivascular paclitaxel treatment in an in vivo model. C57 black mice underwent interposition of the vena cava into the carotid artery. Neointimal hyperplasia, thrombosis, acid mucopolysaccharides (Alcian), collagen fibers (trichrome Masson), elastic fibers, and apoptosis rate (TUNEL) were quantified in paclitaxel treated veins and controls. In both, controls and paclitaxel treated vein grafts acid mucopolysaccharides and elastic fibers were found predominantly in the neointima, whereas collagen fibers were found mainly in the media and adventitia. At 4 weeks postoperatively the neointimal thickness in controls was 52 (13-130) microm, whereas in 0.6 mg/mL l paclitaxel treated veins it was 103 (43-318) microm (P=0.094). At 8 weeks postoperatively paclitaxel treated veins showed a significantly increased neointimal thickness of 136 (87-199) microm compared with 79 (62-146) microm in controls (P=0.032). There was no difference in apoptosis rate between the two groups (P=NS). Even with the lowest concentration of 0.008 mg/mL paclitaxel veins showed a neointimal thickness of 67 (46-205) microm at 4 weeks postoperatively (P=NS vs controls). Early vein graft disease is characterised by an accumulation of acid mucopolysaccharides and elastic fibers in the thickened neointima. Paclitaxel treatment increases the neointimal hyperplasia in mouse vein grafts in vivo.

Attenuation of neointimal formation with netrin-1 and netrin-1 preconditioned endothelial progenitor cells.

PubMed

Liu, Norika Mengchia; Siu, Kin Lung; Youn, Ji Youn; Cai, Hua

2017-03-01

Restenosis after angioplasty is a serious clinical problem that can result in re-occlusion of the coronary artery. Although current drug-eluting stents have proved to be more effective in reducing restenosis, they have drawbacks of inhibiting reendothelialization to promote thrombosis. New treatment options are in urgent need. We have shown that netrin-1, an axon-guiding protein, promotes angiogenesis and cardioprotection via production of nitric oxide (NO). The present study examined whether and how netrin-1 attenuates neointimal formation in a femoral wire injury model. Infusion of netrin-1 into C57BL/6 mice markedly attenuated neointimal formation following wire injury of femoral arteries, measured by intimal to media ratio (from 1.94 ± 0.55 to 0.45 ± 0.86 at 4 weeks). Proliferation of VSMC in situ was largely reduced. This protective effect was absent in DCC +/- animals. NO production was increased by netrin-1 in both intact and injured femoral arteries, indicating netrin-1 stimulation of endogenous NO production from intact endothelium and remaining endothelial cells post-injury. VSMC migration was abrogated by netrin-1 via a NO/cGMP/p38 MAPK pathway, while timely EPC homing was induced. Injection of netrin-1 preconditioned wild-type EPCs, but not EPCs of DCC +/- animals, substantially attenuated neointimal formation. EPC proliferation, NO production, and resistance to oxidative stress induced apoptosis were augmented by netrin-1 treatment. In conclusion, our data for the first time demonstrate that netrin-1 is highly effective in reducing neointimal formation following vascular endothelial injury, which is dependent on DCC, and attributed to inhibition of VSMC proliferation and migration, as well as improved EPC function. These data may support usage of netrin-1 and netrin-1 preconditioned EPCs as novel therapies for post angioplasty restenosis. Netrin-1 attenuates neointimal formation following post endothelial injury via DCC and NO. Netrin-1 inhibits

Midkine is expressed by infiltrating macrophages in in-stent restenosis in hypercholesterolemic rabbits.

PubMed

Narita, Hiroshi; Chen, Sen; Komori, Kimihiro; Kadomatsu, Kenji

2008-06-01

Neointimal hyperplasia is strikingly suppressed in an endothelium injury model in mice deficient in the growth factor midkine. Knockdown of midkine expression by means of antisense oligonucleotide or small interfering RNA has been shown to lead to suppression of neointimal hyperplasia in a balloon injury model and a rabbit vein graft model; therefore, midkine is an essential factor for neointimal hyperplasia. These findings, however, do not necessarily apply to the function of midkine in vascular stenoses such as in-stent restenosis, because human vascular stenosis is often accompanied by atherosclerosis. We investigated midkine expression in the neointima induced by implantation of a bare metal stent in the atheromatous lesions of hypercholesterolemic rabbits. We analyzed midkine expression during a THP-1 cell differentiation and in peritoneal macrophages exposed to low-density lipoprotein or oxidized low-density lipoprotein. Midkine expression reached the maximum level within 7 days after stenting and was detected in infiltrating macrophages. Differentiation of THP-1 cells to macrophage-like cells did not trigger midkine expression. Neither low-density lipoprotein nor oxidized low-density lipoprotein enhanced midkine expression in peritoneal macrophages that had been activated by thioglycollate, although these cells expressed a significant amount of midkine. The results indicate that macrophages are the major source of midkine in the atherosclerotic neointima. The amount of midkine expressed in macrophages may be sufficient (ie, further enhancement of the expression is not necessary) for the pathogenesis, because oxidized low-density lipoprotein stimulation did not induce the midkine expression. The growth factor midkine is induced during vascular stenosis in mouse and rat models with normal diet. Knockdown of midkine expression suppresses neointimal hyperplasia. The vascular response after stenting differs from that after balloon injury in that the inflammation

Topical Application of Glycolipids from Isochrysis galbana Prevents Epidermal Hyperplasia in Mice

PubMed Central

Rodríguez-Luna, Azahara; Talero, Elena; Terencio, María del Carmen; González-Rodríguez, María Luisa; Rabasco, Antonio M.; de los Reyes, Carolina; Motilva, Virginia

2017-01-01

Chronic inflammatory skin diseases such as psoriasis have a significant impact on society. Currently, the major topical treatments have many side effects, making their continued use in patients difficult. Microalgae have emerged as a source of bio-active molecules such as glycolipids with potent anti-inflammatory properties. We aimed to investigate the effects of a glycolipid (MGMG-A) and a glycolipid fraction (MGDG) obtained from the microalga Isochrysis galbana on a TPA-induced epidermal hyperplasia murine model. In a first set of experiments, we examined the preventive effects of MGMG-A and MGDG dissolved in acetone on TPA-induced hyperplasia model in mice. In a second step, we performed an in vivo permeability study by using rhodamine-containing cream, ointment, or gel to determinate the formulation that preserves the skin architecture and reaches deeper. The selected formulation was assayed to ensure the stability and enhanced permeation properties of the samples in an ex vivo experiment. Finally, MGDG-containing cream was assessed in the hyperplasia murine model. The results showed that pre-treatment with acetone-dissolved glycolipids reduced skin edema, epidermal thickness, and pro-inflammatory cytokine production (TNF-α, IL-1β, IL-6, IL-17) in epidermal tissue. The in vivo and ex vivo permeation studies showed that the cream formulation had the best permeability profile. In the same way, MGDG-cream formulation showed better permeation than acetone-dissolved preparation. MGDG-cream application attenuated TPA-induced skin edema, improved histopathological features, and showed a reduction of the inflammatory cell infiltrate. In addition, this formulation inhibited epidermal expression of COX-2 in a similar way to dexamethasone. Our results suggest that an MGDG-containing cream could be an emerging therapeutic strategy for the treatment of inflammatory skin pathologies such as psoriasis. PMID:29295585

A new polymer-free drug-eluting stent with nanocarriers eluting sirolimus from stent-plus-balloon compared with bare-metal stent and with biolimus A9 eluting stent in porcine coronary arteries

PubMed Central

Galon, Micheli Z.; Gutierrez, Paulo S.; Sojitra, Prakash; Vyas, Ashwin; Doshi, Manish; Lemos, Pedro A.

2015-01-01

Background Permanent polymers in first generation drug-eluting stent (DES) have been imputed to be a possible cause of persistent inflammation, remodeling, malapposition and late stent thrombosis. We aim to describe the in vivo experimental result of a new polymer-free DES eluting sirolimus from stent-plus-balloon (Focus np stent, Envision Scientific) compared with a bare-metal stent (BMS) (Amazonia CroCo, Minvasys) and with a biolimus A9 eluting stent (Biomatrix, Biosensors). Methods In 10 juvenile pigs, 23 coronary stents were implanted in the coronary arteries (8 Amazonia CroCo, 8 Focus np, and 7 Biomatrix). At 28-day follow-up, optical coherence tomography (OCT) and histology were used to evaluate neointimal hyperplasia and healing response. Results According to OCT analysis, Focus np stents had a greater lumen area and less neointimal hyperplasia response than BMS and Biomatrix had. Histomorphometry results showed less neointimal hyperplasia in Focus np than in BMS. Histology showed a higher fibrin deposition in Biomatrix stent compared to Focus np and BMS. Conclusions The new polymer-free DES with sirolimus eluted from stent-plus-balloon demonstrated safety and reduced neointimal proliferation compared with the BMS and Biomatrix stents at 28-day follow-up in this porcine coronary model. This new polymer-free DES is promising and warrants further clinical studies. PMID:25984451

Management of adolescents with congenital adrenal hyperplasia

PubMed Central

Merke, Deborah P; Poppas, Dix P

2014-01-01

The management of congenital adrenal hyperplasia involves suppression of adrenal androgen production, in addition to treatment of adrenal insufficiency. Management of adolescents with congenital adrenal hyperplasia is especially challenging because changes in the hormonal milieu during puberty can lead to inadequate suppression of adrenal androgens, psychosocial issues often affect adherence to medical therapy, and sexual function plays a major part in adolescence and young adulthood. For these reasons, treatment regimen reassessment is indicated during adolescence. Patients with non-classic congenital adrenal hyperplasia require reassessment regarding the need for glucocorticoid drug treatment. No clinical trials have compared various regimens for classic congenital adrenal hyperplasia in adults, thus therapy is individualised and based on the prevention of adverse outcomes. Extensive patient education is key during transition from paediatric care to adult care and should include education of females with classic congenital adrenal hyperplasia regarding their genital anatomy and surgical history. Common issues for these patients include urinary incontinence, vaginal stenosis, clitoral pain, and cosmetic concerns; for males with classic congenital adrenal hyperplasia, common issues include testicular adrenal rest tumours. Transition from paediatric to adult care is most successful when phased over many years. Education of health-care providers on how to successfully transition patients is greatly needed. PMID:24622419

Development of occlusive neointimal lesions in distal pulmonary arteries of endothelin B receptor-deficient rats: a new model of severe pulmonary arterial hypertension.

PubMed

Ivy, D Dunbar; McMurtry, Ivan F; Colvin, Kelley; Imamura, Masatoshi; Oka, Masahiko; Lee, Dong-Seok; Gebb, Sarah; Jones, Peter Lloyd

2005-06-07

Human pulmonary arterial hypertension (PAH) is characterized by proliferation of vascular smooth muscle and, in its more severe form, by the development of occlusive neointimal lesions. However, few animal models of pulmonary neointimal proliferation exist, thereby limiting a complete understanding of the pathobiology of PAH. Recent studies of the endothelin (ET) system demonstrate that deficiency of the ET(B) receptor predisposes adult rats to acute and chronic hypoxic PAH, yet these animals fail to develop neointimal lesions. Herein, we determined and thereafter showed that exposure of ET(B) receptor-deficient rats to the endothelial toxin monocrotaline (MCT) leads to the development of neointimal lesions that share hallmarks of human PAH. The pulmonary hemodynamic and morphometric effects of 60 mg/kg MCT in control (MCT(+/+)) and ET(B) receptor-deficient (MCT(sl/sl)) rats at 6 weeks of age were assessed. MCT(sl/sl) rats developed more severe PAH, characterized by elevated pulmonary artery pressure, diminished cardiac output, and right ventricular hypertrophy. In MCT(sl/sl) rats, morphometric evaluation revealed the presence of neointimal lesions within small distal pulmonary arteries, increased medial wall thickness, and decreased arterial-to-alveolar ratio. In keeping with this, barium angiography revealed diminished distal pulmonary vasculature of MCT(sl/sl) rat lungs. Cells within neointimal lesions expressed smooth muscle and endothelial cell markers. Moreover, cells within neointimal lesions exhibited increased levels of proliferation and were located in a tissue microenvironment enriched with vascular endothelial growth factor, tenascin-C, and activated matrix metalloproteinase-9, factors already implicated in human PAH. Finally, assessment of steady state mRNA showed that whereas expression of ET(B) receptors was decreased in MCT(sl/sl) rat lungs, ET(A) receptor expression increased. Deficiency of the ET(B) receptor markedly accelerates the progression of

Development of Occlusive Neointimal Lesions in Distal Pulmonary Arteries of Endothelin B Receptor–Deficient Rats: A New Model of Severe Pulmonary Arterial Hypertension

PubMed Central

Ivy, D. Dunbar; McMurtry, Ivan F.; Colvin, Kelley; Imamura, Masatoshi; Oka, Masahiko; Lee, Dong-Seok; Gebb, Sarah; Jones, Peter Lloyd

2007-01-01

Background Human pulmonary arterial hypertension (PAH) is characterized by proliferation of vascular smooth muscle and, in its more severe form, by the development of occlusive neointimal lesions. However, few animal models of pulmonary neointimal proliferation exist, thereby limiting a complete understanding of the pathobiology of PAH. Recent studies of the endothelin (ET) system demonstrate that deficiency of the ETB receptor predisposes adult rats to acute and chronic hypoxic PAH, yet these animals fail to develop neointimal lesions. Herein, we determined and thereafter showed that exposure of ETB receptor–deficient rats to the endothelial toxin monocrotaline (MCT) leads to the development of neointimal lesions that share hallmarks of human PAH. Methods and Results The pulmonary hemodynamic and morphometric effects of 60 mg/kg MCT in control (MCT+/+) and ETB receptor–deficient (MCTsl/sl) rats at 6 weeks of age were assessed. MCTsl/sl rats developed more severe PAH, characterized by elevated pulmonary artery pressure, diminished cardiac output, and right ventricular hypertrophy. In MCTsl/sl rats, morphometric evaluation revealed the presence of neointimal lesions within small distal pulmonary arteries, increased medial wall thickness, and decreased arterial-to-alveolar ratio. In keeping with this, barium angiography revealed diminished distal pulmonary vasculature of MCTsl/sl rat lungs. Cells within neointimal lesions expressed smooth muscle and endothelial cell markers. Moreover, cells within neointimal lesions exhibited increased levels of proliferation and were located in a tissue microenvironment enriched with vascular endothelial growth factor, tenascin-C, and activated matrix metalloproteinase-9, factors already implicated in human PAH. Finally, assessment of steady state mRNA showed that whereas expression of ETB receptors was decreased in MCTsl/sl rat lungs, ETA receptor expression increased. Conclusions Deficiency of the ETB receptor markedly

Osthole inhibits intimal hyperplasia by regulating the NF-κB and TGF-β1/Smad2 signalling pathways in the rat carotid artery after balloon injury.

PubMed

Li, Yi-Qi; Wang, Jun-Yi; Qian, Zhi-Qiang; Li, Ye-Li; Li, Wen-Na; Gao, Yang; Yang, Dan-Li

2017-09-15

Osthole (7-methoxy-8-isopentenoxy-coumarin), a compound extracted from Cnidiummonnieri (L.) Cusson seeds, has been found to exhibit potent therapeutic effects in cancer due to its ability to inhibit inflammation and cell proliferation. However, its effects on arterial wall hypertrophy-related diseases remain unclear. Therefore, in this study, we aimed to investigate the effects of Osthole on intimal hyperplasia in a rat model of carotid artery balloon injury. We established the balloon-induced carotid artery injury rat model in male Sprague-Dawley rats, after which we administered Osthole (20mg/kg/day or 40mg/kg/day) or volume-matched normal saline orally by gavage for 14 consecutive days. Intimal hyperplasia and the degree of vascular smooth muscle cell proliferation were then evaluated by histopathological examination of the changes in the carotid artery, as well as by examination of proliferating cell nuclear antigen (PCNA) expression. Tumour necrosis factor-ɑ (TNF-α), interleukin-1β (IL-1β), transforming growth factor-beta (TGF-β1) and PCNA mRNA expression levels were examined by real-time RT-PCR, while nuclear factor-κB (NF-κB (p65)), IκB-α, TGF-β1 and phospho-Smad2 (p-Smad2) protein expression levels were analysed by immunohistochemistry or western blot analysis. We found that Osthole significantly attenuated neointimal thickness and decreased the elevations in PCNA protein expression induced by balloon injury. Moreover, Osthole down-regulated the pro-inflammatory factors TNF-α and IL-1β and NF-κB (p65), whose expression had been upregulated after balloon injury. Moreover, IκB-α protein expression levels increased following Osthole treatment. In addition, the elevations in TGF-β1 and p-Smad2 protein expression induced by balloon injury were both significantly attenuated by Osthole administration. We concluded that Osthole significantly inhibited neointimal hyperplasia in balloon-induced rat carotid artery injury and that the mechanism by which

Sustained Thromboresistant Bioactivity with Reduced Intimal Hyperplasia of Heparin-Bonded Polytetrafluoroethylene Propaten Graft in a Chronic Canine Femoral Artery Bypass Model.

PubMed

Freeman, John; Chen, Aaron; Weinberg, Roy J; Okada, Tamuru; Chen, Changyi; Lin, Peter H

2018-05-01

Bypass graft thrombosis remains a significant mode of failure in prosthetic graft revascularization. The purpose of this investigation was to evaluate the long-term thromboresistant effect of heparin-bonded expanded polytetrafluoroethylene (ePTFE) graft using Carmeda BioActive Surface technology in a canine model. Bilateral femorofemoral artery bypass grafts with ePTFE grafts were performed in 25 adult grayhound dogs. In each animal, a heparin-bonded ePTFE graft (Propaten, WL Gore) was placed on one side, whereas a control nonheparin graft was placed on the contralateral side. The graft patency was assessed at 1, 6, 12, 18, and 24 months (n = 5 per group) following the bypass. Heparin bioactivity of the graft material was analyzed. The effect of intimal hyperplasia was also assessed. All bypass grafts were patent at 1 month. Significantly greater patency rates were noted in the Propaten group compared to the control group at 12, 18, and 24 months, which were 84%, 80%, and 80% vs. 55%, 35%, and 20%, respectively (P < 0.02). There was a significant reduction in the anastomotic neointimal area and neointimal cell proliferation in Propaten grafts compared with control grafts at all groups between 6 and 24 months (P < 0.05). Heparin bioactivity as measured by antithrombin binding assay was demonstrated in the Propaten graft between 1 and 24 months. Mean heparin activities on Propaten grafts ranged from 26.3 ± 6.4 pmol/cm 2 to 18.4 ± 8.7 pmol/cm 2 between 1 and 24 months, which were significantly greater than the control group (P < 0.001). Differences between mean heparin activities of explanted Propaten graft samples at the various time points were nonsignificant (P > 0.05). Heparin-bonded ePTFE graft provides a thromboresistant surface and reduced anastomotic intimal hyperplasia at 2 years. The stable heparin bioactivity of the Propaten graft confers an advantage in long-term graft patency. Copyright © 2017 The Author(s). Published by Elsevier Inc

Leptin Induces Sca-1+ Progenitor Cell Migration Enhancing Neointimal Lesions in Vessel-Injury Mouse Models

PubMed Central

Xie, Yao; Potter, Claire M.F.; Le Bras, Alexandra; Nowak, Witold N.; Gu, Wenduo; Bhaloo, Shirin Issa; Zhang, Zhongyi; Hu, Yanhua; Zhang, Li

2017-01-01

Objective— Leptin is an adipokine initially thought to be a metabolic factor. Recent publications have shown its roles in inflammation and vascular disease, to which Sca-1+ vascular progenitor cells within the vessel wall may contribute. We sought to elucidate the effects of leptin on Sca-1+ progenitor cells migration and neointimal formation and to understand the underlying mechanisms. Approach and Results— Sca-1+ progenitor cells from the vessel wall of Lepr+/+ and Lepr−/− mice were cultured and purified. The migration of Lepr+/+ Sca-1+ progenitor cells in vitro was markedly induced by leptin. Western blotting and kinase assays revealed that leptin induced the activation of phosphorylated signal transducer and activator of transcription 3, phosphorylated extracellular signal–regulated kinases 1/2, pFAK (phosphorylated focal adhesion kinase), and Rac1 (ras-related C3 botulinum toxin substrate 1)/Cdc42 (cell division control protein 42 homolog). In a mouse femoral artery guidewire injury model, an increased expression of leptin in both injured vessels and serum was observed 24 hours post-surgery. RFP (red fluorescent protein)-Sca-1+ progenitor cells in Matrigel were applied to the adventitia of the injured femoral artery. RFP+ cells were observed in the intima 24 hours post-surgery, subsequently increasing neointimal lesions at 2 weeks when compared with the arteries without seeded cells. This increase was reduced by pre-treatment of Sca-1+ cells with a leptin antagonist. Guidewire injury could only induce minor neointima in Lepr−/− mice 2 weeks post-surgery. However, transplantation of Lepr+/+ Sca-1+ progenitor cells into the adventitial side of injured artery in Lepr−/− mice significantly enhanced neointimal formation. Conclusions— Upregulation of leptin levels in both the vessel wall and the circulation after vessel injury promoted the migration of Sca-1+ progenitor cells via leptin receptor–dependent signal transducer and activator of

Leptin Induces Sca-1+ Progenitor Cell Migration Enhancing Neointimal Lesions in Vessel-Injury Mouse Models.

PubMed

Xie, Yao; Potter, Claire M F; Le Bras, Alexandra; Nowak, Witold N; Gu, Wenduo; Bhaloo, Shirin Issa; Zhang, Zhongyi; Hu, Yanhua; Zhang, Li; Xu, Qingbo

2017-11-01

Leptin is an adipokine initially thought to be a metabolic factor. Recent publications have shown its roles in inflammation and vascular disease, to which Sca-1 + vascular progenitor cells within the vessel wall may contribute. We sought to elucidate the effects of leptin on Sca-1 + progenitor cells migration and neointimal formation and to understand the underlying mechanisms. Sca-1 + progenitor cells from the vessel wall of Lepr +/+ and Lepr -/- mice were cultured and purified. The migration of Lepr +/+ Sca-1 + progenitor cells in vitro was markedly induced by leptin. Western blotting and kinase assays revealed that leptin induced the activation of phosphorylated signal transducer and activator of transcription 3, phosphorylated extracellular signal-regulated kinases 1/2, pFAK (phosphorylated focal adhesion kinase), and Rac1 (ras-related C3 botulinum toxin substrate 1)/Cdc42 (cell division control protein 42 homolog). In a mouse femoral artery guidewire injury model, an increased expression of leptin in both injured vessels and serum was observed 24 hours post-surgery. RFP (red fluorescent protein)-Sca-1 + progenitor cells in Matrigel were applied to the adventitia of the injured femoral artery. RFP + cells were observed in the intima 24 hours post-surgery, subsequently increasing neointimal lesions at 2 weeks when compared with the arteries without seeded cells. This increase was reduced by pre-treatment of Sca-1 + cells with a leptin antagonist. Guidewire injury could only induce minor neointima in Lepr -/- mice 2 weeks post-surgery. However, transplantation of Lepr +/+ Sca-1 + progenitor cells into the adventitial side of injured artery in Lepr -/- mice significantly enhanced neointimal formation. Upregulation of leptin levels in both the vessel wall and the circulation after vessel injury promoted the migration of Sca-1 + progenitor cells via leptin receptor-dependent signal transducer and activator of transcription 3- Rac1/Cdc42-ERK (extracellular signal

Adrenal medullary hyperplasia. Hyperplasia-pheochromocytoma sequence.

PubMed

Kurihara, K; Mizuseki, K; Kondo, T; Ohoka, H; Mannami, M; Kawai, K

1990-09-01

We present a case of unilateral adrenal medullary hyperplasia in a 63-year-old woman with clinical signs and symptoms of pheochromocytoma unassociated with multiple endocrine neoplasia. The surgically removed adrenal gland revealed diffuse medullary hyperplasia with multiple micronodules measuring up to 2 mm. The micronodules were composed of enlarged chromaffin cells with atypia, histologically similar to those of pheochromocytoma, forming small solid alveolar patterns separated by a fibrovascular stroma. Removal of the hyperplastic adrenal gland resulted in disappearance of paroxysmal nocturnal hypertension and palpitation. These results suggest that diffuse and nodular medullary hyperplasia is the precursor of pheochromocytoma.

Novel Pathological Role of hnRNPA1 (Heterogeneous Nuclear Ribonucleoprotein A1) in Vascular Smooth Muscle Cell Function and Neointima Hyperplasia

PubMed Central

Chen, Qishan; An, Weiwei; Yang, Feng; Maguire, Eithne Margaret; Chen, Dan; Zhang, Cheng; Wen, Guanmei; Yang, Mei; Dai, Bin; Luong, Le Anh; Zhu, Jianhua; Xu, Qingbo

2017-01-01

Objective— hnRNPA1 (heterogeneous nuclear ribonucleoprotein A1) plays a variety of roles in gene expression. However, little is known about the functional involvement of hnRNPA1 in vascular smooth muscle cell (VSMC) function and neointima hyperplasia. In this study, we have attempted to investigate the functional roles of hnRNPA1 in the contexts of VSMC function, injury-induced vessel remodeling, and human atherosclerotic lesions, as well as discern the molecular mechanisms involved. Approach and Results— hnRNPA1 expression levels were consistently modulated during VSMC phenotype switching and neointimal lesion formation induced by wire injury. Functional studies showed that VSMC-specific gene expression, proliferation, and migration were regulated by hnRNPA1. Our data show that hnRNPA1 exerts its effects on VSMC functions through modulation of IQGAP1 (IQ motif containing GTPase activating protein 1). Mechanistically, hnRNPA1 regulates IQGAP1 mRNA degradation through 2 mechanisms: upregulating microRNA-124 (miR-124) and binding to AU-rich element of IQGAP1 gene. Further evidence suggests that hnRNPA1 upregulates miR-124 by modulating miR-124 biogenesis and that IQGAP1 is the authentic target gene of miR-124. Importantly, ectopic overexpression of hnRNPA1 greatly reduced VSMC proliferation and inhibited neointima formation in wire-injured carotid arteries. Finally, lower expression levels of hnRNPA1 and miR-124, while higher expression levels of IQGAP1, were observed in human atherosclerotic lesions. Conclusions— Our data show that hnRNPA1 is a critical regulator of VSMC function and behavior in the context of neointima hyperplasia, and the hnRNPA1/miR-124/IQGAP1 regulatory axis represents a novel therapeutic target for the prevention of cardiovascular diseases. PMID:28912364

Experimental Evaluation of a New Single Wire Stainless Steel Fishscale Coronary Stent (Freedomª).

PubMed

Wang; Verbeken; Mukherjee; Zhou; De Scheerder IK

1996-10-01

Recent randomized clinical trials revealed a significant reduction in angiographic restenosis rates when adjunctive stenting was performed after conventional coronary balloon angioplasty. Current approved coronary stents are however hampered by their rigidity, limiting their trackability in tortuous vessels and furthermore, needing high pressure deployment for optimal vessel apposition. New coronary stents are currently under development, using more biocompatible metal alloys and/or designs which better align to the vessel wall at moderate deployment pressures. We evaluated the safety, efficacy, angiographic and histological effect of a new stainless steel fishscale designed stent (Freedomª, Global Therapeutics, Co., USA) in a porcine coronary and peripheral artery model. Implantation in the right coronary artery was successful in all 20 pigs. Control angiograms at 6 weeks follow-up demonstrated patent vessels and morphologic evaluation showed only a mild fibromuscular neointimal response resulting in an area stenosis of 28.7 +/- 0.18% and a mean neointimal hyperplasia of 0.18 +/- 0.25 mm. Comparison with the Palmaz-Schatzª coronary stent in a porcine peripheral artery model demonstrated similar quantitative angiographic and morphologic vessel analysis results. Also the morphometric data were comparable. Area stenosis: Palmaz-Schatz: 37 +/- 0.24%, Freedom: 21 +/- 0.14%, p = 0.07. Mean neointimal hyperplasia: Palmaz-Schatz: 0.33 +/- 0.24 mm, Freedom: 0.18 +/- 0.08 mm, p = 0.08. CONCLUSION: Freedom coronary stent implantation in a porcine model resulted in a high procedural success without subacute thrombotic occlusions, despite no further anticoagulation nor antiplatelet therapy. Six weeks histopathological and morphometric evaluation demonstrated only a mild fibromuscular neointimal hyperplasia.

Inhibition of cell surface expression of endothelial adhesion molecules by ursolic acid prevents intimal hyperplasia of venous bypass grafts in rats

PubMed Central

Zeller, Iris; Wiedemann, Dominik; Schwaiger, Stefan; Stelzmüller, Marlies; Kreutmayer, Simone; Leberfing, Oliver; Stuppner, Hermann; Bernhard, David

2012-01-01

OBJECTIVES Despite rapid progress in surgical techniques, there is still a significant lack of surgery-supportive pharmacological treatments. The aim of this study was to test the hypothesis that ursolic acid (UA) may prevent intimal hyperplasia of venous bypass grafts. METHODS The hypothesis was tested by means of primary cell isolation and culture followed by real-time polymerase chain reaction, western blotting, fluorescence microscopy and fluorescence-activated cell sorting analyses, as well as an in vivo rat model for intimal hyperplasia of venous bypass grafts and immunohistochemistry and histochemistry. RESULTS The local application of UA significantly inhibited intimal hyperplasia in vivo (intimal thickness control: 25 μm, UA group: 18 μM–8 weeks after surgery). The UA treatment of grafts significantly resulted in reduced endothelial vascular cell adhesion molecule-1 (VCAM-1) expression, reduced infiltration of the grafts vessel wall by CD45-positive cells and increased smooth muscle cell (SMC) death. In in vitro condition, it could be shown that UA inhibits VCAM-1 expression downstream of NFκB and is likely to interfere with VCAM-1 protein synthesis in endothelial cells. Quantification of cell death in vascular smooth muscle cells treated with UA indicated that UA is a potent inducer of SMC apoptosis. CONCLUSIONS Our results suggest that UA-mediated inhibition of endothelial VCAM-1 expression reduces the infiltration of venous bypass grafts by CD45-positive cells and inhibits intimal hyperplasia. Apoptosis induction in SMCs may be another method in which UA reduces intimal thickening. UA may constitute a surgery-supportive pharmacon that reduces intimal hyperplasia of vein grafts. PMID:22551965

Adipose tissue-derived stem cells inhibit neointimal formation in a paracrine fashion in rat femoral artery.

PubMed

Takahashi, Masao; Suzuki, Etsu; Oba, Shigeyoshi; Nishimatsu, Hiroaki; Kimura, Kenjiro; Nagano, Tetsuo; Nagai, Ryozo; Hirata, Yasunobu

2010-02-01

Subcutaneous adipose tissue contains a lot of stem cells [adipose-derived stem cells (ASCs)] that can differentiate into a variety of cell lineages. In this study, we isolated ASCs from Wistar rats and examined whether ASCs would efficiently differentiate into vascular endothelial cells (ECs) in vitro. We also administered ASCs in a wire injury model of rat femoral artery and examined their effects. ASCs expressed CD29 and CD90, but not CD34, suggesting that ASCs resemble bone marrow-derived mesenchymal stem cells. When induced to differentiate into ECs with endothelial growth medium (EGM), ASCs expressed Flt-1, but not Flk-1 or mature EC markers such as CD31 and vascular endothelial cadherin. ASCs produced angiopoietin-1 when they were cultured in EGM. ASCs stimulated the migration of EC, as assessed by chemotaxis assay. When ASCs that were cultured in EGM were injected in the femoral artery, the ASCs potently and significantly inhibited neointimal formation without being integrated in the endothelial layer. EGM-treated ASCs significantly suppressed neointimal formation even when they were administered from the adventitial side. ASC administration significantly promoted endothelial repair. These results suggested that although ASCs appear to have little capacity to differentiate into mature ECs, ASCs have the potential to secrete paracrine factors that stimulate endothelial repair. Our results also suggested that ASCs inhibited neointimal formation via their paracrine effect of stimulation of EC migration in situ rather than the direct integration into the endothelial layer.

Wall Shear Stress Restoration in Dialysis Patient's Venous Stenosis: Elucidation via 3D CFD and Shape Optimization

NASA Astrophysics Data System (ADS)

Mahmoudzadeh Akherat, S. M. Javid; Cassel, Kevin; Hammes, Mary; Boghosian, Michael; Illinois Institute of Technology Team; University of Chicago Team

2016-11-01

Venous stenosis developed after the growth of excessive neointimal hyperplasia (NH) in chronic dialysis treatment is a major cause of mortality in renal failure patients. It has been hypothesized that the low wall shear stress (WSS) triggers an adaptive response in patients' venous system that through the growth of neointimal hyperplastic lesions restores WSS and transmural pressure, which also regulates the blood flow rate back to physiologically acceptable values which is violated by dialysis treatment. A strong coupling of three-dimensional CFD and shape optimization analyses were exploited to elucidate and forecast this adaptive response which correlates very well topographically with patient-specific clinical data. Based on the framework developed, a medical protocol is suggested to predict and prevent dialysis treatment failure in clinical practice. Supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (R01 DK90769).

Mechanisms of tissue uptake and retention of paclitaxel-coated balloons: impact on neointimal proliferation and healing.

PubMed

Granada, Juan F; Stenoien, Mark; Buszman, Piotr P; Tellez, Armando; Langanki, Dan; Kaluza, Greg L; Leon, Martin B; Gray, William; Jaff, Michael R; Schwartz, Robert S

2014-01-01

The efficacy of paclitaxel-coated balloons (PCB) for restenosis prevention has been demonstrated in humans. However, the mechanism of action for sustained drug retention and biological efficacy following single-time drug delivery is still unknown. The pharmacokinetic profile and differences in drug concentration (vessel surface vs arterial wall) of two different paclitaxel coating formulations (3 µg/mm(2)) displaying opposite solubility characteristics (CC=crystalline vs AC=amorphous) were tested in vivo and compared with paclitaxel-eluting stents (PES). Also, the biological effect of both PCB formulations on vascular healing was tested in the porcine coronary injury model. One hour following balloon inflation, both formulations achieved similar arterial paclitaxel levels (CC=310 vs AC=245 ng/mg; p=NS). At 24 h, the CC maintained similar tissue concentrations, whereas the AC tissue levels declined by 99% (p<0.01). At this time point, arterial levels were 20-fold (CC) and 5-fold (AC) times higher compared to the PES group (p<0.05). At 28 days, arterial levels retained were 9.2% (CC) and 0.04% (AC, p<0.01) of the baseline levels. Paclitaxel concentration on the vessel surface was higher in the CC at 1 (CC=36.7% vs AC=13.1%, p<0.05) and 7 days (CC=38.4% vs AC=11%, p<0.05). In addition, the CC induced higher levels of neointimal inhibition, fibrin deposition and delayed healing compared with the AC group. The presence of paclitaxel deposits on the vessel surface driving diffusion into the arterial tissue in a time-dependent fashion supports the mechanism of action of PCB. This specific pharmacokinetic behaviour influences the patterns of neointimal formation and healing.

Mechanisms of tissue uptake and retention of paclitaxel-coated balloons: impact on neointimal proliferation and healing

PubMed Central

Granada, Juan F; Stenoien, Mark; Buszman, Piotr P; Tellez, Armando; Langanki, Dan; Kaluza, Greg L; Leon, Martin B; Gray, William; Jaff, Michael R; Schwartz, Robert S

2014-01-01

Background The efficacy of paclitaxel-coated balloons (PCB) for restenosis prevention has been demonstrated in humans. However, the mechanism of action for sustained drug retention and biological efficacy following single-time drug delivery is still unknown. Methods and results The pharmacokinetic profile and differences in drug concentration (vessel surface vs arterial wall) of two different paclitaxel coating formulations (3 µg/mm2) displaying opposite solubility characteristics (CC=crystalline vs AC=amorphous) were tested in vivo and compared with paclitaxel-eluting stents (PES). Also, the biological effect of both PCB formulations on vascular healing was tested in the porcine coronary injury model. One hour following balloon inflation, both formulations achieved similar arterial paclitaxel levels (CC=310 vs AC=245 ng/mg; p=NS). At 24 h, the CC maintained similar tissue concentrations, whereas the AC tissue levels declined by 99% (p<0.01). At this time point, arterial levels were 20-fold (CC) and 5-fold (AC) times higher compared to the PES group (p<0.05). At 28 days, arterial levels retained were 9.2% (CC) and 0.04% (AC, p<0.01) of the baseline levels. Paclitaxel concentration on the vessel surface was higher in the CC at 1 (CC=36.7% vs AC=13.1%, p<0.05) and 7 days (CC=38.4% vs AC=11%, p<0.05). In addition, the CC induced higher levels of neointimal inhibition, fibrin deposition and delayed healing compared with the AC group. Conclusions The presence of paclitaxel deposits on the vessel surface driving diffusion into the arterial tissue in a time-dependent fashion supports the mechanism of action of PCB. This specific pharmacokinetic behaviour influences the patterns of neointimal formation and healing. PMID:25332821

Future research directions to improve fistula maturation and reduce access failure.

PubMed

Hu, Haidi; Patel, Sandeep; Hanisch, Jesse J; Santana, Jeans M; Hashimoto, Takuya; Bai, Hualong; Kudze, Tambudzai; Foster, Trenton R; Guo, Jianming; Yatsula, Bogdan; Tsui, Janice; Dardik, Alan

2016-12-01

With the increasing prevalence of end-stage renal disease, there is a growing need for hemodialysis. Arteriovenous fistulae (AVF) are the preferred type of vascular access for hemodialysis, but maturation and failure continue to present significant barriers to successful fistula use. AVF maturation integrates outward remodeling with vessel wall thickening in response to drastic hemodynamic changes in the setting of uremia, systemic inflammation, oxidative stress, and pre-existent vascular pathology. AVF can fail due to both failure to mature adequately to support hemodialysis and development of neointimal hyperplasia that narrows the AVF lumen, typically near the fistula anastomosis. Failure due to neointimal hyperplasia involves vascular cell activation and migration and extracellular matrix remodeling with complex interactions of growth factors, adhesion molecules, inflammatory mediators, and chemokines, all of which result in maladaptive remodeling. Different strategies have been proposed to prevent and treat AVF failure based on current understanding of the modes and pathology of access failure; these approaches range from appropriate patient selection and use of alternative surgical strategies for fistula creation, to the use of novel interventional techniques or drugs to treat failing fistulae. Effective treatments to prevent or treat AVF failure require a multidisciplinary approach involving nephrologists, vascular surgeons, and interventional radiologists, careful patient selection, and the use of tailored systemic or localized interventions to improve patient-specific outcomes. This review provides contemporary information on the underlying mechanisms of AVF maturation and failure and discusses the broad spectrum of options that can be tailored for specific therapy. Published by Elsevier Inc.

Imaging Characteristics of Pathologically Proven Thymic Hyperplasia: Identifying Features That Can Differentiate True From Lymphoid Hyperplasia

PubMed Central

Araki, Tetsuro; Sholl, Lynette M.; Gerbaudo, Victor H.; Hatabu, Hiroto; Nishino, Mizuki

2014-01-01

OBJECTIVE The purpose of this article is to investigate the imaging characteristics of pathologically proven thymic hyperplasia and to identify features that can differentiate true hyperplasia from lymphoid hyperplasia. MATERIALS AND METHODS Thirty-one patients (nine men and 22 women; age range, 20–68 years) with pathologically confirmed thymic hyperplasia (18 true and 13 lymphoid) who underwent preoperative CT (n = 27), PET/CT (n = 5), or MRI (n = 6) were studied. The length and thickness of each thymic lobe and the transverse and anterior-posterior diameters and attenuation of the thymus were measured on CT. Thymic morphologic features and heterogeneity on CT and chemical shift on MRI were evaluated. Maximum standardized uptake values were measured on PET. Imaging features between true and lymphoid hyperplasia were compared. RESULTS No significant differences were observed between true and lymphoid hyperplasia in terms of thymic length, thickness, diameters, morphologic features, and other qualitative features (p > 0.16). The length, thickness, and diameters of thymic hyperplasia were significantly larger than the mean values of normal glands in the corresponding age group (p < 0.001). CT attenuation of lymphoid hyperplasia was significantly higher than that of true hyperplasia among 15 patients with contrast-enhanced CT (median, 47.9 vs 31.4 HU; Wilcoxon p = 0.03). The receiver operating characteristic analysis yielded greater than 41.2 HU as the optimal threshold for differentiating lymphoid hyperplasia from true hyperplasia, with 83% sensitivity and 89% specificity. A decrease of signal intensity on opposed-phase images was present in all four cases with in- and opposed-phase imaging. The mean maximum standardized uptake value was 2.66. CONCLUSION CT attenuation of the thymus was significantly higher in lymphoid hyperplasia than in true hyperplasia, with an optimal threshold of greater than 41.2 HU in this cohort of patients with pathologically confirmed

Impact of polymer formulations on neointimal proliferation after zotarolimus-eluting stent with different polymers: insights from the RESOLUTE trial.

PubMed

Waseda, Katsuhisa; Ako, Junya; Yamasaki, Masao; Koizumi, Tomomi; Sakurai, Ryota; Hongo, Yoichiro; Koo, Bon-Kwon; Ormiston, John; Worthley, Stephen G; Whitbourn, Robert J; Walters, Darren L; Meredith, Ian T; Fitzgerald, Peter J; Honda, Yasuhiro

2011-06-01

Polymer formulation may affect the efficacy of drug-eluting stents. Resolute, Endeavor, and ZoMaxx are zotarolimus-eluting stents with different stent platforms and different polymer coatings and have been tested in clinical trials. The aim of this analysis was to compare the efficacy of zotarolimus-eluting stents with different polymers. Data were obtained from the first-in man trial or first randomized trials of each stent, The Clinical RESpOnse EvaLUation of the MedTronic Endeavor CR ABT-578 Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions (RESOLUTE), Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Medtronic AVE ABT-578 Eluting Driver Coronary Stent in De Novo Native Coronary Artery Lesions (ENDEAVOR II), and ZoMaxx I trials. Follow-up intravascular ultrasound analyses (8 to 9 months of follow-up) were possible in 353 patients (Resolute: 88, Endeavor: 98, ZoMaxx: 82, Driver: 85). Volume index (volume/stent length) was obtained for vessel, stent, lumen, peristent plaque, and neointima. Cross-sectional narrowing was defined as neointimal area divided by stent area (%). Neointima-free frame ratio was calculated as the number of frames without intravascular ultrasound-detectable neointima divided by the total number of frames within the stent. At baseline, vessel, lumen, and peristent plaque volume index were not significantly different among the 4 stent groups. At follow-up, percent neointimal obstruction was significantly lower in Resolute compared with Endeavor, ZoMaxx, and Driver (Resolute: 3.7±4.0, Endeavor: 17.5±10.1, ZoMaxx: 14.6±8.1, Driver: 29.4±17.2%; P<0.001). Greater maximum cross-sectional narrowing and higher neointima-free frame ratio, suggesting less neointimal coverage, were observed in Resolute compared with other stent groups. Multiple regression analysis confirmed that the biodurable polymer used in Resolute independently correlated with neointimal suppression among 3 zotarolimus-eluting stents

Rapamycin treatment is associated with an increased apoptosis rate in experimental vein grafts.

PubMed

Schachner, Thomas; Oberhuber, Alexander; Zou, Yping; Tzankov, Alexandar; Ott, Harald; Laufer, Günther; Bonatti, Johannes

2005-02-01

Rapamycin is an immunosuppressive agent with marked antiproliferative properties and is effective in reducing in stent restenosis and vein graft neointimal hyperplasia. Apoptosis is one mechanism counterbalancing cellular proliferation. We therefore investigated the role of apoptosis in rapamycin treated vein grafts in a mouse model. C57BL6J mice underwent interposition of the inferior vena cava from isogenic donor mice into the common carotid artery using a cuff technique. In the treatment group 200 microg of rapamycin were applied locally in pluronic gel. The control group did not receive local treatment. Vein grafts were harvested at 4 weeks postoperatively and underwent morphometric analysis as well as immunohistochemical analysis for apoptosis (TUNEL). In grafted veins without treatment (controls) neointimal thickness was 50 (12-58) microm at 4 weeks postoperatively. In 200 microg rapamycin treated grafts the neointimal thickness was 17 (5-55) microm. Rapamycin treated vein grafts showed a significantly increased rate of apoptosis in the adventitia as compared with controls (P=0.032). In the neointima the apoptosis rate was lower in both groups with no significant difference between rapamycin treated grafts and controls. We conclude that treatment of experimental vein grafts with rapamycin is associated with an increased apoptosis rate in the vascular wall and a trend towards reduction of neointimal hyperplasia. These results suggest that apoptosis may be a beneficial antiproliferative component for the treatment of vein graft disease.

IL-17 suppresses immune effector functions in human papillomavirus-associated epithelial hyperplasia.

PubMed

Gosmann, Christina; Mattarollo, Stephen R; Bridge, Jennifer A; Frazer, Ian H; Blumenthal, Antje

2014-09-01

Persistent infection with high-risk human papillomaviruses (HPV) causes epithelial hyperplasia that can progress to cancer and is thought to depend on immunosuppressive mechanisms that prevent viral clearance by the host. IL-17 is a cytokine with diverse functions in host defense and in the pathology of autoimmune disorders, chronic inflammatory diseases, and cancer. We analyzed biopsies from patients with HPV-associated cervical intraepithelial neoplasia grade 2/3 and murine skin displaying HPV16 E7 protein-induced epithelial hyperplasia, which closely models hyperplasia in chronic HPV lesions. Expression of IL-17 and IL-23, a major inducer of IL-17, was elevated in both human HPV-infected and murine E7-expressing lesions. Using a skin-grafting model, we demonstrated that IL-17 in HPV16 E7 transgenic skin grafts inhibited effective host immune responses against the graft. IL-17 was produced by CD3(+) T cells, predominantly CD4(+) T cells in human, and CD4(+) and γδ T cells in mouse hyperplastic lesions. IL-23 and IL-1β, but not IL-18, induced IL-17 production in E7 transgenic skin. Together, these findings demonstrate an immunosuppressive role for IL-17 in HPV-associated epithelial hyperplasia and suggest that blocking IL-17 in persistent viral infection may promote antiviral immunity and prevent progression to cancer. Copyright © 2014 by The American Association of Immunologists, Inc.

Inflammatory hyperplasia: From diagnosis to treatment

PubMed Central

Shukla, Pradeep; Dahiya, Varun; Kataria, Prerna; Sabharwal, Shreya

2014-01-01

Gingival enlargement, the currently accepted terminology for an increase in the size of the gingiva, is a common feature of gingival disease. Local and systemic factors influence the gingival conditions of the patient. These factors results in a spectrum of diseases that can be developmental, reactive and inflammatory to neoplastic. In this article, the history, etiology, clinical and histopathological features, treatment strategies and preventive protocol of inflammatory hyperplasia are discussed. PMID:24744554

Anovulvar cleft and vaginal prolapse-hyperplasia in a bitch.

PubMed

Mostachio, G Q; Vicente, W R R; Cardilli, D J; Pires, E A; Toniollo, G H

2007-12-01

This report presents the case of a nine-month-old bitch with incomplete occlusion of the skin and mucosa between the anus and dorsal commissure of the vulva. This anomaly, known as anovulvar cleft, was associated with a vaginal prolapse-hyperplasia. Anovulvar cleft is a rare condition in bitches and is caused by incomplete closure of the dorsal urogenital folds. Anovulvar cleft can lead to clitoritis, abrasion, dryness and devitalisation of the smooth exposed mucosa. Surgery can correct the condition. In the present study, surgical resection of the hyperplasic vaginal tissue associated with perineoplasty using an inverted V-shaped incision showed excellent results. An ovariohysterectomy was also performed to prevent recurrence of the vaginal prolapse-hyperplasia.

Histopathology of Veins Obtained at Hemodialysis Arteriovenous Fistula Creation Surgery.

PubMed

Alpers, Charles E; Imrey, Peter B; Hudkins, Kelly L; Wietecha, Tomasz A; Radeva, Milena; Allon, Michael; Cheung, Alfred K; Dember, Laura M; Roy-Chaudhury, Prabir; Shiu, Yan-Ting; Terry, Christi M; Farber, Alik; Beck, Gerald J; Feldman, Harold I; Kusek, John W; Himmelfarb, Jonathan

2017-10-01

Stenosis from venous neointimal hyperplasia is common in native arteriovenous fistulas (AVFs). However, the preexisting histologic characteristics of veins at fistula creation, and associations thereof with baseline patient factors, have not been well characterized. In this study, we conducted histologic analysis of a segment of the vein used for anastomosis creation, obtained during AVF creation from 554 of the 602 participants in the multicenter Hemodialysis Fistula Maturation Cohort Study. We quantified intimal and medial areas and lengths of the internal and external elastic lamina by morphometry and assessed venous wall cells by immunohistochemistry, extracellular matrix with Movat stain, and calcium deposition by alizarin red stain. We also studied a representative subset of veins for markers of monocyte/macrophage content, cell proliferation, apoptosis, and neoangiogenesis. Neointima occupied >20% of the lumen in 57% of fully circumferential vein samples, and neointimal hyperplasia associated positively with age and inversely with black race. The neointima was usually irregularly thickened, sometimes concentric, and contained α -smooth muscle actin-expressing cells of smooth muscle or myofibroblast origin. Proteoglycans admixed with lesser amounts of collagen constituted the predominant matrix in the neointima. In 82% of vein samples, the media of vessel walls contained large aggregates of collagen. A minority of veins expressed markers of inflammation, cell proliferation, cell death, calcification, or neoangiogenesis. In conclusion, we observed preexisting abnormalities, including neointimal hyperplasia and prominent accumulation of extracellular matrix, in veins used for AVF creation from a substantial proportion of this cohort. Copyright © 2017 by the American Society of Nephrology.

Kir2.1 regulates rat smooth muscle cell proliferation, migration, and post-injury carotid neointimal formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiao, Yong; Tang, Chengchun, E-mail: tangchengchun@medmail.com.cn; Wang, Qingjie

Phenotype switching of vascular smooth muscle cells (VSMC) from the contractile type to the synthetic type is a hallmark of vascular disorders such as atherosclerosis and restenosis after angioplasty. Inward rectifier K{sup +} channel 2.1 (Kir2.1) has been identified in VSMC. However, whether it plays a functional role in regulating cellular transformation remains obscure. In this study, we evaluated the role of Kir2.1 on VSMC proliferation, migration, phenotype switching, and post-injury carotid neointimal formation. Kir2.1 knockdown significantly suppressed platelet-derived growth factor BB-stimulated rat vascular smooth muscle cells (rat-VSMC) proliferation and migration. Deficiency in Kir2.1 contributed to the restoration of smoothmore » muscle α-actin, smooth muscle 22α, and calponin and to a reduction in osteopontin expression in rat-VSMC. Moreover, the in vivo study showed that rat-VSMC switched to proliferative phenotypes and that knockdown of Kir2.1 significantly inhibited neointimal formation after rat carotid injury. Kir2.1 may be a potential therapeutic target in the treatment of cardiovascular diseases, such as atherosclerosis and restenosis following percutaneous coronary intervention.« less

Nonclassic Congenital Adrenal Hyperplasia

PubMed Central

Witchel, Selma Feldman; Azziz, Ricardo

2010-01-01

Nonclassic congenital adrenal hyperplasia (NCAH) due to P450c21 (21-hydroxylase deficiency) is a common autosomal recessive disorder. This disorder is due to mutations in the CYP21A2 gene which is located at chromosome 6p21. The clinical features predominantly reflect androgen excess rather than adrenal insufficiency leading to an ascertainment bias favoring diagnosis in females. Treatment goals include normal linear growth velocity and “on-time” puberty in affected children. For adolescent and adult women, treatment goals include regularization of menses, prevention of progression of hirsutism, and fertility. This paper will review key aspects regarding pathophysiology, diagnosis, and treatment of NCAH. PMID:20671993

Fermented dairy products modulate Citrobacter rodentium-induced colonic hyperplasia.

PubMed

Collins, James W; Chervaux, Christian; Raymond, Benoit; Derrien, Muriel; Brazeilles, Rémi; Kosta, Artemis; Chambaud, Isabelle; Crepin, Valerie F; Frankel, Gad

2014-10-01

We evaluated the protective effects of fermented dairy products (FDPs) in an infection model, using the mouse pathogen Citrobacter rodentium (CR). Treatment of mice with FDP formulas A, B, and C or a control product did not affect CR colonization, organ specificity, or attaching and effacing lesion formation. Fermented dairy product A (FDP-A), but neither the supernatant from FDP-A nor β-irradiated (IR) FDP-A, caused a significant reduction in colonic crypt hyperplasia and CR-associated pathology. Profiling the gut microbiota revealed that IR-FDP-A promoted higher levels of phylotypes belonging to Alcaligenaceae and a decrease in Lachnospiraceae (Ruminococcus) during CR infection. Conversely, FDP-A prevented a decrease in Ruminococcus and increased Turicibacteraceae (Turicibacter). Importantly, loss of Ruminococcus and Turicibacter has been associated with susceptibility to dextran sodium sulfate-induced colitis. Our results demonstrate that viable bacteria in FDP-A reduced CR-induced colonic crypt hyperplasia and prevented the loss of key bacterial genera that may contribute to disease pathology. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Stent coverage and neointimal proliferation in bare metal stents postdilated with a Paclitaxel-eluting balloon versus everolimus-eluting stents: prospective randomized study using optical coherence tomography at 6-month follow-up.

PubMed

Poerner, Tudor C; Otto, Sylvia; Gassdorf, Johannes; Nitsche, Kristina; Janiak, Florian; Scheller, Bruno; Goebel, Björn; Jung, Christian; Figulla, Hans R

2014-12-01

In this randomized trial, strut coverage and neointimal proliferation of a therapy of bare metal stents (BMSs) postdilated with the paclitaxel drug-eluting balloon (DEB) was compared with everolimus drug-eluting stents (DESs) at 6-month follow-up using optical coherence tomography. We hypothesized sufficient stent coverage at follow-up. A total of 105 lesions in 90 patients were treated with either XIENCE V DES (n=51) or BMS postdilated with the SeQuent Please DEB (n=54). At follow-up, comparable results on the primary optical coherence tomography end point (percentage uncovered struts 5.64±9.65% in BMS+DEB versus 4.93±9.29% in DES; P=0.366) were found. Thus, BMS+DEB achieved the prespecified noninferiority margin of 5% uncovered struts versus DES (difference between treatment means, 0.71%; one-sided upper 95% confidence interval, 4.14%; noninferiority P=0.04). Optical coherence tomography analysis showed significantly more global neointimal proliferation in the BMS+DEB group (15.7±7.8 versus 11.0±5.2 mm(3) proliferation volume/cm stent length; P=0.002). No significant focal in-stent stenosis analyzed with angiography (percentage diameter stenosis at follow-up, 22.8±11.9 versus 16.9±10.4; P=0.014) and optical coherence tomography (peak local area stenosis, 39.5±13.8% versus 36.8±15.6%; P=0.409) was found. Good stent strut coverage of >94% was found in both therapy groups. Despite greater suppression of global neointimal growth in DES, both DES and BMS+DEB effectively prevented clinically relevant focal restenosis at 6-month follow-up. http://www.clinicaltrials.gov. Unique identifier: NCT01056744. © 2014 American Heart Association, Inc.

Preventive effects of lignan extract from flax hulls on experimentally induced benign prostate hyperplasia.

PubMed

Bisson, Jean-François; Hidalgo, Sophie; Simons, Rudy; Verbruggen, Marian

2014-06-01

Consumption of diet rich in lignans may decrease the risk of some chronic hormonal conditions such as benign prostatic hyperplasia (BPH). This study investigated whether a lignan-rich extract from flaxseed hulls, LinumLife EXTRA (LLE), could prevent BPH using the testosterone propionate (TP)-induced BPH rat model. Male Wistar-Unilever rats were randomly divided into four groups of 12 rats each: a negative control group fed with control diet and receiving daily subcutaneous injections of corn oil without TP, and three groups fed with control diet (positive control), diet containing 0.5% LLE (LLE 0.5) or 1.0% LLE (LLE 1.0) and receiving daily subcutaneous injections of TP in corn oil. Treatments with diets started 2 weeks before the induction of BPH and were carried out for 5 consecutive weeks. The influence of TP and LLE on body weight (BW), food and water consumptions, and enterolactone (ENL) levels in serum and urine of rats was examined at the end of the 5-week treatment period. TP significantly diminished the mean body weight gain (MBWG) of positive control rats and their food and water consumptions while LLE reduced significantly this MBWG reduction in a dose-dependent manner. The lignan-rich extract significantly inhibited TP-induced prostate size ratio (prostate weight/rat BW) increase in comparison with positive controls (P<.001). This effect was dose dependent. Higher serum and urine levels of ENL correlated well with the dose of extract provided to rats. It was concluded that the lignan-rich flaxseed hull extract prevented the TP-induced BPH indicating it might be beneficial in the prevention of BPH.

Benign prostate hyperplasia (BPH) - resources

MedlinePlus

Resources - benign prostatic hyperplasia (BPH); Prostate enlargement resources; BPH resources ... organizations provide information on benign prostatic hyperplasia ( prostate enlargement ): National Institute of Diabetes and Digestive and Kidney ...

Association of neointimal morphology by optical coherence tomography with rupture of neoatherosclerotic plaque very late after coronary stent implantation.

NASA Astrophysics Data System (ADS)

Karanasos, Antonios; Ligthart, Jurgen; Witberg, Karen; Toutouzas, Konstantinos; Daemen, Joost; van Soest, Gijs; Gnanadesigan, Muthukaruppan; van Geuns, Robert-Jan; de Jaegere, Peter; Regar, Evelyn

2013-03-01

Purpose: Neoatherosclerosis within a stent has been recently described as a culprit of late stent failure. We investigated by optical coherence tomography (OCT) the association of neoatherosclerotic plaque morphology with neointimal rupture (NR) and clinical presentation in patients late after coronary stent implantation. Methods: From 1/1/2007 to 31/1/2012, 74 patients from two institutions underwent OCT assessment of a coronary stent implanted at least 18 months prior to OCT study. Native atherosclerosis criteria were used for neointimal characterization. Results: Neoatherosclerosis was observed in 59.5% of the stents (n=44). Stents with neoatherosclerosis were more often associated with symptoms compared to stents without neoatherosclerosis (59.1% acute coronary syndrome (ACS), 25% stable angina (SA), and 15.9% asymptomatic versus 43.3% ACS, 6.7% SA, 50% asymptomatic, p<0.01). Among neoatherosclerotic lesions (n=44), NR was detected in 19 (43.2%) and had higher incidence in ACS (61.5%) than in SA (18.2%) and asymptomatic (14.3%) (p<0.05). Thrombus was detected in all NR cases. Fibrous cap thickness was lower in NR lesions compared to lesions without NR (48+/-21 μm versus 104+/-58μm, p<0.01). Lipid content tended to be higher in lesions with NR (260+/-103° versus 203+/-85°, p=0.051). Lesions with NR had more often dense macrophage infiltration (84.2% versus 44.0%, p<0.05). There were no differences in neovascularization or calcifications between lesions with or without NR. Conclusions: Neoatherosclerosis is frequent and more common among symptomatic patients. Importantly, neointimal rupture is associated with ACS late after stent implantation. Specific morphological characteristics, such as cap thickness and macrophage infiltration are associated with rupture of neoatherosclerotic plaques.

Subareolar Sclerosing Ductal Hyperplasia.

PubMed

Cheng, Esther; D'Alfonso, Timothy M; Arafah, Maria; Marrero Rolon, Rebecca; Ginter, Paula S; Hoda, Syed A

2017-02-01

Subareolar sclerosing duct hyperplasia (SSDH) remains to be fully characterized nearly 20 years after initial description. Thirty-five SSDH cases diagnosed over a 16-year period (January 2000 to December 2015) were reviewed. All patients were female (mean age = 59 years, range = 18-80) who had presented with a unilateral solitary lesion (left 22, right 13) with a mean size of 1.3 cm (range = 0.4-3.0 cm), and showed florid and papillary epithelial hyperplasia with dense sclerosis without involvement of nipple or areolar epidermis. Significant lesions concurrent within SSDH included low-grade adenosquamous carcinoma (n = 1), ductal carcinoma in situ (DCIS; n = 1), lobular carcinoma in situ (LCIS; n = 1), and atypical ductal hyperplasia (ADH; n = 13). No case of SSDH recurred in a mean follow-up of 44 months (range = 6-189). Subsequent significant lesions occurred in 6 patients: DCIS (n = 3; ipsilateral 2, contralateral 1), ipsilateral ADH (n = 2), and ipsilateral atypical lobular hyperplasia (n = 1). Long-term follow-up for patients with SSDH is indicated as DCIS can occur subsequently in either breast.

Antagonistic effect of Lepidium meyenii (red maca) on prostatic hyperplasia in adult mice.

PubMed

Gonzales, G F; Gasco, M; Malheiros-Pereira, A; Gonzales-Castañeda, C

2008-06-01

The plants from the Lepidium gender have demonstrated to have effect on the size of the prostate. Lepidium meyenii (Maca) is a Peruvian plant that grows exclusively over 4000 m above sea level. The present study was designed to determine the effect of red maca (RM) in the prostate hyperplasia induced with testosterone enanthate (TE) in adult mice. Prostate hyperplasia was induced by administering TE, and then these animals (n = 6, each group) were treated with RM or Finasteride (positive control) for 21 days. There was an additional group without prostate hyperplasia (vehicle). Mice were killed on days 7, 14 and 21 after treatment with RM. Testosterone and oestradiol levels were measured on the last day of treatment. Prostatic stroma, epithelium and acini were measured histologically. RM reduced prostate weight at 21 days of treatment. Weights of seminal vesicles, testis and epididymis were not affected by RM treatment. The reduction in prostate size by RM was 1.59 times. Histological analysis showed that TE increased 2-fold the acinar area, effect prevented in the groups receiving TE + RM for 14 (P < 0.05) and 21 (P < 0.05) days and the group receiving TE + Finasteride for 21 days (P < 0.05). TE increased prostatic stroma area and this effect was prevented by treatment with RM since 7 days of treatment or Finasteride. The reduction in prostatic stroma area by RM was 1.42 times. RM has an anti-hyperplastic effect on the prostate of adult mice when hyperplasia was induced with TE acting first at prostatic stromal level.

[Endometrial hyperplasia, diagnosis. Clinical, paraclinical exam and management].

PubMed

Pangal, Alexandra; Costăchescu, Gh; Aldea, Marie Jeanne

2010-01-01

Factors associated with unopposed estrogenic stimulation such as obesity, exogenous hormone use endometrial hyperplasia are related to the development of the most common form of endometrial carcinoma, that is, the endometroid subtype. We selected a group of patients diagnosed with endometrial hyperplasia by endometrial biopsy and histopathological examination. The main complaint in all cases was abnormal uterine bleeding. All patients had gynecological examination, vaginal ultrasound, hysteroscopy endometrial biopsy or D&C. 32 patients had also immunohistochemical staining for Ki67, EGF, ER, PGR. Cases with ages between 24-67 years were classified as: 100 simple hyperplasia, 10 complex hyperplasia, 43 atypical simple hyperplasia, 7 atypical complex hyperplasia. PR were 40-60% at all forms of hyperplasia, E2R were 30-40% in simple hyperplasia without atypia and 50-70% in complex hyperplasia without atypia. Correlation between immunohistochemical expression of E2R, PGR, Ki-67, EGF and body mass revealed an high immunohistochemical expression of E2R and Ki-67 in patients with hyperplasia without atypia and a low expression and high reactivity of EGF in cases with high body mass. Vaginal ultrasound and hysteroscopy are efficacious completion for histopathological diagnosis. We recommend an age/risk appropriate screening to detect risk factors and early disease in the asymptomatic patients.

Florid reactive lymphoid hyperplasia of terminal ileum.

PubMed

Kanakala, Venkatesh; Birch, Peter; Kasaraneni, Ramesh

2010-01-01

Florid lymphoid hyperplasia in the terminal ileum can present to surgeons as an acute abdominal pain. Only few cases were reported in the literature. Our case illustrates that a rare case of florid lymphoid hyperplasia can present to surgeons as acute appendicitis. During the operation the gross appearance may mimic Crohn's disease. A limited resection is sufficient to clinch the diagnosis of florid lymphoid hyperplasia / Crohn's disease. In florid lymphoid hyperplasia limited resection may be curative.

Long term impact of balloon post-dilatation on neointimal formation: an experimental comparative study between second-generation self-expanding versus balloon-expandable stent technologies.

PubMed

Aboodi, Michael S; Milewski, Krzysztof; Tellez, Armando; Cheng, Yanping; Yi, Geng-Hua; Kaluza, Greg L; Granada, Juan F

2014-02-15

Background: Self-expanding stents (SES) are reemerging as therapeutic alternatives to treat coronary artery disease. It has been proposed that SES can improve clinical outcomes by inducing less injury at implantation and achieving better vessel wall apposition.To date, little data exists comparing the vascular response to both methods of deployment in a controlled experimental setting. Objective: To quantify differences in vascular injury and healing between second-generation SES and balloon-expandable stents (BES) and the effects of balloon post-dilatation in a porcine coronary model. Methods: Seventy-five bare SES (AXXESS or vProtect) and 42 BES (Vision) were implanted in porcine coronaries. A subset of these received balloon post-dilatation(SES 1 D 5 22, BES 1 D 5 20). Follow-up was scheduled at 30 (BES 5 10, BES 1 D 56, SES 5 19, SES 1 D 5 8), 90 (BES 5 6, BES 1 D 5 8, SES 5 19, SES 1 D 5 8), and 180 days (BES 5 6, BES 1 D 5 6, SES 5 15, SES 1 D 5 6). Results: In vivo imaging and histological analysis showed that neointimal formation peaks early (30 days) in BES. Conversely, for SES, the peak occurred later (90 days). However, the neointimal formation achieved in either group equalized at 180 days. For SES, post-dilatation shortened the peak of neointimal formation to 30 days. Conversely, for BES, post-dilatation delayed the peak of neointimal formation to 90 days. At 30 days, histology showed that SES had significantly less injury. However, at 90 days, injury scores tended to be higher for SES. By 180 days, injury scores were comparable between both groups. Conclusions: The mechanism of stent expansion influences the degree of vascular injury and healing. The synergistic use of balloon post dilatation changes the dynamics of healing and may impact the potential beneficial effects inherent to SES technologies.

Florid reactive lymphoid hyperplasia of terminal ileum

PubMed Central

Kanakala, Venkatesh; Birch, Peter; Kasaraneni, Ramesh

2010-01-01

Florid lymphoid hyperplasia in the terminal ileum can present to surgeons as an acute abdominal pain. Only few cases were reported in the literature. Our case illustrates that a rare case of florid lymphoid hyperplasia can present to surgeons as acute appendicitis. During the operation the gross appearance may mimic Crohn’s disease. A limited resection is sufficient to clinch the diagnosis of florid lymphoid hyperplasia / Crohn’s disease. In florid lymphoid hyperplasia limited resection may be curative. PMID:22242075

Effect of methanolic extract of Piper sarmentosum leaves on neointimal foam cell infiltration in rabbits fed with high cholesterol diet

PubMed Central

Amran, Adel A.; Zakaria, Zaiton; Othman, Faizah; Das, Srijit; Al-Mekhlafi, Hesham M.; Raj, Santhana; Nordin, Nor-Anita MM

2012-01-01

Previous research has shown the beneficial effects of aqueous extract of Piper sarmentosum (P.s) on atherosclerosis. The first stage in atherosclerosis is the formation of foam cell. The aim of this study was to investigate the effect of the methanol extract of P.s on fatty streaks by calculating neointimal foam cell infiltration in rabbits fed with high cholesterol diet. Thirty six male New Zealand white rabbits were divided equally into six groups: (i) C: control group fed normal rabbit chow; (ii) CH: cholesterol diet (1 % cholesterol); (iii) PM1: 1 % cholesterol with methanol extract of P.s (62.5 mg/kg); (iv) PM2: 1 % cholesterol with methanol extract of P.s (125 mg/kg); (v) PM3: 1 % cholesterol with methanol extract of P.s (250 mg/kg); (vi) SMV group fed 1 % cholesterol supplemented with Simvistatin drug (1.2 mg/kg). All animals were treated for 10 weeks. At the end of the treatment, the rabbits were fasted and sacrificed and the aortic tissues were collected for histological studies to measure the area of the neointimal foam cell infiltration using software. The thickening of intima ratio of atherosclerosis and morphological changes by scanning electron microscope were measured. The results showed that the atherosclerotic group had significantly bigger area of fatty streak compared to the control group. The area of fatty streak in the abdominal aorta was significantly reduced in the treatment groups which were similar with the SMV group. Similarly, there was a reduction in the number of foam cell in the treatment groups compared to the atherosclerotic group as seen under scanning microscope. In conclusion, histological study demonstrated that the methanol extract of the P.s could reduce the neointimal foam cell infiltration in the lumen of the aorta and the atherosclerotic lesion. PMID:27366140

Improved Patency of Transjugular Intrahepatic Portosystemic Shunt: The Efficacy of Cilostazol for the Prevention of Pseudointimal Hyperplasia in Swine TIPS Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Sang Woo; Cha, In Ho; Kim, Chul Hwan

Purpose. To investigate the efficacy of oral administration of cilostazol to inhibit pseudointimal/intimal hyperplasia in swine TIPS models. Methods. Successful TIPS creation was carried out in 11 of 12 healthy young pigs (20-25 kg). In the treatment group (n = 6), both cilostazol and aspirin were administered daily, from the first day of TIPS creation. The control group (n = 5) was administered only aspirin. The animals were followed-up for 2 weeks and then killed. The specimen (including portal vein, hepatic parenchymal tract, hepatic vein, and inferior vena cava) and stents were carefully bisected in a longitudinal fashion. The controlmore » group was compared with the treatment group by means of a gross and histologic evaluation of the degree of pseudointimal/intimal hyperplasia in the shunt. Results. At the gross evaluation, the control group showed considerably more pseudointimal/intimal hyperplasia than the treatment group. Using microscopic evaluation, there was a statistically significant difference (p < 0.05) in the mean maximum pseudointimal/intimal hyperplasia thickness between the control group (2.97 {+-} 0.33 mm) and treatment group (0.73 {+-} 0.27 mm). Conclusion. Oral administration of cilostazol may have been effective in reducing pseudointimal/intimal hyperplasia in swine TIPS models.« less

The prevention of benign prostatic hyperplasia (bph).

PubMed

Roper, W G

2017-03-01

Barry Marshall and Robin Warren were the first to show that the chronic diseases (gastric ulcer and chronic gastritis) were caused by an infection (Helicobacter pylori). The chronic disease benign prostatic hyperplasia belongs to the same ilk, except that the infection process is much more subtle and complex. The enzyme Phospholipase D (PLD) which is attached to the outer membrane of Escherichia coli (E. coli) has now been almost completely proven to be the basic cause of BPH. The evidence for this process is now extremely strong and compelling. PLD obtained from the organism Streptomyces chromofuscus has been used in past research because of its PLD content. It is commercially available. In vitro, on a culture of prostatic smooth muscle, PLD stimulated the production of lysophosphatidic acid (LPA) which acted on and caused substantial growth of that muscle in accordance with the quantity of PLD/ LPA generated. It has been asserted that repeated colonization by E. coli of the transitional zone of the prostate gland and the release of PLD following repeated destruction of these colonized bacteria, is the basic cause of BPH. The evidence for colonizing and re-colonizing infection is now overwhelming. PLD is a simple lipid consisting of a phosphate, glycerol and a fatty acid. After absorption into the prostatic stroma (which consists of connective tissue and of smooth muscle), it stimulates the production of LPA which, in turn, apart from directly stimulating prostatic smooth muscle, also acts on the connective tissue in the prostate and induces a complex mixture of growth regulatory proteins, which include members of the fibroblast, insulin-like and growth transforming factor families and implicates autocrine hormones acting on the stroma and paracrine hormones acting on epithelium. Also involved, are a variety of interleukins and other inflammatory cell cytokines, secreted by the stroma, which may further promote autocrine/paracrine proliferation of BPH cells

Prognostic significance of atypical papillary urothelial hyperplasia.

PubMed

Swierczynski, Sharon L; Epstein, Jonathan I

2002-05-01

Typical papillary hyperplasia, a recently recognized precursor lesion to low-grade papillary urothelial neoplasms, consists of undulating folds of cytologically benign urothelium. Well-developed, branching fibrovascular cores of a papillary neoplasm are not evident. We have noted lesions with the architectural pattern of papillary hyperplasia; however, the overlying urothelium demonstrated varying degrees of cytologic atypia. We identified 15 cases of atypical papillary hyperplasia (13 males, 2 females, age 55 to 92) with overlying urothelium showing cytologic atypia. Of these cases, 8 (53%) were received in consultation. Of the 15 cases, 8 exhibited overlying flat carcinoma in situ (CIS), 4 had overlying dysplasia, and 3 were transitional between papillary hyperplasia with atypia and the earliest lesions of papillary neoplasia. Of these cases, 5 patients had multiple specimens with atypical papillary hyperplasia (range, 2 to 8) over time. Concurrent to the diagnosis of atypical papillary hyperplasia, there were 25 different urothelial lesions: CIS (n = 11), papilloma (n = 1), papillary neoplasm of low malignant potential with CIS (n = 1), high-grade papillary urothelial carcinoma (n = 10; 3 with CIS), small-cell carcinoma (n = 1), and infiltrating urothelial carcinoma (n = 1). Of 11 patients with known prior history, 2 had 12 prior urothelial neoplasms (9 low-grade papillary neoplasms, 2 papillary urothelial neoplasms of low malignant potential, and 1 high-grade papillary cancer). Of 10 patients with atypical papillary hyperplasia and a minimum of 1 year of follow-up, 9 had 19 recurrences: CIS (n = 4), papilloma (n = 1), papillary neoplasm of low malignant potential (n = 1), infiltrating urothelial carcinoma (n = 3; 1 with CIS), and high-grade papillary urothelial carcinoma (n = 10; 5 with invasion and 2 with CIS). Whether the papillary hyperplasia had overlying CIS or dysplasia did not affect the correlation with urothelial neoplasms. Immunohistochemical analysis

Prenatal Diagnosis of Congenital Adrenal Hyperplasia.

PubMed

Yau, Mabel; Khattab, Ahmed; New, Maria I

2016-06-01

Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is a monogenic disorder of adrenal steroidogenesis. To prevent genital ambiguity, in girls, prenatal dexamethasone treatment is administered early in the first trimester. Prenatal genetic diagnosis of CAH and fetal sex determination identify affected female fetuses at risk for genital virilization. Advancements in prenatal diagnosis are owing to improved understanding of the genetic basis of CAH and improved technology. Cloning of the CYP21A2 gene ushered in molecular genetic analysis as the current standard of care. Noninvasive prenatal diagnosis allows for targeted treatment and avoids unnecessary treatment of males and unaffected females. Copyright © 2016 Elsevier Inc. All rights reserved.

Pharmacotherapy for benign prostatic hyperplasia.

PubMed Central

Narayan, P; Indudhara, R

1994-01-01

Benign prostatic hyperplasia is a benign neoplasm of the prostate seen in men of advancing age. Microscopic evidence of the disorder is seen in about 70% of men by 70 years of age, whereas symptoms requiring some form of surgical intervention occur in 30% of men during their lifetime. Although the exact cause of benign prostatic hyperplasia is not clear, it is well recognized that high levels of intraprostatic androgens are required for the maintenance of prostatic growth. In recent years, extensive surveys of patients undergoing transurethral resection of the prostate reveal an 18% incidence of morbidity that has essentially not changed in the past 30 years. This procedure is also the second highest reimbursed surgical therapy under Medicare. These findings have resulted in an intensive search for alternative therapies for prostatic hyperplasia. An alternative that has now been well defined is the use of alpha-adrenergic blockers to relax the prostatic urethra. This is based on findings that a major component of benign prostatic hyperplasia symptoms is spasm of the prostatic urethra and bladder neck, which is mediated by the alpha-adrenergic nerves. A second approach is to block androgens involved in maintaining prostate growth. Several such drugs are now available for clinical use, and we discuss their side effects and use. We also include the newer recommendations on evaluating benign prostatic hyperplasia that are cost-effective yet comprehensive. Images PMID:7528957

Recent Advances in Drug Eluting Stents

PubMed Central

Puranik, Amey S.; Dawson, Eileen R.; Peppas, Nicholas A.

2013-01-01

One of the most common medical interventions to reopen an occluded vessel is the implantation of a coronary stent. While this method of treatment is effective initially, restenosis, or the re-narrowing of the artery frequently occurs largely due to neointimal hyperplasia of smooth muscle cells. Drug eluting stents were developed in order to provide local, site-specific, controlled release of drugs that can inhibit neointima formation. By implementing a controlled release delivery system it may be possible to control the time release of the pharmacological factors and thus be able to bypass some of the critical events associated with stent hyperplasia and prevent the need for subsequent intervention. However, since the advent of first-generation drug eluting stents, long-term adverse effects have raised concerns regarding their safety. These limitations in safety and efficacy have triggered considerable research in developing biodegradable stents and more potent drug delivery systems. In this review, we shed light on the current state-of-the-art in drug eluting stents, problems related to them and highlight some of the ongoing research in this area. PMID:23117022

Effect of fibroin sponge coating on in vivo performance of knitted silk small diameter vascular grafts

PubMed Central

Fukayama, Toshiharu; Ozai, Yusuke; Shimokawadoko, Haruka; Aytemiz, Derya; Tanaka, Ryou; Machida, Noboru; Asakura, Tetsuo

2015-01-01

ABSTRACT Vascular grafts under 5 mm or less in diameter are not developed due to a problem caused by early thrombus formation, neointimal hyperplasia, etc. Bombyx mori silk fibroin (SF) which has biodegradability and tissue infiltration is focused as tube and coating material of vascular grafts. Coating is an important factor to maintain the strength of the anastomotic region of vascular grafts, and to prevent the blood leak from the vascular grafts after implantation. Therefore, in this research, we focused on the SF concentration of the coating solution, and tissue infiltration and remodeling were compared among each SF concentration. Silk poly (-ethylene) glycol diglycidyl ether (PGDE) coating with concentrations of 1.0%, 2.5%, 5.0%, and 7.5% SF were applied for the double-raschel knitted small-sized vessel with 1.5 mm diameter and 1cm in length. The grafts were implanted in the rat abdominal aorta and removed after 3 weeks or 3 months. Vascular grafts patency was monitored by ultrasound, and morphological evaluation was performed by histopathological examination. SF concentration had no significant effects on the patency rate. However, tissue infiltration was significantly higher in the sample of 2.5% SF in 3 weeks, and 1.0% and 2.5% SF in 3 months. Also, in comparison of length inside of the graft, stenosis were not found in 3 weeks, however, found with 5.0% and 7.5% in 3 months. From these results, it is clear that 2.5% SF coating is the most suitable concentration, based on the characteristics of less stenosis, early tissue infiltration, and less neointimal hyperplasia. PMID:26496652

Clinical associations of hepatic stellate cell (HSC) hyperplasia.

PubMed

Mounajjed, Taofic; Graham, Rondell P; Sanderson, Schuyler O; Smyrk, Thomas C

2014-07-01

Hepatic stellate cell (HSC) hyperplasia has been principally attributed to hypervitaminosis A. There are sporadic reports of HSC hyperplasia in other conditions such as chronic biliary disease and hepatitis C, but clinical associations of this entity have not been studied in detail. We aimed to investigate the clinical associations of HSC hyperplasia aside from hypervitaminosis A. We identified 34 patients whose liver histology showed HSC hyperplasia. We reviewed the liver samples; additional histologic findings in addition to HSC hyperplasia were consolidated into a histologic diagnosis. We collected clinical, laboratory, and radiologic data; the histologic diagnosis was combined with this data to reach an "overall diagnosis." Four patients had hypervitaminosis A (all native livers). In native livers (n = 24), HSC hyperplasia also occurred in association with drug-induced hepatitis [n = 6, niacin was the most common inducing agent (n = 3)], reactive hepatitis (n = 4), chronic hepatitis C (n = 4), autoimmune hepatitis (n = 3), steatohepatitis (n = 1), chronic biliary disease (n = 1), and portal venopathy (n = 1). In liver allografts (n = 10), HSC hyperplasia was seen in protocol biopsies without other significant abnormalities (n = 5), chronic biliary disease (n = 4), and acute cellular rejection (n = 1). All patients used medications (total of 99) and 82 % were on multiple medications. HSC hyperplasia is an uncommon and relatively nonspecific finding that most commonly occurs in multimedicated patients, often in the absence of hypervitaminosis A. Associated conditions include drug toxicity (such as niacin), post-liver transplant setting, reactive hepatitis (due to systemic illness or inflammatory disorders of the gastrointestinal tract), and chronic liver disease.

Papillary endothelial hyperplasia in angiokeratoma.

PubMed

Mehta, Anurag; Sayal, Satish Kumar; Raman, Deep Kumar; Sood, Aradhana

2003-01-01

Papillary endothelial hyperplasia (Masson's tumour) is a reactive proliferation of endothelium producing papillary structures with fibrovascular cores. Dilatation, stasis and accompanying inflammation have been incriminated as the inciting events, evident by the presence of this lesion in haemorrhoids, urethral caruncles and laryngeal polyps. We present here a case of papillary endothelial hyperplasia in angiokeratoma hitherto undescribed despite sharing common etiopathogenetic features of dilatation and stasis with other aforementioned lesions.

Nitric oxide treatment reduces neo-intimal formation and modulates osteopontin expression in an ex-vivo human model of intimal hyperplasia.

PubMed

Colotti, Chiara; Vittorini, Simona; Ottaviano, Virginia; Maltinti, Maristella; Angeli, Valeria; Del Ry, Silvia; Giannessi, Daniela

2009-05-01

In this study the effects of nitric oxide (NO) on intimal hyperplasia (IH) were evaluated in an ex-vivo model of human saphenous vein (SV). SV segments were cultured in conditions able to reproduce IH (FCS), or in medium alone (RPMI), or in presence of a NO donor (NO). Osteopontin (OPN) and Interleukin (IL)-6 were determined in the medium at different culture times and in the tissue, at the end of experiment. OPN and IL-6 release in medium was increased in FCS with respect to RPMI (OPN: 13.9+/-2.9 vs. 2.3+/-0.8 microg/ml, p=0.0011; IL-6: 304.2+/-64.7 vs. 42.0+/-10.1 ng/ml, p<0.0006) as well as intima thickness, that positively correlated with OPN production (r=0.81). In tissue OPN was higher in FCS (82.0+/-30.3 ng/mg protein) than in RPMI (13.8+/-4.2, p=0.0051) and at baseline (3.7+/-0.7, p=0.018). NO reduces IH progression (25%) and both OPN and IL-6 expression (OPN/GAPDH: undetectable baseline; 0.27+/-0.06 RPMI; 0.89+/-0.28 FCS; 0.09+/-0.05 NO; p=0.026 FCS vs. baseline, p=0.018 vs. RPMI, p=0.005 vs. NO). The beneficial NO effect on IH reduction appears to be mediated by the indirect inhibition of OPN production. NO could modulates the initial inflammatory signals that induces the OPN over-production with the related cascade of events leading to IH.

Flat epithelial atypia and atypical ductal hyperplasia: carcinoma underestimation rate.

PubMed

Ingegnoli, Anna; d'Aloia, Cecilia; Frattaruolo, Antonia; Pallavera, Lara; Martella, Eugenia; Crisi, Girolamo; Zompatori, Maurizio

2010-01-01

This study was carried out to determine the underestimation rate of carcinoma upon surgical biopsy after a diagnosis of flat epithelial atypia and atypical ductal hyperplasia and 11-gauge vacuum-assisted breast biopsy. A retrospective review was conducted of 476 vacuum-assisted breast biopsy performed from May 2005 to January 2007 and a total of 70 cases of atypia were identified. Fifty cases (71%) were categorized as pure atypical ductal hyperplasia, 18 (26%) as pure flat epithelial atypia and two (3%) as concomitant flat epithelial atypia and atypical ductal hyperplasia. Each group were compared with the subsequent open surgical specimens. Surgical biopsy was performed in 44 patients with atypical ductal hyperplasia, 15 patients with flat epithelial atypia, and two patients with flat epithelial atypia and atypical ductal hyperplasia. Five cases of atypical ductal hyperplasia were upgraded to ductal carcinoma in situ, three cases of flat epithelial atypia yielded one ductal carcinoma in situ and two cases of invasive ductal carcinoma, and one case of flat epithelial atypia/atypical ductal hyperplasia had invasive ductal carcinoma. The overall rate of malignancy was 16% for atypical ductal hyperplasia (including flat epithelial atypia/atypical ductal hyperplasia patients) and 20% for flat epithelial atypia. The presence of flat epithelial atypia and atypical ductal hyperplasia at biopsy requires careful consideration, and surgical excision should be suggested.

Proteus syndrome: association with gingival hyperplasia.

PubMed

Arendorf, T M; Hanslo, B

1995-09-01

A 9-year old Black boy with gigantism of the hands and feet, and recurrent gingival hyperplasia, diagnosed as Proteus syndrome is presented. The oral manifestations of this syndrome are described. To the best of our knowledge, this is the first reported case of gingival hyperplasia associated with Proteus syndrome.

Phloretin Inhibits Platelet-derived Growth Factor-BB-induced Rat Aortic Smooth Muscle Cell Proliferation, Migration, and Neointimal Formation After Carotid Injury.

PubMed

Wang, Dong; Wang, Qingjie; Yan, Gaoliang; Qiao, Yong; Tang, Chengchun

2015-05-01

Abnormal vascular smooth muscle cell proliferation and migration are key factors in many cardiovascular diseases. Here, we investigated the effects of phloretin on platelet-derived growth factor homodimer (PDGF-BB)-induced rat aortic smooth muscle cell (RASMC) proliferation, migration, and neointimal formation after carotid injury. Phloretin significantly inhibited the PDGF-BB-stimulated RASMC proliferation in a concentration-dependent manner (10-100 μM). Also, PDGF-BB-stimulated RASMC migration was inhibited by phloretin at 50 μM. Pretreating RASMC with phloretin dose-dependently inhibited PDGF-BB-induced Akt and p38 mitogen-activated protein kinases activation. Furthermore, phloretin increased p27 and decreased cyclin-dependent kinase 2, CDK4 expression, and p-Rb activation in PDGF-BB-stimulated RASMC in a concentration-dependent manner (10-50 μM). PDGF-BB-induced cell adhesion molecules and matrix metalloproteinase-9 expression were blocked by phloretin at 50 μM. Preincubation with phloretin dose-dependently reduced the intracellular reactive oxygen species production. In vivo study showed that phloretin (20 mg/kg) significantly reduced neointimal formation 14 days after carotid injury in rats. Thus, phloretin may have potential as a treatment against atherosclerosis and restenosis after vascular injury.

Therapeutic options for management of endometrial hyperplasia

PubMed Central

2016-01-01

Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH. PMID:26463434

Therapeutic options for management of endometrial hyperplasia.

PubMed

Chandra, Vishal; Kim, Jong Joo; Benbrook, Doris Mangiaracina; Dwivedi, Anila; Rai, Rajani

2016-01-01

Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH.

Giant fibroadenomatoid hyperplasia of the breast: a case report.

PubMed

Zhang, Hao; Wang, Xin-Lu; Ren, Wei-Dong; Shi, Tie-Mei

2014-01-01

Fibroadenomatoid hyperplasia of the breast (FAHB) is a rare benign breast lesion and its clinical features are similar to fibroadenoma and fibrocystic changes. FAHB has been previously termed sclerosing lobular hyperplasia, fibroadenomatosis, fibroadenomatoid change, or fibroadenomatoid mastopathy. Typically, FAHB is derived from stroma and epithelia. The pathologic characteristics of FAHB are microfocal lobulocentric proliferation of stroma accompanied by epithelial and myoepithelial components resembling similar histological changes, as found in fibroadenoma, apocrine hyperplasia, intraductal hyperplasia, and lobular hyperplasia. FAHB could be present as a localized or diffused pattern in pathology. Most cases show no well-circumscribed mass lesions and no apparent capsules; it is usually identified as an incidental finding in other benign lesions or in random sampling in cancerous breast tissues. FAHB is categorized as a benign proliferative breast disease and it has previously been reported; however, the authors believe this study may be the first case with two giant masses reported. Fiber adenoma hyperplasia is a rare cystic hyperplasia of breast pathology and its ultrasonographic manifestations are easily confused with breast cancer. Comparative MRI ultrasound analysis will help make the differential diagnosis. © 2014 S. Karger AG, Basel.

Congenital adrenal hyperplasia

MedlinePlus

... body produces more androgen, a type of male sex hormone. This causes male characteristics to appear early (or inappropriately). Congenital adrenal hyperplasia can affect both boys and girls. About 1 in 10,000 to ...

Re-examining minimal luminal diameter relocation and quantitative coronary angiography--intravascular ultrasound correlations in stented saphenous vein grafts: methodological insights from the randomised RRISC trial.

PubMed

Semeraro, Oscar; Agostoni, Pierfrancesco; Verheye, Stefan; Van Langenhove, Glenn; Van den Heuvel, Paul; Convens, Carl; Van den Branden, Frank; Bruining, Nico; Vermeersch, Paul

2009-03-01

Angiographic parameters (such as late luminal loss) are common endpoints in drug-eluting stent trials, but their correlation with the neointimal process and their reliability in predicting restenosis are debated. Using quantitative coronary angiography (QCA) data (49 bare metal stent and 44 sirolimus-eluting stent lesions) and intravascular ultrasound (IVUS) data (39 bare metal stent and 34 sirolimus-eluting stent lesions) from the randomised Reduction of Restenosis In Saphenous vein grafts with Cypher stent (RRISC) trial, we analysed the "relocation phenomenon" of QCA-based in-stent minimal luminal diameter (MLD) between post-procedure and follow-up and we correlated QCA-based and IVUS-based restenotic parameters in stented saphenous vein grafts. We expected the presence of MLD relocation for low late loss values, as MLD can "migrate" along the stent if minimal re-narrowing occurs, while we anticipated follow-up MLD to be located close to post-procedural MLD position for higher late loss. QCA-based MLD relocation occurred frequently: the site of MLD shifted from post-procedure to follow-up an "absolute" distance of 5.8 mm [2.5-10.2] and a "relative" value of 29% [10-46]. MLD relocation failed to correlate with in-stent late loss (rho = 0.14 for "absolute" MLD relocation [p = 0.17], and rho=0.03 for "relative" relocation [p = 0.811). Follow-up QCA-based and IVUS-based MLD values well correlated in the overall population (rho = 0.76, p < 0.001), but QCA underestimated MLD on average 0.55 +/- 0.49 mm, and this was mainly evident for lower MLD values. Conversely, the location of QCA-based MLD failed to correlate with the location of IVUS-based MLD (rho = 0.01 for "absolute" values--in mm [p = 0.911, rho = 0.19 for "relative" values--in % [p = 0.111). Overall, the ability of late loss to "predict" IVUS parameters of restenosis (maximum neointimal hyperplasia diameter, neointimal hyperplasia index and maximum neointimal hyperplasia area) was moderate (rho between 0

Role of Excessive Autophagy Induced by Mechanical Overload in Vein Graft Neointima Formation: Prediction and Prevention

NASA Astrophysics Data System (ADS)

Chang, Ya-Ju; Huang, Hui-Chun; Hsueh, Yuan-Yu; Wang, Shao-Wei; Su, Fong-Chin; Chang, Chih-Han; Tang, Ming-Jer; Li, Yi-Shuan; Wang, Shyh-Hau; Shung, Kirk K.; Chien, Shu; Wu, Chia-Ching

2016-02-01

Little is known regarding the interplays between the mechanical and molecular bases for vein graft restenosis. We elucidated the stenosis initiation using a high-frequency ultrasonic (HFU) echogenicity platform and estimated the endothelium yield stress from von-Mises stress computation to predict the damage locations in living rats over time. The venous-arterial transition induced the molecular cascades for autophagy and apoptosis in venous endothelial cells (ECs) to cause neointimal hyperplasia, which correlated with the high echogenicity in HFU images and the large mechanical stress that exceeded the yield strength. The ex vivo perfusion of arterial laminar shear stress to isolated veins further confirmed the correlation. EC damage can be rescued by inhibiting autophagy formation using 3-methyladenine (3-MA). Pretreatment of veins with 3-MA prior to grafting reduced the pathological increases of echogenicity and neointima formation in rats. Therefore, this platform provides non-invasive temporal spatial measurement and prediction of restenosis after venous-arterial transition as well as monitoring the progression of the treatments.

Periadventitial drug delivery for the prevention of intimal hyperplasia following open surgery.

PubMed

Chaudhary, Mirnal A; Guo, Lian-Wang; Shi, Xudong; Chen, Guojun; Gong, Shaoqin; Liu, Bo; Kent, K Craig

2016-07-10

Intimal hyperplasia (IH) remains a major cause of poor patient outcomes after surgical revascularization to treat atherosclerosis. A multitude of drugs have been shown to prevent the development of IH. Moreover, endovascular drug delivery following angioplasty and stenting has been achieved with a marked diminution in the incidence of restenosis. Despite advances in endovascular drug delivery, there is currently no clinically available method of periadventitial drug delivery suitable for open vascular reconstructions. Herein we provide an overview of the recent literature regarding innovative polymer platforms for periadventitial drug delivery in preclinical models of IH as well as insights about barriers to clinical translation. A comprehensive PubMed search confined to the past 15years was performed for studies of periadventitial drug delivery. Additional searches were performed for relevant clinical trials, patents, meeting abstracts, and awards of NIH funding. Most of the research involving direct periadventitial delivery without a drug carrier was published prior to 2000. Over the past 15years there have been a surge of reports utilizing periadventitial drug-releasing polymer platforms, most commonly bioresorbable hydrogels and wraps. These methods proved to be effective for the inhibition of IH in various animal models (e.g. balloon angioplasty, wire injury, and vein graft), but very few have advanced to clinical trials. There are a number of barriers that may account for this lack of translation. Promising new approaches including the use of nanoparticles will be described. No periadventitial drug delivery system has reached clinical application. For periadventitial delivery, polymer hydrogels, wraps, and nanoparticles exhibit overlapping and complementary properties. The ideal periadventitial delivery platform would allow for sustained drug release yet exert minimal mechanical and inflammatory stresses to the vessel wall. A clinically applicable strategy

[Primary hyperaldosteronism due to unilateral adrenal hyperplasia with surgical resolution].

PubMed

Rubio-Puchol, O; Garzón-Pastor, S; Salom-Vendrell, C; Hernández-Mijares, A

Unilateral adrenal hyperplasia is a rare cause of primary hyperaldosteronism (around a 3%) that has surgical treatment. A case of a patient with hypertension resistant to conventional therapy in treatment with 7 drugs who presented with primary hyperaldosteronism due to unilateral adrenal hyperplasia is presented. A left adrenalectomy was performed, and the patient had a good clinical response, with no need of any drug after 2 years of surgery. Unilateral adrenal hyperplasia is a different entity and it is not an asymmetric variant of the bilateral adrenal hyperplasia. In the study of patients with primary hyperaldosteronism and imaging tests with absence of adenoma is a diagnosis that must be considered before cataloguing patients with bilateral adrenal hyperplasia and start a medical treatment, because unilateral adrenal hyperplasia would have a surgical resolution. Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

Role of inducible nitric oxide synthase in transplant arteriosclerosis.

PubMed

Lee, P C; Shears, L L; Billiar, T R

1999-12-01

1. Transplant arteriosclerosis is a major obstacle to long-term allograft survival. Nitric oxide (NO) has been implicated as a mediator in the development of this disease. 2. We and others have shown that inducible nitric oxide synthase (iNOS) is up-regulated in allografts with transplant arteriosclerosis. Despite the acute cytotoxic effects produced by high levels of NO, a chronic increase in NO availability is protective against neointimal hyperplasia, mainly by suppressing the inflammatory cell recruitment and neointimal smooth muscle cell accumulation. 3. Currently, we have the technology to directly transfer the iNOS gene to allografts. We have demonstrated that this exciting strategy is feasible and therapeutic and may improve the long-term survival and function of allografts. Future challenges include optimizing the methods and the vectors of gene delivery.

[Modern tendencies in treatment of atypical glandular hyperplasia--our and foreign experience].

PubMed

Ivanov, S; Kovachev, E; Tsonev, A; Abbud, A

2010-01-01

Our aim was to summarize our and foreign experience in the field of diagnosis, progression and modern treatment of precancer of the endometrium-the atypical glandular hyperplasia. We researched 750 cases with glandular and atypical glandular hyperplasia for 10 years period (2000-2010). The hyperplasia were followed up for progression from glandular hyperplasia into atypical glandular hyperplasia and early endometrial cancer. The hyperplasias were evaluated with or without progestagen hormonal therapy. All patients were treated by D&C before and after the hormonal treatment. The main symptom in all patients was the postmenopausal bleeding (72% from the cases). In 90% of the patients (675) there was obesity. Exogenous use of estrogens was found in 30% (225) of the patients. The cases with complex hyperplasia in 12% (65/525) progressed into atypical glandular hyperplasia and in 4% (21/525) progressed into endometrial cancer. The patients with atypical glandular hyperplasia in 60% (90/150) progressed into endometrial cancer. Remission was observed in 70% of the patients (194/278) with glandular hyperplasia and progestagen treatment. The remission was detected by the golden standart (D&C). The patients without hormonal treatment and with complex glandular hyperplasia have in 15% (37/247) remission. Except with progestagen therapy, we have also 15 patients treated with GnRh-analogs (Zoladex a 3.6 mg) for 3-6 months. For them we have 80% (12/15) remission. The glandular hyperplasia without atypical cells can be influenced by the hormonal treatment with progestagens and GnRh-analogs. Nevertheless this hormonal treatment--before and after we have to perform D&C and to follow up patients by ultrasound measuring the endometrial thickness. If the fertility plans of the patients are over and if they are in postmenopause with histological result from D&C-atypical glandular hyperplasia--we have to treat them more radically with simple total hysterectomy.

Oral intake of hydrogen-rich water inhibits intimal hyperplasia in arterialized vein grafts in rats

PubMed Central

Sun, Qiang; Kawamura, Tomohiro; Masutani, Kosuke; Peng, Ximei; Sun, Qing; Stolz, Donna B.; Pribis, John P.; Billiar, Timothy R.; Sun, Xuejun; Bermudez, Christian A.; Toyoda, Yoshiya; Nakao, Atsunori

2012-01-01

Aims Arterialized vein grafts often fail due to intimal hyperplasia. Hydrogen potently protects organs and cells from many insults via its anti-inflammatory and antioxidant properties. We investigated the efficacy of oral administration of hydrogen-rich water (HW) for prevention of intimal hyperplasia. Methods and results The inferior vena cava was excised, stored in cold Ringer solution for 2 h, and placed as an interposition graft in the abdominal aorta of syngeneic Lewis rats. HW was generated by immersing a magnesium stick in tap water (Mg + 2H2O → Mg (OH)2 + H2). Beginning on the day of graft implantation, recipients were given tap water [regular water (RW)], HW or HW that had been subsequently degassed water (DW). Six weeks after grafting, the grafts in the rats given RW or DW had developed intimal hyperplasia, accompanied by increased oxidative injury. HW significantly suppressed intimal hyperplasia. One week after grafting, the grafts in HW-treated rats exhibited improved endothelial integrity with less platelet and white blood cell aggregation. Up-regulation of the mRNAs for intracellular adhesion molecules was attenuated in the vein grafts of the rats receiving HW. Activation of p38 mitogen-activated protein kinase, matrix metalloproteinase (MMP)-2, and MMP-9 was also significantly inhibited in grafts receiving HW. In rat smooth muscle cell (A7r5) cultures, hydrogen treatment for 24 h reduced smooth muscle cell migration. Conclusion Drinking HW significantly reduced neointima formation after vein grafting in rats. Drinking HW may have therapeutic value as a novel therapy for intimal hyperplasia and could easily be incorporated into daily life. PMID:22287575

Denture hyperplasia with areas simulating oral inverted ductal papilloma.

PubMed

Vargas, Pablo Agustin; Perez, Danyel Elias da Cruz; Jorge, Jacks; Rangel, Ana Lúcia Carrinho Ayrosa; León, Jorge Esquiche; Almeida, Oslei Paes de

2005-07-01

Denture hyperplasia is a reactive lesion of the oral mucosa, usually associated to an ill-fitting denture. This lesion is easily diagnosed and in some cases distinct microscopic variations such as osseous, oncocytic and squamous metaplasia may be found. These metaplastic alterations probably are associated with the lymphocytic infiltrate usually present in denture hyperplasia. We present a case of denture hyperplasia containing salivary gland tissue with ductal alterations mimicking an oral inverted ductal papilloma.

Simvastatin reduces neointimal thickening in low-density lipoprotein receptor-deficient mice after experimental angioplasty without changing plasma lipids.

PubMed

Chen, Zhiping; Fukutomi, Tatsuya; Zago, Alexandre C; Ehlers, Raila; Detmers, Patricia A; Wright, Samuel D; Rogers, Campbell; Simon, Daniel I

2002-07-02

Statins exert antiinflammatory and antiproliferative actions independent of cholesterol lowering. To determine whether these actions might affect neointimal formation, we investigated the effect of simvastatin on the response to experimental angioplasty in LDL receptor-deficient (LDLR-/-) mice, a model of hypercholesterolemia in which changes in plasma lipids are not observed in response to simvastatin. Carotid artery dilation (2.5 atm) and complete endothelial denudation were performed in male C57BL/6J LDLR-/- mice treated with low-dose (2 mg/kg) or high-dose (20 mg/kg) simvastatin or vehicle subcutaneously 72 hours before and then daily after injury. After 7 and 28 days, intimal and medial sizes were measured and the intima to media area ratio (I:M) was calculated. Total plasma cholesterol and triglyceride levels were similar in simvastatin- and vehicle-treated mice. Intimal thickening and I:M were reduced significantly by low- and high-dose simvastatin compared with vehicle alone. Simvastatin treatment was associated with reduced cellular proliferation (BrdU), leukocyte accumulation (CD45), and platelet-derived growth factor-induced phosphorylation of the survival factor Akt and increased apoptosis after injury. Simvastatin modulates vascular repair after injury in the absence of lipid-lowering effects. Although the mechanisms are not yet established, additional research may lead to new understanding of the actions of statins and novel therapeutic interventions for preventing restenosis.

Maxillary sinus marrow hyperplasia in sickle cell anemia.

PubMed

Fernandez, M; Slovis, T L; Whitten-Shurney, W

1995-11-01

Marrow hyperplasia is a sequela of sickle cell anemia (SCA) and may be seen in the skull in children after 5 years of age [1]. The facial bones, except for the mandible and orbits, are usually not involved [1-3]. We report an unusual case of a 28-month-old black boy with SCA who presented with extensive marrow hyperplasia of the maxillary sinuses in addition to severe calvarial and mandibular changes. The imaging characteristics on CT (similar to other sites of marrow hyperplasia) and MR (low signal on both T1 and T2 sequences) should aid in making the correct diagnosis.

Inhibition effects of chlorogenic acid on benign prostatic hyperplasia in mice.

PubMed

Huang, Ya; Chen, Huaguo; Zhou, Xin; Wu, Xingdong; Hu, Enming; Jiang, Zhengmeng

2017-08-15

This study aimed to evaluate the inhibitory effects and explore mechanisms of chlorogenic acid against testosterone-induced benign prostatic hyperplasia (BPH) in mice. Benign prostatic hyperplasia model was induced in experimental groups by daily subcutaneous injections of testosterone propionate (7.5mg/kg/d) consecutively for 14 d. A total of 60 mice were randomly divided into six groups: (Group 1) normal control group, (Group 2) benign prostatic hyperplasia model control group, (Group 3) benign prostatic hyperplasia mice treated with finasteride at a dose of 1mg/kg, (Group 4) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 0.8mg/kg (low dose group), (Group 5) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 1.6mg/kg (medium dose group) and (Group 6) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 3.2mg/kg (high dose group). Animals were sacrificed on the scheduled termination, pick out the eyeball to get blood, then prostates were weighed and prostatic index were determined. Then the serum acid phosphatase (ACP), prostatic acid phosphatase (PACP) and typeⅡ5-alpha-reductase (SRD5A2) levels were measured and observed morphological changes of the prostate. Comparing with benign prostatic hyperplasia model group, the high and medium dose of chlorogenic acid could significantly reduce prostate index and levels of acid phosphatase, prostatic acid phosphatase and typeⅡ5-alpha-reductase (P<0.05 or P<0.01). These findings were supported by histopathological observations of prostate tissues. Histopathological examination also indicated that chlorogenic acid treatment at the high and medium doses inhibited testosterone-induced prostatic hyperplasia. The results indicated that chlorogenic acid exhibited restraining effect on benign prostatic hyperplasia model animals, and its mechanism might be related to inhibit typeⅡ5-alpha reductase activity. Copyright © 2017

Downstream anastomotic hyperplasia. A mechanism of failure in Dacron arterial grafts.

PubMed Central

LoGerfo, F W; Quist, W C; Nowak, M D; Crawshaw, H M; Haudenschild, C C

1983-01-01

The precise location and progression of anastomotic hyperplasia and its possible relationship to flow disturbances was investigated in femoro-femoral Dacron grafts in 28 dogs. In 13 grafts, the outflow from the end-to-side downstream anastomosis was bidirectional (BDO), and in 15 it was unidirectional (UDO) (distally). Grafts were electively removed at intervals of two to 196 days or at the time of thrombosis. Each anastomosis and adjacent artery was perfusion-fixed and sectioned sagittally. The mean sagittal section was projected onto a digitized pad, and the total area of hyperplasia internal to the arterial internal elastic lamina and within the adjacent graft was integrated by computer. The location of the hyperplasia was compared with previously established sites of flow separation and stagnation. The observation was made that hyperplasia is significantly greater at the downstream, as compared with the upstream, anastomosis in both groups (BDO = p less than 0.001 and UDO = p less than 0.001) (analysis of variance for independent groups). Furthermore, this downstream hyperplasia was progressive with time (BDO p less than 0.01) (UDO p less than 0.01); Spearman Rank Correlation. There was no significant increase in the extent of downstream hyperplasia where flow separation was known to be greater (BDO). Five grafts failed (three BDO, two UDO), as a result of complete occlusion of the downstream anastomosis by fibrous hyperplasia. Transmission electron microscopy showed the hyperplasia to consist of collagen-producing smooth muscle cells. Anastomotic hyperplasia is significantly greater at the downstream anastomosis, is progressive with time, and is the primary cause of failure of Dacron arterial grafts in this model. Quantitative analysis of downstream anastomotic hyperplasia may be a valuable measure of the biocompatibility of Dacron grafts. Images Fig. 2. Fig. 3. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:6219641

[Toxoplasmosis in patients with lymphoid hyperplasia of the head and neck].

PubMed

Yariktaş, Murat; Demirci, Mustafa; Döner, Fehmi; Kaya, Selçuk; Doğru, Harun

2004-01-01

To investigate the incidence of toxoplasmosis in patients with lymphoid hyperplasia of the head and neck. In this study, 53 patients (32 males, 21 females; mean age 11.2+/-4.3 years, range 5 to 22) were investigated. There were hypertrophic tonsillitis in 13 patients, hypertrophic tonsillitis and adenoid hyperplasia in 22 patients, adenoid hyperplasia in 10 patients, and lymphadenopathy of the neck in eight patients. In venous blood samples, IgM and IgG antibodies for Toxoplasma gondii were investigated with the enzyme-linked immunoabsorbent assay (Axsym, Abbott). Positive IgG was determined in 23 patients (48%) with hypertrophic tonsillitis (n=6), hypertrophic tonsillitis and adenoid hyperplasia (n=10), adenoid hyperplasia (n=3), and lymphadenopathy of the neck (n=4). Positive IgM was determined in 5 patients (9.4%) with hypertrophic tonsillitis (n=1), hypertrophic tonsillitis and adenoid hyperplasia (n=1), and lymphadenopathy of the neck (n=3). Toxoplasmosis, which is known to cause lymphadenopathy, may be a reason for lymphadenopathy of the neck. Toxoplasmosis should be considered in the differential diagnosis of untreated patients with tonsillitis, adenoid hyperplasia, and chronic neck lymphadenopathy.

Benign Prostatic Hyperplasia (BPH)

MedlinePlus

... Benign prostatic hyperplasia (BPH) — also called prostate gland enlargement — is a common condition as men get older. ... There are several effective treatments for prostate gland enlargement, including medications, minimally invasive therapies and surgery. To ...

Hereditary pituitary hyperplasia with infantile gigantism.

PubMed

Gläsker, Sven; Vortmeyer, Alexander O; Lafferty, Antony R A; Hofman, Paul L; Li, Jie; Weil, Robert J; Zhuang, Zhengping; Oldfield, Edward H

2011-12-01

We report hereditary pituitary hyperplasia. The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. The study is a retrospective analysis of three cases from one family. The study was conducted at the National Institutes of Health, a tertiary referral center. A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. The condition was treated by total hypophysectomy. We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development.

Prediction of concurrent endometrial carcinoma in women with endometrial hyperplasia.

PubMed

Matsuo, Koji; Ramzan, Amin A; Gualtieri, Marc R; Mhawech-Fauceglia, Paulette; Machida, Hiroko; Moeini, Aida; Dancz, Christina E; Ueda, Yutaka; Roman, Lynda D

2015-11-01

Although a fraction of endometrial hyperplasia cases have concurrent endometrial carcinoma, patient characteristics associated with concurrent malignancy are not well described. The aim of our study was to identify predictive clinico-pathologic factors for concurrent endometrial carcinoma among patients with endometrial hyperplasia. A case-control study was conducted to compare endometrial hyperplasia in both preoperative endometrial biopsy and hysterectomy specimens (n=168) and endometrial carcinoma in hysterectomy specimen but endometrial hyperplasia in preoperative endometrial biopsy (n=43). Clinico-pathologic factors were examined to identify independent risk factors of concurrent endometrial carcinoma in a multivariate logistic regression model. The most common histologic subtype in preoperative endometrial biopsy was complex hyperplasia with atypia [CAH] (n=129) followed by complex hyperplasia without atypia (n=58) and simple hyperplasia with or without atypia (n=24). The majority of endometrial carcinomas were grade 1 (86.0%) and stage I (83.7%). In multivariate analysis, age 40-59 (odds ratio [OR] 3.07, p=0.021), age≥60 (OR 6.65, p=0.005), BMI≥35kg/m(2) (OR 2.32, p=0.029), diabetes mellitus (OR 2.51, p=0.019), and CAH (OR 9.01, p=0.042) were independent predictors of concurrent endometrial carcinoma. The risk of concurrent endometrial carcinoma rose dramatically with increasing number of risk factors identified in multivariate model (none 0%, 1 risk factor 7.0%, 2 risk factors 17.6%, 3 risk factors 35.8%, and 4 risk factors 45.5%, p<0.001). Hormonal treatment was associated with decreased risk of concurrent endometrial cancer in those with ≥3 risk factors. Older age, obesity, diabetes mellitus, and CAH are predictive of concurrent endometrial carcinoma in endometrial hyperplasia patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Therapeutic effect of ACTICOA powder, a cocoa polyphenolic extract, on experimentally induced prostate hyperplasia in Wistar-Unilever rats.

PubMed

Bisson, Jean-François; Hidalgo, Sophie; Rozan, Pascale; Messaoudi, Michaël

2007-12-01

Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate that results in obstructive lower urinary tract symptoms. Plant extracts are frequently used to treat BPH rather than therapeutics that can cause severe side effects. ACTICOA() (Ba0rry Callebaut France, Louviers, France) powder (AP) is a cocoa polyphenolic extract, and we have shown in a previous study that oral treatment with AP prevented prostate hyperplasia. This study investigated whether AP could improve established prostate hyperplasia using the same testosterone propionate (TP)-induced prostate hyperplasia model in rats. Male Wistar-Unilever rats were randomly divided in four groups of 12 rats: one group injected with corn oil and orally treated with the vehicle (negative control) and three groups injected subcutaneously with TP and orally treated with the vehicle (positive control) or AP at 24 (AP24) and 48 (AP48) mg/kg/day. Treatments started 1 week after the start of the induction of prostate hyperplasia and lasted for 2 weeks. The influence of TP and AP on body weights, food and water consumptions, plasma polyphenolic concentration, and serum dihydrotestoterone (DHT) level of rats was examined. At completion of the study, rats were sacrificed, and the prostates were removed, cleaned, and weighed. The prostate size ratio (prostate weight/rat body weight) was then calculated. TP significantly influenced the body weight gain of the rats and their food and water consumptions, while AP reduced significantly these differences in a dose-dependent manner. AP significantly reduced serum DHT level and prostate size ratio in comparison with positive controls also dose-dependently. In conclusion, AP orally administered was effective for reducing established prostate hyperplasia, especially at the dose of 48 mg/kg/day.

Biological effect of microengineered grooved stents on strut healing: a randomised OCT-based comparative study in humans.

PubMed

Vesga, Boris; Hernandez, Hector; Higuera, Sergio; Gasior, Pawel; Echeveri, Dario; Delgado, Juan A; Dager, Antonio; Arana, Camilo; Simonton, Charles; Maehara, Akiko; Palmaz, Julio; Granada, Juan F

2017-01-01

To evaluate the biological effect of microengineered stent grooves (MSG) on early strut healing in humans by performing optical coherence tomography (OCT) analysis 3 weeks following the implantation. In the experimental setting, MSG accelerate endothelial cell migration and reduce neointimal proliferation compared with bare metal stent (BMS). A total of 37 patients undergoing percutaneous coronary intervention with de novo coronary lesions were randomly assigned to either MSG (n=19) or an identical BMS controls (n=18). All patients underwent OCT imaging at 3 weeks. A total of 7959 struts were included in the final analysis. At 3 weeks following stent implantation, almost all struts analysed (~97%) had evidence of tissue coverage. The percentage of partially covered struts was comparable between both groups. However, the percentage of fully embedded struts was higher in the BMS group (81.22%, 49.75-95.52) compared with the MSG group (74.21%, 58.85-86.38). The stent-level analysis demonstrated reduction in neointimal formation (neointimal hyperplasia area and volume reduction of ~14% and ~19%, respectively) in the MSG versus the BMS group. In the strut-level analysis, an even greater reduction (~22% in neointimal thickness) was seen in the MSG group. Layered neointimal was present in ~6% of the OCT frames in the BMS group while it was not present in the MSG group. MSG induced a more homogeneous and predictable pattern of surface healing in the early stages following stent implantation. The biological effect of MSG on stent healing has the potential to improve the safety profile of current generation drug-eluting stents. BMS, OCT, clinical trials.

Each Individual Isoform of the Dopamine D2 Receptor Protects from Lactotroph Hyperplasia

PubMed Central

Radl, Daniela; De Mei, Claudia; Chen, Eric; Lee, Hyuna

2013-01-01

Dopamine acting through D2 receptors (D2Rs) controls lactotroph proliferation and prolactin (PRL) levels. Ablation of this receptor in mice results in lactotroph hyperplasia and prolactinomas in aged females. Alternative splicing of the Drd2 gene generates 2 independent isoforms, a long (D2L) and a short (D2S) isoform, which are present in all D2R-expressing cells. Here, we addressed the role of D2L and D2S on lactotroph physiology through the generation and analysis of D2S-null mice and their comparison with D2L-null animals. These mice represent a valuable tool with which to investigate dopamine-dependent isoform-specific signaling in the pituitary gland. We sought to assess the existence of a more prominent role of D2L or D2S in controlling PRL expression and lactotroph hyperplasia. Importantly, we found that D2L and D2S are specifically linked to independent transduction pathways in the pituitary. D2L-mediated signaling inhibits the AKT/protein kinase B kinase activity whereas D2S, in contrast, is required for the activation of the ERK 1/2 pathway. Under normal conditions, presence of only 1 of the 2 D2R isoforms in vivo prevents hyperprolactinemia, formation of lactotroph's hyperplasia, and tumorigenesis that is observed when both isoforms are deleted as in D2R−/− mice. However, the protective function of the single D2R isoforms is overridden when single isoform-knockout mice are challenged by chronic estrogen treatments as they show increased PRL production and lactotroph hyperplasia. Our study indicates that signaling from each of the D2R isoforms is sufficient to maintain lactotroph homeostasis in physiologic conditions; however, signaling from both is necessary in conditions simulating pathologic states. PMID:23608643

Each individual isoform of the dopamine D2 receptor protects from lactotroph hyperplasia.

PubMed

Radl, Daniela; De Mei, Claudia; Chen, Eric; Lee, Hyuna; Borrelli, Emiliana

2013-06-01

Dopamine acting through D2 receptors (D2Rs) controls lactotroph proliferation and prolactin (PRL) levels. Ablation of this receptor in mice results in lactotroph hyperplasia and prolactinomas in aged females. Alternative splicing of the Drd2 gene generates 2 independent isoforms, a long (D2L) and a short (D2S) isoform, which are present in all D2R-expressing cells. Here, we addressed the role of D2L and D2S on lactotroph physiology through the generation and analysis of D2S-null mice and their comparison with D2L-null animals. These mice represent a valuable tool with which to investigate dopamine-dependent isoform-specific signaling in the pituitary gland. We sought to assess the existence of a more prominent role of D2L or D2S in controlling PRL expression and lactotroph hyperplasia. Importantly, we found that D2L and D2S are specifically linked to independent transduction pathways in the pituitary. D2L-mediated signaling inhibits the AKT/protein kinase B kinase activity whereas D2S, in contrast, is required for the activation of the ERK 1/2 pathway. Under normal conditions, presence of only 1 of the 2 D2R isoforms in vivo prevents hyperprolactinemia, formation of lactotroph's hyperplasia, and tumorigenesis that is observed when both isoforms are deleted as in D2R-/- mice. However, the protective function of the single D2R isoforms is overridden when single isoform-knockout mice are challenged by chronic estrogen treatments as they show increased PRL production and lactotroph hyperplasia. Our study indicates that signaling from each of the D2R isoforms is sufficient to maintain lactotroph homeostasis in physiologic conditions; however, signaling from both is necessary in conditions simulating pathologic states.

Detecting DNA synthesis of neointimal formation after catheter balloon injury in GK and in Wistar rats: using 5-ethynyl-2'-deoxyuridine.

PubMed

Guo, Jingsheng; Li, Dongye; Bai, Shiru; Xu, Tongda; Zhou, Zhongmin; Zhang, Yanbin

2012-12-13

Neointimal formation plays an important role in the pathogenesis of coronary restenosis after percutaneous coronary intervention (PCI), especially in patients with diabetes mellitus. Recently, some studies have shown that 5-ethynyl-2'-deoxyuridine (EdU) incorporation can serve as a novel alternative to the 5-bromo-2'-deoxyuridine (BrdU) antibody detection method for detection of DNA synthesis in regenerating avian cochlea, chick embryo and the adult nervous system. However, few studies have been performed to assess the suitability of EdU for detecting DNA synthesis in vascular neointima. The carotid artery balloon injury model was established in Goto-Kakizaki (GK) and Wistar rats. A Cell-LightTM EdU Kit was used to detect EdU-labeled cell nuclei of common carotid arteries at day 7 after catheter balloon injury. Different methods of injecting EdU were tested. The protein levels of proliferating cell nuclear antigen (PCNA) and p-Akt (Ser473), as well as the mRNA levels of PCNA were evaluated by Western blotting and quantitative real-time PCR (qRT-PCR), respectively. Immunohistochemical staining was also employed to visualize PCNA-positive cells. At day 7 after catheter balloon injury, far more EdU-positive and PCNA-positive cells were observed in GK rats. When comparing groups that received different EdU doses, it was found that the percentage of EdU-positive cells at a dose of 100 mg/kg body weight was than at doses of 25 mg/kg and 50 mg/kg. The number of positive cells was significantly higher in the repeated injection group compared to the single injection group. Further, after balloon injury DNA synthesis in GK rats was more notable than in Wistar rats. Neointimal formation in GK rats was more obvious than in Wistar rats. The protein levels of PCNA and p-Akt (Ser473) and the mRNA levels of PCNA were increased in injured rats as compared to uninjured rats, and were significantly higher in GK rats than in Wistar rats. By intraperitoneal injections of EdU at a dose

Diagnosis and management of classical congenital adrenal hyperplasia.

PubMed

Marumudi, Eunice; Khadgawat, Rajesh; Surana, Vineet; Shabir, Iram; Joseph, Angela; Ammini, Ariachery C

2013-08-01

Congenital adrenal hyperplasia (CAH) is among the most common genetic disorders. Deficiency of adrenal steroid 21-hydroxylase deficiency due to mutations in the CYP21A2 gene accounts for about 95% cases of CAH. This disorder manifests with androgen excess with or without salt wasting. It also is a potentially life threatening disorder; neonatal screening with 17-hydroxyprogesterone measurement can diagnose the condition in asymptomatic children. Carefully monitored therapy with glucocorticoid and mineralocorticoid supplementation will ensure optimal growth and development for children with CAH. Genital surgery may be required for girls with CAH. Continued care is required for individuals with CAH as adults to prevent long-term adverse consequences of the disease, including infertility, metabolic syndrome and osteoporosis. Copyright © 2013 Elsevier Inc. All rights reserved.

Thyroid epithelial cell hyperplasia in IFN-gamma deficient NOD.H-2h4 mice.

PubMed

Yu, Shiguang; Sharp, Gordon C; Braley-Mullen, Helen

2006-01-01

The role of inflammatory cells in thyroid epithelial cell (thyrocyte) hyperplasia is unknown. Here, we demonstrate that thyrocyte hyperplasia in IFN-gamma-/- NOD.H-2h4 mice has an autoimmune basis. After chronic exposure to increased dietary iodine, 60% of IFN-gamma-/- mice had severe thyrocyte hyperplasia with minimal or moderate lymphocyte infiltration, and thyroid dysfunction with reduced serum T4. All mice produced anti-thyroglobulin autoantibody. Some wild-type NOD.H-2h4 mice had isolated areas of thyrocyte hyperplasia with predominantly lymphocytic infiltration, whereas IL-4-/- and 50% of wild-type NOD.H-2h4 mice developed lymphocytic thyroiditis but no thyrocyte hyperplasia. Both thyroid infiltrating inflammatory cells and environmental factors (iodine) were required to induce thyrocyte hyperplasia. Splenocytes from IFN-gamma-/- mice with thyrocyte hyperplasia, but not splenocytes from naïve IFN-gamma-/- mice, induced hyperplasia in IFN-gamma-/- NOD.H-2h4.SCID mice. These results may provide clues for understanding the mechanisms underlying development of epithelial cell hyperplasia not only in thyroids but also in other tissues and organs.

Hereditary Pituitary Hyperplasia with Infantile Gigantism

PubMed Central

Gläsker, Sven; Vortmeyer, Alexander O.; Lafferty, Antony R. A.; Hofman, Paul L.; Li, Jie; Weil, Robert J.; Zhuang, Zhengping

2011-01-01

Context: We report hereditary pituitary hyperplasia. Objective: The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. Design: The study is a retrospective analysis of three cases from one family. Setting: The study was conducted at the National Institutes of Health, a tertiary referral center. Patients: A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. Interventions: The condition was treated by total hypophysectomy. Main Outcome Measure(s): We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. Results: All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. Conclusions: This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development. PMID:21976722

Intraadrenal corticotropin in bilateral macronodular adrenal hyperplasia.

PubMed

Louiset, Estelle; Duparc, Céline; Young, Jacques; Renouf, Sylvie; Tetsi Nomigni, Milène; Boutelet, Isabelle; Libé, Rossella; Bram, Zakariae; Groussin, Lionel; Caron, Philippe; Tabarin, Antoine; Grunenberger, Fabienne; Christin-Maitre, Sophie; Bertagna, Xavier; Kuhn, Jean-Marc; Anouar, Youssef; Bertherat, Jérôme; Lefebvre, Hervé

2013-11-28

Bilateral macronodular adrenal hyperplasia is a rare cause of primary adrenal Cushing's syndrome. In this form of hyperplasia, hypersecretion of cortisol suppresses the release of corticotropin by pituitary corticotrophs, which results in low plasma corticotropin levels. Thus, the disease has been termed corticotropin-independent macronodular adrenal hyperplasia. We examined the abnormal production of corticotropin in these hyperplastic adrenal glands. We obtained specimens of hyperplastic macronodular adrenal tissue from 30 patients with primary adrenal disease. The corticotropin precursor proopiomelanocortin and corticotropin expression were assessed by means of a polymerase-chain-reaction assay and immunohistochemical analysis. The production of corticotropin and cortisol was assessed in 11 specimens with the use of incubated explants and cell cultures coupled with hormone assays. Corticotropin levels were measured in adrenal and peripheral venous blood samples from 2 patients. The expression of proopiomelanocortin messenger RNA (mRNA) was detected in all samples of hyperplastic adrenal tissue. Corticotropin was detected in steroidogenic cells arranged in clusters that were disseminated throughout the adrenal specimens. Adrenal corticotropin levels were higher in adrenal venous blood samples than in peripheral venous samples, a finding that was consistent with local production of the peptide within the hyperplastic adrenals. The release of adrenal corticotropin was stimulated by ligands of aberrant membrane receptors but not by corticotropin-releasing hormone or dexamethasone. A semiquantitative score for corticotropin immunostaining in the samples correlated with basal plasma cortisol levels. Corticotropin-receptor antagonists significantly inhibited in vitro cortisol secretion. Cortisol secretion by the adrenals in patients with macronodular hyperplasia and Cushing's syndrome appears to be regulated by corticotropin, which is produced by a subpopulation of

Ultrasound-microbubble-mediated intercellular adhesion molecule-1 small interfering ribonucleic acid transfection attenuates neointimal formation after arterial injury in mice.

PubMed

Suzuki, Jun-ichi; Ogawa, Masahito; Takayama, Kiyoshi; Taniyama, Yoshiaki; Morishita, Ryuichi; Hirata, Yasunobu; Nagai, Ryozo; Isobe, Mitsuaki

2010-03-02

The purpose of this study was to investigate the efficiency of small interfering ribonucleic acid (siRNA) in murine arteries. We transfected it using a nonviral ultrasound-microbubble-mediated in vivo gene delivery system. siRNA is an effective methodology to suppress gene function. The siRNA can be synthesized easily; however, a major obstacle in the use of siRNA as therapeutics is the difficulty involved in effective in vivo delivery. To investigate the efficiency of nonviral ultrasound-microbubble-mediated in vivo siRNA delivery, we used a fluorescein-labeled siRNA, green fluorescent protein (GFP) siRNA, and intercellular adhesion molecule (ICAM)-1 siRNA in murine arteries. Murine femoral arteries were injured using flexible wires to establish arterial injury. The fluorescein-labeled siRNA and GFP siRNA showed that this nonviral approach could deliver siRNA into target arteries effectively without any tissue damage and systemic adverse effects. ICAM-1 siRNA transfection into murine injured arteries significantly suppressed the development of neointimal formation in comparison to those in the control group. Immunohistochemistry revealed that accumulation of T cells and adhesion molecule positive cells was observed in nontreated injured arteries, whereas siRNA suppressed accumulation. The nonviral ultrasound-microbubble delivery of siRNA ensures effective transfection into target arteries. ICAM-1 siRNA has the potential to suppress arterial neointimal formation. Transfection of siRNA can be beneficial for the clinical treatment of cardiovascular and other inflammatory diseases. Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Hidradenitis suppurativa/acne inversa: bilocated epithelial hyperplasia with very different sequelae.

PubMed

von Laffert, M; Stadie, V; Wohlrab, J; Marsch, W C

2011-02-01

Hidradenitis suppurativa/acne inversa is a chronic, inflammatory, scarring disease in the terminal hair follicle and apocrine gland-bearing areas (skin folds). There is considerable histological evidence that perifolliculitis and follicular hyperkeratosis precede the rupture of the follicle. The timing of the epithelial hyperplasia at the infundibula of inflamed terminal follicles has not yet been clarified. To clarify the early histopathological life of lesions ('chronology') in hidradenitis suppurativa/acne inversa, focusing on the terminal follicle structure and its surrounding tissue (hyperkeratosis, hyperplasia of follicular epithelium, perifolliculitis and rupture). In total, 485 operative specimens obtained from 128 patients with diagnosed hidradenitis suppurativa/acne inversa (all surgically treated by wide excision) were examined histologically. Two to five histological preparations (total 485) per operation area (total 196) were prepared by multiple slicing. Hidradenitis suppurativa/acne inversa showed a heterogeneous histological pattern: hyperkeratosis of the terminal follicles (89%), hyperplasia of follicular epithelium (80%), pronounced perifolliculitis (68%) and follicle rupture (24%). Perifolliculitis, follicular hyperkeratosis and hyperplasia occurred prior to the rupture of the follicle. Other histological criteria were: subepidermal cellular inflammatory infiltrate (82%), epidermal psoriasiform hyperplasia (56%), pronounced acute dermal inflammation (28%), pronounced chronic dermal inflammation (49%), and involvement of apocrine glands (52%) and subcutis (31%). Infundibular hyperkeratosis, hyperplasia of the follicular epithelium and perifolliculitis are major histopathological characteristics of hidradenitis suppurativa/acne inversa. These apparently precede rupture of the follicle. In particular, hyperplasia of the follicular epithelium probably marks the beginning of sinus formation, which usually spreads horizontally. Psoriasiform hyperplasia

Multifocal Epithelial Hyperplasia.

PubMed

Agnew, Caitlin; Alexander, Sherene; Prabhu, Neeta

2017-01-15

Multifocal epithelial hyperplasia is a rare disease associated with human papilloma virus types 13 and 32. Diagnosis is based on clinical and histopathological findings, and most lesions are asymptomatic and regress spontaneously with time. The purpose of this paper is to describe a five-year-old girl who presented with multiple intraoral lesions on the buccal mucosa and tongue, which regressed spontaneously in 15 months.

Intestinal nodular lymphoid hyperplasia and extraintestinal lymphoma--a rare association.

PubMed

Monsanto, P; Lérias, C; Almeida, N; Lopes, S; Cabral, J E; Figueiredo, P; Silva, M; Julião, M; Gouveia, H; Sofia, C

2012-06-01

Nodular lymphoid hyperplasia of the gastrointestinal tract is characterized by the presence of innumerable small discrete nodules involving a variable segment of the gastrointestinal tract. The association between nodular lymphoid hyperplasia and other benign and malignant diseases has been clearly described, with an increased risk of gastrointestinal tumours, namely gastrointestinal lymphoma. However, the association with extraintestinal lymphoma seems extremely rare. The authors present a clinical case of a patient with nodular lymphoid hyperplasia of the small and large intestine that subsequently developed an extraintestinal lymphoma (diffuse large B-cell lymphoma).

Anti-atherogenic activity of wild grape (Vitis thunbergii) extract antagonizing smooth muscle cell proliferation and migration promoted by neighboring macrophages.

PubMed

Kang, Sang-Wook; Kim, Min Soo; Kim, Hyun-Sung; Lee, Yong-Jin; Kang, Young-Hee

2012-06-01

The proliferation and migration of vascular smooth muscle cells (SMCs) play critical roles in intimal thickening and neointimal hyperplasia in early-phase atherosclerosis. This study tested whether wild grape extract (WGE) suppressed the proliferation and migration of human aortic SMCs induced by neighboring macrophages. Cellular expression of fibrogenic connective tissue growth factor (CTGF) and secretion of collagen IV and matrix metalloproteinase (MMP)-2 were determined in SMCs exposed to THP-1-differentiated macrophage-conditioned media. Proliferation was enhanced in SMCs exposed to macrophage-conditioned media collected during the early stage of differentiation, which was attenuated by treatment with ≥ 10 µg/ml WGE. Increased secretion of CTGF and collagen IV macrophage-conditioned media was suppressed in WGE-supplemented SMCs. TGF-β1-promoted production of CTGF and collagen IV was suppressed by blocking TGF-β receptors of R1 and R2 in SMCs. WGE repressed macrophage-conditioned media-upregulated MMP-2 secretion, indicating that WGE had an ability to encumber plaque rupture within atherosclerotic lesions. In addition, ≥ 1 µg/ml WGE ameliorated the migration of SMCs promoted by neighboring macrophages. These results demonstrate that WGE retarded neointimal hyperplasia and thickening within atherosclerotic plaques largely comprising of macrophages and SMCs. Therefore, WGE may be developed as an anti-proliferative and anti-migratory agent targeting SMCs in the proximity of newly differentiated and resident macrophages.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Young Il; Chung, Jin Wook, E-mail: chungjw@snu.ac.kr; Kim, Hyun Beom

PurposeThis study was designed to investigate the effects of stenting across the branching arteries on the patency and stent-tissue responses over the branching arterial orifices. Methods: Thirteen dogs were observed after placing aortic stents across the celiac arteries (CA), superior mesenteric arteries (SMA), and renal arteries (RA). The animals were grouped according to stent types: large-cell group (n = 6) and small-cell group (n = 7). Angiography was performed to evaluate the branching artery patency at 2, 6, and 12 months after stent insertion, and the stent-tissue responses covering the orifices were evaluated on histopathologic examination. Results: All branching arteriesmore » were patent on follow-up angiography; however, three patterns of stent-tissue responses over the orifices were observed: neointimal layering, bridging septa, and papillary hyperplasia. Although neointimal layering and bridging septa were evenly observed, severe papillary hyperplasia was more frequent at SMA and CA than RA. Four RA showed less than 50% ostial patency, and localized infarct was observed in six kidneys (24%). The ostial patency tended to decrease with small-cell stent during the follow-up period. Conclusions: Various stent-tissue responses over the branching artery orifices are induced by the aortic stent covering the branching arteries and may not be easily detected by conventional angiography. Subclinical renal infarct also may occur despite patent renal angiography.« less

Focal fibrous hyperplasia: A review of 193 cases.

PubMed

de Santana Santos, Thiago; Martins-Filho, Paulo Ricardo Saquete; Piva, Marta Rabello; de Souza Andrade, Emanuel Sávio

2014-09-01

Focal fibrous hyperplasia, also known as irritation or traumatic fibroma, is a reactive, inflammatory hyperplastic lesion of the connective tissue. The aim of this study is to perform a retrospective study of a focal fibrous hyperplasia of 18 years. We retrospectively reviewed 193 cases of focal fibrous hyperplasia of the oral cavity from the medical and histological reports of the Department of Oral Pathology, Pernambuco University, Brazil, during the period between January 1992 and December 2009. Data with regard to age, gender, location, size of the lesion (equal to or less than 1 cm, between 1 and 2 cm and greater than 2 cm), pain, history of trauma, treatment, length of follow-up (from diagnosis to release or last review) and recurrence, were collected. The most commonly affected site was the buccal mucosa (n = 119, 61.7%). Almost two-thirds of the cases were concentrated from the second to the fifth decade of life. Females were more affected than men and a history of trauma was related by 90.7% of the patients. Two recurrences were notified (1.0%). Further studies are needed on the distribution of the lesion in different ethnic and geographical populations. The influence of sex hormones on the development of focal fibrous hyperplasia must be clarified.

Biological effect of microengineered grooved stents on strut healing: a randomised OCT-based comparative study in humans

PubMed Central

Vesga, Boris; Hernandez, Hector; Higuera, Sergio; Gasior, Pawel; Echeveri, Dario; Delgado, Juan A; Dager, Antonio; Arana, Camilo; Simonton, Charles; Maehara, Akiko; Palmaz, Julio; Granada, Juan F

2017-01-01

Objective To evaluate the biological effect of microengineered stent grooves (MSG) on early strut healing in humans by performing optical coherence tomography (OCT) analysis 3 weeks following the implantation. Background In the experimental setting, MSG accelerate endothelial cell migration and reduce neointimal proliferation compared with bare metal stent (BMS). Methods A total of 37 patients undergoing percutaneous coronary intervention with de novo coronary lesions were randomly assigned to either MSG (n=19) or an identical BMS controls (n=18). All patients underwent OCT imaging at 3 weeks. A total of 7959 struts were included in the final analysis. Results At 3 weeks following stent implantation, almost all struts analysed (~97%) had evidence of tissue coverage. The percentage of partially covered struts was comparable between both groups. However, the percentage of fully embedded struts was higher in the BMS group (81.22%, 49.75–95.52) compared with the MSG group (74.21%, 58.85–86.38). The stent-level analysis demonstrated reduction in neointimal formation (neointimal hyperplasia area and volume reduction of ~14% and ~19%, respectively) in the MSG versus the BMS group. In the strut-level analysis, an even greater reduction (~22% in neointimal thickness) was seen in the MSG group. Layered neointimal was present in ~6% of the OCT frames in the BMS group while it was not present in the MSG group. Conclusions MSG induced a more homogeneous and predictable pattern of surface healing in the early stages following stent implantation. The biological effect of MSG on stent healing has the potential to improve the safety profile of current generation drug-eluting stents. Classifications BMS, OCT, clinical trials. PMID:28674616

Lymphangioma circumscriptum, angiokeratoma, or superficial vascular ectasia with epithelial hyperplasia?

PubMed

Katsoulas, Nikolaos; Tosios, Konstantinos I; Argyris, Prokopios; Koutlas, Ioannis G; Sklavounou, Alexandra

2014-08-01

We report a case of lymphangioma circumscriptum (cavernous lymphangioma with epithelial hyperplasia) in a 12-year-old girl, presenting as a papillary tumor on the right dorsal side of her tongue. Microscopic examination found cavernous vascular channels lined by a single layer of CD31(+), podoplanin-positive, CD34(-) endothelial cells that occupied the papillary lamina propria and were accompanied by epithelial hyperplasia. A review of the literature on oral vascular tumors with epithelial hyperplasia, namely, lymphangioma circumscriptum and angiokeratoma, provided information that draws into question the use of these terms. Copyright © 2014 Elsevier Inc. All rights reserved.

Allium sativum Compared to Cilostazol as an Inhibitor of Myointimal Hyperplasia.

PubMed

Lima, Paulo Roberto da Silva; Bandeira, Francisco Chavier Vieira; Rolim, Janio Cipriano; Nogueira, Manuel Ricardo Sena; Pordeus, Mizael Armando Abrantes; de Oliveira, Andressa Feitosa Bezerra; Pitta, Guilherme Benjamin Brandão

2016-01-01

Intimal hyperplasia is associated with graft failure and vascular sutures in the first year after surgery and in postangioplasty restenosis. Allium sativum (common garlic) lowers cholesterol and has antioxidant effects; it also has antiplatelet and antitumor properties and, therefore, has great potential to reduce or inhibit intimal hyperplasia of the arteries. Our objective is to determine if the garlic has an efficacy to inhibit myointimal hyperplasia compared to cilostazol. Female New Zealand rabbits were divided into the following groups (n=10 each) according to treatment: group A, garlic, 800 µg×kg-1×day-1, orally; group C, cilostazol, 50 mg.day-1, orally; group PS, 10 ml of 0.9% physiological saline solution, orally. Our primary is the difference of the mean of myointimal hyperplasia. Statistical analysis was performed by using ANOVA and Tukey tests, as well as the Chi-square test. We calculated the 95% confidence interval for each point estimate, and the P value was set as < 0.05. Group PS had a mean hyperplasia rate of 35.74% (95% CI, 31.76-39.71%); group C, 16.21% (95% CI, 13.36-19.05%); and group A, 21.12% (95% CI, 17.26-25.01%); P < 0.0001. We conclude that Allium sativum had the same efficacy in inhibiting myointimal hyperplasia when compared to the positive control, cilostazol.

AgNOR histochemical expression in benign prostatic hyperplasia and prostatic adenocarcinoma

NASA Astrophysics Data System (ADS)

Rita, R.; Delyuzar; Laksmi, L. I.

2018-03-01

Benign prostatic hyperplasia and prostatic adenocarcinoma were common diseases and usually occurred after the 5th decade of life. The problem in diagnosing using Hematoxylin and Eosin staining was how to differentiate whether it is benign or malignant zone. Therefore, proliferating markers, such as AgNOR, could be helping to over this difficulty. A descriptive study using consecutive sampling as the method of sample recruiting was conducted to describe AgNOR histochemical expression in benign prostatic hyperplasia and prostatic adenocarcinoma. AgNOR staining was done in 13 benign prostatic hyperplasia samples and 7 prostatic adenocarcinoma samples, which have been confirmed using p63 immunohistochemical staining before. Benign prostatic hyperplasia usually showed lower AgNOR proliferating activity while all of theprostatic adenocarcinoma (100%) had high AgNOR proliferating activity.

Focal fibrous hyperplasia: A review of 193 cases

PubMed Central

de Santana Santos, Thiago; Martins-Filho, Paulo Ricardo Saquete; Piva, Marta Rabello; de Souza Andrade, Emanuel Sávio

2014-01-01

Context: Focal fibrous hyperplasia, also known as irritation or traumatic fibroma, is a reactive, inflammatory hyperplastic lesion of the connective tissue. Aim: The aim of this study is to perform a retrospective study of a focal fibrous hyperplasia of 18 years. Materials and Methods: We retrospectively reviewed 193 cases of focal fibrous hyperplasia of the oral cavity from the medical and histological reports of the Department of Oral Pathology, Pernambuco University, Brazil, during the period between January 1992 and December 2009. Settings and Design: Data with regard to age, gender, location, size of the lesion (equal to or less than 1 cm, between 1 and 2 cm and greater than 2 cm), pain, history of trauma, treatment, length of follow-up (from diagnosis to release or last review) and recurrence, were collected. Results: The most commonly affected site was the buccal mucosa (n = 119, 61.7%). Almost two-thirds of the cases were concentrated from the second to the fifth decade of life. Females were more affected than men and a history of trauma was related by 90.7% of the patients. Two recurrences were notified (1.0%). Conclusion: Further studies are needed on the distribution of the lesion in different ethnic and geographical populations. The influence of sex hormones on the development of focal fibrous hyperplasia must be clarified. PMID:25364187

SIRT1 Limits Adipocyte Hyperplasia through c-Myc Inhibition*

PubMed Central

Abdesselem, Houari; Madani, Aisha; Hani, Ahmad; Al-Noubi, Muna; Goswami, Neha; Ben Hamidane, Hisham; Billing, Anja M.; Pasquier, Jennifer; Bonkowski, Michael S.; Halabi, Najeeb; Dalloul, Rajaa; Sheriff, Mohamed Z.; Mesaeli, Nasrin; ElRayess, Mohamed; Sinclair, David A.; Graumann, Johannes; Mazloum, Nayef A.

2016-01-01

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. We also demonstrate that SIRT1 is a key regulator of proliferation in preadipocytes. Quantitative proteomics reveal that the c-Myc pathway is altered to drive enhanced proliferation in SIRT1-silenced 3T3-L1 cells. Moreover, c-Myc is hyperacetylated, levels of p27 are reduced, and cyclin-dependent kinase 2 (CDK2) is activated upon SIRT1 reduction. Remarkably, differentiating SIRT1-silenced preadipocytes exhibit enhanced mitotic clonal expansion accompanied by reduced levels of p27 as well as elevated levels of CCAAT/enhancer-binding protein β (C/EBPβ) and c-Myc, which is also hyperacetylated. c-Myc activation and enhanced proliferation phenotype are also found to be SIRT1-dependent in proliferating mouse embryonic fibroblasts and differentiating human SW872 preadipocytes. Reducing both SIRT1 and c-Myc expression in 3T3-L1 cells simultaneously does not induce the adipocyte hyperplasia phenotype, confirming that SIRT1 controls adipocyte hyperplasia through c-Myc regulation. A better understanding of the molecular mechanisms of adipocyte hyperplasia will open new avenues toward understanding obesity. PMID:26655722

Allium sativum Compared to Cilostazol as an Inhibitor of Myointimal Hyperplasia

PubMed Central

Lima, Paulo Roberto da Silva; Bandeira, Francisco Chavier Vieira; Rolim, Janio Cipriano; Nogueira, Manuel Ricardo Sena; Pordeus, Mizael Armando Abrantes; de Oliveira, Andressa Feitosa Bezerra; Pitta, Guilherme Benjamin Brandão

2016-01-01

Objective Intimal hyperplasia is associated with graft failure and vascular sutures in the first year after surgery and in postangioplasty restenosis. Allium sativum (common garlic) lowers cholesterol and has antioxidant effects; it also has antiplatelet and antitumor properties and, therefore, has great potential to reduce or inhibit intimal hyperplasia of the arteries. Our objective is to determine if the garlic has an efficacy to inhibit myointimal hyperplasia compared to cilostazol. Methods Female New Zealand rabbits were divided into the following groups (n=10 each) according to treatment: group A, garlic, 800 µg×kg-1×day-1, orally; group C, cilostazol, 50 mg.day-1, orally; group PS, 10 ml of 0.9% physiological saline solution, orally. Our primary is the difference of the mean of myointimal hyperplasia. Statistical analysis was performed by using ANOVA and Tukey tests, as well as the Chi-square test. We calculated the 95% confidence interval for each point estimate, and the P value was set as < 0.05. Results Group PS had a mean hyperplasia rate of 35.74% (95% CI, 31.76–39.71%); group C, 16.21% (95% CI, 13.36–19.05%); and group A, 21.12% (95% CI, 17.26–25.01%); P<0.0001. Conclusion We conclude that Allium sativum had the same efficacy in inhibiting myointimal hyperplasia when compared to the positive control, cilostazol. PMID:27849301

Periostin contributes to epidermal hyperplasia in psoriasis common to atopic dermatitis

PubMed Central

Arima, Kazuhiko; Ohta, Shoichiro; Takagi, Atsushi; Shiraishi, Hiroshi; Masuoka, Miho; Ontsuka, Kanako; Suto, Hajime; Suzuki, Shoichi; Yamamoto, Ken-ichi; Ogawa, Masahiro; Simmons, Olga; Yamaguchi, Yukie; Toda, Shuji; Aihara, Michiko; Conway, Simon J.; Ikeda, Shigaku; Izuhara, Kenji

2016-01-01

Background Epidermal hyperplasia is a histological hallmark observed in both atopic dermatitis (AD) and psoriasis, although the clinical features and the underlying immunological disorders of these diseases are different. We previously showed that periostin, a matricellular protein, plays a critical role in epidermal hyperplasia in AD, using a mouse model and a 3-dimensional organotypic coculture system. In this study, we explore the hypothesis that periostin is involved in epidermal hyperplasia in psoriasis. Methods To examine expression of periostin in psoriasis patients, we performed immunohistochemical analysis on skin biopsies from six such patients. To investigate periostin’s role in the pathogenesis of psoriasis, we evaluated periostin-deficient mice in a psoriasis mouse model induced by topical treatment with imiquimod (IMQ). Results Periostin was substantially expressed in the dermis of all investigated psoriasis patients. Epidermal hyperplasia induced by IMQ treatment was impaired in periostin-deficient mice, along with decreased skin swelling. However, upon treatment with IMQ, periostin deficiency did not alter infiltration of inflammatory cells such as neutrophils; production of IL-17, –22, or –23; or induction/expansion of IL-17– and IL-22–producing group 3 innate lymphoid cells. Conclusions Periostin plays an important role during epidermal hyperplasia in IMQ-induced skin inflammation, independently of the IL-23–IL-17/IL-22 axis. Periostin appears to be a mediator for epidermal hyperplasia that is common to AD and psoriasis. PMID:25572557

Reduction of In-Stent Restenosis by Cholesteryl Ester Transfer Protein Inhibition.

PubMed

Wu, Ben J; Li, Yue; Ong, Kwok L; Sun, Yidan; Shrestha, Sudichhya; Hou, Liming; Johns, Douglas; Barter, Philip J; Rye, Kerry-Anne

2017-12-01

Angioplasty and stent implantation, the most common treatment for atherosclerotic lesions, have a significant failure rate because of restenosis. This study asks whether increasing plasma high-density lipoprotein (HDL) levels by inhibiting cholesteryl ester transfer protein activity with the anacetrapib analog, des-fluoro-anacetrapib, prevents stent-induced neointimal hyperplasia. New Zealand White rabbits received normal chow or chow supplemented with 0.14% (wt/wt) des-fluoro-anacetrapib for 6 weeks. Iliac artery endothelial denudation and bare metal steel stent deployment were performed after 2 weeks of des-fluoro-anacetrapib treatment. The animals were euthanized 4 weeks poststent deployment. Relative to control, dietary supplementation with des-fluoro-anacetrapib reduced plasma cholesteryl ester transfer protein activity and increased plasma apolipoprotein A-I and HDL cholesterol levels by 53±6.3% and 120±19%, respectively. Non-HDL cholesterol levels were unaffected. Des-fluoro-anacetrapib treatment reduced the intimal area of the stented arteries by 43±5.6% ( P <0.001), the media area was unchanged, and the arterial lumen area increased by 12±2.4% ( P <0.05). Des-fluoro-anacetrapib treatment inhibited vascular smooth muscle cell proliferation by 41±4.5% ( P <0.001). Incubation of isolated HDLs from des-fluoro-anacetrapib-treated animals with human aortic smooth muscle cells at apolipoprotein A-I concentrations comparable to their plasma levels inhibited cell proliferation and migration. These effects were dependent on scavenger receptor-B1, the adaptor protein PDZ domain-containing protein 1, and phosphatidylinositol-3-kinase/Akt activation. HDLs from des-fluoro-anacetrapib-treated animals also inhibited proinflammatory cytokine-induced human aortic smooth muscle cell proliferation and stent-induced vascular inflammation. Inhibiting cholesteryl ester transfer protein activity in New Zealand White rabbits with iliac artery balloon injury and stent

Surface modification of endovascular stents with rosuvastatin and heparin-loaded biodegradable nanofibers by electrospinning.

PubMed

Janjic, Milka; Pappa, Foteini; Karagkiozaki, Varvara; Gitas, Christakis; Ktenidis, Kiriakos; Logothetidis, Stergios

2017-01-01

This study describes the development of drug-loaded nanofibrous scaffolds as a nanocoating for endovascular stents for the local and sustained delivery of rosuvastatin (Ros) and heparin (Hep) to injured artery walls after endovascular procedures via the electrospinning process. The proposed hybrid covered stents can promote re-endothelialization; improve endothelial function; reduce inflammatory reaction; inhibit neointimal hyperplasia of the injured artery wall, due to well-known pleiotropic actions of Ros; and prevent adverse events such as in-stent restenosis (ISR) and stent thrombosis (ST), through the antithrombotic action of Hep. Biodegradable nanofibers were prepared by dissolving cellulose acetate (AC) and Ros in N , N -dimethylacetamide (DMAc) and acetone-based solvents. The polymeric solution was electrospun (e-spun) into drug-loaded AC nanofibers onto three different commercially available stents (Co-Cr stent, Ni-Ti stent, and stainless steel stent), resulting in nonwoven matrices of submicron-sized fibers. Accordingly, Hep solution was further used for fibrous coating onto the engineered Ros-loaded stent. The functional encapsulation of Ros and Hep drugs into polymeric scaffolds further underwent physicochemical analysis. Morphological characterization took place via scanning electron microscopy (SEM) and atomic force microscopy (AFM) analyses, while scaffolds' wettability properties were obtained by contact angle (CA) measurements. The morphology of the drug-loaded AC nanofibers was smooth, with an average diameter of 200-800 nm, and after CA measurement, we concluded to the superhydrophobic nature of the engineered scaffolds. In vitro release rates of the pharmaceutical drugs were determined using a high-performance liquid chromatography assay, which showed that after the initial burst, drug release was controlled slowly by the degradation of the polymeric materials. These results imply that AC nanofibers encapsulated with Ros and Hep drugs have great

Impact of Fluoropolymer-Based Paclitaxel Delivery on Neointimal Proliferation and Vascular Healing: A Comparative Peripheral Drug-Eluting Stent Study in the Familial Hypercholesterolemic Swine Model of Femoral Restenosis.

PubMed

Gasior, Pawel; Cheng, Yanping; Valencia, Andres F; McGregor, Jenn; Conditt, Gerard B; Kaluza, Grzegorz L; Granada, Juan F

2017-05-01

A polymer-free peripheral paclitaxel-eluting stent (PES, Zilver PTX, Cook, IN) has shown to improve vessel patency after superficial femoral angioplasty. A new-generation fluoropolymer-based PES (FP-PES; Eluvia, Boston Scientific, MA) displaying more controlled and sustained paclitaxel delivery promise to improve the clinical outcomes of first-generation PES. We sought to compare the biological effect of paclitaxel delivered by 2 different stent-coating technologies (fluoropolymer-based versus polymer-free) on neointimal proliferation and healing response in the familial hypercholesterolemic swine model of femoral restenosis. The biological efficacy of clinically available FP-PES (n=12) and PES (n=12) was compared against a bare metal stent control (n=12; Innova, Boston Scientific, MA) after implantation in the femoral arteries of 18 familial hypercholesterolemic swine. Longitudinal quantitative vascular angiography and optical coherence tomography were performed at baseline and at 30 and 90 days. Histological evaluation was performed at 90 days. Ninety-day quantitative vascular angiography results showed a lower percent diameter stenosis for FP-PES (38.78% [31.27-47.66]) compared with PES (54.16% [42.60-61.97]) and bare metal stent (74.52% [47.23-100.00]; P <0.001). Ninety-day optical coherence tomography results demonstrated significantly lower neointimal area in FP-PES (8.01 mm 2 [7.65-9.21]) compared with PES (10.95 mm 2 [9.64-12.46]) and bare metal stent (13.83 mm 2 [11.53-17.03]; P <0.001). Histological evaluation showed larger lumen areas and evidence of higher biological activity (smooth muscle cell loss and fibrin deposition) in the FP-PES compared with PES and bare metal stent. In the familial hypercholesterolemic swine model of femoral restenosis, the implantation of an FP-PES resulted in lower levels of neointimal proliferation and sustained biological effect ≤90 days compared with a polymer-free stent-based approach. © 2017 American Heart

Hepatocyte growth factor fusion protein having collagen-binding activity (CBD-HGF) accelerates re-endothelialization and intimal hyperplasia in balloon-injured rat carotid artery.

PubMed

Ohkawara, Nana; Ueda, Hiroki; Shinozaki, Shohei; Kitajima, Takashi; Ito, Yoshihiro; Asaoka, Hiroshi; Kawakami, Akio; Kaneko, Eiji; Shimokado, Kentaro

2007-08-01

Hepatocyte growth factor (HGF) is known to stimulate endothelial cell proliferation. However, re-endothelialization is not enhanced when the native protein is administered to the injured artery, probably due to the short half-life of HGF at the site of injury. Therefore, the effects of an HGF fusion protein having collagen-binding activity (CBD-HGF) on re-endothelialization and neointimal formation was studied in the balloon-injured rat carotid artery. The left common carotid artery of male Sprague-Dawley rats was injured with an inflated balloon catheter, and then treated with CBD-HGF 10 microg/mL), HGF (10 micro g/mL) or saline (control) for 15 min. After 14 days, the rats were injected with Evans blue and sacrificed. The re-endothelialized area was significantly greater in the CBD-HGF- treated rats than in the control or HGF -treated rats. Neointimal formation was significantly more pronounced in the CBD-HGF treated rats than in other rat groups. Both HGF and CBD-HGF stimulated proliferation of vascular smooth muscle cells as well as endothelial cells in vitro. Consistent with this, cultured smooth muscle cells were shown to express the HGF receptor (c-Met). CBD-HGF accelerates re-endothelialization and neointimal formation in vivo. CBD fusion protein is a useful vehicle to deliver vascular growth factors to injured arteries.

Extensive Focal Epithelial Hyperplasia: A Case Report.

PubMed

Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab

2015-01-01

Focal epithelial hyperplasia (FEH) or Heck's disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis.

Role of Hyperplasia of Gingival Lymphatics in Periodontal Inflammation.

PubMed

Papadakou, P; Bletsa, A; Yassin, M A; Karlsen, T V; Wiig, H; Berggreen, E

2017-04-01

Lymphatic vessels are important for maintenance of tissue fluid homeostasis and afferent antigen transport. In chronic inflammation, lymphangiogenesis takes place and is characterized by lymphatic endothelial cell proliferation and lymphatic hyperplasia. Vascular endothelial growth factor C (VEGFC) is the main known lymphangiogenic growth factor, and its expression is increased in periodontitis, a common chronic infectious disease that results in tissue destruction and alveolar bone loss. The role of lymphangiogenesis during development of periodontitis is unknown. Here, we test if transgenic overexpression of epithelial VEGFC in a murine model is followed by hyperplasia of lymphatic vessels in oral mucosa and if the lymphatic drainage capacity is altered. We also test if lymphatic hyperplasia protects against periodontal disease development. Transgenic keratin 14 (K14)-VEGFC mice had significant hyperplasia of lymphatics in oral mucosa, including gingiva, without changes in blood vessel vasculature. The basal lymph flow was normal but slightly lower than in wild-type mice when oral mucosa was challenged with lipopolysaccharide from Porphyromonas gingivalis. Under normal conditions, K14-VEGFC mice exhibited an increased number of neutrophils in gingiva, demonstrated enhanced phagocyte recruitment in the cervical lymph nodes, and had more alveolar bone when compared with their wild-type littermates. After induction of periodontitis, no strain differences were observed in the periodontal tissues with respect to granulocyte recruitment, bone resorption, angiogenesis, cytokines, and bone-related protein expressions or in draining lymph node immune cell proportions and vascularization. We conclude that overexpression of VEGFC results in hyperplastic lymphatics, which do not enhance lymphatic drainage capacity but facilitate phagocyte transport to draining lymph nodes. Hyperplasia of lymphatics does not protect against development of ligature-induced periodontitis.

Risk Factors for Atherosclerosis and the Development of Pre-Atherosclerotic Intimal Hyperplasia

PubMed Central

Cizek, Stephanie M.; Bedri, Shahinaz; Talusan, Paul; Silva, Nilsa; Lee, Hang; Stone, James R.

2007-01-01

Summary Intimal hyperplasia or thickening is considered to be the precursor lesion for atherosclerosis in humans; however the factors governing its formation are unclear. In the atherosclerosis-resistant internal thoracic artery, pre-atherosclerotic intimal hyperplasia routinely forms during adulthood after the 4th decade and is associated with at least two traditional risk factors for atherosclerosis: age and smoking. Background Intimal hyperplasia, or thickening, is considered to be the precursor lesion for atherosclerosis in humans; however, the factors governing its formation are unclear. To gain insight into the etiology of pre-atherosclerotic intimal hyperplasia, traditional risk factors for atherosclerosis were correlated with the intimal hyperplasia in an atherosclerosis-resistant vessel, the internal thoracic artery. Methods Paired internal thoracic arteries were obtained from 89 autopsies. Multivariate logistic regression and multiple regression models were used to examine the association of pre-atherosclerotic intimal hyperplasia with traditional risk factors for atherosclerosis: age, gender, hypertension, smoking, body mass index, diabetes, and hypercholesterolemia. Results Atherosclerotic lesions consisting of fatty streaks and/or type III intermediate lesions were identified in 19 autopsies. Only age >75 years was found to be significantly correlated with atherosclerotic lesion development (P=0.01). Multiple regression model of the intima/media ratio in all 89 cases revealed age >75 years (P<0.0001), age 51–75years (P=0.0012), smoking (P=0.008) and hypertension (P=0.02) to be significantly correlated with intimal thickness. In the 70 cases without atherosclerosis, only age 51–75 years (P=0.006) and smoking (P=0.028) were found to be significantly associated with pre-atherosclerotic intimal thickening. Conclusions In the atherosclerosis-resistant internal thoracic artery, pre-atherosclerotic intimal hyperplasia routinely forms during adulthood

Rare presentation of sebaceous hyperplasia

PubMed Central

Lester, Rachael A; Torgerson, Rochelle R; Sandhu, Nicole P

2014-01-01

A 23-year-old woman presented with an 8-month history of asymptomatic thickening of the central areola bilaterally and oily nipple discharge. On examination, there were yellowish-pink papules coalescing into plaques bilaterally. Biopsy showed ectopic sebaceous glands (Montgomery tubercles), known as bilateral areolar sebaceous hyperplasia. PMID:24759166

Contrast media as carriers for local drug delivery. Successful inhibition of neointimal proliferation in the porcine coronary stent model.

PubMed

Scheller, Bruno; Speck, Ulrich; Romeike, Bernd; Schmitt, Alexander; Sovak, Milos; Böhm, Michael; Stoll, Hans Peter

2003-08-01

Lipophilic taxanes can be dissolved in contrast media at significantly higher concentration than in saline. As contrast media have occasionally been observed to delineate the contour of coronary arteries for some seconds they may serve as a matrix for an antiproliferative drug aimed at preventing restenosis. The aim of this study was to test a novel taxane-contrast agent formulation for this new approach in the setting of coronary stenting. In cell culture experiments (bovine vascular smooth muscle cells), 60-min incubation with contrast agent-taxane formulations (iopromide-paclitaxel, iopromide-protaxel) induced a significant, concentration-dependent inhibition of vascular smooth muscle cell (VSMC) proliferation over 12 days. Shorter incubation times of 10 and 3 min showed the same efficacy. For in vivo investigation, 16 stents were implanted into the coronary arteries of eight pigs using a 1.3 to 1 overstretch ratio. A control group received iopromide 370 alone while the treatment group was injected with a iopromide-protaxel formulation at a dose of 74 micromol/l, which is far below protaxel levels inducing systemic toxicity. Quantitative angiography and histomorphometry of the stented arteries asserted statistic equality of the baseline parameters between the control and treatment groups. After 28 days, the treatment group showed a marked reduction of the parameters characterizing in-stent restenosis, especially a 34% reduction of the neointimal area. First evidence is provided that using a contrast agent as solvent for a taxane constitutes a new drug delivery mechanism able to inhibit in-stent restenosis in the porcine restenosis model.

Safety and Efficacy of an Absorbable Filter in the Inferior Vena Cava to Prevent Pulmonary Embolism in Swine.

PubMed

Huang, Steven Y; Eggers, Mitchell; McArthur, Mark J; Dixon, Katherine A; McWatters, Amanda; Dria, Stephen; Hill, Lori R; Melancon, Marites P; Steele, Joseph R; Wallace, Michael J

2017-12-01

Purpose To evaluate the immediate and long-term safety as well as thrombus-capturing efficacy for 5 weeks after implantation of an absorbable inferior vena cava (IVC) filter in a swine model. Materials and Methods This study was approved by the institutional animal care and use committee. Eleven absorbable IVC filters made from polydioxanone suture were deployed via a catheter in the IVC of 11 swine. Filters remained in situ for 2 weeks (n = 2), 5 weeks (n = 2), 12 weeks (n = 2), 24 weeks (n = 2), and 32 weeks (n = 3). Autologous thrombus was administered from below the filter in seven swine from 0 to 35 days after filter placement. Fluoroscopy and computed tomography follow-up was performed after filter deployment from weeks 1-6 (weekly), weeks 7-20 (biweekly), and weeks 21-32 (monthly). The infrarenal IVC, lungs, heart, liver, kidneys, and spleen were harvested at necropsy. Continuous variables were evaluated with a Student t test. Results There was no evidence of IVC thrombosis, device migration, caval penetration, or pulmonary embolism. Gross pathologic analysis showed gradual device resorption until 32 weeks after deployment. Histologic assessment demonstrated neointimal hyperplasia around the IVC filter within 2 weeks after IVC filter deployment with residual microscopic fragments of polydioxanone suture within the caval wall at 32 weeks. Each iatrogenic-administered thrombus was successfully captured by the filter until resorbed (range, 1-4 weeks). Conclusion An absorbable IVC filter can be safely deployed in swine and resorbs gradually over the 32-week testing period. The device is effective for the prevention of pulmonary embolism for at least 5 weeks after placement in swine. © RSNA, 2017.

Lymphoid papillary hyperplasia of the palatine tonsil: a Chinese case report

PubMed Central

Zhao, Ming; Yu, Jingjing; Li, Changshui

2013-01-01

Lymphoid papillary hyperplasia is a rare abnormality of the tonsils with a predilection for affecting young Asian girls. Herein, we report a 31-year-old Chinese woman presented as right lateral recurrent tonsillar hypertrophy with odynophagia and dysphagia over the past 5 years, worsening over a period of for half a year. Clinically, this lesion was similar to papillomatosis or lymphoid polyposis. However, histopathologic study showed a distinctive form of lymphoid hyperplasia with considerable distinct finger-like projections composed of many phyllodes which contained remarkable follicular lymphoid hyperplasia. This is the only Chinese case of lymphoid papillary hyperplasia of the palatine tonsils that has been reported in the most recent English literature so far. The importance of recognizing this disorder rests in the fact that in spite of the clinical features suggestive of both a benign and a malignant tumor, however, the process is a benign tumor-like proliferation, probably non-neoplastic, could easily be cured by tonsillectomy. PMID:24040465

Intimal hyperplasia induced by vascular intervention causes lipoprotein retention and accelerated atherosclerosis.

PubMed

Kijani, Siavash; Vázquez, Ana Maria; Levin, Malin; Borén, Jan; Fogelstrand, Per

2017-07-01

Accelerated atherosclerosis diminishes the long term patency of vascular interventions, such as percutaneous coronary intervention and implantation of saphenous vein grafts. However, the cause of this accelerated atherosclerosis is unclear. In this study, we tested the hypothesis that intimal hyperplasia formed following vascular intervention promotes retention of atherogenic lipoproteins. Intimal hyperplasia was surgically induced in the mouse common carotid artery. The surgery was combined with different mouse models of hypercholesterolemia to obtain different cholesterol levels and to control the onsets of hypercholesterolemia. Three weeks after surgery, samples were immunostained for apoB lipoproteins, smooth muscle cells and leukocytes. Already at mild hypercholesterolemia (193 mg/dL), pronounced apoB lipoprotein retention was found in the extracellular matrix in both intimal hyperplasia and the injured underlying media. In contrast, minimal retention was detected in the uninjured proximal region of the same vessel, or in vessels from mice with normal cholesterol levels (81 mg/dL). Induction of aggravated hypercholesterolemia 3 weeks after surgery, when a mature intimal hyperplasia had been formed, caused a very rapid development of atherosclerotic lesions. Mechanistically, we show that lipoprotein retention was almost exclusively dependent on electrostatic interactions to proteoglycan glycosaminoglycans, and the lipoprotein retention to intimal hyperplasia could be inhibited in vivo using glycosaminoglycan-binding antibodies. Thus, formation of intimal hyperplasia following vascular intervention makes the vessel wall highly susceptible for lipoprotein retention and accelerated atherosclerosis. The increased lipoprotein retention in intimal hyperplasia can be targeted by blocking the interaction between apoB lipoproteins and glycosaminoglycans in the extracellular matrix. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on

Saw palmetto for benign prostatic hyperplasia.

PubMed

Bent, Stephen; Kane, Christopher; Shinohara, Katsuto; Neuhaus, John; Hudes, Esther S; Goldberg, Harley; Avins, Andrew L

2006-02-09

Saw palmetto is used by over 2 million men in the United States for the treatment of benign prostatic hyperplasia and is commonly recommended as an alternative to drugs approved by the Food and Drug Administration. In this double-blind trial, we randomly assigned 225 men over the age of 49 years who had moderate-to-severe symptoms of benign prostatic hyperplasia to one year of treatment with saw palmetto extract (160 mg twice a day) or placebo. The primary outcome measures were changes in the scores on the American Urological Association Symptom Index (AUASI) and the maximal urinary flow rate. Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, quality of life, laboratory values, and the rate of reported adverse effects. There was no significant difference between the saw palmetto and placebo groups in the change in AUASI scores (mean difference, 0.04 point; 95 percent confidence interval, -0.93 to 1.01), maximal urinary flow rate (mean difference, 0.43 ml per minute; 95 percent confidence interval, -0.52 to 1.38), prostate size, residual volume after voiding, quality of life, or serum prostate-specific antigen levels during the one-year study. The incidence of side effects was similar in the two groups. In this study, saw palmetto did not improve symptoms or objective measures of benign prostatic hyperplasia. (ClinicalTrials.gov number, NCT00037154.). Copyright 2006 Massachusetts Medical Society.

Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 1, Pathological Background and Clinical Implications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Fei, E-mail: feisun@ccmijesususon.com; Crisóstomo, Verónica, E-mail: crisosto@ccmijesususon.com; Báez-Díaz, Claudia, E-mail: cbaez@ccmijesususon.com

Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance.more » BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.« less

Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 1, Pathological Background and Clinical Implications.

PubMed

Sun, Fei; Crisóstomo, Verónica; Báez-Díaz, Claudia; Sánchez, Francisco M

2016-01-01

Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance. BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.

AgNORs in hyperplasia, papilloma and oral squamous cell carcinoma.

PubMed

Fonseca, L M; do Carmo, M A

2000-01-01

Ten inflammatory fibrous hyperplasias, ten papillomas, and nineteen oral squamous cell carcinomas were analyzed by the AgNOR technique to determine if different disturbances of oral epithelia presented different AgNOR counts. The papilloma group showed higher mean AgNOR counts (3.15 +/- 0.58) than the hyperplasia group (1.98 +/- 0.24) and smaller than the well-differentiated oral squamous cell carcinoma group (6.56 +/- 1.25) and poorly differentiated oral squamous cell carcinoma group (7.07 +/- 1.60). The differences among the groups of lesions were statistically significant (P < 0.05) except between the well differentiated oral squamous cell carcinoma group and the poorly differentiated oral squamous cell carcinoma group. Our findings suggest that the cellular proliferation ratio in papillomas is greater than hyperplasias and smaller than carcinomas.

Drug-eluting coronary stents – focus on improved patient outcomes

PubMed Central

Jaffery, Zehra; Prasad, Amit; Lee, John H; White, Christopher J

2011-01-01

The development of stent has been a major advance in the treatment of obstructive coronary artery disease since the introduction of balloon angioplasty. Subsequently, neointimal hyperplasia within the stent leading to in-stent restenosis emerged as a major obstacle in long-term success of percutaneous coronary intervention. Recent introduction of drug-eluting stents is a major breakthrough to tackle this problem. This review article summarizes stent technology, reviews progress of drug-eluting stents and discusses quality of life, patient satisfaction, and acceptability of percutaneous coronary intervention. PMID:22915977

Reversion of gingival hyperplasia in a heart transplant patient upon interruption of cyclosporine therapy.

PubMed

Somacarrera, M L; Lucas, M; Acero, J

1996-01-01

A heart transplant patient undergoing a combined cyclosporine and prednisone treatment was monitored during the 18 months following transplantation. A complete oral and dental examination was performed in each of the first six months after transplantation, and then in the 9th, 12th, 15th, and 18th months. The data collected included gingival hyperplasia secondary to cyclosporine use, and clinical and periodontal variables. Histological studies were also conducted on gingival tissue samples in months 1, 3, 9, 15, and 18. Cyclosporine treatment was replaced by azathioprine treatment in month 10 because the patient was experiencing nephrotoxicity. Between months 9 and 18, gingival hyperplasia regressed by 26.5% due to a reduction in the fibrous connective tissue mass, fibroblasts, and inflammatory infiltration. The control group included 13 heart transplant patients subject to equivalent conditions except discontinuance of cyclosporine treatment; seven of the patients had developed hyperplasia by month 9. Average hyperplasia in the control group increased by 2% between months 9 and 18; only one patient showed a 6.2% decrease in hyperplasia. This provides further evidence for the causal relationship between cyclosporine therapy and gingival hyperplasia, and suggests that this side-effect is reversible.

Silodosin in the treatment of benign prostatic hyperplasia

PubMed Central

Rossi, Maxime; Roumeguère, Thierry

2010-01-01

Benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS due to BPH. Alpha-adrenergic receptor blockers remain one of the mainstays in the treatment of male LUTS and clinical BPH. They exhibit early onset of efficacy with regard to both symptoms and flow rate improvement, and this is clearly demonstrated in placebo-controlled trials with extensions out to five years. These agents have been shown to prevent symptomatic progression of the disease. The aim of this article is to offer a critical review of the current literature on silodosin, formerly known as KMD-3213, a novel alpha-blocker with unprecedented selectivity for α1A-adrenergic receptors, as compared with both α1B- and α1D -adrenoceptors, exceeding the selectivity of all currently used α1-blockers, and with clinically promising effects. PMID:21116335

Hypogammaglobulinemia associated with nodular lymphoid hyperplasia of the intestine and pernicious anaemia.

PubMed

Ouakaa-Kchaou, Asma; Trad, Dorra; Boussourra, Houda; Bibani, Norsaf; Elloumi, Héla; Kochlef, Asma; Gargouri, Dalila; Kharrat, Jamel

2015-11-01

Nodular lymphoid hyperplasia of the gastrointestinal tract, recurrent acute pulmonary infections and autoimmune disease are well-recognized complications of common variable immunodeficiency. We aimed to focus on clinical presentation and differential diagnosis of diffuse nodular lymphoid and hyperplasia of the gastrointestinal tract coexisting with hypogammaglobulinemia. We report the case of nodular lymphoid hyperplasia associated with pernicious anaemia in a young man with hypogammaglobulinemia and a long history of pulmonary infections. The considerable point was a mismatch primary clinical diagnosis of familial adenomatous polyposis, due to prominent polyplike endoscopic appearance of the lesions throughout the digestive tract.

Inflammatory papillary hyperplasia: A systematic review

PubMed Central

Gual-Vaqués, Patricia; Jané-Salas, Enric; Egido-Moreno, Sonia; Ayuso-Montero, Raúl; Marí-Roig, Antoni

2017-01-01

Introduction Inflammatory papillary hyperplasia (IPH) is a benign lesion of the palatal mucosa. It is usually found in denture-wearers but also has been reported in patients without a history of use of a maxillary prosthesis use. Objetives The aim of this study is to review the literature to assess the prevalence of denture stomatitis and inflammatory papillary hyperplasia and the etiological factors associated. Material and Methods A search was carried out in PubMed (January 2005 to October 2015) with the key words “inflammatory papillary hyperplasia”, “denture stomatitis”, “granular stomatitis” and “Newton’s type III” The inclusion criteria were studies including at least a sample of 50 apparently healthy patients, articles published from 2005 to 2015 written in English. The exclusion criteria were reviews and non-human studies. Results Out of the 190 studies obtained initially from the search 16 articles were selected to be included in our systematic review. The prevalence of denture stomatitis was 29.56% and 4.44% for IPH. We found 5 cases of denture stomatitis among non-denture-wearer individuals. All IPH cases were associated with the use of prosthesis. Smoking and continued use of ill-fitting dentures turned out to be the most frequent risk factors for developing IPH. Conclusions IPH is a rare oral lesion and its pathogenesis still remains unclear. Its presentation among non-denture-wearers is extremely unusual. Key words:Inflammatory papillary hyperplasia, denture stomatitis, prevalence, granular stomatitis, Newton’s type III stomatitis. PMID:27918740

Molecular classification of benign prostatic hyperplasia: A gene expression profiling study in a rat model.

PubMed

Hata, Junya; Satoh, Yuichi; Akaihata, Hidenori; Hiraki, Hiroyuki; Ogawa, Soichiro; Haga, Nobuhiro; Ishibashi, Kei; Aikawa, Ken; Kojima, Yoshiyuki

2016-07-01

To characterize the molecular features of benign prostatic hyperplasia by carrying out a gene expression profiling analysis in a rat model. Fetal urogenital sinus isolated from 20-day-old male rat embryo was implanted into a pubertal male rat ventral prostate. The implanted urogenital sinus grew time-dependently, and the pathological findings at 3 weeks after implantation showed epithelial hyperplasia as well as stromal hyperplasia. Whole-genome oligonucleotide microarray analysis utilizing approximately 30 000 oligonucleotide probes was carried out using prostate specimens during the prostate growth process (3 weeks after implantation). Microarray analyses showed 926 upregulated (>2-fold change, P < 0.01) and 3217 downregulated genes (<0.5-fold change, P < 0.01) in benign prostatic hyperplasia specimens compared with normal prostate. Gene ontology analyses of upregulated genes showed predominant genetic themes of involvement in development (162 genes, P = 2.01 × 10(-4) ), response to stimulus (163 genes, P = 7.37 × 10(-13) ) and growth (32 genes, P = 1.93 × 10(-5) ). When we used both normal prostate and non-transplanted urogenital sinuses as controls to identify benign prostatic hyperplasia-specific genes, 507 and 406 genes were upregulated and downregulated, respectively. Functional network and pathway analyses showed that genes associated with apoptosis modulation by heat shock protein 70, interleukin-1, interleukin-2 and interleukin-5 signaling pathways, KIT signaling pathway, and secretin-like G-protein-coupled receptors, class B, were relatively activated during the growth process in the benign prostatic hyperplasia specimens. In contrast, genes associated with cholesterol biosynthesis were relatively inactivated. Our microarray analyses of the benign prostatic hyperplasia model rat might aid in clarifying the molecular mechanism of benign prostatic hyperplasia progression, and identifying molecular targets for benign prostatic hyperplasia treatment. �

Predictive diagnosis of endometrial hyperplasia and personalized therapeutic strategy in women of fertile age

PubMed Central

2013-01-01

Introduction Endometrial hyperplasia has a high risk for malignant transformation and relapses; existing mini-invasive treatments may lead to irrevocable endometrium destruction. The aims were to analyze receptor systems in endometrial hyperplasia, to evaluate the capabilities of ultrasonography, sonoelastography for diagnosis and treatment control, and to develop treatment algorithm. Materials and methods We included 313 women (20–45 years), assessed into the following: group 1 (n = 112) with glandular cystic hyperplasia, group 2 (n = 98) endometrial polyps, and group 3 (n = 103) atypical hyperplasia; and 82 controls who have undergone hysteroscopy before in vitro fertilization in tubal origin infertility were also included. Patients underwent clinical examination, transvaginal ultrasound, immunohistochemical study, and hormonal therapy/hysteroresectoscopy. Results In patients with glandular hyperplasia, we registered increase of endometrium estrogen receptors (75.6% in the epithelium and 30.9% in the stroma; in controls, 43.3% and 29.6%, respectively); in polyps, there was a significant estrogen receptor increase in the stroma (48.2% vs 29.6% in controls), and in atypical hyperplasia, progesterone receptors significantly increased in the stroma. Ki-67 increased (40% to 50%) in the epithelium without changes in the stroma. Ultrasound has a sensitivity of 96% and a specificity of 85% for early detection of endometrial pathology and prediction outcome of intervention, and sonoelastography has a sensitivity of 91% and a specificity of 83% for polyp diagnosis. Personalized treatment was effective in 88.8%, relapse was diagnosed in 11.2% after 6 months, and conservative treatment of atypical hyperplasia was effective in 45%: in 25.8%, ablative hysteroresectoscopy was performed, while in 22.6% with comorbidities, hystero/oophorectomies were performed. Conclusions The evaluation of receptor status with ultrasound data in patients with endometrial

Immunohistochemical differentiation of atypical hyperplasia vs. carcinoma in situ of the breast.

PubMed

Masood, S; Sim, S J; Lu, L

1992-01-01

The distinction between atypical hyperplasia and carcinoma in situ in breast lesions can be difficult. The identification of myoepithelial cell layers may be helpful in establishing a diagnosis of proliferative breast disease vs. intraepithelial neoplasia. We reviewed pathologic material on 20 cases of atypical hyperplasia and 29 cases of carcinoma in situ. Immunohistochemical stains were employed against muscle-specific actin, S-100 protein, and cytokeratin to identify myoepithelial cells and to recognize different staining patterns. In atypical hyperplasia, muscle-specific actin staining identified myoepithelial cells in fine branching fibrovascular layers or as scattered cells between other proliferating cells. This pattern was absent in carcinoma in situ. S-100 protein showed more positive staining in atypical hyperplasia than in carcinoma in situ with patterns distinct from muscle-specific actin. Immunostaining for cytokeratin demonstrated distinctly different patterns between the two lesions. This study suggests that muscle-specific actin, S-100 protein, and cytokeratin in combination may assist in distinguishing proliferative breast disease with atypia from carcinoma in situ.

Endometrial cancer arising from atypical complex hyperplasia: The significance in an endometrial biopsy and a diagnostic challenge

PubMed Central

Byun, Jung Mi; Jeong, Dae Hoon; Kim, Young Nam; Cho, En Bee; Cha, Ju Eun; Sung, Moon Su; Lee, Kyung Bok

2015-01-01

Objective We investigated the features of endometrial hyperplasia with concurrent endometrial cancer that had been diagnosed by endometrial sampling. Further, we attempted to identify an accurate differential diagnostic method. Methods We retrospectively studied 125 patients who underwent a diagnostic endometrial biopsy or were diagnosed after the surgical treatment of other gynecological lesions, such as leiomyoma or polyps. Patients were diagnosed between January 2005 and December 2013 at Busan Paik Hospital. Clinical and histopathological characteristics were compared in patients who had atypical endometrial hyperplasia with and without concurrent endometrial cancer. Results The patients were grouped based on the final pathology reports. One hundred seventeen patients were diagnosed with endometrial hyperplasia and eight patients were diagnosed with endometrioid adenocarcinoma arising from atypical hyperplasia. Of the 26 patients who had been diagnosed with atypical endometrial hyperplasia by office-based endometrial biopsy, eight (30.8%) were subsequently diagnosed with endometrial cancer after they had undergone hysterectomy. The patients with endometrial cancer arising from endometrial hyperplasia were younger (39.1 vs. 47.2 years, P=0.0104) and more obese (body mass index 26.1±9.6 vs. 23.8±2.8 kg/m2, P=0.3560) than the patients with endometrial hyperplasia. The correlation rate between the pathology of the endometrial samples and the final diagnosis of endometrial hyperplasia was 67.3%. Conclusion In patients with atypical endometrial hyperplasia, the detection of endometrial cancer before hysterectomy can decrease the risk of suboptimal treatment. The accuracy of endometrial sampling for the diagnosis of concurrent endometrial carcinoma was much lower than that for atypical endometrial hyperplasia. Therefore, concurrent endometrial carcinoma should be suspected and surgical intervention should be considered in young or obese patients who present with

Acute Toxoplasma gondii infection in children with reactive hyperplasia of the cervical lymph nodes.

PubMed

Bilal, Jalal A; Alsammani, Mohamed A; Ahmed, Mohamed I

2014-07-01

To determine the seroprevalence of Toxoplasma gondii (T. gondii) in children with reactive hyperplasia of the cervical lymph nodes. This cross-sectional prospective study was conducted in Khartoum Children Emergency Hospital, Khartoum, Sudan between January 2010 and April 2011. Eighty children with cervical lymphadenopathy were selected using random sampling. Their lymph nodes were aspirated for cytology, and a blood sample was collected from all patients for routine laboratory analysis and T. gondii IgG and IgM antibodies. Among 80 children with cervical lymphadenopathy, 60 (75%) had non-specific reactive hyperplasia. The seroprevalence of T. gondii among children with cervical lymphadenopathy was 27.5% (n=22), and the seropositivity of acute T. gondii among those with reactive hyperplasia was 36.7% (n=22/60). Lymph nodes in the T. gondii positive group were mobile and warm (p<0.05). The clinical features and laboratory tests were insignificant predictors of acute T. gondii infection with reactive hyperplasia of the cervical lymph nodes. The prevalence of acute T. gondii infection is high among children with non-specific reactive hyperplasia of the cervical lymph nodes. Routine laboratory studies are not helpful in the diagnosis of T. gondii infection with reactive hyperplasia of the lymph nodes however, serological studies may be requested prior to invasive procedures.

Radon induced hyperplasia: effective adaptation reducing the local doses in the bronchial epithelium.

PubMed

Madas, Balázs G

2016-09-01

There is experimental and histological evidence that chronic irritation and cell death may cause hyperplasia in the exposed tissue. As the heterogeneous deposition of inhaled radon progeny results in high local doses at the peak of the bronchial bifurcations, it was proposed earlier that hyperplasia occurs in these deposition hot spots upon chronic radon exposure. The objective of the present study is to quantify how the induction of basal cell hyperplasia modulates the microdosimetric consequences of a given radon exposure. For this purpose, computational epithelium models were constructed with spherical cell nuclei of six different cell types based on histological data. Basal cell hyperplasia was modelled by epithelium models with additional basal cells and increased epithelium thickness. Microdosimetry for alpha-particles was performed by an own-developed Monte-Carlo code. Results show that the average tissue dose, and the average hit number and dose of basal cells decrease by the increase of the measure of hyperplasia. Hit and dose distribution reveal that the induction of hyperplasia may result in a basal cell pool which is shielded from alpha-radiation. It highlights that the exposure history affects the microdosimetric consequences of a present exposure, while the biological and health effects may also depend on previous exposures. The induction of hyperplasia can be considered as a radioadaptive response at the tissue level. Such an adaptation of the tissue challenges the validity of the application of the dose and dose rate effectiveness factor from a mechanistic point of view. As the location of radiosensitive target cells may change due to previous exposures, dosimetry models considering the tissue geometry characteristic of normal conditions may be inappropriate for dose estimation in case of protracted exposures. As internal exposures are frequently chronic, such changes in tissue geometry may be highly relevant for other incorporated radionuclides.

Interleukin-Driven Insulin-Like Growth Factor Promotes Prostatic Inflammatory Hyperplasia

PubMed Central

Hahn, Alana M.; Myers, Jason D.; McFarland, Eliza K.; Lee, Sanghee

2014-01-01

Prostatic inflammation is of considerable importance to urologic research because of its association with benign prostatic hyperplasia and prostate cancer. However, the mechanisms by which inflammation leads to proliferation and growth remain obscure. Here, we show that insulin-like growth factors (IGFs), previously known as critical developmental growth factors during prostate organogenesis, are induced by inflammation as part of the proliferative recovery to inflammation. Using genetic models and in vivo IGF receptor blockade, we demonstrate that the hyperplastic response to inflammation depends on interleukin-1–driven IGF signaling. We show that human prostatic hyperplasia is associated with IGF pathway activation specifically localized to foci of inflammation. This demonstrates that mechanisms of inflammation-induced epithelial proliferation and hyperplasia involve the induction of developmental growth factors, further establishing a link between inflammatory and developmental signals and providing a mechanistic basis for the management of proliferative diseases by IGF pathway modulation. PMID:25292180

SPDEF regulates goblet cell hyperplasia in the airway epithelium

PubMed Central

Park, Kwon-Sik; Korfhagen, Thomas R.; Bruno, Michael D.; Kitzmiller, Joseph A.; Wan, Huajing; Wert, Susan E.; Khurana Hershey, Gurjit K.; Chen, Gang; Whitsett, Jeffrey A.

2007-01-01

Goblet cell hyperplasia and mucous hypersecretion contribute to the pathogenesis of chronic pulmonary diseases including cystic fibrosis, asthma, and chronic obstructive pulmonary disease. In the present work, mouse SAM pointed domain-containing ETS transcription factor (SPDEF) mRNA and protein were detected in subsets of epithelial cells lining the trachea, bronchi, and tracheal glands. SPDEF interacted with the C-terminal domain of thyroid transcription factor 1, activating transcription of genes expressed selectively in airway epithelial cells, including Sftpa, Scgb1a1, Foxj1, and Sox17. Expression of Spdef in the respiratory epithelium of adult transgenic mice caused goblet cell hyperplasia, inducing both acidic and neutral mucins in vivo, and stainined for both acidic and neutral mucins in vivo. SPDEF expression was increased at sites of goblet cell hyperplasia caused by IL-13 and dust mite allergen in a process that was dependent upon STAT-6. SPDEF was induced following intratracheal allergen exposure and after Th2 cytokine stimulation and was sufficient to cause goblet cell differentiation of Clara cells in vivo. PMID:17347682

Refractory Cushing's disease caused by multinodular ACTH-cell hyperplasia.

PubMed

McKeever, P E; Koppelman, M C; Metcalf, D; Quindlen, E; Kornblith, P L; Strott, C A; Howard, R; Smith, B H

1982-09-01

A patient with pituitary-dependent hypercortisolism, unresponsive to resection of nodules in the anterior lobe, is described. Histochemical stains of the nodules showed multiple, focal, cellular expansions of the fibrovascular stroma. Transitions between normal and expanded adenohypophysial acini were present. Immunoperoxidase stains for ACTH and other pituitary hormones revealed that these multiple foci contained an excess of ACTH-positive cells. Less than 10% of the cells in these foci were negative for ACTH and positive for other hormones. Serial sections showed that these foci of predominantly ACTH-producing acini were not connected. Clinical, morphological, and immunohistochemical data indicated that ACTH-cell hyperplasia caused Crushing's disease in this patient. Pathologic study of individual cases should concentrate on determining whether hyperplasia or adenoma exist at the time of surgical exploration of the pituitary gland, since this determination is important to proper treatment. Tentative criteria to recognize ACTH-cell hyperplasia are: 1. Multiple foci of ACTH laden cells. 2. A minor subpopulation of cells of alternate hormone series. 3. Expansion without destruction of acini in the adenohypophysis.

Ovarian hilus-cell hyperplasia and high serum testosterone in a patient with postmenopausal virilization.

PubMed

Delibasi, Tuncay; Erdogan, Murat F; Serinsöz, Ebru; Kaygusuz, Gulsah; Erdogan, Gurbuz; Sertçelik, Ayse

2007-09-01

To describe a woman with postmenopausal virilization and hirsutism caused by hilus-cell hyperplasia. We present a case report including laboratory, radiographic, and pathologic findings in a patient with postmenopausal hirsutism and virilization caused by ovarian hilus-cell hyperplasia as well as a brief review of the literature. A 60-year-old postmenopausal woman presented with extensive hirsutism, male-pattern hair loss, and clitoromegaly. The patient's plasma testosterone levels were very high, but computed tomography showed the adrenal glands to be normal in size. Pelvic ultrasonography revealed a cystic lesion in the left ovary. After bilateral salpingo-oophorectomy, histologic examination demonstrated a diffuse pattern of hilus-cell hyperplasia in the ovarian hilum. In the differential diagnosis of postmenopausal virilization, hilus-cell hyperplasia, although rare, should be considered.

Cytokeratin expression in pseudoepitheliomatous hyperplasia of oral paracoccidioidomycosis.

PubMed

Kaminagakura, E; Bonan, P R F; Lopes, M A; Almeida, O P; Scully, C

2006-08-01

Paracoccidioidomycosis (Pmycosis) is one the most prevalent deep systemic mycoses in Latin America. It is characterized by granulomatous inflammation and pseudoepitheliomatous hyperplasia. Cytokeratins (CKs) are a group of intermediate filaments of epithelial cells and their expression varies according to the epithelium type, differentiation and pathological processes. This study describes cytokeratin expression as examined by immunohistochemistry, in 28 cases of oral Pmycosis involving the buccal mucosa, lip, gingiva and hard palate. Expression of CKs in the basal layer of the epithelium in pseudoepitheliomatous hyperplasia of Pmycosis was similar to that in normal oral mucosa (NOM), but in Pmycosis CK1 and CK10 were not expressed in the spinous and superficial layers of the lip, gingiva or hard palate, and, in the spinous and superficial layers of the lip and buccal mucosa, CK14 was positive in contrast to NOM where it was negative. In Pmycosis, CK6 was more frequently expressed in the spinous layer of the lip, gingiva and hard palate, but nevertheless CK16 expression was decreased in the spinous and superficial layers of the gingiva and hard palate. We conclude that pseudoepitheliomatous hyperplasia in oral Pmycosis shows a different pattern of CK expression, particularly CKs 1, 10 and 14, compared with NOM.

Study of denture-induced fibrous hyperplasia cases diagnosed from 1979 to 2001.

PubMed

Macedo Firoozmand, Leily; Dias Almeida, Janete; Guimarães Cabral, Luiz Antonio

2005-01-01

The purpose of this research was to study the cases of inflammatory fibrous hyperplasia (IFH) at the Clinic of Semiology, Department of Bioscience and Oral Diagnosis, São Jose dos Campos Dental School, State University of São Paulo, Brazil. A total of 141 clinical file cards indicating a final diagnosis of IFH, from the archives of the Department of Bioscience and Oral Diagnosis and dated from 1979 to 2001, were included in the study. Of these files, 50 indicated a diagnosis of denture-induced fibrous hyperplasia. Sex, age, race, duration, and clinical features that confirm their classification in the non-neoplastic proliferating process were analyzed statistically. Of the 50 analyzed cases of denture-induced lesion, 22% occurred in men and 78% in women. Patients in the age group of 41 to 50 years presented the highest frequency of the lesion. Inflammatory fibrous hyperplasia occurs more frequently in women (71.63%), and denture-induced lesions appear mainly in patients over 40 years of age (70% of cases). Patients with denture-induced hyperplasia reported pain associated with the lesion (70%).

Fibro-epithelial hyperplasia mimicking mucocele.

PubMed

Jain, K; Singh, B D; Dubey, A; Avinash, A

2014-01-01

The effects of chronic local irritation have been seen commonly in the form of fibroma or mucocele in children. We report a ten year old girl with the chief complaint of swelling in the lower right region of labial mucosa which was diagnosed clinically as mucocele and histologically as fibro-epithelial hyperplasia. Surgical excision was done under local anesthesia with no post-operative complication.

Flow cytometric analysis of immunoglobulin heavy chain expression in B-cell lymphoma and reactive lymphoid hyperplasia

PubMed Central

Grier, David D; Al-Quran, Samer Z; Cardona, Diana M; Li, Ying; Braylan, Raul C

2012-01-01

The diagnosis of B-cell lymphoma (BCL) is often dependent on the detection of clonal immunoglobulin (Ig) light chain expression. In some BCLs, the determination of clonality based on Ig light chain restriction may be difficult. The aim of our study was to assess the utility of flow cytometric analysis of surface Ig heavy chain (HC) expression in lymphoid tissues in distinguishing lymphoid hyperplasias from BCLs, and also differentiating various BCL subtypes. HC expression on B-cells varied among different types of hyperplasias. In follicular hyperplasia, IgM and IgD expression was high in mantle cells while germinal center cells showed poor HC expression. In other hyperplasias, B cell compartments were blurred but generally showed high IgD and IgM expression. Compared to hyperplasias, BCLs varied in IgM expression. Small lymphocytic lymphomas had lower IgM expression than mantle cell lymphomas. Of importance, IgD expression was significantly lower in BCLs than in hyperplasias, a finding that can be useful in differentiating lymphoma from reactive processes. PMID:22400070

A Recurrence of Bilateral Diffuse Sclerosing Lobular Hyperplasia of Breast: A Case Report.

PubMed

Elfituri, Osama; Sonawane, Snehal; Xu, Haoliang; Warso, Michael A; Wiley, Elizabeth

2017-12-01

Mammary sclerosing lobular hyperplasia is an uncommon benign fibroproliferative lesion of adolescent and young women, often of African American heritage with an incidence of ~3%. Patients generally complain of a palpable, painless, or slightly tender and well-defined lump in breast. Very rarely, this lesion may be bilateral and diffuse. The definitive diagnosis of sclerosing lobular hyperplasia requires histopathologic evaluation. Here, we describe a case of diffuse sclerosing lobular hyperplasia in a 29-year-old African American woman that required bilateral mastectomy and recurred bilaterally requiring second resections. This appears to be the first report of this phenomenon.

Epithelial tissue hyperplasia induced by the RAF inhibitor PF-04880594 is attenuated by a clinically well-tolerated dose of the MEK inhibitor PD-0325901.

PubMed

Torti, Vince R; Wojciechowicz, Donald; Hu, Wenyue; John-Baptiste, Annette; Evering, Winston; Troche, Gabriel; Marroquin, Lisa D; Smeal, Tod; Yamazaki, Shinji; Palmer, Cynthia L; Burns-Naas, Leigh Ann; Bagrodia, Shubha

2012-10-01

Clinical trials of selective RAF inhibitors in patients with melanoma tumors harboring activated BRAFV600E have produced very promising results, and a RAF inhibitor has been approved for treatment of advanced melanoma. However, about a third of patients developed resectable skin tumors during the course of trials. This is likely related to observations that RAF inhibitors activate extracellular signal-regulated kinase (ERK) signaling, stimulate proliferation, and induce epithelial hyperplasia in preclinical models. Because these findings raise safety concerns about RAF inhibitor development, we further investigated the underlying mechanisms. We showed that the RAF inhibitor PF-04880594 induces ERK phosphorylation and RAF dimerization in those epithelial tissues that undergo hyperplasia. Hyperplasia and ERK hyperphosphorylation are prevented by treatment with the mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor PD-0325901 at exposures that extrapolate to clinically well-tolerated doses. To facilitate mechanistic and toxicologic studies, we developed a three-dimensional cell culture model of epithelial layering that recapitulated the RAF inhibitor-induced hyperplasia and reversal by MEK inhibitor in vitro. We also showed that PF-04880594 stimulates production of the inflammatory cytokine interleukin 8 in HL-60 cells, suggesting a possible mechanism for the skin flushing observed in dogs. The complete inhibition of hyperplasia by MEK inhibitor in epithelial tissues does not seem to reduce RAF inhibitor efficacy and, in fact, allows doubling of the PF-04880594 dose without toxicity usually associated with such doses. These findings indicated that combination treatment with MEK inhibitors might greatly increase the safety and therapeutic index of RAF inhibitors for the treatment of melanoma and other cancers. ©2012 AACR.

Angiolymphoid Hyperplasia with Eosinophilia: A Case Report

PubMed Central

Esteves, Paola; Barbalho, Marcella; Lima, Tiago; Quintella, Leonardo; Niemeyer-Corbellini, João Paulo; Ramos-e-Silva, Marcia

2015-01-01

Angiolymphoid hyperplasia with eosinophilia is a rare disease considered as being a vascular malformation resulting from a subjacent arteriovenous shunt. It affects mostly the head of women between 20 and 40 years old and may present spontaneous involution. PMID:26120306

[Immunomorphologic features of epithelial-stromal relationships at hyperplasia and endometrial carcinoma].

PubMed

Bantysh, B B; Paukov, v S; Kogan, E A

2012-01-01

The results of a immunomorphologic comprehensive study of epithelial-stromal relationships in the uterus hyperplasia and endometrial cancer suggest that the suppressor gene of cancer (PTEN) plays a key role in the process of neoplastic transformation of endometrial hyperplasia and adenocarcinoma development. For the first time the existence of two highly differentiated endometrial adenocarcinoma immunophenotype were detected The first one is a PTEN-negative endometrial aedenocarcinoma, characterized by an almost complete inhibition of tumor suppressor gene PTEN in the epithelium of the glands and stromal cell of the tumor The second type is a PTEN-positive endometrial adenocarcinoma, in which epithelial and stromal tumor suppressor gene PTEN activity has retained Based on these results we have formulated a hypothesis about the different types of endometrial hyperplasia morphogenesis and its possible transfer to cervical cancer associated with features of tumor suppressor gene PTEN.

Intravascular papillary endothelial hyperplasia of the foot.

PubMed

Cisco, R W; McCormac, R M

1994-01-01

Intravascular papillary endothelial hyperplasia is a rare benign reactive lesion usually found in thrombosed subcutaneous blood vessels. The lesion resembles malignant angiosarcoma clinically and histopathologically, and must be diagnosed correctly to avoid inappropriate treatment. The following is a case presentation involving the foot.

Oral desmoplastic melanoma mimicking inflammatory hyperplasia.

PubMed

Jou, Adriana; Miranda, Fábio V; Oliveira, Márcia G; Martins, Manoela D; Rados, Pantelis V; Filho, Manoel S

2012-06-01

Desmoplastic melanoma (DM) arising in the oral cavity is a rare neoplasm that may be confused with a variety of non-melanocytic benign or malignant lesions. To present a case of DM in the oral mucosa mimicking fibrous inflammatory hyperplasia, discusses the difficulties involved in the diagnosis and offers a literature review on the clinicopathologic and immunohistochemincal aspects of this neoplasm. A 62-year-old white male, smoker, was referred with a chief complaint of pain and swelling in the palate. The oral examination revealed multiple brown-to-black patches and a non-pigmented sessile nodule located on the mucosa of the hard palate. The clinical diagnosis of the pigmented lesions was either oral melanosis or melanoma. The nodular lesion was clinically diagnosed as fibrous inflammatory hyperplasia. Incisional biopsy was performed on the pigmented lesion and the microscopic sections revealed a melanotic macule. The nodular lesions histologically revealed an amelanotic desmoplastic melanoma. Reactive lesions close to a pigmented area should be investigated with great care. © 2010 The Gerodontology Society and John Wiley & Sons A/S.

Overexpression of mutated IkappaBalpha inhibits vascular smooth muscle cell proliferation and intimal hyperplasia formation.

PubMed

Zuckerbraun, Brian S; McCloskey, Carol A; Mahidhara, Raja S; Kim, Peter K M; Taylor, Bradley S; Tzeng, Edith

2003-10-01

Vascular injury and inflammation are associated with elaboration of a number of cytokines that signal through multiple pathways to act as smooth muscle cell (SMC) mitogens. Activation of the nuclear factor-kappa B (NF-kappaB) transcription factor is essential for SMC proliferation in vitro and is activated by vascular injury in vivo. Activation of NF-kappaB is controlled by several upstream regulators, including the inhibitors of kappa B (IkappaB). These proteins bind to and keep NF-kappaB inactivated. The purpose of this study was to determine whether adenoviral gene transfer of a mutated IkappaBalpha super-repressor (AdIkappaBalphaSR) could inhibit development of intimal hyperplasia in vivo and to investigate how over-expression of this construct influences in vitro SMC proliferation and cell cycle regulatory proteins. A rat carotid injury model was used to study prevention of intimal hyperplasia. Arteries were assayed 14 days after injury and infection with AdIkappaBalphaSR or adenoviral beta-galactosidase (AdLacZ). Untreated SMC or SMC infected with AdLacZ or AdIkappaBalphaSR were stimulated with 10% fetal bovine serum, interleukin-1beta, or tumor necrosis factor-alpha. Electrophoretic mobility shift assays were used to assay for NF-kappaB activation. Protein levels of IkappaBalpha and cyclin-dependent kinase inhibitors p21(Cip1/Waf1) and p27(Kip1) were determined with Western blot analysis. Proliferation was measured with (3)H-thymidine incorporation assays. AdIkappaBalphaSR inhibited the development of intimal hyperplasia by 49% (P <.05). Infection with AdIkappaBalphaSR significantly suppressed in vitro SMC proliferation when stimulated with serum, interleukin 1, or tumor necrosis factor alpha, and did not result in cell death. Inhibition of proliferation was associated with increased p21(Cip1/Waf1) and p27(Kip1) protein levels. Gene transfer of IkappaBalpha super-repressor inhibited development of intimal hyperplasia in vivo and SMC proliferation in vitro

Valsartan attenuates intimal hyperplasia in balloon-injured rat aortic arteries through modulating the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor axis.

PubMed

Li, Yonghong; Cai, Shanglang; Wang, Qixin; Zhou, Jingwei; Hou, Bo; Yu, Haichu; Ge, Zhiming; Guan, Renyan; Liu, Xu

2016-05-15

The role of the Mas receptor in the activity of valsartan against intimal hyperplasia is unclear. Herein, we investigated the role of the angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas receptor axis on the activity of valsartan against intimal hyperplasiain balloon-injured rat aortic arteries. Wistar rats were randomized equally into the sham control group, injured group, and injured plus valsartan (20 mg/kg/d)-treated group. Valsartan significantly attenuated the vascular smooth muscle cell proliferation and intimal and medial thickening on days 14 and 28 after injury. The angiotensin-(1-7) levels as well as ACE2 and Mas receptor mRNA/protein expression were significantly decreased in the injured rats, compared to the uninjured rats; meanwhile, the angiotensin II level as well as the ACE and AT1 receptor mRNA/protein expression were increased (all P < 0.05 or < 0.01). Additionally, the p-ERK protein expression was increased (P < 0.01). Treatment with valsartan significantly increased the angiotensin-(1-7) levels as well as ACE2 and Mas receptor mRNA/protein expression but decreased the angiotensin II level, ACE and AT1 receptor mRNA/protein expression, as well as the p-ERK protein expression, compared to the injured group (all P < 0.05 or < 0.01). These results suggest that valsartan attenuates neointimal hyperplasiain balloon-injured rat aortic arteries through activation of the ACE2-angiotensin-(1-7)-Mas axis as well as inhibition of the ACE-angiotensin II-AT1 and p-ERK pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

Thymic cystic degeneration, pseudoepitheliomatous hyperplasia, and hemorrhage in a dog with brodifacoum toxicosis.

PubMed

Rickman, B H; Gurfield, N

2009-05-01

Thymic cysts with pseudoepitheliomatous hyperplasia are described in a 7-month-old female American Eskimo Dog that died of complications from brodifacoum poisoning. Grossly, there was hemothorax with marked cranial mediastinal hemorrhage. Histologically, thymic lobules were expanded and distorted by irregular cysts, lined by single to multiple layers of plump to slightly attenuated polygonal squamous epithelial cells supported by a basement membrane (pseudoepitheliomatous hyperplasia). The thymus had a paucity of lymphocytes and lacked corticomedullary differentiation. Extensive hemorrhage within the cysts and thymic parenchyma extended into the adjacent adipose tissue. To the authors' knowledge, this is the first report of cystic thymic degeneration with pseudoepitheliomatous hyperplasia in a nonhuman species.

Noninvasive Prenatal Diagnosis of Congenital Adrenal Hyperplasia.

PubMed

Khattab, Ahmed; Yuen, Tony; Sun, Li; Yau, Mabel; Barhan, Ariella; Zaidi, Mone; Lo, Y M Dennis; New, Maria I

2016-01-01

A major hallmark of classical congenital adrenal hyperplasia (CAH) is genital ambiguity noted at birth in affected females, which leads to psychological and psychosexual issues in adult life. Attempts to correct genital ambiguity through surgical intervention have been partially successful. Fetal hyperandrogenemia and genital ambiguity have been shown to be preventable by prenatal administration of low-dose dexamethasone initiated before the 9th week of gestation. In 7 of 8 at-risk pregnancies, the unaffected fetus is unnecessarily exposed to dexamethasone for weeks until the diagnosis of classical CAH is ruled out by invasive procedures. This therapeutic dilemma calls for early prenatal diagnosis so that dexamethasone treatment can be directed to affected female fetuses only. We describe the utilization of cell-free fetal DNA in mothers carrying at-risk fetuses as early as 6 gestational weeks by targeted massively parallel sequencing of the genomic region including and flanking the CYP21A2 gene. Our highly personalized and innovative approach should permit the diagnosis of CAH before genital development begins, therefore restricting the purposeful administration of dexamethasone to mothers carrying affected females. © 2016 S. Karger AG, Basel.

Mammary fibroadenomatous hyperplasia in a young cat attributed to treatment with megestrol acetate.

PubMed

MacDougall, Lori D

2003-03-01

A male, neutered cat was presented for lethargy, reluctance to walk, and mammary enlargement after recent treatment with megestrol acetate. Mammary fibroadenomatous hyperplasia was diagnosed on the basis of history, clinical signs, and histopathological findings. Pathogenesis, clinical signs, and treatment options for mammary fibroadenomatous hyperplasia attributed to megestrol acetate treatment are discussed.

Estrogen Receptor Expression in Atypical Hyperplasia: Lack of Association with Breast Cancer

PubMed Central

Barr Fritcher, Emily G.; Degnim, Amy C.; Hartmann, Lynn C.; Radisky, Derek C.; Boughey, Judy C.; Anderson, Stephanie S.; Vierkant, Robert A.; Frost, Marlene H.; Visscher, Daniel W.; Reynolds, Carol

2011-01-01

Background Estrogen receptor (ER) is expressed in normal and malignant breast epithelium, and expression levels have been found to increase with age in normal breast epithelium but not in atypical hyperplasia (AH) and carcinoma in situ. Here we assess ER expression in AH and its association with later breast cancer. Methods ER expression was assessed immunohistochemically in archival sections from 246 women with AH who had open benign breast biopsy from 1967–1991. The ACISRIII (Dako, Carpinteria, CA) was utilized to calculate ER expression in all atypical foci. Using multivariate linear regression, we examined associations of ER expression with age at biopsy, indication for biopsy, type of atypia, number of atypical foci, involution status, and family history. Breast cancer risk across levels of ER expression was also assessed compared to the Iowa SEER control population. Results Among 246 women, 87 (35%) had atypical ductal hyperplasia (ADH), 141 (57%) had atypical lobular hyperplasia (ALH), and 18 (7%) had both. Forty-nine (20%) developed breast cancer (median follow-up of 14.4 years). Multivariate analysis indicated that type of atypia and age at diagnosis were significantly associated with ER percent staining and intensity [p<0.05]. ER expression was increased in women with ADH and/or those over age 55. ER expression did not significantly impact breast cancer risk in patients diagnosed with atypia. Conclusion We found increasing ER expression in atypical hyperplasia with increasing age. ER expression in atypical hyperplasia does not further discriminate breast cancer risk in women with atypia. PMID:21209395

Oral focal epithelial hyperplasia: report of three cases.

PubMed

Ghalayani, Parichehr; Tavakoli, Payam; Eftekhari, Mehdi; Haghighi, Mohammad Akhondzadeh

2015-01-01

Focal epithelial hyperplasia or Heck's disease is an infrequent asymptomatic condition caused by human papillomavirus types 13 or 32 affecting the mucous membrane of the mouth and is commonly seen in young individuals. Firstly, it was described in Indians and Eskimos, but it exists in various populations. We present three cases of Heck's disease in an Afghan immigrant family group living in Iran that seem to have familial predominance. The disease was identified as oral focal epithelial hyperplasia on the basis of histopathologic and clinical findings. The lesions were reduced significantly after 4 months of good oral hygiene. Dentists should be familiar with the clinical manifestations of these types of lesions that affect the oral cavity. In fact, histopathologic assessment and clinical observation are necessary to establish the diagnosis.

Mammary fibroadenomatous hyperplasia in a young cat attributed to treatment with megestrol acetate

PubMed Central

MacDougall, Lori D.

2003-01-01

A male, neutered cat was presented for lethargy, reluctance to walk, and mammary enlargement after recent treatment with megestrol acetate. Mammary fibroadenomatous hyperplasia was diagnosed on the basis of history, clinical signs, and histopathological findings. Pathogenesis, clinical signs, and treatment options for mammary fibroadenomatous hyperplasia attributed to megestrol acetate treatment are discussed. PMID:12677692

Somatostatin inhibits intestinal mucosal mast cell degranulation in normal conditions and during mast cell hyperplasia.

PubMed

Saavedra, Y; Vergara, P

2003-03-28

Several studies demonstrate that intestinal mucosal mast cells (IMMC) are modulated by nervous reflexes as well as by intraluminal content. We recently demonstrated that peptones, such as ovalbumin hydrolysate (OVH), induce the release of rat mast cell protease II (RMCP II), indicating IMMC degranulation. The response is due to complex neuroendocrine reflexes. Somatostatin (SS) and its analogues have been used as potential treatments for inflammation in other body systems with contradictory results. The aim of this study was to evaluate if somatostatin could contribute to the reduction of intestinal mucosal mast cell degranulation. Anesthetized rats were prepared for duodenal perfusion and mast cell activation was measured by analysis of RMCP II concentration in the duodenal perfusate. Somatostatin significantly decreased RMCP II concentration in both nonstimulated conditions and after ovalbumin hydrolysate perfusion. However, when somatostatin was given previously to OVH, the peptone still induced a slight increase of RMCP II. Similar effects were observed in animals previously treated with capsaicin. These protocols were repeated in animals infected with Trichinella spiralis, which induces mucosal mast cell hyperplasia. In these cases, somatostatin blocked the effect of OVH, thus, preventing an increase in RMCP II concentration. Fresh frozen tissue sections from the duodenum were processed in an attempt to demonstrate the presence of SS receptors in mast cells using immunofluorescence and Fluo-peptide labeling techniques. Confocal images from duodenum specimens demonstrate the existence of SS receptors in positive cells for RMCP II. Taken together, these results indicate that somatostatin diminishes mast cell activity and in consequence could prevent the intestinal responses to mast cell hyperplasia. Copyright 2002 Elsevier Science B.V.

Social dominance in tilapia is associated with gonadotroph hyperplasia.

PubMed

Golan, Matan; Levavi-Sivan, Berta

2013-10-01

Tilapias are emerging as one of the most important fish in worldwide aquaculture and are also widely used as model fish in the study of reproduction and behavior. During the reproductive season, male tilapia are highly territorial and form spawning pits in which the dominant males court and spawn with available females. Non-territorial males stand a much lower chance of reproducing. Using transgenic tilapia in which follicle stimulating hormone (FSH) gonadotrophs were fluorescently labeled with enhanced green fluorescent protein (EGFP), we studied the effect of social dominance on the hormonal profile and pituitary cell populations in dominant and non-dominant males. Immunofluorescence studies showed that FSH-EGFP-transgenic fish reliably express EGFP in FSH-secreting cells. EGFP expression pattern differed from that of luteinizing hormone. Dominant males had larger gonads as well as higher levels of androgens and gonadotropins in the plasma. Pituitaries of dominant males exhibited higher gonadotropin content and gene expression. Flow cytometry revealed pituitary hyperplasia as well as FSH cell hyperplasia and increased granulation. Taken together, these findings suggest that gonadotroph hyperplasia as well as increased production by individual cells underlie the increased reproductive activity of dominant tilapia males. Copyright © 2013 Elsevier Inc. All rights reserved.

Somatotroph Hyperplasia

PubMed Central

Thorner, M. O.; Perryman, R. L.; Cronin, M. J.; Rogol, A. D.; Draznin, M.; Johanson, A.; Vale, W.; Horvath, E.; Kovacs, K.

1982-01-01

A 21-yr-old woman with Turner's syndrome presented with signs and symptoms of acromegaly. The serum growth hormone (GH) (95±9.4 ng/ml; mean±SEM) and somatomedin C (11 U/ml) levels were elevated, and an increase in GH levels after glucose instead of normal suppression, increase after thyrotropin-releasing hormone (TRH) administration instead of no change, and decrease after dopamine administration instead of stimulation were observed. The pituitary fossa volume was greater than normal (1,440 mm3) and the presence of a pituitary tumor was assumed. After tissue removal at transsphenoidal surgery, histological study revealed somatotroph hyperplasia rather than a discrete adenoma. Postoperatively, she remained clinically acromegalic and continued to show increased GH and somatomedin levels. A search was made for ectopic source of a growth hormone-releasing factor (GRF). Computer tomographic scan revealed a 5-cm Diam tumor in the tail of the pancreas. Following removal of this tumor, serum GH fell from 70 to 3 ng/ml over 2 h, and remained low for the subsequent 5 mo. Serum somatomedin C levels fell from 7.2 to normal by 6 wk postoperatively. There were no longer paradoxical GH responses to glucose, TRH, and dopamine. Both the medium that held the tumor cells at surgery and extracts of the tumor contained a peptide with GRF activity. The GRF contained in the tumor extract coeluted on Sephadex G-50 chromatography with rat hypothalamic GH-releasing activity. Stimulation of GH from rat somatotrophs in vitro was achieved at the nanomolar range, using the tumor extract. The patient's course demonstrates the importance of careful interpretation of pituitary histology. Elevated serum GH and somatomedin C levels in a patient with an enlarged sella turcica and the characteristic responses seen in acromegaly to TRH, dopamine, and glucose do not occur exclusively in patients with discrete pituitary tumors and acromegaly. This condition can also occur with somatotroph hyperplasia

New therapeutic possibilities for vein graft disease in the post-edifoligide era.

PubMed

Cai, Xinjiang; Freedman, Neil J

2006-07-01

Vein graft neointimal hyperplasia involves proliferation and migration of vascular smooth muscle cells into the vessel intima, and ultimately engenders accelerated atherosclerosis and vein graft failure. Since a myriad of stimuli provoke smooth muscle cell proliferation, molecular therapies for vein graft disease have targeted mechanisms fundamental to all cell proliferation - the 'cell-cycle' machinery. Preclinically, the most successful of these therapies has been edifoligide (E2F decoy), a double-stranded oligodeoxynucleotide that binds to the transcription factor known as E2F. Recently, PRoject of Ex vivo vein GRaft Engineering via Transfection (PREVENT) III and IV demonstrated that edifoligide failed to benefit human vein grafts employed to treat lower-extremity ischemia and coronary heart disease, respectively. The clinical failure of edifoligide calls into question previous models of vein graft disease and lends credence to recent animal studies demonstrating that vein graft arterialization substantially involves the immigration into the vein graft of a variety of vascular progenitor cells. Future vein graft disease therapies will likely target not only proliferation of graft-intrinsic cells, but also immigration of graft-extrinsic cells.

Epidermal psoriasiform hyperplasia, an unrecognized sign of folliculitis decalvans: A histological study of 26 patients.

PubMed

Matard, Bruno; Cavelier-Balloy, Benedicte; Reygagne, Pascal

2017-04-01

Follicular hyperkeratosis along with hyperplasia of the follicular and interfollicular epithelia are major histopathological characteristics of hidradenitis suppurativa (HS). The presence of an occasional thickening of lesional skin in some folliculitis decalvans (FD) patients and histological similarities between FD and HS led us to look for epidermal hyperplasia and follicular hyperkeratosis in FD patients. We performed a retrospective histological analysis of 26 patients with FD. We sought to find out whether the presence of hyperplasia of the interfollicular epidermis and of the follicular epithelia could be verified in FD, with reference to the work of von Laffert et al. concerning HS. The main quantitative and qualitative data were: follicular hyperkeratosis (77%), hyperplasia of the interfollicular epidermis (92%) with a psoriasiform aspect (88%), atrophy of the follicular epithelia (85%), plasma cells in infiltrate (92%) in large quantities (42%), follicular microcysts (60%), atrophy of the sebaceous glands (85%) and polytrichia (54%). Epidermal hyperplasia, sometimes psoriasiform and follicular microcysts, are significant histological signs of FD, which have been ignored until now although they seem very common. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Induction of hyperplasia in the bladder epithelium of rats by a dietary excess of acid or base: implications for toxicity/carcinogenicity testing.

PubMed

de Groot, A P; Feron, V J; Immel, H R

1988-05-01

In previous studies we observed an increased incidence of hyperplasia in the epithelium of the urinary bladder of rats fed cereal-based stock diet supplemented with 6% monosodium glutamate (MSG) for 3 months. Hyperplasia was not enhanced, however, when 6% MSG was fed in a purified casein diet. Further studies have been conducted to identify the dietary factor that caused the different response with the two diets. Feeding MSG had a marked alkalizing effect on the urine. Rats fed purified diet produced urine of higher acidity than did those fed stock diet, a finding attributed to the greater excess of base in the stock diet. When diets with a considerable excess of cations were fed, urinary pH showed a characteristic pattern of widely differing values during a 24-hr period, with high values (pH greater than or equal to 8] for several hours of darkness, when food intake was high, declining during the day to a minimum at the end of the light period. Hyperplasia of the bladder epithelium was induced not only by feeding MSG, but also by feeding 5% of the alkalizing salt KHCO3, both in purified diet and in stock diet. The epithelial response to an alkalizing substance was prevented by simultaneous feeding of the acidifying salt NH4Cl. These findings indicate that the bladder changes induced by MSG are attributable to its alkalizing properties rather than to MSG per se. Moderate to severe hyperplasia of the bladder epithelium was induced also by feeding 5% NH4Cl in purified diet, a procedure accompanied by a further lowering of urinary pH. These findings showed that hyperplasia of the bladder epithelium of rats can be induced both by acidifying and by alkalizing the urine through manipulation of the acid-base balance of the basal diet. There is thus a possibility that, in carcinogenicity studies, administration of compounds to rats in the form of a salt may lead to erroneous conclusions.

Pictures of focal nodular hyperplasia and hepatocellular adenomas

PubMed Central

Sempoux, Christine; Balabaud, Charles; Bioulac-Sage, Paulette

2014-01-01

This practical atlas aims to help liver and non liver pathologists to recognize benign hepatocellular nodules on resected specimen. Macroscopic and microscopic views together with immunohistochemical stains illustrate typical and atypical aspects of focal nodular hyperplasia and of hepatocellular adenoma, including hepatocellular adenomas subtypes with references to clinical and imaging data. Each step is important to make a correct diagnosis. The specimen including the nodule and the non-tumoral liver should be sliced, photographed and all different looking areas adequately sampled for paraffin inclusion. Routine histology includes HE, trichrome and cytokeratin 7. Immunohistochemistry includes glutamine synthase and according to the above results additional markers such as liver fatty acid binding protein, C reactive protein and beta catenin may be realized to differentiate focal nodular hyperplasia from hepatocellular adenoma subtypes. Clues for differential diagnosis and pitfalls are explained and illustrated. PMID:25232451

[Rapidly-growing nodular pseudoangiomatous stromal hyperplasia of the breast: case report].

PubMed

Elıyatkin, Nuket; Karasu, Başak; Selek, Elif; Keçecı, Yavuz; Postaci, Hakan

2011-01-01

Pseudoangiomatous stromal hyperplasia is a benign proliferative lesion of the mammary stroma that rarely presents as a localized mass. Pseudoangiomatous stromal hyperplasia is characterized by a dense, collagenous proliferation of the mammary stroma, associated with capillary-like spaces. Pseudoangiomatous stromal hyperplasia can be mistaken with fibroadenoma on radiological examination or with low-grade angiosarcoma on histological examination. Its main importance is its distinction from angiosarcoma. The presented case was a 40-year-old woman who was admitted with a rapidly growing breast tumor. Physical examination revealed an elastic-firm, well-defined, mobile and painless mass in her right breast. Mammograms revealed a 6.7 x 3.7 cm, lobulated, well-circumscribed mass in her right breast but no calcification. Sonographic examination showed a well-defined and homogenous mass, not including any cyst. Based on these findings, a provisional diagnosis of fibroadenoma was made. Considering the rapid growth history of the mass, tumor excision was performed. The excised tumor was well demarcated and had a smooth external surface. Histological examination revealed the tumor to be composed of markedly increased fibrous stroma and scattered epithelial components (cystic dilatation of the ducts, blunt duct adenosis). The fibrous stroma contained numerous anastomosing slit-like spaces. Isolated spindle cells appeared intermittently at the margins of the spaces resembled endothelial cells. Immunohistochemical staining showed that the spindle cells were positive for CD34 and negative for Factor VIII-related antigen. The lesion was diagnosed as nodular pseudoangiomatous stromal hyperplasia.

Decreased Neointimal Extracellular Matrix Formation in RAGE-Knockout Mice After Microvascular Denudation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Groezinger, Gerd, E-mail: gerd.groezinger@med.uni-tuebingen.de; Schmehl, Joerg, E-mail: joerg.schmehl@med.uni-tuebingen.de; Bantleon, Ruediger, E-mail: ruediger.bantleon@med.uni-tuebingen.de

2012-12-15

Purpose: To evaluate in vivo the role of RAGE (receptor for advanced glycated end products) in the development of restenosis and neointimal proliferation in RAGE-deficient knockout (KO) mice compared with wild-type (WT) mice in an animal model. Materials and Methods: Sixteen WT and 15 RAGE-deficient mice underwent microvascular denudation of the common femoral artery under general anaesthesia. Contralateral arteries underwent a sham operation and served as controls. Four weeks after the intervention, all animals were killed, and paraformaldehyde-fixed specimens of the femoral artery were analysed with different stains (hematoxylin and eosin and Elastica van Gieson) and several different types ofmore » immunostaining (proliferating cell nuclear antigen, {alpha}-actin, collagen, von Willebrand factor, RAGE). Luminal area, area of the neointima, and area of the media were measured in all specimens. In addition, colony-formation assays were performed, and collagen production by WT smooth muscle cells (SMCs) and RAGE-KO SMCs was determined. For statistical analysis, P < 0.05 was considered statistically significant. Results: Four weeks after denudation, WT mice showed a 49.6% loss of luminal area compared with 14.9% loss of luminal area in RAGE-deficient mice (sham = 0% loss) (P < 0.001). The neointima was 18.2 (*1000 {mu}m{sup 2} [n = 15) in the WT group compared with only 8.4 (*1000 {mu}m{sup 2} [n = 16]) in the RAGE-KO group. RAGE-KO SMCs showed significantly decreased proliferation activity and production of extracellular matrix protein. Conclusion: RAGE may be shown to play a considerable role in the formation of neointima leading to restenosis after vascular injury.« less

Proteomics Analysis of Tissue Samples Reveals Changes in Mitochondrial Protein Levels in Parathyroid Hyperplasia over Adenoma

PubMed Central

AKPINAR, GURLER; KASAP, MURAT; CANTURK, NUH ZAFER; ZULFIGAROVA, MEHIN; ISLEK, EYLÜL ECE; GULER, SERTAC ATA; SIMSEK, TURGAY; CANTURK, ZEYNEP

2017-01-01

Background/Aim: To unveil the pathophysiology of primary hyperparathyroidism, molecular details of parathyroid hyperplasia and adenoma have to be revealed. Such details will provide the tools necessary for differentiation of these two look-alike diseases. Therefore, in the present study, a comparative proteomic study using postoperative tissue samples from the parathyroid adenoma and parathyroid hyperplasia patients was performed. Materials and Methods: Protein extracts were prepared from tissue samples (n=8 per group). Protein pools were created for each group and subjected to DIGE and conventional 2DE. Following image analysis, spots representing the differentially regulated proteins were excised from the and used for identification via MALDI-TOF/TOF analysis. Results: The identities of 40 differentially-expressed proteins were revealed. Fourteen of these proteins were over-expressed in the hyperplasia while 26 of them were over-expressed in the adenoma. Conclusion: Most proteins found to be over-expressed in the hyperplasia samples were mitochondrial, underlying the importance of the mitochondrial activity as a potential biomarker for differentiation of parathyroid hyperplasia from adenoma. PMID:28446534

The histological and histometrical effects of Urtica dioica extract on rat's prostate hyperplasia.

PubMed

Moradi, Hamid Reza; Erfani Majd, Naeem; Esmaeilzadeh, Saleh; Fatemi Tabatabaei, Sayed Reza

2015-01-01

Benign prostatic hyperplasia (BPH) is a common disease in human that gradual overgrowth of the prostate gland leads to impinge on the urethra with impairment in urinary function. Numerous plants improve uncontrolled growth of the prostate gland and improve urinary tract symptoms associated with BPH. In this study, 25 healthy adult male Wistar rats were divided randomly in five groups: G1 (Control group) received ordinary feed without any treatment, G2 received 10 mg kg(-1) testosterone subcutaneously, G3 received 50 mg kg(-1) nettle root extract orally, G4 received 50 mg kg(-1) nettle root extract orally and 10 mg kg(-1) testosterone, G5 received 10 mg kg(-1) almond oil (Almond oil was used as testosterone solvent) subcutaneously. After six weeks, volume and weight of each lobe were measured and samples were taken. The 5 to 6 µm thickness sections were made using paraffin embedding method and stained by hematoxylin and eosin and periodic acid-Schiff. The results showed that prostate volume and ratio of prostate to body weight were increased significantly in the testosterone. Histological and histometrical results showed that dorsal and lateral type 1 and 2 lobes were not changed significantly but the ventral and anterior lobes have changed significantly. Over all, the nettle root could prevent from some of prostatic hyperplasia effects, so that percentage of folded alveoli in ventral lobe reduced insignificantly.

Thymic hyperplasia in a patient with Grave's disease.

PubMed

Hamzaoui, Amira A; Klii, Rim R; Salem, Randa R; Kochtali, Ines I; Golli, Mondher M; Mahjoub, Silvia S

2012-02-09

Hyperplastic changes of the thymus may be found in patients with Graves' disease. However, this rarely presents as an anterior mediastinal mass, particularly among adults. In this report, we describe a 46-year old woman with Graves' disease and thymic hyperplasia.

A Study of Using Massage Therapy Accompanied with Stretching Exercise for Rehabilitation of Mammary Gland Hyperplasia.

PubMed

Lv, Pin; Chong, Yuping; Zou, Huagang; Chen, Xiangxian

2016-01-01

To apply massage therapy accompanied with stretching exercises for treatment of mammary gland hyperplasia, evaluate the clinical outcome in patients, and estimate the therapy as a novel treatment method for mammary hyperplasia. 28 adult female patients were selected and treated with massage therapy and stretching exercises focusing on skeleton muscles of chest, abdomen, and axilla. The mammary gland oxyhemoglobin (OxyHb) and deoxyhemoglobin (DeoxyHb) levels were detected before and after treatment after 15, 30, and 45 days. In this cohort, pretreatment OxyHb (mean ± SD) is 1.32 ± 0.14 (medium-high), and DeoxyHb is 0.87 ± 0.13 (normal). All patients were clinically diagnosed with benign mammary gland hyperplasia and mastitis. The posttreatment OxyHb levels are 1.23 ± 0.09 (normal-medium, 15-day), 1.16 ± 0.08 (normal, 30-day), and 1.05 ± 0.04 (normal, 45-day), and DeoxyHb levels are 0.90 ± 0.11 (normal, 15-day), 0.94 ± 0.18 (normal, 30-day), and 0.98 ± 0.12 (normal, 45-day). Patients were diagnosed with decreased hyperplasia 15 and 30 days after treatment and with no symptom of hyperplasia in mammary gland 45 days after treatment. Mammary gland hyperplasia is closely correlated with pathological changes of skeletal muscles and could be significantly improved by massage therapy and stretching exercises targeting neighboring skeletal muscles.

Multifocal epithelial hyperplasia: a forgotten condition in the elderly.

PubMed

Shamloo, Nafiseh; Mortazavi, Hamed; Taghavi, Nasim; Baharvand, Maryam

2016-01-01

Multifocal epithelial hyperplasia (MEH), also known as focal epithelial hyperplasia and Heck disease, is a relatively rare condition caused by the human papillomavirus. This case report describes a 92-year-old man who presented with multiple, asymptomatic, circumscribed, soft, flattened papules in different sizes on the retrocommissure of his lower lip. The lesions were of 2 months' duration and had the same coloration as the adjacent normal mucosa. Histopathologic examination showed orthokeratinized stratified squamous epithelium with acanthosis, some areas of club-shaped rete ridges, and a few superficial epithelial cells with koilocytic changes and a mitosoid-like appearance. A diagnosis of MEH was established. Although MEH tends to occur in the first 2 decades of life, it can be encountered in elderly patients as well.

Prognosis of thymectomy in myasthenia gravis patients with thymus hyperplasia.

PubMed

Yang, Jing; Liu, Chanchan; Li, Tao; Li, Chengyan

2017-09-01

To compare the post-thymectomy prognosis in different conditions of myasthenia gravis (MG) patients with thymus hyperplasia. Collecting medical record and carrying out the follow-up study of 123 myasthenia gravis patients with thymus hyperplasia who have underwent thymectomy during the period between 2003 and 2013. Dividing into different groups based on gender, age of onset, duration of disease and Myasthenia Gravis Association of America (MGFA) clinical classification to analyze different prognosis in different groups. Complete stable remission (CSR) was achieved in 71 of 123 patients (59.5%). There is no gender-related difference in achieving CSR. Patients with early onset of MG (≤40 years old) or disease duration less than 12 months had significantly higher CSR rates than those with late onset of MG (>40 years old) or disease duration more than 12 months respectively, while no difference was found in remission rate between MGFA clinical classification I and MGFA II. Myasthenia gravis patients with thymus hyperplasia who had thymectomy are proved to possess greater chance of achieving CSR. The onset age of disease and duration are the prognostic factors.

Effects of pumpkin seed oil and saw palmetto oil in Korean men with symptomatic benign prostatic hyperplasia.

PubMed

Hong, Heeok; Kim, Chun-Soo; Maeng, Sungho

2009-01-01

This study was to investigate the role of complementary and alternative medicine in the prevention and treatment of benign prostatic hyperplasia. For this purpose, a randomized, double-blind, placebo-controlled trial was performed over 12 months on 47 benign prostatic hyperplasia patients with average age of 53.3 years and international prostate symptom score over 8. Subjects received either sweet potato starch (group A, placebo, 320 mg/day), pumpkin seed oil (group B, 320 mg/day), saw palmetto oil (group C, 320 mg/day) or pumpkin seed oil plus saw palmetto oil (group D, each 320 mg/day). International prostate symptom score, quality of life, serum prostate specific antigen, prostate volume and maximal urinary flow rate were measured. In groups B, C and D, the international prostate symptom score were reduced by 3 months. Quality of life score was improved after 6 months in group D, while those of groups B and C were improved after 3 months, compared to the baseline value. Serum prostate specific antigen was reduced only in group D after 3 months, but no difference was observed in prostate volume in all treatment groups. Maximal urinary flow rate were gradually improved in groups B and C, with statistical significance after 6 months in group B and after 12 months in group C. None of the parameters were significantly improved by combined treatment with pumpkin seed oil and saw palmetto oil. From these results, it is suggested that administrations of pumpkin seed oil and saw palmetto oil are clinically safe and may be effective as complementary and alternative medicine treatments for benign prostatic hyperplasia.

Effects of pumpkin seed oil and saw palmetto oil in Korean men with symptomatic benign prostatic hyperplasia

PubMed Central

Hong, Heeok; Kim, Chun-Soo

2009-01-01

This study was to investigate the role of complementary and alternative medicine in the prevention and treatment of benign prostatic hyperplasia. For this purpose, a randomized, double-blind, placebo-controlled trial was performed over 12 months on 47 benign prostatic hyperplasia patients with average age of 53.3 years and international prostate symptom score over 8. Subjects received either sweet potato starch (group A, placebo, 320 mg/day), pumpkin seed oil (group B, 320 mg/day), saw palmetto oil (group C, 320 mg/day) or pumpkin seed oil plus saw palmetto oil (group D, each 320 mg/day). International prostate symptom score, quality of life, serum prostate specific antigen, prostate volume and maximal urinary flow rate were measured. In groups B, C and D, the international prostate symptom score were reduced by 3 months. Quality of life score was improved after 6 months in group D, while those of groups B and C were improved after 3 months, compared to the baseline value. Serum prostate specific antigen was reduced only in group D after 3 months, but no difference was observed in prostate volume in all treatment groups. Maximal urinary flow rate were gradually improved in groups B and C, with statistical significance after 6 months in group B and after 12 months in group C. None of the parameters were significantly improved by combined treatment with pumpkin seed oil and saw palmetto oil. From these results, it is suggested that administrations of pumpkin seed oil and saw palmetto oil are clinically safe and may be effective as complementary and alternative medicine treatments for benign prostatic hyperplasia. PMID:20098586

Symptomatic and asymptomatic benign prostatic hyperplasia: Molecular differentiation by using microarrays

NASA Astrophysics Data System (ADS)

Prakash, Kulkarni; Pirozzi, Gregorio; Elashoff, Michael; Munger, William; Waga, Iwao; Dhir, Rajiv; Kakehi, Yoshiyuki; Getzenberg, Robert H.

2002-05-01

Benign prostatic hyperplasia (BPH) is a disease of unknown etiology that significantly affects the quality of life in aging men. Histologic BPH may present itself either as symptomatic or asymptomatic in nature. To elucidate the molecular differences underlying BPH, gene expression profiles from the prostate transition zone tissue have been analyzed by using microarrays. A set of 511 differentially expressed genes distinguished symptomatic and asymptomatic BPH. This genetic signature separates BPH from normal tissue but does not seem to change with age. These data could provide novel approaches for alleviating symptoms and hyperplasia in BPH.

Vascular Proteomics Reveal Novel Proteins Involved in SMC Phenotypic Change: OLR1 as a SMC Receptor Regulating Proliferation and Inflammatory Response

PubMed Central

Kang, Dong Hoon; Choi, Mina; Chang, Soyoung; Lee, Min Young; Lee, Doo Jae; Choi, Kyungsun; Park, Junseong; Han, Eun Chun; Hwang, Daehee; Kwon, Kihwan; Jo, Hanjoong; Choi, Chulhee; Kang, Sang Won

2015-01-01

Neointimal hyperplasia of vascular smooth muscle cells (VSMC) plays a critical role in atherosclerotic plaque formation and in-stent restenosis, but the underlying mechanisms are still incompletely understood. We performed a proteomics study to identify novel signaling molecules organizing the VSMC hyperplasia. The differential proteomics analysis in a balloon-induced injury model of rat carotid artery revealed that the expressions of 44 proteins are changed within 3 days post injury. The combination of cellular function assays and a protein network analysis further demonstrated that 27 out of 44 proteins constitute key signaling networks orchestrating the phenotypic change of VSMC from contractile to epithelial-like synthetic. Among the list of proteins, the in vivo validation specifically revealed that six proteins (Rab15, ITR, OLR1, PDHβ, PTPε) are positive regulators for VSMC hyperplasia. In particular, the OLR1 played dual roles in the VSMC hyperplasia by directly mediating oxidized LDL-induced monocyte adhesion via NF-κB activation and by assisting the PDGF-induced proliferation/migration. Importantly, OLR1 and PDGFRβ were associated in close proximity in the plasma membrane. Thus, this study elicits the protein network organizing the phenotypic change of VSMC in the vascular injury diseases such as atherosclerosis and discovers OLR1 as a novel molecular link between the proliferative and inflammatory responses of VSMCs. PMID:26305474

Potential advantages of treatment of transplanted saphenous vein aorto-coronary artery bypass grafts with beta irradiation to prevent graft occlusion.

PubMed

Smith, R G

1997-01-01

Intimal proliferation or Neointimal hyperplasia (NIH) is a vascular lesion that often arises in arteries after balloon angioplasty or other vessel wall injuries. FIH is a vascular lesion that develops in autologous saphenous vein grafts (SVG) after transplantation into the aorto-coronary circulation or the peripheral vascular circulation. FIH shares elements of smooth muscle migration, proliferation and fibrous tissue deposition in common with nibrointimal proliferation (NIH). Either NIH of a coronary artery or FIH of a SVG obstruct the vascular lumen and result in myocardial dysfunction. Local radiotherapy has been used for several decades to reduce the post-operative recurrence of the fibrovascular proliferations of pterygia and keloids. Similarly, in animal and human experiments, endovascular radiotherapy has been shown to reduce arterial smooth muscle proliferation. Consideration of the similarities of vascular smooth muscle cell proliferation in NIH and FIH leads one to suggest that endovascular beta irradiation can reduce FIH as well as it reduces NIH. The goal of such treatment is to achieve a clinically significant decrease in the morbidity and mortality resulting from SVG occlusions. The potential for large reduction of the consequences of SVG occlusion, the very large number of patients at risk, and the simplicity of the proposed intervention encourages prompt scientific evaluation of this technique.

Thymic hyperplasia in a patient with Grave's disease

PubMed Central

2012-01-01

Hyperplastic changes of the thymus may be found in patients with Graves' disease. However, this rarely presents as an anterior mediastinal mass, particularly among adults. In this report, we describe a 46-year old woman with Graves' disease and thymic hyperplasia. PMID:22321290

High prevalence of atypical hyperplasia in the endometrium of patients with epithelial ovarian cancer.

PubMed

Mingels, Marjanka J J M; Masadah, Rina; Geels, Yvette P; Otte-Höller, Irene; de Kievit, Ineke M; van der Laak, Jeroen A W M; van Ham, Maaike A P C; Bulten, Johan; Massuger, Leon F A G

2014-08-01

The aim of the present study is to determine the prevalence of endometrial premalignancies in women diagnosed with epithelial ovarian cancer (EOC). Endometrial and ovarian specimens of 186 patients with EOC were retrospectively selected using the nationwide pathology network and registry, and sections were comprehensively reviewed: 136 (73%) serous, 19 (10%) endometrioid, 15 (8%) mucinous, seven (4%) clear cell, and nine (5%) undifferentiated. Immunohistochemical phenotypes were compared for patients with serous EOC with concurrent endometrial pathology. In 31%, endometrial (pre)malignancy was found: carcinoma in 3%, endometrial intraepithelial carcinoma (EIC) in 4%, and atypical hyperplasia in 24%. Atypical hyperplasia was found in 47% of endometrioid EOCs but in 7% to 33% of other subtypes. Body mass index was higher concurrent to atypical hyperplasia (P=.001). Serous EOC and EIC immunophenotypes were comparable, whereas atypical hyperplasia was expressed differently. Apart from synchronous endometrial carcinoma, endometrial premalignancies should be taken into account when determining optimal treatment for women diagnosed with EOC. Copyright© by the American Society for Clinical Pathology.

The therapeutic effects of docosahexaenoic acid on oestrogen/androgen-induced benign prostatic hyperplasia in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Chao; Luo, Fei; Zhou, Ying

Benign prostatic hyperplasia (BPH) is one of the major disorders of the urinary system in elderly men. Docosahexaenoic acid (DHA) is the main component of n-3 polyunsaturated fatty acids (n-3 PUFAs) and has nerve protective, anti-inflammatory and tumour-growth inhibitory effects. Here, the therapeutic potential of DHA in treating BPH was investigated. Seal oil effectively prevented the development of prostatic hyperplasia induced by oestradiol/testosterone in a rat model by suppressing the increase of the prostatic index (PI), reducing the thickness of the peri-glandular smooth muscle layer, inhibiting the proliferation of both prostate epithelial and stromal cells, and downregulating the expression ofmore » androgen receptor (AR) and oestrogen receptor α (ERα). An in vitro study showed that DHA inhibited the growth of the human prostate stromal cell line WPMY-1 and the epithelial cell line RWPE-1 in a dose- and time-dependent manner. In both cell lines, the DHA arrested the cell cycle in the G2/M phase. In addition, DHA also reduced the expression of ERα and AR in the WPMY-1 and RWPE-1 cells. These results indicate that DHA inhibits the multiplication of prostate stromal and epithelial cells through a mechanism that may involve cell cycle arrest and the downregulation of ERα and AR expression. - Highlights: • Seal oil prevents oestradiol/testosterone (E2/T)-induced BPH in castrated rats. • Seal oil downregulates the expression of oestrogen receptor α(ERα) and androgen receptor (AR) in rat BPH tissues. • DHA inhibits the growth of human prostate stromal and epithelial cells in vitro. • DHA arrests human prostate stromal and epithelial cells in the G2/M phase and downregulates the expression of cyclin B1. • DHA inhibits the expression of ERα and AR in human prostate stromal and epithelial cells.« less

CD8+ T cells induce thyroid epithelial cell hyperplasia and fibrosis.

PubMed

Yu, Shiguang; Fang, Yujiang; Sharav, Tumenjargal; Sharp, Gordon C; Braley-Mullen, Helen

2011-02-15

CD8(+) T cells can be important effector cells in autoimmune inflammation, generally because they can damage target cells by cytotoxicity. This study shows that activated CD8(+) T cells induce thyroid epithelial cell hyperplasia and proliferation and fibrosis in IFN-γ(-/-) NOD.H-2h4 SCID mice in the absence of CD4(+) T cells. Because CD8(+) T cells induce proliferation rather than cytotoxicity of target cells, these results describe a novel function for CD8(+) T cells in autoimmune disease. In contrast to the ability of purified CD8(+) T cells to induce thyrocyte proliferation, CD4(+) T cells or CD8 T cell-depleted splenocytes induced only mild thyroid lesions in SCID recipients. T cells in both spleens and thyroids highly produce TNF-α. TNF-α promotes proliferation of thyrocytes in vitro, and anti-TNF-α inhibits development of thyroid epithelial cell hyperplasia and proliferation in SCID recipients of IFN-γ(-/-) splenocytes. This suggests that targeting CD8(+) T cells and/or TNF-α may be effective for treating epithelial cell hyperplasia and fibrosis.

First in human evaluation of the vascular biocompatibility and biomechanical performance of a novel ultra high molecular weight amorphous PLLA bioresorbable scaffold in the absence of anti-proliferative drugs: Two-year imaging results in humans.

PubMed

Moncada, Miguel; Delgado, Juan A; Colombo, Antonio; Gasior, Pawel; Ramzipoor, Kamal; Estrada, Alex; Lee, Chang; Dokko, Danny; Granada, Juan F

2017-12-15

In this first-in-human study, we prospectively studied the vascular compatibility and mechanical performance of a novel bare ultra-high molecular weight amorphous PLLA bioresorbable scaffold (BRS, FORTITUDE®, Amaranth Medical, Mountain View, California) up to two years after implantation using multimodality imaging techniques. The vascular biocompatibility of polymers used in BRS has not been fully characterized in the absence of anti-proliferative drugs. A total of 10 patients undergoing single scaffold implantation were included in the final analysis and were followed up using optical coherence tomography (OCT) at 2-years. All devices were implanted under angiographic and intravascular ultrasound (IVUS) guidance. Angiographic and IVUS follow up was performed at 6 months. Additionally, angiography and OCT imaging were performed at 2-years. At 6 months, mean intra-scaffold angiographic MLD slightly decreased from baseline procedural values. However, at 2 years, mean angiographic MLD increased (post procedure; 2.9 [2.7, 3.1] mm vs. 6 months; 2.1 [1.6, 2.5] vs. 2 years; 2.4 [2.1, 2.6], P = .001). Also, angiographic percent diameter stenosis decreased and late lumen gain increased between 6 months and 2 years follow up. Mean neointimal hyperplasia volume assessed by IVUS at 6 months was 26% [15.2, 29.3]. At 2 years OCT follow up neointimal hyperplasia volume was 24.2% [19.4, 28.9]. No presence of neoatherosclerosis was identified in any of the analyzed cases. At 2 years, this novel PLLA-based BRS induced expansive vascular remodeling from 6 to 24 months, a biological phenomenon that appears to be independent of the presence of anti-proliferative drugs. © 2017 Wiley Periodicals, Inc.

Peri-strut low-intensity areas in optical coherence tomography correlate with peri-strut inflammation and neointimal proliferation: an in-vivo correlation study in the familial hypercholesterolemic coronary swine model of in-stent restenosis.

PubMed

Tellez, Armando; Afari, Maxwell E; Buszman, Piotr P; Seifert, Paul; Cheng, Yanping; Milewski, Krzysztof; McGregor, Jennifer C; Garza, Javier A; Roberts, Mary B; Yi, Geng Hua; Kaluza, Greg L; Granada, Juan F

2014-11-01

Peri-strut low-intensity area (PLI) is a common imaging finding during the evaluation of in-stent neointima using optical coherence tomography (OCT). We aimed to determine the biological significance of PLI by comparing in-vivo OCT images with the corresponding histological sections obtained from the familial hypercholesterolemic swine model of coronary stenosis. A total of 26 coronary vessels of nine familial hypercholesterolemic swine were injured with 30% balloon overstretch and then immediately followed by everolimus eluting or bare metal stent placement at 20% overstretch. At 30 days, all stented vessels were subjected to in-vivo OCT analysis and were harvested for histological evaluation. For OCT analysis, stent cross-sections (three per stent) were categorized into presence (PLI+) or absence (PLI-) of PLI. In histology, inflammation and fibrin deposition were scored semiquantitatively from 0 (none) to 3 (severe). PLI was found in 64.9% of stent sections. Peri-strut inflammation was more frequently observed in OCT sections PLI (+) compared with PLI (-) (56.0 vs. 7.4%, P=0.01). In contrast, peri-strut fibrin deposits was similar in both groups (PLI+=58.0% vs. PLI-=59.3%, P=0.94). Histological neointimal thickness was significantly higher in PLI (+) sections (mean±SE: 0.68±0.06 vs. 0.34±0.02 mm; P<0.01), yielding a higher percent area stenosis compared with PLI (-) (mean±SE: 59.0±4.4 vs. 34.1±2.2%, P<0.01). The PLI diagnostic sensitivity and specificity for inflammation were 80 and 76.1%, respectively (>56% PLI, area under the curve=0.86, P<0.01), whereas for fibrin deposition, the sensitivity and specificity were 42.2 and 76.1%, respectively (area under the curve=0.56, P=NS). Area under the receiver operating characteristic curve was significantly higher for identifying inflammation than fibrin (0.86 vs. 0.56, P<0.01). The severity of PLI correlated with the neointimal thickness when assessed by OCT (R=0.79, P<0.001). The presence of PLI in OCT

Long-term surgical-orthodontic management of hemimandibular hyperplasia.

PubMed

Bennett, Samuel C; Goonewardene, Mithran S

2016-05-01

Hemimandibular hyperplasia (HH), also known as hemimandibular hypertrophy, is characterised by excessive unilateral three-dimensional growth of the mandible after birth. Vertical unilateral elongation of the mandible becomes clinically evident as a rare form of vertical facial asymmetry. Aberrant growth of the facial skeleton affects the developing dentition and the dental compensatory mechanism is usually unable to maintain optimal occlusal relationships. The resulting malocclusion is effectively managed by combined surgical-orthodontic care to address the facial, skeletal and dental problems that confront clinicians. Orthodontists are advised to assess patients with HH during the post-treatment retention stage for continuing mandibular growth and assess the stability of treatment outcomes with long-term follow-up and records as required. To present a case of hemimandibular hyperplasia treated successfully by combined surgical-orthodontic care and evaluated for stability over a seven-year follow-up period. Surgical-orthodontic management was accomplished in four stages: 1) pre-surgical orthodontic; 21 surgical; 3) post-surgical orthodontic; and 4) post-treatment orthodontic retention. Complete orthodontic records, including extra- and intra-oral photographs, study models, and cephalograms plus panoramic radiographs were taken at the pretreatment, post-treatment, and seven-year orthodontic retention time-points. Facial, skeletal and dental goals were achieved in the three planes of space and the long-term stability of the treatment results was shown during a post-treatment orthodontic retention period of seven years. Hemimandibular hyperplasia is a true growth anomaly which may be managed effectively. Clinicians may expect successful long-term correction and stability by utilising a comprehensive surgical-orthodontic treatment approach.

Comparison of 99mTc-MDP SPECT qualitative vs quantitative results in patients with suspected condylar hyperplasia.

PubMed

López Buitrago, D F; Ruiz Botero, J; Corral, C M; Carmona, A R; Sabogal, A

To compare qualitative vs quantitative results of Single Photon Emission Computerised Tomography (SPECT), calculated from percentage of 99m Tc-MDP (methylene diphosphonate) uptake, in condyles of patients with a presumptive clinical diagnosis of condylar hyperplasia. A retrospective, descriptive study was conducted on the 99m Tc-MDP SPECT bone scintigraphy reports from 51 patients, with clinical impression of facial asymmetry related to condylar hyperplasia referred by their specialist in orthodontics or maxillofacial surgery, to a nuclear medicine department in order to take this type of test. Quantitative data from 99m Tc-MDP condylar uptake of each were obtained and compared with qualitative image interpretation reported by a nuclear medicine expert. The concordances between the 51 qualitative and quantitative reports results was established. The total sample included 32 women (63%) and 19 men (37%). The patient age range was 13-45 years (21±8 years). According to qualitative reports, 19 patients were positive for right side condylar hyperplasia, 12 for left side condylar hyperplasia, with 8 bilateral, and 12 negative. The quantitative reports diagnosed 16 positives for right side condylar hyperplasia, 10 for left side condylar hyperplasia, and 25 negatives. Nuclear medicine images are an important diagnostic tool, but the qualitative interpretation of the images is not as reliable as the quantitative calculation. The agreement between the two types of report is low (39.2%, Kappa=0.13; P>.2). The main limitation of quantitative reports is that they do not register bilateral condylar hyperplasia cases. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Pseudocarcinomatous hyperplasia of the fallopian tube mimicking tubal cancer: a radiological and pathological diagnostic challenge.

PubMed

Lee, Nam Kyung; Choi, Kyung Un; Han, Ga Jin; Kwon, Byung Su; Song, Yong Jung; Suh, Dong Soo; Kim, Ki Hyung

2016-11-14

Pseudocarcinomatous hyperplasia of the fallopian tube is a rare, benign disease characterized by florid epithelial hyperplasia. The authors present the history and details of a 22-year-old woman with bilateral pelvic masses and a highly elevated serum CA-125 level (1,056 U/ml). Ultrasonography and magnetic resonance imaging (MRI) of the pelvis showed bilateral adnexal complex cystic masses with a fusiform or sausage-like shape. Contrast-enhanced fat-suppressed T1-weighted images showed enhancement of papillary projections of the right adnexal mass and enhancement of an irregular thick wall on the left adnexal mass, suggestive of tubal cancer. Based on MRI and laboratory findings, laparotomy was performed under a putative preoperative diagnosis of tubal cancer. The final pathologic diagnosis was pseudocarcinomatous hyperplasia of tubal epithelium associated with acute and chronic salpingitis in both tubes. The authors report a rare case of pseudocarcinomatous hyperplasia of the fallopian tubes mimicking tubal cancer.

Treatment of Low-Risk Endometrial Cancer and Complex Atypical Hyperplasia With the Levonorgestrel-Releasing Intrauterine Device.

PubMed

Pal, Navdeep; Broaddus, Russell R; Urbauer, Diana L; Balakrishnan, Nyla; Milbourne, Andrea; Schmeler, Kathleen M; Meyer, Larissa A; Soliman, Pamela T; Lu, Karen H; Ramirez, Pedro T; Ramondetta, Lois; Bodurka, Diane C; Westin, Shannon N

2018-01-01

To assess efficacy of the levonorgestrel-releasing intrauterine device (LNG-IUD) for treatment of complex atypical hyperplasia or low-grade endometrial cancer. This retrospective case series included all patients treated with the LNG-IUD for complex atypical hyperplasia or early-grade endometrial cancer from January 2003 to June 2013. Response rates were calculated and the association of response with clinicopathologic factors, including age, body mass index, and uterine size, was determined. Forty-six patients diagnosed with complex atypical hyperplasia or early-grade endometrial cancer were treated with the LNG-IUD. Of 32 evaluable patients at the 6-month time point, 15 had complex atypical hyperplasia (47%), nine had G1 endometrial cancer (28%), and eight had grade 2 endometrial cancer (25%). Overall response rate was 75% (95% CI 57-89) at 6 months; 80% (95% CI 52-96) in complex atypical hyperplasia, 67% (95% CI 30-93) in grade 1 endometrial cancer, and 75% (CI 35-97) in grade 2 endometrial cancer. Of the clinicopathologic features evaluated, there was a trend toward the association of lack of exogenous progesterone effect in the pathology specimen with nonresponse to the IUD (P=.05). Median uterine diameter was 1.3 cm larger in women who did not respond to the IUD (P=.04). Levonorgestrel-releasing IUD therapy for the conservative treatment of complex atypical hyperplasia or early-grade endometrial cancer resulted in return to normal histology in a majority of patients.

Correlation between nasopharyngoscopy and cephalometry in the diagnosis of hyperplasia of the pharyngeal tonsils

PubMed Central

Ritzel, Rodrigo Agne; Berwig, Luana Cristina; da Silva, Ana Maria Toniolo; Corrêa, Eliane Castilhos Rodrigues; Serpa, Eliane Oliveira

2012-01-01

Summary Introduction: Hyperplasia of the pharyngeal tonsil is one of the main causes of mouth breathing, and accurate diagnosis of this alteration is important for proper therapeutic planning. Therefore, studies have been conducted in order to provide information regarding the procedures that can be used for the diagnosis of pharyngeal obstruction. Objective: To verify the correlation between nasopharyngoscopy and cephalometric examinations in the diagnosis of pharyngeal tonsil hyperplasia. Method: This was a cross-sectional, clinical, experimental, and quantitative study. Fifty-five children took part in this study, 30 girls and 25 boys, aged between 7 and 11 years. The children underwent nasofibropharyngoscopic and cephalometric evaluation to determine the grade of nasopharyngeal obstruction. The Spearman's rank correlation coefficient at the 5% significance level was used to verify the correlation between these exams. Results: In the nasopharyngoscopy evaluation, most children showed grade 2 and 3 hyperplasia of the pharyngeal tonsil, which was followed by grade 1. In the cephalometry assessment, most children showed grade 1 hyperplasia of the pharyngeal tonsil, which was followed by grade 2. A statistically significant regular positive correlation was observed between the exams. Conclusion: It was concluded that the evaluation of the pharyngeal tonsil hyperplasia could be carried out by fiber optic nasopharyngoscopy and cephalometry, as these examinations were regularly correlated. However, it was found that cephalometry tended to underestimate the size of the pharyngeal tonsil relative to nasopharyngoscopy. PMID:25991937

Angiolymphoid hyperplasia with eosinophilia versus Kimura's disease: a case report and a clinical and histopathological comparison*

PubMed Central

de Bastos, Julien Totti; da Rocha, Camila Roos Mariano; Silva, Priscila Mara Chaves e; de Freitas, Bruno Messias Pires; Cassia, Flávia de Freire; Avelleira, João Carlos Regazzi

2017-01-01

Angiolymphoid hyperplasia with eosinophilia is a rare and benign vascular tumor whose etiology remains uncertain. It clinically presents itself by angiomatous papules or nodules located on the head and neck. Many controversies in the literature are found in relation to angiolymphoid hyperplasia with eosinophilia and Kimura's disease - its main differential diagnosis - due to their clinical and histopathological similarities. However, currently, most studies agree that they are distinct diseases. The present case illustrates a characteristic description of angiolymphoid hyperplasia with eosinophilia and also highlights the main differences with Kimura's disease. PMID:29186256

Effects of angiopoietin-1 on inflammatory injury in endothelial progenitor cells and blood vessels.

PubMed

Wang, Yi-Qing; Song, Jing-Jin; Han, Xiao; Liu, Yi-Ye; Wang, Xi-Huang; Li, Zhi-Ming; Tzeng, Chi-Meng

2014-01-01

Endothelial progenitor cells (EPCs) and angiopoietin-1 (Ang-1) play important roles in vasculogenesis and angiogenesis, respectively. Thus, targeting both aspects of cardiovascular tissue regeneration may offer promising therapeutic options for cardiovascular disorders. To this end, we constructed a lentiviral vector (pNL) with the Ang-1 gene and transfected EPCs with it (Ang-1-EPCs) to investigate vasculogenesis in both cellular and animal models. Compared to controls, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) increased significantly in both untreated EPCs and in the pNL vector group. After Ang-1 transcription, ICAM-1 and VCAM-1 decreased considerably in those treatment groups. Ang-1-modified EPCs alleviated inflammatory responses induced by tumor-necrosis factor-α (TNF-α) in vitro. Moreover, Ang-1-EPC implantation inhibited neointimal hyperplasia after balloon catheter injury in rats, dramatically diminishing the intimal-media (I/M) ratio and decreasing the neointimal area. Proliferating cell nuclear antigen expression in the Ang-1-EPC group was lower than the EPC non-treatment group as well, suggesting that Ang-1-EPC improved cell survival during inflammation and promoted endothelialization in damaged blood vessels.

The common parasite Toxoplasma gondii induces prostatic inflammation and microglandular hyperplasia in a mouse model.

PubMed

Colinot, Darrelle L; Garbuz, Tamila; Bosland, Maarten C; Wang, Liang; Rice, Susan E; Sullivan, William J; Arrizabalaga, Gustavo; Jerde, Travis J

2017-07-01

Inflammation is the most prevalent and widespread histological finding in the human prostate, and associates with the development and progression of benign prostatic hyperplasia and prostate cancer. Several factors have been hypothesized to cause inflammation, yet the role each may play in the etiology of prostatic inflammation remains unclear. This study examined the possibility that the common protozoan parasite Toxoplasma gondii induces prostatic inflammation and reactive hyperplasia in a mouse model. Male mice were infected systemically with T. gondii parasites and prostatic inflammation was scored based on severity and focality of infiltrating leukocytes and epithelial hyperplasia. We characterized inflammatory cells with flow cytometry and the resulting epithelial proliferation with bromodeoxyuridine (BrdU) incorporation. We found that T. gondii infects the mouse prostate within the first 14 days of infection and can establish parasite cysts that persist for at least 60 days. T. gondii infection induces a substantial and chronic inflammatory reaction in the mouse prostate characterized by monocytic and lymphocytic inflammatory infiltrate. T. gondii-induced inflammation results in reactive hyperplasia, involving basal and luminal epithelial proliferation, and the exhibition of proliferative inflammatory microglandular hyperplasia in inflamed mouse prostates. This study identifies the common parasite T. gondii as a new trigger of prostatic inflammation, which we used to develop a novel mouse model of prostatic inflammation. This is the first report that T. gondii chronically encysts and induces chronic inflammation within the prostate of any species. Furthermore, T. gondii-induced prostatic inflammation persists and progresses without genetic manipulation in mice, offering a powerful new mouse model for the study of chronic prostatic inflammation and microglandular hyperplasia. © 2017 Wiley Periodicals, Inc.

Changes in initial expenditures for benign prostatic hyperplasia evaluation in the Medicare population: a comparison to overall Medicare inflation.

PubMed

Bellinger, Adam S; Elliott, Sean P; Yang, Liu; Wei, John T; Saigal, Christopher S; Smith, Alexandria; Wilt, Timothy J; Strope, Seth A

2012-05-01

Benign prostatic hyperplasia creates significant expenses for the Medicare program. We determined expenditure trends for benign prostatic hyperplasia evaluative testing after urologist consultation and placed these trends in the context of overall Medicare expenditures. Using a 5% national sample of Medicare beneficiaries from 2000 to 2007 we developed a cohort of 40,253 with claims for new visits to urologists for diagnoses consistent with symptomatic benign prostatic hyperplasia. We assessed trends in initial inflation and geography adjusted expenditures within 12 months of diagnosis by evaluative test categories derived from the 2003 American Urological Association guideline on the management of benign prostatic hyperplasia. Using governmental reports on Medicare expenditure trends for benign prostatic hyperplasia we compared expenditures to overall and imaging specific Medicare expenditures. Comparisons were assessed by the Z-test and regression analysis for linear trends, as appropriate. Between 2000 and 2007 inflation adjusted total Medicare expenditures per patient for the initial evaluation of patients with benign prostatic hyperplasia seen by urologists increased from $255.44 to $343.98 (p <0.0001). Benign prostatic hyperplasia related imaging increases were significantly less than overall Medicare imaging expenditure increases (55% vs 104%, p <0.001). The increase in per patient expenditures for benign prostatic hyperplasia was significantly lower than the increase in overall Medicare expenditures per enrollee (35% vs 45%, p = 0.0015). From 2000 to 2007 inflation adjusted expenditures increased for benign prostatic hyperplasia related evaluations. This growth was slower than the overall growth in Medicare expenditures. The increase in BPH related imaging expenditures was restrained compared to that of the Medicare program as a whole. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights

Focal nodular hyperplasia with major sinusoidal dilatation: a misleading entity

PubMed Central

Laumonier, Hervé; Frulio, Nora; Laurent, Christophe; Balabaud, Charles; Zucman-Rossi, Jessica; Bioulac-Sage, Paulette

2010-01-01

Focal nodular hyperplasia (FNH) is a benign liver lesion thought to be a non-specific response to locally increased blood flow. Although the diagnosis of FNH and hepatocellular adenoma (HCA) has made great progress over the last few years using modern imaging techniques, there are still in daily practice some difficulties concerning some atypical nodules. Here, the authors report the case of a 47-year-old woman with a single liver lesion thought to be, by imaging, an inflammatory HCA with major sinusoidal congestion. This nodule was revealed to be, at the microscopical level and after specific immunostaining and molecular analysis, an FNH with sinusoidal dilatation (so-called telangiectatic focal nodular hyperplasia). PMID:22798311

Titanium-nitride-oxide-coated coronary stents: insights from the available evidence.

PubMed

Karjalainen, Pasi P; Nammas, Wail

2017-06-01

Coating of stent surface with a biocompatible material is suggested to improve stent safety profile. A proprietary process was developed to coat titanium-nitride-oxide on the stent surface, based on plasma technology that uses the nano-synthesis of gas and metal. Preclinical in vitro and in vivo investigation confirmed blood compatibility of titanium (nitride-) oxide films. Titanium-nitride-oxide-coated stents demonstrated a better angiographic outcome, compared with bare-metal stents at mid-term follow-up; however, they failed to achieve non-inferiority for angiographic outcome versus second-generation drug-eluting stents. Observational studies showed adequate clinical outcome at mid-term follow-up. Non-randomized studies showed an outcome of titanium-nitride-oxide-coated stents comparable to - or better than - first-generation drug-eluting stents at long-term follow-up. Two randomized controlled trials demonstrated comparable efficacy outcome, and a better safety outcome of titanium-nitride-oxide-coated stents versus drug-eluting stents at long-term follow-up. Evaluation by optical coherence tomography at mid-term follow-up revealed better neointimal strut coverage associated with titanium-nitride-oxide-coated stents versus drug-eluting stents; yet, neointimal hyperplasia thickness was greater. Key messages Stents coated with titanium-nitride-oxide demonstrated biocompatibility in preclinical studies: they inhibit platelet and fibrin deposition, and reduce neointimal growth. In observational and non-randomized studies, titanium-nitride-oxide-coated stents were associated with adequate safety and efficacy outcome. In randomized trials of patients with acute coronary syndrome, titanium-nitride-oxide-coated stents were associated with a better safety outcome, compared with drug-eluting stents; efficacy outcome was comparable.

Finasteride Reduces the Risk of Incident Clinical Benign Prostatic Hyperplasia

PubMed Central

Parsons, J. Kellogg; Schenk, Jeannette M.; Arnold, Kathryn B.; Messer, Karen; Till, Cathee; Thompson, Ian M.; Kristal, Alan R.

2014-01-01

Background Despite the high prevalence of clinical benign prostatic hyperplasia (BPH) among older men, there remains a notable absence of studies focused on BPH prevention. Objective To determine if finasteride prevents incident clinical BPH in healthy older men. Design, setting, and participants Data for this study are from the Prostate Cancer Prevention Trial. After excluding those with a history of BPH diagnosis or treatment, or an International Prostate Symptom Score (IPSS) ≥8 at study entry, 9253 men were available for analysis. Outcome measurements and statistical analysis The primary outcome was incident clinical BPH, defined as the initiation of medical treatment, surgery, or sustained, clinically significant urinary symptoms (IPSS >14). Finasteride efficacy was estimated using Cox proportional regression models to generate hazards ratios (HRs). Results and limitations Mean length of follow-up was 5.3 yr. The rate of clinical BPH was 19 per 1000 person-years in the placebo arm and 11 per 1000 person-years in the finasteride arm (p < 0.001). In a covariate-adjusted model, finasteride reduced the risk of incident clinical BPH by 40% (HR: 0.60; 95% confidence interval, 0.51–0.69; p < 0.001). The effect of finasteride on incident clinical BPH was attenuated in men with a body mass index ≥30 kg/m2 (pinteraction = 0.04) but otherwise did not differ significantly by physical activity, age, race, current diabetes, or current smoking. The post hoc nature of the analysis is a potential study limitation. Conclusions Finasteride substantially reduces the risk of incident clinical BPH in healthy older men. These results should be considered in formulating recommendations for the use of finasteride to prevent prostate diseases in asymptomatic older men. PMID:22459892

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palena, Luis Mariano, E-mail: marianopalena@hotmail.com; Cester, Giacomo; Manzi, Marco

In-stent reocclusion is a frequent complication of endovascular treatment and stenting, especially in the superficial femoral artery. Neointimal hyperplasia is the main cause of this problem, but in many cases, it occurs as a result of the presence of stent strut fractures. The two treatment options are endovascular and surgical intervention. The effectiveness of endovascular interventions in patients with critical limb ischemia has been well established, but in some cases, crossing the occluded stent is difficult. We describe a new technique to recanalize long in-stent superficial femoral artery occlusions characterized by direct stent puncture, followed by retrograde-antegrade recanalization after antegrademore » failures.« less

Adrenomegaly and septic adrenal hemorrhage (Waterhouse-Friderichsen syndrome) in the setting of congenital adrenal hyperplasia.

PubMed

Saad, Amin F; Ford, Kenneth L; Deprisco, Gregory; Smerud, Michael J

2013-07-01

Congenital adrenal hyperplasia refers to a spectrum of autosomal recessive inherited disorders of steroidogenesis most commonly identified on newborn screenings. We describe a young woman who presented with abdominal pain and on subsequent imaging was found to have features of congenital adrenal hyperplasia. Imaging findings, treatment, and potential complications are discussed.

The histological and histometrical effects of Urtica dioica extract on rat’s prostate hyperplasia

PubMed Central

Moradi, Hamid Reza; Erfani Majd, Naeem; Esmaeilzadeh, Saleh; Fatemi Tabatabaei, Sayed Reza

2015-01-01

Benign prostatic hyperplasia (BPH) is a common disease in human that gradual overgrowth of the prostate gland leads to impinge on the urethra with impairment in urinary function. Numerous plants improve uncontrolled growth of the prostate gland and improve urinary tract symptoms associated with BPH. In this study, 25 healthy adult male Wistar rats were divided randomly in five groups: G1 (Control group) received ordinary feed without any treatment, G2 received 10 mg kg-1 testosterone subcutaneously, G3 received 50 mg kg-1 nettle root extract orally, G4 received 50 mg kg-1 nettle root extract orally and 10 mg kg-1 testosterone, G5 received 10 mg kg-1 almond oil (Almond oil was used as testosterone solvent) subcutaneously. After six weeks, volume and weight of each lobe were measured and samples were taken. The 5 to 6 µm thickness sections were made using paraffin embedding method and stained by hematoxylin and eosin and periodic acid-Schiff. The results showed that prostate volume and ratio of prostate to body weight were increased significantly in the testosterone. Histological and histometrical results showed that dorsal and lateral type 1 and 2 lobes were not changed significantly but the ventral and anterior lobes have changed significantly. Over all, the nettle root could prevent from some of prostatic hyperplasia effects, so that percentage of folded alveoli in ventral lobe reduced insignificantly. PMID:25992248

Adrenomegaly and septic adrenal hemorrhage (Waterhouse-Friderichsen syndrome) in the setting of congenital adrenal hyperplasia

PubMed Central

Ford, Kenneth L.; dePrisco, Gregory; Smerud, Michael J.

2013-01-01

Congenital adrenal hyperplasia refers to a spectrum of autosomal recessive inherited disorders of steroidogenesis most commonly identified on newborn screenings. We describe a young woman who presented with abdominal pain and on subsequent imaging was found to have features of congenital adrenal hyperplasia. Imaging findings, treatment, and potential complications are discussed. PMID:23814386

Large telangiectatic focal nodular hyperplasia presenting with normal radionuclide studies: Case report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peterfy, C.G.; Rosenthall, L.

1990-12-01

A 9 cm-lesion of telangiectatic focal nodular hyperplasia was incidentally identified in a 31-yr-old female. Despite a typical appearance by X-ray computed tomography and ultrasonography, scintigraphy with technetium-99m-({sup 99m}Tc) colloid, {sup 99m}Tc-diethyliminodiacetic acid, and {sup 99m}Tc-labeled red cells failed to demonstrate any abnormalities. These findings are felt to reflect the relative lack of architectural disruption that histologically characterizes this particular lesion. The present report described the imaging characteristics of the telangiectatic form of focal nodular hyperplasia.

Impact of preventive therapy on the risk of breast cancer among women with benign breast disease.

PubMed

Cuzick, Jack; Sestak, Ivana; Thorat, Mangesh A

2015-11-01

There are three main ways in which women can be identified as being at high risk of breast cancer i) family history of breast and/or ovarian cancer, which includes genetic factors ii) mammographically identified high breast density, and iii) certain types of benign breast disease. The last category is the least common, but in some ways the easiest one for which treatment can be offered, because these women have already entered into the treatment system. The highest risk is seen in women with lobular carcinoma in situ (LCIS), but this is very rare. More common is atypical hyperplasia (AH), which carries a 4-5-fold risk of breast cancer as compared to general population. Even more common is hyperplasia of the usual type and carries a roughly two-fold increased risk. Women with aspirated cysts are also at increased risk of subsequent breast cancer. Tamoxifen has been shown to be particularly effective in preventing subsequent breast cancer in women with AH, with a more than 70% reduction in the P1 trial and a 60% reduction in IBIS-I. The aromatase inhibitors (AIs) also are highly effective for AH and LCIS. There are no published data on the effectiveness of tamoxifen or the AIs for breast cancer prevention in women with hyperplasia of the usual type, or for women with aspirated cysts. Improving diagnostic consistency, breast cancer risk prediction and education of physicians and patients regarding therapeutic prevention in women with benign breast disease may strengthen breast cancer prevention efforts. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Impact of preventive therapy on the risk of breast cancer among women with benign breast disease

PubMed Central

Cuzick, Jack; Sestak, Ivana; Thorat, Mangesh A.

2015-01-01

There are three main ways in which women can be identified as being at high risk of breast cancer i) family history of breast and/or ovarian cancer, which includes genetic factors ii) mammographically identified high breast density, and iii) certain types of benign breast disease. The last category is the least common, but in some ways the easiest one for which treatment can be offered, because these women have already entered into the treatment system. The highest risk is seen in women with lobular carcinoma in situ (LCIS), but this is very rare. More common is atypical hyperplasia (AH), which carries a 4–5-fold risk of breast cancer as compared to general population. Even more common is hyperplasia of the usual type and carries a roughly two-fold increased risk. Women with aspirated cysts are also at increased risk of subsequent breast cancer. Tamoxifen has been shown to be particularly effective in preventing subsequent breast cancer in women with AH, with a more than 70% reduction in the P1 trial and a 60% reduction in IBIS-I. The aromatase inhibitors (AIs) also are highly effective for AH and LCIS. There are no published data on the effectiveness of tamoxifen or the AIs for breast cancer prevention in women with hyperplasia of the usual type, or for women with aspirated cysts. Improving diagnostic consistency, breast cancer risk prediction and education of physicians and patients regarding therapeutic prevention in women with benign breast disease may strengthen breast cancer prevention efforts. PMID:26255741

Is intimal hyperplasia a marker of neuro-ophthalmic complications of giant cell arteritis?

PubMed

Makkuni, D; Bharadwaj, A; Wolfe, K; Payne, S; Hutchings, A; Dasgupta, B

2008-04-01

The ischaemic complications of giant cell arteritis (GCA) such as blindness and stroke may result from luminal narrowing of the affected arteries. This study focuses on the association between the severity of intimal proliferation on temporal artery biopsy (TAB) histology and neuro-ophthalmic complications (NOCs) of GCA. We identified 30 cases of biopsy-proven temporal arteritis. One histopathologist (blinded to the clinical details) evaluated the TAB specimens and categorized the degree of maximum stenosis due to intimal hyperplasia into four grades: grade 1 is <50% luminal occlusion due to intimal hyperplasia, grade 2 is 50-75%, grade 3 is >75% and grade 4 is complete luminal occlusion. A second histopathologist (also blinded to the clinical details) independently evaluated the TAB specimens using the same grading system. The NOCs in these patients were noted after a case record review. Of the 30 patients, 12 had NOC-10 with eye complications (complete visual loss, anterior ischaemic neuropathy, visual field defects), one patient had cerebral infarcts and one had both cerebral infarcts and vision loss. There was evidence for a statistically significant trend of NOC associated with higher intimal hyperplasia scores (P = 0.001). The scores of the histopathologists agreed for 23 (77%) patients and differed by 1 category for the remaining 7 (kappa-statistic 0.88). Our study suggests that the degree of intimal hyperplasia on TAB histology (routinely available to all hospital units) seems to be closely associated with NOCs of GCA. The study highlights the possible prognostic as well as diagnostic role of the biopsy. We feel that intimal hyperplasia noted in biopsy specimens may help us in the risk stratification of GCA patients and targeting of appropriate and novel therapies.

[The treatment of benign prostatic hyperplasia using the Mumie-Vitas preparation].

PubMed

Andriukhova, N N

1997-01-01

Overall thirty-eight patients presenting with stage I-II benign prostate hyperplasia received treatment with a new local drug preparation Mumiyo-Vitas, 0.2 g on a once- or twice-daily basis over six months. Effects were studied of the drug on the urologic symptomatology and quality of life of patients presenting with ongoing micturitional disturbances, functional state of detrusor vesicae, prostate volume and urethral resistance. Efficiency of the treatment given was assessed by the International system, uroflowmetry, ultrasonic investigation. Mumiyo-Vitas appeared to be of therapeutic benefit in those patients with subjective and objective symptoms of the urinary bladder obstruction who had innocent prostate hyperplasia.

Oral focal epithelial hyperplasia: report of 3 cases with human papillomavirus DNA sequencing analysis.

PubMed

Gültekin, S E; Tokman Yildirim, Benay; Sarisoy, S

2011-01-01

Focal epithelial hyperplasia (FEH), or Heck's disease, is a benign proliferative viral infection of the oral mucosa that is related to Human Papil-lomavirus (HPV), mainly subtypes 13 and 32. Although this condition is known to exist in numerous populations and ethnic groups, the reported cases among Caucasians are relatively rare. It presents as asymptomatic papules or nodules on the oral mucosa, gingiva, tongue, and lips. Histopathologically, it is characterized by parakeratosis, epithelial hyperplasia, focal acanthosis, fusion, and horizontal outgrowth of epithelial ridges and the cells named mitozoids. The purpose of this case report was to present 3 cases of focal epithelial hyperplasia in a pediatric age group. Histopathological and clinical features of cases are discussed and DNA sequencing analysis is reported in which HPV 13, HPV 32, and HPV 11 genomes are detected.

Extranodal posttransplant plasmacytic hyperplasia with subsequent posttransplant plasmacytic malignancy: six-year interval case report and review of the literature.

PubMed

Dunphy, Cherie H; Galambos, Csaba; Polski, Jacek M; Evans, H Lance; Gardner, Laura J; Grosso, Leonard E; Montone, Kathleen T

2002-03-01

Posttransplant lymphoproliferative disorders (PTLDs) represent a morphologic, immunophenotypic, and genotypic spectrum of disease. Most recently, Knowles et al divided PTLDs into 3 distinct categories: (1) plasmacytic hyperplasia, (2) polymorphic B-cell hyperplasia and polymorphic B-cell lymphoma, and (3) immunoblastic lymphoma and multiple myeloma. Although one form of PTLD may progress to another form, only 1 previous case has been reported in which multiple myeloma developed 14 months after an original diagnosis of plasmacytic hyperplasia. The type of solid organ transplant was not specified in that case. We report a post--cardiac transplant plasmacytic hyperplasia developing 7 years posttransplant. Six years subsequent to the plasmacytic hyperplasia, the patient developed a posttransplant plasmacytic malignancy, supported by morphology, flow cytometric immunophenotyping, and genotypic studies. Since we have no data to support disseminated bony disease or an abnormal serum protein, we have not used the term "multiple myeloma" for this case.

Cyclooxygenase 2 Promotes Parathyroid Hyperplasia in ESRD

PubMed Central

Zhang, Qian; Qiu, Junsi; Li, Haiming; Lu, Yanwen; Wang, Xiaoyun; Yang, Junwei; Wang, Shaoqing; Zhang, Liyin; Gu, Yong; Hao, Chuan-Ming

2011-01-01

Hyperplasia of the PTG underlies the secondary hyperparathyroidism (SHPT) observed in CKD, but the mechanism underlying this hyperplasia is incompletely understood. Because aberrant cyclooxygenase 2 (COX2) expression promotes epithelial cell proliferation, we examined the effects of COX2 on the parathyroid gland in uremia. In patients with ESRD who underwent parathyroidectomy, clusters of cells within the parathyroid glands had increased COX2 expression. Some COX2-positive cells exhibited two nuclei, consistent with proliferation. Furthermore, nearly 78% of COX2-positive cells expressed proliferating cell nuclear antigen (PCNA). In the 5/6-nephrectomy rat model, rats fed a high-phosphate diet had significantly higher serum PTH levels and larger parathyroid glands than sham-operated rats. Compared with controls, the parathyroid glands of uremic rats exhibited more PCNA-positive cells and greater COX2 expression in the chief cells. Treatment with COX2 inhibitor celecoxib significantly reduced PCNA expression, attenuated serum PTH levels, and reduced the size of the glands. In conclusion, COX2 promotes the pathogenesis of hyperparathyroidism in ESRD, suggesting that inhibiting the COX2 pathway could be a potential therapeutic target. PMID:21335517

Conditional Deletion of Pten Causes Bronchiolar Hyperplasia

PubMed Central

Davé, Vrushank; Wert, Susan E.; Tanner, Tiffany; Thitoff, Angela R.; Loudy, Dave E.; Whitsett, Jeffrey A.

2008-01-01

Tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid phosphatase that regulates multiple cellular processes including cell polarity, migration, proliferation, and carcinogenesis. In this work, we demonstrate that conditional deletion of Pten (PtenΔ/Δ) in the respiratory epithelial cells of the developing mouse lung caused epithelial cell proliferation and hyperplasia as early as 4 to 6 weeks of age. While bronchiolar cell differentiation was normal, as indicated by β-tubulin and FOXJ1 expression in ciliated cells and by CCSP expression in nonciliated cells, cell proliferation (detected by expression of Ki-67, phospho-histone-H3, and cyclin D1) was increased and associated with activation of the AKT/mTOR survival pathway. Deletion of Pten caused papillary epithelial hyperplasia characterized by a hypercellular epithelium lining papillae with fibrovascular cores that protruded into the airway lumens. Cell polarity, as assessed by subcellular localization of cadherin, β-catenin, and zonula occludens-1, was unaltered. PTEN is required for regulation of epithelial cell proliferation in the lung and for the maintenance of the normal simple columnar epithelium characteristics of bronchi and bronchioles. PMID:17921358

Conditional deletion of Pten causes bronchiolar hyperplasia.

PubMed

Davé, Vrushank; Wert, Susan E; Tanner, Tiffany; Thitoff, Angela R; Loudy, Dave E; Whitsett, Jeffrey A

2008-03-01

Tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid phosphatase that regulates multiple cellular processes including cell polarity, migration, proliferation, and carcinogenesis. In this work, we demonstrate that conditional deletion of Pten (Pten(Delta/Delta)) in the respiratory epithelial cells of the developing mouse lung caused epithelial cell proliferation and hyperplasia as early as 4 to 6 weeks of age. While bronchiolar cell differentiation was normal, as indicated by beta-tubulin and FOXJ1 expression in ciliated cells and by CCSP expression in nonciliated cells, cell proliferation (detected by expression of Ki-67, phospho-histone-H3, and cyclin D1) was increased and associated with activation of the AKT/mTOR survival pathway. Deletion of Pten caused papillary epithelial hyperplasia characterized by a hypercellular epithelium lining papillae with fibrovascular cores that protruded into the airway lumens. Cell polarity, as assessed by subcellular localization of cadherin, beta-catenin, and zonula occludens-1, was unaltered. PTEN is required for regulation of epithelial cell proliferation in the lung and for the maintenance of the normal simple columnar epithelium characteristics of bronchi and bronchioles.

MX-INDUCED URINARY BLADDER EPITHELIAL HYPERPLASIA IN EKER RATS

EPA Science Inventory

MX-INDUCED URINARY BLADDER EPITHELIAL HYPERPLASIA IN EKER RATS

Epidemiological studies have shown a positive association between chronic exposure to chlorinated drinking water and human cancer, particularly of the urinary bladder. MX (3- chloro-4-(dichloromethyl)-5-hydrox...

Canine prostate models in preclinical studies of minimally invasive interventions: part II, benign prostatic hyperplasia models

PubMed Central

Báez-Díaz, Claudia; Sánchez-Margallo, Francisco Miguel

2017-01-01

Canine prostate is widely used as animal model in the preclinical evaluation of emerging therapeutic interventions. Spontaneous benign prostatic hyperplasia (BPH) is common in adult intact male dogs with two distinct pathological types: glandular and complex form of prostatic hyperplasia. The complex form of prostatic hyperplasia, usually occurring in older dogs, represents an ideal model because of its unique pathologic feature, including not only glandular hyperplasia but also an increase in prostate stromal components. The limited commercial availability of adult dogs with spontaneous BPH motivates experimentally induced BPH in young dogs. Hormone-induced canine BPH model has been well established with various hormonal treatment regimens and administration approaches. The goal of this review is to provide the veterinary background in spontaneous BPH in dogs, summarize the techniques in hormonal induction of canine BPH, and highlight the pathological and clinical limitations of the canine models that may lead to distinct therapeutic responses compared to clinical trials in humans. PMID:28725598

Impact of Leukocyte Function-Associated Antigen-1 Blockade on Endogenous Allospecific T Cells to Multiple Minor Histocompatibility Antigen Mismatched Cardiac Allograft.

PubMed

Kwun, Jean; Farris, Alton B; Song, Hyunjin; Mahle, William T; Burlingham, William J; Knechtle, Stuart J

2015-12-01

Blocking leukocyte function-associated antigen (LFA)-1 in organ transplant recipients prolongs allograft survival. However, the precise mechanisms underlying the therapeutic potential of LFA-1 blockade in preventing chronic rejection are not fully elucidated. Cardiac allograft vasculopathy (CAV) is the preeminent cause of late cardiac allograft failure characterized histologically by concentric intimal hyperplasia. Anti-LFA-1 monoclonal antibody was used in a multiple minor antigen-mismatched, BALB.B (H-2B) to C57BL/6 (H-2B), cardiac allograft model. Endogenous donor-specific CD8 T cells were tracked down using major histocompatibility complex multimers against the immunodominant H4, H7, H13, H28, and H60 minor Ags. The LFA-1 blockade prevented acute rejection and preserved palpable beating quality with reduced CD8 T-cell graft infiltration. Interestingly, less CD8 T cell infiltration was secondary to reduction of T-cell expansion rather than less trafficking. The LFA-1 blockade significantly suppressed the clonal expansion of minor histocompatibility antigen-specific CD8 T cells during the expansion and contraction phase. The CAV development was evaluated with morphometric analysis at postoperation day 100. The LFA-1 blockade profoundly attenuated neointimal hyperplasia (61.6 vs 23.8%; P < 0.05), CAV-affected vessel number (55.3 vs 15.9%; P < 0.05), and myocardial fibrosis (grade 3.29 vs 1.8; P < 0.05). Finally, short-term LFA-1 blockade promoted long-term donor-specific regulation, which resulted in attenuated transplant arteriosclerosis. Taken together, LFA-1 blockade inhibits initial endogenous alloreactive T-cell expansion and induces more regulation. Such a mechanism supports a pulse tolerance induction strategy with anti-LFA-1 rather than long-term treatment.

Sebaceous hyperplasia of the vulva: a series of cases reporting no association with the Muir-Torre syndrome.

PubMed

Roma, Andres A; Barry, Jessica; Pai, Rish K; Billings, Steven D

2014-07-01

Sebaceous gland hyperplasia is a common skin condition, very rarely reported in the female genital region. We present 13 cases from 12 patients, the first case series of sebaceous gland hyperplasia of the vulva. Differences in age at presentation and clinical presentation compared with classic sebaceous gland hyperplasia from the head and neck region were noted. Also, it was rarely included in the clinical differential diagnosis. Immunohistochemical studies to determine any possible association with the Muir-Torre syndrome were performed and mismatch repair protein loss was not identified.

Temporal Evaluation of Cardiac Myocyte Hypertrophy and Hyperplasia in Male Rats Secondary to Chronic Volume Overload

PubMed Central

Du, Yan; Plante, Eric; Janicki, Joseph S.; Brower, Gregory L.

2010-01-01

The temporal myocardial remodeling induced by chronic ventricular volume overload in male rats was examined. Specifically, left ventricular (LV) cardiomyocyte length and width, sarcomere length, and number of nuclei were measured in male rats (n = 8 to 17) at 1, 3, 5, 7, 21, 35, and 56 days after creation of an infrarenal aortocaval fistula. In contrast to previously published reports of progressive increases in cardiomyocyte length and cross-sectional area at 5 days post-fistula and beyond in female hearts, cardiomyocyte length and width did not increase significantly in males during the first 35 days of volume overload. Furthermore, a significant decrease in cardiomyocyte length relative to age-matched controls, together with a reduced number of sarcomeres per cell, was noted in male hearts at 5 days post-fistula. There was a concurrent increase in the percentage of mononucleated cardiomyocytes from 11.6% to 18% at 5 days post-fistula. These initial differences could not be attributed to cardiomyocyte proliferation, and treatment with a microtubule stabilizing agent prevented them from occurring. The subsequent significant increase in LV weight without corresponding increases in cardiomyocyte dimensions is indicative of hyperplasia. Thus, these findings indicate hyperplasia resulting from cytokinesis of cardiomyocytes is a key mechanism, independent of hypertrophy, that contributes to the significant increase in LV mass in male hearts subjected to chronic volume overload. PMID:20651227

MMP-1 and MMP-8 expression in giant-cell fibroma and inflammatory fibrous hyperplasia.

PubMed

de Oliveira, Henrique Climeck; Tschoeke, André; da Cruz, Gabriele Claudino; Noronha, Lúcia; de Moraes, Rafaela Scariot; Mesquita, Ricardo Alves; de Aguiar, Maria Cássia Ferreira; Caldeira, Patrícia Carlos; de Oliveira Ribas, Marina; Grégio, Ana Maria Trindade; Alanis, Luciana Reis Azevedo; Ignácio, Sérgio Aparecido; Dos Santos, Jean Nunes; de Lima, Antonio Adilson Soares; Johann, Aline Cristina Batista Rodrigues

2016-12-01

The aim of this study is to compare the immunoexpression of metalloproteinases 1 and 8 in giant-cell fibroma, inflammatory fibrous hyperplasia and normal mucosa. Twenty-two cases of giant-cell fibroma, inflammatory fibrous hyperplasia and oral mucosa (control) each were subjected to immunohistochemistry using anti-metalloproteinase-1 and anti-metalloproteinase-8 antibodies. Eight images of each case were captured and analysed through the a) application of a count grid to count the number of positive neutrophils, macrophages, lymphocytes, plasma cells, fibroblasts and blood vessels to obtain the percentage of staining and b) semi-automated segmentation quantifying the stained area in square micrometres. Statistical tests included ANOVA Two-way, Kruskal Wallis and Games-Howell, with a significance level of 5%. An increased percentage of metalloproteinase-1-immunopositive blood vessels were observed in giant-cell fibroma (26.6±22.4; p=0.02) and inflammatory fibrous hyperplasia (34.3±31.5; p=0.01) compared with the control group (19.6±9.2). No significant differences in inflammatory cells, fibroblasts and total area of metalloproteinase-1 and -8 were noted among the three groups. Metalloproteinase-1 apparently acts within the pathogenesis of giant-cell fibroma and inflammatory fibrous hyperplasia. Copyright © 2016 Elsevier GmbH. All rights reserved.

Evaluation of a levonorgestrel-releasing intrauterine system for treating endometrial hyperplasia in patients with polycystic ovary syndrome.

PubMed

Lin, Min; Xu, XiaoWen; Wang, Yi; Hu, Yue; Zhao, Yu

2014-01-01

To evaluate the use of a levonorgestrel-releasing intrauterine system (LNG-IUS) for treating endometrial hyperplasia in patients with polycystic ovary syndrome (PCOS). LNG-IUSs were inserted in 60 PCOS patients with simple (40 cases), irregular (12 cases), or complex (8 cases) endometrial hyperplasia. Follow-ups were performed at 3, 6, 12, and 24 months after insertion. At each time point, changes in menstruation, hemoglobin level, and endometrial thickness and pathology were recorded. Menstrual changes were assessed with the Pictorial Blood Assessment Chart. Hemoglobin levels were measured by the Blood Routine Test. Endometrial thickness was determined by transvaginal ultrasound. Endometrial pathology was defined as simple, irregular, or complex endometrial hyperplasia by a pathologist after curettage. Outcomes at each time point were compared to baseline (pre-insertion) measurements by Student's t test or ANOVA (for multiple comparisons) with the post hoc Dunnett's test. Differences with a p < 0.05 were considered statistically significant. At all time points after LNG-IUS insertion and in all patients, menstrual blood loss was decreased and hemoglobin level was increased significantly compared to pre-insertion levels. The endometrial thickness was significantly reduced in all groups after 12 months. Most patients showed transformation of the endometrial pathology, with complete disappearance of simple and irregular cases of endometrial hyperplasia and a decreased number of complex endometrial hyperplasia cases. LNG-IUS is an effective, safe, nonsurgical, and atraumatic approach with few side effects for the treatment of endometrial hyperplasia in patients with PCOS. © 2014 S. Karger AG, Basel.

[Atelocollagen-mediated small interfering RNA delivery for effective gene silencing in rat vein grafts].

PubMed

Qiu, Xue-feng; Dong, Nian-guo; Sun, Zong-quan; Su, Wei; Shi, Jia-wei

2009-07-01

To evaluate the efficacy of using small interfering RNA targeting TF as a therapy for vein graft failure. External jugular vein to carotid artery interposition vein grafts, which were applied to a low flow condition, were made in 120 Sprague-Dawley rats weighing 260 to 300 g. These rats were randomly divided into 4 groups, 30 rats each group. Group A was atelocollagen-TF Stealth Select RNAi group. Group B was atelocollagen-TF Stealth RNAi group. Group C was atelocollagen group. Group D was control group. Small interfering RNA mixed with atelocollagen was administrated to the external wall of grafted veins. The TF protein expression of vein grafts was analyzed by Western blot at 1, 3, 7, 14, and 28 d postoperatively, and by immunochemistry at 3 d postoperatively. The proliferation index was determined at 14 d postoperatively. Neointimal hyperplasia was evaluated at 28 d postoperatively. BLOCK-iT fluorescent oligo was used to confirm its stability and successful transfer into the vein graft wall at 3 and 7 d postoperatively for another group (n=12). Fluorescence of BLOCK-iT fluorescent oligo could be detected in the graft wall even at 7 d postoperatively. Knockdown of the TF expression was achieved by perivascular application of siRNA using atelocollagen. Compared with control group, the intima thickness at 28 d after grafting was significantly reduced (P < 0.05). This phenomenon was preceded by significant reduction of cell proliferation in siRNA-treated grafts at 14 d postoperatively (P < 0.05). The expression of TF in vein grafts can be effectively inhibited by specific siRNAs using a atelocollagen-based nonviral delivery approach in vivo, so that the neointimal thickening can be prevented. Transplants;

Unusually high incidence of multifocal epithelial hyperplasia in children of the Nahuatl population of Mexico.

PubMed

Ledesma-Montes, Constantino; Mendez-Mendoza, Amilcar

2017-01-01

Multifocal epithelial hyperplasia is an uncommon disease of the oral mucosa caused by the human papilloma virus. To study the clinical and pathological findings of multifocal epithelial hyperplasia detected during an oral examination of 343 Mexican Nahuatl children from a single primary school in El Paso de Cupilco, Mexico. A thorough oral examination was performed in all children and clinical data (age, gender, location and number of lesions) were documented and analyzed. Multifocal epithelial hyperplasia was diagnosed in 110 of the 343 children (32.3%). The ages of the children varied from 5 to 15 years, and of these, 56.3% were girls. The lesions were asymptomatic, 0.2 to 3.0 cm in diameter, soft, round to oval, smooth surfaced, sessile papulonodules, similar in colour to that of the surrounding mucosa. The lesions were commonly seen on the buccal mucosa and tongue, and most affected children (85%) had less than 5 lesions. Children in the 7 to 10 years age group were most often affected. Human papillomavirus typing was not done owing to a lack of facilities. There is a high incidence of multifocal epithelial hyperplasia in Nahuatl children with a predilection for females.

[Steroid balance in patients with breast hyperplasia].

PubMed

Samundzhan, E M; Gorevaia, A N; Kartavova, N S; Makarchuk, N M; Nekrasov, P Ia

1978-01-01

A correlation was found between the character of hormonal disorders and the morphological organization of dyshormonal hyperplasias of the mammary gland. Patients with fibroadenoma and fibrous-cystic mastopathy are characterized by a high diurnal urine content of glucocorticoids and low estrogens level, especially estradiol. Patients with cystic fibroadenomatosis of the mammary gland show the high level of the excretion of classical and total phenolsteroids and low androsterone level.

p53 nuclear accumulation and ERα expression in ductal hyperplasia of breast in a cohort of 215 Chinese women

PubMed Central

2010-01-01

Introduction Women with ductal hyperplasia including usual ductal hyperplasia (UDH) and atypical ductal hyperplasia (ADH) have an increased risk of developing invasive ductal carcinoma (IDC) of breast. The importance of several molecular markers in breast cancer has been of considerable interest during recent years such as p53 and estrogen receptor alpha (ERα). However, p53 nuclear accumulation and ERα expression have not been assessed in ductal hyperplasia co-existing with ductal carcinoma in situ (DCIS) or IDC versus pure ductal hyperplasia without DCIS or IDC. Materials and methods We investigated p53 nuclear accumulation and ERα expression in breast ductal hyperplasia in a cohort of 215 Chinese women by immunohistochemistry (IHC), which included 129 cases of pure ductal hyperplasia, 86 cases of ductal hyperplasia co-existing with DCIS (41 cases) or IDC (45 cases). Results Nuclear p53 accumulation was identified in 22.8% of ADH (31/136), 41.5% of DCIS (17/41) and 42.2% of IDC (19/45), and no case of UDH (0/79). No difference in nuclear p53 accumulation was observed between pure ADH and ADH co-existing with DCIS (ADH/DCIS) or IDC (ADH/IDC) (P > 0.05). The positive rate of ERα expression was lower in ADH (118/136, 86.8%) than that in UDH (79/79, 100%) (P < 0.001), but higher than that in DCIS (28/41, 68.3%) or IDC (26/45, 57.8%) respectively (P < 0.001). The frequency of ERα expression was lower in ADH/DCIS (23/29, 79.31%) and ADH/IDC (23/30, 76.67%) than that in pure ADH (72/77, 93.51%) respectively (P < 0.05). There was a negative weak correlation between p53 nuclear accumulation and ERα expression as for ADH (coefficient correlation -0.51; P < 0.001). Conclusions Different pathological types of ductal hyperplasia of breast are accompanied by diversity in patterns of nuclear p53 accumulation and ERα expression. At least some pure ADH is molecularly distinct from ADH/CIS or ADH/IDC which indicated the two types of ADH are molecularly distinct entities

Different cytokeratin and neuronal cell adhesion molecule staining patterns in focal nodular hyperplasia and hepatic adenoma and their significance

PubMed Central

Iyer, Anita; Robert, Marie E.; Bifulco, Carlo B.; Salem, Ronald R.; Jain, Dhanpat

2013-01-01

Summary Differentiating focal nodular hyperplasia from hepatic adenoma can be challenging. Cytokeratin 7, neuronal cell adhesion molecule, and cytokeratin 19 are differentially expressed in hepatocytes, biliary epithelium, and possibly hepatic progenitor/stem cells. CD34 is known to have altered expression patterns in the hepatic endothelium in conditions associated with abnormal perfusion and in hepatocellular carcinoma. The purpose of this study was to examine the expression pattern of these markers in focal nodular hyperplasia and hepatic adenoma and assess their diagnostic use. Ten resection specimens each of hepatic adenoma and focal nodular hyperplasia (including a case of telangiectatic focal nodular hyperplasia) were selected for the study. Immunohistochemical analysis was performed using antibodies against cytokeratin 7, cytokeratin 19, neuronal cell adhesion molecule, and CD34 on formalin-fixed, paraffin-embedded sections from each case. The staining patterns and intensity for each marker were analyzed. In hepatic adenoma, the cytokeratin 7 stain revealed strong positivity in hepatocytes in patches, with a gradual decrease in the staining intensity as the cells differentiated towards mature hepatocytes. Although bile ducts were typically absent in hepatic adenoma, occasional ductules could be identified with cytokeratin 7 stain. In focal nodular hyperplasia, cytokeratin 7 showed strong staining of the biliary epithelium within the fibrous septa and staining of the peripheral hepatocytes of most lobules that was focal and weaker than hepatic adenoma. Cytokeratin 19 and neuronal cell adhesion molecule showed patchy and moderate staining in the biliary epithelium of the ductules in focal nodular hyperplasia. While in the hepatic adenoma, cytokeratin 19 showed only rare positivity in occasional cells within ductules, and neuronal cell adhesion molecule marked occasional isolated cells in the lesion. CD34 showed staining of sinusoids in the inflow areas

[Development of a High Power Green Laser Therapeutic Equipment for Hyperplasia of Prostate].

PubMed

Liang, Jie; Kang, Hongxiang; Shen, Benjian; Zhao, Lusheng; Wu, Xinshe; Chen, Peng; Chang, Aihong; Guo Hua; Guo, Jiayu

2015-09-01

The basic theory of high power green laser equipment for prostate hyperplasia therapy and the components of the system developed are introduced. Considering the requirements of the clinical therapy, the working process of the high power green laser apparatus are designed and the laser with stable output at 120 W is achieved. The controlling hardware and application software are developed, and the safety step is designed. The high power green laser apparatus manufactured with characteristics of stable output, multifunctional and friendly interface provides a choices of prostate hyperplasia therapy for using nationalization instrument.

Intimal Hyperplasia, Stenosis, and Arteriovenous Fistula Maturation Failure in the Hemodialysis Fistula Maturation Study.

PubMed

Cheung, Alfred K; Imrey, Peter B; Alpers, Charles E; Robbin, Michelle L; Radeva, Milena; Larive, Brett; Shiu, Yan-Ting; Allon, Michael; Dember, Laura M; Greene, Tom; Himmelfarb, Jonathan; Roy-Chaudhury, Prabir; Terry, Christi M; Vazquez, Miguel A; Kusek, John W; Feldman, Harold I

2017-10-01

Intimal hyperplasia and stenosis are often cited as causes of arteriovenous fistula maturation failure, but definitive evidence is lacking. We examined the associations among preexisting venous intimal hyperplasia, fistula venous stenosis after creation, and clinical maturation failure. The Hemodialysis Fistula Maturation Study prospectively observed 602 men and women through arteriovenous fistula creation surgery and their postoperative course. A segment of the vein used to create the fistula was collected intraoperatively for histomorphometric examination. On ultrasounds performed 1 day and 2 and 6 weeks after fistula creation, we assessed fistula venous stenosis using pre-specified criteria on the basis of ratios of luminal diameters and peak blood flow velocities at certain locations along the vessel. We determined fistula clinical maturation using criteria for usability during dialysis. Preexisting venous intimal hyperplasia, expressed per 10% increase in a hyperplasia index (range of 0%-100%), modestly associated with lower fistula blood flow rate (relative change, -2.5%; 95% confidence interval [95% CI], -4.6% to -0.4%; P =0.02) at 6 weeks but did not significantly associate with stenosis (odds ratio [OR], 1.07; 95% CI, 1.00 to 1.16; P =0.07) at 6 weeks or failure to mature clinically without procedural assistance (OR, 1.07; 95% CI, 0.99 to 1.15; P =0.07). Fistula venous stenosis at 6 weeks associated with maturation failure (OR, 1.98; 95% CI, 1.25 to 3.12; P =0.004) after controlling for case mix factors, dialysis status, and fistula location. These findings suggest that postoperative fistula venous stenosis associates with fistula maturation failure. Preoperative venous hyperplasia may associate with maturation failure but if so, only modestly. Copyright © 2017 by the American Society of Nephrology.

Management of cyclosporine-induced gingival hyperplasia by use of an argon laser

NASA Astrophysics Data System (ADS)

Blankenau, Richard J.; Triolo, P.; Powell, G. L.

1994-09-01

This is a report of a case study with interesting laser applications. A 7 year old female was referred to us for treatment of hyperplastic tissue. At age two the patient had successfully undergone a liver transplant. She had undergone two periodontal surgeries under general anesthetic for the same soft tissue problem. Other possible complications were chronic sinusitis and frequent headaches. She has allergies to penicillin and sulfa. Her daily medications are Predisone and Cyclosporin. We consulted with her transplant team and they had no contraindication for the proposed dental surgery. The doctor placed her on prophylactic erythromycin for the procedure, as a preventive measure. The patient desired not to have any more general anesthetics administered. Clinical examination revealed electric pulp tests were normal for all teeth tested. No visible carious lesions were observed and there was no need for radiographs at this time. Soft tissue revealed red inflamed fibrous tissue consistent with gingival hyperplasia. Probing demonstrated 4 - 6 mm pockets around the anterior teeth.

Transgenic expression of human amphiregulin in mouse skin: inflammatory epidermal hyperplasia and enlarged sebaceous glands.

PubMed

Li, Yong; Stoll, Stefan W; Sekhon, Sahil; Talsma, Caroline; Camhi, Maya I; Jones, Jennifer L; Lambert, Sylviane; Marley, Hue; Rittié, Laure; Grachtchouk, Marina; Fritz, Yi; Ward, Nicole L; Elder, James T

2016-03-01

To explore the role of amphiregulin in inflammatory epidermal hyperplasia, we overexpressed human AREG (hAREG) in FVB/N mice using a bovine K5 promoter. A construct containing AREG coding sequences flanked by 5' and 3' untranslated region sequences (AREG-UTR) led to a >10-fold increase in hAREG expression compared to an otherwise-identical construct containing only the coding region (AREG-CDR). AREG-UTR mice developed tousled, greasy fur as well as elongated nails and thickened, erythematous tail skin. No such phenotype was evident in AREG-CDR mice. Histologically, AREG-UTR mice presented with marked epidermal hyperplasia of tail skin (2.1-fold increase in epidermal thickness with a 9.5-fold increase in Ki-67(+) cells) accompanied by significantly increased CD4+ T-cell infiltration. Dorsal skin of AREG-UTR mice manifested lesser but still significant increases in epidermal thickness and keratinocyte hyperplasia. AREG-UTR mice also developed marked and significant sebaceous gland enlargement, with corresponding increases in Ki-67(+) cells. To determine the response of AREG-UTR animals to a pro-inflammatory skin challenge, topical imiquimod (IMQ) or vehicle cream was applied to dorsal and tail skin. IMQ increased dorsal skin thickness similarly in both AREG-UTR and wild type mice (1.7- and 2.2-fold vs vehicle, P < 0.001 each), but had no such effect on tail skin. These results confirm that keratinocyte expression of hAREG elicits inflammatory epidermal hyperplasia, and are consistent with prior reports of tail epidermal hyperplasia and increased sebaceous gland size in mice expressing human epigen. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Aromatase activities of endometrial carcinomas and both basic and clinical analyses of endometrial hyperplasia as a premalignant disease].

PubMed

Sasaki, H

1993-08-01

Paraffin-embedded materials obtained from 117 cases of endometrial hyperplasia and 84 cases of carcinoma were used for measurement of both ki-ras and p53 gene mutation and aromatase (ARO) and TGF-alpha immunostaining. The overall incidence of ki-ras mutations in the hyperplasia specimens (16%) was similar to the incidence detected in carcinomas (18%). None of 117 endometrial hyperplasias were found to have mutations in the p53 gene, whereas mutations were seen in 3 (13.3%) endometrial carcinomas. The intensity of both ARO and TGF-alpha immunostaining was increased in glands of both hyperplasia and carcinoma, and also in the interstitium of carcinoma. The positive sites of both ARO and TGF-alpha were almost the same, with an incidence below 40% in both hyperplasias and carcinomas. The cultured cells of endometrial carcinoma showed aromatase activity below MCF-7 cells, because testosterone was converted to estradiol (E2). TGF-alpha induced cell growth with at an optimal concentration. In HEC-59 cells, TGF-alpha increased both ARO-activity and mRNA. Some promoters on ARO-exon 1 in HEC-59 cells were different from those in BeWo cells. Progesterone inhibited the E2-induced excretion of pre TGF-alpha in endometrial carcinoma cells. These findings suggest that endometrial hyperplasia can be a premalignant condition of carcinoma, and can be initiated by both ki-ras codon 12 mutation and abnormal activity of ARO induced by TGF-alpha. In addition, HEC-59 cells may possess autocrine/paracrine properties involving ARO, E2 and TGF-alpha.

Interleukin-33 induces mucin gene expression and goblet cell hyperplasia in human nasal epithelial cells.

PubMed

Ishinaga, Hajime; Kitano, Masako; Toda, Masaaki; D'Alessandro-Gabazza, Corina N; Gabazza, Esteban C; Shah, Said Ahmad; Takeuchi, Kazuhiko

2017-02-01

We investigated whether IL-33 is involved in mucus overproduction and goblet cell hyperplasia in eosinophilic chronic rhinosinusitis (ECRS). IL-33 mRNA was significantly higher in the eosinophilic CRS group than in the non-eosinophilic CRS group from human nasal polyps. IL-33 induced MUC5AC mRNA and MUC5AC protein, and also goblet cell hyperplasia at air liquid interface culture in human nasal epithelial cells. In addition to that, IL-33 induced MUC5B and FOXA3, and reduces FOXJmRNA. In conclusion, our present study demonstrated that the direct evidence of IL-33 which lead to increase mucin gene and protein expression, as well as goblet cell hyperplasia. This study provides novel insights into the role of IL-33 on mucus overproduction in eosinophilic inflammation of human airways. Copyright © 2016 Elsevier Ltd. All rights reserved.

Oral focal fibrous hyperplasia and squamous cell papilloma treated with an erbium laser. Case presentation.

PubMed

Boj, J; Hernandez, M; Espasa, E; Espanya, A

2014-01-01

Mouth and oropharynx cancer constitute 5% of all malignancies; 95% of them are head and neck squamous cell carcinomas. Carcinogenesis is a multifactor process. Mutagenesis is also determined by the human papilloma virus which has recently been found to be etiologically associated with 20 to 25% of head and neck squamous cell carcinomas, mostly in the oropharinx. Focal fibrous hyperplasia of the connective tissue comes up as an answer to a chronic irritation in which a big amount of collagen can be found. As there exist certain clinical resemblance between squamous cell papilloma, fibrous focal hyperplasia and other mesenchimal tumors it is recommended to proceed, always, with removal and study. Two cases, one of an oral papilloma and another of a focal fibrous hyperplasia in pediatric patients, treated with an Er,Cr:YSGG laser wave length (mu) of 2780 nm are presented.

Nodular regenerative hyperplasia: Evolving concepts on underdiagnosed cause of portal hypertension

PubMed Central

Hartleb, Marek; Gutkowski, Krzysztof; Milkiewicz, Piotr

2011-01-01

Nodular regenerative hyperplasia (NRH) is a rare liver condition characterized by a widespread benign transformation of the hepatic parenchyma into small regenerative nodules. NRH may lead to the development of non-cirrhotic portal hypertension. There are no published systematic population studies on NRH and our current knowledge is limited to case reports and case series. NRH may develop via autoimmune, hematological, infectious, neoplastic, or drug-related causes. The disease is usually asymptomatic, slowly or non-progressive unless complications of portal hypertension develop. Accurate diagnosis is made by histopathology, which demonstrates diffuse micronodular transformation without fibrous septa. Lack of perinuclear collagen tissue distinguishes NRH from typical regenerative nodules in the cirrhotic liver. While the initial treatment is to address the underlying disease, ultimately the therapy is directed to the management of portal hypertension. The prognosis of NRH depends on both the severity of the underlying illness and the prevention of secondary complications of portal hypertension. In this review we detail the epidemiology, pathogenesis, diagnosis, management, and prognosis of NRH. PMID:21472097

The expanding role of epigenetics in the development, diagnosis and treatment of prostate cancer and benign prostatic hyperplasia.

PubMed

Dobosy, Joseph R; Roberts, J Lea W; Fu, Vivian X; Jarrard, David F

2007-03-01

the prostate to developing cancer. Treatments involving 5-aza-deoxycytosine and other, more selective DNA methyltransferase inhibitors remove methyl residues from silenced genes, generating re-expression, and are currently being used in therapeutic trials. Histone deacetylase inhibitors have shown promise, not only by directly reactivating silenced genes, but also as regulators of apoptosis and sensitizers to radiation therapy. Evolving data support a significant role for epigenetic processes in the development of prostate cancer and benign prostatic hyperplasia. Epigenetic changes can predict tumor behavior and often distinguish between genetically identical tumors. Targeted drugs that alter epigenetic modifications hold promise as a tool for curing and preventing these diseases.

External heating of stents by radio waves Pilot studies in rabbit aorta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levitt, Adam B.; Robinson, Keith; Chronos, Nicolas A.F.

Purpose: This experiment was designed to assess the feasibility of radio frequency energy delivered by a prototype radio frequency generator inductive heating device (REVAX) positioned external to the body, for transient heating of stents after arterial implant. Methods and Materials: Twenty-one New Zealand White rabbits underwent stenting of their infrarenal aorta. Nine rabbits were stented and immediately placed in the REVAX for external stent heating with internal temperature probes in place. Twelve rabbits were stented and 3 days later either heated or placed in the generator as a sham for 20 min. The animals were terminated 28 days later. Results:more » The REVAX was able to heat the aortic stents in a controlled fashion; in Phase II experiments, the stent temperature was raised to 42 deg. C for 20 min. In Phase I mild necrosis was noted at the stent struts. In Phase II, necrosis and mineralization of the media was seen at the stent struts, and evidence of neointimal suppression was observed. Conclusion: This study demonstrated that external heating of stents in a blood vessel in a live animal via radio frequency energy is feasible. Further studies will be needed to assess whether any specific heating regimen might inhibit fibrocellular neointimal hyperplasia.« less

Pediatric Helicobacter pylori gastropathy demonstrates a unique pattern of gastric foveolar hyperplasia.

PubMed

Saghier, Sadaf; Schwarz, Steven M; Anderson, Virginia; Gupta, Raavi; Heidarian, Amin; Rabinowitz, Simon S

2018-04-25

Helicobacter pylori (Hp) are the most common agents causing gastric mucosal injury worldwide. Foveolar hyperplasia is a key component of the stomach's reaction to injury. This study examines histopathologic characteristics associated with Helicobacter pylori and with non- Helicobacter pylori-associated gastropathy in children and adolescents, and compares the prevalence of foveolar hyperplasia among these disease subgroups and normal control subjects. Eighty-one gastric antral and corpus biopsies from subjects 2-19 years of age were studied. Twenty-two subjects with Helicobacter pylori gastritis were compared to 23 with non-Helicobacter pylori gastropathy and to 36 controls (normal biopsies). Foveolar length, full mucosal thickness, and the foveolar length: full mucosal thickness ratio were derived by a morphometric technique previously developed to analyze adult gastric tissue. Compared to controls, Helicobacter pylori gastritis demonstrated significant increases in antral foveolar length (P < .0001), full mucosal thickness (P < .0001), as well as corpus foveolar length (P < .05) and corpus full mucosal thickness (P < .05). Non-Helicobacter pylori-associated gastropathy also was characterized by increased antral foveolar length (P < .0001) and full mucosal thickness (P < .001) but corresponding corpus measurements did not differ from controls. Antral foveolar length in non-Helicobacter pylori gastropathy was increased, when compared to Helicobacter pylori gastritis (P < .05), while corpus values were not. The non-Helicobacter pylori gastropathy group demonstrated increased antral foveolar length: full mucosal thickness ratios, compared with Helicobacter pylori gastritis (P < .001) and with normal controls (P < .0001). An objective, quantitative approach to measuring foveolar hyperplasia in adults was successfully applied to pediatric biopsies and yielded a richer characterization of gastric pathology in children. Foveolar hyperplasia appears to

Hypoxia-inducible factor-1 signalling promotes goblet cell hyperplasia in airway epithelium

PubMed Central

Polosukhin, Vasiliy V; Cates, Justin M; Lawson, William E; Milstone, Aaron P; Matafonov, Anton G; Massion, Pierre P; Lee, Jae Woo; Randell, Scott H; Blackwell, Timothy S

2018-01-01

Goblet cell hyperplasia is a common feature of chronic obstructive pulmonary disease (COPD) airways, but the mechanisms that underlie this epithelial remodelling in COPD are not understood. Based on our previous finding of hypoxia-inducible factor-1α (HIF-1α) nuclear localization in large airways from patients with COPD, we investigated whether hypoxia-inducible signalling could influence the development of goblet cell hyperplasia. We evaluated large airway samples obtained from 18 lifelong non-smokers and 13 former smokers without COPD, and 45 former smokers with COPD. In these specimens, HIF-1α nuclear staining occurred almost exclusively in COPD patients in areas of airway remodelling. In COPD patients, 93.2 ± 3.9% (range 65 – 100%) of goblet cells were HIF-1α positive in areas of goblet cell hyperplasia, whereas nuclear HIF-1α was not detected in individuals without COPD or in normal-appearing pseudostratified epithelium from COPD patients. To determine the direct effects of hypoxia-inducible signalling on epithelial cell differentiation in vitro, human bronchial epithelial cells (HBECs) were grown in air-liquid interface cultures under hypoxia (1% O2) or following treatment with a selective HIF-1α stabilizer, (2R)-[(4-biphenylylsulphonyl)amino]-N-hydroxy-3-phenyl-propionamide (BiPS). HBECs grown in hypoxia or with BiPS treatment were characterized by HIF-1α activation, carbonic anhydrase IX expression, mucus-producing cell hyperplasia and increased expression of MUC5AC. Analysis of signal transduction pathways in cells with HIF-1α activation showed increased ERK1/2 phosphorylation without activation of epidermal growth factor receptor, Ras, PI3K-Akt or STAT6. These data indicate an important effect of hypoxia-inducible signalling on airway epithelial cell differentiation and identify a new potential target to limit mucus production in COPD. PMID:21557221

Study of some invasiveness markers as pathogenic factors in oral pseudoepitheliomatous hyperplasia.

PubMed

Pascu, Roxana Maria; Mărgăritescu, Claudiu; CrăiŢoiu, Monica Mihaela; Florescu, Alma Maria; Croitoru, Ileana Cristiana; Bobic, Adelina Gabriela; Pătru, Ciprian LaurenŢiu; Mălăescu, Gheorghe Dan; CrăiŢoiu, Ştefania

2016-01-01

Pseudoepitheliomatous hyperplasia is a benign reactivated epithelial lesion secondary to another pathology, whose incidence is difficult to establish. There still exist controversies regarding the origin and pathogenesis of these lesions. For this purpose, we performed an immuno-histochemical study upon 20 cases of oral pseudoepitheliomatous hyperplasia associated with inflammatory and neoplastic conditions, investigating a series of markers with a possible pathogenic potential in developing this type of lesions. Thus, the immunoreactivity study for β-catenin showed the presence of a membrane reactivity in all the stratum spinosum and a predominantly cytoplasmatic reactivity, more rarely a nuclear one, in the cells of the basal stratum cells, especially in the epithelial apices that descend deeply in the chorion. Instead, in the case of vimentin, the reactivity was present only in the epithelial apices, especially in the peripheral cells, in comparison to the central ones, and especially in the cases where the epithelial apices descended deeply in the sublesional chorion. Moreover, we observed that the MMP9 reactivity in pseudoepitheliomatous hyperplasia lesions was present in the cells at the epithelium-chorion interface and especially in the epithelial apices that descend deeply into the chorion, and also in the epithelial chorion and networks. The study for CXCR4 immuno-reactivity showed a good reactivity in almost all layers of this hyperplastic lesion, with a maximum reactivity especially inside the epithelial apices that descend deeply in the sublesional chorion. Such an immunoprofile suggests the ability of the oral epithelial cells to undergo an epithelial mesenchymal transition process, thus acquiring mesenchymal characteristics through which it deeply migrates in the subadjacent chorion and contributes to the formation of epithelial apices in pseudoepitheliomatous hyperplasia. Moreover, the invasive ability of these lesions is also given by the average

Management of mastitis and abscessation of mammary glands secondary to fibroadenomatous hyperplasia in a primiparturient cat.

PubMed

Burstyn, Uri

2010-02-01

A 1-year-old sexually intact female domestic shorthair cat was evaluated because of an 8-week history of pronounced mammary gland hyperplasia that had progressed to mastitis and abscessation of the mammary glands since parturition 7 days earlier. The cat was anorectic, was febrile, and had signs of discomfort. Its kittens were weak and appeared to have difficulty nursing. Physical examination revealed pyrexia, mastitis with abscessation in the 6 caudal mammary glands, skin ulceration over the nipples, and areas of skin necrosis over the abscessed mammary glands. A CBC revealed nonregenerative anemia and leukocytosis with a left shift (2.160 x 10(9) band cells/L) and toxic changes. Mastitis and incipient septicemia were considered the most likely causes. The history of mammary gland hyperplasia since the second week of pregnancy suggested a diagnosis of fibroadenomatous hyperplasia that predisposed the cat to subsequent mastitis. Surgical drainage of the abscessed mammary glands, debridement of necrotic skin, and placement of a Penrose drain resulted in rapid improvement in clinical status. Broad-spectrum antimicrobial treatment (amoxicillin-clavulanic acid) was prescribed, and the cat was discharged from the hospital. Mastitis and fibroadenomatous mammary gland hyperplasia resolved rapidly afterward. Management of abscessed mammary glands through surgical drainage and drain placement is an option for treatment of cats with complications of fibroadenomatous hyperplasia. In the cat of this report, the treatment approach resulted in rapid resolution of mastitis, was less invasive than mastectomy, and avoided the potential complications of treatment with a progesterone-receptor antagonist.

Expression of HOXA10 in endometrial hyperplasia and adenocarcinoma and regulation by sex hormones in vitro.

PubMed

Zhong, Gang; Wang, Yan; Liu, Xuemei

2011-07-01

The objective of the study was to determine the expression of HOXA10 in human endometrial tissue in endometrial hyperplasia and carcinomas, and regulation by sex steroids in Ishikawa cells. Endometrial tissue was obtained from 133 subjects with normal endometria, endometrial hyperplasia, or endometrial adenocarcinoma. Among 133 specimens, 20 were normal endometria, 19 were simple hyperplasias without atypia, 20 were complex hyperplasias without atypia, 33 were atypical hyperplasias, and 41 were endometrial adenocarcinomas. The expression of HOXA10 was analyzed by immunohistochemistry. Ishikawa cell lines were incubated with 17β estradiol (10⁻⁸ mol/L) alone, medroxyprogesterone acetate (10⁻⁶ mol/L) alone, or the combination of estrogen and progesterone for 48 hours, respectively. In certain experiments, the antiprogestin antagonist, RU486 (10⁻⁵ mol/L), was also added to Ishikawa cells along with estradiol and medroxyprogesterone acetate for 48 hours. The expression of HOXA10 gene was detected by reverse transcriptase-polymerase chain reaction and Western blotting. HOXA10 was expressed in both normal and neoplastic endometria. No significant difference in HOXA10 expression was found between normal and hyperplastic endometrial tissues. The expression of HOXA10 was decreased in endometrial adenocarcinomas compared with normal endometria. Estrogen alone, progestin alone, or progestin combined with estrogen could significantly increase the expression of HOXA10 gene (P<0.05). RU486 could inhibit the effect of up-regulation of HOXA10 expression by progestin. The expression of HOXA10 was deregulated in endometrial carcinomas and up-regulated by sex hormones.

Benign hepatocellular nodules of healthy liver: focal nodular hyperplasia and hepatocellular adenoma

PubMed Central

Roncalli, Massimo; Sciarra, Amedeo; Tommaso, Luca Di

2016-01-01

Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed. PMID:27189732

Effect of letrozole in carcinogen-plus-estrogen-induced endometrial hyperplasia in mice.

PubMed

Lara, Alessandra Cerávolo; Cândido, Eduardo Batista; Vidigal, Paula Vieira; Rocha, Ana Luiza Lunardi; Carvalho-Macedo, Alessandra Costa; Carneiro, Márcia Mendonça; Silva-Filho, Agnaldo Lopes

2016-04-01

To evaluate the effects of letrozole (Ltz) in carcinogen+estrogen-induced endometrial hyperplasia. BALB/c female mice were divided into four groups of 12 animals each receiving an intrauterine dose of N-ethyl-N-nitrosourea (ENU) and weekly subcutaneous injections of estradiol hexaidrobenzoate (EHB), except for group I(control). The groups were divided in I (control), II (ENU+EHB), III (ENU+EHB+MPA) and IV (ENU+EHB+Ltz). Group III also received intramuscular injections of MPA (medroxy progesterone acetate) every four weeks, while group IV received oral doses of Ltz daily. At the end of 16 weeks, the animals were sacrificed, and blood samples were collected for the measurement of serum estradiol and progesterone levels. Uterine histological sections were made to evaluate the presence of endometrial proliferative lesions. Differences between groups were evaluated with student's t test, ANOVA and chi-square test. Groups ENU+EHB, ENU+EHB+MPA and ENU+EHB+Ltz showed varying degrees of endometrial hyperplasia. The incidence of hyperplasia in groups ENU+EHB and ENU+EHB+Ltz was higher and more severe than in group ENU+EHB+MPA. Control group showed lower levels of serum estradiol than the other groups. There was no evidence that letrozole could act as an antiestrogenic drug in the development of endometrial proliferative lesions.

Nodular lymphoid hyperplasia in the gastrointestinal tract in adult patients: A review.

PubMed

Albuquerque, Andreia

2014-11-16

Nodular lymphoid hyperplasia of the gastrointestinal tract is characterized by the presence of multiple small nodules, normally between between 2 and 10 mm in diameter, distributed along the small intestine (more often), stomach, large intestine, or rectum. The pathogenesis is largely unknown. It can occur in all age groups, but primarily in children and can affect adults with or without immunodeficiency. Some patients have an associated disease, namely, common variable immunodeficiency, selective IgA deficiency, Giardia infection, or, more rarely, human immunodeficiency virus infection, celiac disease, or Helicobacter pylori infection. Nodular lymphoid hyperplasia generally presents as an asymptomatic disease, but it may cause gastrointestinal symptoms like abdominal pain, chronic diarrhea, bleeding or intestinal obstruction. A diagnosis is made at endoscopy or contrast barium studies and should be confirmed by histology. Its histological characteristics include markedly hyperplasic, mitotically active germinal centers and well-defined lymphocyte mantles found in the lamina propria and/or in the superficial submucosa, distributed in a diffuse or focal form. Treatment is directed towards associated conditions because the disorder itself generally requires no intervention. Nodular lymphoid hyperplasia is a risk factor for both intestinal and, very rarely, extraintestinal lymphoma. Some authors recommend surveillance, however, the duration and intervals are undefined.

Early Hormonal Influences on Cognitive Functioning in Congenital Adrenal Hyperplasia.

ERIC Educational Resources Information Center

Resnick, Susan M.; And Others

1986-01-01

Reports the results of cognitive test performance and early childhood activities in individuals with congenital adrenal hyperplasia, an autosomal recessive disorder associated with elevated prenatal adrenal androgen levels, demonstrating the effects of early exposure to excess androgenizing hormones on sexually dimorphic cognitive functioning.…

Mistaken gender identity in non-classical congenital adrenal hyperplasia.

PubMed

Kukreti, Prerna; Kandpal, Manish; Jiloha, R C

2014-04-01

Gender identity is the sense of belonging that one feels for a particular sex psychologically and socially, independent of one's biological sex. There is much less systematic data on gender identity in females with congenital adrenal hyperplasia (CAH). We report a case of non-classical CAH presenting as a case of gender identity disorder.

A Computational Framework to Optimize Subject-Specific Hemodialysis Blood Flow Rate to Prevent Intimal Hyperplasia

NASA Astrophysics Data System (ADS)

Mahmoudzadeh, Javid; Wlodarczyk, Marta; Cassel, Kevin

2017-11-01

Development of excessive intimal hyperplasia (IH) in the cephalic vein of renal failure patients who receive chronic hemodialysis treatment results in vascular access failure and multiple treatment complications. Specifically, cephalic arch stenosis (CAS) is known to exacerbate hypertensive blood pressure, thrombosis, and subsequent cardiovascular incidents that would necessitate costly interventional procedures with low success rates. It has been hypothesized that excessive blood flow rate post access maturation which strongly violates the venous homeostasis is the main hemodynamic factor that orchestrates the onset and development of CAS. In this article, a computational framework based on a strong coupling of computational fluid dynamics (CFD) and shape optimization is proposed that aims to identify the effective blood flow rate on a patient-specific basis that avoids the onset of CAS while providing the adequate blood flow rate required to facilitate hemodialysis. This effective flow rate can be achieved through implementation of Miller's surgical banding method after the maturation of the arteriovenous fistula and is rooted in the relaxation of wall stresses back to a homeostatic target value. The results are indicative that this optimized hemodialysis blood flow rate is, in fact, a subject-specific value that can be assessed post vascular access maturation and prior to the initiation of chronic hemodialysis treatment as a mitigative action against CAS-related access failure. This computational technology can be employed for individualized dialysis treatment.

Decreasing mitochondrial fission diminishes vascular smooth muscle cell migration and ameliorates intimal hyperplasia

PubMed Central

Wang, Li; Yu, Tianzheng; Lee, Hakjoo; O'Brien, Dawn K.; Sesaki, Hiromi; Yoon, Yisang

2015-01-01

Aims Vascular smooth muscle cell (VSMC) migration in response to arterial wall injury is a critical process in the development of intimal hyperplasia. Cell migration is an energy-demanding process that is predicted to require mitochondrial function. Mitochondria are morphologically dynamic, undergoing continuous shape change through fission and fusion. However, the role of mitochondrial morphology in VSMC migration is not well understood. The aim of the study is to understand how mitochondrial fission contributes to VSMC migration and provides its in vivo relevance in the mouse model of intimal hyperplasia. Methods and results In primary mouse VSMCs, the chemoattractant PDGF induced mitochondrial shortening through the mitochondrial fission protein dynamin-like protein 1 (DLP1)/Drp1. Perturbation of mitochondrial fission by expressing the dominant-negative mutant DLP1-K38A or by DLP1 silencing greatly decreased PDGF-induced lamellipodia formation and VSMC migration, indicating that mitochondrial fission is an important process in VSMC migration. PDGF induced an augmentation of mitochondrial energetics as well as ROS production, both of which were found to be necessary for VSMC migration. Mechanistically, the inhibition of mitochondrial fission induced an increase of mitochondrial inner membrane proton leak in VSMCs, abrogating the PDGF-induced energetic enhancement and an ROS increase. In an in vivo model of intimal hyperplasia, transgenic mice expressing DLP1-K38A displayed markedly reduced ROS levels and neointima formation in response to femoral artery wire injury. Conclusions Mitochondrial fission is an integral process in cell migration, and controlling mitochondrial fission can limit VSMC migration and the pathological intimal hyperplasia by altering mitochondrial energetics and ROS levels. PMID:25587046

Mistaken gender identity in non-classical congenital adrenal hyperplasia

PubMed Central

Kukreti, Prerna; Kandpal, Manish; Jiloha, R. C.

2014-01-01

Gender identity is the sense of belonging that one feels for a particular sex psychologically and socially, independent of one's biological sex. There is much less systematic data on gender identity in females with congenital adrenal hyperplasia (CAH). We report a case of non-classical CAH presenting as a case of gender identity disorder. PMID:24891708

Atypical epithelial hyperplasia of the breast: state of the art.

PubMed

Dion, Ludivine; Racin, Adelaïde; Brousse, Susie; Beltjens, Françoise; Cauchois, Aurélie; Levêque, Jean; Coutant, Charles; Lavoué, Vincent

2016-09-01

Atypical epithelial hyperplasia (AEH) of the breast is considered benign histological lesions with breast cancer risk. This review focuses on clinical signification and management of AEH that remains controversial. A review of published studies was performed using medline database. In this review, we fully describe the current evidence available. In particular, we describe 1) data from immunohistochemistry and molecular studies that suggest AEH is a precursor of breast cancer; 2) epidemiological studies demonstrate low rate of breast cancer in women with AEH; 3) surgical excision is necessary after diagnosis of AEH, such as lobular carcinoma in situ or atypical ductal hyperplasia, on core needle biopsy; 4) although current recommendations are evolving to fewer (if not no) excisions for flat epithelial with atypia and classic lobular neoplasia found on percutaneous biopsy (without radiologic indications for excision). Expert commentary: HEA management steel need prospective evidences, but recent retrospective data give some clue for less invasive management for some of HEA.

Benign prostatic hyperplasia.

PubMed

Chughtai, Bilal; Forde, James C; Thomas, Dominique Dana Marie; Laor, Leanna; Hossack, Tania; Woo, Henry H; Te, Alexis E; Kaplan, Steven A

2016-05-05

Benign prostatic hyperplasia (BPH), which causes lower urinary tract symptoms (LUTS), is a common diagnosis among the ageing male population with increasing prevalence. Many risks factors, both modifiable and non-modifiable, can increase the risk of development and progression of BPH and LUTS. The symptoms can be obstructive (resulting in urinary hesitancy, weak stream, straining or prolonged voiding) or irritative (resulting in increased urinary frequency and urgency, nocturia, urge incontinence and reduced voiding volumes), or can affect the patient after micturition (for example, postvoid dribble or incomplete emptying). BPH occurs when both stromal and epithelial cells of the prostate in the transitional zone proliferate by processes that are thought to be influenced by inflammation and sex hormones, causing prostate enlargement. Patients with LUTS undergo several key diagnostic investigations before being diagnosed with BPH. Treatment options for men with BPH start at watchful waiting and progress through medical to surgical interventions. For the majority of patients, the starting point on the treatment pathway will be dictated by their symptoms and degree of bother.

Mandibular pseudocarcinomatous hyperplasia.

PubMed

Warter, A; Walter, P; Meyer, C; Barrière, P; Galatir, L; Wilk, A

2000-08-01

Three unusual cases of pseudocarcinomatous (pseudoepitheliomatous) hyperplasia (PH) affecting chronic osteomyelitic mandibular sequestra are reported to highlight the differences with the various squamous neoplasms which occur in that site. In two patients carrying a mandibular graft following the excision of an ameloblastoma, mucosal ulcers resulted in chronic osteomyelitis. In a third patient, an apical dental infection was associated with fistulated osteomyelitis. Histology of the three sequestra showed an intraosseous squamous proliferation. It was characterized by a peripheral involvement of medullary spaces, the more mature epithelial layer covering the bone trabeculae without intervening stroma, and the basal type epithelial layer surrounding a central fibrovascular core. There were no histological or cytological signs of malignancy. PH shows an inverted pattern when compared with the centro-medullary tumoural islands seen in the various oral or odontogenic squamous neoplasms which occur in the jaws. The lack of signs of malignancy distinguish PH from common squamous cell carcinomas. A short clinical course is an important feature in the distinction of PH from the well differentiated squamous cell carcinomas which may develop in fistulated chronic osteomyelitis.

Lymphomatoid papulosis with pseudocarcinomatous hyperplasia in a 7-year-old girl: a case report.

PubMed

Xiong, Jingshu; Ma, Yiping; Chen, Hao; Xu, Xiulian; Sun, Jianfang

2016-05-01

Lymphomatoid papulosis (LyP) belongs to the group of cutaneous CD30+ lymphoproliferative disorders. Pseudocarcinomatous hyperplasia has rarely been reported in patients with LyP. In this report, we describe a case of LyP presenting as pseudocarcinomatous hyperplasia. The patient was a 7-year-old girl who presented with a recurrent papulonodular eruption on her face and trunk for 2 months. Histopathologic examination revealed an irregular growth of hyperkeratotic epidermis into the whole dermal layer with marked nests of squamous cells in the background of diffuse atypical lymphoid cells, eosinophils and neutrophils. The large atypical cells were positive for CD30 and CD3, but negative for CD4, CD5, CD8, CD20 and CD56. A TCR-γ clone was identified by polymerase chain reaction (PCR). The correct diagnosis in cases of LyP with overlying pseudocarcinomatous epithelial hyperplasia can be very difficult both clinically and histopathologically. Clinical and histopathologic characteristics should be integrated to avoid an erroneous diagnosis of squamous cell carcinoma or keratoacanthoma. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cryotherapy for localized juvenile spongiotic gingival hyperplasia: preliminary findings on two cases.

PubMed

Nogueira, Vinícius Krieger Costa; Fernandes, Darcy; Navarro, Cláudia Maria; Giro, Elisa Maria Aparecida; de Almeida, Luciana Yamamoto; León, Jorge Esquiche; Bufalino, Andreia

2017-05-01

Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a distinct subtype of inflammatory gingival hyperplasia that shows lack of response to traditional periodontal treatment, and after surgical excision, recurrence rate of 6-16% has been reported. Two girls (11- and 9-year-old) with multifocal red patches along the maxillary and mandibular labial gingiva showed no regression of the lesions after basic periodontal treatment. Surgical excision of focal lesion in each case was performed, which showed typical features of LJSGH. In both cases, the lesions presented recurrence. Hence, cryotherapy sessions in all lesions were performed. Cryotherapy appears to be successfully in LJSGH and well received by paediatric patients. © 2016 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Panhypopituitarism with empty sella a sequel of pituitary hyperplasia due to chronic primary hypothyroidism.

PubMed

Dutta, Deep; Maisnam, Indira; Ghosh, Sujoy; Mukhopadhyay, Pradip; Mukhopadhyay, Satinath; Chowdhury, Subhankar

2012-12-01

Asymptomatic reversible pituitary hyperplasia is common in patients with untreated primary hypothyroidism. Occurrence of empty sella (ES) in this scenario is extremely rare (only three reports till the date) and panhypopituitarism has not been reported in such patients. We report a 27 year man with severe short stature (height-133 cm; standard deviation score-7.36) and delayed puberty who had symptoms suggestive of hypothyroidism along with chronic persistent headache since 6 years of age. Pituitary imaging done for headache at 11 years age showed pituitary hyperplasia. He was diagnosed of primary hypothyroidism for the 1(st) time at 21 year age, a diagnosis which was likely missed for 15 years. Levothyroxine therapy leads to resolution of all symptoms and a height gain of 28 cm over last 6 years. Evaluation for lack of progression of puberty along with chronic nausea, vomiting, fatigue and weight loss for the last 1 year revealed secondary hypocortisolism (9 am cortisol-4.8 mcg/dl; ACTH-3.2 pg/ml), growth hormone deficiency (IGF-1: 65 ng/ml; normal: 117-325 ng/ml) and hypogonadotrophic hypogonadism (9 am testosterone: 98 ng/dl; [280-1500] LH-0.01 mIU/L [1.14-5.75]) with ES on magnetic resonance imaging (MRI) brain. Uncontrolled thyrotroph hyperplasia due to chronic untreated primary hypothyroidism for 15 years may have been damaging the adjacent corticotrophs, somatotrophs and gonadotrophs resulting in panhypopituitarism and empty sella. This is perhaps the first report of panhypopituitarism with empty sella syndrome developing in a patient with pituitary hyperplasia, a sequel of chronic untreated primary hypothyroidism.

Role of Inflammation in Benign Prostatic Hyperplasia

PubMed Central

Chughtai, Bilal; Lee, Richard; Te, Alexis; Kaplan, Steven

2011-01-01

Inflammation of the prostate may represent a mechanism for hyperplastic changes to occur in the prostate. There are a variety of growth factors and cytokines that may lead to a proinflammatory process within the prostate. There are several proposed mechanisms that lead to both the intrinsic and extrinsic basis of inflammation. Prostatic inflammation may represent an important factor in influencing prostatic growth and progression of symptoms. This article reviews the recent literature on inflammation leading to chronic prostatic diseases, such as benign prostatic hyperplasia. PMID:22110398

Korean clinical practice guideline for benign prostatic hyperplasia

PubMed Central

Yeo, Jeong Kyun; Choi, Hun; Bae, Jae Hyun; Kim, Jae Heon; Yang, Seong Ok; Oh, Chul Young; Cho, Young Sam; Kim, Kyoung Woo

2016-01-01

In 2014, the Korean Urological Association organized the Benign Prostatic Hyperplasia Guideline Developing Committee composed of experts in the field of benign prostatic hyperplasia (BPH) with the participation of the Korean Academy of Family Medicine and the Korean Continence Society to develop a Korean clinical practice guideline for BPH. The purpose of this clinical practice guideline is to provide current and comprehensive recommendations for the evaluation and treatment of BPH. The committee developed the guideline mainly by adapting existing guidelines and partially by using the de novo method. A comprehensive literature review was carried out primarily from 2009 to 2013 by using medical search engines including data from Korea. Based on the published evidence, recommendations were synthesized, and the level of evidence of the recommendations was determined by using methods adapted from the 2011 Oxford Centre for Evidence-Based Medicine. Meta-analysis was done for one key question and four recommendations. A draft guideline was reviewed by expert peer reviewers and discussed at an expert consensus meeting until final agreement was achieved. This evidence-based guideline for BPH provides recommendations to primary practitioners and urologists for the diagnosis and treatment of BPH in men older than 40 years. PMID:26966724

Cutaneous papillomatous hyperplasia in cyclosporine-A treated beagles.

PubMed

Seibel, W; Sundberg, J P; Lesko, L J; Sauk, J J; McCleary, L B; Hassell, T M

1989-08-01

All twelve Beagle dogs undergoing long-term therapy (26 weeks) with the immunosuppressive drug cyclosporine-A (30 mg/kg), developed cutaneous papillomatous hyperplasia. By week 7 all dogs developed generalized lesions distributed over the entire body. These occurred as irregular, oval, sessile, unpigmented, firm masses. The incidence and severity of the skin lesions varied among dogs and anatomic site, with no correlation to the blood level of cyclosporine. Microscopic analysis revealed that the epidermis formed short papillary folds on broad fibrovascular stalks and was hyperkeratotic and acanthotic. Mild hyperplasia of hair follicles and sebaceous glands was also evident. A mild diffuse infiltrate of lymphocytes and plasma cells was present in the papillary dermis. No histopathologic changes typical of papillomavirus infection were identified, nor were papillomavirus group-specific antigens or viral DNA detected. Other cutaneous side effects included hyperkeratosis of footpads, increased growth of hair and nails, and hyperkeratinization of the haired skin of the prepuce. All cutaneous lesions regressed spontaneously within 8 weeks following termination of cyclosporine administration. The hyperplastic lesions may have resulted from the action of cyclosporine via the T-lymphocyte system. Conversely a direct action of this drug on epithelial cells may have stimulated proliferation and keratinization.

Noninvasive inductive stent heating: alternative approach to prevent instent restenosis?

PubMed

Floren, Michael G; Günther, Rolf W; Schmitz-Rode, Thomas

2004-05-01

To test noninvasive inductive heating of implanted vascular stents as an alternative approach for reduction or prevention of neointimal hyperplasia. Calorimetric pretests were performed to get an orientation on the different parameters of influence for inductive heating of stents. The field strength was set to a maximum of 90 kA/m within a frequency range from 80 kHz to 320 kHz. The electromagnetic field was emitted by a custom-made water-cooled copper winding antenna. A flow model for stent heating was set up to assess the increase in temperature of an expanded 316L stainless steel stent with typical coronary stent dimensions of 3.5 mm diameter and 14.5 mm in length, and in a second setup with 4.5 mm diameter and 13 mm in length, respectively. The stent was located in a bioartificial artery, simulated by a fibrinogen matrix with a defined number of vital cells. The system was exposed to a pulsating perfusion and to an electromagnetic field of 200 kHz over a period of 20 minutes and in a second setup to an electromagnetic field of 300 kHz and increasing intensity up to maximum power-output. Afterward, the artificial vessel was sliced and examined by fluorescence microscopy to evaluate the number and location of damaged cells. The calorimetric tests show an exponential correlation of energy uptake in the stent with an increase in frequency and a constant generator output. At a frequency of 80 kHz, the power uptake accounts for 0.1 W (250 kHz 1.0 W; 320 kHz 1.9 W, respectively). The flow tests confirmed feasibility to elevate the stent temperature from 37 degrees C body temperature to 44 degrees C at 200 kHz within 55 seconds. The temperature increase of the fluid passing the heated vessel region was only marginal (maximum of 0.5 degrees C). Cell necrosis after 20 minutes of treatment was not observed. In a second set-up with 4.5 mm stent diameter, a frequency of 300 kHz and with maximum power output, the stent temperature was increased to 80 degrees C and there was

Ibuprofen induces reduction of the proliferation-seeking radiotracer 99mTc-(V)DMSA uptake in severe epithelial breast hyperplasia without atypia.

PubMed

Papantoniou, Vassilios; Tsaroucha, Angeliki; Valsamaki, Pipitsa; Tsiouris, Spyridon; Sotiropoulou, Evangelia; Karianos, Theodore; Marinopoulos, Spyridon; Fothiadaki, Athina; Sotiropoulou, Maria; Archontaki, Aikaterini; Syrgiannis, Konstantinos; Dimitrakakis, Konstantinos; Antsaklis, Aris

2010-10-01

The purpose of this study was to investigate if ibuprofen intake can influence mammary uptake of the proliferation-seeking radiotracer technetium 99m-pentavalent dimercaptosuccinic acid (99mTc-(V)DMSA) in women with severe epithelial and atypical epithelial breast hyperplasia. Eight patients with histologically confirmed severe epithelial breast hyperplasia with (n  =  4) and without atypia (n  =  4) were submitted prospectively to 99mTc-(V)DMSA scintimammography before and after a 4-week course of 400 mg ibuprofen daily oral intake. Lesion to background ratios 60 minutes postinjection were calculated and compared (t-test) before and after ibuprofen administration. Prior to ibuprofen, the patients with severe epithelial hyperplasia displayed a significantly higher 99mTc-(V)DMSA uptake ratio compared to those with atypical epithelial hyperplasia (2.40 ± 0.32 vs 1.67 ± 0.09, respectively; p  =  .003). They also exhibited a more substantial percent decline in tracer uptake postibuprofen compared to women with atypical epithelial hyperplasia (62.0 ± 7.1 vs 15.0 ± 0.2, respectively; p  =  .001). Ibuprofen induces significant uptake reduction of the proliferation-seeking radiotracer 99mTc-(V)DMSA in severe epithelial breast hyperplasia without atypia. This agent could therefore constitute a potential imaging tool for monitoring chemoprophylaxis effectiveness in women at the early stages of malignant transformation.

Paleoandrology and prostatic hyperplasia in Italian mummies (XV-XIX century).

PubMed

Fornaciari, G; Ciranni, R; Ventura, L

2001-01-01

Prostatic hyperplasia, a very common condition today, was well known in the past as cause for bladder distension. The difficulty to identify, at autopsy of natural or artificial mummies, even a normal-sized prostate is probably the result of putrefaction processes and its usually dramatic size reduction as well. We report two ancient cases of prostatic hyperplasia recently observed in natural mummies from Italy. The first case regards Pandolfo III Malatesta (1370-1427), a leading figure of the Italian Renaissance. He was a valiant soldier and horseman with a very active life style. The tomb, containing his naturally mummified body, has recently been discovered in Fano (Marche, Central Italy). After careful X-ray and videographic examination, the autopsy showed good preservation of the skeletal muscles, cartilage, internal and external organs, included prostate gland and penis. Macroscopic examination revealed a staghorn calculus (calcium urate) of the left kidney and a severe enlargement of the prostate, with calcifications detectable by X-ray and large nodules protruding in the lumen of an ectatic urethra. Histology shows fibrous brands of connective and muscular tissue surrounding circular and oblong lacunae, with no preservation of epithelial structures. The macroscopic and histological picture allowed us to diagnose prostatic nodular hyperplasia. The second case (XIX century) concerns the natural mummy of an anonymous 50-60 years old man, found in ancient friary near L'Aquila (central Italy), which underwent computed tomography and a complete autopsy. Pelvic CT scans showed distended urinary bladder and a ring of dense tissue at the site of the prostate. At autopsy the bladder measured 7 x 6 x 5 cm and the prostate was 4 x 5 x 3 cm; prostatic urethra had a diameter of x 2 cm. Histology revealed dense fibrous tissue containing muscular fibers and roundish cavities of variable size, filled with eosinophil, PAS-positive material. Concretions were also present in

Intravenous calcitriol therapy in an early stage prevents parathyroid gland growth

PubMed Central

Taniguchi, Masatomo; Tokumoto, Masanori; Tsuruya, Kazuhiko; Hirakata, Hideki; Iida, Mitsuo

2008-01-01

Background. Both the phenotypic alterations of parathyroid (PT) cells, e.g. down-regulation of the calcium-sensing receptor, and the increase of the PT cell number in nodular hyperplasia are the main causes of refractory secondary hyperparathyroidism. It is of great importance to prevent PT growth in an early stage. Methods. To examine a more effective method of calcitriol therapy for the prevention of PT hyperplasia, we randomized haemodialysis patients with mild hyperparathyroidism to receive either daily orally administered calcitriol (n = 33) or intravenous calcitriol (n = 27) over a 12-month study period. Calcitriol was modulated so as to keep the serum intact PTH level between 100 and 150 pg/ml. Results. Both groups showed similar reductions of the serum PTH level and similar increases in serum calcium. In both groups, there were no significant changes in the serum phosphate level. Long-term daily oral calcitriol therapy failed to prevent the increase of both maximum PT volume and total volume, as assessed by ultrasonography; however, intravenous calcitriol therapy successfully suppressed this progression. In the daily, oral group, both the bone-specific alkaline phosphatase (BAP) and the N-telopeptide cross-linked of type I collagen (NTX) significantly decreased, which was probably due to the PTH suppression. However, these bone metabolism markers remained stable in the intravenous group. The total dosage of calcitriol during the study was comparable in both groups. Conclusions. These data indicate that intravenous calcitriol therapy in an early stage of secondary hyperparathyroidism is necessary to prevent PT growth and to keep a good condition of bone metabolism. PMID:18515308

A novel approach to breast cancer prevention: reducing excessive ovarian androgen production in elderly women.

PubMed

Secreto, Giorgio; Sieri, Sabina; Agnoli, Claudia; Grioni, Sara; Muti, Paola; Zumoff, Barnett; Sant, Milena; Meneghini, Elisabetta; Krogh, Vittorio

2016-08-01

Minimizing endogenous estrogen production and activity in women at high risk for breast cancer is a prominent approach to prevention of the disease. A number of clinical trials have shown that the administration of selective-estrogen receptor modulators or aromatase inhibitors significantly reduces the incidence of breast cancer in healthy women. Unfortunately, these drugs often produce adverse effects on the quality of life and are, therefore, poorly accepted by many women, even those who are at high risk for breast cancer. We propose a novel alternative approach to decreasing estrogen production: suppression of ovarian synthesis of the androgen precursors of estrogens by administration of long-acting gonadotropin-releasing hormone analogs to women with ovarian stromal hyperplasia. The specific target population would be elderly postmenopausal women, at increased risk of breast cancer, and with high blood levels of testosterone, marker of ovarian hyperandrogenemia, and recognized factor of risk for breast cancer. Testosterone levels are measured at baseline to identify women at risk and during the follow-up to evaluate the effectiveness of therapy. The postmenopausal ovary is an important source of excessive androgen production which originates from the ovarian interstitial cell hyperplasia frequently present in breast cancer patients. We propose to counter the source of androgen excess in women with ovarian stromal hyperplasia, thus reducing the substrate for estrogen formation without completely inhibiting estrogen synthesis. Available evidence indicates that gonadotropin-releasing hormone analogs can be safely used for breast cancer prevention in postmenopausal women.

Giant prostatic hyperplasia: report of a previously asymptomatic man presenting with gross hematuria and hypovolemic shock

PubMed Central

Wroclawski, Marcelo Langer; Carneiro, Ariê; Tristão, Rodrigo Alves; Sakuramoto, Paulo Kouiti; Youssef, Jorg Daoud Merched; Lopes, Antonio Correa; Santiago, Lucila Heloísa Simardi; Pompeo, Antonio Carlos Lima

2015-01-01

Giant prostatic hyperplasia is a rare condition characterized by very high volume benign prostatic enlargement (>500g). Few cases have been reported so far and most of them are associated with severe lower urinary symptoms. We report the first case of asymptomatic giant prostatic hyperplasia in an elderly man who had a 720g prostate adenoma, sudden gross hematuria and hypovolemic shock. The patient was successfully treated with open transvesical prostatectomy and had an uneventful postoperative recovery. PMID:26132361

Sulforaphane inhibits PDGF-induced proliferation of rat aortic vascular smooth muscle cell by up-regulation of p53 leading to G1/S cell cycle arrest.

PubMed

Yoo, Su-Hyang; Lim, Yong; Kim, Seung-Jung; Yoo, Kyu-Dong; Yoo, Hwan-Soo; Hong, Jin-Tae; Lee, Mi-Yea; Yun, Yeo-Pyo

2013-01-01

Vascular diseases such as atherosclerosis and restenosis artery angioplasty are associated with vascular smooth muscle cell (VSMC) proliferation and intimal thickening arterial walls. In the present study, we investigated the inhibitory effects of sulforaphane, an isothiocyanate produced in cruciferous vegetables, on VSMC proliferation and neointimal formation in a rat carotid artery injury model. Sulforaphane at the concentrations of 0.5, 1.0, and 2.0 μM significantly inhibited platelet-derived growth factor (PDGF)-BB-induced VSMC proliferation in a concentration-dependent manner, determined by cell count. The IC50 value of sulforaphane-inhibited VSMC proliferation was 0.8 μM. Sulforaphane increased the cyclin-dependent kinase inhibitor p21 and p53 levels, while it decreased CDK2 and cyclin E expression. The effects of sulforaphane on vascular thickening were determined 14 days after the injury to the rat carotid artery. The angiographic mean luminary diameters of the group treated with 2 and 4 μM sulforaphane were 0.25±0.1 and 0.09±0.1 mm², respectively, while the value of the control groups was 0.40±0.1 mm², indicating that sulforaphane may inhibit neointimal formation. The expression of PCNA, maker for cell cycle arrest, was decreased, while that of p53 and p21 was increased, which showed the same pattern as one in in-vitro study. These results suggest that sulforaphane-inhibited VSMC proliferation may occur through the G1/S cell cycle arrest by up-regulation of p53 signaling pathway, and then lead to the decreased neointimal hyperplasia thickening. Thus, sulforaphane may be a promising candidate for the therapy of atherosclerosis and post-angiography restenosis. © 2013.

Multifocal Epithelial Hyperplasia of Oral Cavity Expressing HPV 16 Gene: A Rare Entity

PubMed Central

Prabhat, M. P. V.; Raja Lakshmi, Chintamaneni; Sai Madhavi, N.; Bhavana, Sujana Mulk; Sarat, Gummadapu; Ramamohan, Kodali

2013-01-01

Focal epithelial hyperplasia is a rare contagious disease caused by human papilloma virus. Usually HPV involves either cutaneous or mucosal surfaces, whereas concomitant mucocutaneous involvement is extremely rare. We report such a unique case of multifocal epithelial hyperplasia involving multiple sites of oral cavity along with skin lesions in a 65-year-old female. We also discuss the probable multifactorial etiology and variable clinical presentations of the lesions, including evidence of HPV 16 expression, as detected by polymerase chain reaction. The present report illustrates the need for careful examination and prompt diagnosis of the disease, as it might be associated with high risk genotypes such as HPV 16 and 18. PMID:24455323

Leoligin, the major lignan from Edelweiss, inhibits intimal hyperplasia of venous bypass grafts

PubMed Central

Reisinger, Ute; Schwaiger, Stefan; Zeller, Iris; Messner, Barbara; Stigler, Robert; Wiedemann, Dominik; Mayr, Tobias; Seger, Christoph; Schachner, Thomas; Dirsch, Verena M.; Vollmar, Angelika M.; Bonatti, Johannes O.; Stuppner, Hermann; Laufer, Günther; Bernhard, David

2009-01-01

Aims Despite the lower patency of venous compared with arterial coronary artery bypass grafts, ∼50% of grafts used are saphenous vein conduits because of their easier accessibility. In a search for ways to increase venous graft patency, we applied the results of a previous pharmacological study screening for non-toxic compounds that inhibit intimal hyperplasia of saphenous vein conduits in organ cultures. Here we analyse the effects and mechanism of action of leoligin [(2S,3R,4R)-4-(3,4-dimethoxybenzyl)-2-(3,4-dimethoxyphenyl)tetrahydrofuran-3-yl]methyl (2Z)-2-methylbut-2-enoat, the major lignan from Edelweiss (Leontopodium alpinum Cass.). Methods and results We found that leoligin potently inhibits vascular smooth muscle cell (SMC) proliferation by inducing cell cycle arrest in the G1-phase. Leoligin induced cell death neither in SMCs nor, more importantly, in endothelial cells. In a human saphenous vein organ culture model for graft disease, leoligin potently inhibited intimal hyperplasia, and even reversed graft disease in pre-damaged vessels. Furthermore, in an in vivo mouse model for venous bypass graft disease, leoligin potently inhibited intimal hyperplasia. Conclusion Our data suggest that leoligin might represent a novel non-toxic, non-thrombogenic, endothelial integrity preserving candidate drug for the treatment of vein graft disease. PMID:19228707

Surface Papillary Epithelial Hyperplasia (Rough Mucosa) is a Helpful Clue for Identification of Polymorphous Low-Grade Adenocarcinoma.

PubMed

Chi, Angela C; Neville, Brad W

2015-06-01

The purpose of this study is to evaluate surface papillary epithelial hyperplasia, a microscopic finding that corresponds to the clinical finding of rough or stippled mucosa, as a predictor of polymorphous low-grade adenocarcinoma (PLGA). We conducted a retrospective review of minor salivary gland neoplasms submitted to our biopsy service from 1991 to 2013. Our review was limited to lesions involving the oral cavity/soft palate with the following diagnoses: PLGA, pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC). A total of 202 minor salivary gland neoplasms were included in the study. Among cases in which surface epithelium was present for evaluation (n = 112), surface papillary epithelial hyperplasia was evident in 30 % of PLGA and 1 % of non-PLGA (i.e., MEC, ACC, PA). The greater frequency of surface papillary epithelial hyperplasia in the PLGA versus non-PLGA cases and in the benign versus malignant cases was significant (p = .0001 and p = .041, respectively). The sensitivity and specificity of papillary epithelial hyperplasia for PLGA were 30 % (95 % confidence interval (CI) 11.97-54.27 %) and 99 % (95 % CI 94-99.82 %), respectively. The clinical presentation of PLGA appeared relatively nonspecific, with all analyzed tumor types exhibiting a predilection for females, middle-aged to older adults, palatal location, pink/tan/normal color, and firm consistency. In conclusion, papillary epithelial hyperplasia was evident in only a minority of PLGA. However, when present within the context of a palatal salivary gland neoplasm, it appears to indicate a high probability of PLGA. Accordingly, rough mucosa may be a useful clinical pearl for identification of PLGA.

Similar degree of intimal hyperplasia in surgically detected stenotic and nonstenotic arteriovenous fistula segments: a preliminary report.

PubMed

Duque, Juan C; Tabbara, Marwan; Martinez, Laisel; Paez, Angela; Selman, Guillermo; Salman, Loay H; Velazquez, Omaida C; Vazquez-Padron, Roberto I

2018-04-01

Intimal hyperplasia has been historically associated with improper venous remodeling and stenosis after creation of an arteriovenous fistula. Recently, however, we showed that intimal hyperplasia by itself does not explain the failure of maturation of 2-stage arteriovenous fistulas. We seek to evaluate whether intimal hyperplasia plays a role in the development of focal stenosis of an arteriovenous fistula. This study compares intimal hyperplasia lesions in stenotic and nearby nonstenotic segments collected from the same arteriovenous fistula. Focal areas of stenosis were detected in the operating room in patients (n= 14) undergoing the second-stage vein transposition procedure. The entire vein was inspected, and areas of stenosis were visually located with the aid of manual palpation and hemodynamic changes in the vein peripheral and central to the narrowing. Stenotic and nonstenotic segments were documented by photography before tissue collection (14 tissue pairs). Intimal area and thickness, intima-media thickness, and intima to media area ratio were measured in hematoxylin and eosin stained cross-sections followed by pairwise statistical comparisons. The intimal area in stenotic and nonstenotic segments ranged from 1.25 to 11.61 mm 2 and 1.29 to 5.81 mm 2 , respectively. There was no significant difference between these 2 groups (P=.26). Maximal intimal thickness (P=.22), maximal intima-media thickness (P=.13), and intima to media area ratio (P=.73) were also similar between both types of segments. This preliminary study indicates that postoperative intimal hyperplasia by itself is not associated with the development of focal venous stenosis in 2-stage fistulas. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of chronic prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH).

PubMed

Gandaglia, Giorgio; Briganti, Alberto; Gontero, Paolo; Mondaini, Nicola; Novara, Giacomo; Salonia, Andrea; Sciarra, Alessandro; Montorsi, Francesco

2013-08-01

Several different stimuli may induce chronic prostatic inflammation, which in turn would lead to tissue damage and continuous wound healing, thus contributing to prostatic enlargement. Patients with chronic inflammation and benign prostatic hyperplasia (BPH) have been shown to have larger prostate volumes, more severe lower urinary tract symptoms (LUTS) and a higher probability of acute urinary retention than their counterparts without inflammation. Chronic inflammation could be a predictor of poor response to BPH medical treatment. Thus, the ability to identify patients with chronic inflammation would be crucial to prevent BPH progression and develop target therapies. Although the histological examination of prostatic tissue remains the only available method to diagnose chronic inflammation, different parameters, such as prostatic calcifications, prostate volume, LUTS severity, storage and prostatitis-like symptoms, poor response to medical therapies and urinary biomarkers, have been shown to be correlated with chronic inflammation. The identification of patients with BPH and chronic inflammation might be crucial in order to develop target therapies to prevent BPH progression. In this context, clinical, imaging and laboratory parameters might be used alone or in combination to identify patients that harbour chronic prostatic inflammation. © 2013 BJU International.

Clinical Trials in Benign Prostatic Hyperplasia: A Moving Target of Success.

PubMed

Thomas, Dominique; Chung, Caroline; Zhang, Yiye; Te, Alexis; Gratzke, Christian; Woo, Henry; Chughtai, Bilal

2018-05-24

Benign prostatic hyperplasia (BPH) affects over 50% of men above the age of 50 yr. With half of these men having bothersome lower urinary tract symptoms, this area represents a hot bed of novel treatments. Many BPH therapies have favorable short-term outcomes but lack durability or well-defined adverse events (AEs). Clinical trials are a gold standard for comparing treatments. We characterized all BPH clinical trials registered worldwide from inception to 2017. A total of 251 clinical trials were included. Of the studies, 30.1% used patient-reported outcomes such as the American Urological Association Symptom Score. Approximately 70% of clinical trials studied medical interventions, while the remaining trials investigated surgical approaches. Seventy-nine percent of trials were industry sponsored, while a minority were funded without commercial interest. Only 42% of trials had 12-mo follow-up, with the majority with <3 mo of follow-up. No trials evaluated prevention, diet, behavior, or alternative methods Overall, only 23% of trials reported results. Management options for BPH need unified benchmarks of success, AEs, durability, and standard reporting for all clinical trials, regardless of outcomes. We found that the majority of clinical trials were medical intervention, with very few trials evaluating prevention, diet, behavior, or alternative methods Furthermore, a few trials reported results in peer-reviewed journals. All clinical trials need to report results regardless of outcome, and in conclusion, standardized methods are needed in order to document the successes, adverse events, and durability for all clinical trials. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Genetic Disruption of 21-Hydroxylase in Zebrafish Causes Interrenal Hyperplasia.

PubMed

Eachus, Helen; Zaucker, Andreas; Oakes, James A; Griffin, Aliesha; Weger, Meltem; Güran, Tülay; Taylor, Angela; Harris, Abigail; Greenfield, Andy; Quanson, Jonathan L; Storbeck, Karl-Heinz; Cunliffe, Vincent T; Müller, Ferenc; Krone, Nils

2017-12-01

Congenital adrenal hyperplasia is a group of common inherited disorders leading to glucocorticoid deficiency. Most cases are caused by 21-hydroxylase deficiency (21OHD). The systemic consequences of imbalanced steroid hormone biosynthesis due to severe 21OHD remains poorly understood. Therefore, we developed a zebrafish model for 21OHD, which focuses on the impairment of glucocorticoid biosynthesis. A single 21-hydroxylase gene (cyp21a2) is annotated in the zebrafish genome based on sequence homology. Our in silico analysis of the 21-hydroxylase (Cyp21a2) protein sequence suggests a sufficient degree of similarity for the usage of zebrafish cyp21a2 to model aspects of human 21OHD in vivo. We determined the spatiotemporal expression patterns of cyp21a2 by whole-mount in situ hybridization and reverse transcription polymerase chain reaction throughout early development. Early cyp21a2 expression is restricted to the interrenal gland (zebrafish adrenal counterpart) and the brain. To further explore the in vivo consequences of 21OHD we created several cyp21a2 null-allele zebrafish lines by using a transcription activator-like effector nuclease genomic engineering strategy. Homozygous mutant zebrafish larvae showed an upregulation of the hypothalamic-pituitary-interrenal (HPI) axis and interrenal hyperplasia. Furthermore, Cyp21a2-deficient larvae had a typical steroid profile, with reduced concentrations of cortisol and increased concentrations of 17-hydroxyprogesterone and 21-deoxycortisol. Affected larvae showed an upregulation of the HPI axis and interrenal hyperplasia. Downregulation of the glucocorticoid-responsive genes pck1 and fkbp5 indicated systemic glucocorticoid deficiency. Our work demonstrates the crucial role of Cyp21a2 in glucocorticoid biosynthesis in zebrafish larvae and establishes an in vivo model allowing studies of systemic consequences of altered steroid hormone synthesis.

The Functional Role of Reactive Stroma in Benign Prostatic Hyperplasia

PubMed Central

Schauer, Isaiah G.; Rowley, David R.

2011-01-01

The human prostate gland is one of the only internal organs that continue to enlarge throughout adulthood. The specific mechanisms that regulate this growth, as well as the pathological changes leading to the phenotype observed in the disease benign prostatic hyperplasia (BPH), are essentially unknown. Recent studies and their associated findings have made clear that many complex alterations occur, involving persistent and chronic inflammation, circulating hormonal level deregulation, and aberrant wound repair processes. BPH has been etiologically characterized as a progressive, albeit discontinuous, hyperplasia of both the glandular epithelial and stromal cell compartments coordinately yielding an expansion of the prostate gland and clinical symptoms. Interestingly, the inflammatory and repair responses observed in BPH are also key components of general wound repair in post-natal tissues. These responses include altered expression of chemokines, cytokines, matrix remodeling factors, chronic inflammatory processes, altered immune surveillance and recognition, as well as the formation of a prototypical ‘reactive’ stroma which is similar to that observed across various fibroplasias and malignancies of a variety of tissue sites. Stromal tissue, both embryonic mesenchyme, and adult reactive stroma myofibroblasts, has been shown to exert potent and functional regulatory control over epithelial proliferation and differentiation as well as immunoresponsive modulation. Thus, the functional biology of a reactive stroma, within the context of an adult disease typified by epithelial and stromal aberrant hyperplasia, is critical to understand within the context of prostate disease and beyond. The mechanisms that regulate reactive stroma biology in BPH represent targets of opportunity for new therapeutic approaches that may extend to other tissue contexts. Accordingly, this review seeks to address the dissection of important factors, signaling pathways, genes, and other

Hyperplasia vs hypertrophy in tissue regeneration after extensive liver resection.

PubMed

Marongiu, Fabio; Marongiu, Michela; Contini, Antonella; Serra, Monica; Cadoni, Erika; Murgia, Riccardo; Laconi, Ezio

2017-03-14

To address to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss. The ability of the liver to regenerate is remarkable on both clinical and biological grounds. Basic mechanisms underlying this process have been intensively investigated. However, it is still debated to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss. We addressed this issue using a genetically tagged system. We were able to follow the fate of single transplanted hepatocytes during the regenerative response elicited by 2/3 partial surgical hepatectomy (PH) in rats. Clusters of transplanted cells were 3D reconstructed and their size distribution was evaluated over time after PH. Liver size and liver DNA content were largely recovered 10 d post-PH, as expected ( e.g ., total DNA/liver/100 g b.w. was 6.37 ± 0.21 before PH and returned to 6.10 ± 0.36 10 d after PH). Data indicated that about 2/3 of the original residual hepatocytes entered S-phase in response to PH. Analysis of cluster size distribution at 24, 48, 96 h and 10 d after PH revealed that about half of the remnant hepatocytes completed at least 2 cell cycles. Average size of hepatocytes increased at 24 h (248.50 μm 2 ± 7.82 μm 2 , P = 0.0015), but returned to control values throughout the regenerative process (up to 10 d post-PH, 197.9 μm 2 ± 6.44 μm 2 , P = 0.11). A sizeable fraction of the remnant hepatocyte population does not participate actively in tissue mass restoration. Hyperplasia stands as the major mechanism contributing to liver mass restoration after PH, with hypertrophy playing a transient role in the process.

Adenoid basal hyperplasia of the uterine cervix: a lesion of reserve cell type, distinct from adenoid basal carcinoma.

PubMed

Kerdraon, Olivier; Cornélius, Aurélie; Farine, Marie-Odile; Boulanger, Loïc; Wacrenier, Agnès

2012-12-01

Adenoid basal hyperplasia is an underrecognized cervical lesion, resembling adenoid basal carcinoma, except the absence of deep invasion into the stroma. We report a series of 10 cases, all extending less than 1 mm from the basement membrane. Our results support the hypothesis that adenoid basal hyperplasia arises from reserve cells of the cervix. Lesions were found close to the squamocolumnar junction, in continuity with the nearby subcolumnar reserve cells. They shared the same morphology and immunoprofile using a panel of 4 antibodies (keratin 5/6, keratin 14, keratin 7 and p63) designed to differentiate reserve cells from mature squamous cells and endocervical columnar cells. We detected no human papillomavirus infection by in situ hybridization targeting high-risk human papillomavirus, which was concordant with the absence of immunohistochemical p16 expression. We demonstrated human papillomavirus infection in 4 (80%) of 5 adenoid basal carcinoma, which is in the same range as previous studies (88%). Thus, adenoid basal hyperplasia should be distinguished from adenoid basal carcinoma because they imply different risk of human papillomavirus infection and of subsequent association with high-grade invasive carcinoma. In our series, the most reliable morphological parameters to differentiate adenoid basal hyperplasia from adenoid basal carcinoma were the depth of the lesion and the size of the lesion nests. Furthermore, squamous differentiation was rare in adenoid basal hyperplasia and constant in adenoid basal carcinoma. Finally, any mitotic activity and/or an increase of Ki67 labeling index should raise the hypothesis of adenoid basal carcinoma. Copyright © 2012 Elsevier Inc. All rights reserved.

Understanding the premalignant potential of atypical hyperplasia through its natural history: A longitudinal cohort study

PubMed Central

Hartmann, Lynn C; Radisky, Derek C; Frost, Marlene H; Santen, Richard J; Vierkant, Robert A; Benetti, Lorelle L; Tarabishy, Yaman; Ghosh, Karthik; Visscher, Daniel W; Degnim, Amy C

2014-01-01

Atypical hyperplasia is a high risk premalignant lesion of the breast, but its biology is poorly understood. Many believe that atypical ductal hyperplasia (ADH) is a direct precursor for low-grade ductal breast cancer (BC) while atypical lobular hyperplasia (ALH) serves as a risk indicator. These assumptions underlie current clinical recommendations. We tested these assumptions by studying the characteristics of the breast cancers (BCs) that develop in women with ADH or ALH. Using the Mayo Benign Breast Disease Cohort, we identified all women with ADH or ALH from 1967–2001 and followed them for later BCs, characterizing side of BC vs side of atypia; time to BC; type, histology and grade of BC, looking for patterns consistent with precursors vs risk indicators. 698 women with atypical hyperplasia were followed a mean of 12.5 years; 143 developed BC. For both ADH and ALH, there is a 2:1 ratio of ipsilateral to contralateral BCs. The ipsilateral predominance is marked in the first five years, consistent with a precursor phenotype for both ADH and ALH. For both, there is a predominance of invasive ductal cancers with 69% of moderate or high-grade. 25% are node positive. Both ADH and ALH portend risk for DCIS and invasive BCs, predominantly ductal, with two thirds moderate or high-grade. The ipsilateral breast is at especially high risk for BC in the first five years after atypia, with risk remaining elevated in both breasts long-term. ADH and ALH behave similarly in terms of later BC endpoints. PMID:24480577

Pulsed electromagnetic field with or without exercise therapy in the treatment of benign prostatic hyperplasia

PubMed Central

Elgohary, Hany M; Tantawy, Sayed A

2017-01-01

[Purpose] To investigate the effect of pulsed electromagnetic field with or without exercise therapy in the treatment of benign prostatic hyperplasia. [Subjects and Methods] Sixty male patients aged 55–65 years with benign prostatic hyperplasia were invited to participate in this study. Patients were randomly assigned to Group A (n=20; patients who received pulsed electromagnetic field in addition to pelvic floor and aerobic exercises), Group B (n=20; patients who received pulsed electromagnetic field), and Group C (n=20; patients who received placebo electromagnetic field). The assessments included post-void residual urine, urine flow rate, prostate specific antigen, white blood cells count, and International Prostate Symptom Score were weighed, before and after a 4-week intervention. [Results] There were significant differences in Group A and B in all parameters. Group C showed non-significant differences in all measured variables except for International Prostate Symptom Score. Among groups, all parameters showed highly significant differences in favor of Group A. There were non-significant differences between Group A and B and significant difference between Groups A and C and between Groups B and C. [Conclusion] The present study demonstrated that electromagnetic field had a significant impact on the treatment of benign prostatic hyperplasia. Accordingly, electromagnetic field can be utilized alone or in combination with other physiotherapy modalities. Moreover, clinicians should have the capacity to perceive the advantages accomplished using extra treatment alternatives. Electromagnetic field is a safe, noninvasive method and can be used for the treatment of benign prostatic hyperplasia. PMID:28878453

Fetal endocrine therapy for congenital adrenal hyperplasia should not be done.

PubMed

Miller, Walter L

2015-06-01

Prenatal treatment of congenital adrenal hyperplasia by administering dexamethasone to a woman presumed to be carrying an at-risk fetus remains a controversial experimental treatment. Review of data from animal experimentation and human trials indicates that dexamethasone cannot be considered safe for the fetus. In animals, prenatal dexamethasone decreases birth weight, affects renal, pancreatic beta cell and brain development, increases anxiety and predisposes to adult hypertension and hyperglycemia. In human studies, prenatal dexamethasone is associated with orofacial clefts, decreased birth weight, poorer verbal working memory, and poorer self-perception of scholastic and social competence. Numerous medical societies have cautioned that prenatal treatment of adrenal hyperplasia with dexamethasone is not appropriate for routine clinical practice and should only be done in Institutional Review Board approved, prospective clinical research settings with written informed consent. The data indicate that this treatment is inconsistent with the classic medical ethical maxim to 'first do no harm'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinical and molecular profile of newborns with confirmed or suspicious congenital adrenal hyperplasia detected after a public screening program implementation.

PubMed

Kopacek, Cristiane; Prado, Mayara J; da Silva, Claudia M D; de Castro, Simone M; Beltrão, Luciana A; Vargas, Paula R; Grandi, Tarciana; Rossetti, Maria L R; Spritzer, Poli Mara

2018-04-30

To describe the results obtained in a neonatal screening program after its implementation and to assess the clinical and molecular profiles of confirmed and suspicious congenital adrenal hyperplasia cases. A cross-sectional study was conducted. Newborns with suspected disease due to high 17-hydroxyprogesterone levels and adjusted for birth weight were selected. Classical congenital adrenal hyperplasia (salt-wasting and simple virilizing forms) was diagnosed by an increase in 17-hydroxyprogesterone levels as confirmed in the retest, clinical evaluation, and genotype determined by SNaPshot and multiplex ligation-dependent probe amplification. After 24 months, 15 classic congenital adrenal hyperplasia cases were diagnosed in a total of 217,965 newborns, with an estimated incidence of 1:14,531. From 132 patients, seven non-classical and 14 heterozygous patients were screened for CYP21A2 mutations, and 96 patients presented false positives with wild type CYP21A2. On retest, increased 17-hydroxyprogesterone levels were found in classical congenital adrenal hyperplasia patients and showed significant correlation with genotype-related classical genital adrenal hyperplasia. The most frequent mutations were IVS2-13A/C>G followed by gene deletion or rearrangement events in the classical form. In non-classical and heterozygous diseases, p.Val282Leu was the most common mutation. The results underscore the effectiveness of congenital adrenal hyperplasia neonatal screening in the public health system and indicate that the adopted strategy was appropriate. The second sample collection along with genotyping of suspected cases helped to properly diagnose both severe and milder cases and delineate them from false positive patients. Copyright © 2018. Published by Elsevier Editora Ltda.

Recent advances in treatment for Benign Prostatic Hyperplasia.

PubMed

van Rij, Simon; Gilling, Peter

2015-01-01

Clinical benign prostatic hyperplasia (BPH), often identified as a worsening ability of a male to pass urine, is a significant problem for men in our society. In 2015, the use of personalised medicine is tailoring treatment to individual patient needs and to genetic characteristics. Technological advances in surgical treatment are changing the way BPH is treated and are resulting in less morbidity. The future of BPH treatments is exciting, and a number of novel techniques are currently under clinical trial.

Inhibition of plaque neovascularization and intimal hyperplasia by specific targeting vascular endothelial growth factor with bevacizumab-eluting stent: an experimental study.

PubMed

Stefanadis, Christodoulos; Toutouzas, Konstantinos; Stefanadi, Elli; Lazaris, Andreas; Patsouris, Efstratios; Kipshidze, Nicholas

2007-12-01

Neovascularization is associated with destabilization of atheromatic plaques. Increased expression of vascular endothelial growth factor (VEGF) is important in the process of neovascularization. We assessed the effect of bevacizumab, a monoclonal antibody specific for VEGF, on neovascularization. We used 12 New Zealand rabbits under atherogenic diet for 3 weeks. We immersed a phosphorycholine coated stent into a solution of 4 ml bevacizumab according to previous studies. Twelve eluting stents and 12 non-eluting stents were implanted in the middle segment of the rabbit's iliac arteries. Follow-up angiography was performed at 4 weeks and tissues were obtained for histological analysis. The procedure of stent loading with bevacizumab and stent implantation was successful. There was no difference in angiographic measurements before, after implantation and at follow-up between the two groups. mean neointimal thickness (0.09+/-0.02 versus 0.12+/-0.02 mm, p<0.01), and mean neointimal area (1.08+/-0.09 versus 1.20+/-0.12 mm(2), p<0.01) were less in the bevacizumab treated segments. bevacizumab-treated arterial segments demonstrated significantly decreased microvessel density compared with the control group (1.69+/-0.06 CI: 1.65-1.73 versus 15.68+/-0.56 CI: 15.32-16.04 vessels per mm(2), p<0.001) and vegf expression was decreased in the media and adventitia of bevacizumab group. Endothelialization, inflammation and injury scores were similar between the two groups. These results suggest that bevacizumab-eluting stent implantation in rabbit iliac arteries is safe, and inhibits neovascularization without affecting the endothelialization.

Irradiation inhibits vascular anastomotic stenosis in a canine model.

PubMed

Saito, Takeshi; Iguchi, Atsushi; Tabayashi, Koichi

2009-08-01

The graft patency rate after coronary artery bypass grafting (CABG) correlates with anastomotic stenosis. Intracoronary radiation therapy is effective for preventing restenosis after percutaneous coronary intervention (PCI). We postulated that intracoronary radiation therapy could prevent anastomotic stenosis and tested this hypothesis in an animal model. Femoral arteries and veins of beagle dogs were harvested, and composite arterioarterial and arteriovenous grafts were prepared. After external irradiation of the anastomotic sites, these composite grafts were transplanted into femoral arteries. Histomorphometric and immunohistological analyses of the anastomotic sites were performed. The study groups consisted of controls and animals exposed to 10 Gy, 20 Gy, and 30 Gy (n = 5, in each group). In the artery graft model, the ratio of negative remodeling was significantly increased in all groups exposed to >or=10 Gy. The ratio of neointimal hyperplasia was significantly decreased in all groups exposed to >or=10 Gy. Cell density of anti-alpha-actin antibody-positive cells and anti-proliferating cell nuclear antigen (PCNA) antibody-positive cells was highest in the adventitial layer, and the density decreased as the dosage increased. Experimental results were almost the same in the vein graft models as in the artery graft models. With double immunohistostaining, the anti-PCNA antibody-positive cells expressed alpha-actin. Irradiation can inhibit anastomotic stenosis in a canine model. Adventitia is a factor in the creation of stenosis, and irradiation appears to target the adventitia. We speculate that there might be a possible role for intracoronary irradiation in the future to prevent anastomotic stenosis.

Diagnostic utility and limitations of glutamine synthetase and serum amyloid-associated protein immunohistochemistry in the distinction of focal nodular hyperplasia and inflammatory hepatocellular adenoma.

PubMed

Joseph, Nancy M; Ferrell, Linda D; Jain, Dhanpat; Torbenson, Michael S; Wu, Tsung-Teh; Yeh, Matthew M; Kakar, Sanjay

2014-01-01

Inflammatory hepatocellular adenoma can show overlapping histological features with focal nodular hyperplasia, including inflammation, fibrous stroma, and ductular reaction. Expression of serum amyloid-associated protein in inflammatory hepatocellular adenoma and map-like pattern of glutamine synthetase in focal nodular hyperplasia can be helpful in this distinction, but the pitfalls and limitations of these markers have not been established. Morphology and immunohistochemistry were analyzed in 54 inflammatory hepatocellular adenomas, 40 focal nodular hyperplasia, and 3 indeterminate lesions. Morphological analysis demonstrated that nodularity, fibrous stroma, dystrophic blood vessels, and ductular reaction were more common in focal nodular hyperplasia, while telangiectasia, hemorrhage, and steatosis were more common in inflammatory hepatocellular adenoma, but there was frequent overlap of morphological features. The majority of inflammatory hepatocellular adenomas demonstrated perivascular and/or patchy glutamine synthetase staining (73.6%), while the remaining cases had diffuse (7.5%), negative (3.8%), or patchy pattern of staining (15%) that showed subtle differences from the classic map-like staining pattern and was designated as pseudo map-like staining. Positive staining for serum amyloid-associated protein was seen in the majority of inflammatory hepatocellular adenomas (92.6%) and in the minority of focal nodular hyperplasia (17.5%). The glutamine synthetase staining pattern was map-like in 90% of focal nodular hyperplasia cases, with the remaining 10% of cases showing pseudo map-like staining. Three cases were labeled as indeterminate and showed focal nodular hyperplasia-like morphology but lacked map-like glutamine synthetase staining pattern; these cases demonstrated a patchy pseudo map-like glutamine synthetase pattern along with the expression of serum amyloid-associated protein. Our results highlight the diagnostic errors that can be caused by variant

Development of Bioelastic Materials for the Prevention of Adhesions: Polypenta- and Polytetrapeptides

DTIC Science & Technology

1993-03-14

shows promise in of orbital fat. Fibrovascular and fibrofatty scarring can preventing the occurrence of scar tissue in biologic sys- occur with poor...demonstrated a dense fibrovascular scar. For the test animals two compositions of bioelastic materials were used, X2 0 -poly(GVGVP) with three animals and...pericardium may have occurred following a previous operation. There are many conditions necessitating reoperation 5 °,6 5 : "intimal hyperplasia of

Expression of cyclin D{sub 1} during endotoxin-induced aleveolar type II cell hyperplasia in rat lung and the detection of apoptotic cells during the remodeling process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tesfaigzi, J.; Wood, M.B.; Johnson, N.F.

Our studies have shown that endotoxin intratracheally instilled into the rat lung induces proliferation of alveolar type II cells. In that study, the alveolar type II cells. In that study, the alveolar type II cell hyperplasia occurred 2 d after instillation of endotoxin and persisted for a further 2 d. After hyperplasia, the lung remodeled and returned to a normal state within 24-48 h. Understanding the mechanisms involved in the remodeling process of this transient hyperplasia may be useful to identify molecular changes that are altered in neoplasia. The purpose of the present study was to corroborate induction of epithelialmore » cell hyperplasia by endotoxin and to delineate mechanisms involved in tissue remodeling after endotoxin-induced alveolar type II cell hyperplasia. In conclusion, immonostaining with cyclin D1 and cytokeratin shows that endotoxin induced epithelial cell proliferation and resulted in hyperplasia in the lung which persisted through 4 d post-instillation.« less

Atypical hyperplasia, proliferative fibrocystic change, and exogenous hormone use.

PubMed

Zera, R T; Danielson, D; Van Camp, J M; Schmidt-Steinbrunn, B; Hong, J; McCoy, M; Anderson, W R; Linzie, B M; Rodriguez, J L

2001-10-01

The association between breast cancer development and exogenous hormone use (EHU) is suggested by indirect clinical evidence. We undertook this study to better define the relationship that EHU has with proliferative fibrocystic change (PFC) and atypical hyperplasia (AH). Women diagnosed with AH without associated carcinoma from January 1990 to December 1999 were compared with control subjects who underwent breast biopsy procedures during the same interval and who were diagnosed with either a proliferative fibrocystic change (PFC) or a nonproliferative fibrocystic change (NPFC). EHU was defined as the use of estrogen or progesterone taken together or separately within 3 months of biopsy. EHU was significantly higher in patients with AH compared with women with NPFC (P =.01). This observation was also significant if all proliferative change (both AH and PFC) was compared with NPFC (P =.03); it was not significant when PFC alone was compared with NPFC. No significant difference in EHU was demonstrated between women with AH and those with PFC. There is strong association between AH and EHU. These results support the theory that a continuum exists between hyperplasia and carcinoma and that EHU may influence the transition from one to the other in an undefined subset of women. We encourage our patients with AH to discontinue EHU.

Pseudocarcinomatous urothelial hyperplasia of the bladder: clinical findings and followup of 70 patients.

PubMed

Kryvenko, Oleksandr N; Epstein, Jonathan I

2013-06-01

Pseudocarcinomatous urothelial hyperplasia is rare and almost exclusively described in the pathology literature. We reviewed 70 cases during a 9.5-year period. Two specimens were taken from biopsies done at our institution and 68 were from cases referred for consultation. Samples were obtained from a total of 60 men and 10 women with a mean age of 67 years (range 33 to 85). Of 68 patients with information available 52 (76.5%) underwent prior pelvic irradiation, 2 received systemic chemotherapy only, 3 had an indwelling bladder catheter, 2 received intravesical chemotherapy, 1 had been treated with radical prostatectomy, 4 had severe peripheral vascular disease, 1 had an arteriovenous malformation, 1 had sickle cell disease and only 2 (2.9%) had no identifiable contributing factors. Pseudocarcinomatous urothelial hyperplasia developed an average of 54.6 months (range 9 months to 13 years) after prior irradiation. Hematuria was the most common clinical presentation, noted in 45 of 51 patients with data available. Of 48 patients with data endoscopy revealed erythema in 20, a papillary/polypoid lesion in 12, broad-based elevated erythematous lesions in 6, erythematous bullous edema in 5, shallow bleeding ulcers in 4 and prominent trabeculation in 1. Additional findings in the bladder were carcinoma in situ in 3 cases, and dysplasia, low grade papillary urothelial carcinoma and papillary urothelial hyperplasia in 1 each. Three of the 40 patients with an average followup of 27 months (range 1 to 94) subsequently had urothelial carcinoma, including 1 who had prior positive cytology and fluorescence in situ hybridization, 1 with prior high grade papillary urothelial carcinoma and 1 with an unknown history. Although pseudocarcinomatous urothelial hyperplasia mimics invasive urothelial carcinoma clinically and histologically, it is not related to urothelial neoplasms. Almost all patients have causes of bladder ischemia, most commonly a history of remote prior pelvic

Multinucleate cell angiohistiocytoma: a fibrohistiocytic proliferation with increased mast cell numbers and vascular hyperplasia.

PubMed

Puig, Lluís; Fernández-Figueras, María-Teresa; Bielsa, Isabel; Lloveras, Betlem; Alomar, Agustín

2002-04-01

Multinucleate cell angiohistiocytoma (MCAH) is an uncommon lesion clinically characterized by multiple papules usually located on the face and acral regions of elderly women. Histopathologically, MCAH is characterized by dermal vascular hyperplasia associated with increased number of factor XIIIa-positive fibrohistiocytic cells and multinucleate cells with scalloped borders. We report the clinical, histopathological and immunohistochemical features of three cases of MCAH, with ulstrastructural study in one of them. The patients were a woman and two men of 56, 40 and 70 years of age, respectively. They all had multiple dull-red papules, which had appeared over several years and were located on the face, the trunk and the dorsa of the hands, respectively. The reticular dermis presented a fibrohistiocytic proliferation of factor XIIIa-positive cells, with abundant bizarre multinucleate cells and vascular hyperplasia. Increased mast cell numbers were seen in all cases, often in apposition to multinucleate cells. Histopathological differential diagnosis of MCAH includes mainly angiofibromas and dermatofibromas, even though vascular hyperplasia can be prominent and has led to many authors to classify MCAH among vascular tumors. Bizarre multinucleate cells can be found in reactive, neoplastic and inflammatory lesions in many sites of the body, and mast cells can play a role in their morphogenesis.

[Effects of soy bean isoflavone on inhibition of benign prostatic hyperplasia and the expressions of NO and NOS of rats].

PubMed

Yang, Aiqing; Ren, Guofeng; Tang, Ling; Jiang, Weiwei

2009-03-01

To explore the inhibitive effect of soybean isoflavone on the prostatic hyperplasia on the expressions of nitric oxid and nitric oxide synthase in the prostatic hyperplasia rats. Subcutaneously injected testosterone propionate were to induce prostate hyperplasia in rats. The changes of prostate wet weight, prostatic index, liver index, the changes of some biochemical indexes in rat prostate tissue in the control and the treatment, the low, moderate, high dose groups of soybean isoflavone groups were observed. The prostate wet weight and prostatic index in all dose groups were merely lower than those in the treatment and the moderate groups were lowest in all dose group. There were no significant differences in liver index, urea nitrogen, glutamic-pyruvic transaminase of each group. Acid phosphatase, prostatic acid phosphatase and lactate dehydrogenase in all dose groups were merely lower than those in the treatment group. Nitric oxide and nitric oxide synthase in all dose groups were merely higher than those in the treatment group. Soybean isoflavone could inhibit prostate hyperplasia and increase the expressions of nitric oxide and nitric oxide synthase in rats.

Cyclooxygenase-2 expression and clinical parameters in laryngeal squamous cell carcinoma, vocal fold nodule, and laryngeal atypical hyperplasia.

PubMed

Sayar, Cağdaş; Sayar, Hamide; Özdemir, Süleyman; Selçuk, Tahsin; Görgülü, Orhan; Akbaş, Yücel; Kemal Olgun, Mustafa

2013-01-01

The diagnostic role of cyclooxygenase-2 (COX-2) expression in laryngeal atypical hyperplasia, vocal fold nodule, and laryngeal squamous cell carcinoma was examined. Specimens obtained from patients diagnosed with vocal fold nodule (n = 35), atypical hyperplasia (n = 35), laryngeal squamous cell carcinoma (n = 35), and clinical parameters were evaluated retrospectively. Although no staining was observed in patients with vocal fold nodules, staining was noted in laryngeal atypical hyperplasia and squamous cell carcinoma. The percentage of COX-2 staining was the highest in the carcinoma group. It was determined that COX-2 staining was significantly associated with laryngeal squamous cell carcinoma. It should be noted that overexpression of COX-2, a potentially important factor in the evolution of carcinogenesis in precancerous lesions, might be an indicator of the development of carcinoma. Copyright © 2012 Wiley Periodicals, Inc.

K+ channels expression in hypertension after arterial injury, and effect of selective Kv1.3 blockade with PAP-1 on intimal hyperplasia formation.

PubMed

Cidad, P; Novensà, L; Garabito, M; Batlle, M; Dantas, A P; Heras, M; López-López, J R; Pérez-García, M T; Roqué, M

2014-12-01

K(+) channels are central to vascular pathophysiology. Previous results demonstrated that phenotypic modulation associates with a change in Kv1.3 to Kv1.5 expression, and that Kv1.3 blockade inhibits proliferation of VSMCs cultures. To explore whether the Kv1.3 to Kv1.5 switch could be a marker of the increased risk of intimal hyperplasia in essential hypertension and whether systemic treatment with Kv1.3 blockers can prevent intimal hyperplasia after endoluminal lesion . Morphometric and immunohistochemical analysis were performed in arterial segments following arterial injury and constant infusion of the Kv1.3 blocker PAP-1 during 28 days. Differential expression of K(+) channel genes was studied in VSMC from hypertensive (BPH) and normotensive (BPN) mice, both in control and after endoluminal lesion. Finally, the migration and proliferation rate of BPN and BPH VSMCs was explored in vitro. Changes in mRNA expression led to an increased Kv1.3/Kv1.5 ratio in BPH VSMC. Consistent with this, arterial injury in BPH mice induced a higher degree of luminal stenosis, (84 ± 4% vs. 70 ± 5% in BPN, p < 0.01), although no differences in migration and proliferation rate were observed in cultured VSMCs. The in vivo proliferative lesions were significantly decreased upon PAP-1 systemic infusion (18 ± 6% vs. 58 ± 20% with vehicle, p < 0.05). Hypertension leads to a higher degree of luminal stenosis in our arterial injury model, that correlates with a decreased expression of Kv1.5 channels. Kv1.3 blockers decreased in vitro VSMCs proliferation, migration, and in vivo intimal hyperplasia formation, pointing to Kv1.3 channels as promising therapeutical targets against restenosis.

[Effect of nattokinase on restenosis after percutaneous transluminal angioplasty of the abdominal artery in rabbits].

PubMed

Gong, Min; Lin, Huan-bing; Wang, Qian; Xu, Jiang-ping

2008-08-01

To investigate the effect of nattokinase on intimal hyperplasia in rabbit abdominal artery after balloon injury and explore a novel strategy for the preventing restenosis after percutaneous transluminal angioplasty. Fifty-six New Zealand rabbits were randomly divided into 7 groups, namely the solvent control group, model group, natto extract lavage group, refined nattokinse lavage group, intravenous refined nattokinse injection group, clopidogrel group and clopidogrel-aspirin group. Balloon injury was induced by inserting the catheter through the femoral artery into the thoracic aorta of the rabbits. The platelet counts were notad and platelet aggregation was observed, and the abdominal artery was taken for pathological analysis. The expressions of MMP-2 and -9 in the abdominal artery were detected immunohistochemically. There was no significant difference in the platelet counts, platelet aggregation rate or MMP-2 and -9 expression between the model group and the nattokinse-treated groups (P>0.05). The stenosis index in each nattokinse-treated group was significantly greater and the neointimal proliferation index smaller than that of the model group (P<0.01 or 0.05). Nattokinse can inhibit restenosis of rabbit abdominal artery after percutaneous transluminal angioplasty, which is independent of its actions on the platelet or MMP-2 and -9 expressions.

Early diagnosis of salt-losing congenital adrenal hyperplasia in a newborn boy.

PubMed Central

Hughes, I. A.; Winter, J. S.

1977-01-01

Assays of serum 17-hydroxyprogesterone concentration may be relied upon to establish a diagnosis of congenital adrenal hyperplasia within a few hours of birth. In a male infant the concentration of 17-hydroxyprogesterone was increased in cord serum and remained elevated until glucocorticoid therapy was started on the 5th day of life. Plasma renin activity was increased only slightly in the first few days, but a striking increase on day 5, along with a gradual increase in the serum potassium concentration, confirmed that the infant had the salt-losing form of congenital adrenal hyperplasia. It was not possible to demonstrate an increased concentration of 17-hydroxyprogesterone, in amniotic fluid obtained at 30 weeks' gestation, presumably because of interference in this assay by cross-reacting steroids. Studies of the mother's serum concentration of 17-hydroxyprogesterone and cortisol during delivery did not disclose any deviation from normal. PMID:890632

Perforating elastic fibers ('elastic fiber trapping') in the differentiation of keratoacanthoma, conventional squamous cell carcinoma and pseudocarcinomatous epithelial hyperplasia.

PubMed

Shah, Kabeer; Kazlouskaya, Viktoryia; Lal, Karan; Molina, David; Elston, Dirk M

2014-02-01

Keratoacanthoma (KA), an epithelial neoplasm occurring in sun-exposed skin of the elderly, is considered a well-differentiated form of conventional squamous cell carcinoma (SCC) that often follows a course of spontaneous regression. Distinguishing KA from conventional SCC or pseudocarcinomatous epithelial hyperplasia ensures proper diagnosis, treatment and management. For some time, perforating elastic fibers have been utilized in differentiating KA from SCC. This phenomenon may also occur in association with scars and hypertrophic lupus erythematosus (LE). To assess the diagnostic utility of perforating elastic fibers, we compared their incidence in KA, SCC, scars with overlying pseudocarcinomatous hyperplasia, hypertrophic LE, hypertrophic lichen planus (LP) and lichen simplex chronicus (LSC). A retrospective case search identified 359 lesions and the presence of perforating elastic fibers was evaluated using routinely stained sections. This phenomenon was documented in all studied groups except hypertrophic LP. The incidence was found to be 71% in KA, 37% in SCC, and was lowest in inflammatory conditions with associated pseudocarcinomatous hyperplasia (hypertrophic LP 0%, hypertrophic LE 5.9% and LSC 28.2%). The observed frequency in pseudocarcinomatous hyperplasia overlying scars (57.8%) vs. KA (71%) was not statistically different. Although elastic fiber trapping has potential value as a diagnostic criterion for KA, dermatopathologists should consider its limitations. Its diagnostic utility was greatest in distinguishing KA from hypertrophic LE and hypertrophic LP. Conversely, elastic trapping is not helpful differentiating pseudocarcinomatous hyperplasia from recurrent/persistent KA following surgery. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An assessment of mast cells and myofibroblasts in denture-induced fibrous hyperplasia.

PubMed

Kiuchi, Misa; Yamamura, Takashi; Okudera, Michisato; Souksavanh, Vongsa; Ishigami, Tomohiko; Iwase, Takashi; Warnakulasuriya, Saman; Komiyama, Kazuo

2014-01-01

The pathogenesis of denture-induced fibrous hyperplasias has not been examined in detail to explain how tissue injury results in fibrous hyperplasia of the oral mucosa. We examined the presence of mast cells and myofibroblasts in 33 denture-induced fibrous hyperplasias (DIFH) compared with 10 healthy gingival tissues. The parameters examined included mast cell numbers, tissue distribution, degranulation, and cell subtypes using immunohistochemistry. The presence of myofibroblasts and their likely origin was also examined by double immunofluorescense staining. Furthermore, we investigated the synthesis of osteopontin and TGF-β, considered to be involved in the transformation of a fibroblast to a myofibroblast. The results demonstrated that the mast cell numbers are significantly increased in the DIFH compared with non-disease controls. The mast cell localization in lesions was higher in the superficial areas with inflammatory cell infiltration compared with the deep fibrotic area (P < 0.01). The number of tryptase-positive mast cells was significantly higher compared with chymase-positive ones. The TGF-β- or osteopontin-positive cell infiltration into the lesion was found in high numbers. The presence of myofibroblasts was identified in 14 of 33 cases (42%), and some of these cells showed apoptosis when assessed by the TUNEL assay. On the survey of the origin of myofibroblasts, results showed αSMA and vimentin positivity indicating these transformed from fibroblasts. These results are the first to show that mast cells and myofibroblasts can be detected in DIFH, indicating important roles of these cells in the pathogenesis of this lesion. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A three-year follow-up of congenital adrenal hyperplasia newborn screening.

PubMed

Pezzuti, Isabela L; Barra, Cristina B; Mantovani, Rafael M; Januário, José N; Silva, Ivani N

2014-01-01

congenital adrenal hyperplasia (CAH) newborn screening can prevent neonatal mortality in children with the salt-wasting form of the disease and prevent incorrect gender assignments, which can occur in females. However, the occurrence of false-positive results in preterm or low-birth-weight newborns creates some diagnostic difficulties, with consequent therapeutic implications. This study aimed to report the results of a pilot project for neonatal CAH screening conducted in the state of Minas Gerais, Brazil from 09/2007 to 05/2008 with a three-year follow-up. dried blood specimens were collected on filter paper cards three to seven days after birth of all newborns in the period. Samples were analyzed for 17-hydroxyprogesterone using an enzyme-linked immunosorbent assay (ELISA). a total of 159,415 children were screened. The apparent incidence of the classic variant of the disease was 1:9,963, based on initial diagnoses following newborn screening. During the follow-up period, eight of 16 children initially diagnosed with CAH were reclassified as unaffected, resulting in a revised incidence of 1:19,927. The false-positive rate was 0.31%, and the positive predictive value was 2.1%. Sensitivity and specificity were 100% and 99.7%, respectively. newborn screening is an important public health policy in developing countries such as Brazil, where CAH remains underdiagnosed. It has great potential to identify children with the disease who otherwise cannot be diagnosed earlier. Long-term follow-up and monitoring of all children with positive screening results are crucial to ensure a correct diagnosis and to calculate a reliable incidence ratio of the disease. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Experimental pancreatic hyperplasia and neoplasia: effects of dietary and surgical manipulation.

PubMed Central

Watanapa, P.; Williamson, R. C.

1993-01-01

Several studies carried out during the past two decades have investigated the effect of dietary and surgical manipulation on pancreatic growth and carcinogenesis. Diets high in trypsin inhibitor stimulate pancreatic growth and increase the formation of preneoplastic lesions and carcinomas in the rat pancreas. Cholecystokinin (CCK) is the key intermediary in this response, since both natural and synthetic trypsin inhibitors increase circulating levels of the hormone and CCK antagonists largely prevent these changes. Fatty acids enhance pancreatic carcinogenesis in both rats and hamsters, whereas protein appears to have a protective role in the rat, but to increase tumour yields in the hamster. Several surgical operations affect the pancreas. Pancreatobiliary diversion and partial gastrectomy stimulate pancreatic growth and enhance carcinogenesis, probably by means of increased CCK release. Complete duodenogastric reflux has similar effects on the pancreas but the gut peptide involved is gastrin. Although massive small bowel resection increases pancreatic growth, the marked reduction in caloric absorption probably explains its failure to enhance carcinogenesis. CCK and enteroglucagon might work in concert to modulate the tropic response of the pancreas to small bowel resection. In the pancreas, as in the large intestine, hyperplasia appears to precede and predispose to neoplasia. PMID:8494719

Denture-related hyperplasia: a clinical study of a Turkish population group.

PubMed

Canger, Emin Murat; Celenk, Peruze; Kayipmaz, Saadettin

2009-01-01

Inflammatory fibrous hyperplasia (epulis fissuratum) (IFH) and inflammatory papillary hyperplasia (IPH) are oral mucosal diseases caused by ill-fitting denture wearing. A study was carried out on a group of Turkish people consisted of 131 female and 39 male complete denture wearers (n= 170) distributed in two age groups (30-60 and 60-80 years old). The analysis of data collected from patients showed that while the incidence of IFH was higher in women than in men, the incidence of IPH was similar. Most lesions were found in the 30-60 year-old group. The incidence of lesions increased as the denture wearing period increased. Soft tissue growth was the main complaint of the patients with IFH and IPH. In the maxilla, the incidence of IFH was higher than IPH. There was also a significant difference between the distribution of the lesion types in the jaws. There were a larger number of lesions in the maxilla compared to the mandible and most IFH lesions were located in the anterior region of the jaws.

Levonorgestrel-releasing intrauterine device versus dydrogesterone for management of endometrial hyperplasia without atypia.

PubMed

El Behery, Manal M; Saleh, Hend S; Ibrahiem, Moustafa A; Kamal, Ebtesam M; Kassem, Gamal A; Mohamed, Mohamed El Sayed

2015-03-01

To compare the efficacy and safety of the levonorgestrel-releasing intrauterine device (LNG-IUD) with dydrogesterone applied for the same duration in patients having endometrial hyperplasia (EH) without atypia. One hundred thirty eight women aged between 30 and 50 years with abnormal uterine bleeding and diagnosed as EH by transvaginal ultrasound were randomized to receive either LNG-IUD or dydrogesterone for 6 months. Primary outcome measures were regression of hyperplasia after 6 months of therapy. Secondary outcome measures were occurrence of side effects during treatment or recurrence of hyperplasia during follow-up period. After 6 months of treatment, regression of EH occurs in 96% of women in the levonorgestrel-releasing intrauterine system (LNG-IUS) group versus 80% of women in the oral group (P < .001). Adverse effects were relatively common with minimal differences between the 2 groups. Intermenstrual vaginal spotting and amenorrhea were more common in the LNG-IUD group (P value .01 and .0001). Patient satisfaction was significantly higher in the LNG-IUS group (P value .0001). Hysterectomy rates were lower in the LNG-IUS group than in the oral group (P = .001). Recurrence rate was 0% in the LNG-IUD group compared to 12.5% in the oral group. In management of EH without atypia, LNG-IUS achieves a higher regression and a lower hysterectomy rate than oral progesterone and could be used as a first-line therapy. © The Author(s) 2014.

Feminising genitoplasty: one-stage genital reconstruction in congenital adrenal hyperplasia: 30 years' experience.

PubMed

Roll, M F; Kneppo, C; Roth, H; Bettendorf, M; Waag, K-L; Holland-Cunz, S

2006-10-01

The study objective is to evaluate the results of our surgical technique for children with congenital adrenal hyperplasia and ambiguous genitalia at the University Hospital of Heidelberg, Department of Paediatric Surgery. The records of 19 patients with congenital adrenal hyperplasia treated between 1972 and 2004 were reviewed with respect to age at surgery, operative procedures and outcome. We describe the recession clitoroplasty technique currently used in our hospital and highlight the importance of short and long-term follow-up results with respect to appearance, position and size of the clitoris and quality of the vagina. One-stage recession clitoroplasty and vaginoplasty gives very satisfactory cosmetic and functional results, with few complications and a reduced need for secondary surgical interventions. The results of this study support the assumption that total correction can be achieved through a single-stage operation, performed in infancy.

A case of adenocarcinoma of the rete testis accompanied by focal adenomatous hyperplasia

PubMed Central

2013-01-01

Abstract Adenocarcinoma of the rete testis is very rare. There is still little knowledge about its etiology and pathogenesis. Herein, we present a case of rete testis adenocarcinoma in a 36-year-old Chinese male. The tumor was predominantly composed of irregular small tubules and papillary structures with cuboidal or polygonal cells. In peripheral area of the tumor, the remaining normal rete testis and adenomatous hyperplasia of the rete testis could also be seen, indicating the possible relationship between adenomatous hyperplasia and adenocarcinoma. In addition, the patient underwent a left hydrocelectomy because of the existence of hydrocele 3 years ago. But, it is unclear whether hydrocele and hydrocelectomy is its cause or just the early clinical presentation of the adenocarcinoma. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6757609119625499 PMID:23800084

Anoctamin 1 (TMEM16A) is essential for testosterone-induced prostate hyperplasia.

PubMed

Cha, Joo Young; Wee, Jungwon; Jung, Jooyoung; Jang, Yongwoo; Lee, Byeongjun; Hong, Gyu-Sang; Chang, Beom Chul; Choi, Yoon-La; Shin, Young Kee; Min, Hye-Young; Lee, Ho-Young; Na, Tae-Young; Lee, Mi-Ock; Oh, Uhtaek

2015-08-04

Benign prostatic hyperplasia (BPH) is characterized by an enlargement of the prostate, causing lower urinary tract symptoms in elderly men worldwide. However, the molecular mechanism underlying the pathogenesis of BPH is unclear. Anoctamin1 (ANO1) encodes a Ca(2+)-activated chloride channel (CaCC) that mediates various physiological functions. Here, we demonstrate that it is essential for testosterone-induced BPH. ANO1 was highly amplified in dihydrotestosterone (DHT)-treated prostate epithelial cells, whereas the selective knockdown of ANO1 inhibited DHT-induced cell proliferation. Three androgen-response elements were found in the ANO1 promoter region, which is relevant for the DHT-dependent induction of ANO1. Administration of the ANO1 blocker or Ano1 small interfering RNA, inhibited prostate enlargement and reduced histological abnormalities in vivo. We therefore concluded that ANO1 is essential for the development of prostate hyperplasia and is a potential target for the treatment of BPH.

Anoctamin 1 (TMEM16A) is essential for testosterone-induced prostate hyperplasia

PubMed Central

Cha, Joo Young; Wee, Jungwon; Jung, Jooyoung; Jang, Yongwoo; Lee, Byeongjun; Hong, Gyu-Sang; Chang, Beom Chul; Choi, Yoon-La; Shin, Young Kee; Min, Hye-Young; Lee, Ho-Young; Na, Tae-Young; Lee, Mi-Ock; Oh, Uhtaek

2015-01-01

Benign prostatic hyperplasia (BPH) is characterized by an enlargement of the prostate, causing lower urinary tract symptoms in elderly men worldwide. However, the molecular mechanism underlying the pathogenesis of BPH is unclear. Anoctamin1 (ANO1) encodes a Ca2+-activated chloride channel (CaCC) that mediates various physiological functions. Here, we demonstrate that it is essential for testosterone-induced BPH. ANO1 was highly amplified in dihydrotestosterone (DHT)-treated prostate epithelial cells, whereas the selective knockdown of ANO1 inhibited DHT-induced cell proliferation. Three androgen-response elements were found in the ANO1 promoter region, which is relevant for the DHT-dependent induction of ANO1. Administration of the ANO1 blocker or Ano1 small interfering RNA, inhibited prostate enlargement and reduced histological abnormalities in vivo. We therefore concluded that ANO1 is essential for the development of prostate hyperplasia and is a potential target for the treatment of BPH. PMID:26153424

Sonographic Appearance of Testicular Adrenal Rest Tumour in a Patient with Congenital Adrenal Hyperplasia.

PubMed

Deshpande, Saurabh S; Shetty, Devdas; Saifi, Shenaz

2017-01-01

Testicular adrenal rest tumours (TARTs) are benign testicular masses that are found in inadequately treated patients with congenital adrenal hyperplasia (CAH). Recognizing this association and identifying characteristic ultrasound features of TARTs is important so as to avoid misdiagnosing them as malignancies, which can lead to unnecessary interventions. We describe a case of a 9-year-old boy, with a diagnosis of CAH and precocious puberty, who was referred to our department for an ultrasound evaluation of the abdomen and scrotum. On ultrasound, there were well-defined, heterogeneous, predominantly hypoechoic, round-to-oval masses in both testes. Taking into account the presence of CAH and a typical sonographic appearance of bilateral testicular masses, a diagnosis of testicular adrenal rest tumour was made; biopsy was deferred and hormonal treatment was modified. Prompt diagnosis of testicular adrenal rest tumours is essential, as it only indicates inadequate hormonal control. Moreover, it can prevent unnecessary biopsies and orchidectomies, and can maintain fertility. TARTs have a typical imaging appearance that every radiologist must be aware of.

Sonographic Appearance of Testicular Adrenal Rest Tumour in a Patient with Congenital Adrenal Hyperplasia

PubMed Central

Shetty, Devdas; Saifi, Shenaz

2017-01-01

Summary Background Testicular adrenal rest tumours (TARTs) are benign testicular masses that are found in inadequately treated patients with congenital adrenal hyperplasia (CAH). Recognizing this association and identifying characteristic ultrasound features of TARTs is important so as to avoid misdiagnosing them as malignancies, which can lead to unnecessary interventions. Case Report We describe a case of a 9-year-old boy, with a diagnosis of CAH and precocious puberty, who was referred to our department for an ultrasound evaluation of the abdomen and scrotum. On ultrasound, there were well-defined, heterogeneous, predominantly hypoechoic, round-to-oval masses in both testes. Taking into account the presence of CAH and a typical sonographic appearance of bilateral testicular masses, a diagnosis of testicular adrenal rest tumour was made; biopsy was deferred and hormonal treatment was modified. Conclusions Prompt diagnosis of testicular adrenal rest tumours is essential, as it only indicates inadequate hormonal control. Moreover, it can prevent unnecessary biopsies and orchidectomies, and can maintain fertility. TARTs have a typical imaging appearance that every radiologist must be aware of. PMID:29662583

Elucidating encounters of atypical ductal hyperplasia arising in gynaecomastia.

PubMed

Wells, Justin M; Liu, Yifang; Ginter, Paula S; Nguyen, Michaela T; Shin, Sandra J

2015-02-01

Atypical ductal hyperplasia (ADH) rarely arises in gynaecomastia. We set out to understand more clearly the clinical, histological and immunohistochemical features of ADH in this setting. Twenty-five cases of ADH arising in gynaecomastia, nine cases of ductal carcinoma in situ (DCIS) and 36 cases of gynaecomastia with usual ductal hyperplasia (UDH) were studied. Reviews of clinical, morphological and immunohistochemical findings were performed. The extent of cytokeratin 5/6 (CK5/6) luminal epithelial cell staining was assessed (0% = 0, < 10% = 1, 10-50% = 2 and > 50% = 3). Oestrogen receptor (ER) was evaluated using the H-scoring system. The average age of ADH patients was 35 years (range 14-78). ADH was bilateral in 20% and less frequent in active gynaecomastia (24%). ADH often showed a cribriform pattern (72%), with less nuclear variation/size and similar frequency of mitoses than UDH cells. CK5/6 luminal epithelial staining was decreased in ADH (68%) versus UDH (11%). ADH showed high ER expression compared to UDH (H score > 270 in 88% and 14%, respectively). ADH in gynaecomastia can be distinguished from UDH by morphological and immunohistochemical features. We also identified a subset of young patients (< 25 years) with extensive bilateral ADH. More studies are needed to characterize this patient subset more clearly. © 2014 John Wiley & Sons Ltd.

Angiotensin II type 1 receptor-associated protein regulates carotid intimal hyperplasia through controlling apoptosis of vascular smooth muscle cells.

PubMed

Yue, Yongqiang; Ma, Ke; Li, Zhen; Wang, Zhonggao

2018-01-08

Intimal hyperplasia is the main cause of restenosis after carotid artery injury, and the underlying mechanism involves the proliferation and migration of vascular smooth muscle cells (VSMCs). Angiotensin II Type 1 Receptor-Associated Protein (ATRAP) has been reported to withstand intimal hyperplasia by inhibiting VSMCs proliferation and migration; however, whether the beneficial effect of ATRAP associates with VSMCs apoptosis remains unclarified. We demonstrated that the adenoviral-mediated overexpression of ATRAP induced VSMC apoptosis, alleviating the balloon injury-induced neointima formation in rats. Under the condition of Angiotensin-II stimulation, ATRAP overexpression induced the apoptosis of rat VSMCs by depressing the PI3K-Akt signaling; whereas up-regulation of Akt by PTEN inhibitor abolished the apoptotic death. Thus, ATRAP regulates carotid intimal hyperplasia through controlling the PI3K-Akt signal-mediated VSMCs apoptosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Islets of Langerhans from prohormone convertase-2 knockout mice show α-cell hyperplasia and tumorigenesis with elevated α-cell neogenesis

PubMed Central

Jones, Huw B; Reens, Jaimini; Brocklehurst, Simon R; Betts, Catherine J; Bickerton, Sue; Bigley, Alison L; Jenkins, Richard P; Whalley, Nicky M; Morgan, Derrick; Smith, David M

2014-01-01

Antagonism of the effects of glucagon as an adjunct therapy with other glucose-lowering drugs in the chronic treatment of diabetes has been suggested to aggressively control blood glucose levels. Antagonism of glucagon effects, by targeting glucagon secretion or disabling the glucagon receptor, is associated with α-cell hyperplasia. We evaluated the influence of total glucagon withdrawal on islets of Langerhans using prohormone convertase-2 knockout mice (PC2-ko), in which α-cell hyperplasia is present from a young age and persists throughout life, in order to understand whether or not sustained glucagon deficit would lead to islet tumorigenesis. PC2-ko and wild-type (WT) mice were maintained drug-free, and cohorts of these groups sampled at 3, 12 and 18 months for plasma biochemical and morphological (histological, immunohistochemical, electron microscopical and image analytical) assessments. WT mice showed no islet tumours up to termination of the study, but PC2-ko animals displayed marked changes in islet morphology from α-cell hypertrophy/hyperplasia/atypical hyperplasia, to adenomas and carcinomas, these latter being first encountered at 6–8 months. Islet hyperplasias and tumours primarily consisted of α-cells associated to varying degrees with other islet endocrine cell types. In addition to substantial increases in islet neoplasia, increased α-cell neogenesis associated primarily with pancreatic duct(ule)s was present. We conclude that absolute blockade of the glucagon signal results in tumorigenesis and that the PC2-ko mouse represents a valuable model for investigation of islet tumours and pancreatic ductal neogenesis. PMID:24456331

New concepts for an old problem: the diagnosis of endometrial hyperplasia.

PubMed

Sanderson, Peter A; Critchley, Hilary O D; Williams, Alistair R W; Arends, Mark J; Saunders, Philippa T K

2017-03-01

Endometrial hyperplasia (EH) is a uterine pathology representing a spectrum of morphological endometrial alterations. It is predominantly characterized by an increase in the endometrial gland-to-stroma ratio when compared to normal proliferative endometrium. The clinical significance of EH lies in the associated risk of progression to endometrioid endometrial cancer (EC) and 'atypical' forms of EH are regarded as premalignant lesions. Traditional histopathological classification systems for EH exhibit wide and varying degrees of diagnostic reproducibility and, as a consequence, standardized patient management can be challenging. EC is the most common gynaecological malignancy in developed countries. The incidence of EC is rising, with alarming increases described in the 40-44-year-old age group. This review appraises the current EH classification systems used to stratify women at risk of malignant progression to EC. In addition, we summarize the evidence base regarding the use of immunohistochemical biomarkers for EH and discuss an emerging role for genomic analysis. PubMed, Medline and the Cochrane Database were searched for original peer-reviewed primary and review articles, from January 2000 to January 2016. The following search terms were used: 'endometrial hyperplasia', 'endometrial intraepithelial neoplasia', 'atypical hyperplasia', 'complex atypical hyperplasia', 'biomarker', 'immunohistochemistry', 'progression', 'genomic', 'classification' and 'stratification'. Recent changes to EH classification reflect our current understanding of the genesis of endometrioid ECs. The concept of endometrial intraepithelial neoplasia (EIN) as a mutationally activated, monoclonal pre-malignancy represents a fundamental shift from the previously held notion that unopposed oestrogenic stimulation causes ever-increasing hyperplastic proliferation, with accumulating cytological atypia that imperceptibly leads to the development of endometrioid EC. Our review highlights several

Congenital adrenal hyperplasia with localized aggressive periodontitis and amelogenesis imperfecta.

PubMed

Ajlan, Sumaiah Abdulbaqi

2015-11-01

Congenital adrenal hyperplasia (CAH) is an inherited medical condition that implies defects in steroid biosynthesis. The dental findings of a female patient with CAH are reported. The patient suffered from severe periodontal tissue destruction, obvious enamel defects, as well as some occlusal problems. The management approach is presented and the possibility of interrelation of her dental findings with her medical condition is discussed. © 2015 Japanese Teratology Society.

The anti-hyperplasia, anti-oxidative and anti-inflammatory properties of Qing Ye Dan and swertiamarin in testosterone-induced benign prostatic hyperplasia in rats.

PubMed

Wu, Xinying; Gu, Ye; Li, Lun

2017-01-04

Qing Ye Dan (QYD) is the whole plant of Swertia mileensis and used in Chinese folk medicine for the treatment of prostatitis, benign prostatic hyperplasia (BPH) and so on. This study was to investigate the effects of QYD and its main component swertiamarin on BPH induced by testosterone in rats. The prostatic expressions of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor (βFGF) and proliferating cell nuclear antigen (PCNA) were detected by immunohistochemistry assay. Prostatic levels of oxidative stress and inflammatory-related factors were also analyzed. Additionally, the prostatic expressions of androgen receptor (AR), estrogen receptor (ER)-α, ER-β, hypoxia-inducible factor (HIF)-1α, B-cell CLL/lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot. The epithelial-mesenchymal transition (EMT) associated factors were evaluated by quantitative RT-PCR. It showed that QYD and swertiamarin ameliorated the testosterone-induced prostatic hyperplasia and collagen deposition, attenuated the over-expressions of HIF-1α, VEGF, EGF, βFGF, PCNA, AR and ER-α, reduced the ratio of Bcl-2/Bax, enhanced the expression of ER-β, inhibited the oxidative stress and local inflammation, as well as relieved prostatic EMT. It suggested that QYD and swertiamarin had prostatic protective potential against BPH. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Adenomyoepithelioma of the breast with associated atypical lobular hyperplasia: a previously unrecognized association with management implications.

PubMed

Zhang, Shuang; Huo, Lei; Arribas, Elsa; Middleton, Lavinia P

2015-02-01

Adenomyoepitheliomas of breast are rare tumors. We report for the first time a case of an adenomyoepithelioma of the breast with associated lobular neoplasia. A 53-year-old woman had an annual screening mammogram, which identified areas of asymmetry in her left breast at 4-5-o'clock position. Resection of the masses revealed a well-circumscribed, gray-white, firm discrete nodule (0.8 × 0.4 × 0.3 cm). The tumor was composed of both adenomyoepithelial cell hyperplasia and focal atypical lobular hyperplasia. The 2 cell populations had some overlapping histologic features. Immunohistochemical analysis demonstrated a biphasic proliferation with approximately equal parts of luminal epithelial cells with clear and rounded appearance and myoepithelial cells. The myoepithelial component of the proliferation expressed myosin, p63, CK5/6, S-100, and dimly expressed E-cadherin. The epithelial component of the proliferation strongly expressed E-cadherin. In the areas of atypical lobular hyperplasia, there was distinct loss E-cadherin expression. Awareness of this association is highly important to provide these patients adequate follow-up and treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

β-Cell Hyperplasia Induced by Hepatic Insulin Resistance

PubMed Central

Escribano, Oscar; Guillén, Carlos; Nevado, Carmen; Gómez-Hernández, Almudena; Kahn, C. Ronald; Benito, Manuel

2009-01-01

OBJECTIVE Type 2 diabetes results from a combination of insulin resistance and impaired insulin secretion. To directly address the effects of hepatic insulin resistance in adult animals, we developed an inducible liver-specific insulin receptor knockout mouse (iLIRKO). RESEARCH DESIGN AND METHODS Using this approach, we were able to induce variable insulin receptor (IR) deficiency in a tissue-specific manner (liver mosaicism). RESULTS iLIRKO mice presented progressive hepatic and extrahepatic insulin resistance without liver dysfunction. Initially, iLIRKO mice displayed hyperinsulinemia and increased β-cell mass, the extent of which was proportional to the deletion of hepatic IR. Our studies of iLIRKO suggest a cause-and-effect relationship between progressive insulin resistance and the fold increase of plasma insulin levels and β-cell mass. Ultimately, the β-cells failed to secrete sufficient insulin, leading to uncontrolled diabetes. We observed that hepatic IGF-1 expression was enhanced in iLIRKO mice, resulting in an increase of circulating IGF-1. Concurrently, the IR-A isoform was upregulated in hyperplastic β-cells of iLIRKO mice and IGF-1–induced proliferation was higher than in the controls. In mouse β-cell lines, IR-A, but not IR-B, conferred a proliferative capacity in response to insulin or IGF-1, providing a potential explanation for the β-cell hyperplasia induced by liver insulin resistance in iLIRKO mice. CONCLUSIONS Our studies of iLIRKO mice suggest a liver-pancreas endocrine axis in which IGF-1 functions as a liver-derived growth factor to promote compensatory pancreatic islet hyperplasia through IR-A. PMID:19136656

Management of benign prostatic hyperplasia with silodosin

PubMed Central

Yamanishi, Tomonori; Mizuno, Tomoya; Kamai, Takao; Yoshida, Ken-Ichiro; Sakakibara, Ryuji; Uchiyama, Tomoyuki

2009-01-01

It has been reported that blockade of α1A-adrenoceptor (AR) relieves bladder outlet obstruction, while blockade of α1D-AR is believed to alleviate storage symptoms due to detrusor overactivity. Silodosin, (−)-1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2trifluoroethoxy) phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7- carboxamide, is a new α1A-AR selective antagonist. Silodosin is highly selective for the α1A-AR subtype, showing an affinity for the α1A-AR that is 583- and 55.5-fold higher than its affinity for the α1B-and α1D-ARs, respectively. In randomized, double-blind, placebo-controlled phase III studies performed in Japan and the United States, silodosin has been shown to be effective for both storage and voiding symptoms associated with benign prostatic hyperplasia. Early effects of silodosin (after 2–6 hours or day 1) on lower urinary tract symptoms have also been reported. In urodynamic studies, detrusor overactivity disappeared in 40% and improved in 35% of patients after administration. In pressure flow studies, the grade of obstruction on the International Continence Society nomogram showed improvement in 56% of patients. The rate of adverse events in the silodosin, tamsulosin and placebo groups was 88.6%, 82.3%, and 71.6%, respectively. The most common adverse event was (mostly mild) abnormal ejaculation (28.1%). However, few patients (2.8%) discontinued silodosin because of abnormal ejaculation. Orthostatic hypotension showed a similar incidence in the silodosin (2.6%) and placebo (1.5%) groups. In conclusion, silodosin improves detrusor overactivity and obstruction and thus may be effective for both storage and voiding symptoms in patients with benign prostatic hyperplasia. PMID:24198606

Experimental study on the clinical effects of Xiaoru Sanjie Jiaonang on mammary glands hyperplasia and ki-67

PubMed Central

Zheng, Zi-Hao; Liu, Lin; Zou, Shi-Fang; Xu, Yu-Ting; Chen, Cui-Cui; Liang, Wen-Long; Guo, Bao-Liang; Wang, Yu; Zhu, Kai-Yuan; Liu, Jie-Na; Xu, Dan-Dan; Wang, Ji-Yan; Lin, Jia-Yan; Liu, Li; Zhang, Jian Guo; Chen, Xi

2018-01-01

Objective: This study aims to observe the effect and mechanism of Xiaoru Sanjie Jiaonang (XRSJ) on the treatment of mammary gland hyperplasia, and provide a theoretical basis and clinical evidence for clinical expansion. Methods: Japanese white rabbits were randomly divided into three groups: high-, middle- and low-dose groups; Xiaoyao Pill group; model control group; normal control group. The observation points were as follows: before XRSJ administration, three months after XRSJ administration, and three months after XRSJ discontinuance. Changes in breast height, morphological changes of the mammary gland under a light and electron microscope, and the expression of ki-67 were observed. At the same time, patients diagnosed with mammary gland hyperplasia at an Outpatient Clinic were selected and divided into treatment groups. These patients received XRSJ and Xiaoyao Pills, respectively, for one month, while patients in the control group did not receive any drug treatment. Clinical efficacy was observed while rechecking at the Outpatient Clinic after three months. Treatment with a therapeutic dose of XRSJ could significantly reduce breast height, decrease the number of lobules and acini in hyperplastic mammary glands and the layer number of ductal glandular epithelial cells, substantially lower the content of serum estradiol (E2), significantly downregulate the expression of ki-67 protein in mammary tissues, and inhibit mammary gland hyperplasia. Conclusion: XRSJ treatment can relieve mammary tissue hyperplastic lesions, reduce E2 levels and downregulate the expression of ki-67. It has a significant therapeutic effect on mammary gland hyperplasia. PMID:29636873

Reactive localised inflammatory hyperplasia of the oral mucosa.

PubMed

Awange, D O; Wakoli, K A; Onyango, J F; Chindia, M L; Dimba, E O; Guthua, S W

2009-02-01

To document the histopathological pattern and distribution of reactive localised inflammatory hyperplastic lesions of the oral mucosa diagnosed at the University of Nairobi Dental Hospital over a 14 year period. A retrospective, cross-sectional descriptive study. Division of Oral Pathology and Oral Medicine, histopathology laboratory, School of Dental Sciences, University of Nairobi. A total of 3135 oral biopsies were accessioned in the oral diagnostic histopathological Laboratory registry over a period of 14 years from March 1991 to December 2005. Three hundred and thirty three cases were histopathologically diagnosed as reactive inflammatory hyperplasias of the oral mucosa. This constituted 10.6% of the total oral biopsy specimens analysed during this period. Fibrous epulis was the most common histological sub-type with 129 cases (38.7%) followed by pyogenic granuloma with 94 (28.3%) cases. Six (1.8%) cases were peripheral giant cell granuloma and three cases (0.9%) were those of denture irritation hyperplasia. The age distribution ranged from 2 to 78 years (mean = 30.5 years) with a peak at 20-29 years. Gender distribution showed that 107 (32%) cases occurred in males and 226 (68%) cases females. Similar trends were observed in most of the histological sub-types. Fibrous epulis occurred in 41 male (31.8%) cases and in 88 (68.2%) females with an age range of 2 to 78 years (mean = 30.5 years). As for the pyogenic granuloma, 26 (27.7%) lesions occurred in males and 68 (72.3%) in females with an age range of 2 to 75 years (mean = 30.1 years). Among all the histopathological sub-types it was shown that 223 (67.0%) cases were fibrous, 104 (31.2%) vascular and six (1.8%) peripheral giant cell granuloma. Gingival lesions were the most common with 257 (77.2%) cases followed by 28 (8.4%) in the tongue, 16 (4.8%) lips, 15 (4.5%) cheek, six (1.8%) palate and the rest on the floor of the mouth and other mucosal sites. The duration of these lesions was recorded in 182 (54

[Atypical epithelial hyperplasia of the breast: current state of knowledge and clinical practice].

PubMed

Lavoué, V; Bertel, C; Tas, P; Bendavid, C; Rouquette, S; Foucher, F; Audrain, O; Bouriel, C; Levêque, J

2010-02-01

The diagnosis of atypical epithelial hyperplasia (AEH) increases with breast cancer screening. AEH is divided in three groups: atypical ductal hyperplasia, columnar cell lesions with atypia, lobular neoplasia. The management of women with AEH is not consensual because of uncertainty about their diagnosis related to the type of the biopsy sampling (core needle biopsy or surgical excision) and their controversial clinical signification between risk marker and true precursor of breast cancer. A systematic review of published studies was performed. Medline baseline interrogation was performed with the following keywords: atypical ductal hyperplasia, columnar cell lesions with atypia, lobular neoplasia, core needle biopsy, breast cancer, precursor lesion, hormonal replacement therapy. For each breast lesion, identified publications (English or French) were assessed for clinical practise in epidemiology, diagnosis and patient management. With immunohistochemistry and molecular studies, AEH seems to be precursor of breast cancer. But, epidemiological studies show low rate of breast cancer in women with AEH. AEH were still classified as risk factor of breast cancer. Because of high rate of breast cancer underestimation, surgical excision is necessary after the diagnosis of AEH at core needle biopsy. Surgical oncology rules and collaboration with radiologist are required for this surgery. A second operation was not required due to involved margins by AEH (except with pleiomorphic lobular neoplasia) because local control of breast cancer seems to be unchanged. Besides, hormonal replacement therapy for patient with AEH is not recommended because of lack of studies about this subject. Copyright 2009 Elsevier Masson SAS. All rights reserved.

Protective constriction of coronary vein grafts with knitted nitinol

PubMed Central

Moodley, Loven; Franz, Thomas; Human, Paul; Wolf, Michael F.; Bezuidenhout, Deon; Scherman, Jacques; Zilla, Peter

2013-01-01

OBJECTIVES Different flow patterns and shear forces were shown to cause significantly more luminal narrowing and neointimal tissue proliferation in coronary than in infrainguinal vein grafts. As constrictive external mesh support of vein grafts led to the complete suppression of intimal hyperplasia (IH) in infrainguinal grafts, we investigated whether mesh constriction is equally effective in the coronary position. METHODS Eighteen senescent Chacma baboons (28.8 ± 3.6 kg) received aorto-coronary bypass grafts to the left anterior descending artery (LAD). Three groups of saphenous vein grafts were compared: untreated controls (CO); fibrin sealant-sprayed controls (CO + FS) and nitinol mesh-constricted grafts (ME + FS). Meshes consisted of pulse-compliant, knitted nitinol (eight needles; 50 μm wire thickness; 3.4 mm resting inner diameter, ID) spray attached to the vein grafts with FS. After 180 days of implantation, luminal dimensions and IH were analysed using post-explant angiography and macroscopic and histological image analysis. RESULTS At implantation, the calibre mismatch between control grafts and the LAD expressed as cross-sectional quotient (Qc) was pronounced [Qc = 0.21 ± 0.07 (CO) and 0.18 ± 0.05 (CO + FS)]. Mesh constriction resulted in a 29 ± 7% reduction of the outer diameter of the vein grafts from 5.23 ± 0.51 to 3.68 ± 0 mm, significantly reducing the calibre discrepancy to a Qc of 0.41 ± 0.17 (P < 0.02). After 6 months of implantation, explant angiography showed distinct luminal irregularities in control grafts (ID difference between widest and narrowest segment 74 ± 45%), while diameter variations were mild in mesh-constricted grafts. In all control grafts, thick neointimal tissue was present [600 ± 63 μm (CO); 627 ± 204 μm (CO + FS)] as opposed to thin, eccentric layers of 249 ± 83 μm in mesh-constricted grafts (ME + FS; P < 0.002). The total wall thickness had increased by 363 ± 39% (P < 0.00001) in CO and 312 ± 61% (P < 0

GLUT-1 Expression in Proliferative Endometrium, Endometrial Hyperplasia, Endometrial Adenocarcinoma and the Relationship Between GLUT-1 Expression and Prognostic Parameters in Endometrial Adenocarcinoma.

PubMed

Canpolat, Tuba; Ersöz, Canan; Uğuz, Aysun; Vardar, Mehmet Ali; Altintaş, Aytekin

2016-01-01

Malignant cells show increased glucose uptake in in vitro and in vivo studies. This uptake is mediated by glucose transporter proteins. GLUT-1 is the most common transporter protein, and its expression is reported to be increase in many human cancers. The aim of this study is to determine the GLUT-1 overexpression in benign, hyperplastic, and malignant endometrial tissues, to evaluate the usefulness of GLUT-1 expression in endometrial hyperplasia, and to determine its role in the neoplastic progression to endometrioid type adenocarcinoma. We also aimed to analyze prognostic clinical parameters, predict prognosis, and survival. We examined immunohistochemical expression of GLUT-1 in 91 cases of endometrial hyperplasia, 100 cases of endometrioid type adenocarcinoma, and 10 proliferative endometrial tissues. The percentage of positive cells and staining intensity were assessed in a semi quantitative fashion and scored (1+ to 3+). GLUT-1 immunoreactivity was not present in proliferative endometrium. Twenty-nine (31.9%) of 91 endometrial hyperplasia cases showed positive immunoreactivity, of which only six were cases of hyperplasia without atypia while 23 of them were cases with atypia. We found GLUT-1 positivity of 95% in endometrioid type adenocarcinoma. GLUT-1 overexpression was not significantly correlated with any of the clinicopathological parameters except histological grade in endometrioid adenocarcinoma; the survival was not found to be correlated with GLUT-1 expression. GLUT-1 immunostaining may be useful in distinguishing hyperplasia without atypia from hyperplasia with atypia; GLUT-1 overexpression is a consistent feature of endometrioid adenocarcinoma. A correlation between GLUT -1 expression and tumor grade has been found, although other prognostic parameters and survival has no meaningful correlation.

Targeting Stromal Androgen Receptor Suppresses Prolactin-Driven Benign Prostatic Hyperplasia (BPH)

PubMed Central

Lai, Kuo-Pao; Huang, Chiung-Kuei; Fang, Lei-Ya; Izumi, Kouji; Lo, Chi-Wen; Wood, Ronald; Kindblom, Jon; Yeh, Shuyuan

2013-01-01

Stromal-epithelial interaction plays a pivotal role to mediate the normal prostate growth, the pathogenesis of benign prostatic hyperplasia (BPH), and prostate cancer development. Until now, the stromal androgen receptor (AR) functions in the BPH development, and the underlying mechanisms remain largely unknown. Here we used a genetic knockout approach to ablate stromal fibromuscular (fibroblasts and smooth muscle cells) AR in a probasin promoter-driven prolactin transgenic mouse model (Pb-PRL tg mice) that could spontaneously develop prostate hyperplasia to partially mimic human BPH development. We found Pb-PRL tg mice lacking stromal fibromuscular AR developed smaller prostates, with more marked changes in the dorsolateral prostate lobes with less proliferation index. Mechanistically, prolactin mediated hyperplastic prostate growth involved epithelial-stromal interaction through epithelial prolactin/prolactin receptor signals to regulate granulocyte macrophage-colony stimulating factor expression to facilitate stromal cell growth via sustaining signal transducer and activator of transcription-3 activity. Importantly, the stromal fibromuscular AR could modulate such epithelial-stromal interacting signals. Targeting stromal fibromuscular AR with the AR degradation enhancer, ASC-J9®, led to the reduction of prostate size, which could be used in future therapy. PMID:23893956

Intra-stent tissue evaluation within bare metal and drug-eluting stents > 3 years since implantation in patients with mild to moderate neointimal proliferation using optical coherence tomography and virtual histology intravascular ultrasound.

PubMed

Kitabata, Hironori; Loh, Joshua P; Pendyala, Lakshmana K; Omar, Alfazir; Ota, Hideaki; Minha, Sa'ar; Magalhaes, Marco A; Torguson, Rebecca; Chen, Fang; Satler, Lowell F; Pichard, Augusto D; Waksman, Ron

2014-04-01

We aimed to compare neointimal tissue characteristics between bare-metal stents (BMS) and drug-eluting stents (DES) at long-term follow-up using optical coherence tomography (OCT) and virtual histology intravascular ultrasound (VH-IVUS). Neoatherosclerosis in neointima has been reported in BMS and in DES. Thirty patients with 36 stented lesions [BMS (n=17) or DES (n=19)] >3years after implantation were prospectively enrolled. OCT and VH-IVUS were performed and analyzed independently. Stents with ≥70% diameter stenosis were excluded. The median duration from implantation was 126.0months in the BMS group and 60.0months in the DES group (p <0.001). Lipid-laden intima (58.8% vs. 42.1%, p=0.317), thrombus (17.6% vs. 5.3%, p=0.326), and calcification (35.3% vs. 26.3%, p=0.559) did not show significant differences between BMS and DES. When divided into 3 time periods, the cumulative incidence of lipid-laden neointima from >3years to <9years was similar between BMS and DES (42.9% vs. 42.1%, p=1.000). Furthermore, it continued to gradually increase over time in both groups. OCT-derived thin-cap fibroatheroma (TCFA) was observed in 17.6% of BMS- and 5.3% of DES-treated lesions (p=0.326). No stents had evidence of intimal disruption. The percentage volume of necrotic core (16.1% [9.7, 20.3] vs. 9.7% [7.0, 16.5], p=0.062) and dense calcium (9.5% [3.8, 13.6] vs. 2.7% [0.4, 4.9], p=0.080) in neointima tended to be greater in BMS-treated lesions. Intra-stent VH-TCFA (BMS vs. DES 45.5% vs. 18.2%, p=0.361) did not differ significantly. At long-term follow-up beyond 3 years after implantation, the intra-stent neointimal tissue characteristics appeared similar for both BMS and DES. Copyright © 2014 Elsevier Inc. All rights reserved.

Distinction between papillary thyroid hyperplasia and papillary thyroid carcinoma by immunohistochemical staining for cytokeratin 19, galectin-3, and HBME-1.

PubMed

Casey, Mary B; Lohse, Christine M; Lloyd, Ricardo V

2003-01-01

The histopathology of papillary thyroid hyperplasia and papillary thyroid carcinoma is similar enough to cause a diagnostic dilemma in a few cases. Both lesions may have papillary fronds with fibrovascular cores, nuclear crowding, and nuclear anisocytosis. Formalin- fixed paraffin-embedded tissues from 30 randomly selected patients with papillary thyroid hyperplasia and an equal number from patients with papillary thyroid carcinoma were analyzed for expression of cytokeratin 19 (CK19), galectin-3, and HBME-1. Cases of papillary thyroid carcinoma had moderate to strong CK19, galectin-3, and HBME-1 reactivity although both CK19 and galectin-3 showed positive staining in a significant number of nonneoplastic thyroid cases. HBME-1 was uncommon in the nonneoplastic cases. These results indicate that HBME-1 may be useful in helping to distinguish papillary thyroid carcinoma from hyperplasia in diagnostically difficult cases.

Reduced Intimal Hyperplasia in Rabbits via Medical Therapy after Carotid Venous Bypass

PubMed Central

Yucel, Semih; Bahcivan, Muzaffer; Gol, Mehmet Kamil; Erenler, Behice H.; Kolbakir, Fersat; Keceligil, Hasan T.

2009-01-01

Intimal hyperplasia is a major cause of restenosis after the interventional or surgical treatment of occlusive arterial disease. We investigated the effects of clopidogrel, calcium dobesilate, nebivolol, and atorvastatin on the development of intimal hyperplasia in rabbits after carotid venous bypass surgery. We divided 40 male New Zealand rabbits into 4 study groups and 1 control group. After occluding the carotid arteries of the rabbits, we constructed jugular venous grafts between the proximal and the distal segments of the occluded artery. Thereafter, group 1 (control) received no medication. We administered daily oral doses of clopidogrel to group 2, calcium dobesilate to group 3, nebivolol to group 4, and atorvastatin to group 5. The rabbits were killed 28 days postoperatively. The arterialized jugular venous grafts were extracted for histopathologic examination. Intimal thicknesses were 42.87 ± 6.95 μm (group 2), 46.5 ± 9.02 μm (group 3), 34.12 ± 5.64 μm (group 4), and 48.37 ± 6.16 μm (group 5), all significantly less than the 95.12 ± 9.93 μm in group 1 (all P < 0.001). Medial thicknesses were 94 ± 6 μm (group 2), 101.5 ± 13.52 μm (group 3), 90.5 ± 9.69 μm (group 4), and 101.37 ± 7.99 μm (group 5), all significantly thinner than the 126.62 ± 13.53 μm in group 1 (all P < 0.001). In our experimental model of carotid venous bypass grafting in rabbits, clopidogrel, calcium dobesilate, nebivolol, and atorvastatin each effectively reduced the development of intimal hyperplasia. Herein, we discuss our findings and review the medical literature. PMID:19876413

Should male gender assignment be considered in the markedly virilized patient With 46,XX and congenital adrenal hyperplasia?

PubMed

Lee, Peter A; Houk, Christopher P; Husmann, Douglas A

2010-10-01

We assess the outcome in 46,XX men with congenital adrenal hyperplasia who were born with Prader 4 or 5 genitalia and assigned male gender at birth. After receiving institutional review board approval and subject consent we reviewed the medical records of 12 men 35 to 69 years old with 46,XX congenital adrenal hyperplasia, of whom 6 completed social and gender issue questionnaires. All subjects were assigned male gender at birth, were diagnosed with virilizing congenital adrenal hyperplasia at age greater than 3 years and indicated a male gender identity with sexual orientation to females. Ten of the 12 subjects had always lived as male and 2 who were reassigned to female gender in childhood subsequently self-reassigned as male. Nine of the 12 men had long-term female partners, including 7 married 12 years or more. The 3 subjects without a long-term female partner included 1 priest, 1 who was reassigned female gender, married, divorced and self-reassigned as male, and 1 with a girlfriend and sexual activity. All except the priest and the subject who was previously married when female indicated a strong libido and frequent orgasmic sexual activity. Responses to self-esteem, masculinity, body image, social adjustment and symptom questionnaires suggested adjustments related to the extent of familial and social support. Outcome data on severely masculinized 46,XX patients with congenital adrenal hyperplasia who were assigned male gender at birth indicate male gender identity in adulthood with satisfactory male sexual function in those retaining male genitalia. In men who completed questionnaires results were poorer in those lacking familial/social support. Male gender of rearing may be a viable option for parents whose children are born with congenital adrenal hyperplasia, a 46,XX karyotype and male genitalia, although positive parental and other support, and counseling are needed for adjustment. Copyright © 2010 American Urological Association Education and Research

Focal nodular hyperplasia coexistent with hepatoblastoma in a 36-d-old infant

PubMed Central

Gong, Ying; Chen, Lian; Qiao, Zhong-Wei; Ma, Yang-Yang

2015-01-01

Focal nodular hyperplasia (FNH) is a benign hepatic tumor characterized by hepatocyte hyperplasia and a central stellate scar. The association of FNH with other hepatic lesions, such as adenomas, hemangiomas and hepatocellular carcinoma, has been previously reported, but FNH associated with another hepatic tumor is rare in infants. Here we report a case of FNH coexistent with hepatoblastoma in a 36-d-old girl. Computed tomography (CT) imaging showed an ill-delineated, inhomogeneous enhanced mass with a central star-like scar in the right lobe of the liver. The tumor showed early mild enhancement at the arterial phase (from 40HU without contrast to 52HU at the arterial phase), intense enhancement at the portal phase (87.7HU) and 98.1HU in the 3-min delay scan. A central scar in the tumor presented as low density on non-contrast CT and slightly enhanced at delayed contrast-enhanced scanning. This infant underwent surgical resection of the tumor. Histopathology demonstrated typical FNH coexistent with a focal hepatoblastoma, which showed epithelioid tumor cells separated by proliferated fibrous tissue. PMID:25624742

Focal nodular hyperplasia coexistent with hepatoblastoma in a 36-d-old infant.

PubMed

Gong, Ying; Chen, Lian; Qiao, Zhong-Wei; Ma, Yang-Yang

2015-01-21

Focal nodular hyperplasia (FNH) is a benign hepatic tumor characterized by hepatocyte hyperplasia and a central stellate scar. The association of FNH with other hepatic lesions, such as adenomas, hemangiomas and hepatocellular carcinoma, has been previously reported, but FNH associated with another hepatic tumor is rare in infants. Here we report a case of FNH coexistent with hepatoblastoma in a 36-d-old girl. Computed tomography (CT) imaging showed an ill-delineated, inhomogeneous enhanced mass with a central star-like scar in the right lobe of the liver. The tumor showed early mild enhancement at the arterial phase (from 40HU without contrast to 52HU at the arterial phase), intense enhancement at the portal phase (87.7HU) and 98.1HU in the 3-min delay scan. A central scar in the tumor presented as low density on non-contrast CT and slightly enhanced at delayed contrast-enhanced scanning. This infant underwent surgical resection of the tumor. Histopathology demonstrated typical FNH coexistent with a focal hepatoblastoma, which showed epithelioid tumor cells separated by proliferated fibrous tissue.

[Evaluation of risk of progression of endometrial hyperplasia in patients with metabolic syndrome].

PubMed

Bochkareva, N V; Kolomiets, L A; Chernyshova, A L; Stukanov, S L; Savenkova, O V

2010-01-01

A mathematical model based on principles of multifactor analysis was developed to predict clinical outcome of endometrial hyperplasia (EH) in patients with metabolic syndrome (80). Seventy-seven factors--anthropometric, clinical, anamnestic, hormono-metabolic, immunohistochemical, etc.--were included. Evaluation of the most informative indices integrated with the discriminative model showed that anthropometric (waist and hip circumference, sagittal diameter, etc.) and clinico-anamnestic (age, age of secondary sexual characters appearance, body weight at birth, suckling pattern, etc.) ones are of similar significance. A profile of hormono-metabolic parameters (cholesterol-low density lipoprotein, leptin, testosterone, progesterone and fasting glucose levels) helped identify a wide range of EH-related disorders in patients with metabolic syndrome. Consistently with the literature data, level of PTEN expression pointed to the presence of this tumor's suppressor in most EH cases which was matched by absence of its expression in endometrial carcinoma. Our model provided high sensitivity (89%) and specificity (82%) in predicting risk of progression in patients with endometrial hyperplasia and metabolic syndrome.

Polycystic ovary syndrome and endometrial hyperplasia: an overview of the role of bariatric surgery in female fertility.

PubMed

Charalampakis, Vasileios; Tahrani, Abd A; Helmy, Ahmed; Gupta, Janesh K; Singhal, Rishi

2016-12-01

One of the most effective methods to tackle obesity and its related comorbidities is bariatric surgery. Polycystic ovary syndrome (PCOS) and endometrial hyperplasia (EH), which are associated with increased risk of endometrial carcinoma, have been identified as potentially new indications for bariatric surgery. PCOS is the most common endocrine disorder in women in the reproductive age and is associated with several components of the metabolic syndrome such as obesity, insulin resistance and hypertension. EH is a pre-cancerous condition which arises in the presence of chronic exposure to estrogen unopposed by progesterone such as both in PCOS and obesity. The main bariatric procedures are Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy and laparoscopic adjustable gastric banding. These procedures are well established and when correctly selected and performed by experienced bariatric surgeons, they can achieve significant weight loss and remission of obesity related co-morbidities. Studies have shown that bariatric surgery can play an important role in the management of patients with PCOS and improve fertility. Similarly, bariatric surgery has a positive effect on endometrial hyperplasia, making surgically induced weight loss a potentially attractive option for endometrial cancer prevention and treatment. Obesity has an adverse impact on spontaneous pregnancy, assisted reproduction methods and feto-maternal outcomes. After bariatric surgery obese women with subfertility can achieve spontaneous pregnancy. However, while bariatric surgery reduces the risk of pre-eclampsia and gestational diabetes, there is an increased risk of small for gestational age and possible increased risk of stillborn or neonatal death. In this article we will review the evidence regarding the use of bariatric surgery as a treatment modality in patients with PCOS and EH. We also provide an overview of the common bariatric procedures. Copyright © 2016 Elsevier Ireland Ltd. All rights

Congenital supratentorial meningeal arteriovenous malformation with hemangioma and massive arachnoid cell hyperplasia.

PubMed

Nabeel, Alnaghmoosh; Lach, Boleslaw; Al-Shail, Essam; Patay, Zoltan

2005-11-01

We describe the clinical, radiological and pathological findings of concurrent, congenital leptomeningeal arteriovenous malformation with hemangioma diagnosed in a newborn by prenatal and immediately postnatal magnetic resonance imaging. Vascular abnormalities were accompanied by massive arachnoidal cell hyperplasia reminiscent of meningioma. To the best of our knowledge, this is the first case of such a lesion reported in the literature.

Polymeric stent materials dysregulate macrophage and endothelial cell functions: implications for coronary artery stent

PubMed Central

Wang, Xintong; Zachman, Angela L.; Chun, Young Wook; Shen, Fang-Wen; Hwang, Yu-Shik; Sung, Hak-Joon

2014-01-01

Background Biodegradable polymers have been applied as bulk or coating materials for coronary artery stents. The degradation of polymers, however, could induce endothelial dysfunction and aggravate neointimal formation. Here we use polymeric microparticles to simulate and demonstrate the effects of degraded stent materials on phagocytic activity, cell death and dysfunction of macrophages and endothelial cells. Methods Microparticles made of low molecular weight polyesters were incubated with human macrophages and coronary artery endothelial cells (ECs). Microparticle-induced phagocytosis, cytotoxicity, apoptosis, cytokine release and surface marker expression were determined by immunostaining or ELISA. Elastase expression was analyzed by ELISA and the elastase-mediated polymer degradation was assessed by mass spectrometry. Results We demonstrated poly(D,L-lactic acid) (PLLA) and polycaprolactone (PCL) microparticles induced cytotoxicity in macrophages and ECs, partially through cell apoptosis. The particle treatment alleviated EC phagocytosis, as opposed to macrophages, but enhanced the expression of vascular cell adhesion molecule-1 (VCAM) along with decreased nitric oxide production, indicating ECs were activated and lost their capacity to maintain homeostasis. The activation of both cell types induced release of elastase or elastase-like protease, which further accelerated polymer degradation. Conclusions This study revealed that low molecule weight PLLA and PCL microparticles increased cytotoxicity and dysregulated endothelial cell function, which in turn enhanced elastase release and polymer degradation. These indicate polymer or polymer-coated stents impose a risk of endothelial dysfunction after deployment which can potentially lead to delayed endothelialization, neointimal hyperplasia and late thrombosis. PMID:24820736

Pseudocarcinomatous hyperplasia in anaplastic large cell lymphoma, a mimicker of poorly differentiated squamous cell carcinoma: report of a case and review of the literature.

PubMed

Price, Alexandra; Miller, Jason H; Junkins-Hopkins, Jacqueline M

2015-11-01

Pseudocarcinomatous hyperplasia can occasionally be observed in biopsies of CD30-positive lymphoproliferative disorders. It is important to be cognizant of this association, because epithelial hyperproliferation can overshadow large atypical lymphoid cells, leading to an erroneous diagnosis of squamous cell carcinoma (SCC) or keratoacanthoma. Herein, we present a case of anaplastic large cell lymphoma (ALCL) with pseudocarcinomatous hyperplasia simulating a poorly differentiated carcinoma and review the literature on this subject. Immunohistochemical staining with p63 helped delineate the infiltrating tongues of pseudocarcinomatous hyperplasia from the malignant infiltrate. We present this case to raise awareness of the potential for pseudocarcinomatous hyperplasia to occur in the setting of CD30+ lymphoproliferative disorders. Clinicians and dermatopathologists should consider the possibility of ALCL or lymphomatoid papulosis when examining lesions with features of inflamed SCC, especially if the tumor presents on a site or in a patient that is not typical of SCC. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

p27kip1 expression distinguishes papillary hyperplasia in Graves' disease from papillary thyroid carcinoma.

PubMed

Erickson, L A; Yousef, O M; Jin, L; Lohse, C M; Pankratz, V S; Lloyd, R V

2000-09-01

In most cases, the histopathologic and cytologic distinction between Graves' disease and papillary thyroid carcinoma is relatively easy, but on occasion Graves' disease may simulate a thyroid papillary carcinoma. For example, papillary fronds with fibrovascular cores may be present in both Graves' disease and papillary carcinoma. p27kip1 (p27) is a cyclin-dependent kinase inhibitory protein that has been shown to be an independent prognostic factor in a variety of human tumors. Our previous studies of p27 expression in hyperplastic and neoplastic endocrine lesions showed that the level of p27 was quite different in these two conditions. To determine if this distinction could also be made between Graves' disease and papillary carcinoma, we analyzed expression of p27 and other cell cycle proteins in a series of cases of Graves' disease with papillary hyperplasia and a series of papillary thyroid carcinomas. Formalin-fixed paraffin-embedded tissues from 61 randomly selected patients with thyroid disease, including 29 cases of Graves' disease with papillary architectural features and 32 cases of papillary carcinoma, were analyzed for expression of p27, Ki-67, and DNA topoisomerase II alpha (topo II alpha) by immunostaining. The distribution of immunoreactivity was analyzed by quantifying the percentage of positive nuclei that was expressed as the labeling index (LI) plus or minus the standard error of the mean. The papillary hyperplasia of Graves' disease had a p27 LI of 68.2 +/- 3.1 (range, 24 to 88), whereas papillary carcinomas had a LI of 25.6 +/- 2.5 (range, 12 to 70) (P < .0001). No significant differences in Ki-67 or topo II alpha expression were identified between papillary hyperplasia in Graves' disease and papillary carcinoma. These results indicate that p27 protein expression is significantly higher in papillary hyperplasia of Graves' disease compared to papillary carcinoma, which may be diagnostically useful in difficult cases.

The Role of Repeat Administration of Adventitial Delivery of Lentivirus-shRNA-Vegf-A in Arteriovenous Fistula to Prevent Venous Stenosis Formation.

PubMed

Janardhanan, Rajiv; Yang, Binxia; Kilari, Sreenivasulu; Leof, Edward B; Mukhopadhyay, Debabrata; Misra, Sanjay

2016-04-01

To determine if a second dose of a lentivirus mediated small hairpin RNA that inhibits Vegf-A gene expression (LV-shRNA-Vegf-A) can improve lumen vessel area (LVA) of the outflow vein of an arteriovenous fistula (AVF) and decrease venous neointimal hyperplasia. Chronic kidney disease was created in C57BL/6 mice; 28 days later, an AVF was created by connecting the right carotid artery to the ipsilateral jugular vein. Immediately after AVF creation, 5 × 10(6) plaque-forming units of LV-shRNA-Vegf-A or control shRNA was administered to the adventitia of the outflow vein, and a second dose of the same treatment was administered 14 days later. Animals were sacrificed at 21 days, 28 days, and 42 days after AVF creation for reverse transcription polymerase chain reaction and histomorphometric analyses. By day 21, there was a 125% increase in the average LVA (day 21, P = .11), with a decrease in cell proliferation (day 21, P = .0079; day 28, P = .28; day 42, P = .5), decrease in α-smooth muscle cell actin staining (day 21, P < .0001; day 28, P < .05; day 42, P = .59), and decrease in hypoxic stress (day 21, P < .001; day 28, P = .28; day 42, P = .46) in LV versus control shRNA vessels. A second dose of LV-shRNA-Vegf-A administration results in a moderate improvement in LVA at day 21. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

Microwave Treatment of Prostate Cancer and Hyperplasia

NASA Technical Reports Server (NTRS)

Arndt, G. Dickey; Ngo, Phong; Carl, J. R.; Raffoul, George

2005-01-01

Microwave ablation in the form of microwave energy applied to a heart muscle by a coaxial catheter inserted in a vein in the groin area can be used to heat and kill diseased heart cells. A microwave catheter has been developed to provide deep myocardial ablation to treat ventricular tachycardia by restoring appropriate electrical activity within the heart and eliminating irregular heartbeats. The resulting microwave catheter design, which is now being developed for commercial use in treating ventricular tachycardia, can be modified to treat prostate cancer and benign prostatic hyperplasia (BPH). Inasmuch as the occurrence of BPH is increasing currently 350,000 operations per year are performed in the United States alone to treat this condition this microwave catheter has significant commercial potential.

Advanced intimal hyperplasia without luminal narrowing of leptomeningeal arteries in CADASIL.

PubMed

Dong, Hairong; Ding, Haixia; Young, Kelly; Blaivas, Mila; Christensen, Paul J; Wang, Michael M

2013-05-01

Leptomeningeal artery abnormalities in Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) have not been extensively characterized. We quantified substructure and diameter of leptomeningeal arteries in CADASIL compared with age-matched controls and the very old; in addition, we characterized intimal thickening in CADASIL using immunohistochemistry. Frontal and temporal cortex of 6 genetically proven CADASIL brains (average age, 66 years), 6 controls without symptoms of cerebrovascular disease, and 6 very old brains (average age, 89 years) were examined for leptomeningeal artery intimal, medial, and adventitial thickness; inner diameter; and sclerotic index and for smooth muscle markers. The intima of CADASIL arteries was thickened 5-fold compared with controls and the very aged (P<0.0001). Medial thickness was lower in CADASIL compared with controls and the very old (P<0.01). The adventitia was not significantly increased in CADASIL compared with age-matched controls. Arterial diameters were not smaller in CADASIL compared with controls. Sclerotic index was significantly increased in CADASIL compared with other groups (P<0.00001). Intimal cells in CADASIL expressed smooth muscle actin, S100A4, and vimentin but not desmin. Principle changes of leptomeningeal arteries in CADASIL include intimal thickening and medial thinning, but not luminal narrowing. Smooth muscle-like cells participate in neointimal thickening of CADASIL arteries.

Reduction of intimal hyperplasia and enhanced reactivity of experimental vein bypass grafts with verapamil treatment.

PubMed Central

el-Sanadiki, M N; Cross, K S; Murray, J J; Schuman, R W; Mikat, E; McCann, R L; Hagen, P O

1990-01-01

Recent studies have shown that calcium antagonists exert an antiatherogenic effect in animals fed cholesterol. Vein graft intimal hyperplasia is believed to be an early event in atherosclerotic lesion formation, which is a significant cause of graft failure. Altered vasoreactivity has also been postulated in the etiology of vein graft failure. Therefore this study examined the effect of verapamil treatment on the development of intimal hyperplasia and the vasoreactivity of experimental vein bypass grafts. The right external jugular vein was grafted into the right carotid artery of 30 male New Zealand white rabbits fed normal rabbit chow. The left external jugular vein was used as the control vein. Fifteen animals received verapamil (1.25 mg/day for 28 days) via the femoral vein by means of an osmotic pump. In 15 control animals the pump contained saline. Plasma verapamil concentration was 50.9 +/- 13.2 ng/mL (x +/- SEM), a dose that showed no effect on either blood pressure, total serum cholesterol, or in vitro platelet aggregation to ADP. Fourteen of fifteen grafts were patent in each group, for a patency rate of 93%. Histologic examination using computer morphometry showed significant reduction of intimal hyperplasia at the proximal, middle, and distal graft segments (p less than 0.05). In addition in vitro isometric tension studies of the vein grafts and control veins showed that verapamil causes enhanced reactivity of both vein grafts and control veins in response to norepinephrine and histamine (p less than 0.05). Reactivity of vein grafts to serotonin was unaltered. While none of the normal veins in the control group responded to serotonin, normal veins treated with verapamil contracted readily in response to serotonin. Endothelial-dependent relaxation to acetylcholine was absent in both control and verapamil-treated vein grafts, while normal veins from both groups responded to the same extent to acetylcholine. Because we could not demonstrate any difference

PREVALENCE OF BENIGN PROSTATIC HYPERPLASIA AND PROSTATE CANCER IN AFRICANS AND AFRICANS IN THE DIASPORA.

PubMed

Yeboah, E D

2016-01-01

There have been several publications on population or community prevalence of benign prostatic hyperplasia and prostate cancer from various countries and races but few reports are from Africa on Africans. A review on the prevalence of benign prostatic hyperplasia and prostate cancer in Africans and other races. The current literature on prevalence of benign prostatic hyperplasia (BPH), prostate cancer (PC), and benign prostatic hyperplasia co-existing with prostate cancer in Africans and other races is reviewed. Benign prostatic hyperplasia (BPH) prevalence in Ghana is responsible for 60% acute retention of urine and 28.6% of haematuria. Worldwide prevalence of BPH varies from 20 - 62% in men over 50 years and this includes USA, UK, Japan and Ghana. Reports from South Africa indicate prevalence of over 50% in adult males of 60 years. BPH co-existing with PC - Reports from USA, UK and Japan and Ghana reveal moderate association of BPH and PC. The co-existence of PC in patients being treated for BPH is 3 - 20% Prostate Cancer prevalence - There is high prevalence in USA, Scandinavian Countries, African Americans (AA) and Caribbean blacks. Ghana, Trinidad & Tobago have reported high prevalence of 6 -10% in men aged 50 years and above but others reported low prevalence in Africans from Africa. The low reporting from Africa of 10 - 40:100,000 is attributable to under reporting, absence of PSA screening/testing, lack of reliable cancer registries and poor medical facilities. Economic Costs of BPH and PC: BPH in the USA national direct costs are estimated at U$4Billion and individual costs of US$1536 annually. In Ghana, individual costs for BPH medications range from US$300 - 550 per year and cost for simple prostatectomy/TURP is estimated at US$1100. For prostate cancer, individual direct costs from Europe range from 6,575 - 12,000 euros, £2818.00 UK and over U$12,000 - 20,000 in USA per annum. In Ghana, individual direct costs ranges, for radical prostatectomy and

Regenerative nodular hyperplasia, portal vein thrombosis and primary myelofibrosis: an unusual triple association.

PubMed

Sández Montagut, Víctor Manuel; Giráldez Gallego, Álvaro; Ontanilla Clavijo, Guilermo

2018-03-01

We report a case of a regenerative nodular hyperplasia with a portal vein cavernomatosis with a subsequent progression to symptomatic, occlusive thrombosis of the superior mesenteric vein. A thorough investigation resulted in a final diagnosis of primary myelofibrosis associated with the V617F mutation in the JAK2 gene.

Saw palmetto and benign prostatic hyperplasia.

PubMed

Gong, Edward M; Gerber, Glenn S

2004-01-01

Benign prostatic hyperplasia (BPH) is a common health issue that affects 8% of all men at the age of 40, 60% of men in their 70s, and 90% of those greater than 80 years of age. One-fourth of these men will develop moderate to severe lower urinary tract symptoms that greatly affect their quality of life. Recent evidence suggests that the use of saw palmetto leads to improvements in urinary function for those suffering from BPH. The favorable comparison of saw palmetto with tamsulosin, a well-known first line agent in the treatment of urinary tract symptoms, demonstrates promise towards a beneficial effect of this herbal agent, with very few, if any, adverse effects. However, what degree of this beneficial activity is due to placebo effects is yet to be determined. In addition, the precise mechanism of action of saw palmetto in men with BPH remains unclear.

Management issues of congenital adrenal hyperplasia during the transition from pediatric to adult care.

PubMed

Choi, Jin-Ho; Yoo, Han-Wook

2017-02-01

Steroid 21-hydroxylase deficiency is the most prevalent form of congenital adrenal hyperplasia (CAH), accounting for approximately 95% of cases. With the advent of newborn screening and hormone replacement therapy, most children with CAH survive into adulthood. Adolescents and adults with CAH experience a number of complications, including short stature, obesity, infertility, tumor, osteoporosis, and reduced quality of life. Transition from pediatric to adult care and management of long-term complications are challenging for both patients and health-care providers. Psychosocial issues frequently affect adherence to glucocorticoid treatment. Therefore, the safe transition of adolescents to adult care requires regular follow-up of patients by a multidisciplinary team including pediatric and adult endocrinologists. The major goals for management of adults with 21-hydroxylase deficiency are to minimize the long-term complications of glucocorticoid therapy, reduce hyperandrogenism, prevent adrenal or testicular adrenal rest tumors, maintain fertility, and improve quality of life. Optimized medical or surgical treatment strategies should be developed through coordinated care, both during transition periods and throughout patients' lifetimes. This review will summarize current knowledge on the management of adults with CAH, and suggested appropriate approaches to the transition from pediatric to adult care.

Treatment and Prevention of Oral Candidiasis in Elderly Patients.

PubMed

Sakaguchi, Hideo

2017-01-01

The incidence of oral candidiasis has increased in the elderly in recent years. Although the increase of the elderly population plays a big role in this rise of oral candidiasis, the broader recognition that elderly people have higher infection rates for oral candidiasis is considered to be also an important factor. Oral candidiasis can be categorized into three types. Pseudomembranous oral candidiasis is characterized by the appearance of white moss, erythematous oral candidiasis by the eruption of erythema, and hyperplastic oral candidiasis by mucosal hyperplasia. Miconazole has been commonly used when treating oral candidiasis. Elderly patients, however, have a tendency to develop oral candidiasis repeatedly. It is therefore critical to take measures to prevent recurrence. We recommend the use an oral moisturizer containing hinokitiol, an antifungal substance, on a regular basis, to help prevent recurrence of oral candidiasis.

Cellular features of endometrial hyperplasia and well differentiated adenocarcinoma using the Endocyte sampler: Diagnostic criteria based on the cytoarchitecture of tissue fragments.

PubMed

Norimatsu, Yoshiaki; Shimizu, Keiko; Kobayashi, Tadao K; Moriya, Takuya; Tsukayama, Choutatsu; Miyake, Yasuyuki; Ohno, Eiji

2006-04-25

Because cellular atypia is often limited in endometrial hyperplasia and well-differentiated endometrial adenocarcinoma (WHO Grade 1 adenocarcinoma), diagnostic criteria for endometrial cytology have not been fully established. New diagnostic criteria based on the composition and architecture of tissue fragments (cytoarchitecture) in the smears were used in the present study. Cytologic features are of less importance because the distinction between endometrial hyperplasia and Grade 1 adenocarcinoma relies more on architectural features than cellular changes. Cell clumps of various size are usually collected abundantly with cytologic material using a disposable scraping device and it was noticed that those cell clumps reflected the histologic architecture. The purpose of the current study was to determine the form of the cytoarchitecture that reflects the histologic structure and to examine the cellular features in endometrial hyperplasia and Grade 1 adenocarcinoma. The frequency of each type of cell clump (tube or sheet-shaped pattern, dilated or branched pattern, irregular protrusion, and papillotubular pattern) were obtained from 49 cases of normal proliferative endometrium (NPE) (patient age range, 28-51 yrs; average age, 39.9 yrs), 63 cases of endometrial hyperplasia without atypia (EH) (patient age range, 35-65 yrs; average age, 47.7 yrs), 13 cases of endometrial hyperplasia with atypia (AEH) (patient age range 47-65 yrs; average age, 53.8 yrs), and 49 cases of Grade 1 adenocarcinoma (patient age range, 42-73 yrs; average age, 58.9 yrs). Certain characteristics of the cytoarchitecture were observed. In the NPE, cell clumps with a tube or sheet-shaped pattern were found in 97.5% of cases. In the EH, cell clumps with a dilated or branched pattern were found in 34.9% of cases. In the Grade 1 adenocarcinoma, cell clumps with irregular protrusions were found in 61.8% cases, whereas a papillotubular pattern was present in 29.7% of cases. The results of the current

Future research directions to improve fistula maturation and reduce access failure

PubMed Central

Hu, Haidi; Patel, Sandeep; Hanisch, Jesse J.; Santana, Jeans M.; Hashimoto, Takuya; Bai, Hualong; Kudze, Tambudzai; Foster, Trenton R.; Guo, Jianming; Yatsula, Bogdan; Tsui, Janice; Dardik, Alan

2016-01-01

With the increasing prevalence of end stage renal disease there is a growing need for hemodialysis. Arteriovenous fistulae (AVF) are the preferred type of vascular access for hemodialysis but maturation and failure continue to present significant barriers to successful fistula use. AVF maturation integrates outward remodeling with vessel wall thickening in response to drastic hemodynamic changes, in the setting of uremia, systemic inflammation, oxidative stress and preexistent vascular pathology. AVF can fail due to both failure to mature adequately to support hemodialysis, as well as development of neointimal hyperplasia (NIH) that narrows the AVF lumen, typically near the fistula anastomosis. Failure due to NIH involves vascular cell activation and migration and extracellular matrix remodeling with complex interactions of growth factors, adhesion molecules, inflammatory mediators, and chemokines, all of which result in maladaptive remodeling. Different strategies have been proposed to prevent and treat AVF failure, based on current understanding of the modes and pathology of access failure; these approaches range from appropriate patient selection and use of alternative surgical strategies for fistula creation, to the use of novel interventional techniques or drugs to treat failing fistulae. Effective treatments to prevent or treat AVF failure requires a multidisciplinary approach involving nephrologists, vascular surgeons and interventional radiologists, allowing careful patient selection and the use of tailored systemic or localized interventions to improve patient-specific outcomes. This review provides contemporary information on the underlying mechanisms of AVF maturation and failure and discusses the broad spectrum of options that can be tailored for specific therapy. PMID:28779782

Oxytocin: its role in benign prostatic hyperplasia via the ERK pathway.

PubMed

Xu, Huan; Fu, Shi; Chen, Yanbo; Chen, Qi; Gu, Meng; Liu, Chong; Qiao, Zhiguang; Zhou, Juan; Wang, Zhong

2017-04-01

The aim of the present study was to evaluate oxytocin and benign prostatic hyperplasia (BPH), and study the cell signalling mechanism. Investigation was performed in patients about the correlation between oxytocin level and BPH. Mice were injected with oxytocin or oxytocin antagonist for 2 weeks and the prostate morphology was studied after their sacrifice. Furthermore, in vitro experiments were performed to evaluate the oxytocin effect through the MEK/ERK/RSK pathway. Oxytocin was significantly elevated in the serum and prostate tissue of patients with BPH, and a positive correlation with prostate volume indicated. In the animal experiments, prostate enlargement was observed in the oxytocin-treated group, whereas oxytocin antagonist reduced prostate hyperplasia. The in vitro study confirmed this result and also revealed activation of the MEK/ERK/RSK pathway. Oxytocin is highly expressed in the serum and prostate tissue of patients with BPH. In addition, oxytocin aggravates BPH and the oxytocin-induced proliferative effect on prostatic cells is mediated through the MEK/ERK/RSK pathway, at least partly. Thus, the hypothalamic regulation may be involved in development of BPH, which may open a new door to more medications for BPH in the future. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

IL-17A GENE TRANSFER INDUCES BONE LOSS AND EPIDERMAL HYPERPLASIA ASSOCIATED WITH PSORIATIC ARTHRITIS

PubMed Central

ADAMOPOULOS, IANNIS E.; SUZUKI, ERIKA; CHAO, CHENG-CHI; GORMAN, DAN; ADDA, SARVESH; MAVERAKIS, EMANUAL; ZARBALIS, KONSTANTINOS; GEISSLER, RICHARD; ASIO, AGELIO; BLUMENSCHEIN, WENDY M; McCLANAHAN, TERRILL; DE WAAL MALEFYT, RENE; GERSHWIN, M. ERIC; BOWMAN, EDWARD P.

2014-01-01

Background Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by clinical features that include bone loss and epidermal hyperplasia. Aberrant cytokine expression has been linked to joint and skin pathology; however, it is unclear which cytokines are critical for disease initiation. IL-17A participates in many pathologic immune responses; however, its role in PsA has not been fully elucidated. Objective To determine the role of IL-17A in epidermal hyperplasia and bone destruction associated with psoriatic arthritis. Design An in vivo gene transfer approach was used to investigate the role of IL-17A in animal models of inflammatory (Collagen-induced arthritis) and non-inflammatory (RANKL-gene transfer) bone loss. Results IL-17A gene transfer induced the expansion of IL-17RA+CD11b+Gr1low osteoclast precursors and a concomitant elevation of biomarkers indicative of bone resorption. This occurred at a time preceding noticeable joint inflammation suggesting that IL-17A is critical for the induction of pathological bone resorption through direct activation of osteoclast precursors. Moreover, IL-17A induced a second myeloid population CD11b+Gr1high neutrophil-like cells which was associated with cutaneous pathology including epidermal hyperplasia, parakeratosis, and Munro’s microabscesses formation. Conclusion Collectively, these data support that IL-17A can play a key role in the pathogenesis of inflammation-associated arthritis and/or skin disease, as observed in PsA. PMID:24567524

Culture promotes transfer of thyroid epithelial cell hyperplasia and proliferation by reducing regulatory T cell numbers.

PubMed

Kayes, Timothy D; Braley-Mullen, Helen

2013-01-01

IFN-γ(-/-) NOD.H-2h4 mice develop a spontaneous autoimmune thyroid disease, thyroid epithelial cell hyperplasia and proliferation (TEC H/P) when given NaI in their water for 7+ mo. TEC H/P can be transferred to IFN-γ(-/-) SCID mice by splenocytes from mice with severe (4-5+) disease, and transfer of TEC H/P is improved when splenocytes are cultured prior to transfer. Older (9+ mo) IFN-γ(-/-) NOD.H-2h4 mice have elevated numbers of FoxP3(+) T reg cells, up to 2-fold greater than younger (2 mo) mice. During culture, the number of T reg decreases and this allows the improved transfer of TEC H/P. Co-culture with IL-2 prior to transfer prevents the decrease of T reg and improves their in vitro suppressive ability resulting in reduced TEC H/P in recipient mice. Therefore, culturing splenocytes improves transfer of TEC H/P by reducing the number of T reg and IL-2 inhibits transfer by preserving T reg number and function. Copyright © 2013 Elsevier Inc. All rights reserved.

Establishment of a rat and guinea pig aortic interposition graft model reveals model-specific patterns of intimal hyperplasia.

PubMed

Gregory, Elaine K; Vercammen, Janet M; Flynn, Megan E; Kibbe, Melina R

2016-12-01

Although the aortic interposition bypass model has been widely used to evaluate biomaterials for bypass grafting, there is no comprehensive description of the procedure or of the distribution of intimal hyperplasia that results. The objectives of this study were to (1) review and summarize approaches of aortic interposition grafting in animal models, (2) determine the pertinent anatomy for this procedure, (3) validate this model in the rat and guinea pig, and (4) compare the distribution of intimal hyperplasia that develops in each species. A literature search was performed in PubMed from 1980 to the present to analyze the use of anesthesia, anticoagulation, antiplatelet agents, graft material, suture, and anastomotic techniques. Using 10-week-old male Sprague-Dawley rats and Hartley guinea pigs, we established pertinent aortic anatomy, developed comparable models, and assessed complications for each model. At 30 days, the graft and associated aorta were explanted, intimal formation was assessed morphometrically, and cellularity was assessed via nuclear counting. We reviewed 30 articles and summarized the pertinent procedural findings. Upon establishing both animal models, key anatomic differences between the species that affect this model were noted. Guinea pigs have a much larger cecum, increased retroperitoneal fat, and lack the iliolumbar vessels compared with the rat. Surgical outcomes for the rat model included a 53% technical success rate and a 32% technical error rate. Surgical outcomes for the guinea pig model included a 69% technical success rate and a 31% technical error rate. These two species demonstrated unique distribution of intimal hyperplasia at 30 days. Intimal hyperplasia in the rat model was greatest at two areas, the proximal graft (5400 μm 2 ; P < .001) and distal graft (2800 μm 2 ; P < .04), whereas the guinea pig model developed similar intimal hyperplasia throughout the graft (4500-5100 μm 2 ; P < .01). In this report, we summarize

Diode laser surgery versus scalpel surgery in the treatment of fibrous hyperplasia: a randomized clinical trial.

PubMed

Amaral, M B F; de Ávila, J M S; Abreu, M H G; Mesquita, R A

2015-11-01

Fibrous hyperplasia is treated by surgical incision using a scalpel, together with removal of the source of chronic trauma. However, scalpel techniques do not provide the haemostasis that is necessary when dealing with highly vascular tissues. Diode laser surgery can be used in the management of oral tissues due to its high absorption by water and haemoglobin, and has provided good results in both periodontal surgery and oral lesions. The aim of the present study was to compare the effects of diode laser surgery to those of the conventional technique in patients with fibrous hyperplasia. A randomized clinical trial was performed in which surgical and postoperative evaluations were analyzed. On comparison of the laser-treated (study group) patients to those treated with a scalpel (control group), significant differences were observed in the duration of surgery and the use of analgesic medications. Over a 3-week period, clinical healing of the postoperative wound was significantly faster in the control group as compared to the study group. In conclusion, diode laser surgery proved to be more effective and less invasive when compared to scalpel surgery in the management of fibrous hyperplasia. However, wound healing proved to be faster when using scalpel surgery. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Mesenchymal stem cell sheets exert anti-stenotic effects in a rat arterial injury model.

PubMed

Homma, Jun; Sekine, Hidekazu; Matsuura, Katsuhisa; Kobayashi, Eiji; Shimizu, Tatsuya

2018-05-04

Restenosis after catheter or surgical intervention substantially affects the prognosis of arterial occlusive disease. Mesenchymal stem cells (MSCs) may have anti-stenotic effects on injured arteries. MSC transplantation from the adventitial side of an artery is safer than endovascular transplantation but has not been extensively examined. In this study, a rat model of femoral artery injury was used to compare the anti-stenotic effects of transplanted cell sheets and transplanted cell suspensions. Rat adipose-derived stem cells (ASCs) were used as the source of MSCs. For both cell sheets and suspensions, 6×106 MSCs were transplanted on the day of arterial injury. MSC sheets attenuated neointimal hyperplasia more than MSC suspensions (intima-to-media ratio in haematoxylin/eosin-stained sections: 0.55±0.13 vs. 1.14±0.12; P<0.05). Cell engraftment (assessed by immunohistochemistry or bioluminescence imaging of luciferase-expressing cells), arterial re-endothelialisation (evaluated by immunohistochemical staining for rat endothelial cell antigen-1) and restriction of vascular smooth muscle cell proliferation in the neointima (double-staining of alpha-smooth muscle actin and phospho-histone H3) were greater when MSC sheets were applied than when MSC suspensions were used. In conclusion, MSC sheets exhibited better anti-stenotic and cell engraftment properties than MSC suspensions. MSC sheet transplantation from the adventitial side is a promising therapy for prevention of arterial restenosis.

Smooth Muscle Hyperplasia/Hypertrophy is the Most Prominent Histological Change in Crohn's Fibrostenosing Bowel Strictures: A Semiquantitative Analysis by Using a Novel Histological Grading Scheme.

PubMed

Chen, Wenqian; Lu, Cathy; Hirota, Christina; Iacucci, Marietta; Ghosh, Subrata; Gui, Xianyong

2017-01-01

The simplistically and ambiguously termed 'fibrostenosis' of bowel is a hallmark of severe Crohn's disease [CD] and a major contributor to medical treatment failure. Non-invasive imaging assessment and novel medical therapy targeting this condition are under investigation, which particularly requires a better understanding of the underlying histological basis. We analysed 48 patients with stricturing Crohn's ileitis or/and colitis that required surgical resection. The most representative sections of the fibrostenotic, non-stenotic and uninvolved regions were reviewed for histological analysis. For each layer of bowel wall (mucosa including muscularis mucosae [MU], submucosa [SM], muscularis propria [MP], subserosal adventitia [SS]), histological abnormalities were evaluated individually, including active and chronic inflammation, fibrosis, smooth muscle hyperplasia or hypertrophy, neuronal hypertrophy and adipocyte proliferation. A novel semiquantitative histological grading scheme was created. The most significant histopathological features characterizing the stricturing intestines were smooth muscle hyperplasia of SM, hypertrophy of MP and chronic inflammation. The muscular alteration was predominant in all layers. The overall muscular hyperplasia/hypertrophy was positively correlated with chronic inflammation and negatively correlated with fibrosis, whereas SM muscular hyperplasia was also associated with MU active inflammation. Similar changes, to a lesser extent, occurred in the adjacent non-stenotic inflamed bowel as well. In CD-associated 'fibrostenosis', it is the smooth muscle hyperplasia/hypertrophy that contributes most to the stricturing phenotype, whereas fibrosis is less significant. The 'inflammation-smooth muscle hyperplasia axis' may be the most important in the pathogenesis of Crohn's strictures. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please

Efficacy and safety of the urolift® system for the treatment of benign prostate hyperplasia symptoms: systematic review.

PubMed

Sánchez-Gómez, L M; Polo-deSantos, M; Gómez-Sancha, F; Luengo-Matos, S

2015-06-01

Interest in having alternatives in the treatment of benign prostate hyperplasia. To assess the efficacy and safety of the Urolift® system for treating the symptoms of benign prostate hyperplasia. Systematic review of the literature through searches on PubMed, Cochrane Library, CRD, Clinical Trials and EuroScan, collecting indicators of efficacy and safety. We included 5 case series and one clinical trial. The patients' mean age ranged from 65-74.3 years, and the mean prostate volume was 41-55cm3. The mean number of Urolif® implants was 3.7-5.5. The maximum follow-up in months was 24, 12 (3 studies) and one (2 studies). Improvements were found in lower urinary tract symptoms, as measured with the International Prostate Symptom Score, Benign Prostatic Hyperplasia Impact Index (BPHII), maximum urinary flow (Qmax) and postvoid residual (PVR) volume. Improvements were in found sexual dysfunction symptoms, as measured with the Sexual Health Inventory for Men (SHIM) and the Male Sexual Health Questionnaire or Ejaculatory Dysfunction (MHSQ-EjD), and in quality of life (QoL). In the clinical trial, the differences were significant for International Prostate Symptom Score, BPHII, Qmax and QoL (p<.05). The adverse effects were mild. Although the quality of evidence is low, Urolift® constitutes a good therapeutic alternative for patients with benign prostate hyperplasia. The short to medium-term results show that the technique contributes to improving lower urinary tract symptoms, with no relevant side effects, does not affect sexual function and improves quality of life. Further research is required, especially on long-term results. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Denture-induced fibrous inflammatory hyperplasia: a retrospective study in a school of dentistry.

PubMed

Coelho, C M; Zucoloto, S; Lopes, R A

2000-01-01

The aim of this study was to investigate the denture-induced fibrous inflammatory hyperplasia (FIH) that occurs around the borders of an ill-fitting denture, in relation to frequency of the lesion, age and sex distribution, length of denture use, and frequency of dysplasia. A comprehensive review of FIH diagnosed in patients wearing dentures by the oral pathology diagnostic service at the University of São Paulo over 26 years (1971 to 1996) was undertaken, based on retrospective analysis of the oral histopathologic files. The frequency of FIH was 15% of the total number of pathologies diagnosed at the service of oral pathology in that period. The disorder occurred predominantly in the fifth and sixth decades of life and more often among females, at a proportion of 5:1. The frequency of FIH was higher for a length of denture use of between 1 and 10 years. Dysplasia was found in 4% of cases. The knowledge of some aspects of FIH, especially the possible histologic alteration of dysplasia, supports the importance of the diagnosis and treatment of the lesion and suggests that any excised tissue should be submitted to histopathologic evaluation. Education and regular review of patients who have worn dentures are essential if the development of FIH is to be prevented.

Activation of innate anti-viral immune response genes in symptomatic benign prostatic hyperplasia

PubMed Central

Madigan, Allison A.; Sobek, Kathryn M.; Cummings, Jessica L.; Green, William R.; Bacich, Dean J.; O’Keefe, Denise S.

2012-01-01

Benign Prostatic Hyperplasia (BPH)is the most common urologic disease in men over age 50. Symptoms include acute urinary retention, urgency to urinate and nocturia. For patients with severe symptoms, surgical treatment is used to remove the affected tissue. Interestingly, the presence of histologic BPH does not always correlate with symptoms. The molecular basis of symptomatic BPH and how it differs from asymptomatic BPH is unknown. Investigation into the molecular players involved in symptomatic BPH will likely give insight into novel therapeutic, and potentially preventative, targets. We determined the expression of genes involved in the innate anti-viral immune response in tissues from patients undergoing surgery to alleviate the symptoms of BPH, and compared the results to prostate tissue with histologic BPH, but from patients with few urinary issues (asymptomatic BPH). We found that expression of CFI, APOBEC3G, OAS2, and IFIT1, four genes whose protein products are involved in the innate anti-viral immune response, were significantly transcriptionally upregulated in symptomatic BPH. Additionally we observe hypomethylation and concomitant expression of ancient retroviral-like sequences, the LINE-1 retrotransposons, in symptomatic BPH when compared to normal prostate tissue. These findings merit further investigation into the anti-viral immune response in symptomatic BPH. PMID:22952051

Uncommon case of symmetrical fibrous hyperplasia of the hard palate.

PubMed

Di Lorenzo, S; Milia, A; Corradino, B; Cordova, A

2010-02-01

The fibrous hyperplasia of the palate (fibroma) is a benign tumor which has its origin in the soft tissue and whose frequency is estimated to be 1.2% on adult subjects. Rarely the size exceeds the cm, but in these cases a complaint of increasing difficulty of mastication and swallowing appears. We describe the case of a young white woman affected with two peculiar symmetric lesions of the secondary hard palate, that could be the consequence of an abnormal answer to a chronic inflammatory stimulation.

Abnormal liver function in common variable immunodeficiency disorders due to nodular regenerative hyperplasia.

PubMed

Ward, C; Lucas, M; Piris, J; Collier, J; Chapel, H

2008-09-01

Patients with common variable immunodeficiency disorders are monitored for liver function test abnormalities. A proportion of patients develop deranged liver function and some also develop hepatomegaly. We investigated the prevalence of abnormalities and types of liver disease, aiming to identify those at risk and determine outcomes. The local primary immunodeficiency database was searched for patients with a common variable immunodeficiency disorder and abnormal liver function and/or a liver biopsy. Patterns of liver dysfunction were determined and biopsies reviewed. A total of 47 of 108 patients had deranged liver function, most commonly raised alkaline phosphatase levels. Twenty-three patients had liver biopsies. Nodular regenerative hyperplasia was found in 13 of 16 with unexplained pathology. These patients were more likely to have other disease-related complications of common variable immunodeficiency disorders, in particular non-coeliac (gluten insensitive) lymphocytic enteropathy. However, five had no symptoms of liver disease and only one died of liver complications. Nodular regenerative hyperplasia is a common complication of common variable immunodeficiency disorders but was rarely complicated by portal hypertension.

Genetic podocyte lineage reveals progressive podocytopenia with parietal cell hyperplasia in a murine model of cellular/collapsing focal segmental glomerulosclerosis.

PubMed

Suzuki, Taisei; Matsusaka, Taiji; Nakayama, Makiko; Asano, Takako; Watanabe, Teruo; Ichikawa, Iekuni; Nagata, Michio

2009-05-01

Focal segmental glomerulosclerosis (FSGS) is a progressive renal disease, and the glomerular visceral cell hyperplasia typically observed in cellular/collapsing FSGS is an important pathological factor in disease progression. However, the cellular features that promote FSGS currently remain obscure. To determine both the origin and phenotypic alterations in hyperplastic cells in cellular/collapsing FSGS, the present study used a previously described FSGS model in p21-deficient mice with visceral cell hyperplasia and identified the podocyte lineage by genetic tagging. The p21-deficient mice with nephropathy showed significantly higher urinary protein levels, extracapillary hyperplastic indices on day 5, and glomerular sclerosis indices on day 14 than wild-type controls. X-gal staining and immunohistochemistry for podocyte and parietal epithelial cell (PEC) markers revealed progressive podocytopenia with capillary collapse accompanied by PEC hyperplasia leading to FSGS. In our investigation, non-tagged cells expressed neither WT1 nor nestin. Ki-67, a proliferation marker, was rarely associated with podocytes but was expressed at high levels in PECs. Both terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and electron microscopy failed to show evidence of significant podocyte apoptosis on days 5 and 14. These findings suggest that extensive podocyte loss and simultaneous PEC hyperplasia is an actual pathology that may contribute to the progression of cellular/collapsing FSGS in this mouse model. Additionally, this is the first study to demonstrate the regulatory role of p21 in the PEC cell cycle.

A Systematic Review of Paradoxical Adipose Hyperplasia (PAH) Post-Cryolipolysis.

PubMed

Ho, Derek; Jagdeo, Jared

2017-01-01

Body sculpting, or body contouring, is among the fastest growing areas in cosmetic dermatology. Cryolipolysis, or "fat freezing," was FDA-cleared (CoolSculpting System, ZELTIQ Aesthetics, Pleasanton, CA) initially in 2010 for fat removal of the anks, and subsequently received FDA-clearance for other anatomical locations. Over the past several years, there have been increasing published reports and physician discussion regarding paradoxical adipose hyperplasia (PAH) post-cryolipolysis, previously identified as a "rare" adverse effect. To review published reports of PAH post-cryolipolysis, expand on previously proposed hypothesis of PAH, and provide rec- ommendations for prevention and treatment of PAH. On July 26, 2016, we systematically searched the computerized medical bibliographic databases PubMed, EMBASE, Web of Science, and CINAHL with the search term "cryolipolysis." A total of 314 records were returned from our search terms and 10 records were found to be suitable for our review. We identi- ed a total of 16 cases of PAH post-cryolipolysis in the published literature. Based upon the published literature, we identi ed that the current incidence of PAH may be higher than previously re- ported. Although the pathoetiology of PAH is currently unknown, we hypothesize that some adipocytes may be "naturally selected" for survival due to their inherent tolerance to cryolipolysis. We believe that while cryolipolysis is an effective non-invasive treatment option for body contouring, physicians and patients should be aware of PAH as a potential adverse effect and treatment options. J Drugs Dermatol. 2017;16(1):62-67..

Extent of Atypical Hyperplasia Stratifies Breast Cancer Risk in Two Independent Cohorts of Women

PubMed Central

Degnim, Amy C.; Dupont, William D.; Radisky, Derek C.; Vierkant, Robert A.; Frank, Ryan D.; Frost, Marlene H.; Winham, Stacey J.; Sanders, Melinda E.; Smith, Jeffrey R.; Page, David L.; Hoskin, Tanya L.; Vachon, Celine M.; Ghosh, Karthik; Hieken, Tina J.; Denison, Lori A.; Carter, Jodi M.; Hartmann, Lynn C.; Visscher, Daniel W.

2016-01-01

Background Women with atypical hyperplasia (AH) on breast biopsy have a substantially increased risk of breast cancer (BC). Here we report BC risk with AH extent and subtype in two separate cohorts. Methods All samples containing AH were included from two cohorts of benign breast disease, Mayo Clinic and Nashville. Histology review quantified the number of foci of atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH). BC risk was stratified for number of AH foci within AH subtypes. Results The study included 708 Mayo and 466 Nashville AH subjects. In the Mayo Cohort, increasing foci of AH was associated with a significant increase in risk of BC, both for ADH (RR’s of 2.61, 5.21, and 6.36 for 1, 2, and 3+ foci, p=0.006 for linear trend) and for ALH (RR’s of 2.56, 3.50, and 6.79 for 1, 2, and 3+ foci, p=0.001 for linear trend). In the Nashville Cohort, RR’s of BC for ADH were 2.70, 5.17, and 15.06 for 1, 2, and 3+ foci respectively (p<0.001 for linear trend); for ALH, RR’s also increased but not significantly (2.61, 3.48, and 4.02, p=0.148). Combining both Mayo and Nashville samples, risk increased significantly for 1, 2, and 3+ foci: RR’s of 2.65, 5.19, and 8.94 for ADH (p<0.001), and 2.58, 3.49, and 4.97 for ALH (p=0.001). Conclusions In two independent cohort studies of benign breast disease, extent of atypia stratifies long-term breast cancer risk for ADH and ALH. PMID:27352219

Pituitary hyperplasia: case series and literature review of an under-recognised and heterogeneous condition

PubMed Central

Earls, Peter; McCormack, Ann I

2015-01-01

Summary Pituitary hyperplasia (PH) occurs in heterogeneous settings and remains under-recognised. Increased awareness of this condition and its natural history should circumvent unnecessary trans-sphenoidal surgery. We performed an observational case series of patients referred to a single endocrinologist over a 3-year period. Four young women were identified with PH manifesting as diffuse, symmetrical pituitary enlargement near or touching the optic apparatus on MRI. The first woman presented with primary hypothyroidism and likely had thyrotroph hyperplasia given prompt resolution with thyroxine. The second and third women were diagnosed with pathological gonadotroph hyperplasia due to primary gonadal insufficiency, with histopathological confirmation including gonadal-deficiency cells in the third case where surgery could have been avoided. The fourth woman likely had idiopathic PH, though she had concomitant polycystic ovary syndrome which is a debated cause of PH. Patients suspected of PH should undergo comprehensive hormonal, radiological and sometimes ophthalmological evaluation. This is best conducted by a specialised multidisciplinary team with preference for treatment of underlying conditions and close monitoring over surgical intervention. Learning points Normal pituitary dimensions are influenced by age and gender with the greatest pituitary heights seen in young adults and perimenopausal women.Pituitary enlargement may be seen in the settings of pregnancy, end-organ insufficiency with loss of negative feedback, and excess trophic hormone from the hypothalamus or neuroendocrine tumours.PH may be caused or exacerbated by medications including oestrogen, GNRH analogues and antipsychotics.Management involves identification of cases of idiopathic PH suitable for simple surveillance and reversal of pathological or iatrogenic causes where they exist.Surgery should be avoided in PH as it rarely progresses. PMID:26124954

Dutasteride reduces prostate size and prostate specific antigen in older hypogonadal men with benign prostatic hyperplasia undergoing testosterone replacement therapy.

PubMed

Page, Stephanie T; Hirano, Lianne; Gilchriest, Janet; Dighe, Manjiri; Amory, John K; Marck, Brett T; Matsumoto, Alvin M

2011-07-01

Benign prostatic hyperplasia and hypogonadism are common disorders in aging men. There is concern that androgen replacement in older men may increase prostate size and symptoms of benign prostatic hyperplasia. We examined whether combining dutasteride, which inhibits testosterone to dihydrotestosterone conversion, with testosterone treatment in older hypogonadal men with benign prostatic hyperplasia reduces androgenic stimulation of the prostate compared to testosterone alone. We conducted a double-blind, placebo controlled trial of 53 men 51 to 82 years old with symptomatic benign prostatic hyperplasia, prostate volume 30 cc or greater and serum total testosterone less than 280 ng/dl (less than 9.7 nmol/l). Subjects were randomized to daily transdermal 1% T gel plus oral placebo or dutasteride for 6 months. Testosterone dosing was adjusted to a serum testosterone of 500 to 1,000 ng/dl. The primary outcomes were prostate volume measured by magnetic resonance imaging, serum prostate specific antigen and androgen levels. A total of 46 subjects completed all procedures. Serum testosterone increased similarly into the mid-normal range in both groups. Serum dihydrotestosterone increased in the testosterone only but decreased in the testosterone plus dutasteride group. In the testosterone plus dutasteride group prostate volume and prostate specific antigen (mean ± SEM) decreased 12% ± 2.5% and 35% ± 5%, respectively, compared to the testosterone only group in which prostate volume and prostate specific antigen increased 7.5% ± 3.3% and 19% ± 7% (p = 0.03 and p = 0.008), respectively, after 6 months of treatment. Prostate symptom scores improved in both groups. Combined treatment with testosterone plus dutasteride reduces prostate volume and prostate specific antigen compared to testosterone only. Coadministration of a 5α-reductase inhibitor with testosterone appears to spare the prostate from androgenic stimulation during testosterone replacement in older

Condylectomy and "surgery first" approach: An expedited treatment for condylar hyperplasia in a patient with facial asymmetry.

PubMed

López, Diego Fernando; Aristizábal, Juan Fernando; Martínez-Smit, Rosana

2017-01-01

Condylar Hyperplasia (CH) is a self-limiting pathology condition that produces severe facial deformity at the expense of mandibular asymmetry. In this case report a 15-year-old female patient was diagnosed with Unilateral Condylar Hiperplasia (UCH) by mean of single-photon emission computed tomography (SPECT) and histological study. A high condylectomy in the right condyle was performed to stop the active status of the hyperplasia. A month after condylectomy, orthognathic jaw impaction and asymmetric mandibular setback surgery was performed with the Surgery First Approach (SFA). After 10 days, orthodontic appointments were made every two weeks during 4 months. The active phase of treatment lasted 14 months. Excellent facial and occlusal outcomes were obtained and after 24 months in retention the results remained stable.

Telangiectatic focal nodular hyperplasia: a variant of hepatocellular adenoma.

PubMed

Paradis, Valerie; Benzekri, Asmae; Dargère, Delphine; Bièche, Ivan; Laurendeau, Ingrid; Vilgrain, Valerie; Belghiti, Jacques; Vidaud, Michel; Degott, Claude; Bedossa, Pierre

2004-05-01

"Telangiectatic focal nodular hyperplasia" designate atypical lesions considered as variants of focal nodular hyperplasia (FNH). However, because "telangiectatic FNH" share several morphologic patterns with hepatocellular adenomas, classification of such lesions deserve further clarification. Therefore, the aim of the present study was to reconsider the classification of telangiectatic FNH with the help of a molecular approach. Ten telangiectatic FNH, 6 typical FNH, and 6 hepatocellular adenomas were studied. DNA, RNA, and protein from each lesion were extracted. Clonality was assessed by the study of the X chromosome inactivation pattern (HUMARA assay). Angiopoietin (ANGPT-1 and ANGPT-2) mRNA, genes the expression of which is typically modified in FNH, were quantified by a real-time RT-PCR procedure. Protein profiles were analyzed by SELDI-TOF PROTEINCHIP (Cyphergen Biosystem, Inc., Fremont, CA) technology. Although all informative cases of FNH (5 of 6) and hepatocellular adenomas (6 of 6) were polyclonal and monoclonal, respectively, clonal analysis showed a nonrandom pattern of X chromosome inactivation consistent with a monoclonal lesion in 6 of 8 cases of telangiectatic FNH. The mean value of the ANGPT-1/ANGPT-2 mRNA ratio was 21.4 in FNH, 2.6 in adenomas, and 2.1 in telangiectatic FNH (P

Pseudoangiomatous stromal hyperplasia causing massive breast enlargement

PubMed Central

Bourke, Anita Geraldine; Tiang, Stephen; Harvey, Nathan; McClure, Robert

2015-01-01

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign mesenchymal proliferative process, initially described by Vuitch et al. We report an unusual case of a 46-year-old woman who presented with a 6-week history of bilateral massive, asymmetrical, painful enlargement of her breasts, without a history of trauma. On clinical examination, both breasts were markedly enlarged and oedematous, but there were no discrete palpable masses. Preoperative image-guided core biopsies and surgery showed PASH. PASH is increasingly recognised as an incidental finding on image-guided core biopsy performed for screen detected lesions. There are a few reported cases of PASH presenting as rapid breast enlargement. In our case, the patient presented with painful, asymmetrical, massive breast enlargement. Awareness needs to be raised of this entity as a differential diagnosis in massive, painful breast enlargement. PMID:26475873

The effectiveness of reducing the daily dose of finasteride in men with benign prostatic hyperplasia

PubMed Central

Sullivan, Michael J; Geller, Jack

2002-01-01

Background Finasteride, a 5 alpha reductase inhibitor, is an established treatment for benign prostatic hyperplasia. The recommended dosage is 5 mg a day, however case reports have show effectiveness with lower doses. The objective of the current study was to determine in men with benign prostatic hyperplasia, previously treated for at least one year with finasteride 5 mg daily, if they will maintain subjective and objective improvements in urinary obstruction when treated with 2.5 mg of finasteride daily for one year. Methods In an open label, prospective study, 40 men with benign prostatic hyperplasia, previously treated for at least one year with 5 mg of finasteride, took 2.5 mg of finasteride daily for one year. Measurements included AUA symptom score, maximum flow rate, voided volume and PSA. Results There were no significant changes in maximum flow rate, voided volume, or AUA symptom score after one year of finasteride 2.5 mg daily therapy. PSA increased significantly, p < .01, after one year of finasteride 2.5 mg daily, 2.0 +1.4 ng/ml, when compared to finasteride 5 mg daily, 1.4+ 1.0 ng/ml. Conclusions The daily dose of finasteride can be reduced to 2.5 mg daily without significant effect on subjective and objective measures of urinary obstruction. Although statistically significant increases in PSA are noted when reducing the daily finasteride dose from 5 mg to 2.5 mg, the clinical significance of a mean .6 ng/ml increase in PSA is questionable. PMID:11818031

Improved dosimetry techniques for intravascular brachytherapy

NASA Astrophysics Data System (ADS)

Sehgal, Varun

Coronary artery disease leads to the accumulation of atheromatous plaque leading to coronary stenosis. Coronary intervention techniques such as balloon angioplasty and atherectomy are used to address coronary stenosis and establish a stable lumen thus enhancing blood flow to the myocardium. Restenosis or re-blockage of the arteries is a major limitation of the above mentioned interventional techniques. Neointimal hyperplasia or proliferation of cells in response to the vascular injury as a result of coronary intervention is considered to be one of the major causes of restenosis. Recent studies indicated that irradiation of the coronary lesion site, with radiation doses ranging from 15 to 30 Gy, leads to diminishing neointimal hyperplasia with subsequent reduction in restenosis. The radiation dose is given by catheter-based radiation delivery systems using beta-emitters 90Sr/90Y, 32P and gamma-emitting 192Ir among others. However the dose schema used for dose prescription for these sources are relatively simplistic, and are based on calculations using uniform homogenous water or tissue media and simple cylinder geometry. Stenotic coronary vessels are invariably lined with atheromatous plaque of heterogeneous composition, the radiation dose distribution obtained from such dosimetry data can cause significant variations in the actual dose received by a given patient. Such discrepancies in dose calculation can introduce relatively large uncertainties in the limits of dose window for effective and safe application of intravascular brachytherapy, and consequently in the clinical evaluation of the efficacy of this modality. In this research study we investigated the effect of different geometrical and material heterogeneities, including residual plaque, catheter non-centering, lesion eccentricity and cardiac motion on the radiation dose delivered at the lesion site. Correction factors including dose perturbation factors and dose variation factors have been calculated

Heparin-binding peptide amphiphile supramolecular architectures as platforms for angiogenesis and drug delivery

NASA Astrophysics Data System (ADS)

Chow, Lesleyann W.

to attach and maintain viability on these membranes. Finally, HBPA nanofibers were used to control the release of small hydrophobic molecules. HBPA nanofiber gels released nitric oxide (NO) to inhibit neointimal hyperplasia, a major cause for vascular graft or stent failure. HBPA/heparin gels were shown to prolong the release of NO generated from NO donors, significantly reducing neointimal hyperplasia in injured carotid arteries in vivo.

Denture-induced fibrous inflammatory hyperplasia (epulis fissuratum): research aspects.

PubMed

Thomas, G A

1993-01-01

Denture-induced fibrous inflammatory hyperplasia (FIH) is a common lesion of the oral mucosa which can be treated by either surgical excision, conservative methods or both combined. Clinical aspects are briefly reviewed and a newer conservative approach to treatment is suggested. This is based on the observation that light pressure using soft lining materials may facilitate shrinkage of the fibrous mass. The histopathogenesis is discussed from the view point of the modern technologies of immunocytochemistry, and digital image analysis. The recent development of a microwave instrument with sophisticated control of power and temperature is discussed and its use in the field of histotechnology outlined.

Combination of Autoantibody Signature with PSA Level Enables a Highly Accurate Blood-Based Differentiation of Prostate Cancer Patients from Patients with Benign Prostatic Hyperplasia.

PubMed

Leidinger, Petra; Keller, Andreas; Milchram, Lisa; Harz, Christian; Hart, Martin; Werth, Angelika; Lenhof, Hans-Peter; Weinhäusel, Andreas; Keck, Bastian; Wullich, Bernd; Ludwig, Nicole; Meese, Eckart

2015-01-01

Although an increased level of the prostate-specific antigen can be an indication for prostate cancer, other reasons often lead to a high rate of false positive results. Therefore, an additional serological screening of autoantibodies in patients' sera could improve the detection of prostate cancer. We performed protein macroarray screening with sera from 49 prostate cancer patients, 70 patients with benign prostatic hyperplasia and 28 healthy controls and compared the autoimmune response in those groups. We were able to distinguish prostate cancer patients from normal controls with an accuracy of 83.2%, patients with benign prostatic hyperplasia from normal controls with an accuracy of 86.0% and prostate cancer patients from patients with benign prostatic hyperplasia with an accuracy of 70.3%. Combining seroreactivity pattern with a PSA level of higher than 4.0 ng/ml this classification could be improved to an accuracy of 84.1%. For selected proteins we were able to confirm the differential expression by using luminex on 84 samples. We provide a minimally invasive serological method to reduce false positive results in detection of prostate cancer and according to PSA screening to distinguish men with prostate cancer from men with benign prostatic hyperplasia.

Surgical treatment of unilateral condylar hyperplasia with piezosurgery.

PubMed

Chiarini, Luigi; Albanese, Massimo; Anesi, Alexandre; Galzignato, Pier-Francesco; Mortellaro, Carmen; Nocini, Pierfrancesco; Bertossi, Dario

2014-05-01

Unilateral condylar hyperplasia (UCH) is a disorder of unknown etiology mainly seen in growing patients, which results in facial asymmetry. High condylectomy alone or in association with orthognathic surgery can improve the occlusion and the facial aesthetics. Between 2005 and 2012, a total of 5 patients underwent high condylectomy for UCH using a piezoelectric cutting device. All patients were treated postoperatively with functional rehabilitation. The long-term follow-up showed that all patients had a satisfactory temporomandibular joint articular function associated with stable occlusion without any recurrence of further condylar growth. High condylectomy in the surgical treatment of unilateral UCH seems to be the procedure of choice in growing patients. The use of a piezoelectric cutting device allows a safe and less invasive high condylectomy.

Targeted overexpression of EZH2 in the mammary gland disrupts ductal morphogenesis and causes epithelial hyperplasia.

PubMed

Li, Xin; Gonzalez, Maria E; Toy, Katherine; Filzen, Tracey; Merajver, Sofia D; Kleer, Celina G

2009-09-01

The Polycomb group protein enhancer of zeste homolog 2 (EZH2), which has roles during development of numerous tissues, is a critical regulator of cell type identity. Overexpression of EZH2 has been detected in invasive breast carcinoma tissue samples and is observed in human breast tissue samples of morphologically normal lobules up to 12 years before the development of breast cancer. The function of EZH2 during preneoplastic progression in the mammary gland is unknown. To investigate the role of EZH2 in the mammary gland, we targeted the expression of EZH2 to mammary epithelial cells using the mouse mammary tumor virus long terminal repeat. EZH2 overexpression resulted in aberrant terminal end bud architecture. By the age of 4 months, 100% of female mouse mammary tumor virus-EZH2 virgin mice developed intraductal epithelial hyperplasia resembling the human counterpart accompanied by premature differentiation of ductal epithelial cells and up-regulation of the luminal marker GATA-3. In addition, remodeling of the mammary gland after parturition was impaired and EZH2 overexpression caused delayed involution. Mechanistically, we found that EZH2 physically interacts with beta-catenin, inducing beta-catenin nuclear accumulation in mammary epithelial cells and activating Wnt/beta-catenin signaling. The biological significance of these data to human hyperplasias is demonstrated by EZH2 up-regulation and colocalization with beta-catenin in human intraductal epithelial hyperplasia, the earliest histologically identifiable precursor of breast carcinoma.

Targeted Overexpression of EZH2 in the Mammary Gland Disrupts Ductal Morphogenesis and Causes Epithelial Hyperplasia

PubMed Central

Li, Xin; Gonzalez, Maria E.; Toy, Katherine; Filzen, Tracey; Merajver, Sofia D.; Kleer, Celina G.

2009-01-01

The Polycomb group protein enhancer of zeste homolog 2 (EZH2), which has roles during development of numerous tissues, is a critical regulator of cell type identity. Overexpression of EZH2 has been detected in invasive breast carcinoma tissue samples and is observed in human breast tissue samples of morphologically normal lobules up to 12 years before the development of breast cancer. The function of EZH2 during preneoplastic progression in the mammary gland is unknown. To investigate the role of EZH2 in the mammary gland, we targeted the expression of EZH2 to mammary epithelial cells using the mouse mammary tumor virus long terminal repeat. EZH2 overexpression resulted in aberrant terminal end bud architecture. By the age of 4 months, 100% of female mouse mammary tumor virus-EZH2 virgin mice developed intraductal epithelial hyperplasia resembling the human counterpart accompanied by premature differentiation of ductal epithelial cells and up-regulation of the luminal marker GATA-3. In addition, remodeling of the mammary gland after parturition was impaired and EZH2 overexpression caused delayed involution. Mechanistically, we found that EZH2 physically interacts with β-catenin, inducing β-catenin nuclear accumulation in mammary epithelial cells and activating Wnt/β-catenin signaling. The biological significance of these data to human hyperplasias is demonstrated by EZH2 up-regulation and colocalization with β-catenin in human intraductal epithelial hyperplasia, the earliest histologically identifiable precursor of breast carcinoma. PMID:19661437

Drug eluting stents: To evolve or dissolve?

PubMed

Bharadwaj, Prashant; Chadha, D S

2016-10-01

Currently, percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is the most commonly employed modality in the treatment of patients with coronary artery disease. PCI has come of age over the last four decades with enormous forays in the technology and drugs which have greatly enhanced its capability. Angioplasty and bare metal stents were plagued by high failure rates on account of restenosis leading to repeat revascularization procedures. Insights into pathophysiology of instent restenosis (ISR) and neointimal hyperplasia triggered the development of DES. The dreamlike remarkable reduction in ISR with DES was enthusiastically welcomed. Soon thereafter emerged the spectre of very late stent thrombosis (VLST) with DES. VLST was a new entity seen predominantly with DES and pathological insights as to the cause was instrumental in the development and efficacy of new generation DES. This review will highlight the evolution and present day DES for coronary interventions.

Allergen-induced resistin-like molecule-α promotes esophageal epithelial cell hyperplasia in eosinophilic esophagitis

PubMed Central

Mavi, Parm; Niranjan, Rituraj; Dutt, Parmesh; Zaidi, Asifa; Shukla, Jai Shankar; Korfhagen, Thomas

2014-01-01

Resistin-like molecule (Relm)-α is a secreted, cysteine-rich protein belonging to a newly defined family of proteins, including resistin, Relm-β, and Relm-γ. Although resistin was initially defined based on its insulin-resistance activity, the family members are highly induced in various inflammatory states. Earlier studies implicated Relm-α in insulin resistance, asthmatic responses, and intestinal inflammation; however, its function still remains an enigma. We now report that Relm-α is strongly induced in the esophagus in an allergen-challenged murine model of eosinophilic esophagitis (EoE). Furthermore, to understand the in vivo role of Relm-α, we generated Relm-α gene-inducible bitransgenic mice by using lung-specific CC-10 promoter (CC10-rtTA-Relm-α). We found Relm-α protein is significantly induced in the esophagus of CC10-rtTA-Relm-α bitransgenic mice exposed to doxycycline food. The most prominent effect observed by the induction of Relm-α is epithelial cell hyperplasia, basal layer thickness, accumulation of activated CD4+ and CD4− T cell subsets, and eosinophilic inflammation in the esophagus. The in vitro experiments further confirm that Relm-α promotes primary epithelial cell proliferation but has no chemotactic activity for eosinophils. Taken together, our studies report for the first time that Relm-α induction in the esophagus has a major role in promoting epithelial cell hyperplasia and basal layer thickness, and the accumulation of activated CD4+ and CD4− T cell subsets may be responsible for partial esophageal eosinophilia in the mouse models of EoE. Notably, the epithelial cell hyperplasia and basal layer thickness are the characteristic features commonly observed in human EoE. PMID:24994859

Allergen-induced resistin-like molecule-α promotes esophageal epithelial cell hyperplasia in eosinophilic esophagitis.

PubMed

Mavi, Parm; Niranjan, Rituraj; Dutt, Parmesh; Zaidi, Asifa; Shukla, Jai Shankar; Korfhagen, Thomas; Mishra, Anil

2014-09-01

Resistin-like molecule (Relm)-α is a secreted, cysteine-rich protein belonging to a newly defined family of proteins, including resistin, Relm-β, and Relm-γ. Although resistin was initially defined based on its insulin-resistance activity, the family members are highly induced in various inflammatory states. Earlier studies implicated Relm-α in insulin resistance, asthmatic responses, and intestinal inflammation; however, its function still remains an enigma. We now report that Relm-α is strongly induced in the esophagus in an allergen-challenged murine model of eosinophilic esophagitis (EoE). Furthermore, to understand the in vivo role of Relm-α, we generated Relm-α gene-inducible bitransgenic mice by using lung-specific CC-10 promoter (CC10-rtTA-Relm-α). We found Relm-α protein is significantly induced in the esophagus of CC10-rtTA-Relm-α bitransgenic mice exposed to doxycycline food. The most prominent effect observed by the induction of Relm-α is epithelial cell hyperplasia, basal layer thickness, accumulation of activated CD4(+) and CD4(-) T cell subsets, and eosinophilic inflammation in the esophagus. The in vitro experiments further confirm that Relm-α promotes primary epithelial cell proliferation but has no chemotactic activity for eosinophils. Taken together, our studies report for the first time that Relm-α induction in the esophagus has a major role in promoting epithelial cell hyperplasia and basal layer thickness, and the accumulation of activated CD4(+) and CD4(-) T cell subsets may be responsible for partial esophageal eosinophilia in the mouse models of EoE. Notably, the epithelial cell hyperplasia and basal layer thickness are the characteristic features commonly observed in human EoE. Copyright © 2014 the American Physiological Society.

Management of Benign Prostatic Hyperplasia: Could Dietary Polyphenols Be an Alternative to Existing Therapies?

PubMed Central

Eleazu, Chinedum; Eleazu, Kate; Kalu, Winner

2017-01-01

The incidence of benign prostatic hyperplasia (BPH) is gradually on the increase. While conventional drugs such as the α1-adrenergic receptor antagonists and 5α-reductase inhibitors have been found to be useful in the treatment of BPH, the adverse side effects associated with their usage, have led to increased search for alternative means of managing this disease. Furthermore, although surgery has also been suggested to be a sure method, the cost and risks associated with it excludes it as a routine treatment. Dietary polyphenols have gained public interest in recent times due to their roles in the prevention of various diseases that implicate free radicals/reactive oxygen species. However, their roles in the management of BPH have not been explored. Hence, this review on their prospects in the management of BPH and their mechanisms of action. Literature search was carried out in several electronic data bases such as PubMed, Google Scholar, Medline, Agora, and Hinari from1970 to 2017 to identify the current status of knowledge on this concept. The findings from these data bases suggest that while dietary polyphenols may not replace the need for the existing therapies in the management of BPH, they hold promise in BPH management which could be explored by researchers working in this field. PMID:28503148

Claudin-4 Deficiency Results in Urothelial Hyperplasia and Lethal Hydronephrosis

PubMed Central

Fujita, Harumi; Hamazaki, Yoko; Noda, Yumi; Oshima, Masanobu; Minato, Nagahiro

2012-01-01

Claudin (Cld)-4 is one of the dominant Clds expressed in the kidney and urinary tract, including selective segments of renal nephrons and the entire urothelium from the pelvis to the bladder. We generated Cldn4 −/− mice and found that these mice had increased mortality due to hydronephrosis of relatively late onset. While the renal nephrons of Cldn4 −/− mice showed a concomitant diminution of Cld8 expression at tight junction (TJ), accumulation of Cld3 at TJ was markedly enhanced in compensation and the overall TJ structure was unaffected. Nonetheless, Cldn4 −/− mice showed slightly yet significantly increased fractional excretion of Ca2+ and Cl−, suggesting a role of Cld4 in the specific reabsorption of these ions via a paracellular route. Although the urine volume tended to be increased concordantly, Cldn4 −/− mice were capable of concentrating urine normally on dehydration, with no evidence of diabetes insipidus. In the urothelium, the formation of TJs and uroplaques as well as the gross barrier function were also unaffected. However, intravenous pyelography analysis indicated retarded urine flow prior to hydronephrosis. Histological examination revealed diffuse hyperplasia and a thickening of pelvic and ureteral urothelial layers with markedly increased BrdU uptake in vivo. These results suggest that progressive hydronephrosis in Cldn4 −/− mice arises from urinary tract obstruction due to urothelial hyperplasia, and that Cld4 plays an important role in maintaining the homeostatic integrity of normal urothelium. PMID:23284964

Smooth muscle cells improve endothelial cell retention on polytetrafluoroethylene grafts in vivo.

PubMed

Yu, Hong; Dai, Wangde; Yang, Zhe; Kirkman, Paul; Weaver, Fred A; Eton, Darwin; Rowe, Vincent L

2003-09-01

We investigated the influence of smooth muscle cells (SMC) on endothelial cell (EC) retention on polytetrafluoroethylene (PTFE) grafts and the effect of SMC seeding on intimal hyperplasia in vivo in a rabbit model. Fibronectin-coated PTFE grafts (4 mm diameter) were seeded with either EC alone, SMC alone, or SMC followed 24 hours later by EC. The grafts were connected to an extracorporal aortic shunt for 1 hour or were individually implanted for 1, 30, and 100 days into the infrarenal aorta as an end-to-side bypass graft. The number of retained cells was compared at 1 hour and at 1 day after implantation. Neointimal thickness was measured 30 and 100 days after implantation. After 1-hour exposure to blood flow, EC retention rate was greater (P <.005) if seeded on top of SMC (98% +/- 2%; n = 8) versus being seeded alone (65 +/- 11%; n = 8). SMC retention rate was 95 +/- 5% (n = 8) when seeded alone. Similar cell retention was obtained 1 day after implantation. After 30-day implantation the neointima was thicker in grafts seeded with EC and SMC (282 +/- 136 microm; n = 3) than with EC only (52 +/- 45 microm; n = 3; P <.001). However, the neointimal thickness for dual-cell-seeded grafts (126 +/- 60 microm; n = 3) was not significantly different (P =.09) from EC-seeded grafts (79 +/- 48 microm; n = 3) after 100-day implantation. EC retention on PTFE grafts in vivo is improved if seeded over a layer of SMC. Further studies are needed to determine whether overlying EC modulate proliferation of underlying SMC.

Cardiac mesothelial papillary hyperplasia in four dogs.

PubMed

Kirejczyk, Shannon G; Burnum, Anne L; Brown, Corrie C; Sakamoto, Kaori; Rissi, Daniel R

2018-05-01

Mesothelial papillary hyperplasia (MPH) has been described as an incidental finding on the epicardial surface of clinically normal laboratory Beagle dogs. We describe MPH in 4 dogs diagnosed with acute cardiac tamponade (1 case) or chronic cardiac disease (3 cases). Cardiac MPH appeared as distinct, soft, irregular villous plaques on the epicardial surface of the auricles and occasionally the ventricles. Histologically, areas of MPH were composed of multiple papillary fronds arising from the epicardial surface and projecting into the pericardial space. Fronds were covered by cuboidal and occasionally vacuolated mesothelial cells and were supported by loose fibrovascular stroma with various degrees of edema and inflammation. Although these may represent incidental findings with no clinical significance, the gross appearance warrants differentiation from other conditions. Additional insight into the pathogenesis of MPH is needed to fully understand its significance in the face of concurrent cardiac disease.

Etiology and Effects of Ciomiphene on Cystic Endometrial Hyperplasia in the Miniature Pig

DTIC Science & Technology

1986-12-17

progesterone influences on the endometrium. Perhaps the presence of this imbalance over a prolonged period of time could lead to the development of...consequently this imbalance in the estrogenic and progestational influence on the endometrium over a prolonged period of time could lead to the development ...endometrial hyperplasia (CEH) has been attributed to a prolonged , unopposed estrogenic influence on the endometrium (Jones et al. 1981). Endometrial

Effects of pulsed electromagnetic fields on benign prostate hyperplasia.

PubMed

Giannakopoulos, Xenophon K; Giotis, Christos; Karkabounas, Spyridon Ch; Verginadis, Ioannis I; Simos, Yannis V; Peschos, Dimitrios; Evangelou, Angelos M

2011-12-01

Benign prostate hyperplasia (BPH) has been treated with various types of electromagnetic radiation methods such as transurethral needle ablation (TUNA), interstitial laser therapy (ILC), holmium laser resection (HoLRP). In the present study, the effects of a noninvasive method based on the exposure of patients with BPH to a pulsative EM Field at radiofrequencies have been investigated. Twenty patients with BPH, aging 68-78 years old (y.o), were enrolled in the study. Patients were randomly divided into two groups: the treatment group (10 patients, 74.0 ± 5.7 y.o) treated with the α-blocker Alfusosin, 10 mg/24 h for at least 4 weeks, and the electromagnetic group (10 patients, 73.7 ± 6.3 y.o) exposed for 2 weeks in a very short wave duration, pulsed electromagnetic field at radiofrequencies generated by an ion magnetic inductor, for 30 min daily, 5 consecutive days per week. Patients of both groups were evaluated before and after drug and EMF treatment by values of total PSA and prostatic PSA fraction, acid phosphate, U/S estimation of prostate volume and urine residue, urodynamic estimation of urine flow rate, and International Prostate Symptom Score (IPSS). There was a statistically significant decrease before and after treatment of IPSS (P < 0.02), U/S prostate volume (P < 0.05), and urine residue (P < 0.05), as well as of mean urine flow rate (P < 0.05) in patients of the electromagnetic group, in contrast to the treatment group who had only improved IPSS (P < 0.05). There was also a significant improvement in clinical symptoms in patients of the electromagnetic group. Follow-up of the patients of this group for one year revealed that results obtained by EMFs treatment are still remaining. Pulsed electromagnetic field at radiofrequencies may benefit patients with benign prostate hyperplasia treated by a non-invasive method.

Cutaneous Angiolymphoid Hyperplasia in a Dog.

PubMed

Michishita, M; Katori, Y; Sasaki, H; Obara, R D; Furumoto, R; Kato, M; Nakahira, R; Yoshimura, H; Soeta, S; Ishiwata, T; Takahashi, K

2017-07-01

A 5-year-old male miniature dachshund was presented with a dermal nodule on the left forelimb that increased to 5 mm in diameter over a 2-month period. Grossly, the nodule was firm, and both the external and cut surfaces were homogeneously pale pink in colour. Microscopically, the nodule was comprised of mainly plump endothelial cells and inflammatory cells; among the latter, lymphocytes were predominant, with few scattered plasma cells, mast cells and macrophages. Lymphoid follicles with germinal centres were often observed. Mitotic figures were not observed amongst the endothelial cells. Immunohistochemically, the endothelial cells were positive for vimentin, factor VIII-related antigen and CD31, and the surrounding cells were positive for smooth muscle actin. Lymphocytes expressed CD3 or BLA36. These findings led to a diagnosis of cutaneous angiolymphoid hyperplasia. To the best of our knowledge, this is the first report of a cutaneous proliferative disorder comprising an admixture of proliferating vascular endothelial cells and lymphocytic infiltration with follicle formation in a dog. Copyright © 2017 Elsevier Ltd. All rights reserved.

Condylectomy and “surgery first” approach: An expedited treatment for condylar hyperplasia in a patient with facial asymmetry

PubMed Central

López, Diego Fernando; Aristizábal, Juan Fernando; Martínez-Smit, Rosana

2017-01-01

ABSTRACT Condylar Hyperplasia (CH) is a self-limiting pathology condition that produces severe facial deformity at the expense of mandibular asymmetry. In this case report a 15-year-old female patient was diagnosed with Unilateral Condylar Hiperplasia (UCH) by mean of single-photon emission computed tomography (SPECT) and histological study. A high condylectomy in the right condyle was performed to stop the active status of the hyperplasia. A month after condylectomy, orthognathic jaw impaction and asymmetric mandibular setback surgery was performed with the Surgery First Approach (SFA). After 10 days, orthodontic appointments were made every two weeks during 4 months. The active phase of treatment lasted 14 months. Excellent facial and occlusal outcomes were obtained and after 24 months in retention the results remained stable. PMID:28902254

Inducible Knockdown of Endothelial Protein Tyrosine Phosphatase-1B Promotes Neointima Formation in Obese Mice by Enhancing Endothelial Senescence.

PubMed

Jäger, Marianne; Hubert, Astrid; Gogiraju, Rajinikanth; Bochenek, Magdalena L; Münzel, Thomas; Schäfer, Katrin

2018-02-01

Protein tyrosine phosphatase-1B (PTP1B) is a negative regulator of receptor tyrosine kinase signaling. In this study, we determined the importance of PTP1B expressed in endothelial cells for the vascular response to arterial injury in obesity. Morphometric analysis of vascular lesions generated by 10% ferric chloride (FeCl 3 ) revealed that tamoxifen-inducible endothelial PTP1B deletion (Tie2.ER T2 -Cre × PTP1B fl/fl ; End.PTP1B knockout, KO) significantly increased neointima formation, and reduced numbers of (endothelial lectin-positive) luminal cells in End.PTP1B-KO mice suggested impaired lesion re-endothelialization. Significantly higher numbers of proliferating cell nuclear antigen (PCNA)-positive proliferating cells as well as smooth muscle actin (SMA)-positive or vascular cell adhesion molecule-1 (VCAM1)-positive activated smooth muscle cells or vimentin-positive myofibroblasts were detected in neointimal lesions of End.PTP1B-KO mice, whereas F4/80-positive macrophage numbers did not differ. Activated receptor tyrosine kinase and transforming growth factor-beta (TGFβ) signaling and oxidative stress markers were also significantly more abundant in End.PTP1B-KO mouse lesions. Genetic knockdown or pharmacological inhibition of PTP1B in endothelial cells resulted in increased expression of caveolin-1 and oxidative stress, and distinct morphological changes, elevated numbers of senescence-associated β-galactosidase-positive cells, and increased expression of tumor suppressor protein 53 (p53) or the cell cycle inhibitor cyclin-dependent kinase inhibitor-2A (p16INK4A) suggested senescence, all of which could be attenuated by small interfering RNA (siRNA)-mediated downregulation of caveolin-1. In vitro, senescence could be prevented and impaired re-endothelialization restored by preincubation with the antioxidant Trolox. Our results reveal a previously unknown role of PTP1B in endothelial cells and provide mechanistic insights how PTP1B deletion or inhibition

The induction of C/EBPβ contributes to vitamin D inhibition of ADAM17 expression and parathyroid hyperplasia in kidney disease.

PubMed

Arcidiacono, Maria Vittoria; Yang, Jing; Fernandez, Elvira; Dusso, Adriana

2015-03-01

In secondary hyperparathyroidism (SHPT), enhanced parathyroid levels of transforming growth factor-α (TGFα) increase EGF receptor (EGFR) activation causing parathyroid hyperplasia, high parathyroid hormone (PTH) and also reductions in vitamin D receptor (VDR) that limit vitamin D suppression of SHPT. Since anti-EGFR therapy is not an option in human SHPT, we evaluated ADAM17 as a therapeutic target to suppress parathyroid hyperplasia because ADAM17 is required to release mature TGFα, the most potent EGFR-activating ligand. Computer analysis of the ADAM17 promoter identified TGFα and C/EBPβ as potential regulators of the ADAM17 gene. Their regulation of ADAM17 expression, TGFα/EGFR-driven growth and parathyroid gland (PTG) enlargement were assessed in promoter-reporter assays in A431 cells and corroborated in rat and human SHPT, using erlotinib as anti-EGFR therapy to suppress TGFα signals, active vitamin D to induce C/EBPβ or the combination. While TGFα induced ADAM17-promoter activity by 2.2-fold exacerbating TGFα/EGFR-driven growth, ectopic C/EBPβ expression completely prevented this vicious synergy. Accordingly, in advanced human SHPT, parathyroid ADAM17 levels correlated directly with TGFα and inversely with C/EBPβ. Furthermore, combined erlotinib + calcitriol treatment suppressed TGFα/EGFR-cell growth and PTG enlargement more potently than erlotinib in part through calcitriol induction of C/EBPβ to inhibit ADAM17-promoter activity, mRNA and protein. Importantly, in rat SHPT, the correction of vitamin D deficiency effectively reversed the resistance to paricalcitol induction of C/EBPβ to suppress ADAM17 expression and PTG enlargement, reducing PTH by 50%. In SHPT, correction of vitamin D and calcitriol deficiency induces parathyroid C/EBPβ to efficaciously attenuate the severe ADAM17/TGFα synergy, which drives PTG enlargement and high PTH. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Adenomatous hyperplasia of the mucous glands in captive Archey's frogs (Leiopelma archeyi).

PubMed

Shaw, S D; Berger, L; Harvey, C; Alley, M R; Bishop, P J; Speare, R

2017-05-01

associated with an increased risk of death. The skin lesions had the gross and microscopic characteristics of adenomatous hyperplasia of the dermal mucous glands. The aetiology of this adenomatous hyperplasia is unknown, but factors associated with the captive environment are the most likely cause. This is the first description of adenomatous hyperplasia of the cutaneous mucous glands in amphibians.

Effect of two different extracts of red maca in male rats with testosterone-induced prostatic hyperplasia.

PubMed

Gonzales, Gustavo F; Vasquez, Vanessa; Rodriguez, Daniella; Maldonado, Carmen; Mormontoy, Juliet; Portella, Jimmy; Pajuelo, Monica; Villegas, León; Gasco, Manuel

2007-03-01

To determine the effect of two different extracts of red maca in male rats. Prostatic hyperplasia was induced in male rats with testosterone enanthate (TE). The study comprised six groups: one control group (group 1), one group treated with TE (group 2), two groups treated with TE and aqueous extract of red maca (groups 3 and 4), one group treated with hydroalcoholic extract of red maca (group 5) and one group treated with finasteride (0.1 mg, group 6). Differences in the aqueous extract dependent on the length of time of boiling, whether for 2 or 3 hours, for groups 3 and 4 was assessed. Extracts of red maca contained 0.1 mg of benzylglucosinolate. Thereafter, a dose-response effect of different doses of benzylglucosinolates (0.02-0.08 mg) in red maca extracts was assessed. Prostate weight was similar in rats treated with freeze-dried aqueous extract of red maca prepared after 2 and 3 hours of boiling. Freeze-dried aqueous extract of red maca, hydroalcoholic extract of red maca and finasteride reduced prostate weight in rats with prostatic hyperplasia. No difference was observed between the data obtained from aqueous extract or hydroalcoholic extract of red maca. A dose dependent reduction of prostate weight was observed with the increase of the dose of benzylglucosinolates in red maca extracts. The present study showed that hydroalcoholic or aqueous extract of red maca containing 0.1 mg of benzylglucosinolate can reduce prostate size in male rats in which prostatic hyperplasia had been induced by TE.

Inflammatory Responses in a Benign Prostatic Hyperplasia Epithelial Cell Line (BPH-1) Infected with Trichomonas vaginalis.

PubMed

Kim, Sang-Su; Kim, Jung-Hyun; Han, Ik-Hwan; Ahn, Myoung-Hee; Ryu, Jae-Sook

2016-04-01

Trichomonas vaginalis causes the most prevalent sexually transmitted infection worldwide. Trichomonads have been detected in prostatic tissues from prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer. Chronic prostatic inflammation is known as a risk factor for prostate enlargement, benign prostatic hyperplasia symptoms, and acute urinary retention. Our aim was to investigate whether T. vaginalis could induce inflammatory responses in cells of a benign prostatic hyperplasia epithelial cell line (BPH-1). When BPH-1 cells were infected with T. vaginalis, the protein and mRNA of inflammatory cytokines, such as CXCL8, CCL2, IL-1β, and IL-6, were increased. The activities of TLR4, ROS, MAPK, JAK2/STAT3, and NF-κB were also increased, whereas inhibitors of ROS, MAPK, PI3K, NF-κB, and anti-TLR4 antibody decreased the production of the 4 cytokines although the extent of inhibition differed. However, a JAK2 inhibitor inhibited only IL-6 production. Culture supernatants of the BPH-1 cells that had been incubated with live T. vaginalis (trichomonad-conditioned medium, TCM) contained the 4 cytokines and induced the migration of human monocytes (THP-1 cells) and mast cells (HMC-1 cells). TCM conditioned by BPH-1 cells pretreated with NF-κB inhibitor showed decreased levels of cytokines and induced less migration. Therefore, it is suggested that these cytokines are involved in migration of inflammatory cells. These results suggest that T. vaginalis infection of BPH patients may cause inflammation, which may induce lower urinary tract symptoms (LUTS).

Inflammatory Responses in a Benign Prostatic Hyperplasia Epithelial Cell Line (BPH-1) Infected with Trichomonas vaginalis

PubMed Central

Kim, Sang-Su; Kim, Jung-Hyun; Han, Ik-Hwan; Ahn, Myoung-Hee; Ryu, Jae-Sook

2016-01-01

Trichomonas vaginalis causes the most prevalent sexually transmitted infection worldwide. Trichomonads have been detected in prostatic tissues from prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer. Chronic prostatic inflammation is known as a risk factor for prostate enlargement, benign prostatic hyperplasia symptoms, and acute urinary retention. Our aim was to investigate whether T. vaginalis could induce inflammatory responses in cells of a benign prostatic hyperplasia epithelial cell line (BPH-1). When BPH-1 cells were infected with T. vaginalis, the protein and mRNA of inflammatory cytokines, such as CXCL8, CCL2, IL-1β, and IL-6, were increased. The activities of TLR4, ROS, MAPK, JAK2/STAT3, and NF-κB were also increased, whereas inhibitors of ROS, MAPK, PI3K, NF-κB, and anti-TLR4 antibody decreased the production of the 4 cytokines although the extent of inhibition differed. However, a JAK2 inhibitor inhibited only IL-6 production. Culture supernatants of the BPH-1 cells that had been incubated with live T. vaginalis (trichomonad-conditioned medium, TCM) contained the 4 cytokines and induced the migration of human monocytes (THP-1 cells) and mast cells (HMC-1 cells). TCM conditioned by BPH-1 cells pretreated with NF-κB inhibitor showed decreased levels of cytokines and induced less migration. Therefore, it is suggested that these cytokines are involved in migration of inflammatory cells. These results suggest that T. vaginalis infection of BPH patients may cause inflammation, which may induce lower urinary tract symptoms (LUTS). PMID:27180569

Drug- and Gene-eluting Stents for Preventing Coronary Restenosis

PubMed Central

Lekshmi, Kamali Manickavasagam; Che, Hui-Lian; Cho, Chong-Su

2017-01-01

Coronary artery disease (CAD) has been reported to be a major cause of death worldwide. Current treatment methods include atherectomy, coronary angioplasty (as a percutaneous coronary intervention), and coronary artery bypass. Among them, the insertion of stents into the coronary artery is one of the commonly used methods for CAD, although the formation of in-stent restenosis (ISR) is a major drawback, demanding improvement in stent technology. Stents can be improved using the delivery of DNA, siRNA, and miRNA rather than anti-inflammatory/anti-thrombotic drugs. In particular, genes that could interfere with the development of plaque around infected regions are conjugated on the stent surface to inhibit neointimal formation. Despite their potential benefits, it is necessary to explore the various properties of gene-eluting stents. Furthermore, multifunctional electronic stents that can be used as a biosensor and deliver drug- or gene-based on physiological condition will be a very promising way to the successful treatment of ISR. In this review, we have discussed the molecular mechanism of restenosis, the use of drug- and gene-eluting stents, and the possible roles that these stents have in the prevention and treatment of coronary restenosis. Further, we have explained how multifunctional electronic stents could be used as a biosensor and deliver drugs based on physiological conditions. PMID:28184335

Congenital Adrenal Hyperplasia: Unresolved Issues.

PubMed

Yau, Mabel; Khattab, Ahmed; Poppas, Dix; Ghizzoni, Lucia; New, Maria

2016-01-01

Congenital adrenal hyperplasia (CAH) describes a family of disorders that comes from enzymatic deficiencies in cortisol production, with 21-hydroxylase deficiency causing ∼90% of cases. Distinction is made between the severe classical form and milder nonclassical form of CAH. Molecular genetic analysis is used to confirm the hormonal diagnosis. A high rate of genotype-phenotype disconcordance has been found in 21-hydroxylase deficiency. The goal of treatment is to replace with synthetic glucocorticoids and mineralocorticoids and suppress adrenal androgen production. The treatment of patients affected with nonclassical CAH, particularly males, remains controversial. Variable synthetic glucocorticoids are used and new modes of glucocorticoid delivery are under investigation. To improve height, growth hormone and other adjuvant therapies are employed. Long-term outcomes of genital surgery using modern techniques in females affected with classical CAH continue to be investigated. Prenatal treatment with dexamethasone is available to avoid ambiguous genitalia in these females. Although studies have shown its safety to mother and fetus, prenatal treatment is still regarded as experimental. Currently, prenatal diagnosis of CAH can only be obtained through invasive methods. Recently, the detection of cell-free fetal DNA in maternal plasma has made it possible to make this diagnosis earlier and noninvasively. © 2016 S. Karger AG, Basel.

Long term omeprazole therapy for reflux esophagitis: Follow-up in serum gastrin levels, EC cell hyperplasia and neoplasia

PubMed Central

Singh, Pankaj; Indaram, Anant; Greenberg, Ronald; Visvalingam, Vernu; Bank, Simmy

2000-01-01

AIM: To evaluate the long-term safety of omeprazole in patients of gastroesophageal reflux disease resistant to treatment with H2 receptor antagonist. METHODS: We prospectively followed 33 patients on omeprazole therapy for severe erosive esophagitis for 5-8 years, with periodic gastrin levels, H. pylori infection, gastric biopsies for incidence of ECL cell hyperplasia, carcinoids, gastric atrophy and neoplasia. A total 185 patient follow-up years and 137 gastric biopsies were done. RESULTS: Among the 33 patients, 36% reached their peak gastrin levels in an average of 8 mo to one year, then drifted Down slowly over 1-2 year period to just above their baseline level, 24% of the patients had a peak gastrin level above 400 ng·L-1 and one patient had a peak level above 1000 ng·L-1. One patient had a mild ECL cell hyperplasia which was self-limiting and did not show any dysplastic changes. Eighteen percent of patients were positive for H. pylori infection. The gastric biopsies did not show gastric atrophy, intestinal metaplasia or neoplastic changes. CONCLUSION: In a series of 33 patients followed for 5-8 years on omeprazole therapy for severe reflux esophagitis, we did not observe any evidence of significant ECL cell hyperplasia, gastric atrophy, intestinal metaplasia, dysplasia or neoplastic changes. PMID:11819697

Discovery of human immunodeficiency virus infection by immunohistochemistry on lymph node biopsies from patients with unexplained follicular hyperplasia.

PubMed

de Paiva, Geisilene Russano; Laurent, Camille; Godel, Aurélie; da Silva, Nivaldo Adolfo; March, Michel; Delsol, Georges; Brousset, Pierre

2007-10-01

Over the last 10 years, 240 cases of hyperplasic lymphadenitis have been systematically tested in our institution for the presence of the human immunodeficiency virus (HIV). This series comprised patients between 15 and 90 years (median of age: 38.51) without a past history of HIV infection. The technical approach consisted in an immunohistochemical procedure with a monoclonal antibody against the p24-gag protein of HIV. Among the 240 cases, 105 had a true follicular hyperplasia. Overall, this survey found that 4 cases (3 males and 1 female) were positive for p24-gag without previous knowledge of HIV infection (4/240=1.66%). HIV infection was further confirmed by serologic and molecular investigations in all cases. These results were seen exclusively in those cases with prominent follicular hyperplasia (4/105=3.80%). Staining with the anti-p24 antibody was intense and restricted to the follicular dendritic cell networks. In one case, beside hyperplasic germinal centers, one could see a regressed onion bulblike structure. One important conclusion can be drawn from this study. A systematic research of HIV proteins should be performed in all lymph node biopsies with marked follicular hyperplasia, in a context of polyadenopathy, fever, and general status alteration. Besides giving an accurate diagnosis, this approach may be helpful in cases of recent infection in which anti-p24 antibodies are not yet detectable in the serum.

Idiopathic osseous hyperplasia of the nasal turbinates in a Welsh terrier.

PubMed

Rutherford, S; Whitbread, T; Ness, M

2011-09-01

A three-year-old Welsh terrier was presented with a 6-month history of progressive stertor, exercise intolerance and sneezing which was unresponsive to symptomatic treatment. A large calcified mass occupying the entire rostral right nasal cavity was defined with computed tomography. The mass was completely removed via a dorsal rhinotomy. Histopathological examination of the mass revealed osseous hyperplasia of the nasal turbinates. The excision led to complete resolution of clinical signs and there has been no recurrence 18 months after surgery. © 2011 British Small Animal Veterinary Association.

Multifocal epithelial hyperplasia in a community in the Mayan area of Mexico.

PubMed

González-Losa, Maria R; Suarez-Allén, Rosa E; Canul-Canche, Jaqueline; Conde-Ferráez, Laura; Eljure-Lopez, Nixma

2011-03-01

Multifocal epithelial hyperplasia is a pathology of the oral mucosa which has been reported in diverse ethnic groups. Human papillomavirus (HPV) types 13 and 32 DNA has been detected in these lesions. The aims of this paper are to describe the epidemiological and clinical characteristics of an outbreak in a rural community in the Mayan area of Mexico and to identify a possible route of transmission through saliva. A cross-sectional study was conducted in Chemax (Yucatan, Mexico). Clinical and epidemiological data were obtained through direct interviews. Samples of oral cells and saliva were taken. HPV 13 and 32 were identified by polymerase chain reaction using specific primers. A total of 57 patients were studied, of whom 79.1% were aged <15 years, 38.6% were male, and 61.3% were female. The duration of lesions ranged from one month to 50 years. Lesions were located on the lips, jugal mucosa, and more frequently, the tongue. HPV 13 was found in all the patients and HPV 32 in none. A total of 42 saliva samples were positive for HPV 13. Human papillomavirus type 13 is involved in multifocal epithelial hyperplasia among the Mexican Mayan population. The presence of HPV 13 in cells from saliva, combined with poor hygiene behaviors, may explain the familial distribution of the pathology. © 2011 The International Society of Dermatology.

RNA sequencing reveals significant miRNAs in Atypical endometrial hyperplasia.

PubMed

Tang, Shiqian; Dai, Yinmei

2018-06-01

In this paper, we aimed to investigate the miRNAs that played a regulatory role in the development of atypical endometrial hyperplasia (AEH). RNA sequencing was performed for endometrial tissues from 3 AEH patients and 3 endometrial normal hyperplasia patients. RNA sequencing data were processed and differentially expressed (DE) miRNAs were identified between AEH and controls. The target genes for DE miRNAs were identified and mapped to the protein-protein interaction (PPI) network. The miRNA related functions were predicted and miRNA-disease gene network was constructed. Total 18 DE miRNAs were overlapped in three sample groups, among which hsa-miR-577, hsa-miR-182-5p and hsa-miR-183-5p were top three miRNAs that targeting largest number of genes. Function analysis showed that the 18 overlapped miRNAs mainly related with cancer and signaling transduction related pathways. PPI network showed that total 12 genes were among top 20 genes based on three network topological features including BCL2, UMPS, MAPK13, PRKCB, CREB1, IGF1, SP1, SMAD3, IGF1R, NOTCH2, WNT5A, TK2. Top 10 miRNAs in miRNA-disease gene network were identified such as hsa-miR-577 (degree = 17), hsa-miR-182-5p (degree = 16) and hsa-miR-3609 (degree = 13). hsa-miR-577 and hsa-miR-182-5p may play regulatory role in AEH through AMPK signal pathway and Wnt signaling pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

Megestrol Acetate or Levonorgestrel-Releasing Intrauterine System in Treating Patients With Atypical Endometrial Hyperplasia or Endometrial Cancer

ClinicalTrials.gov

2014-09-09

Atypical Endometrial Hyperplasia; Endometrial Adenocarcinoma; Recurrent Endometrial Carcinoma; Stage IA Endometrial Carcinoma; Stage IB Endometrial Carcinoma; Stage II Endometrial Carcinoma; Stage IIIA Endometrial Carcinoma; Stage IIIB Endometrial Carcinoma; Stage IIIC Endometrial Carcinoma; Stage IVA Endometrial Carcinoma; Stage IVB Endometrial Carcinoma

[KTP (green light) laser for the treatment of benign prostatic hyperplasia. Preliminary evaluation].

PubMed

Coz, Fernando; Domenech, Alfredo

2007-09-01

Photoselective vaporization of benign prostatic hyperplasia (BPH) is a minimally invasive technique, consisting of vaporization of prostatic tissue by KTP green light laser with a power of 80 W. The purpose of this study was to describe our experience with this technique. KTP laser photoselective vaporization was performed in 18 patients, with lower obstructive uropathy secondary to benign prostatic hyperplasia at Santiago Military hospital from December 2005. Preoperative characteristics, postoperative results and complications were recorded. Mean prostatic volume was 55 cc (range: 24 to 78). Mean operating time was 83 minutes (range: 40 to 120). In sixteen patients, the Foley catheter was removed before 24 hours. The mean preoperative AUA score was 22 and decreased to 11.4 after 30 days. The mean maximum preoperative urine flow rate was 9 ml/s and increased to 18.2; 22.1; 22.5; 25.3 and 27.2 ml/s on days 1, 7, 14, 21 and 30, respectively. Only minor complications were observed: delayed removal of the Foley catheter (11.1%), dysuria (16.6%) and late haematuria (11.1%). KTP laser photoselective vaporization of BPH is a safe technique, that is easy to learn, with good short-term functional results, associated with low complication rate.

[National screening for phenylketonuria, congenital hypothyroidism and congenital adrenal hyperplasia].

PubMed

Osório, R V; Vilarinho, L; Soares, J P

1992-03-01

In Portugal the screening for phenylketonuria (PKU) and congenital hypothyroidism (CH) was begun towards the end of 1979, and by 1990 59 cases of PKU and 227 cases of CH had been detected. The early initiation of treatment and the observed mental and motor development, point towards a normal development in these children. A trial screen for congenital adrenal hyperplasia was carried out in 100.000 newborns, from which it was concluded that, under the present conditions, screening at a national level is not justified. A similar study is currently being undertaken for biotinidase deficiency and cystic fibrosis. The results ares discussed, as are the cost/benefits evaluations.

Trends in Simple Prostatectomy for Benign Prostatic Hyperplasia.

PubMed

Pariser, Joseph J; Packiam, Vignesh T; Adamsky, Melanie A; Bales, Gregory T

2016-08-01

The definitive treatment for symptomatic large volume (>80 mL) benign prostatic hyperplasia (BPH) is simple prostatectomy (SP). This can be performed by utilizing a retropubic, suprapubic, or a combined approach. The latter two approaches allow for the management of concomitant bladder diverticulum or stones through the same incision. Each approach affords unique technical strengths and weaknesses that must be considered in light of patient characteristics and concomitant pathology. SP allows for removal of the entire prostatic adenoma while obviating some of the neurovascular and continence issues that can arise from radical prostatectomy. Concerns with SP include its relatively high perioperative morbidity, notably bleeding. Therefore, there is increasing interest in less invasive options, including enucleation procedures and minimally invasive SP. This review presents an update regarding trends and outcomes of SP, as well as the effectiveness and popularity of alternative treatments.

The therapeutic potential of royal jelly in benign prostatic hyperplasia. Comparison with contemporary literature.

PubMed

Pajovic, Bogdan; Radojevic, Nemanja; Dimitrovski, Antonio; Tomovic, Savo; Vukovic, Marko

2016-09-01

The aim of this study is to establish the scientific benefit of royal jelly (RJ) on prostatic-specific antigen (PSA), post-void residual (PVR) volume and International Prostate Symptom Score (IPSS) in benign prostatic hyperplasia. For the study, a group of 40 men were administered 38 mg of RJ over a period of three months, their PSA values, prostate volumes and the volumes of their transitory prostate zones, PVR and IPPS values were measured at the end of the first month, and at the end of the third month. The results of this study confirm the potential of RJ in reducing PSA scores and improving IPSS values. Since the use of RJ did not lead to any significant reduction in PVR, prostate volume, or to any involution of the transitory zone, it appears that it may only affect the blood marker of prostatic hyperplasia and to improve quality-of-life (QoL) in those patients. Overall, in comparison to phytotherapy and conventional therapy, RJ had similar positive effects on QoL in patients with BPH, however it exhibited markedly better effects on reducing PSA levels in blood. The therapeutical use of RJ exhibited no side effects.

Ameliorative effects of stinging nettle (Urtica dioica) on testosterone-induced prostatic hyperplasia in rats.

PubMed

Nahata, A; Dixit, V K

2012-05-01

The present study investigated the effects of stinging nettle (Urtica dioica L.) (UD) on benign prostatic hyperplasia (BPH) induced by testosterone. In vitro studies were conducted to assess the 5α-reductase inhibitory potential of UD. Two biochemical markers viz., β-sitosterol and scopoletin, were isolated and characterised in the extracts utilising High-performance thin layer chromatographic, FTIR, NMR and overlain UV spectral studies. Hyperplasia was induced in rats by subcutaneous administration of testosterone (3 mg kg(-1) s.c.) for 28 days in all the groups except the vehicle-treated group. Simultaneous administration of petroleum ether and ethanolic extracts (10, 20 and 50 mg kg(-1) p.o.) and isolated β-sitosterol (10 and 20 mg kg(-1) p.o.) was undertaken. Finasteride was used as a positive control (1 mg kg(-1) p.o.). Measurement of prostate/body weight ratio, weekly urine output and serum testosterone levels, prostate-specific antigen levels (on day 28) and histological examinations carried out on prostates from each group led us to conclude that UD can be used as an effective drug for the management of BPH. © 2011 Blackwell Verlag GmbH.

An observational analysis of provider adherence to AUA guidelines on the management of benign prostatic hyperplasia.

PubMed

Auffenberg, Gregory B; Gonzalez, Chris M; Wolf, J Stuart; Clemens, J Quentin; Meeks, William; McVary, Kevin T

2014-11-01

We retrospectively evaluated urologist adherence to the AUA guidelines on the management of new patients with benign prostatic hyperplasia related lower urinary tract symptoms in a large university urology group. All first time benign prostatic hyperplasia/lower urinary tract symptom visits to the urology clinic at the Northwestern Medical Faculty Foundation between January 1, 2008 and December 31, 2012 were evaluated using an institutionally managed electronic medical record data repository. Clinical documentation and orders from each encounter were assessed to determine the rate of performance of guideline measures. Approximately 1% of all results were manually reviewed in a validation process designed to determine the reliability of the electronic medical record based system. A total of 3,494 eligible encounters were evaluated in the final analysis. Provider adherence rates with the 9 measures recommended in the guidelines varied by measure from 53.0% to 92.8%. The rate of performance of 5 not routinely recommended measures was 10.2% or less. Post-void residual and urinary flow measurement were optional measures, and were performed on 68.1% and 4.6% of new encounters respectively. Manual validation revealed the electronic medical record data extraction was concordant with manual review in 96.7% of cases (95% CI 94.8-98.5). Using electronic medical record based data extraction techniques, we reliably document a baseline adherence rate with AUA guidelines on the management of benign prostatic hyperplasia. Establishing this benchmark will be important for future investigation into patient outcomes related to guideline adherence and into methods for improving provider adherence. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Comparison of Anti BPH capsule (herbal) and Terazosin HCl in the treatment of benign prostate hyperplasia.

PubMed

Nadeem, Hafiz Mohammad Rashid; Mohiuddin, Ejaz; UdDin, Shahab; Daniyal, Muhammad; Usmanghani, Khan

2017-01-01

Benign prostatic hyperplasia (BPH) is a disease of senile age, usually occurring> 60 years of age. BPH is a disease that involves cell proliferation of the prostate. Pathological hyperplasia affects the elements of the glandular and connective tissue of the prostate. This study is designed to scrutinize the efficacy and tolerability of herbal drug Anti BPH capsule for the management of benign prostate hyperplasia (BPH), in this study we select the 100 patients in which 50 received the Anti BPH capsule and 50 received the Terazosin HCl. We use the American Urological Association BPH Symptom Score Index Questionnaire to measure the quality of life of the patients. We compare the before treatment and after treatment results for each symptom. We record the following symptoms, incomplete emptying of bladder, Frequency, Intermittency, Urgency, Weak stream, Straining, Nocturia and weight of prostate gland by USG. We compare the both drug by using paired sample t-test. The level of significance of incomplete emptying of bladder before treatment and after treatment is 0.013 in test group and 0.032 in control group. Similarly the level of significance of Frequency before treatment and after treatment in test groups in, intermittency, Urgency, Weak stream, staining, Nocturia and mean weight of prostate gland are 0.007, 0.015, 0.044, 0.012, 0.017, 0.004 and 0.020; where as in control group afford as 0.031, 0.044, 0.044, 0.032, 0.024, 0.009 and 0.035 respectively. The herbal drug Anti BPH capsule is more effective in the treatment of BPH than Allopathic medicine Terazosin HCl.

High Background Incidence of Spontaneous Subcapsular Adrenal Gland Hyperplasia of Tg.rasH2 Mice Used in 26-week Carcinogenicity Studies.

PubMed

Boyle, Molly H; Paranjpe, Madhav G; Creasy, Dianne M

2018-06-01

The Tg.rasH2 model was accepted by regulatory agencies worldwide for 26-week carcinogenicity assays as an alternative to the standard 2-year assays in conventional mice in 2003. Several references documenting spontaneous nonneoplastic findings and incidences of spontaneous tumors in the Tg.rasH2 mice have been published. The purpose of this publication is to add adrenal gland subcapsular hyperplasia to the database pertaining to spontaneous lesions noted in Tg.rasH2 mice, review physiology related to this finding, and discuss its significance. The incidence of spontaneous subcapsular adrenal gland hyperplasia was determined in control Tg.rasH2 mice from nine 26-week carcinogenicity studies carried out within the last 5 years at two contract research organizations. Incidence of this finding ranged from 56% to 79% in males and 88% to 100% in females, with an incidence average of 62% in males and 93% in females. Adrenal gland subcapsular hyperplasia is a common finding in male and female Tg.rasH2 mice that did not progress to neoplasia in Tg.rasH2 mice. In general, it tends to be more frequent and severe in females in comparison to males.

Adenomatous hyperplasia of the thyroid gland in beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary and Hudson Bay, Quebec, Canada.

PubMed

Mikaelian, I; Labelle, P; Kopal, M; De Guise, S; Martineau, D

2003-11-01

We evaluated thyroid gland lesions in beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary (n = 16) and Hudson Bay (n = 14). Follicular cysts and nodules of adenomatous hyperplasia of the thyroid gland were found in eight and nine adults from the St. Lawrence Estuary (n = 10), respectively, and in four and six adults from Hudson Bay (n = 14), respectively. The total volume of the lesions of thyroid adenomatous hyperplasia was positively correlated with age in both populations. Comparison between populations could not be performed because of differences in age structures of sample groups. Beluga whales from both populations have unique thyroid lesions among marine mammals.

Flaxseed reduces epithelial proliferation but does not affect basal cells in induced benign prostatic hyperplasia in rats.

PubMed

de Amorim Ribeiro, Ilma Cely; da Costa, Carlos Alberto Soares; da Silva, Vivian Alves Pereira; Côrrea, Lanna Beatriz Neves Silva; Boaventura, Gilson Teles; Chagas, Mauricio Alves

2017-04-01

This study aimed to quantitatively and qualitatively evaluate the effects of a flaxseed-based diet on the histoarchitecture of the prostate of normal Wistar rats and of rats with induced BPH. The study included four experimental groups of ten animals each: casein control group (CCG), who were fed a casein-based diet; flaxseed control group (FCG), who were fed a flaxseed-based diet; hyperplasia-induced casein group (HICG), who were fed a casein-based diet; and hyperplasia-induced flaxseed group (HIFG), who were fed a flaxseed-based diet. Hyperplasia was induced by the subcutaneous implantation of silicone pellets containing testosterone propionate. After 20 weeks, the rats were euthanized and their prostate fixed in buffered formalin. Tissue sections were stained with HE, picrosirius red and immunostained for nuclear antigen p63. Histomorphometric analysis evaluated the epithelial thickness, epithelial area, individual luminal area, and total area of prostatic alveoli. The mean epithelial thickness obtained for HIFG and HICG was 16.52 ± 1.65 and 20.58 ± 2.86 µm, respectively. The mean epithelial thickness in HICG was greater than that in the other groups tested. HIFG had a smaller epithelial thickness and lower percentage of papillary projections in the prostatic alveoli. No significant difference was observed between CCG and FCG. The total area and mean alveolar area showed no significant differences between the groups. The number of cells immunostained for p63 was not significantly different between the groups evaluated. These results suggest that flaxseed has a protective effect on the prostate epithelium in BPH-induced animals.

A Novel Technique for Cervical Facet Joint Hyperplasia-Spondylotic Radiculopathy by Laminar and Lateral Mass Screw Cofixations.

PubMed

Sheng, Sun-Ren; Wang, Ke; Nisar, Majid; Chen, Jiao-Xiang; Wu, Ai-Min; Wang, Xiang-Yang

2018-02-01

We sought to describe the novel technique and report the outcomes of cervical spondylotic radiculopathy caused by facet joint hyperplasia treated with minimally invasive surgery by laminar and lateral mass screw cofixations. In this retrospective study, patients with spondylotic radiculopathy caused by facet joint hyperplasia underwent this technique in our unit between January 2010 and June 2015. Hospital charts, magnetic resonance imaging studies, and follow-up records for all the patients were reviewed. Outcomes were assessed on the basis of neurologic status, magnetic resonance imaging, and visual analog scale for neck and radicular pain and by the short form-36 health survey questionnaire. Thirteen men and 5 women, aged 47-73 years (mean, 61.8 years), were included in this study. The follow-up time ranged from 19-50 months (mean, 32.4 months). The mean visual analog scale scores for radicular pain and neck pain, as well as the scores for all 8 domains of the short form-36 health survey questionnaire, showed significant improvements (P < 0.05). Cervical lordosis showed bending, whereas the height of the targeted disk segment showed no change (P > 0.05). Complications included 2 cases of neck pain that lasted for 3 months. Minimally invasive surgery by lamina and lateral mass screw cofixation is safe and effective for the treatment of cervical spondylotic radiculopathy caused by facet joint hyperplasia. In addition to sufficient decompression, this technique provides relative stability to the cervical spine. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Glucose transporter member 1 is involved in UVB-induced epidermal hyperplasia by enhancing proliferation in epidermal keratinocytes.

PubMed

Tochio, Takumi; Tanaka, Hiroshi; Nakata, Satoru

2013-03-01

Glucose transporter member 1 (GLUT-1) is one of the major facilitated glucose transporters and contributes to the promotion of keratinocyte proliferation in psoriasis and carcinogenic lesions. In this study, we postulate that GLUT-1 is involved in ultraviolet B (UVB)-induced epidermal hyperplasia. The purpose of this study is to investigate the possible role of GLUT-1 in UVB-induced hyperplasia. The effects of UVB on GLUT-1 expression levels were investigated in in vitro and in vivo studies. In addition, the involvement of epidermal growth factor (EGF) and hypoxia inducible factor-1 alpha (HIF-1α), transcriptional factors for GLUT-1, in GLUT-1-related events were investigated. GLUT-1 mRNA and its protein levels were markedly increased by UVB irradiation in HaCaT cells. In in vivo studies, a strong immunofluorescence signal of GLUT-1 was clearly observed around the basal layer of the epidermis, which proliferated excessively by UVB irradiation. In HaCaT cells, EGF mRNA and its protein levels were markedly increased by UVB irradiation, and then the GLUT-1 mRNA level was significantly increased by treatment with EGF. Additionally, the upregulation of GLUT-1 by both UVB irradiation and treatment with EGF was significantly suppressed by transfection with HIF-1α siRNA. We conclude that GLUT-1 is involved in UVB-induced epidermal hyperplasia by enhancing proliferation of epidermal basal cells, and the GLUT-1-related event might be regulated by an increase in HIF-1α stimulated by EGF. © 2013 The International Society of Dermatology.

Phloem-limited reoviruses universally induce sieve element hyperplasia and more flexible gateways, providing more channels for their movement in plants.

PubMed

Lv, Ming-Fang; Xie, Li; Song, Xi-Jiao; Hong, Jian; Mao, Qian-Zhuo; Wei, Tai-Yun; Chen, Jian-Ping; Zhang, Heng-Mu

2017-11-28

Virion distribution and ultrastructural changes induced by the infection of maize or rice with four different reoviruses were examined. Rice black streaked dwarf virus (RBSDV, genus Fijivirus), Rice ragged stunt virus (RRSV, genus Oryzavirus), and Rice gall dwarf virus (RGDV, genus Phytoreovirus) were all phloem-limited and caused cellular hyperplasia in the phloem resulting in tumors or vein swelling and modifying the cellular arrangement of sieve elements (SEs). In contrast, virions of Rice dwarf virus (RDV, genus Phytoreovirus) were observed in both phloem and mesophyll and the virus did not cause hyperplasia of SEs. The three phloem-limited reoviruses (but not RDV) all induced more flexible gateways at the SE-SE interfaces, especially the non-sieve plate interfaces. These flexible gateways were also observed for the first time at the cellular interfaces between SE and phloem parenchyma (PP). In plants infected with any of the reoviruses, virus-like particles could be seen within the flexible gateways, suggesting that these gateways may serve as channels for the movement of plant reoviruses with their large virions between SEs or between SEs and PP. SE hyperplasia and the increase in flexible gateways may be a universal strategy for the movement of phloem-limited reoviruses.

SRD5A1 and SRD5A2 are associated with treatment for benign prostatic hyperplasia with the combination of 5α-reductase inhibitors and α-adrenergic receptor antagonists.

PubMed

Gu, Xin; Na, Rong; Huang, Tao; Wang, Li; Tao, Sha; Tian, Lu; Chen, Zhuo; Jiao, Yang; Kang, Jian; Zheng, Siqun; Xu, Jianfeng; Sun, Jielin; Qi, Jun

2013-08-01

Common treatments for benign prostatic hyperplasia include 5α-reductase inhibitors and α-adrenergic receptor antagonists. However, these treatments can only partially decrease the risk of benign prostatic hyperplasia progression. SRD5A1 and SRD5A2 are 5α-reductase inhibitor targets. We investigated the association between drug efficacy and single nucleotide polymorphisms in the SRD5A1 and SRD5A2 genes in a Chinese population. We genotyped 11 tagging single nucleotide polymorphisms in the SRD5A1 and SRD5A2 genes in a total of 426 benign prostatic hyperplasia cases and 1,008 controls from Xinhua Hospital, Shanghai, People's Republic of China. Cases were treated with type II 5α-reductase inhibitors and α-adrenergic receptor antagonists. We tested the association of tagging single nucleotide polymorphisms with benign prostatic hyperplasia risk/progression, clinical characteristics at baseline, including the I-PSS (International Prostate Symptom Score) and total prostate volume, and changes in clinical characteristics after treatment. The 11 tagging single nucleotide polymorphisms were not significantly associated with benign prostatic hyperplasia risk or progression (each p >0.05). In the SRD5A1 gene rs6884552 and rs3797177 were significantly associated with baseline I-PSS (p = 0.04 and 0.003, respectively). In the SRD5A2 gene rs523349 (V89L) and rs9332975 were significantly associated with baseline total prostate volume (p = 0.01 and 0.001, respectively). In SRD5A1 rs166050 was significantly associated with the posttreatment change in total prostate volume (p = 0.04). In SRD5A2 rs523349 and rs612224 were significantly associated with the posttreatment I-PSS change (p = 0.03 and 0.009, respectively). SRD5A1 and SRD5A2 single nucleotide polymorphisms are significantly associated with the clinical characteristics of benign prostatic hyperplasia and the efficacy of benign prostatic hyperplasia treatment. Copyright © 2013 American Urological Association Education and

Disruptive technological advances in vascular access for dialysis: an overview.

PubMed

Yeo, Wee-Song; Ng, Qin Xiang

2017-11-29

End-stage kidney disease (ESKD), one of the most prevalent diseases in the world and with increasing incidence, is associated with significant morbidity and mortality. Current available modes of renal replacement therapy (RRT) include dialysis and renal transplantation. Though renal transplantation is the preferred and ideal mode of RRT, this modality may not be available to all patients with ESKD. Moreover, renal transplant recipients are constantly at risk of complications associated with immunosuppression and immunosuppressant use, and posttransplant lymphoproliferative disorder. Dialysis may be the only available modality in certain patients. However, dialysis has its limitations, which include issues associated with lack of vascular access, risks of infections and vascular thrombosis, decreased quality of life, and absence of biosynthetic functions of the kidney. In particular, the creation and maintenance of hemodialysis vascular access in children poses a unique set of challenges to the pediatric nephrologist owing to the smaller vessel diameters and vascular hyperreactivity compared with adult patients. Vascular access issues continue to be one of the major limiting factors prohibiting the delivery of adequate dialysis in ESKD patients and is the Achilles' heel of hemodialysis. This review aims to provide a critical overview of disruptive technological advances and innovations for vascular access. Novel strategies in preventing neointimal hyperplasia, novel bioengineered products, grafts and devices for vascular access will be discussed. The potential impact of these solutions on improving the morbidity encountered by dialysis patients will also be examined.

Natal Tooth Associated with Fibrous Hyperplasia – A Rare Case Report

PubMed Central

Munjal, Deepti; Dhingra, Renuka; Malik, Narender Singh; Sidhu, Gagandeep Kaur

2015-01-01

Eruption of tooth at about 6 months of age is a significant stage in child’s life and is an emotional event for parents. However, a tooth present in the oral cavity of newborn can lead to a lot of delusions. Natal and neonatal teeth are of utmost importance not only for a dentist but also for a paediatrician due to parent’s anxiety, folklore superstitions and numerous associated complications with it. This paper reports a rare case, wherein a natal tooth has led to the development of a reactive fibrous hyperplasia in an 8-week-old infant. PMID:26023656

Risk factors for bladder calculi in patients with benign prostatic hyperplasia.

PubMed

Huang, Wei; Cao, Jun-Jie; Cao, Min; Wu, Hong-Shen; Yang, Yong-Yi; Xu, Zi-Meng; Jin, Xiao-Dong

2017-08-01

We aim to find the risk factors that influence the formation of bladder calculi in patients with benign prostate hyperplasia (BPH) and to reduce the surgical intervention related to bladder calculi.Between January 2015 and October 2016, 332 patients with BPH underwent surgical therapy were retrospectively evaluated. Patients with BPH were categorized into 2 groups: 94 patients with bladder calculi in group 1 and 238 patients without bladder calculi in group 2. Medical history, age, body mass index (BMI), total prostate specific antigen, total prostate volume (TPV), International Prostate Symptom Score (IPSS), intravesical prostatic protrusion (IPP), urodynamic parameters, and urine culture were compared between groups.There was no significant difference in the age, BMI, peak flow rate, and total IPSS between groups. TPV, total prostate specific antigen, and duration of BPH were significantly lower in group 1 than those in group 2. In addition, IPP was significantly higher in group 1 than group 2 (P < .001). Besides, after exclusion of patients with urinary retention and indwelling catheter, group 1 associated with a significantly higher preoperative positive rate of urine culture than that of group 2 (P = .046). Multivariate analysis indicated that IPP was a significant independent risk factor for the presence of bladder calculi.The incidence of bladder calculi in patients with BPH was proved to be closely associated with preoperative positive urine culture and longer IPP in our study. Furthermore, the IPP was presented to be an independent risk factor for the formation of bladder calculi. And early antibacterial therapy of urinary tract infection (UTI) may help to prevent the presence of bladder calculi in patients with BPH.

Magnetic Resonance Imaging of the Vocal Folds in Women with Congenital Adrenal Hyperplasia and Virilized Voices

ERIC Educational Resources Information Center

Nygren, Ulrika; Isberg, Bengt; Arver, Stefan; Hertegård, Stellan; Södersten, Maria; Nordenskjöld, Agneta

2016-01-01

Purpose: Women with congenital adrenal hyperplasia (CAH) may develop a virilized voice due to late diagnosis or suboptimal suppression of adrenal androgens. Changes in the vocal folds due to virilization have not been studied in vivo. The purpose was to investigate if the thyroarytenoid (TA) muscle is affected by virilization and correlate…

Uterine epithelial cell proliferation and endometrial hyperplasia: evidence from a mouse model

PubMed Central

Gao, Yang; Li, Shu; Li, Qinglei

2014-01-01

In the uterus, epithelial cell proliferation changes during the estrous cycle and pregnancy. Uncontrolled epithelial cell proliferation results in implantation failure and/or cancer development. Transforming growth factor-β (TGF-β) signaling is a fundamental regulator of diverse biological processes and is indispensable for multiple reproductive functions. However, the in vivo role of TGF-β signaling in uterine epithelial cells remains poorly defined. We have shown that in the uterus, conditional deletion of the Type 1 receptor for TGF-β (Tgfbr1) using anti-Müllerian hormone receptor type 2 (Amhr2) Cre leads to myometrial defects. Here, we describe enhanced epithelial cell proliferation by immunostaining of Ki67 in the uteri of these mice. The aberration culminated in endometrial hyperplasia in aged females. To exclude the potential influence of ovarian steroid hormones, the proliferative status of uterine epithelial cells was assessed following ovariectomy. Increased uterine epithelial cell proliferation was also revealed in ovariectomized Tgfbr1 Amhr2-Cre conditional knockout mice. We further demonstrated that transcript levels for fibroblast growth factor 10 (Fgf10) were markedly up-regulated in Tgfbr1 Amhr2-Cre conditional knockout uteri. Consistently, treatment of primary uterine stromal cells with TGF-β1 significantly reduced Fgf10 mRNA expression. Thus, our findings suggest a potential involvement of TGFBR1-mediated signaling in the regulation of uterine epithelial cell proliferation, and provide genetic evidence supporting the role of uterine epithelial cell proliferation in the pathogenesis of endometrial hyperplasia. PMID:24770950

Immunohistochemical distribution of collagens type I, III, IV and VI, of undulin and of tenascin in oral fibrous hyperplasia.

PubMed

Becker, J; Schuppan, D; Müller, S

1993-11-01

The distribution of collagens type I, IV and VI, of procollagen type III, of undulin and of tenascin was studied in 10 lesions which were clinically and histologically diagnosed as localized oral fibrous hyperplasias. The immunohistochemical distribution of these proteins was similar to that observed for normal oral mucosa. Undulin showed a pattern of parallel fibers throughout. Collagen type VI was pronounced in the subepithelial connective tissue, whereas the collagen fiber bundles were equally reactive for collagens type I and III. Tenascin was observed close to the subepithelial basement membrane and in proximity to collagen fiber bundles in the upper connective tissue. The present findings indicate that oral fibrous hyperplasias that are probably caused by inflammation or chronic irritation show the differentiated and ordered pattern of extracellular matrix proteins characteristic of normal oral mucosa.

State of the art of prostatic arterial embolization for benign prostatic hyperplasia.

PubMed

Petrillo, Mario; Pesapane, Filippo; Fumarola, Enrico Maria; Emili, Ilaria; Acquasanta, Marzia; Patella, Francesca; Angileri, Salvatore Alessio; Rossi, Umberto G; Piacentini, Igor; Granata, Antonio Maria; Ierardi, Anna Maria; Carrafiello, Gianpaolo

2018-04-01

Prostatectomy via open surgery or transurethral resection of the prostate (TURP) is the standard treatment for benign prostatic hyperplasia (BPH). Several patients present contraindication for standard approach, individuals older than 60 years with urinary tract infection, strictures, post-operative pain, incontinence or urinary retention, sexual dysfunction, and blood loss are not good candidates for surgery. Prostatic artery embolization (PAE) is emerging as a viable method for patients unsuitable for surgery. In this article, we report results about technical and clinical success and safety of the procedure to define the current status.

Interstitial laser coagulation of benign prostatic hyperplasia: a minimally invasive treatment alternative

NASA Astrophysics Data System (ADS)

Ordonez, Robert F.; Mittemeyer, Bernhard T.; Aronoff, David R.; de Riese, Werner T. W.

2003-06-01

The use of minimally invasive treatments for benign prostatic hyperplasia (BPH) have been introduced into the medical community. Over the last decade several minimally invasive treatment techniques have been approved for use. In particular, interstitial laser coagulation (ILC) has shown pomise as an alternative to the current gold standard, transurethral resection of prostate (TURP). Studies show ILC to have equal efficacy as TURP while causing less side effects. Future technical advances as well as increased physician experience with ILC could lead to the replacement of TURP as the gold standard in trestment of BPH.

Pharmacologic Therapy in Men's Health: Hypogonadism, Erectile Dysfunction, and Benign Prostatic Hyperplasia.

PubMed

Berkseth, Kathryn E; Thirumalai, Arthi; Amory, John K

2016-07-01

This article reviews current pharmacologic treatment options for 3 common men's health concerns: hypogonadism, erectile dysfunction (ED), and benign prostatic hyperplasia (BPH). Specific topics addressed include: management of male hypogonadism using testosterone replacement therapy, use of oral phosphodiesterase inhibitors as first-line therapy for men with ED and the utility of intraurethral and intrapenile alprostadil injections for patients who do not respond to oral medications, and the role of alpha1-adrenergic antagonists, 5-alpha-reductase inhibitors, anticholinergic agents, and herbal therapies in the management of BPH. Copyright © 2016 Elsevier Inc. All rights reserved.

Sampling in Atypical Endometrial Hyperplasia: Which Method Results in the Lowest Underestimation of Endometrial Cancer? A Systematic Review and Meta-analysis.

PubMed

Bourdel, Nicolas; Chauvet, Pauline; Tognazza, Enrica; Pereira, Bruno; Botchorishvili, Revaz; Canis, Michel

2016-01-01

Our objective was to identify the most accurate method of endometrial sampling for the diagnosis of complex atypical hyperplasia (CAH), and the related risk of underestimation of endometrial cancer. We conducted a systematic literature search in PubMed and EMBASE (January 1999-September 2013) to identify all registered articles on this subject. Studies were selected with a 2-step method. First, titles and abstracts were analyzed by 2 reviewers, and 69 relevant articles were selected for full reading. Then, the full articles were evaluated to determine whether full inclusion criteria were met. We selected 27 studies, taking into consideration the comparison between histology of endometrial hyperplasia obtained by diagnostic tests of interest (uterine curettage, hysteroscopically guided biopsy, or hysteroscopic endometrial resection) and subsequent results of hysterectomy. Analysis of the studies reviewed focused on 1106 patients with a preoperative diagnosis of atypical endometrial hyperplasia. The mean risk of finding endometrial cancer at hysterectomy after atypical endometrial hyperplasia diagnosed by uterine curettage was 32.7% (95% confidence interval [CI], 26.2-39.9), with a risk of 45.3% (95% CI, 32.8-58.5) after hysteroscopically guided biopsy and 5.8% (95% CI, 0.8-31.7) after hysteroscopic resection. In total, the risk of underestimation of endometrial cancer reaches a very high rate in patients with CAH using the classic method of evaluation (i.e., uterine curettage or hysteroscopically guided biopsy). This rate of underdiagnosed endometrial cancer leads to the risk of inappropriate surgical procedures (31.7% of tubal conservation in the data available and no abdominal exploration in 24.6% of the cases). Hysteroscopic resection seems to reduce the risk of underdiagnosed endometrial cancer. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

STAT6 deficiency ameliorates Graves' disease severity by suppressing thyroid epithelial cell hyperplasia.

PubMed

Jiang, Xuechao; Zha, Bingbing; Liu, Xiaoming; Liu, Ronghua; Liu, Jun; Huang, Enyu; Qian, Tingting; Liu, Jiajing; Wang, Zhiming; Zhang, Dan; Wang, Luman; Chu, Yiwei

2016-12-01

Signal transducer and activator of transcription 6 (STAT6) is involved in epithelial cell growth. However, little is known regarding the STAT6 phosphorylation status in Graves' disease (GD) and its role in thyroid epithelial cells (TECs). In this study, we found that STAT6 phosphorylation (p-STAT6) was significantly increased in TECs from both GD patients and experimental autoimmune Graves' disease mice and that STAT6 deficiency ameliorated GD symptoms. Autocrine IL-4 signalling in TECs activated the phosphorylation of STAT6 via IL-4 R engagement, and the downstream targets of STAT6 were Bcl-xL and cyclin D1. Thus, the IL-4-STAT6-Bcl-xL/cyclin D1 pathway is crucial for TEC hyperplasia, which aggravates GD. More importantly, in vitro and in vivo experiments demonstrated that STAT6 phosphorylation inhibited by AS1517499 decreased TEC hyperplasia, thereby reducing serum T3 and T4 and ameliorating GD. Thus, our study reveals that in addition to the traditional pathogenesis of GD, in which autoantibody TRAb stimulates thyroid-stimulating hormone receptors and consequently produces T3, T4, TRAb could also trigger TECs producing IL-4, and IL-4 then acts in an autocrine manner to activate p-STAT6 signalling and stimulate unrestricted cell growth, thus aggravating GD. These findings suggest that STAT6 inhibitors could be potent therapeutics for treating GD.

Osteopontin mediates Citrobacter rodentium-induced colonic epithelial cell hyperplasia and attaching-effacing lesions.

PubMed

Wine, Eytan; Shen-Tu, Grace; Gareau, Mélanie G; Goldberg, Harvey A; Licht, Christoph; Ngan, Bo-Yee; Sorensen, Esben S; Greenaway, James; Sodek, Jaro; Zohar, Ron; Sherman, Philip M

2010-09-01

Although osteopontin (OPN) is up-regulated in inflammatory bowel diseases, its role in disease pathogenesis remains controversial. The objective of this study was to determine the role of OPN in host responses to a non-invasive bacterial pathogen, Citrobacter rodentium, which serves as a murine infectious model of colitis. OPN gene knockout and wild-type mice were infected orogastrically with either C. rodentium or Luria-Bertani (LB) broth. Mouse-derived OPN(+/+) and OPN(-/-) fibroblasts were incubated with C. rodentium and attaching-effacing lesions were demonstrated using transmission electron microscopy and immunofluorescence. Colonic expression of OPN was increased by C. rodentium infection of wild-type mice. Furthermore, colonic epithelial cell hyperplasia, the hallmark of C. rodentium infection, was reduced in OPN(-/-) mice, and spleen enlargement by infection was absent in OPN(-/-) mice. Rectal administration of OPN to OPN(-/-) mice restored these effects. There was an 8- to 17-fold reduction in bacterial colonization in OPN(-/-) mice, compared with wild-type mice, which was accompanied by reduced attaching-effacing lesions, both in infected OPN(-/-) mice and OPN(-/-) mouse fibroblasts. Moreover, adhesion pedestals were restored in OPN(-/-) cells complemented with human OPN. Therefore, lack of OPN results in decreased pedestal formation, colonization, and colonic epithelial cell hyperplasia responses to C. rodentium infection, indicating that OPN impacts disease pathogenesis through bacterial attachment and altered host immune responses.

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

PubMed

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.

Vinpocetine Suppresses Pathological Vascular Remodeling by Inhibiting Vascular Smooth Muscle Cell Proliferation and Migration

PubMed Central

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

2012-01-01

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

Microsomal Prostaglandin E2 Synthase-1 Modulates the Response to Vascular Injury

PubMed Central

Wang, Miao; Ihida-Stansbury, Kaori; Kothapalli, Devashish; Tamby, Mathieu C.; Yu, Zhou; Chen, Lihong; Grant, Gregory; Cheng, Yan; Lawson, John A.; Assoian, Richard K.; Jones, Peter L.; FitzGerald, Garret A.

2013-01-01

Background Microsomal (m) prostaglandin (PG) E2 synthase (S)-1 catalyzes the formation of PGE2 from PGH2, a cyclooxygenase (COX) product that is derived from arachidonic acid. Previous studies in mice suggest that targeting mPGES-1 may be less likely to cause hypertension or thrombosis than COX-2 selective inhibition or deletion in vivo. Indeed, deletion of mPGES-1 retards atherogenesis and angiotensin II-induced aortic aneurysm formation. The role of mPGES-1 in the response to vascular injury is unknown. Methods and Results Mice were subjected to wire injury of the femoral artery. Both neointimal area and vascular stenosis were reduced significantly four weeks after injury in mPGES-1 knock out (KO) mice compared to wild type (WT) controls (65.6±5.7 vs 37.7±5.1×103 pixel area and 70.5±13.4% vs 47.7±17.4%, respectively; p < 0.01). Induction of tenascin C (TN-C) after injury, a pro-proliferative and promigratory extracellular matrix protein, was attenuated in the KOs. Consistent with in vivo rediversion of PG biosynthesis, mPGES-1 deleted vascular smooth muscle cells (VSMC) generated less PGE2, but more PGI2 and expressed reduced TN-C when compared with WT cells. Both suppression of PGE2 and augmentation of PGI2 attenuate TN-C expression, VSMC proliferation and migration in vitro. Conclusions Deletion of mPGES-1 in mice attenuates neointimal hyperplasia after vascular injury, in part by regulating TN-C expression. This raises for consideration the therapeutic potential of mPGES-1 inhibitors as adjuvant therapy for percutaneous coronary intervention. PMID:21282500

Experimental Percutaneous Extrahepatic Portacaval Shunt Creation by Transjugular Approach in Swine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seong, Chang Kyu; Pavcnik, Dusan, E-mail: pavcnikd@ohsu.edu; Uchida, Barry T.

2005-06-15

The purpose of the study was to evaluate the feasibility of the creation of a percutaneous extrahepatic portacaval shunt (PEPS) in swine by a transjugular approach and to find a suitable stent-graft to use in PEPS. In 12 swine, the extrahepatic portal vein (PV) was entered from the inferior vena cava (IVC) by a needle system introduced from the transjugular approach. A catheter introduced through the transhepatic approach served as a target. Five types of stent-graft consisting of homemade Z stents and a polytetrafluoethylene cover were explored for PEPS creation. Eight animals had follow-up venograms up to 6 weeks ormore » until the shunt became severely stenotic. Gross and histologic examinations were performed after the final follow-up venography. The PV punctures and stent-graft placement were difficult, but the PEPS was established in all animals. In four animals, the stent-graft failed to adequately cover the tract, causing severe hemorrhage. Only two shunts remained patent up to 6 weeks. The other shunts exhibited severe stenosis or occlusion. At gross examination, all shunts traversed the liver parenchyma of the caudate lobe surrounding the IVC. The extravascular PEPS portion was 4 mm to 2 cm long. All shunts entered the PV close to the splenomesenteric junction and exhibited neointimal formation. Shunt stenoses were caused by neointimal hyperplasia and occlusions by a superimposed thrombus. PEPS can be created by the transjugular approach in swine, but only the PV shunt entrance is extrahepatic. None of the tested rigid stent-grafts were suitable for PEPS creation. A short flexible stent-graft with flanged ends is suggested for further exploration.« less

Protective effect of dietary potassium against vascular injury in salt-sensitive hypertension.

PubMed

Kido, Makiko; Ando, Katsuyuki; Onozato, Maristela L; Tojo, Akihiro; Yoshikawa, Masahiro; Ogita, Teruhiko; Fujita, Toshiro

2008-02-01

Hypertensive cardiovascular damage is accelerated by salt loading but counteracted by dietary potassium supplementation. We suggested recently that antioxidant actions of potassium contribute to protection against salt-induced cardiac dysfunction. Therefore, we examined whether potassium supplementation ameliorated cuff-induced vascular injury in salt-sensitive hypertension via suppression of oxidative stress. Four-week-old Dahl salt-sensitive rats were fed a normal-salt (0.3% NaCl), high-salt (8% NaCl), or high-salt plus high-potassium (8% KCl) diet for 5 weeks, and some of the rats fed a high-salt diet were also given antioxidants. One week after the start of the treatments, a silicone cuff was implanted around the femoral artery. Examination revealed increased cuff-induced neointimal proliferation with adventitial macrophage infiltration in arteries from salt-loaded Dahl salt-sensitive rats compared with that in arteries from non-salt-loaded animals (intima/media ratio: 0.471+/-0.070 versus 0.302+/-0.037; P<0.05), associated with regional superoxide overproduction and reduced nicotinamide-adenine dinucleotide phosphate oxidase activation and mRNA overexpression. On the other hand, simultaneous potassium supplementation attenuated salt-induced neointimal hyperplasia (intima/media ratio: 0.205+/-0.012; P<0.001), adventitial macrophage infiltration, superoxide overproduction, and reduced nicotinamide-adenine dinucleotide phosphate oxidase activation and overexpression. Antioxidants, which decrease vascular oxidative stress, also reduced neointima formation induced by salt excess. In conclusion, high-potassium diets seems to have a protective effect against the development of vascular damage induced by salt loading mediated, at least in part, through suppression of the production of reactive oxygen species probably generated by reduced nicotinamide-adenine dinucleotide phosphate oxidase.

Bexarotene in Preventing Breast Cancer in Patients at High Risk for Breast Cancer

ClinicalTrials.gov

2018-05-16

Atypical Ductal Breast Hyperplasia; Atypical Lobular Breast Hyperplasia; BRCA1 Gene Mutation; BRCA2 Gene Mutation; Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Lobular Breast Carcinoma In Situ; No Evidence of Disease

Effects of different natural extracts in an experimental model of benign prostatic hyperplasia (BPH).

PubMed

Paterniti, Irene; Campolo, Michela; Cordaro, Marika; Siracusa, Rosalba; Filippone, Antonio; Esposito, Emanuela; Cuzzocrea, Salvatore

2018-04-20

To characterize the impact of inflammatory process and oxidative stress in the degree of benign prostatic hyperplasia (BPH), a common condition in which chronic inflammation plays a crucial role, we investigated the effect of different plant extract preparations in an in vivo model of BPH as new therapeutic target. BPH was made in rats with daily administration of testosterone propionate (3 mg/kg) for 14 days. Rats were randomized into different groups to receive oral administration of plant extract preparations: Serenoa repens with selenium (SeR 28.5 mg/kg associated with Se 0.005 mg/kg), Teoside (2 mg/kg), and Puryprost (14 mg/kg containing Teoside 50% 2 mg/kg and Epilobium 12 mg/kg). After 14 days, rats were killed and histological changes, prostate weight and apoptotic pathways were assayed. The results obtained demonstrated that the association of treatments reduced prostate weight and hyperplasia, while treatment with Puryprost demonstrated a greater trend of protection compared to the other treatments. Thus, our results indicate that plant extract could be considered as new useful therapy in the treatment of BPH with particular attention on Puryprost that represents a rational approach to reduce BPH through modulation of inflammatory process and anti-oxidant process.

Mechanisms and Patterns of Intravascular Ultrasound In-Stent Restenosis Among Bare Metal Stents and First- and Second-Generation Drug-Eluting Stents.

PubMed

Goto, Kosaku; Zhao, Zhijing; Matsumura, Mitsuaki; Dohi, Tomotaka; Kobayashi, Nobuaki; Kirtane, Ajay J; Rabbani, LeRoy E; Collins, Michael B; Parikh, Manish A; Kodali, Susheel K; Leon, Martin B; Moses, Jeffrey W; Mintz, Gary S; Maehara, Akiko

2015-11-01

The most common causes of in-stent restenosis (ISR) are intimal hyperplasia and stent under expansion. The purpose of this study was to use intravascular ultrasound (IVUS) to compare the ISR mechanisms of bare metal stents (BMS), first-generation drug-eluting stents (DES), and second-generation DES. There were 298 ISR lesions including 52 BMS, 73 sirolimus-eluting stents, 52 paclitaxel-eluting stents, 16 zotarolimus-eluting stents, and 105 everolimus-eluting stent. Mean patient age was 66.6 ± 1.1 years, 74.2% were men, and 48.3% had diabetes mellitus. BMS restenosis presented later (70.0 ± 66.7 months) with more intimal hyperplasia compared with DES (BMS 58.6 ± 15.5%, first-generation DES 52.6 ± 20.9%, second-generation DES 48.2 ± 22.2%, p = 0.02). Although reference lumen areas were similar in BMS and first- and second-generation DES, restenotic DES were longer (BMS 21.8 ± 13.5 mm, first-generation DES 29.4 ± 16.1 mm, second-generation DES 32.1 ± 18.7 mm, p = 0.003), and stent areas were smaller (BMS 7.2 ± 2.4 mm(2), first-generation DES 6.1 ± 2.1 mm(2), second-generation DES 5.7 ± 2.0 mm(2), p <0.001). Stent fracture was seen only in DES (first-generation DES 7 [5.0%], second-generation DES 8 [7.4%], p = 0.13). In conclusion, restenotic first- and second-generation DES were characterized by less neointimal hyperplasia, smaller stent areas, longer stent lengths, and more stent fractures than restenotic BMS. Copyright © 2015 Elsevier Inc. All rights reserved.

Graft protective effect and induction of CD4+Foxp3+ cell by Thrombomodulin on allograft arteriosclerosis in mice.

PubMed

Yin, Enzhi; Matsuyama, Shigefumi; Uchiyama, Masateru; Kawai, Kento; Niimi, Masanori

2018-05-21

Thrombomodulin (TM) is a promising therapeutic natural anti-coagulant, which exerts the effects to control disseminated intravascular coagulation. However, little is known whether TM on micro-vessels could play an important role in the regulation of intimal hyperplasia. We investigated the vessel-protective effect of TM in the survival of fully major histocompatibility complex (MHC)-mismatched murine cardiac allograft transplantation. CBA recipients transplanted with a C57BL/6 heart received intraperitoneal administration of normal saline or 0.2, 2.0, and 20.0 μg/day of TM for 7 days (n = 5, 7, 11, and 11, respectively). Immunohistochemical and fluorescent staining studies were performed to determine whether CD4 + Foxp3 + regulatory T cell were generated at 2 and 4 weeks after grafting. Morphometric analysis for neointimal formation in the coronary arteries of the transplanted allograft was conducted at 2 and 4 weeks after grafting. Untreated CBA recipients rejected C57BL/6 cardiac grafts acutely (median survival time [MST], 7 days). CBA recipients exposed with the above doses had significantly prolonged allograft survival (MSTs, 17, 24 and 50 days, respectively). Morphometric assessment showed that intimal hyperplasia was clearly suppressed in the left and right coronary arteries or allografts from TM-exposed recipients 2 and 4 weeks. Immunohistochemical studies at 2 weeks showed more CD4 + Foxp3 + cells and lower myocardial damage in the allografts from TM-exposed recipients. Notably, fluorescent staining studies demonstrated that TM-exposed recipients 4 weeks post-engraftment had strong aggregation of CD4 + Foxp3 + cells in the intima of the coronary arteries of the cardiac allografts. TM may prolong the survival of fully MHC-mismatched cardiac allografts through suppressing intimal hyperplasia and inducing the accumulation of regulatory CD4 + Foxp3 + cells within coronary arteries.

Tubercular thyroiditis with multinodular goitre with adenomatous hyperplasia: a rare coexistence.

PubMed

Chaurasia, Jai Kumar; Garg, Cheena; Agarwal, Arjun; Naim, Mohammed

2013-09-25

A 32-year-old Indian woman presented with swelling in the anterior part of the neck for the last 3 years. Clinical and radiological examination and fine needle aspiration cytology suggested the diagnosis of multinodular goitre. A subtotal thyroidectomy was performed by the surgeon and the specimen was submitted for the final diagnosis. Histological examination of the specimen revealed multiple caseating tubercular granulomas coexistent with multinodular goitre and adenomatous hyperplasia. The sections demonstrated acid-fast tubercle bacteria, confirming the diagnosis of tubercular thyroiditis. This case emphasises that tubercular thyroiditis should always be considered in patients with thyroid swelling or nodule, in countries where the prevalence of tuberculosis is high.

68Ga-PSMA Expression in Pseudoangiomatous Stromal Hyperplasia of the Breast.

PubMed

Malik, Dharmender; Basher, Rajender K; Mittal, Bhagwant Rai; Jain, Tarun Kumar; Bal, Amanjit; Singh, Shrawan Kumar

2017-01-01

Ga-labeled prostate-specific membrane antigen ligand PET-CT has emerged as a promising technique to evaluate the extent of disease in patients with prostate carcinoma. We are reporting a 63-year-old man with prostatic carcinoma subjected to Ga-prostate-specific membrane antigen ligand PET-CT for initial staging. In addition to the radiotracer uptake in known primary site (prostate), focal increased radiotracer uptake was also noticed in the left breast. Subsequent biopsy of the breast lesion revealed PASH (pseudoangiomatous stromal hyperplasia), which is a benign mesenchymal proliferative lesion that may present clinically as palpable mass requiring further evaluation to rule out malignancy.

Unexpected Role of the Copper Transporter ATP7A in PDGF-Induced Vascular Smooth Muscle Cell Migration

PubMed Central

Ashino, Takashi; Sudhahar, Varadarajan; Urao, Norifumi; Oshikawa, Jin; Chen, Gin-Fu; Wang, Huan; Huo, Yuqing; Finney, Lydia; Vogt, Stefan; McKinney, Ronald D.; Maryon, Edward B.; Kaplan, Jack H.; Ushio-Fukai, Masuko; Fukai, Tohru

2010-01-01

Rationale Copper, an essential nutrient, has been implicated in vascular remodeling and atherosclerosis with unknown mechanism. Bioavailability of intracellular copper is regulated not only by the copper importer CTR1, but also by the copper exporter ATP7A (Menke ATPase) whose function is achieved through copper-dependent translocation from trans-Golgi network (TGN). Platelet-derived growth factor (PDGF) promotes vascular smooth muscle cell (VSMC) migration, a key component of neointimal formation. Objective To determine the role of copper transporter ATP7A in PDGF-induced VSMC migration. Methods and Results Depletion of ATP7A inhibited VSMC migration in response to PDGF or wound scratch in a CTR1/copper-dependent manner. PDGF stimulation promoted ATP7A translocation from the TGN to lipid rafts which localized at the leading edge, where it colocalized with PDGF receptor and Rac1, in migrating VSMCs. Mechanistically, ATP7A siRNA or CTR siRNA prevented PDGF-induced Rac1 translocation to the leading edge, thereby inhibiting lamellipodia formation. In addition, ATP7A depletion prevented a PDGF-induced decrease in copper level and secretory copper enzyme precursor pro-lysyl oxidase (Pro-LOX) in lipid raft fraction as well as PDGF-induced increase in LOX activity. In vivo, ATP7A expression was markedly increased and copper accumulation was observed by synchrotron-based X-ray fluorescence microscopy at neointimal VSMCs in wire injury model. Conclusions These findings suggest that ATP7A plays an important role in copper-dependent PDGF-stimulated VSMC migration via recruiting Rac1 to lipid rafts at the leading edge as well as regulating LOX activity. This may contribute to neointimal formation after vascular injury. Our findings provide insight into ATP7A as a novel therapeutic target for vascular remodeling and atherosclerosis. PMID:20671235

Unexpected role of the copper transporter ATP7A in PDGF-induced vascular smooth muscle cell migration.

PubMed

Ashino, Takashi; Sudhahar, Varadarajan; Urao, Norifumi; Oshikawa, Jin; Chen, Gin-Fu; Wang, Huan; Huo, Yuqing; Finney, Lydia; Vogt, Stefan; McKinney, Ronald D; Maryon, Edward B; Kaplan, Jack H; Ushio-Fukai, Masuko; Fukai, Tohru

2010-09-17

Copper, an essential nutrient, has been implicated in vascular remodeling and atherosclerosis with unknown mechanism. Bioavailability of intracellular copper is regulated not only by the copper importer CTR1 (copper transporter 1) but also by the copper exporter ATP7A (Menkes ATPase), whose function is achieved through copper-dependent translocation from trans-Golgi network (TGN). Platelet-derived growth factor (PDGF) promotes vascular smooth muscle cell (VSMC) migration, a key component of neointimal formation. To determine the role of copper transporter ATP7A in PDGF-induced VSMC migration. Depletion of ATP7A inhibited VSMC migration in response to PDGF or wound scratch in a CTR1/copper-dependent manner. PDGF stimulation promoted ATP7A translocation from the TGN to lipid rafts, which localized at the leading edge, where it colocalized with PDGF receptor and Rac1, in migrating VSMCs. Mechanistically, ATP7A small interfering RNA or CTR small interfering RNA prevented PDGF-induced Rac1 translocation to the leading edge, thereby inhibiting lamellipodia formation. In addition, ATP7A depletion prevented a PDGF-induced decrease in copper level and secretory copper enzyme precursor prolysyl oxidase (Pro-LOX) in lipid raft fraction, as well as PDGF-induced increase in LOX activity. In vivo, ATP7A expression was markedly increased and copper accumulation was observed by synchrotron-based x-ray fluorescence microscopy at neointimal VSMCs in wire injury model. These findings suggest that ATP7A plays an important role in copper-dependent PDGF-stimulated VSMC migration via recruiting Rac1 to lipid rafts at the leading edge, as well as regulating LOX activity. This may contribute to neointimal formation after vascular injury. Our findings provide insight into ATP7A as a novel therapeutic target for vascular remodeling and atherosclerosis.

Hepatic focal nodular hyperplasia with congenital portosystemic shunt.

PubMed

Cho, Yuki; Shimono, Taro; Morikawa, Hiroyasu; Shintaku, Haruo; Tokuhara, Daisuke

2014-12-01

Hepatic focal nodular hyperplasia (FNH) is a rare benign tumor in children. Vascular anomalies have been identified as pathological features of FNH, but the etiology remains unclear. We describe a rare case including the time course of formation of hepatic FNH in response to congenital portosystemic shunt (PSS). A 4-month-old girl was identified on newborn mass screening to have hypergalactosemia, but no inherited deficiencies in galactose-metabolizing enzymes were found. Ultrasonography and per-rectal portal scintigraphy showed intrahepatic PSS of the right lobe as a cause of the hypergalactosemia. At age 12 months, the patient had elevated hepatic enzymes and small hypoechoic hepatic lesions around the shunt. On abdominal contrast-enhanced ultrasonography spoke-wheel sign and central stellate scar were seen, which are typical features of hepatic FNH without biopsy. Congenital intrahepatic PSS should be evaluated on abdominal contrast-enhanced ultrasonography and observed over time because of its potential to develop into hepatic FNH. © 2014 Japan Pediatric Society.

A pro-inflammatory role of deubiquitinating enzyme cylindromatosis (CYLD) in vascular smooth muscle cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Shuai; Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208; Lv, Jiaju

2012-03-30

Highlights: Black-Right-Pointing-Pointer Cyld deficiency suppresses pro-inflammatory phenotypic switch of VSMCs. Black-Right-Pointing-Pointer Cyld deficiency inhibits MAPK rather than NF-kB activity in inflamed VSMCs. Black-Right-Pointing-Pointer CYLD is up-regulated in the coronary artery with neointimal hyperplasia. -- Abstract: CYLD, a deubiquitinating enzyme (DUB), is a critical regulator of diverse cellular processes, ranging from proliferation and differentiation to inflammatory responses, via regulating multiple key signaling cascades such as nuclear factor kappa B (NF-{kappa}B) pathway. CYLD has been shown to inhibit vascular lesion formation presumably through suppressing NF-{kappa}B activity in vascular cells. However, herein we report a novel role of CYLD in mediating pro-inflammatory responsesmore » in vascular smooth muscle cells (VSMCs) via a mechanism independent of NF-{kappa}B activity. Adenoviral knockdown of Cyld inhibited basal and the tumor necrosis factor alpha (TNF{alpha})-induced mRNA expression of pro-inflammatory cytokines including monocyte chemotactic protein-1 (Mcp-1), intercellular adhesion molecule (Icam-1) and interleukin-6 (Il-6) in rat adult aortic SMCs (RASMCs). The CYLD deficiency led to increases in the basal NF-{kappa}B transcriptional activity in RASMCs; however, did not affect the TNF{alpha}-induced NF-{kappa}B activity. Intriguingly, the TNF{alpha}-induced I{kappa}B phosphorylation was enhanced in the CYLD deficient RASMCs. While knocking down of Cyld decreased slightly the basal expression levels of I{kappa}B{alpha} and I{kappa}B{beta} proteins, it did not alter the kinetics of TNF{alpha}-induced I{kappa}B protein degradation in RASMCs. These results indicate that CYLD suppresses the basal NF-{kappa}B activity and TNF{alpha}-induced I{kappa}B kinase activation without affecting TNF{alpha}-induced NF-{kappa}B activity in VSMCs. In addition, knocking down of Cyld suppressed TNF{alpha}-induced activation of mitogen activated

Alterations in regional vascular geometry produced by theoretical stent implantation influence distributions of wall shear stress: analysis of a curved coronary artery using 3D computational fluid dynamics modeling.

PubMed

LaDisa, John F; Olson, Lars E; Douglas, Hettrick A; Warltier, David C; Kersten, Judy R; Pagel, Paul S

2006-06-16

The success of stent implantation in the restoration of blood flow through areas of vascular narrowing is limited by restenosis. Several recent studies have suggested that the local geometric environment created by a deployed stent may influence regional blood flow characteristics and alter distributions of wall shear stress (WSS) after implantation, thereby rendering specific areas of the vessel wall more susceptible to neointimal hyperplasia and restenosis. Stents are most frequently implanted in curved vessels such as the coronary arteries, but most computational studies examining blood flow patterns through stented vessels conducted to date use linear, cylindrical geometric models. It appears highly probable that restenosis occurring after stent implantation in curved arteries also occurs as a consequence of changes in fluid dynamics that are established immediately after stent implantation. In the current investigation, we tested the hypothesis that acute changes in stent-induced regional geometry influence distributions of WSS using 3D coronary artery CFD models implanted with stents that either conformed to or caused straightening of the primary curvature of the left anterior descending coronary artery. WSS obtained at several intervals during the cardiac cycle, time averaged WSS, and WSS gradients were calculated using conventional techniques. Implantation of a stent that causes straightening, rather than conforms to the natural curvature of the artery causes a reduction in the radius of curvature and subsequent increase in the Dean number within the stented region. This straightening leads to modest skewing of the velocity profile at the inlet and outlet of the stented region where alterations in indices of WSS are most pronounced. For example, time-averaged WSS in the proximal portion of the stent ranged from 8.91 to 11.7 dynes/cm2 along the pericardial luminal surface and 4.26 to 4.88 dynes/cm2 along the myocardial luminal surface of curved coronary

Significant role of Fas ligand-binding but defective Fas receptor (CD95) in lymph node hyperplasia composed of abnormal double-negative T cells

PubMed Central

Matsuzawa, Akio; Shimizu, Motomu; Takeda, Yasutaka; Nagase, Hisashi; Sayama, Kazutoshi; Kimura, Mikio

2002-01-01

The functional differences between two mutations of the Fas (CD95) locus, Faslpr (lpr) and Faslprcg (lprcg), were investigated using bone marrow (BM) transplantation on the C3H mouse background. Both lpr/lpr and lprcg/lprcg BM transferred caused lymph node (LN) hyperplasia in lpr/+ and lprcg/+ recipients, although it was clearly smaller than that in lpr/lpr and lprcg/lprcg recipients of lpr/lpr and lprcg/lprcg BM. In addition, both BM induced significantly larger LN hyperplasia in lprcg/+ than lpr/+ recipients. Appearance of CD4− CD8−[double negative (DN)] T cells in the periphery is the most consistent phenotype of Fas mutations. Importantly, the proportion of DN T cells was higher in larger LN hyperplasia in the order of lpr/+, lprcg/+ and lpr/lpr or lprcg/lprcg recipients. On the other hand, both lpr/lpr and lprcg/lprcg BM transferred into wild-type (+/+) mice caused marked LN atrophy. The former, but not the latter, induced wasting syndrome. Faslg1d (gld)-homozygous lpr/lpr BM transferred into +/+ mice elicited LN hyperplasia of the same extent as that in lpr/lpr mice transferred with lpr/lpr BM, but not wasting syndrome. Taken together with the fact that DN T cells massively express Fas ligand (FasL), this study implied that FasL overexpressed on DN cells may be involved in the accumulation of DN T cells in LN, LN atrophy and wasting syndrome, and that lprcg Fas, which can bind to Fas ligand but not transduce apoptosis signal into cells, may modulate these pathological conditions by interfering with the binding of FasL to Fas. PMID:12153509

Cell Selective Cardiovascular Biology of Microsomal Prostaglandin E Synthase-1

PubMed Central

Chen, Lihong; Yang, Guangrui; Xu, Xiufeng; Grant, Gregory; Lawson, John A.; Bohlooly-Y, Mohammad; FitzGerald, Garret A.

2013-01-01

Background Global deletion of microsomal prostaglandin E synthase (mPGES) -1 in mice attenuates the response to vascular injury without a predisposition to thrombogenesis or hypertension. However, enzyme deletion results in cell specific differential utilization by prostaglandin (PG) synthases of the accumulated PGH2 substrate. Here, we generated mice deficient in mPGES-1 in vascular smooth muscle cells (VSMCs), endothelial cells (ECs) and myeloid cells further to elucidate the cardiovascular function of this enzyme. Methods and Results VSMC and EC mPGES-1 deletion did not alter blood pressure at baseline or in response to a high salt diet. The propensity to evoked macrovascular and microvascular thrombogenesis was also unaltered. However, both VSMC and EC mPGES-1 deficient mice exhibited a markedly exaggerated neointimal hyperplastic response to wire injury of the femoral artery compared to their littermate controls. The hyperplasia was associated with increased proliferating cell nuclear antigen (PCNA) and tenascin-C (TN-C) expression. In contrast, the response to injury was markedly suppressed by myeloid cell depletion of mPGES-1 with decreased hyperplasia, leukocyte infiltration and expression of PCNA and TN-C. Conditioned medium derived from mPGES-1 deficient macrophages less potently induced VSMC proliferation and migration than that from wild type macrophages. Conclusion Deletion of mPGES-1 in the vasculature and myeloid cells differentially modulates the response to vascular injury, implicating macrophage mPGES-1 as a cardiovascular drug target. PMID:23204105

Transient up- and down-regulation of expression of myosin light chain 2 and myostatin mRNA mark the changes from stratified hyperplasia to muscle fiber hypertrophy in larvae of gilthead sea bream (Sparus aurata L.).

PubMed

Georgiou, Stella; Alami-Durante, Hélène; Power, Deborah M; Sarropoulou, Elena; Mamuris, Zissis; Moutou, Katerina A

2016-02-01

Hyperplasia and hypertrophy are the two mechanisms by which muscle develops and grows. We study these two mechanisms, during the early development of white muscle in Sparus aurata, by means of histology and the expression of structural and regulatory genes. A clear stage of stratified hyperplasia was identified early in the development of gilthead sea bream but ceased by 35 dph when hypertrophy took over. Mosaic recruitment of new white fibers began as soon as 60 dph. The genes mlc2a and mlc2b were expressed at various levels during the main phases of hyperplasia and hypertrophy. The genes myog and mlc2a were significantly up-regulated during the intensive stratified formation of new fibers and their expression was significantly correlated. Expression of mstn1 and igf1 increased at 35 dph, appeared to regulate the hyperplasia-to-hypertrophy transition, and may have stimulated the expression of mlc2a, mlc2b and col1a1 at the onset of mosaic hyperplasia. The up-regulation of mstn1 at transitional phases in muscle development indicates a dual regulatory role of myostatin in fish larval muscle growth.

Telangiectatic focal nodular hyperplasia of the liver in an infant with spontaneous regression: a case report.

PubMed

Hirakawa, Hitoshi; Ueno, Shigeru; Matuda, Hiromitu; Hinoki, Tomoya; Kato, Yuko

2009-04-20

A distinctive mass in the liver in a two-month-old girl with elevated serum alpha-fetoprotein (AFP) level was diagnosed as telangiectatic focal nodular hyperplasia (FNH) after biopsy. The tumor spontaneously regressed and finally became no longer detectable by any imaging study within normal range of AFP. The nature of this novel entity and its management are discussed based on literature review.

STAT6 deficiency ameliorates Graves' disease severity by suppressing thyroid epithelial cell hyperplasia

PubMed Central

Jiang, Xuechao; Zha, Bingbing; Liu, Xiaoming; Liu, Ronghua; Liu, Jun; Huang, Enyu; Qian, Tingting; Liu, Jiajing; Wang, Zhiming; Zhang, Dan; Wang, Luman; Chu, Yiwei

2016-01-01

Signal transducer and activator of transcription 6 (STAT6) is involved in epithelial cell growth. However, little is known regarding the STAT6 phosphorylation status in Graves' disease (GD) and its role in thyroid epithelial cells (TECs). In this study, we found that STAT6 phosphorylation (p-STAT6) was significantly increased in TECs from both GD patients and experimental autoimmune Graves' disease mice and that STAT6 deficiency ameliorated GD symptoms. Autocrine IL-4 signalling in TECs activated the phosphorylation of STAT6 via IL-4 R engagement, and the downstream targets of STAT6 were Bcl-xL and cyclin D1. Thus, the IL-4-STAT6-Bcl-xL/cyclin D1 pathway is crucial for TEC hyperplasia, which aggravates GD. More importantly, in vitro and in vivo experiments demonstrated that STAT6 phosphorylation inhibited by AS1517499 decreased TEC hyperplasia, thereby reducing serum T3 and T4 and ameliorating GD. Thus, our study reveals that in addition to the traditional pathogenesis of GD, in which autoantibody TRAb stimulates thyroid-stimulating hormone receptors and consequently produces T3, T4, TRAb could also trigger TECs producing IL-4, and IL-4 then acts in an autocrine manner to activate p-STAT6 signalling and stimulate unrestricted cell growth, thus aggravating GD. These findings suggest that STAT6 inhibitors could be potent therapeutics for treating GD. PMID:27906181

Osteopontin Mediates Citrobacter rodentium-Induced Colonic Epithelial Cell Hyperplasia and Attaching-Effacing Lesions

PubMed Central

Wine, Eytan; Shen-Tu, Grace; Gareau, Mélanie G.; Goldberg, Harvey A.; Licht, Christoph; Ngan, Bo-Yee; Sorensen, Esben S.; Greenaway, James; Sodek, Jaro; Zohar, Ron; Sherman, Philip M.

2010-01-01

Although osteopontin (OPN) is up-regulated in inflammatory bowel diseases, its role in disease pathogenesis remains controversial. The objective of this study was to determine the role of OPN in host responses to a non-invasive bacterial pathogen, Citrobacter rodentium, which serves as a murine infectious model of colitis. OPN gene knockout and wild-type mice were infected orogastrically with either C. rodentium or Luria-Bertani (LB) broth. Mouse-derived OPN+/+ and OPN−/− fibroblasts were incubated with C. rodentium and attaching-effacing lesions were demonstrated using transmission electron microscopy and immunofluorescence. Colonic expression of OPN was increased by C. rodentium infection of wild-type mice. Furthermore, colonic epithelial cell hyperplasia, the hallmark of C. rodentium infection, was reduced in OPN−/− mice, and spleen enlargement by infection was absent in OPN−/− mice. Rectal administration of OPN to OPN−/− mice restored these effects. There was an 8- to 17-fold reduction in bacterial colonization in OPN−/− mice, compared with wild-type mice, which was accompanied by reduced attaching–effacing lesions, both in infected OPN−/− mice and OPN−/− mouse fibroblasts. Moreover, adhesion pedestals were restored in OPN−/− cells complemented with human OPN. Therefore, lack of OPN results in decreased pedestal formation, colonization, and colonic epithelial cell hyperplasia responses to C. rodentium infection, indicating that OPN impacts disease pathogenesis through bacterial attachment and altered host immune responses. PMID:20651246

p.R182C mutation in Korean twin with congenital lipoid adrenal hyperplasia

PubMed Central

Park, Hye Won; Kwak, Byung Ok; Kim, Gu-Hwan; Yoo, Han-Wook

2013-01-01

Congenital lipoid adrenal hyperplasia (CLAH) is the most severe form of congenital adrenal hyperplasia which is caused by mutations in the steroidogenic acute regulatory protein (StAR). The mutations in StAR gene resulted in failure of the transport cholesterol into mitochondria for steroidogenesis in the adrenal gland. Twin sisters (A, B) with normal 46, XX were born at 36+2 gestational week, premature to nonrelated parents. They had symptoms as hyperpigmentation, slightly elevated potassium level and low level of sodium. Laboratory finding revealed normal 17-hydroxyprogesterone level, elevated adrenocorticotropin hormone (A, 4,379.2 pg/mL; B, 11,616.1 pg/mL), and high plasma renin activity (A, 49.02 ng/mL/hr; B, 52.7 ng mL/hr). However, the level of plasma cortisol before treatment was low (1.5 µg/dL) in patient B but normal (8.71 µg/dL) in patient A. Among them, only patient A was presented with adrenal insufficiency symptoms which was suggestive of CLAH and prompted us to order a gene analysis in both twin. The results of gene analysis of StAR in twin revealed same heterozygous conditions for c.544C>T (Arg182Cys) in exon 5 and c.722C>T (Gln258*) in exon 7. We report the first case on the mutation of p.R182C in exon 5 of the StAR gene in Korea. PMID:24904850

Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children.

PubMed

Wakefield, A J; Murch, S H; Anthony, A; Linnell, J; Casson, D M; Malik, M; Berelowitz, M; Dhillon, A P; Thomson, M A; Harvey, P; Valentine, A; Davies, S E; Walker-Smith, J A

1998-02-28

We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder. 12 children (mean age 6 years [range 3-10], 11 boys) were referred to a paediatric gastroenterology unit with a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain. Children underwent gastroenterological, neurological, and developmental assessment and review of developmental records. Ileocolonoscopy and biopsy sampling, magnetic-resonance imaging (MRI), electroencephalography (EEG), and lumbar puncture were done under sedation. Barium follow-through radiography was done where possible. Biochemical, haematological, and immunological profiles were examined. Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with age-matched controls (p=0.003), low haemoglobin in four children, and a low serum IgA in four children. We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.

Breast cancer risk by extent and type of atypical hyperplasia: An update from the Nurses' Health Studies.

PubMed

Collins, Laura C; Aroner, Sarah A; Connolly, James L; Colditz, Graham A; Schnitt, Stuart J; Tamimi, Rulla M

2016-02-15

Women with atypical hyperplasia (AH) on a benign breast biopsy specimen are at increased risk for the development of breast cancer. However, the relation between the type and extent of AH (atypical ductal hyperplasia [ADH] vs atypical lobular hyperplasia [ALH]) and the magnitude of the breast cancer risk is not well defined. A nested case-control study of benign breast disease and breast cancer risk was conducted. Women with breast cancer and prior benign breast biopsy findings (488 cases) were matched to women with prior benign breast biopsy findings who were free from breast cancer (1907 controls). Benign breast biopsy slides were reviewed and categorized as nonproliferative, proliferative without atypia, or AH (ADH or ALH). The number of foci of AH was also recorded. Among women with ADH, the interrelation between the extent of atypia and breast cancer risk was not significant (odds ratio [OR] for 1 or 2 foci, 3.5; 95% confidence interval [CI], 2.2-5.6; OR for ≥3 foci, 2.7; 95% CI, 1.4-5.1; P = .41). Similarly, although the risk with ALH was higher for those with ≥3 foci than for those with <3 foci, the difference was not statistically significant (OR for 1 or 2 foci, 5.2; 95% CI, 2.7-10.0; OR for ≥3 foci, 8.0; 95% CI, 4.5-14.2; P = .19). This analysis demonstrates that the extent of ADH or ALH does not significantly contribute to breast cancer risk. The lack of a significant dose-response relation between the extent and type of atypia and breast cancer risk suggests that it would be premature to use the extent of atypia to influence management decisions for women with ADH or ALH. © 2015 American Cancer Society.

Breast Cancer Risk by Extent and Type of Atypical Hyperplasia: An Update from the Nurses’ Health Studies

PubMed Central

Collins, Laura C.; Aroner, Sarah; Connolly, James L.; Colditz, Graham A.; Schnitt, Stuart J.; Tamimi, Rulla M.

2015-01-01

Background Women with atypical hyperplasia (AH) on a benign breast biopsy (BBB) are at increased risk for the development of breast cancer. However, the relationship between type and extent of AH (atypical ductal hyperplasia (ADH) vs. atypical lobular hyperplasia (ALH)) and magnitude of breast cancer risk is not well-defined. Methods We conducted a nested case-control study of benign breast disease and breast cancer risk. Women with breast cancer and a prior BBB (cases=488) were matched to women with a prior BBB but free from breast cancer (controls=1907). BBB slides were reviewed and categorized as either non-proliferative, proliferative without atypia, or AH (ADH or ALH). The number of foci of AH was also recorded. Results Among women with ADH, the inter-relationship between extent of atypia and breast cancer risk was not significant (OR=3.5; 95%CI 2.2-5.6 for 1-2 foci, OR= 2.7; 95%CI 1.4-5.1 for ≥3 foci; p=0.58). Similarly, while the risk with ALH was higher for those with ≥3 foci than for those with <3 foci, the difference was not statistically significant (OR=5.2; 95%CI 2.7-10.0 for 1-2 foci; OR=8.0; 95%CI 4.5-14.2 for ≥3 foci; p=0.66). Conclusion This analysis demonstrates that the extent of ADH or ALH did not significantly contribute to breast cancer risk. The lack of a significant dose-response relationship between extent and type of atypia and breast cancer risk suggests that it would be premature to use extent of atypia to influence management decisions in women with ADH or ALH. PMID:26565738

Benign Prostatic Hyperplasia: A New Metabolic Disease of the Aging Male and Its Correlation with Sexual Dysfunctions

PubMed Central

Corona, Giovanni; Vignozzi, Linda; Lotti, Francesco; Cipriani, Sarah

2014-01-01

Metabolic syndrome (MetS) is a well-recognized cluster of cardiovascular (CV) risk factors including obesity, hypertension, dyslipidemia, and hyperglycaemia, closely associated with an increased risk of forthcoming cardiovascular disease and type 2 diabetes mellitus. Emerging evidence indicates that benign prostate hyperplasia (BPH) and its related lower urinary tract symptoms (LUTS) represent other clinical conditions frequently observed in subjects with MetS. Several modifiable factors involved in MetS determinism, such as inadequate diet, lack of physical exercise, and smoking and drinking behaviours are emerging as main contributors to the development of BPH. The pathogenetic mechanisms underlying the connection between MetS and BPH have not been completely clarified. MetS and its components, hypogonadism, and prostate inflammation probably play an important role in inducing BPH/LUTS. Although historically considered as a “normal” consequence of the aging process, BPH/LUTS should now be faced proactively, as a preventable disorder of the elderly. Type of diet and level of physical activity are now considered important factors affecting prostate health in the aging male. However, whether physical exercise, weight loss, and modifications of dietary habit can really alter the natural history of BPH/LUTS remains to be determined. Further research is advisable to better clarify these points. PMID:24688539

Human papillomavirus-32-associated focal epithelial hyperplasia accompanying HPV-16-positive papilloma-like lesions in oral mucosa.

PubMed

Liu, Na; Wang, Jiayi; Lei, Lei; Li, Yanzhong; Zhou, Min; Dan, Hongxia; Zeng, Xin; Chen, Qianming

2013-05-01

Human papillomavirus infection can cause a variety of benign or malignant oral lesions, and the various genotypes can cause distinct types of lesions. To our best knowledge, there has been no report of 2 different human papillomavirus-related oral lesions in different oral sites in the same patient before. This paper reported a patient with 2 different oral lesions which were clinically and histologically in accord with focal epithelial hyperplasia and oral papilloma, respectively. Using DNA extracted from these 2 different lesions, tissue blocks were tested for presence of human papillomavirus followed by specific polymerase chain reaction testing for 6, 11, 13, 16, 18, and 32 subtypes in order to confirm the clinical diagnosis. Finally, human papillomavirus-32-positive focal epithelial hyperplasia accompanying human papillomavirus-16-positive oral papilloma-like lesions were detected in different sites of the oral mucosa. Nucleotide sequence sequencing further confirmed the results. So in our clinical work, if the simultaneous occurrences of different human papillomavirus associated lesions are suspected, the multiple biopsies from different lesions and detection of human papillomavirus genotype are needed to confirm the diagnosis.

A comparison of microRNA expression profiles from splenic hemangiosarcoma, splenic nodular hyperplasia, and normal spleens of dogs.

PubMed

Grimes, Janet A; Prasad, Nripesh; Levy, Shawn; Cattley, Russell; Lindley, Stephanie; Boothe, Harry W; Henderson, Ralph A; Smith, Bruce F

2016-12-03

Splenic masses are common in older dogs; yet diagnosis preceding splenectomy and histopathology remains elusive. MicroRNAs (miRNAs) are short, non-coding RNAs that play a role in post-transcriptional regulation, and differential expression of miRNAs between normal and tumor tissue has been used to diagnose neoplastic diseases. The objective of this study was to determine differential expression of miRNAs by use of RNA-sequencing in canine spleens that were histologically confirmed as hemangiosarcoma, nodular hyperplasia, or normal. Twenty-two miRNAs were found to be differentially expressed in hemangiosarcoma samples (4 between hemangiosarcoma and both nodular hyperplasia and normal spleen and 18 between hemangiosarcoma and normal spleen only). In particular, mir-26a, mir-126, mir-139, mir-140, mir-150, mir-203, mir-424, mir-503, mir-505, mir-542, mir-30e, mir-33b, mir-365, mir-758, mir-22, and mir-452 are of interest in the pathogenesis of hemangiosarcoma. Findings of this study confirm the hypothesis that miRNA expression profiles are different between canine splenic hemangiosarcoma, nodular hyperplasia, and normal spleens. A large portion of the differentially expressed miRNAs have roles in angiogenesis, with an additional group of miRNAs being dysregulated in vascular disease processes. Two other miRNAs have been implicated in cancer pathways such as PTEN and cell cycle checkpoints. The finding of multiple miRNAs with roles in angiogenesis and vascular disease is important, as hemangiosarcoma is a tumor of endothelial cells, which are driven by angiogenic stimuli. This study shows that miRNA dysregulation is a potential player in the pathogenesis of canine splenic hemangiosarcoma.

TRPA1 channels: expression in non-neuronal murine lung tissues and dispensability for hyperoxia-induced alveolar epithelial hyperplasia.

PubMed

Kannler, Martina; Lüling, Robin; Yildirim, Ali Önder; Gudermann, Thomas; Steinritz, Dirk; Dietrich, Alexander

2018-05-12

Transient receptor potential A1 (TRPA1) channels were originally characterized in neuronal tissues but also identified in lung epithelium by staining with fluorescently coupled TRPA1 antibodies. Its exact function in non-neuronal tissues, however, is elusive. TRPA1 is activated in vitro by hypoxia and hyperoxia and is therefore a promising TRP candidate for sensing hyperoxia in pulmonary epithelial cells and for inducing alveolar epithelial hyperplasia. Here, we isolated tracheal, bronchial, and alveolar epithelial cells and show low but detectable TRPA1 mRNA levels in all these cells as well as TRPA1 protein by Western blotting in alveolar type II (AT II) cells. We quantified changes in intracellular Ca 2+ ([Ca 2+ ] i ) levels induced by application of hyperoxic solutions in primary tracheal epithelial, bronchial epithelial, and AT II cells isolated from wild-type (WT) and TRPA1-deficient (TRPA1-/-) mouse lungs. In all cell types, we detected hyperoxia-induced rises in [Ca 2+ ] i levels, which were not significantly different in TRPA1-deficient cells compared to WT cells. We also tested TRPA1 function in a mouse model for hyperoxia-induced alveolar epithelial hyperplasia. A characteristic significant increase in thickening of alveolar tissues was detected in mouse lungs after exposure to hyperoxia, but not in normoxic WT and TRPA1-/- controls. Quantification of changes in lung morphology in hyperoxic WT and TRPA1-/- mice, however, again revealed no significant changes. Therefore, TRPA1 expression does neither appear to be a key player for hyperoxia-induced changes in [Ca 2+ ] i levels in primary lung epithelial cells, nor being essential for the development of hyperoxia-induced alveolar epithelial hyperplasia.

Spontaneous ovarian hyperstimulation syndrome and pituitary hyperplasia mimicking macroadenoma associated with primary hypothyroidism

PubMed Central

Kanza, Rene Epunza; Gagnon, Sylvain; Villeneuve, Helene; Laverdiere, David; Rousseau, Isabelle; Bordeleau, Edith; Berube, Michel

2013-01-01

We report an unusual case of spontaneous ovarian hyperstimulation syndrome and pituitary hyperplasia mimicking macroadenoma in an adult, non-pregnant woman. Her condition was triggered by unrecognized primary hypothyroidism, which regressed after thyroid hormone replacement therapy. This case highlights the need for clinicians and radiologists to familiarize themselves with the clinical and imaging features detected in case of these complications of primary hypothyroidism, which are not well known in the medical and radiological profession. Such improved knowledge will help avoid delays in diagnosis, progression to life-threatening complications, and unnecessary surgery. PMID:23494012

Role of GPR30 in estrogen-induced prostate epithelial apoptosis and benign prostatic hyperplasia.

PubMed

Yang, Deng-Liang; Xu, Jia-Wen; Zhu, Jian-Guo; Zhang, Yi-Lin; Xu, Jian-Bang; Sun, Qing; Cao, Xiao-Nian; Zuo, Wu-Lin; Xu, Ruo-Shui; Huang, Jie-Hong; Jiang, Fu-Neng; Zhuo, Yang-Jia; Xiao, Bai-Quan; Liu, Yun-Zhong; Yuan, Dong-Bo; Sun, Zhao-Lin; He, Hui-Chan; Lun, Zhao-Rong; Zhong, Wei-De; Zhou, Wen-Liang

2017-06-03

Several studies have implicated estrogen and the estrogen receptor (ER) in the pathogenesis of benign prostatic hyperplasia (BPH); however, the mechanism underlying this effect remains elusive. In the present study, we demonstrated that estrogen (17β-estradiol, or E2)-induced activation of the G protein-coupled receptor 30 (GPR30) triggered Ca 2+ release from the endoplasmic reticulum, increased the mitochondrial Ca 2+ concentration, and thus induced prostate epithelial cell (PEC) apoptosis. Both E2 and the GPR30-specific agonist G1 induced a transient intracellular Ca 2+ release in PECs via the phospholipase C (PLC)-inositol 1, 4, 5-triphosphate (IP 3 ) pathway, and this was abolished by treatment with the GPR30 antagonist G15. The release of cytochrome c and activation of caspase-3 in response to GPR30 activation were observed. Data generated from the analysis of animal models and human clinical samples indicate that treatment with the GPR30 agonist relieves testosterone propionate (TP)-induced prostatic epithelial hyperplasia, and that the abundance of GPR30 is negatively associated with prostate volume. On the basis of these results, we propose a novel regulatory mechanism whereby estrogen induces the apoptosis of PECs via GPR30 activation. Inhibition of this activation is predicted to lead to abnormal PEC accumulation, and to thereby contribute to BPH pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

[Condylar hyperplasia: qualitative and quantitative study of temporomandibular joints remodeling before and after condylectomy].

PubMed

Rojare, Camille; Wojcik, Thomas; Coussens, Camille; Ferri, Joël; Pertuzon, Bruno; Raoul, Gwénaël

2014-06-01

This retrospective study aimed to evaluate bone remodeling of temporo-mandibular joints (TMJ) using computed tomography (CT) before and after condylectomy for condylar hyperplasia. TMJ bone remodeling was studied by comparing the pre and postoperative CT scan of ten patients. Qualitative evaluation was performed by two-dimensional analysis. Three-dimensional analysis superimpositions were done after digital condylar units isolation. Condylar volume modifications were measured and compared on both sides. Lastly, before and after surgery, we studied the radio-clinic correlations. After surgery, all the operated condyles developed a new cortical bone. We noticed also a thickening of the glenoid fossa. Surgical condylectomy leaded to a 43.5% volume reduction on the operated side and 2.14% on the controlateral side. On the controlateral side, most of abnormalities seen preoperatively disappeared after surgery. For two patients, the condylar resection took away over 80% of the initial volume. For these patients, we observed major radiologic modifications on the controlateral TMJ associated with symptoms of dysfunction. These problems did not worsen their quality of life. Both TMJ presented with bone remodelling after condylectomy. In condylar hyperplasia, condylectomy provides orthopaedic results on dysmorphia and removal of the pathological prechondroblastic zone. In the future, an earlier detection of this pathology may help the surgeon to treat in childhood. This would limit surgical excision and would avoid important dysmorphia. © EDP Sciences, SFODF, 2014.

Activation of the Wnt/β-catenin pathway in pancreatic beta cells during the compensatory islet hyperplasia in prediabetic mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maschio, D. A.; Oliveira, R. B.; Santos, M. R.

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 genesmore » of the Wnt pathway) but not of Tcf7l2 (the transcription factor). Meanwhile, these alterations were not observed in pancreatic islets from 30 d HFD-fed mice, that do not display significant beta cell hyperplasia. These data suggest that the Wnt/β-catenin pathway is activated in pancreatic islets during prediabetes and may play a role in the induction of the compensatory beta cell hyperplasia observed at early phase of T2DM. - Highlights: • Exposure to high-fat diet for 60 days induced prediabetes and beta cell mass expansion. • Hyperplastic pancreatic islets displayed nuclear translocation of active β-catenin. • Hyperplastic islets showed increased expression of target genes of the Wnt/β-catenin pathway. • Wnt/β-catenin pathway is activated during compensatory beta cell hyperplasia in mice.« less

[Final height in symptomatic boys with late-onset adrenal hyperplasia (LOCAH), treated with glucocorticoids. Clinical cases].

PubMed

Pasqualini, Titania; Alonso, Guillermo; Fernández, Cecilia; Buzzalino, Noemí; Dain, Liliana

2013-04-01

Although corticoid replacement is recommended for those late-onset adrenal hyperplasia with clinical manifestations, asymptomatic patients do not need treatment. We describe clinical features at diagnosis, treatment, and growth till adult- height, in 4 boys. At diagnosis, age ranged from 9.2-11.6 years. The initial symptoms/signs were: precocious pubarche (n = 2), accelerated bone age (n = 1) and precocious puberty (n = 1). All of them presented elevated 17 hydroxyprogesterone levels and were compound heterozygotes carrying p.V281L mutation. Since, at diagnosis, bone age was significantly advanced for chronological age (13.1 ± 0.5 vs. 10.2 ± 1.1 p = 0.008), hydrocortisone therapy was initiated. During follow-up, mean height Z score decreased 1.4 ± 0.4 SDS (p = 0.007), though adult mean height was not different from target height (-0.39 ± 0.7 vs. -0.04 ± 0.5 SDS, p = 0.054). In conclusion, in 4 symptomatic patients, accurate treatment of late-onset adrenal hyperplasia led to an adult mean height not different from target height. Advanced bone age at diagnosis and the loss of height during pubertal development suggest the need of therapy.

Pathological and Genetic Characterization of Bilateral Adrenomedullary Hyperplasia in a Patient with Germline MAX Mutation.

PubMed

Romanet, Pauline; Guerin, Carole; Pedini, Pascal; Essamet, Wassim; Castinetti, Frédéric; Sebag, Fréderic; Roche, Philippe; Cascon, Alberto; Tischler, Arthur S; Pacak, Karel; Barlier, Anne; Taïeb, David

2017-12-01

In recent years, familial pheochromocytoma (PHEO) with germline mutations in the MAX (MYC associated factor X) gene has been reported in a few cases. Here, we investigated a 25-year-old patient with multiple PHEOs associated with a non-sense germline MAX mutation. Preoperative 18 F-FDOPA PET/CT revealed bilateral adrenal involvement with multiple tumors. In addition, both adrenal glands were found to have diffuse or nodular adrenal medullary hyperplasia (AMH), a histopathological feature previously described as a precursor of MEN2- and SDHB-related PHEOs but not MAX. After bilateral adrenalectomy, different paraffin-embedded and frozen samples were analyzed for allelic imbalances of the MAX gene using allelic quantification by pyrosequencing. The expression of the protein MAX was studied by immunohistochemistry. All PHEOs but also nodular AMH exhibited a loss of the normal allele. By contrast, the diffuse AMH did not show loss-of-heterozygosity. Nevertheless, immunohistochemistry demonstrated loss of protein MAX expression in all samples including diffuse hyperplasia, suggesting a causative role of MAX mutation for both PHEOs and AMH. The present case shows that both nodular and diffuse AMH belongs to the spectrum of MAX-related disease. These data support the possible continuum between nodular AMH and PHEO, expanding the qualification of micro-PHEO to nodular AMH.