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.

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.

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.

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.

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.

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

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.

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.

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

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.

Pituitary hyperplasia and gigantism in mice caused by a cholera toxin transgene.

PubMed

Burton, F H; Hasel, K W; Bloom, F E; Sutcliffe, J G

1991-03-07

Cyclic AMP is thought to act as an intracellular second messenger, mediating the physiological response of many cell types to extracellular signals. In the pituitary, growth hormone (GH)-producing cells (somatotrophs) proliferate and produce GH in response to hypothalamic GH-releasing factor, which binds a receptor that stimulates Gs protein activation of adenylyl cyclase. We have now determined whether somatotroph proliferation and GH production are stimulated by cAMP alone, or require concurrent, non-Gs-mediated induction of other regulatory molecules by designing a transgene to induce chronic supraphysiological concentrations of cAMP in somatotrophs. The rat GH promoter was used to express an intracellular form of cholera toxin, a non-cytotoxic and irreversible activator of Gs. Introduction of this transgene into mice caused gigantism, elevated serum GH levels, somatotroph proliferation and pituitary hyperplasia. These results support the direct triggering of these events by cAMP, and illustrate the utility of cholera toxin transgenes as a tool for physiological engineering.

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.

Activation of cathepsin L contributes to the irreversible depolarization induced by oxygen and glucose deprivation in rat hippocampal CA1 neurons.

PubMed

Kikuta, Shogo; Murai, Yoshinaka; Tanaka, Eiichiro

2017-01-01

Oxygen and glucose deprivation (OGD) elicits a rapid and irreversible depolarization with a latency of ∼5min in intracellular recordings of hippocampal CA1 neurons in rat slice preparations. In the present study, we examined the role of cathepsin L in the OGD-induced depolarization. OGD-induced depolarizations were irreversible as no recovery of membrane potential was observed. The membrane potential reached 0mV when oxygen and glucose were reintroduced immediately after the onset of the OGD-induced rapid depolarization. The OGD-induced depolarizations became reversible when the slice preparations were pre-incubated with cathepsin L inhibitors (types I and IV at 0.3-2nM and 0.3-30nM, respectively). Moreover, pre-incubation with these cathepsin inhibitors prevented the morphological changes, including swelling of the cell soma and fragmentation of dendrites, observed in control neurons after OGD. These findings suggest that the activation of cathepsin L contributes to the irreversible depolarization produced by OGD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

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

Regression of nifedipine-induced gingival hyperplasia following switch to a same class calcium channel blocker, isradipine.

PubMed

Westbrook, P; Bednarczyk, E M; Carlson, M; Sheehan, H; Bissada, N F

1997-07-01

Patients with nifedipine-induced gingival hyperplasia (GH) often require continued calcium channel blocker therapy. Switches to diltiazem and verapamil have been described; however, these drugs are of a different chemical class and present therapeutic limitations in some patients. The purpose of this study was to evaluate the effect on nifedipine-induced GH of a switch to a dihydropyridine derivative with a low incidence of GH. Fourteen patients with nifedipine-induced GH were given a medical exam and a periodontal exam. The following parameters were assessed: probing depth (PD), gingival margin (GM), gingival thickness (GT), plaque index (PI), and gingival index (GI). Intraoral photographs, study models, and a gingival biopsy for histological examination were taken. Following baseline measures, patients were randomized to continued treatment with nifedipine or an equivalent dose of isradipine in a single-blind fashion. Biweekly periodontal parameters were taken for 8 weeks. At the end of 8 weeks, some patients elected to receive 4 weeks of open label isradipine therapy, with biweekly examination continuing through the open label phase. The isradipine treatment arm showed a mean decrease in PD of 0.59 mm at week 8 (P < 0.05). No other measured parameter (GM, GT, PI, GI) was significantly changed, compared either to baseline or to the alternate treatment arm. Clinically, 60% of patients treated with isradipine exhibited a decrease in hyperplasia, while 66% of patients treated with nifedipine demonstrated an increase in hyperplasia, a significant difference (P < 0.05). When combined with open label data, patients switching therapy to isradipine exhibited an increase in GM (increase in recession) of 0.74 mm from baseline to week 12 (P < 0.05). No patients treated with isradipine exhibited an increase in gingival overgrowth. All patients exhibited adequate control of hypertension. We conclude that in hypertensive patients with nifedipine-induced GH, switching

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.

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.

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.

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.

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.

Suppressive activities and mechanisms of ugonin J on vascular smooth muscle cells and balloon angioplasty-induced neointimal hyperplasia.

PubMed

Pan, Chun-Hsu; Li, Pei-Chuan; Chien, Yi-Chung; Yeh, Wan-Ting; Liaw, Chih-Chuang; Sheu, Ming-Jyh; Wu, Chieh-Hsi

2018-02-01

Neointimal hyperplasia (or restenosis) is primarily attributed to excessive proliferation and migration of vascular smooth muscle cells (VSMCs). In this study, we investigated the inhibitory effects and mechanisms of ugonin J on VSMC proliferation and migration as well as neointimal formation. Cell viability and the cell-cycle distribution were, respectively, analyzed using an MTT assay and flow cytometry. Cell migration was examined using a wound-healing analysis and a transwell assay. Protein expressions and gelatinase activities were, respectively, measured using Western blot and gelatin zymography. Balloon angioplasty-induced neointimal formation was induced in a rat carotid artery model and then examined using immunohistochemical staining. Ugonin J induced cell-cycle arrest at the G 0 /G 1 phase and apoptosis to inhibit VSMC growth. Ugonin J also exhibited marked suppressive activity on VSMC migration. Ugonin J significantly reduced activations of focal adhesion kinase, phosphoinositide 3-kinase, v-akt murine thymoma viral oncogene homolog 1, and extracellular signal-regulated kinase 1/2 proteins. Moreover, ugonin J obviously reduced expressions and activity levels of matrix metalloproteinase-2 and matrix metalloproteinase-9. In vivo data indicated that ugonin J prevented balloon angioplasty-induced neointimal hyperplasia. Our study suggested that ugonin J has the potential for application in the prevention of balloon injury-induced neointimal formation. Copyright © 2017 John Wiley & Sons, Ltd.

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.

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.

The inhibiting effects of Urtica dioica root extracts on experimentally induced prostatic hyperplasia in the mouse.

PubMed

Lichius, J J; Muth, C

1997-08-01

Extracts of stinging nettle roots (Urtica dioica L. Urticaceae) are used in the treatment of benign prostatic hyperplasia (BPH). We established a BPH-model by directly implanting an urogenital sinus (UGS) into the ventral prostate gland of an adult mouse. Five differently prepared stinging nettle root extracts were tested in this model. The 20% methanolic extract was the most effective with a 51.4% inhibition of induced growth.

HO-1 inhibits IL-13-induced goblet cell hyperplasia associated with CLCA1 suppression in normal human bronchial epithelial cells.

PubMed

Mishina, Kei; Shinkai, Masaharu; Shimokawaji, Tadasuke; Nagashima, Akimichi; Hashimoto, Yusuke; Inoue, Yoriko; Inayama, Yoshiaki; Rubin, Bruce K; Ishigatsubo, Yoshiaki; Kaneko, Takeshi

2015-12-01

Mucus hypersecretion and goblet cell hyperplasia are common features that characterize asthma. IL-13 increases mucin (MUC) 5AC, the major component of airway mucus, in airway epithelial cells. According to the literature, IL-13 receptor activation leads to STAT6 activation and consequent induction of chloride channel accessory 1 (CLCA1) gene expression, associated with the induction of MUC5AC. Heme oxygenase-1 (HO-1) is an enzyme that catalyzes oxidation of heme to biliverdin, and has anti-inflammatory and anti-oxidant properties. We examined the effects of HO-1 on mucin production and goblet cell hyperplasia induced by IL-13. Moreover, we assessed the cell signaling intermediates that appear to be responsible for mucin production. Normal human bronchial epithelial (NHBE) cells were grown at air liquid interface (ALI) in the presence or absence of IL-13 and hemin, a HO-1 inducer, for 14 days. Protein concentration was analyzed using ELISA, and mRNA expression was examined by real-time PCR. Histochemical analysis was performed using HE staining, andWestern blotting was performed to evaluate signaling transduction pathway. Hemin (4 μM) significantly increased HO-1 protein expression (p b 0.01) and HO-1 mRNA expression (p b 0.001). IL-13 significantly increased goblet cells, MUC5AC protein secretion (p b 0.01) and MUC5AC mRNA (p b 0.001), and these were decreased by hemin by way of HO-1. Tin protoporphyrin (SnPP)-IX, a HO-1 inhibitor, blocked the effect of hemin restoring MUC5AC protein secretion (p b 0.05) and goblet cell hyperplasia. Hemin decreased the expression of CLCA1 mRNA (p b 0.05) and it was reversed by SnPP-IX, but could not suppress IL-13-induced phosphorylation of STAT6 or SAM pointed domain-containing ETS transcription factor (SPDEF) and Forkhead box A2 (FOXA2) mRNA expression. In summary, HO-1 overexpression suppressed IL-13-induced goblet cell hyperplasia and MUC5AC production, and involvement of CLCA1 in the mechanism was suggested.

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

Traditional Chinese medicine formula Bi-Qi capsule alleviates rheumatoid arthritis-induced inflammation, synovial hyperplasia, and cartilage destruction in rats.

PubMed

Wang, Kai; Zhang, Dongmei; Liu, Yan; Wang, Xuan; Zhao, Jiantong; Sun, Tingting; Jin, Tingting; Li, Baoli; Pathak, Janak L

2018-03-14

Traditional Chinese medicine (TCM) formula Bi-Qi capsule (Bi-Qi) is a commonly prescribed drug to treat rheumatoid arthritis (RA). However, the mechanism of Bi-Qi-mediated amelioration of RA pathogenesis is still a mystery. Collagen induced arthritis (CIA) in rats is an established model that shares many similarities with RA in humans. In this study we investigated the effect of Bi-Qi on the pathogenesis of CIA in rats. CIA was developed in Sprague-Dawley (S.D) rats (n = 60, female) and used as a model resembling RA in humans. Rats were treated with a high or moderate dose of Bi-Qi, or methotrexate (MTX). Effects of the treatment on local joint and systemic inflammation, synovial hyperplasia, cartilage destruction, and other main features in the pathogenesis of CIA were analyzed. Inflamed and swollen ankles and joints were observed in arthritic rats, while Bi-Qi or MTX treatment alleviated these symptoms. Only the Bi-Qi moderate dose decreased RA-induced serum levels of tumor necrosis factor-alpha (TNF-α). Both Bi-Qi and MTX reduced the interleukin (IL)-18 serum level. Protein levels of cartilage oligomeric matrix protein and osteopontin in serum, synovium, and cartilage were elevated in arthritic rats, while Bi-Qi alleviated these effects. Synovial hyperplasia, inflammatory cell infiltration in synovium and a high degree of cartilage degradation was observed in RA, and Bi-Qi or MTX alleviated this effect. Bi-Qi at the moderate dose was the most effective in mitigating CIA-related clinical complications. Our findings showed that Bi-Qi alleviates CIA-induced inflammation, synovial hyperplasia, cartilage destruction, and the other main features in the pathogenesis of CIA. This provides fundamental evidence for the anti-arthritic properties of Bi-Qi and corroborates the use of Bi-Qi TCM formula for the treatment of RA.

Effect of red maca (Lepidium meyenii) on prostate zinc levels in rats with testosterone-induced prostatic hyperplasia.

PubMed

Gonzales, C; Leiva-Revilla, J; Rubio, J; Gasco, M; Gonzales, G F

2012-05-01

Lepidium meyenii (maca) is a plant that grows exclusively above 4000 m in the Peruvian central Andes. Red maca (RM) extract significantly reduced prostate size in rats with benign prostatic hyperplasia (BPH) induced by testosterone enanthate (TE). Zinc is an important regulator of prostate function. This study aimed to determine the effect of RM on prostate zinc levels in rats with BPH induced by TE. Also, the study attempted to determine the best marker for the effect of RM on sex accessory glands. Rats treated with RM extract from day 1 to day 14 reversed the effect of TE administration on prostate weight and zinc levels. However, RM administered from day 7 to day 14 did not reduce the effect of TE on all studied variables. Finasteride (FN) reduced prostate, seminal vesicle and preputial gland weights in rats treated with TE. Although RM and FN reduced prostate zinc levels, the greatest effect was observed in TE-treated rats with RM from day 1 to day 14. In addition, prostate weight and zinc levels showed the higher diagnosis values than preputial and seminal vesicle weights. In conclusion, RM administered from day 1 to day 14 reduced prostate size and zinc levels in rats where prostatic hyperplasia was induced with TE. Also, this experimental model could be used as accurately assay to determine the effect of maca obtained under different conditions and/or the effect of different products based on maca. © 2011 Blackwell Verlag GmbH.

Dapoxetine attenuates testosterone-induced prostatic hyperplasia in rats by the regulation of inflammatory and apoptotic proteins

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

Sayed, Rabab H., E-mail: rabab.sayed@pharma.cu.edu

Serotonin level plays a role in suppressing the pathological findings of benign prostatic hyperplasia (BPH). Thus a new selective serotonin reuptake inhibitor, dapoxetine was used to test its ability to ameliorate the pathological changes in the rat prostate. A dose response curve was constructed between the dose of dapoxetine and prostate weight as well as relative prostate weight, then a 5 mg/kg dose was used as a representative dose for dapoxetine administration. Rats were divided into four groups; the control group that received the vehicle; the BPH-induced group received daily s.c injection of 3 mg/kg testosterone propionate dissolved in olivemore » oil for four weeks; BPH-induced group treated with finasteride 5 mg/kg/day p.o and BPH-induced group treated with dapoxetine 5 mg/kg/day p.o. Injection of testosterone increased prostate weight and relative prostate weight which were both returned back to the normal value after treatment with dapoxetine as well as finasteride. Testosterone also upregulated androgen receptor (AR) and proliferating cell nuclear antigen gene expression. Furthermore, testosterone injection elevated cyclooxygenase-II (COX II), inducible nitric oxide synthase (iNOS), B-cell lymphoma-2 (Bcl2) expression and tumor necrosis factor alpha content and reduced caspase-3 activity, Bcl-2-associated X protein (Bax) expression and Bax/Bcl2 ratio. Dapoxetine and finasteride administration reverted most of the changes made by testosterone injection. In conclusion, the current study provides an evidence for the protective effects of dapoxetine against testosterone-induced BPH in rats. This can be attributed, at least in part, to decreasing AR expression, and the anti-proliferative, anti-inflammatory and pro-apoptotic activities of dapoxetine in BPH. - Highlights: • Dapoxetine attenuates testosterone-induced prostatic hyperplasia in rats. • Dapoxetine decreased androgen receptor gene expression in rat prostate. • Dapoxetine possess anti

Nuclear Receptor CAR Specifically Activates the Two-Pore K+ Channel Kcnk1 Gene in Male Mouse Livers, Which Attenuates Phenobarbital-Induced Hepatic Hyperplasia

PubMed Central

Negishi, Masahiko

2013-01-01

KCNK1, a member of the family of two-pore K+ ion channels, is specifically induced in the livers of male mice after phenobarbital treatment. Here, we have determined the molecular mechanism of this male-specific activation of the Kcnk1 gene and characterized KCNK1 as a phenobarbital-inducible antihyperplasia factor. Upon activation by phenobarbital, nuclear receptor CAR binds the 97-bp response element (−2441/−2345) within the Kcnk1 promoter. This binding is observed in the livers of male mice, but not in the livers of female mice and requires the pituitary gland, because hypophysectomy abrogates it. Hyperplasia further progressed in the livers of Kcnk1 −/− male mice compared with those of Kcnk1 +/+ males after phenobarbital treatment. Thus, KCNK1 suppresses phenobarbital-induced hyperplasia. These results indicate that phenobarbital treatment induces KCNK1 to elicit a male-specific and growth-suppressing signal. Thus, KCNK1 and Kcnk1 −/− mice provide an experimental tool for further investigation into the molecular mechanism of CAR-mediated promotion of the development of hepatocellular carcinoma in mice. PMID:23291559

Nuclear receptor CAR specifically activates the two-pore K+ channel Kcnk1 gene in male mouse livers, which attenuates phenobarbital-induced hepatic hyperplasia.

PubMed

Saito, Kosuke; Moore, Rick; Negishi, Masahiko

2013-03-01

KCNK1, a member of the family of two-pore K(+) ion channels, is specifically induced in the livers of male mice after phenobarbital treatment. Here, we have determined the molecular mechanism of this male-specific activation of the Kcnk1 gene and characterized KCNK1 as a phenobarbital-inducible antihyperplasia factor. Upon activation by phenobarbital, nuclear receptor CAR binds the 97-bp response element (-2441/-2345) within the Kcnk1 promoter. This binding is observed in the livers of male mice, but not in the livers of female mice and requires the pituitary gland, because hypophysectomy abrogates it. Hyperplasia further progressed in the livers of Kcnk1 ( -/- ) male mice compared with those of Kcnk1 ( +/+ ) males after phenobarbital treatment. Thus, KCNK1 suppresses phenobarbital-induced hyperplasia. These results indicate that phenobarbital treatment induces KCNK1 to elicit a male-specific and growth-suppressing signal. Thus, KCNK1 and Kcnk1 ( -/- ) mice provide an experimental tool for further investigation into the molecular mechanism of CAR-mediated promotion of the development of hepatocellular carcinoma in mice.

Altered gene expression patterns during the initiation and promotion stages of neonatally diethylstilbestrol-induced hyperplasia/dysplasia/neoplasia in the hamster uterus.

PubMed

Hendry, William J; Hariri, Hussam Y; Alwis, Imala D; Gunewardena, Sumedha S; Hendry, Isabel R

2014-12-01

Neonatal treatment of hamsters with diethylstilbestrol (DES) induces uterine hyperplasia/dysplasia/neoplasia (endometrial adenocarcinoma) in adult animals. We subsequently determined that the neonatal DES exposure event directly and permanently disrupts the developing hamster uterus (initiation stage) so that it responds abnormally when it is stimulated with estrogen in adulthood (promotion stage). To identify candidate molecular elements involved in progression of the disruption/neoplastic process, we performed: (1) immunoblot analyses and (2) microarray profiling (Affymetrix Gene Chip System) on sets of uterine protein and RNA extracts, respectively, and (3) immunohistochemical analysis on uterine sections; all from both initiation stage and promotion stage groups of animals. Here we report that: (1) progression of the neonatal DES-induced hyperplasia/dysplasia/neoplasia phenomenon in the hamster uterus involves a wide spectrum of specific gene expression alterations and (2) the gene products involved and their manner of altered expression differ dramatically during the initiation vs. promotion stages of the phenomenon. Copyright © 2014 Elsevier Inc. All rights reserved.

Reversible and irreversible vascular bioeffects induced by ultrasound and microbubbles in chorioallantoic membrane model

NASA Astrophysics Data System (ADS)

Tarapacki, Christine; Kuebler, Wolfgang M.; Tabuchi, Arata; Karshafian, Raffi

2017-03-01

Background: The application of ultrasound and microbubbles at therapeutic conditions has been shown to improve delivery of molecules, cause vasoconstriction, modulate blood flow and induce a vascular shut down in in vivo cancerous tissues. The underlying mechanism has been associated with the interaction of ultrasonically-induced microbubble oscillation and cavitation with the blood vessel wall. In this study, the effect of ultrasound and microbubbles on blood flow and vascular architecture was studied using a fertilized chicken egg CAM (chorioallantoic membrane) model. Methods: CAM at day 12 of incubation (Hamburger-Hamilton stage 38-40) were exposed to ultrasound at varying acoustic pressures (160, 240 and 320 kPa peak negative pressure) in the presence of Definity microbubbles and 70 kDa FITC dextran fluorescent molecules. A volume of 50 µL Definity microbubbles were injected into a large anterior vein of the CAM prior to ultrasound exposure. The ultrasound treatment sequence consisted of 5 s exposure at 500 kHz frequency, 8 cycles and 1 kHz pulse repetition frequency with 5 s off for a total exposure of 2 minutes. Fluorescent videos and images of the CAM vasculature were acquired using intravital microscopy prior, during and following the ultrasound exposure. Perfusion was quantified by measuring the length of capillaries in a region of interest using Adobe Illustrator. Results and Discussion: The vascular bioeffects induced by USMB increased with acoustic peak negative pressure. At 160 kPa, no visible differences were observed compared to the control. At 240 kPa, a transient decrease in perfusion with subsequent recovery within 15 minutes was observed, whereas at 320 kPa, the fluorescent images showed an irreversible vascular damage. The study indicates that a potential mechanism for the transient decrease in perfusion may be related to blood coagulation. The results suggest that ultrasound and microbubbles can induce reversible and irreversible vascular

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

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.

Heat-induced Irreversible Denaturation of the Camelid Single Domain VHH Antibody Is Governed by Chemical Modifications

PubMed Central

Akazawa-Ogawa, Yoko; Takashima, Mizuki; Lee, Young-Ho; Ikegami, Takahisa; Goto, Yuji; Uegaki, Koichi; Hagihara, Yoshihisa

2014-01-01

The variable domain of camelid heavy chain antibody (VHH) is highly heat-resistant and is therefore ideal for many applications. Although understanding the process of heat-induced irreversible denaturation is essential to improve the efficacy of VHH, its inactivation mechanism remains unclear. Here, we showed that chemical modifications predominantly governed the irreversible denaturation of VHH at high temperatures. After heat treatment, the activity of VHH was dependent only on the incubation time at 90 °C and was insensitive to the number of heating (90 °C)-cooling (20 °C) cycles, indicating a negligible role for folding/unfolding intermediates on permanent denaturation. The residual activity was independent of concentration; therefore, VHH lost its activity in a unimolecular manner, not by aggregation. A VHH mutant lacking Asn, which is susceptible to chemical modifications, had significantly higher heat resistance than did the wild-type protein, indicating the importance of chemical modifications to VHH denaturation. PMID:24739391

Immunomodulatory Effect of Red Onion (Allium cepa Linn) Scale Extract on Experimentally Induced Atypical Prostatic Hyperplasia in Wistar Rats

PubMed Central

Elberry, Ahmed A.; Al-Maghrabi, Jaudah; Abdel Sattar, Essam; Ghareib, Salah A.; Mosli, Hisham A.; Gabr, Salah A.

2014-01-01

Red onion scales (ROS) contain large amounts of flavonoids that are responsible for the reported antioxidant activity, immune enhancement, and anticancer property. Atypical prostatic hyperplasia (APH) was induced in adult castrated Wistar rats by both s.c. injection of testosterone (0.5 mg/rat/day) and by smearing citral on shaved skin once every 3 days for 30 days. Saw palmetto (100 mg/kg) as a positive control and ROS suspension at doses of 75, 150, and 300 mg/kg/day were given orally every day for 30 days. All medications were started 7 days after castration and along with testosterone and citral. The HPLC profile of ROS methanolic extract displayed two major peaks identified as quercetin and quercetin-4′-β-O-D-glucoside. Histopathological examination of APH-induced prostatic rats revealed evidence of hyperplasia and inflammation with cellular proliferation and reduced apoptosis Immunohistochemistry showed increased tissue expressions of IL-6, IL-8, TNF-α, IGF-1, and clusterin, while TGF-β1 was decreased, which correlates with the presence of inflammation. Both saw palmetto and RO scale treatment have ameliorated these changes. These ameliorative effects were more evident in RO scale groups and were dose dependent. In conclusion, methanolic extract of ROS showed a protective effect against APH induced rats that may be attributed to potential anti-inflammatory and immunomodulatory effects. PMID:24829522

Human SolCD39 Inhibits Injury-induced Development of Neointimal Hyperplasia

PubMed Central

Drosopoulos, Joan H. F.; Kraemer, Rosemary; Shen, Hao; Upmacis, Rita K.; Marcus, Aaron J.; Musi, Elgilda

2010-01-01

SUMMARY Blood platelets provide the initial response to vascular endothelial injury, becoming activated as they adhere to the injured site. Activated platelets recruit leukocytes, and initiate proliferation and migration of vascular smooth muscle cells (SMC) within the injured vessel wall, leading to development of neointimal hyperplasia. Endothelial CD39/NTPDase1 and recombinant solCD39 rapidly metabolize nucleotides, including stimulatory ADP released from activated platelets, thereby suppressing additional platelet reactivity. Using a murine model of vascular endothelial injury, we investigated whether circulating human solCD39 could reduce platelet activation and accumulation, thus abating leukocyte infiltration and neointimal formation following vascular damage. Intraperitoneally-administered solCD39 ADPase activity in plasma peaked 1 hr post-injection, with an elimination half-life of 43 hr. Accordingly, mice were administered solCD39 or saline 1 hr prior to vessel injury, then either sacrificed 24 hr post-injury or treated with solCD39 or saline (3X weekly) for an additional 18 days. 24 hr post-injury, solCD39-treated mice displayed a reduction in platelet activation and recruitment, P-selectin expression, and leukocyte accumulation in the arterial lumen. Furthermore, repeated administration of solCD39 modulated the late stage of vascular injury by suppressing leukocyte deposition, macrophage infiltration and SMC proliferation/migration, resulting in abrogation of neointimal thickening. In contrast, injured femoral arteries of saline-injected mice exhibited massive platelet thrombus formation, marked P-selectin expression, and leukocyte infiltration. Pronounced neointimal growth with macrophage and SMC accretion was also observed (intimal-to-medial area ratio 1.56±0.34 at 19 days). Thus, systemic administration of solCD39 profoundly affects injury-induced cellular responses, minimizing platelet deposition and leukocyte recruitment, and suppressing

Safety and efficacy of a novel Prunus domestica extract (Sitoprin, CR002) on testosterone-induced benign prostatic hyperplasia (BPH) in male Wistar rats.

PubMed

Swaroop, Anand; Bagchi, Manashi; Kumar, Pawan; Preuss, Harry G; Bagchi, Debasis

2015-01-01

The efficacy of a novel Prunus domestica bark extract (Sitoprin, CR002) was investigated on testosterone propionate (TP)-induced benign prostatic hyperplasia (BPH) in male Wistar rats. BPH was induced by daily subcutaneous administration of TP (3.0 mg/kg) over a period of 15 days (interim sacrifice group) and for an additional 21 days (terminal sacrifice group). We evaluated the dose-dependent efficacy (0, 50, 100 and 200 mg/kg body weight/day) of CR002 and a control group against BPH, and compared with a reference standard Prunus africana extract (CR001). Extensive clinical examinations were carried out on days 1, 7, 14, 21, 28 and 35 of treatment period to determine the onset, duration and severity of clinical signs. Clinical pathology, hematology, biochemistry and histopathology were performed on days 15 and 35, prior to necropsy. Animals were fasted overnight prior to blood collection. Prostate glands and tissues were examined. On day 36, histopathology of ventral prostrate of control rats demonstrates single layer of columnar mucin secreting epithelial cells along with a lumen occupied with eosinophilic secretion. In contrast, CR002 and CR001 groups (100 and 200 mg/kg/day) exhibited no hyperplasia and proliferation of epithelial cells. Prostate histopathology of these treated groups was comparable with control rats. The hyperplasia and hypertrophy of prostrate was reduced to single-layered cell indicating the efficacy of CR002 and CR001. Overall, results demonstrate that CR002 exhibits therapeutic efficacy/activity in TP-induced BPH in rats, which is comparable to CR001.

Anti-inflammatory and antiproliferative activities of date palm pollen (Phoenix dactylifera) on experimentally-induced atypical prostatic hyperplasia in rats

PubMed Central

2011-01-01

Background Atypical prostatic hyperplasia (APH) is a pseudoneoplastic lesion that can mimic prostate adenocarcinoma because of its cytologic and architectural features. Suspension of date palm pollen (DPP) is an herbal mixture that is widely used in folk medicine for male infertility. The aim of the present study was to evaluate the effect of DPP suspension and extract on APH-induced rats. Methods APH was induced in adult castrated Wistar rats by both s.c. injection of testosterone (0.5 mg/rat/day) and smearing citral on shaved skin once every 3 days for 30 days. Saw palmetto (100mg/kg), DPP suspension (250, 500 and 1000 mg/kg), and lyophilized DPP extract (150,300 and 600 mg/kg) were given orally daily for 30 days. All medications were started 7 days after castration and along with testosterone and citral. Results The histopathological feature in APH-induced prostate rats showed evidence of hyperplasia and inflammation. Immunohistochemical examination revealed that the expressions of IL-6, IL-8, TNF-α, IGF-1 and clusterin were increased, while the expression of TGF-β1 was decreased that correlates with presence of inflammation. Moreover, histopathological examination revealed increased cellular proliferation and reduced apoptosis in ventral prostate. Both saw palmetto and DPP treatment has ameliorated these histopathological and immunohistochemical changes in APH-induced rats. These improvements were not associated with reduction in the prostatic weight that may be attributed to the persistence of edema. Conclusion DPP may have a potential protective effect in APH-induced Wistar rats through modulation of cytokine expression and/or upregulation of their autocrine/paracrine receptors. PMID:22195697

Spectral line intensity irreversibility in circulatory plasma magnetization processes

NASA Astrophysics Data System (ADS)

Qu, Z. Q.; Dun, G. T.

2012-01-01

Spectral line intensity variation is found to be irreversible in circulatory plasma magnetization process by experiments described in this paper, i.e., the curves illustrating spectral line photon fluxes irradiated from a light source immerged in a magnetic field by increasing the magnetic induction cannot be reproduced by decreasing the magnetic induction within the errors. There are two plasma magnetization patterns found. One shows that the intensities are greater at the same magnetic inductions during the magnetic induction decreasing process after the increasing, and the other gives the opposite effect. This reveals that the magneto-induced excitation and de-excitation process is irreversible like ferromagnetic magnetization. But the two irreversible processes are very different in many aspects stated in the text.

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

Nanosized zinc oxide particles do not promote DHPN-induced lung carcinogenesis but cause reversible epithelial hyperplasia of terminal bronchioles.

PubMed

Xu, Jiegou; Futakuchi, Mitsuru; Alexander, David B; Fukamachi, Katsumi; Numano, Takamasa; Suzui, Masumi; Shimizu, Hideo; Omori, Toyonori; Kanno, Jun; Hirose, Akihiko; Tsuda, Hiroyuki

2014-01-01

Zinc oxide (ZnO) is known to induce lung toxicity, including terminal bronchiolar epithelial hyperplasia, which gives rise to concerns that nanosized ZnO (nZnO) might lead to lung carcinogenesis. We studied the tumor promoting activity of nZnO by an initiation-promotion protocol using human c-Ha-ras proto-oncogene transgenic rats (Hras128 rats). The rats were given 0.2 % N-nitrosobis(2-hydroxypropyl)amine (DHPN) in the drinking water for 2 weeks and then treated with 0.5 ml of 250 or 500 μg/ml nZnO suspension by intra-pulmonary spraying once every 2 weeks for a total of 7 times. Treatment with nZnO particles did not promote DHPN-induced lung carcinogenesis. However, nZnO dose-dependently caused epithelial hyperplasia of terminal bronchioles (EHTB) and fibrosis-associated interstitial pneumonitis (FAIP) that were independent of DHPN treatment. Tracing the fate of EHTB lesions in wild-type rats indicated that the hyperplastic lesions almost completely disappeared within 12 weeks after the last nZnO treatment. Since nZnO particles were not found in the lung and ZnCl2 solution induced similar lung lesions and gene expression profiles, the observed lesions were most likely caused by dissolved Zn(2+). In summary, nZnO did not promote carcinogenesis in the lung and induced EHTB and FAIP lesions that regressed rapidly, probably due to clearance of surplus Zn(2+) from the lung.

Irreversible climate change due to carbon dioxide emissions.

PubMed

Solomon, Susan; Plattner, Gian-Kasper; Knutti, Reto; Friedlingstein, Pierre

2009-02-10

The severity of damaging human-induced climate change depends not only on the magnitude of the change but also on the potential for irreversibility. This paper shows that the climate change that takes place due to increases in carbon dioxide concentration is largely irreversible for 1,000 years after emissions stop. Following cessation of emissions, removal of atmospheric carbon dioxide decreases radiative forcing, but is largely compensated by slower loss of heat to the ocean, so that atmospheric temperatures do not drop significantly for at least 1,000 years. Among illustrative irreversible impacts that should be expected if atmospheric carbon dioxide concentrations increase from current levels near 385 parts per million by volume (ppmv) to a peak of 450-600 ppmv over the coming century are irreversible dry-season rainfall reductions in several regions comparable to those of the "dust bowl" era and inexorable sea level rise. Thermal expansion of the warming ocean provides a conservative lower limit to irreversible global average sea level rise of at least 0.4-1.0 m if 21st century CO(2) concentrations exceed 600 ppmv and 0.6-1.9 m for peak CO(2) concentrations exceeding approximately 1,000 ppmv. Additional contributions from glaciers and ice sheet contributions to future sea level rise are uncertain but may equal or exceed several meters over the next millennium or longer.

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

Beta-lactam antibiotic-induced platelet dysfunction: Evidence for irreversible inhibition of platelet activation in vitro and in vivo after prolonged exposure to penicillin

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

Burroughs, S.F.; Johnson, G.J.

beta-Lactam antibiotics cause platelet dysfunction with bleeding complications. Previous in vitro studies documented reversible inhibition of agonist-receptor interaction. This mechanism is inadequate to explain the effect of beta-lactam antibiotics in vivo. Platelet function does not return to normal immediately after drug treatment, implying irreversible inhibition of platelet function. We report here evidence of irreversible platelet functional and biochemical abnormalities after in vitro and in vivo exposure to beta-lactam antibiotics. Irreversible binding of (14C)-penicillin (Pen) occurred in vitro. After 24 hours' in vitro incubation with 10 to 20 mmol/L Pen, or ex vivo after antibiotic treatment, irreversible functional impairment occurred; butmore » no irreversible inhibition of alpha 2 adrenergic receptors, measured with (3H)-yohimbine, or high-affinity thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors, measured with agonist (3H)-U46619 and antagonist (3H)-SQ29548, occurred. However, low-affinity platelet TXA2/PGH2 receptors were decreased 40% after Pen exposure in vitro or in vivo, indicating irreversible membrane alteration. Two postreceptor biochemical events were irreversibly inhibited in platelets incubated with Pen for 24 hours in vitro or ex vivo after antibiotic treatment. Thromboxane synthesis was inhibited 28.3% to 81.7%. Agonist-induced rises in cytosolic calcium ((Ca2+)i) were inhibited 40.1% to 67.5% in vitro and 26.6% to 52.2% ex vivo. Therefore, Pen binds to platelets after prolonged exposure, resulting in irreversible dysfunction attributable to inhibition of TXA2 synthesis and impairment of the rise in (Ca2+)i. The loss of low-affinity TXA2/PGH2 receptors suggests that the primary site of action of these drugs is on the platelet membrane.« less

Reversible and irreversible drought-induced changes in the anther proteome of rice (Oryza sativa L.) genotypes IR64 and Moroberekan.

PubMed

Liu, Jian-Xiang; Bennett, John

2011-01-01

Crop yield is most sensitive to water deficit during the reproductive stage. For rice, the most sensitive yield component is spikelet fertility and the most sensitive stage is immediately before heading. Here, we examined the effect of drought on the anther proteome of two rice genotypes: Moroberekan and IR64. Water was withheld for 3 d before heading (3DBH) in well watered controls for 5 d until the flag leaf relative water content (RWC) had declined to 45-50%. Plants were then re-watered and heading occurred 2-3 d later, representing a delay of 4-5 d relative to controls. The anther proteins were separated at 3 DBH, at the end of the stress period, and at heading in stressed/re-watered plants and controls by two-dimensional (2-D) gel electrophoresis, and 93 protein spots were affected reproducibly in abundance by drought during the experiment across two rice genotypes. After drought stress, upon re-watering, expressions of 24 protein spots were irreversible in both genotypes, 60 protein spots were irreversible in IR64 but reversible in Moroberekan, only nine protein spots were irreversible in Moroberekan while reversible in IR64. Among them, there were 14 newly drought-induced protein spots in IR64; none of them was reversible on re-watering. However, there were 13 newly drought-induced protein spots in Moroberekan, 10 of them were reversible on re-watering, including six drought-induced protein spots that were not reversed in IR64. Taken together, our proteomics data reveal that drought-tolerant genotype Moroberekan possessed better recovery capability following drought and re-watering at the anther proteome level than the drought-sensitive genotype IR64. The disruptions of drought to rice anther development and pollen cell functions are also discussed in the paper.

Positive Feedback of NDT80 Expression Ensures Irreversible Meiotic Commitment in Budding Yeast

PubMed Central

Tsuchiya, Dai; Yang, Yang; Lacefield, Soni

2014-01-01

In budding yeast, meiotic commitment is the irreversible continuation of the developmental path of meiosis. After reaching meiotic commitment, cells finish meiosis and gametogenesis, even in the absence of the meiosis-inducing signal. In contrast, if the meiosis-inducing signal is removed and the mitosis-inducing signal is provided prior to reaching meiotic commitment, cells exit meiosis and return to mitosis. Previous work has shown that cells commit to meiosis after prophase I but before entering the meiotic divisions. Since the Ndt80 transcription factor induces expression of middle meiosis genes necessary for the meiotic divisions, we examined the role of the NDT80 transcriptional network in meiotic commitment. Using a microfluidic approach to analyze single cells, we found that cells commit to meiosis in prometaphase I, after the induction of the Ndt80-dependent genes. Our results showed that high-level expression of NDT80 is important for the timing and irreversibility of meiotic commitment. A modest reduction in NDT80 levels delayed meiotic commitment based on meiotic stages, although the timing of each meiotic stage was similar to that of wildtype cells. A further reduction of NDT80 resulted in the surprising finding of inappropriately uncommitted cells: withdrawal of the meiosis-inducing signal and addition of the mitosis-inducing signal to cells at stages beyond metaphase I caused return to mitosis, leading to multi-nucleate cells. Since Ndt80 enhances its own transcription through positive feedback, we tested whether positive feedback ensured the irreversibility of meiotic commitment. Ablating positive feedback in NDT80 expression resulted in a complete loss of meiotic commitment. These findings suggest that irreversibility of meiotic commitment is a consequence of the NDT80 transcriptional positive feedback loop, which provides the high-level of Ndt80 required for the developmental switch of meiotic commitment. These results also illustrate the

Chrysophanic acid reduces testosterone-induced benign prostatic hyperplasia in rats by suppressing 5α-reductase and extracellular signal-regulated kinase

PubMed Central

Kim, Hye-Lin; Jung, Yunu; Kang, JongWook; Jeong, Mi-Young; Sethi, Gautam; Ahn, Kwang Seok; Um, Jae-Young

2017-01-01

Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases in male population, of which incidence increases gradually with age. In this study, we investigated the effect of chrysophanic acid (CA) on BPH. BPH was induced by a 4-week injection of testosterone propionate (TP). Four weeks of further injection with vehicle, TP, TP + CA, TP + finasteride was carried on. In the CA treatment group, the prostate weight was reduced and the TP-induced histological changes were restored as the normal control group. CA treatment suppressed the TP-elevated prostate specific antigen (PSA) expression. In addition, 5α-reductase, a crucial factor in BPH development, was suppressed to the normal level close to the control group by CA treatment. The elevated expressions of androgen receptor (AR), estrogen receptor α and steroid receptor coactivator 1 by TP administration were also inhibited in the CA group when compared to the TP-induced BPH group. Then we evaluated the changes in three major factors of the mitogen-activated protein kinase chain during prostatic hyperplasia; extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38). While ERK was elevated in the process of BPH, JNK and p38 was not changed. This up-regulated ERK was also reduced as normal by CA treatment. Further in vitro studies with RWPE-1 cells confirmed TP-induced proliferation and elevated AR, PSA and p-ERK were all reduced by CA treatment. Overall, these results suggest a potential pharmaceutical feature of CA in the treatment of BPH. PMID:27880726

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

Irreversible climate change due to carbon dioxide emissions

PubMed Central

Solomon, Susan; Plattner, Gian-Kasper; Knutti, Reto; Friedlingstein, Pierre

2009-01-01

The severity of damaging human-induced climate change depends not only on the magnitude of the change but also on the potential for irreversibility. This paper shows that the climate change that takes place due to increases in carbon dioxide concentration is largely irreversible for 1,000 years after emissions stop. Following cessation of emissions, removal of atmospheric carbon dioxide decreases radiative forcing, but is largely compensated by slower loss of heat to the ocean, so that atmospheric temperatures do not drop significantly for at least 1,000 years. Among illustrative irreversible impacts that should be expected if atmospheric carbon dioxide concentrations increase from current levels near 385 parts per million by volume (ppmv) to a peak of 450–600 ppmv over the coming century are irreversible dry-season rainfall reductions in several regions comparable to those of the “dust bowl” era and inexorable sea level rise. Thermal expansion of the warming ocean provides a conservative lower limit to irreversible global average sea level rise of at least 0.4–1.0 m if 21st century CO2 concentrations exceed 600 ppmv and 0.6–1.9 m for peak CO2 concentrations exceeding ≈1,000 ppmv. Additional contributions from glaciers and ice sheet contributions to future sea level rise are uncertain but may equal or exceed several meters over the next millennium or longer. PMID:19179281

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

Nitric oxide-related species-induced protein oxidation: reversible, irreversible, and protective effects on enzyme function of papain.

PubMed

Väänänen, Antti J; Kankuri, Esko; Rauhala, Pekka

2005-04-15

Protein oxidation, irreversible modification, and inactivation may play key roles in various neurodegenerative disorders. Therefore, we studied the effects of the potentially in vivo occurring nitric oxide-related species on two different markers of protein oxidation: protein carbonyl generation on bovine serum albumine (BSA) and loss of activity of a cysteine-dependent protease, papain, in vitro by using Angeli's salt, papanonoate, SIN-1, and S-nitrosoglutathione (GSNO) as donors of nitroxyl, nitric oxide, peroxynitrite, and nitrosonium ions, respectively. Angeli's salt, SIN-1, and papanonoate (0-1000 microM) all generated a concentration-dependent increase in carbonyl formation on BSA (107, 60, and 45%, respectively). GSNO did not affect carbonyl formation. Papain was inhibited by Angeli's salt, SIN-1, papanonoate, and GSNO with IC50 values of 0.62, 2.3, 54, and 80 microM, respectively. Angeli's salt (3.16 microM)-induced papain inactivation was only partially reversible, while the effects of GSNO (316 microM) and papanonoate (316 microM) were reversible upon addition of excess DTT. The Angeli's salt-mediated DTT-irreversible inhibition of papain was prevented by GSNO or papanonoate pretreatment, hypothetically through mixed disulfide formation or S-nitrosylation of the catalytically critical thiol group of papain. These results, for the first time, compare the generation of carbonyls in proteins by Angeli's salt, papanonoate, and SIN-1. Furthermore, these results suggest that S-nitrosothiols may have a novel function in protecting critical thiols from irreversible oxidative damage.

Discovery of Novel Irreversible Inhibitors of Interleukin (IL)-2-inducible Tyrosine Kinase (Itk) by Targeting Cysteine 442 in the ATP Pocket

PubMed Central

Harling, John D.; Deakin, Angela M.; Campos, Sébastien; Grimley, Rachel; Chaudry, Laiq; Nye, Catherine; Polyakova, Oxana; Bessant, Christina M.; Barton, Nick; Somers, Don; Barrett, John; Graves, Rebecca H.; Hanns, Laura; Kerr, William J.; Solari, Roberto

2013-01-01

IL-2-inducible tyrosine kinase (Itk) plays a key role in antigen receptor signaling in T cells and is considered an important target for anti-inflammatory drug discovery. In order to generate inhibitors with the necessary potency and selectivity, a compound that targeted cysteine 442 in the ATP binding pocket and with an envisaged irreversible mode of action was designed. We incorporated a high degree of molecular recognition and specific design features making the compound suitable for inhaled delivery. This study confirms the irreversible covalent binding of the inhibitor to the kinase by x-ray crystallography and enzymology while demonstrating potency, selectivity, and prolonged duration of action in in vitro biological assays. The biosynthetic turnover of the kinase was also examined as a critical factor when designing irreversible inhibitors for extended duration of action. The exemplified Itk inhibitor demonstrated inhibition of both TH1 and TH2 cytokines, was additive with fluticasone propionate, and inhibited cytokine release from human lung fragments. Finally, we describe an in vivo pharmacodynamic assay that allows rapid preclinical development without animal efficacy models. PMID:23935099

[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.

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.

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 ...

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.

Inverted electro-mechanical behaviour induced by the irreversible domain configuration transformation in (K,Na)NbO3-based ceramics

PubMed Central

Huan, Yu; Wang, Xiaohui; Koruza, Jurij; Wang, Ke; Webber, Kyle G.; Hao, Yanan; Li, Longtu

2016-01-01

Miniaturization of domains to the nanometer scale has been previously reported in many piezoelectrics with two-phase coexistence. Despite the observation of nanoscale domain configuration near the polymorphic phase transition (PPT) regionin virgin (K0.5Na0.5)NbO3 (KNN) based ceramics, it remains unclear how this domain state responds to external loads and influences the macroscopic electro-mechanical properties. To this end, the electric-field-induced and stress-induced strain curves of KNN-based ceramics over a wide compositional range across PPT were characterized. It was found that the coercive field of the virgin samples was highest in PPT region, which was related to the inhibited domain wall motion due to the presence of nanodomains. However, the coercive field was found to be the lowest in the PPT region after electrical poling. This was related to the irreversible transformation of the nanodomains into micron-sized domains during the poling process. With the similar micron-sized domain configuration for all poled ceramics, the domains in the PPT region move more easily due to the additional polarization vectors. The results demonstrate that the poling process can give rise to the irreversible domain configuration transformation and then account for the inverted macroscopic piezoelectricity in the PPT region of KNN-based ceramics. PMID:26915972

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.

Altered Gene Expression Patterns During the Initiation and Promotion Stages of Neonatally Diethylstilbestrol-Induced Hyperplasia/Dysplasia/Neoplasia in the Hamster Uterus

PubMed Central

Hendry, William J.; Hariri, Hussam Y.; Alwis, Imala D.; Gunewardena, Sumedha S.; Hendry, Isabel R.

2014-01-01

Neonatal treatment of hamsters with diethylstilbestrol (DES) induces uterine hyperplasia/dysplasia/neoplasia (endometrial adenocarcinoma) in adult animals. We subsequently determined that the neonatal DES exposure event directly and permanently disrupts the developing hamster uterus (initiation stage) so that it responds abnormally when it is stimulated with estrogen in adulthood (promotion stage). To identify candidate molecular elements involved in progression of the disruption/neoplastic process, we performed: 1) immunoblot analyses and 2) microarray profiling (Affymetrix Gene Chip System) on sets of uterine protein and RNA extracts, respectively, and 3) immunohistochemical analysis on uterine sections; all from both initiation stage and promotion stage groups of animals. Here we report that: 1) progression of the neonatal DES-induced hyperplasia/dysplasia/neoplasia phenomenon in the hamster uterus involves a wide spectrum of specific gene expression alterations and 2) the gene products involved and their manner of altered expression differ dramatically during the initiation vs. promotion stages of the phenomenon. Particularly interesting changes included members in the functional categories of nuclear receptors (progesterone receptor), cell-cell interactions (E-cadherin, connexins), cytokine action (IRF-1, Stat5A), growth factor action (IRS-1), extracellular matrix component (tenascin-C), transcription factors (Nrf2, Sp1), and multi-functional nuclear protein (SAFB1). PMID:25242112

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.

[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.

IRREVERSIBLE HEMORRHAGIC SHOCK IN GERMFREE RATS

PubMed Central

Zweifach, B. W.; Gordon, H. A.; Wagner, M.; Reyniers, J. A.

1958-01-01

Evidence has been provided that a state of irreversible hemorrhagic shock can be induced in a bacteria-free environment in rats reared under germfree conditions. The response to bleeding, the duration of the hypotensive episode and the pathological changes were the same in the germfree and in normal stock rats. The findings are interpreted as evidence opposed to the concept that bacteria or bacterial products are implicated, as primary factors, in the pathogenicity of shock. PMID:13513911

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.

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

Interleukin (IL)-18, cooperatively with IL-23, induces prominent inflammation and enhances psoriasis-like epidermal hyperplasia.

PubMed

Shimoura, Noriko; Nagai, Hiroshi; Fujiwara, Susumu; Jimbo, Haruki; Yoshimoto, Takayuki; Nishigori, Chikako

2017-05-01

The interleukin (IL)-23/IL-17 axis is strongly implicated in the pathogenesis of psoriasis. Previous studies showed that IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index. However, the mechanism whereby IL-18 affects disease severity remains unknown. In this study, we investigated the effects of IL-18 on a psoriasis-like skin inflammation model induced by recombinant mouse IL-23. We found that IL-18, cooperatively with IL-23, induced prominent inflammation and enhanced psoriasis-like epidermal hyperplasia. In the skin of mice treated with IL-23 plus IL-18, the expression of interferon-γ was significantly upregulated and that of chemokine (C-X-C motif) ligand 9 (CXCL9) was synergistically increased. Histologically, strong positive signals of CXCL9 were observed around the infiltrating inflammatory cells. The current results suggest that IL-18 might synergize with IL-23 to induce a T helper 1 immune reaction, without inhibiting the IL-23/IL-17 axis, and thus may aggravate psoriatic inflammation.

The Cytoplasmic Domain of MUC1 Induces Hyperplasia in the Mammary Gland and Correlates with Nuclear Accumulation of β-Catenin

PubMed Central

Li, Yuan; Yi, Haiying; Yao, Yixin; Liao, Xiaodong; Xie, Yiqun; Yang, Jie; Yan, Zheng; Wang, Long; Lu, Shunyuan; Kuang, Ying; Gu, Mingmin; Fei, Jian; Wang, Zhugang; Huang, Lei

2011-01-01

MUC1 is an oncoprotein that is overexpressed in up to 90% of breast carcinomas. A previous in vitro study by our group demonstrated that the cytoplasmic domain of MUC1 (MUC1-CD), the minimal functional unit of MUC1, contributes to the malignant phenotype in cells by binding directly to β-catenin and protecting β-catenin from GSK3β-induced degradation. To understand the in vivo role of MUC1-CD in breast development, we generated a MUC1-CD transgenic mouse model under the control of the MMTV promoter in a C57BL/6J background, which is more resistant to breast tumor. We show that the expression of MUC1-CD in luminal epithelial cells of the mammary gland induced a hyperplasia phenotype characterized by the development of hyper-branching and extensive lobuloalveoli in transgenic mice. In addition to this hyperplasia, there was a marked increase in cellular proliferation in the mouse mammary gland. We further show that MUC1-CD induces nuclear localization of β-catenin, which is associated with a significant increase of β-catenin activity, as shown by the elevated expression of cyclin D1 and c-Myc in MMTV-MUC1-CD mice. Consistent with this finding, we observed that overexpression of MUC1-C is associated with β-catenin nuclear localization in tumor tissues and increased expression of Cyclin D1 and c-Myc in breast carcinoma specimens. Collectively, our data indicate a critical role for MUC1-CD in the development of mammary gland preneoplasia and tumorigenesis, suggesting MUC1-CD as a potential target for the diagnosis and chemoprevention of human breast cancer. PMID:21533058

Cholera toxin, a potent inducer of epidermal hyperplasia but with no tumor promoting activity in mouse skin carcinogenesis

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

Kuroki, T.; Chida, K.; Munakata, K.

1986-05-29

Intracutaneous injection of cholera toxin into mice induced epidermal hyperplasia to a greater extent than 12-O-tetra-decanoylphorbol-13-acetate. It also induced adenylate cyclase and through weakly, ornithine decarboxylase of the epidermis. Cholera toxin, however, showed no tumor promoting activity in mouse skin carcinogenesis. In the single stage promotion, cholera toxin (50 ng) was injected once a week for 10 weeks into the skin of SENCAR mice initiated with 25 ..mu..g 7,12-dimethyl-benz(a)anthracene, but no tumors developed. In the two-stage promotion test, cholera toxin (10-100 ng) was injected for one or two weeks into the initiated skin and then mezerein (4 ..mu..g) was appliedmore » twice a week for 18 weeks, but the toxin did not increase incidence or numbers of papillomas.« less

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

Amelioration of testosterone induced benign prostatic hyperplasia by Prunus species.

PubMed

Jena, Ashish Kumar; Vasisht, Karan; Sharma, Neetika; Kaur, Ramdeep; Dhingra, Mamta Sachdeva; Karan, Maninder

2016-08-22

Benign prostatic hyperplasia (BPH) is a common urological disorder of men. The ethnomedicinal use of an African plant Prunus africana (Hook.f.) Kalkman (Pygeum) in treating men's problems made it a popular remedy all over the globe for the treatment of BPH and related disorders. However, rampant collections made from the wild in Africa have pushed the plant to Appendix II of CITES demanding conservation of the species. In the present study, the aim was to unearth the protective effect of bark of different species of Prunus against BPH. The five selected Indian plants of family Rosaceae viz. Prunus amygdalus Stokes, Prunus armeniaca L., Prunus cerasoides Buch.-Ham. ex D. Don, Prunus domestica L. and Prunus persica (L.) Batsch were evaluated against P. africana (Hook.f.) Kalkman for a suitable comparison of efficacy as antiBPH agents. The antiBPH activity was evaluated in testosterone (2mg/kg/day, s.c, 21 days) induced BPH in Wistar rats. The parameters studied were body weights; histopathological examination, immunohistochemistry (PCNA) and biochemical estimations of the prostate; supported by prostatic index, testicular index, creatinine, testosterone levels; antioxidant and anti-inflammatory evaluation. The study also included chemical profiling using three markers (β-sitosterol, docosyl ferulate and ursolic acid) and estimation of β-sitosterol content through GC. The Prunus species showed the presence of all the three markers in their TLC fingerprint profile and maximum amount of β-sitosterol by GC was observed in P. domestica. Interestingly, all the species exhibited significant amelioration in testosterone induced parameters with P. domestica showing the most encouraging effect as indicated from histopathological examination, immunohistochemistry and biochemical studies. The Prunus species further showed remarkable anti-inflammatory and antioxidant activity signifying their role in interfering with various possible factors involved in BPH. These findings are

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

Differences between reversible (self-association) and irreversible aggregation of rHuG-CSF in carbohydrate and polyol formulations.

PubMed

Pavišić, Renata; Dodig, Ivana; Horvatić, Anita; Mijić, Lucija; Sedić, Mirela; Linarić, Maša Rajić; Sovulj, Ita Gruić; Preočanin, Tajana; Krajačić, Mirjana Bukvić; Cindrić, Mario

2010-11-01

Severe immunogenic and other debilitating human disorders potentially induced by protein aggregates have brought this phenomenon into the focus of biopharmaceutical science over the past decade. Depending on its driving forces, the process induced in the model protein rHuG-CSF may be either reversible or irreversible, resulting in the assembly of self-associated protein species or irreversible aggregates of various final morphologies. The aim of our work was to investigate the correlation between irreversible and reversible aggregation and the protective effect of non-specific formulation stabilisers, selected from the group of carbohydrates and polyols including trehalose, xylitol, cellobiitol, turanose, cellobiose, leucrose, lactitol, lyxose, and sorbitol, against both irreversible protein aggregation and reversible self-association processes of the rHuG-CSF. The formation of irreversible aggregates was thermally induced and evaluated using differential scanning calorimetry and size-exclusion chromatography. As opposed to the irreversible aggregation process, the process of self-association was induced by the agitation experiment by directly augmenting the protein solution contact surfaces. Absence of statistical connectivity between different stabilisers' ability to inhibit self-association or aggregation reactions indicates that these are two distinct physicochemical processes with different formulation stabilizing outcomes. Reaction mechanism of thermally induced aggregation observed in the study was in line with published literature data, while the reaction mechanism for self-association process was postulated. The postulate has been verified experimentally by isothermal calorimetry and agitation set of experiments conducted after size-exclusion chromatography and asymmetrical flow field-flow fractionation separation of monomeric, dimeric, trimeric, oligomeric, and large self-associated forms detected on multi-angle light scattering, fluorescence, UV, and

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

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

Multiscale multifractal time irreversibility analysis of stock markets

NASA Astrophysics Data System (ADS)

Jiang, Chenguang; Shang, Pengjian; Shi, Wenbin

2016-11-01

Time irreversibility is one of the most important properties of nonstationary time series. Complex time series often demonstrate even multiscale time irreversibility, such that not only the original but also coarse-grained time series are asymmetric over a wide range of scales. We study the multiscale time irreversibility of time series. In this paper, we develop a method called multiscale multifractal time irreversibility analysis (MMRA), which allows us to extend the description of time irreversibility to include the dependence on the segment size and statistical moments. We test the effectiveness of MMRA in detecting multifractality and time irreversibility of time series generated from delayed Henon map and binomial multifractal model. Then we employ our method to the time irreversibility analysis of stock markets in different regions. We find that the emerging market has higher multifractality degree and time irreversibility compared with developed markets. In this sense, the MMRA method may provide new angles in assessing the evolution stage of stock markets.

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.

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.

Effects on coagulation factor production following primary hepatomitogen-induced direct hyperplasia.

PubMed

Tatsumi, Kohei; Ohashi, Kazuo; Taminishi, Sanae; Takagi, Soichi; Utoh, Rie; Yoshioka, Akira; Shima, Midori; Okano, Teruo

2009-11-14

To investigate the molecular mechanisms involved in coagulation factor expression and/or function during direct hyperplasia (DH)-mediated liver regeneration. Direct hyperplasia-mediated liver regeneration was induced in female C57BL/6 mice by administering 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), a representative hepatomitogen. Mice were weighed and sacrificed at various time points [Day 0 (D0: prior to injection), 3 h, D1, D2, D3, and D10] after TCPOBOP administration to obtain liver and blood samples. Using the RNA samples extracted from the liver, a comprehensive analysis was performed on the hepatic gene expression profiling of coagulation-related factors by real-time RT-PCR (fibrinogen, prothrombin, factors V, VII, VIII, IX, X, XI, XII, XIIIbeta, plasminogen, antithrombin, protein C, protein S, ADAMTS13, and VWF). The corresponding plasma levels of coagulation factors (fibrinogen, prothrombin, factors V, VII, VIII, IX, X, XI, XII, XIII, and VWF) were also analyzed and compared with their mRNA levels. Gavage administration of TCPOBOP (3 mg/kg body weight) resulted in a marked and gradual increase in the weight of the mouse livers relative to the total body weight to 220% by D10 relative to the D0 (control) ratios. At the peak of liver regeneration (D1 and D2), the gene expression levels for most of the coagulation-related factors (fibrinogen, prothrombin, factors V, VII, VIII, IX, XI, XII, XIIIbeta, plasminogen, antithrombin, protein C, ADAMTS13, VWF) were found to be down-regulated in a time-dependent manner, and gradually recovered by D10 to the basal levels. Only mRNA levels of factor X and protein S failed to show any decrease during the regenerative phase. As for the plasma levels, 5 clotting factors (prothrombin, factors VIII, IX, XI, and XII) demonstrated a significant decrease (P<0.05) during the regeneration phase compared with D0. Among these 5 factors, factor IX and factor XI showed the most dramatic decline in their activities by about

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.

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

Reversible simulation of irreversible computation

NASA Astrophysics Data System (ADS)

Li, Ming; Tromp, John; Vitányi, Paul

1998-09-01

Computer computations are generally irreversible while the laws of physics are reversible. This mismatch is penalized by among other things generating excess thermic entropy in the computation. Computing performance has improved to the extent that efficiency degrades unless all algorithms are executed reversibly, for example by a universal reversible simulation of irreversible computations. All known reversible simulations are either space hungry or time hungry. The leanest method was proposed by Bennett and can be analyzed using a simple ‘reversible’ pebble game. The reachable reversible simulation instantaneous descriptions (pebble configurations) of such pebble games are characterized completely. As a corollary we obtain the reversible simulation by Bennett and, moreover, show that it is a space-optimal pebble game. We also introduce irreversible steps and give a theorem on the tradeoff between the number of allowed irreversible steps and the memory gain in the pebble game. In this resource-bounded setting the limited erasing needs to be performed at precise instants during the simulation. The reversible simulation can be modified so that it is applicable also when the simulated computation time is unknown.

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 ...

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.

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

Pacific Ciguatoxin Induces Excitotoxicity and Neurodegeneration in the Motor Cortex Via Caspase 3 Activation: Implication for Irreversible Motor Deficit.

PubMed

Asthana, Pallavi; Zhang, Ni; Kumar, Gajendra; Chine, Virendra Bhagawan; Singh, Kunal Kumar; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

2018-01-18

Consumption of fish containing ciguatera toxins or ciguatoxins (CTXs) causes ciguatera fish poisoning (CFP). In some patients, CFP recurrence occurs even years after exposure related to CTXs accumulation. Pacific CTX-1 (P-CTX-1) is one of the most potent natural substances known that causes predominantly neurological symptoms in patients; however, the underlying pathogenies of CFP remain unknown. Using clinically relevant neurobehavioral tests and electromyography (EMG) to assess effects of P-CTX-1 during the 4 months after exposure, recurrent motor strength deficit occurred in mice exposed to P-CTX-1. We detected irreversible motor strength deficits accompanied by reduced EMG activity, demyelination, and slowing of motor nerve conduction, whereas control unexposed mice fully recovered in 1 month after peripheral nerve injury. Finally, to uncover the mechanism underlying CFP, we detected reduction of spontaneous firing rate of motor cortical neurons even 6 months after exposure and increased number of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes. Increased numbers of motor cortical neuron apoptosis were detected by dUTP-digoxigenin nick end labeling assay along with activation of caspase 3. Taken together, our study demonstrates that persistence of P-CTX-1 in the nervous system induces irreversible motor deficit that correlates well with excitotoxicity and neurodegeneration detected in the motor cortical neurons.

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.

Irreversible electroporation in the treatment of locally advanced pancreas and liver metastases of colorectal carcinoma.

PubMed

Wichtowski, Mateusz; Nowaczyk, Piotr; Kocur, Jacek; Murawa, Dawid

2016-01-01

Irreversible electroporation is a new, non-thermal ablation technique in the treatment of parenchymal organ tumors which uses short high voltage pulses of electricity in order to induce apoptosis of targeted cells. In this paper the application of this method of treatment in locally advanced pancreatic cancer (LAPC) and liver cancer is analyzed. Between 04.2014 and 09.2014 two patients with LAPC and one with colorectal liver metastasis (CRLM) were qualified for treatment with irreversible electroporation. Both patients remained under constant observation and control. PubMed/Medline, Embase and Google Scholar databases were searched and eight original reports on irreversible electroporation of pancreatic and liver tumors based on the biggest groups of patients were found. Two patients with LAPC and one with CRLM were qualified for ablation with irreversible electroporation. In all three patients a successful irreversible electroporation (IRE) procedure of the whole tumor was conducted. In the minimum seven-month follow-up 100% local control was achieved - without progression. In the literature review the local response to treatment ranged from 41% to 100%. The event-free survival rate in six-month observation was 94%. Ablation with irreversible electroporation is a new non-thermal ablation technique which has been demonstrated, both in the previously published studies and in the cases described in this paper, as a safe and efficient therapeutic method for patients with LAPC and CRLM.

[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.

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.

Protective effects of seahorse extracts in a rat castration and testosterone-induced benign prostatic hyperplasia model and mouse oligospermatism model.

PubMed

Xu, Dong-Hui; Wang, Li-Hong; Mei, Xue-Ting; Li, Bing-Ji; Lv, Jun-Li; Xu, Shi-Bo

2014-03-01

This study investigated the effects of seahorse (Hippocampus spp.) extracts in a rat model of benign prostatic hyperplasia (BPH) and mouse model of oligospermatism. Compared to the sham operated group, castration and testosterone induced BPH, indicated by increased penile erection latency; decreased penis nitric oxide synthase (NOS) activity; reduced serum acid phosphatase (ACP) activity; increased prostate index; and epithelial thickening, increased glandular perimeter, increased proliferating cell nuclear antigen (PCNA) index and upregulation of basic fibroblast growth factor (bFGF) in the prostate. Seahorse extracts significantly ameliorated the histopathological changes associated with BPH, reduced the latency of penile erection and increased penile NOS activity. Administration of seahorse extracts also reversed epididymal sperm viability and motility in mice treated with cyclophosphamide (CP). Seahorse extracts have potential as a candidate marine drug for treating BPH without inducing the side effects of erectile dysfunction (ED) or oligospermatism associated with the BPH drug finasteride. Copyright © 2014 Elsevier B.V. All rights reserved.

[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.

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.

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.

Irreversible electroporation in the treatment of locally advanced pancreas and liver metastases of colorectal carcinoma

PubMed Central

Wichtowski, Mateusz; Nowaczyk, Piotr; Kocur, Jacek

2016-01-01

Aim of the study Irreversible electroporation is a new, non-thermal ablation technique in the treatment of parenchymal organ tumors which uses short high voltage pulses of electricity in order to induce apoptosis of targeted cells. In this paper the application of this method of treatment in locally advanced pancreatic cancer (LAPC) and liver cancer is analyzed. Material and methods Between 04.2014 and 09.2014 two patients with LAPC and one with colorectal liver metastasis (CRLM) were qualified for treatment with irreversible electroporation. Both patients remained under constant observation and control. PubMed/Medline, Embase and Google Scholar databases were searched and eight original reports on irreversible electroporation of pancreatic and liver tumors based on the biggest groups of patients were found. Results Two patients with LAPC and one with CRLM were qualified for ablation with irreversible electroporation. In all three patients a successful irreversible electroporation (IRE) procedure of the whole tumor was conducted. In the minimum seven-month follow-up 100% local control was achieved – without progression. In the literature review the local response to treatment ranged from 41% to 100%. The event-free survival rate in six-month observation was 94%. Conclusions Ablation with irreversible electroporation is a new non-thermal ablation technique which has been demonstrated, both in the previously published studies and in the cases described in this paper, as a safe and efficient therapeutic method for patients with LAPC and CRLM. PMID:27095938

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.

Inhibitory effect of rape pollen supercritical CO2 fluid extract against testosterone-induced benign prostatic hyperplasia in rats

PubMed Central

YANG, BI-CHENG; JIN, LI-LI; YANG, YI-FANG; LI, KUN; PENG, DAN-MING

2014-01-01

Benign prostatic hyperplasia (BPH) can lead to lower urinary tract symptoms. Rape pollen is an apicultural product that is composed of nutritionally valuable and biologically active substances. The aim of the present study was to investigate the protective effect of rape pollen supercritical CO2 fluid extract (SFE-CO2) in BPH development using a testosterone-induced BPH rat model. BPH was induced in the experimental groups by daily subcutaneous injections of testosterone for a period of 30 days. Rape pollen SFE-CO2 was administered daily by oral gavage concurrently with the testosterone injections. Animals were sacrificed at the scheduled termination and the prostates were weighed and subjected to histopathological examination. Testosterone, dihydrotestosterone (DHT), 5α-reductase and cyclooxygenase-2 (COX-2) levels were also measured. BPH-induced animals exhibited an increase in prostate weight with increased testosterone, DHT, 5α-reductase and COX-2 expression levels. However, rape pollen SFE-CO2 treatment resulted in significant reductions in the prostate index and testosterone, DHT, 5α-reductase and COX-2 levels compared with those in BPH-induced animals. Histopathological examination also demonstrated that rape pollen SFE-CO2 treatment suppressed testosterone-induced BPH. These observations indicate that rape pollen SFE-CO2 inhibits the development of BPH in rats and these effects are closely associated with reductions in DHT, 5α-reductase and COX-2 levels. Therefore, the results of the present study clearly indicate that rape pollen SFE-CO2 extract may be a useful agent in BPH treatment. PMID:24944593

Inhibitory effect of rape pollen supercritical CO2 fluid extract against testosterone-induced benign prostatic hyperplasia in rats.

PubMed

Yang, Bi-Cheng; Jin, Li-Li; Yang, Yi-Fang; Li, Kun; Peng, Dan-Ming

2014-07-01

Benign prostatic hyperplasia (BPH) can lead to lower urinary tract symptoms. Rape pollen is an apicultural product that is composed of nutritionally valuable and biologically active substances. The aim of the present study was to investigate the protective effect of rape pollen supercritical CO 2 fluid extract (SFE-CO 2 ) in BPH development using a testosterone-induced BPH rat model. BPH was induced in the experimental groups by daily subcutaneous injections of testosterone for a period of 30 days. Rape pollen SFE-CO 2 was administered daily by oral gavage concurrently with the testosterone injections. Animals were sacrificed at the scheduled termination and the prostates were weighed and subjected to histopathological examination. Testosterone, dihydrotestosterone (DHT), 5α-reductase and cyclooxygenase-2 (COX-2) levels were also measured. BPH-induced animals exhibited an increase in prostate weight with increased testosterone, DHT, 5α-reductase and COX-2 expression levels. However, rape pollen SFE-CO 2 treatment resulted in significant reductions in the prostate index and testosterone, DHT, 5α-reductase and COX-2 levels compared with those in BPH-induced animals. Histopathological examination also demonstrated that rape pollen SFE-CO 2 treatment suppressed testosterone-induced BPH. These observations indicate that rape pollen SFE-CO 2 inhibits the development of BPH in rats and these effects are closely associated with reductions in DHT, 5α-reductase and COX-2 levels. Therefore, the results of the present study clearly indicate that rape pollen SFE-CO 2 extract may be a useful agent in BPH treatment.

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.

Emergent Irreversibility and Entanglement Spectrum Statistics

NASA Astrophysics Data System (ADS)

Chamon, Claudio; Hamma, Alioscia; Mucciolo, Eduardo R.

2014-06-01

We study the problem of irreversibility when the dynamical evolution of a many-body system is described by a stochastic quantum circuit. Such evolution is more general than a Hamiltonian one, and since energy levels are not well defined, the well-established connection between the statistical fluctuations of the energy spectrum and irreversibility cannot be made. We show that the entanglement spectrum provides a more general connection. Irreversibility is marked by a failure of a disentangling algorithm and is preceded by the appearance of Wigner-Dyson statistical fluctuations in the entanglement spectrum. This analysis can be done at the wave-function level and offers an alternative route to study quantum chaos and quantum integrability.

Trehalose delays the reversible but not the irreversible thermal denaturation of cutinase.

PubMed

Baptista, R P; Cabral, J M; Melo, E P

2000-12-20

The effect of trehalose (0.5 M) on the thermal stability of cutinase in the alkaline pH range was studied. The thermal unfolding induced by increasing temperature was analyzed in the absence and in the presence of trehalose according to a two-state model (which assumes that only the folded and unfolded states of cutinase were present). Trehalose delays the reversible unfolding. The midpoint temperature of the unfolding transition (Tm) increases by 4.0 degrees C and 2. 6 degrees C at pH 9.2 and 10.5, respectively, in the presence of trehalose. At pH 9.2 the thermal unfolding occurs at higher temperatures (Tm is 52.6 degrees C compared to 42.0 degrees C at pH 10.5) and a refolding yield of around 80% was obtained upon cooling. This pH value was chosen to study the irreversible inactivation (long-term stability) of cutinase. Temperatures in the transition range from folded to unfolded state were selected and the rate constants of irreversible inactivation determined. Inactivation followed first-order kinetics and trehalose reduced the observed rate constants of inactivation, pointing to a stabilizing effect on the irreversible inactivation step of thermal denaturation. However, if the contribution of reversible unfolding on the irreversible inactivation of cutinase was taken into account, i.e., considering the fraction of cutinase molecules in the reversible unfolded conformation, the intrinsic rate constants can be calculated. Based on the intrinsic rate constants it was concluded that trehalose does not delay the irreversible inactivation. This conclusion was further supported by comparing the activation energy of the irreversible inactivation in the absence and in the presence of trehalose. The apparent activation energy in the absence and in the presence of trehalose were 67 and 99 Kcal/mol, respectively. The activation energy calculated from intrinsic rate constants was higher in the absence (30 Kcal/mol) than in the presence of trehalose (16 Kcal/mol), showing

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

Dose-response effect of Red Maca (Lepidium meyenii) on benign prostatic hyperplasia induced by testosterone enanthate.

PubMed

Gasco, M; Villegas, L; Yucra, S; Rubio, J; Gonzales, G F

2007-08-01

The main goal of this study was to determine the effect of a freeze-dried aqueous extract of the red variety of Lepidium meyenii (Red Maca) on testosterone-induced benign prostatic hyperplasia (BPH) in adult rats of the Holtzman strain. Rats were treated with freeze-dried aqueous extract of Red Maca at doses of 0, 0.01, 0.05, 0.1, and 0.5 g/kg body wt. A positive control group received Finasteride (0.6 mg/kg body wt.). After treatment, the animals were sacrificed, and the ventral prostate was extracted, and weighed. HPLC was used to determine the presence of glucosinolates in Red Maca. The prostate weight diminished in a dose-dependent fashion in rats treated with Red Maca. The effect of Red Maca was better than that observed with Finasteride. Finasteride, but not Red Maca, reduced seminal vesicles weight. Analysis of the HPLC indicated the presence of benzyl glucosinolate (Glucotropaeolin) with a content of 0.639%. Serum testosterone levels were not affected by Red Maca. Moreover, serum testosterone levels were not related to prostate or seminal vesicles weight in rats treated with vehicle and Red Maca. In conclusion, Red Maca administered orally in rats seems to exert an inhibitory effect at a level post DHT conversion, on the BPH-induced experimentally, although a direct measure of reductase action would still be required.

The recovery of bladder epithelial hyperplasia caused by a melamine diet-induced bladder calculus in mice.

PubMed

Sun, Ying; Jiang, Yi-Na; Xu, Chang-Fu; Du, Yun-Xia; Zhang, Jiao-Jiao; Yan, Yang; Gao, Xiao-Li

2014-02-01

Applying a model of bladder epithelial hyperplasia (BEH) caused by melamine-induced bladder calculus (BC), the recovery of BEH after melamine withdrawal was investigated. One experiment, comprising untreated, melamine and recovery groups, was conducted in Balb/c mice. Each group included 4 subgroups. Mice were fed normal-diet in untreated or a melamine-diet in other groups. The melamine-diet was then substituted with normal-diet in recovery group. Both of BC and BEH were observed after 14 and 56 days of melamine-diet. The BC is relatively uniform at the same melamine-diet durations. The BEH was diffuse with many mitotic figures, 4-7 rows of nuclei, and well-defined umbrella/intermediate cells. No marked differences in BEH degree were observed in the two different melamine-diet durations. On 4-42 days after melamine withdrawal, BC was not found, as the progressive regression with complete regression of BEH was observed, along with well-defined ageing/apoptotic cells in the superficial regions of BEH regression tissue. Conclusion, the melamine-induced BEH is relatively uniform, may be self-limiting in rows of nuclei, and can return to normal. Melamine withdrawal duration is critical for the BEH regression. Tissue of the BEH and its regression is ideal for exploring the renewal as well as growth biology of mammalian urothelium. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Irreversible entropy model for damage diagnosis in resistors

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

Cuadras, Angel, E-mail: angel.cuadras@upc.edu; Crisóstomo, Javier; Ovejas, Victoria J.

2015-10-28

We propose a method to characterize electrical resistor damage based on entropy measurements. Irreversible entropy and the rate at which it is generated are more convenient parameters than resistance for describing damage because they are essentially positive in virtue of the second law of thermodynamics, whereas resistance may increase or decrease depending on the degradation mechanism. Commercial resistors were tested in order to characterize the damage induced by power surges. Resistors were biased with constant and pulsed voltage signals, leading to power dissipation in the range of 4–8 W, which is well above the 0.25 W nominal power to initiate failure. Entropymore » was inferred from the added power and temperature evolution. A model is proposed to understand the relationship among resistance, entropy, and damage. The power surge dissipates into heat (Joule effect) and damages the resistor. The results show a correlation between entropy generation rate and resistor failure. We conclude that damage can be conveniently assessed from irreversible entropy generation. Our results for resistors can be easily extrapolated to other systems or machines that can be modeled based on their resistance.« less

Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer

PubMed Central

Hu, YunLong; Chen, TingTing; Peng, BoYa; Gao, NingNing; Jin, ZhenChao; Jia, TieLiu; Zhang, Na; Wang, ZhuLin; Jin, GuangYi

2016-01-01

Prolonged treatment of breast cancer with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) often results in acquired resistance and a narrow therapeutic index. One strategy to improve the therapeutic effects of EGFR TKIs is to combine them with drugs used for other clinical indications. Ethacrynic acid (EA) is an FDA approved drug that may have antitumor effects and may enhance the cytotoxicity of chemotherapeutic agents by binding to glutathione and inhibiting WNT signaling. While the α,β-unsaturated-keto structure of EA is similar to that of irreversible TKIs, the mechanism of action of EA when combined with irreversible EGFR TKIs in breast cancer remains unknown. We therefore investigated the combination of irreversible EGFR TKIs and EA. We found that irreversible EGFR TKIs and EA synergistically inhibit breast cancer both in vitro and in vivo. The combination of EGFR TKIs and EA induces necrosis and cell cycle arrest and represses WNT/β-catenin signaling as well as MAPK-ERK1/2 signaling. We conclude that EA synergistically enhances the antitumor effects of irreversible EGFR TKIs in breast cancer. PMID:27487128

Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer.

PubMed

Liu, Bing; Huang, XinPing; Hu, YunLong; Chen, TingTing; Peng, BoYa; Gao, NingNing; Jin, ZhenChao; Jia, TieLiu; Zhang, Na; Wang, ZhuLin; Jin, GuangYi

2016-09-06

Prolonged treatment of breast cancer with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) often results in acquired resistance and a narrow therapeutic index. One strategy to improve the therapeutic effects of EGFR TKIs is to combine them with drugs used for other clinical indications. Ethacrynic acid (EA) is an FDA approved drug that may have antitumor effects and may enhance the cytotoxicity of chemotherapeutic agents by binding to glutathione and inhibiting WNT signaling. While the α,β-unsaturated-keto structure of EA is similar to that of irreversible TKIs, the mechanism of action of EA when combined with irreversible EGFR TKIs in breast cancer remains unknown. We therefore investigated the combination of irreversible EGFR TKIs and EA. We found that irreversible EGFR TKIs and EA synergistically inhibit breast cancer both in vitro and in vivo. The combination of EGFR TKIs and EA induces necrosis and cell cycle arrest and represses WNT/β-catenin signaling as well as MAPK-ERK1/2 signaling. We conclude that EA synergistically enhances the antitumor effects of irreversible EGFR TKIs in breast cancer.

[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.

Magnetic-field-induced irreversible antiferromagnetic-ferromagnetic phase transition around room temperature in as-cast Sm-Co based SmCo7-xSix alloys

NASA Astrophysics Data System (ADS)

Feng, D. Y.; Zhao, L. Z.; Liu, Z. W.

2016-04-01

A magnetic-field-induced irreversible metamagnetic phase transition from antiferro- to ferromagnetism, which leads to an anomalous initial-magnetization curve lying outside the magnetic hysteresis loop, is reported in arc-melted SmCo7-xSix alloys. The transition temperatures are near room temperature, much higher than other compounds with similar initial curves. Detailed investigation shows that this phenomenon is dependent on temperature, magnetic field and Si content and shows some interesting characteristics. It is suggested that varying interactions between the Sm and Co layers in the crystal are responsible for the formation of a metastable AFM structure, which induces the anomalous phenomenon in as-cast alloys. The random occupation of 3g sites by Si and Co atoms also has an effect on this phenomenon.

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 ...

Ischemia-induced glomerular parietal epithelial cells hyperplasia: Commonly misdiagnosed cellular crescent in renal biopsy.

PubMed

Zeng, Yeting; Wang, Xinrui; Xie, Feilai; Zheng, Zhiyong

2017-08-01

Ischemic pseudo-cellular crescent (IPCC) that is induced by ischemia and composed of hyperplastic glomerular parietal epithelial cells resembles cellular crescent. In this study, we aimed to assess the clinical and pathological features of IPCC in renal biopsy to avoid over-diagnosis and to determine the diagnostic basis. 4 IPCC cases diagnosed over a 4-year period (2012-2015) were evaluated for the study. Meanwhile, 5 cases of ANCA-associated glomerulonephritis and 5 cases of lupus nephritis (LN) were selected as control. Appropriate clinical data, morphology, and immunohistochemical features of all cases were retrieved. Results showed that the basement membrane of glomerulus with IPCC appeared as a concentric twisted ball, and glomerular cells of the lesion were reduced even entirely absent, and the adjacent afferent arterioles showed sclerosis or luminal stenosis. Furthermore, immune globulin deposition, vasculitis, and fibrinous exudate have not been observed in IPCC. While the cellular crescents showed diverse characteristics in both morphology and immunostaining in the control group. Therefore, these results indicated that IPCC is a sort of ischemic reactive hyperplasia and associated with sclerosis, stenosis, or obstruction of adjacent afferent arterioles, which is clearly different from cellular crescents result from glomerulonephritis. Copyright © 2017 Elsevier GmbH. All rights reserved.

Attribution of irreversible loss to anthropogenic climate change

NASA Astrophysics Data System (ADS)

Huggel, Christian; Bresch, David; Hansen, Gerrit; James, Rachel; Mechler, Reinhard; Stone, Dáithí; Wallimann-Helmer, Ivo

2016-04-01

The Paris Agreement (2015) under the UNFCCC has anchored loss and damage in a separate article which specifies that understanding and support should be enhanced in areas addressing loss and damage such as early warning, preparedness, insurance and resilience. Irreversible loss is a special category under loss and damage but there is still missing clarity over what irreversible loss actually includes. Many negative impacts of climate change may be handled or mitigated by existing risk management, reduction and absorption approaches. Irreversible loss, however, is thought to be insufficiently addressed by risk management. Therefore, countries potentially or actually affected by irreversible loss are calling for other measures such as compensation, which however is highly contested in international climate policy. In Paris (2015) a decision was adopted that loss and damage as defined in the respective article of the agreement does not involve compensation and liability. Nevertheless, it is likely that some sort of mechanism will eventually need to come into play for irreversible loss due to anthropogenic climate change, which might involve compensation, other forms of non-monetary reparation, or transformation. Furthermore, climate litigation has increasingly been attempted to address negative effects of climate change. In this context, attribution is important to understand the drivers of change, what counts as irreversible loss due to climate change, and, possibly, who or what is responsible. Here we approach this issue by applying a detection and attribution perspective on irreversible loss. We first analyze detected climate change impacts as assessed in the IPCC Fifth Assessment Report. We distinguish between irreversible loss in physical, biological and human systems, and accordingly identify the following candidates of irreversible loss in these systems: loss of glaciers and ice sheets, loss of subsurface ice (permafrost) and related loss of lake systems; loss

Bee venom suppresses testosterone-induced benign prostatic hyperplasia by regulating the inflammatory response and apoptosis.

PubMed

Chung, Kyung-Sook; An, Hyo-Jin; Cheon, Se-Yun; Kwon, Ki-Rok; Lee, Kwang-Ho

2015-12-01

Benign prostatic hyperplasia (BPH), which is a common disorder in aging men, involves inflammation that is associated with an imbalance between cell proliferation and cell death. Because current BPH drug treatments have undesirable side effects, the development of well-tolerated and effective alternative medicines to treat BPH is of interest. Bee venom (BV) has been used in traditional medicine to treat conditions, such as arthritis and rheumatism, and pain. Although inflammation has been associated with BPH and BV has strong anti-inflammatory effects, the effects of BV on BPH are not fully understood. Therefore, in this study, we evaluated the efficacy of BV against testosterone-induced BPH in rats. BV decreased prostate weight compared to the untreated group. In addition, BV suppressed serum dihydrotestosterone concentration levels and the levels of proliferating cell nuclear antigen in the histological analysis. Furthermore, BV significantly decreased the levels of the apoptotic suppressors, Bcl-2 and Bcl-xL, and increased the levels of the proapoptotic factors, Bax and caspase-3 activation. These results suggested that BV suppressed the development of BPH and has good potential as a treatment for BPH. © 2015 by the Society for Experimental Biology and Medicine.

Bee venom suppresses testosterone-induced benign prostatic hyperplasia by regulating the inflammatory response and apoptosis

PubMed Central

Chung, Kyung-Sook; An, Hyo-Jin; Cheon, Se-Yun; Kwon, Ki-Rok

2015-01-01

Benign prostatic hyperplasia (BPH), which is a common disorder in aging men, involves inflammation that is associated with an imbalance between cell proliferation and cell death. Because current BPH drug treatments have undesirable side effects, the development of well-tolerated and effective alternative medicines to treat BPH is of interest. Bee venom (BV) has been used in traditional medicine to treat conditions, such as arthritis and rheumatism, and pain. Although inflammation has been associated with BPH and BV has strong anti-inflammatory effects, the effects of BV on BPH are not fully understood. Therefore, in this study, we evaluated the efficacy of BV against testosterone-induced BPH in rats. BV decreased prostate weight compared to the untreated group. In addition, BV suppressed serum dihydrotestosterone concentration levels and the levels of proliferating cell nuclear antigen in the histological analysis. Furthermore, BV significantly decreased the levels of the apoptotic suppressors, Bcl-2 and Bcl-xL, and increased the levels of the proapoptotic factors, Bax and caspase-3 activation. These results suggested that BV suppressed the development of BPH and has good potential as a treatment for BPH. PMID:26085572

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.

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.

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.

Partially-irreversible sorption of formaldehyde in five polymers

NASA Astrophysics Data System (ADS)

Ye, Wei; Cox, Steven S.; Zhao, Xiaomin; Frazier, Charles E.; Little, John C.

2014-12-01

Due to its environmental ubiquity and concern over its potential toxicity, the mass-transfer characteristics of formaldehyde are of critical importance to indoor air quality research. Previous studies have suggested that formaldehyde mass transfer in polymer is partially irreversible. In this study, mechanisms that could cause the observed irreversibility were investigated. Polycarbonate and four other polymeric matrices were selected and subjected to formaldehyde sorption/desorption cycles. Mass transfer of formaldehyde was partially irreversible in all cases, and three potential mechanisms were evaluated. First, attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) analysis was used to investigate possible formaldehyde polymerization on polymer surfaces. ATR-FTIR showed no detectable paraformaldehyde or formaldehyde on the film surfaces that had been exposed to formaldehyde and air. ATR-FTIR did detect aliphatic acids suggesting oxidation had occurred on film surfaces as a result of exposure to formaldehyde. However, additional study suggested that air is not the primary cause for irreversibility. Second, statistical physics theory was tested as a possible explanation. According to this theory, reversible and irreversible sorption could be taking place simultaneously. The irreversible fraction should be constant during sorption and the fraction could be determined by performing a complete sorption/desorption test. The sorption/desorption data was consistent with this theory. Third, chemisorption was considered as another possible cause for irreversibility. Extraction/fluorimetry testing of post-sorption and post-desorption polymer films showed measurable quantities of formaldehyde suggesting that some of the chemisorbed formaldehyde was reversible at the higher extraction temperature. Further quantitative study on chemical reaction products is needed.

[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.

On irreversible adsorption of electron-donating compounds in aqueous solution

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

Tamon, Hajime; Atsushi, Masanori; Okazaki, Morio

Activated carbons and synthetic adsorbents have been used for liquid purification and wastewater treatment. The feasibility of an adsorption process depends greatly on the cost of regeneration of spent adsorbents. If irreversible adsorption occurs, regeneration of spent adsorbent is very difficult. Hence, it is very important to understand why irreversible adsorption appears in aqueous solution. In the adsorption of electron-donating compounds such as phenol, aniline, L-phenylalanine, and L-tyrosine from aqueous solution, irreversibility was observed on activated carbon and graphite. The compounds, except L-tyrosine, were reversibly adsorbed on a synthetic adsorbent. In the case where the carbonaceous adsorbents contacted the aqueousmore » solution containing electron-donating compounds for a long time, the irreversible amount adsorbed increased with the contact time. A two-state adsorption model was used to explain why the irreversible adsorption of electron-donating compound appears in aqueous solution. First, the compound is adsorbed in the precursor state for irreversible adsorption, and then moves into its irreversible state over a potential energy barrier after a long contact time. The appearance of irreversible adsorption was qualitatively explained by the two-state adsorption model.« less

A statistical model describing combined irreversible electroporation and electroporation-induced blood-brain barrier disruption.

PubMed

Sharabi, Shirley; Kos, Bor; Last, David; Guez, David; Daniels, Dianne; Harnof, Sagi; Mardor, Yael; Miklavcic, Damijan

2016-03-01

Electroporation-based therapies such as electrochemotherapy (ECT) and irreversible electroporation (IRE) are emerging as promising tools for treatment of tumors. When applied to the brain, electroporation can also induce transient blood-brain-barrier (BBB) disruption in volumes extending beyond IRE, thus enabling efficient drug penetration. The main objective of this study was to develop a statistical model predicting cell death and BBB disruption induced by electroporation. This model can be used for individual treatment planning. Cell death and BBB disruption models were developed based on the Peleg-Fermi model in combination with numerical models of the electric field. The model calculates the electric field thresholds for cell kill and BBB disruption and describes the dependence on the number of treatment pulses. The model was validated using in vivo experimental data consisting of rats brains MRIs post electroporation treatments. Linear regression analysis confirmed that the model described the IRE and BBB disruption volumes as a function of treatment pulses number (r(2) = 0.79; p < 0.008, r(2) = 0.91; p < 0.001). The results presented a strong plateau effect as the pulse number increased. The ratio between complete cell death and no cell death thresholds was relatively narrow (between 0.88-0.91) even for small numbers of pulses and depended weakly on the number of pulses. For BBB disruption, the ratio increased with the number of pulses. BBB disruption radii were on average 67% ± 11% larger than IRE volumes. The statistical model can be used to describe the dependence of treatment-effects on the number of pulses independent of the experimental setup.

A statistical model describing combined irreversible electroporation and electroporation-induced blood-brain barrier disruption

PubMed Central

Sharabi, Shirley; Kos, Bor; Last, David; Guez, David; Daniels, Dianne; Harnof, Sagi; Miklavcic, Damijan

2016-01-01

Background Electroporation-based therapies such as electrochemotherapy (ECT) and irreversible electroporation (IRE) are emerging as promising tools for treatment of tumors. When applied to the brain, electroporation can also induce transient blood-brain-barrier (BBB) disruption in volumes extending beyond IRE, thus enabling efficient drug penetration. The main objective of this study was to develop a statistical model predicting cell death and BBB disruption induced by electroporation. This model can be used for individual treatment planning. Material and methods Cell death and BBB disruption models were developed based on the Peleg-Fermi model in combination with numerical models of the electric field. The model calculates the electric field thresholds for cell kill and BBB disruption and describes the dependence on the number of treatment pulses. The model was validated using in vivo experimental data consisting of rats brains MRIs post electroporation treatments. Results Linear regression analysis confirmed that the model described the IRE and BBB disruption volumes as a function of treatment pulses number (r2 = 0.79; p < 0.008, r2 = 0.91; p < 0.001). The results presented a strong plateau effect as the pulse number increased. The ratio between complete cell death and no cell death thresholds was relatively narrow (between 0.88-0.91) even for small numbers of pulses and depended weakly on the number of pulses. For BBB disruption, the ratio increased with the number of pulses. BBB disruption radii were on average 67% ± 11% larger than IRE volumes. Conclusions The statistical model can be used to describe the dependence of treatment-effects on the number of pulses independent of the experimental setup. PMID:27069447

Cigarette smoke suppresses Bik to cause epithelial cell hyperplasia and mucous cell metaplasia.

PubMed

Mebratu, Yohannes A; Schwalm, Kurt; Smith, Kevin R; Schuyler, Mark; Tesfaigzi, Yohannes

2011-06-01

Aberrant regulation of airway epithelial cell numbers in airways leads to increased mucous secretions in chronic lung diseases such as chronic bronchitis. Because the Bcl-2 family of proteins is crucial for airway epithelial homeostasis, identifying the players that reduce cigarette smoke (CS)-induced mucous cell metaplasia can help to develop effective therapies. To identify the Bcl-2 family of proteins that play a role in reducing CS-induced mucous cell metaplasia. We screened for dysregulated expression of the Bcl-2 family members. We identified Bik to be significantly reduced in bronchial brushings of patients with chronic epithelial cell hyperplasia compared with nondiseased control subjects. Reduced Bik but increased MUC5AC mRNA levels were also detected when normal human airway epithelial cells (HAECs) were exposed to CS or when autopsy tissues from former smokers with and without chronic bronchitis were compared. Similarly, exposure of C57Bl/6 mice to CS resulted in increased numbers of epithelial and mucous cells per millimeter of basal lamina, along with reduced Bik but increased Muc5ac expression, and this change was sustained even when mice were allowed to recover in filtered air for 8 weeks. Restoring Bik expression significantly suppressed CS-induced mucous cell metaplasia in differentiated primary HAEC cultures and in airways of mice in vivo. Bik blocked nuclear translocation of phospho-ERK1/2 to induce apoptosis of HAECs. The conserved Leu61 within Bik and ERK1/2 activation were essential to induce cell death in hyperplastic mucous cells. These studies show that CS suppresses Bik expression to block airway epithelia cell death and thereby increases epithelial cell hyperplasia in chronic bronchitis.

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

Time irreversibility from symplectic non-squeezing

NASA Astrophysics Data System (ADS)

Kalogeropoulos, Nikolaos

2018-04-01

The issue of how time reversible microscopic dynamics gives rise to macroscopic irreversible processes has been a recurrent issue in Physics since the time of Boltzmann whose ideas shaped, and essentially resolved, such an apparent contradiction. Following Boltzmann's spirit and ideas, but employing Gibbs's approach, we advance the view that macroscopic irreversibility of Hamiltonian systems of many degrees of freedom can be also seen as a result of the symplectic non-squeezing theorem.

Testosterone-induced benign prostatic hyperplasia rat and dog as facile models to assess drugs targeting lower urinary tract symptoms

PubMed Central

Li, Jing; Tian, Yanxin; Guo, Shimeng; Gu, Haifeng; Yuan, Qianting; Xie, Xin

2018-01-01

Benign prostatic hyperplasia (BPH) is an age-related disease, affecting a majority of elderly men worldwide. Medical management of BPH is an alternative to surgical treatment of this disease. Currently, α1-adrenergic receptor (α1-AR) antagonists are among the first line drugs to treat BPH by reducing the tension of urinary track and thus the obstructive symptoms in voiding. In drug development, old male dogs with spontaneous BPH are considered the golden standard of the animal models. However, old dogs (>6 years) are expensive and not all old dogs develop BPH. So it is necessary to develop more accessible animal models for drug efficacy evaluation. Here we describe the development of testosterone-induced BPH models in both rats and young adult dogs and their applications in the in vivo evaluation of α1-AR antagonist. The BPH rats and dogs induced by chronic testosterone treatment have significantly increased micturition frequency and reduced mean voided volume, very similar to the clinical symptoms of BPH patients. Silodosin, an α1-AR antagonist, significantly reduces the urinary frequency and increases the voided volume in BPH model animals in a dose-dependent manner. The results demonstrate that testosterone-induced BPH rat and dog models might provide a more efficient way to evaluate micturition behavior in anti-BPH drug studies. PMID:29351556

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

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

Absorption media for irreversibly gettering thionyl chloride

DOEpatents

Buffleben, George; Goods, Steven H.; Shepodd, Timothy; Wheeler, David R.; Whinnery, Jr., LeRoy

2002-01-01

Thionyl chloride is a hazardous and reactive chemical used as the liquid cathode in commercial primary batteries. Contrary to previous thinking, ASZM-TEDA.RTM. carbon (Calgon Corporation) reversibly absorbs thionyl chloride. Thus, several candidate materials were examined as irreversible getters for thionyl chloride. The capacity, rate and effect of temperature were also explored. A wide variety of likely materials were investigated through screening experiments focusing on the degree of heat generated by the reaction as well as the material absorption capacity and irreversibility, in order to help narrow the group of possible getter choices. More thorough, quantitative measurements were performed on promising materials. The best performing getter was a mixture of ZnO and ASZM-TEDA.RTM. carbon. In this example, the ZnO reacts with thionyl chloride to form ZnCl.sub.2 and SO.sub.2. The SO.sub.2 is then irreversibly gettered by ASZM-TEDA.RTM. carbon. This combination of ZnO and carbon has a high capacity, is irreversible and functions effectively above -20.degree. C.

Spectral dependence of irreversible light-induced fluorescence quenching: Chlorophyll forms with maximal emission at 700-702 and 705-710nm as spectroscopic markers of conformational changes in the core complex.

PubMed

Nematov, Sherzod; Casazza, Anna Paola; Remelli, William; Khuvondikov, Vakhobjon; Santabarbara, Stefano

2017-07-01

The spectral dependence of the irreversible non-photochemical fluorescence quenching associated with photoinhibition in vitro has been comparatively investigated in thylakoid membranes, PSII enriched particles and PSII core complexes isolated from spinach. The analysis of the fluorescence emission spectra of dark-adapted and quenched samples as a function of the detection temperature in the 280-80K interval, indicates that Chlorophyll spectral forms having maximal emission in the 700-702nm and 705-710nm ranges gain relative intensity in concomitance with the establishment of irreversible light-induced quenching, acting thereby as spectroscopic markers. The relative enhancement of the 700-702nm and 705-710nm forms emission could be due either to an increase of their stoichiometric abundance or to their intrinsically low fluorescence quantum yields. These two factors, that can also coexist, need to be promoted by light-induced alterations in chromophore-protein as well as chromophore-chromophore interactions. The bands centred at about 701 and 706nm are also observed in the PSII core complex, suggesting their, at least partial, localisation in proximity to the reaction centre, and the occurrence of light-induced conformational changes in the core subunits. Copyright © 2017 Elsevier B.V. All rights reserved.

Vanillic acid attenuates testosterone-induced benign prostatic hyperplasia in rats and inhibits proliferation of prostatic epithelial cells.

PubMed

Jung, Yunu; Park, Jinbong; Kim, Hye-Lin; Youn, Dong-Hyun; Kang, JongWook; Lim, Seona; Jeong, Mi-Young; Sethi, Gautam; Park, Sung-Joo; Ahn, Kwang Seok; Um, Jae-Young

2017-10-20

Benign prostatic hyperplasia (BPH) is a common disease in the male population, especially in elderly men. Vanillic acid (VA), a dihydroxybenzoic derivative used as a flavoring agent, is reported to have an anti-inflammatory effect. However, there are no reports of its effects on BPH to date. BPH was induced with a pre-4-week treatment of daily subcutaneous injections of testosterone propionate (TP), and the normal control group received injections of ethanol with corn oil instead. Six weeks of further injections were done with (a) ethanol with corn oil, (b) TP only, (c) TP + finasteride, and (d) TP + VA. Finasteride was used as a positive control group. VA had protective effects on the TP-induced BPH. In the VA treatment group, the prostate weight was reduced, and the histological changes including the epithelial thickness and lumen area were restored like in the normal control group. Furthermore, in the VA treatment group, two proliferation related factors, high molecular weight cytokeratin 34βE12 and α smooth muscle actin, were significantly down-regulated compared to the TP-induced BPH group. The expressions of dihydrotestosterone and 5α-reductase, the most crucial factors in BPH development, were suppressed by VA treatment. Expressions of the androgen receptor, estrogen receptor α and steroid receptor coactivator 1 were also significantly inhibited by VA compared to the TP-induced BPH group. In addition, we established an in vitro model for BPH by treating a normal human prostatic epithelial cell line RWPE-1 with TP. VA successfully inhibited proliferation and BPH-related factors in a concentration-dependent manner in this newly established model. These results suggest a new and potential pharmaceutical therapy of VA in the treatment of BPH.

Vanillic acid attenuates testosterone-induced benign prostatic hyperplasia in rats and inhibits proliferation of prostatic epithelial cells

PubMed Central

Kim, Hye-Lin; Youn, Dong-Hyun; Kang, JongWook; Lim, Seona; Jeong, Mi-Young; Sethi, Gautam; Park, Sung-Joo; Ahn, Kwang Seok; Um, Jae-Young

2017-01-01

Benign prostatic hyperplasia (BPH) is a common disease in the male population, especially in elderly men. Vanillic acid (VA), a dihydroxybenzoic derivative used as a flavoring agent, is reported to have an anti-inflammatory effect. However, there are no reports of its effects on BPH to date. BPH was induced with a pre-4-week treatment of daily subcutaneous injections of testosterone propionate (TP), and the normal control group received injections of ethanol with corn oil instead. Six weeks of further injections were done with (a) ethanol with corn oil, (b) TP only, (c) TP + finasteride, and (d) TP + VA. Finasteride was used as a positive control group. VA had protective effects on the TP-induced BPH. In the VA treatment group, the prostate weight was reduced, and the histological changes including the epithelial thickness and lumen area were restored like in the normal control group. Furthermore, in the VA treatment group, two proliferation related factors, high molecular weight cytokeratin 34βE12 and α smooth muscle actin, were significantly down-regulated compared to the TP-induced BPH group. The expressions of dihydrotestosterone and 5α-reductase, the most crucial factors in BPH development, were suppressed by VA treatment. Expressions of the androgen receptor, estrogen receptor α and steroid receptor coactivator 1 were also significantly inhibited by VA compared to the TP-induced BPH group. In addition, we established an in vitro model for BPH by treating a normal human prostatic epithelial cell line RWPE-1 with TP. VA successfully inhibited proliferation and BPH-related factors in a concentration-dependent manner in this newly established model. These results suggest a new and potential pharmaceutical therapy of VA in the treatment of BPH. PMID:29152074

Irreversible thermodynamic analysis and application for molecular heat engines

NASA Astrophysics Data System (ADS)

Lucia, Umberto; Açıkkalp, Emin

2017-09-01

Is there a link between the macroscopic approach to irreversibility and microscopic behaviour of the systems? Consumption of free energy keeps the system away from a stable equilibrium. Entropy generation results from the redistribution of energy, momentum, mass and charge. This concept represents the essence of the thermodynamic approach to irreversibility. Irreversibility is the result of the interaction between systems and their environment. The aim of this paper is to determine lost works in a molecular engine and compare results with macro (classical) heat engines. Firstly, irreversible thermodynamics are reviewed for macro and molecular cycles. Secondly, irreversible thermodynamics approaches are applied for a quantum heat engine with -1/2 spin system. Finally, lost works are determined for considered system and results show that macro and molecular heat engines obey same limitations. Moreover, a quantum thermodynamic approach is suggested in order to explain the results previously obtained from an atomic viewpoint.

Irreversibility and entanglement spectrum statistics in quantum circuits

NASA Astrophysics Data System (ADS)

Shaffer, Daniel; Chamon, Claudio; Hamma, Alioscia; Mucciolo, Eduardo R.

2014-12-01

We show that in a quantum system evolving unitarily under a stochastic quantum circuit the notions of irreversibility, universality of computation, and entanglement are closely related. As the state evolves from an initial product state, it gets asymptotically maximally entangled. We define irreversibility as the failure of searching for a disentangling circuit using a Metropolis-like algorithm. We show that irreversibility corresponds to Wigner-Dyson statistics in the level spacing of the entanglement eigenvalues, and that this is obtained from a quantum circuit made from a set of universal gates for quantum computation. If, on the other hand, the system is evolved with a non-universal set of gates, the statistics of the entanglement level spacing deviates from Wigner-Dyson and the disentangling algorithm succeeds. These results open a new way to characterize irreversibility in quantum systems.

Maternal obesogenic diet induces endometrial hyperplasia, an early hallmark of endometrial cancer, in a diethylstilbestrol mouse model.

PubMed

Owuor, Theresa O; Reid, Michaela; Reschke, Lauren; Hagemann, Ian; Greco, Suellen; Modi, Zeel; Moley, Kelle H

2018-01-01

Thirty-eight percent of US adult women are obese, meaning that more children are now born of overweight and obese mothers, leading to an increase in predisposition to several adult onset diseases. To explore this phenomenon, we developed a maternal obesity animal model by feeding mice a diet composed of high fat/ high sugar (HF/HS) and assessed both maternal diet and offspring diet on the development of endometrial cancer (ECa). We show that maternal diet by itself did not lead to ECa initiation in wildtype offspring of the C57Bl/6J mouse strain. While offspring fed a HF/HS post-weaning diet resulted in poor metabolic health and decreased uterine weight (regardless of maternal diet), it did not lead to ECa. We also investigated the effects of the maternal obesogenic diet on ECa development in a Diethylstilbestrol (DES) carcinogenesis mouse model. All mice injected with DES had reproductive tract lesions including decreased number of glands, condensed and hyalinized endometrial stroma, and fibrosis and increased collagen deposition that in some mice extended into the myometrium resulting in extensive disruption and loss of the inner and outer muscular layers. Fifty percent of DES mice that were exposed to maternal HF/HS diet developed several features indicative of the initial stages of carcinogenesis including focal glandular and atypical endometrial hyperplasia versus 0% of their Chow counterparts. There was an increase in phospho-Akt expression in DES mice exposed to maternal HF/HS diet, a regulator of persistent proliferation in the endometrium, and no difference in total Akt, phospho-PTEN and total PTEN expression. In summary, maternal HF/HS diet exposure induces endometrial hyperplasia and other precancerous phenotypes in mice treated with DES. This study suggests that maternal obesity alone is not sufficient for the development of ECa, but has an additive effect in the presence of a secondary insult such as DES.

The detection of local irreversibility in time series based on segmentation

NASA Astrophysics Data System (ADS)

Teng, Yue; Shang, Pengjian

2018-06-01

We propose a strategy for the detection of local irreversibility in stationary time series based on multiple scale. The detection is beneficial to evaluate the displacement of irreversibility toward local skewness. By means of this method, we can availably discuss the local irreversible fluctuations of time series as the scale changes. The method was applied to simulated nonlinear signals generated by the ARFIMA process and logistic map to show how the irreversibility functions react to the increasing of the multiple scale. The method was applied also to series of financial markets i.e., American, Chinese and European markets. The local irreversibility for different markets demonstrate distinct characteristics. Simulations and real data support the need of exploring local irreversibility.

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

Proliferative activity of denture-induced fibrous inflammatory hyperplasia analyzed by proliferating cell nuclear antigen labeling index.

PubMed

Coelho, C M; Zucoloto, S

1999-01-01

Denture-induced fibrous inflammatory hyperplasia (FIH) occurs around the borders of an ill-fitting denture. There has been no report in the literature concerning epithelial proliferative activity in FIH. The purpose of this study was to observe the labeling of proliferating cell nuclear antigen (PCNA) and evaluate its clinicopathologic results. The labeling index (LI) was assessed by using the PCNA, a nuclear protein synthesized mainly in the G1-S stages of the cell cycle that could be detected immunohistochemically by the monoclonal antibody PC10. The PCNA LI was assessed in FIH specimens, in clinically normal specimens 1 cm from the FIH margin (adjacent group), and in clinically normal specimens located at least 2 cm from the adjacent group; the last were considered the control group. The mean PCNA LI values in the basal, parabasal, and overall epithelial layers were similar in FIH and in the adjacent group and were significantly higher than in the control group. These data support the importance of the surgical treatment of FIH with wide excision (about 1 cm) since the clinically normal tissue around the lesion could be histologically altered.

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).

Emergent irreversibility and entanglement spectrum statistics

NASA Astrophysics Data System (ADS)

Mucciolo, Eduardo; Chamon, Claudio; Hamma, Alioscia

2014-03-01

We study the problem of irreversibility when the dynamical evolution of a many-body system is described by a stochastic quantum circuit. Such evolution is more general than Hamitonian, and since energy levels are not well defined, the well-established connection between the statistical fluctuations of the energy spectrum and irreversibility cannot be made. We show that the entanglement spectrum provides a more general connection. Irreversibility is marked by a failure of a disentangling algorithm and is preceded by the appearance of Wigner-Dyson statistical fluctuations in the entanglement spectrum. This analysis can be done at the wavefunction level and offers a new route to study quantum chaos and quantum integrability. We acknowledge financial support from the U.S. National Science Foundation through grants CCF 1116590 and CCF 1117241, from the National Basic Research Program of China through grants 2011CBA00300 and 2011CBA00301, and from the National Natural Science Fo.

Hydrogen-rich saline attenuates vascular smooth muscle cell proliferation and neointimal hyperplasia by inhibiting reactive oxygen species production and inactivating the Ras-ERK1/2-MEK1/2 and Akt pathways.

PubMed

Chen, Yali; Jiang, Jinyao; Miao, Huibing; Chen, Xingjuan; Sun, Xuejun; Li, Yongjun

2013-03-01

Hydrogen-rich saline has been reported to prevent neointimal hyperplasia induced by carotid balloon injury. The purpose of the present study was to further investigate the molecular mechanisms underlying this phenomenon. Daily injection of a hydrogen-rich saline solution (HRSS) in rats was employed to study the effect of hydrogen on balloon injury-induced neointimal hyperplasia and the neointima/media ratio was assessed. HRSS significantly decreased the neointima area and neointima/media ratio in a dose-dependent manner. In vitro effects of hydrogen on fetal bovine serum (FBS)-induced vascular smooth muscle cell (VSMC) proliferation were also investigated. Hydrogen-rich medium (HRM) inhibited rat VSMC proliferation and migration induced by 10% FBS. FBS-induced reactive oxygen species (ROS) production and activation of intracellular Ras, MEK1/2, ERK1/2, proliferative cell nuclear antigen (PCNA), Akt were significantly inhibited by HRM. In addition, HRM blocked FBS-induced progression from the G0/G1 to the S-phase and increased the apoptosis rate of VSMCs. These results showed that hydrogen-rich saline was able to attenuate FBS-induced VSMC proliferation and neointimal hyperplasia by inhibiting ROS production and inactivating the Ras-ERK1/2-MEK1/2 and Akt pathways. Thus, HRSS may have potential therapeutic relevance for the prevention of human restenosis.

Cigarette Smoke Suppresses Bik To Cause Epithelial Cell Hyperplasia and Mucous Cell Metaplasia

PubMed Central

Mebratu, Yohannes A.; Schwalm, Kurt; Smith, Kevin R.; Schuyler, Mark; Tesfaigzi, Yohannes

2011-01-01

Rationale: Aberrant regulation of airway epithelial cell numbers in airways leads to increased mucous secretions in chronic lung diseases such as chronic bronchitis. Because the Bcl-2 family of proteins is crucial for airway epithelial homeostasis, identifying the players that reduce cigarette smoke (CS)-induced mucous cell metaplasia can help to develop effective therapies. Objectives: To identify the Bcl-2 family of proteins that play a role in reducing CS-induced mucous cell metaplasia. Methods: We screened for dysregulated expression of the Bcl-2 family members. Measurements and Main Results: We identified Bik to be significantly reduced in bronchial brushings of patients with chronic epithelial cell hyperplasia compared with nondiseased control subjects. Reduced Bik but increased MUC5AC mRNA levels were also detected when normal human airway epithelial cells (HAECs) were exposed to CS or when autopsy tissues from former smokers with and without chronic bronchitis were compared. Similarly, exposure of C57Bl/6 mice to CS resulted in increased numbers of epithelial and mucous cells per millimeter of basal lamina, along with reduced Bik but increased Muc5ac expression, and this change was sustained even when mice were allowed to recover in filtered air for 8 weeks. Restoring Bik expression significantly suppressed CS-induced mucous cell metaplasia in differentiated primary HAEC cultures and in airways of mice in vivo. Bik blocked nuclear translocation of phospho-ERK1/2 to induce apoptosis of HAECs. The conserved Leu61 within Bik and ERK1/2 activation were essential to induce cell death in hyperplastic mucous cells. Conclusions: These studies show that CS suppresses Bik expression to block airway epithelia cell death and thereby increases epithelial cell hyperplasia in chronic bronchitis. PMID:21317312

Withania coagulans Extract Induces Cell Apoptosis and Inhibits COX-2 Expression in a Rat Model of Benign Prostatic Hyperplasia

PubMed Central

Sarbishegi, Maryam; Khajavi, Ozra; Arab, Mohammad Reza

2016-01-01

Background Phytotherapy is a popular treatment option in cases of benign prostatic hyperplasia (BPH), with many different herbal products being used for the treatment of this condition. Withania coagulans (WC) is an herbal medicine that has shown anti-tumoral, anti-inflammatory, and antioxidant effects. Objectives This study examined the effect of Withania coagulans extract (WCE) on prostatic cell apoptosis and cyclooxygenase-2 (COX-2) expression in cases of benign prostatic hyperplasia (BPH) in rats. Methods Forty Wistar rats were equally divided into five groups: control, sham, BPH, BPH + WCE, and BPH + CLX (celecoxib) as a positive control group. The induction of BPH was achieved via the subcutaneous injection of 3 mg/kg of testosterone propionate (TP) daily for 28 days. The animals received WCE, celecoxib, or distilled water by oral gavage accompanied by the TP injection. After four weeks, the prostate glands of the rats were weighed to measure the prostatic index (PI). The ventral lobes of the prostates were dissected and processed with paraffin blocks in order to study the number of mast cells. A TUNEL analysis was performed to evaluate the cell apoptosis, while the expression of COX-2 was examined using immunohistochemistry. Results BPH was obvious in the ventral lobe of the prostate, and the administration of WCE markedly decreased the PI and the number of mast cells (P < 0.001) in the BPH rats. Additionally, the WCE treatment induced prostatic cell apoptosis when compared to the BPH group. Furthermore, following the WCE treatment, the expression of COX-2 in the prostatic tissues was significantly decreased when compared to the BPH groups. Conclusions According to the results of this study, WCE was effective in the treatment of BPH in rats. It may therefore have beneficial effects in the treatment of patients with BPH. PMID:27878112

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.

Pathology of non-thermal irreversible electroporation (N-TIRE)-induced ablation of the canine brain.

PubMed

Rossmeisl, John H; Garcia, Paulo A; Roberston, John L; Ellis, Thomas L; Davalos, Rafael V

2013-01-01

This study describes the neuropathologic features of normal canine brain ablated with non-thermal irreversible electroporation (N-TIRE). The parietal cerebral cortices of four dogs were treated with N-TIRE using a dose-escalation protocol with an additional dog receiving sham treatment. Animals were allowed to recover following N-TIRE ablation and the effects of treatment were monitored with clinical and magnetic resonance imaging examinations. Brains were subjected to histopathologic and ultrastructural assessment along with Bcl-2, caspase-3, and caspase-9 immunohistochemical staining following sacrifice 72 h post-treatment. Adverse clinical effects of N-TIRE were only observed in the dog treated at the upper energy tier. MRI and neuropathologic examinations indicated that N-TIRE ablation resulted in focal regions of severe cytoarchitectural and blood-brain-barrier disruption. Lesion size correlated to the intensity of the applied electrical field. N-TIRE-induced lesions were characterized by parenchymal necrosis and hemorrhage; however, large blood vessels were preserved. A transition zone containing parenchymal edema, perivascular inflammatory cuffs, and reactive gliosis was interspersed between the necrotic focus and normal neuropil. Apoptotic labeling indices were not different between the N-TIRE-treated and control brains. This study identified N-TIRE pulse parameters that can be used to safely create circumscribed foci of brain necrosis while selectively preserving major vascular structures.

Irreversibility of financial time series: A graph-theoretical approach

NASA Astrophysics Data System (ADS)

Flanagan, Ryan; Lacasa, Lucas

2016-04-01

The relation between time series irreversibility and entropy production has been recently investigated in thermodynamic systems operating away from equilibrium. In this work we explore this concept in the context of financial time series. We make use of visibility algorithms to quantify, in graph-theoretical terms, time irreversibility of 35 financial indices evolving over the period 1998-2012. We show that this metric is complementary to standard measures based on volatility and exploit it to both classify periods of financial stress and to rank companies accordingly. We then validate this approach by finding that a projection in principal components space of financial years, based on time irreversibility features, clusters together periods of financial stress from stable periods. Relations between irreversibility, efficiency and predictability are briefly discussed.

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.

Protective Effects of Lepidium meyenii (Maca) Aqueous Extract and Lycopene on Testosterone Propionate-Induced Prostatic Hyperplasia in Mice.

PubMed

Zou, Ying; Aboshora, Waleed; Li, Jing; Xiao, Tiancun; Zhang, Lianfu

2017-08-01

The inhibitory effect of maca extractant, lycopene, and their combination was evaluated in benign prostatic hyperplasia (BPH) mice induced by testosterone propionate. Mice were divided into a saline group, solvent control group and testosterone propionate-induced BPH mice [BPH model group, solvent BPH model group, benzyl glucosinolate group (1.44 mg/kg), maca group (60 mg/kg), lycopene treated (15, 5, and 2.5 mg/kg), maca (30 mg/kg) combine lycopene treated (7.5, 2.5, and 1.25 mg/kg), and finasteride treated]. Benzyl glucosinolate was used in order to evaluate its pharmacological activity on BPH to find out whether it is the major active component of maca aqueous extract. Finasteride was used as positive control. The compounds were administered once for 30 successive days. Compared with solvent BPH model group, BPH mice fed with maca (30 mg/kg) and lycopene (7.5 mg/kg) combination exhibited significant reductions in the prostatic index, prostatic acid phospatase, estradiol, testosterone, and dihydrotestosterone levels in serum. They also had similar histological compared with those aspects observed in the mice in the solvent control group. The results indicated that combination of maca and lycopene synergistically inhibits BPH in mice. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Irreversible thermodynamics of Poisson processes with reaction.

PubMed

Méndez, V; Fort, J

1999-11-01

A kinetic model is derived to study the successive movements of particles, described by a Poisson process, as well as their generation. The irreversible thermodynamics of this system is also studied from the kinetic model. This makes it possible to evaluate the differences between thermodynamical quantities computed exactly and up to second-order. Such differences determine the range of validity of the second-order approximation to extended irreversible thermodynamics.

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.

Hypoxic Stress Forces Irreversible Differentiation of a Majority of Mouse Trophoblast Stem Cells Despite FGF4.

PubMed

Yang, Yu; Arenas-Hernandez, Marcia; Gomez-Lopez, Nardhy; Dai, Jing; Parker, Graham C; Puscheck, Elizabeth E; Rappolee, Daniel A

2016-11-01

Hypoxic, hyperosmotic, and genotoxic stress slow mouse trophoblast stem cell (mTSC) proliferation, decrease potency/stemness, and increase differentiation. Previous reports suggest a period of reversibility in stress-induced mTSC differentiation. Here we show that hypoxic stress at 0.5% O 2 decreased potency factor protein by ∼60%-90% and reduced growth to nil. Hypoxia caused a 35-fold increase in apoptosis at Day 3 and a 2-fold increase at Day 6 above baseline. The baseline apoptosis rate was only 0.3%. Total protein was never less than baseline during hypoxic treatment, suggesting 0.5% O 2 is a robust, nonmorbid stressor. Hypoxic stress induced ∼50% of trophoblast giant cell (TGC) differentiation with a simultaneous 5- to 6-fold increase in the TGC product antiluteolytic prolactin family 3, subfamily d, member 1 (PRL3D1), despite the presence of fibroblast growth factor 4 (FGF4). Hypoxia-induced TGC differentiation was also supported by potency and differentiation mRNA marker analysis. FGF4 removal at 20% O 2 committed cell fate towards irreversible differentiation at 2 days, with similar TGC percentages after an additional 3 days of culture under potency conditions when FGF4 was readded or under differentiation conditions without FGF4. However, hypoxic stress required 4 days to irreversibly differentiate cells. Runted stem cell growth, forced differentiation of fewer cells, and irreversible differentiation limit total available stem cell population. Were mTSCs to respond to stress in a similar mode in vivo, miscarriage might occur as a result, which should be tested in the future. © 2016 by the Society for the Study of Reproduction, Inc.

Flaxseed suppressed prostatic epithelial proliferation in a rat model of benign prostatic hyperplasia.

PubMed

Said, Mahmoud M; Hassan, Nahla S; Schlicht, Michael J; Bosland, Maarten C

2015-01-01

Benign prostatic hyperplasia (BPH), a disease occurring frequently among elderly males, is a slow progressive enlargement of the fibromuscular and epithelial structures of the prostate gland. Dietary factors may influence the prostate and exert an influence on prostatic growth and disease. The current study was undertaken to investigate the protective effect of dietary flaxseed supplementation against testosterone-induced prostatic hyperplasia in male rats. Forty male Wistar rats were divided into 5 groups: (1) untreated control; (2) treatment with testosterone propionate (TP) to induce prostate enlargement; (3) TP-treated group fed a diet containing 5% milled flaxseed; (4) TP-treated group fed a diet containing 10% milled flaxseed; and (5) TP-treated group fed a diet containing 20 ppm finasteride. Treatment with TP significantly increased the absolute and relative weights of different prostatic lobes, serum testosterone (T), and testosterone/estradiol ratio, as well as prostatic vascular endothelial growth factor (VEGF) expression, RNA synthesis per cell, and epithelial cell proliferation, detected as Ki67 labeling. Histopathological examination did not reveal marked differences in acinar morphology in ventral prostate, whereas morphometric analysis showed significantly increased epithelial cell height. Co-administration of flaxseed or finasteride with TP significantly reduced prostatic VEFG, epithelial cell proliferation, and RNA/DNA ratio, along with a significant increase in serum T and testosterone/estradiol ratio compared with TP-only-treated rats. Our results indicate that flaxseed, similar to the 5α-reductase inhibitor finasteride, blocked TP-induced prostate enlargement in a rat model of BPH, likely through suppression of prostatic VEFG and cellular proliferation.

Observer detection of image degradation caused by irreversible data compression processes

NASA Astrophysics Data System (ADS)

Chen, Ji; Flynn, Michael J.; Gross, Barry; Spizarny, David

1991-05-01

Irreversible data compression methods have been proposed to reduce the data storage and communication requirements of digital imaging systems. In general, the error produced by compression increases as an algorithm''s compression ratio is increased. We have studied the relationship between compression ratios and the detection of induced error using radiologic observers. The nature of the errors was characterized by calculating the power spectrum of the difference image. In contrast with studies designed to test whether detected errors alter diagnostic decisions, this study was designed to test whether observers could detect the induced error. A paired-film observer study was designed to test whether induced errors were detected. The study was conducted with chest radiographs selected and ranked for subtle evidence of interstitial disease, pulmonary nodules, or pneumothoraces. Images were digitized at 86 microns (4K X 5K) and 2K X 2K regions were extracted. A full-frame discrete cosine transform method was used to compress images at ratios varying between 6:1 and 60:1. The decompressed images were reprinted next to the original images in a randomized order with a laser film printer. The use of a film digitizer and a film printer which can reproduce all of the contrast and detail in the original radiograph makes the results of this study insensitive to instrument performance and primarily dependent on radiographic image quality. The results of this study define conditions for which errors associated with irreversible compression cannot be detected by radiologic observers. The results indicate that an observer can detect the errors introduced by this compression algorithm for compression ratios of 10:1 (1.2 bits/pixel) or higher.

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

Reversible and irreversible heat engine and refrigerator cycles

NASA Astrophysics Data System (ADS)

Leff, Harvey S.

2018-05-01

Although no reversible thermodynamic cycles exist in nature, nearly all cycles covered in textbooks are reversible. This is a review, clarification, and extension of results and concepts for quasistatic, reversible and irreversible processes and cycles, intended primarily for teachers and students. Distinctions between the latter process types are explained, with emphasis on clockwise (CW) and counterclockwise (CCW) cycles. Specific examples of each are examined, including Carnot, Kelvin and Stirling cycles. For the Stirling cycle, potentially useful task-specific efficiency measures are proposed and illustrated. Whether a cycle behaves as a traditional refrigerator or heat engine can depend on whether it is reversible or irreversible. Reversible and irreversible-quasistatic CW cycles both satisfy Carnot's inequality for thermal efficiency, η ≤ η C a r n o t . Irreversible CCW cycles with two reservoirs satisfy the coefficient of performance inequality K ≤ K C a r n o t . However, an arbitrary reversible cycle satisfies K ≥ K C a r n o t when compared with a reversible Carnot cycle operating between its maximum and minimum temperatures, a potentially counterintuitive result.

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

Formation of Irreversible H-bonds in Cellulose Materials

Treesearch

Umesh P. Agarwal; Sally A. Ralph; Rick S. Reiner; Nicole M. Stark

2015-01-01

Understanding of formation of irreversible Hbonds in cellulose is important in a number of fields. For example, fields as diverse as pulp and paper and enzymatic saccharification of cellulose are affected. In the present investigation, the phenomenon of formation of irreversible H-bonds is studied in a variety of celluloses and under two different drying conditions....

Cynanchum wilfordii Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia by Regulating 5α-Reductase and Androgen Receptor Activities in a Rat Model

PubMed Central

Lee, Gyuok; Shin, Jawon; Choi, Hakjoon; Jo, Ara; Pan, SangO; Bae, Donghyuck; Lee, Yongwook; Choi, Chulyung

2017-01-01

Benign prostatic hyperplasia (BPH) is characterized by uncontrolled proliferation of the prostate gland. Cynanchum wilfordii has been reported to improve sexual behavior in male rats. In this study, we investigated the protective effect of an aqueous extract of C. wilfordii (CWW) against BPH development in a testosterone-induced BPH rat model. The rats were divided into the following six groups: sham/vehicle; BPH/vehicle; BPH/finasteride; and three CWW doses (50, 100, and 200 mg/kg). After a 4-week treatment with CWW, the rats were euthanized at scheduled times, and their prostates were weighed, followed by a histopathological examination. Prostate growth inhibition rates in rats administered CWW 50, 100, and 200 mg/kg were 54.5%, 51.8%, and 50.1%, respectively. The BPH/CWW group showed decreased serum testosterone and dihydrotestosterone (DHT) levels compared to the BPH/vehicle group. Furthermore, the BPH/CWW group showed reduced prostate testosterone and DHT levels compared to the BPH/vehicle group. Mechanistically, the reverse transcription-polymerase chain reaction revealed downregulated mRNA expression levels of the androgen receptor, 5α-reductase, and B-cell lymphoma-2 (Bcl-2) in the BPH/CWW200 group compared with those in the testosterone-induced groups. In conclusion, these findings show the effectiveness of CWW in slowing the progression of testosterone-induced BPH in rats. PMID:28953224

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.

Non-input analysis for incomplete trapping irreversible tracer with PET.

PubMed

Ohya, Tomoyuki; Kikuchi, Tatsuya; Fukumura, Toshimitsu; Zhang, Ming-Rong; Irie, Toshiaki

2013-07-01

When using metabolic trapping type tracers, the tracers are not always trapped in the target tissue; i.e., some are completely trapped in the target, but others can be eliminated from the target tissue at a measurable rate. The tracers that can be eliminated are termed 'incomplete trapping irreversible tracers'. These incomplete trapping irreversible tracers may be clinically useful when the tracer β-value, the ratio of the tracer (metabolite) elimination rate to the tracer efflux rate, is under approximately 0.1. In this study, we propose a non-input analysis for incomplete trapping irreversible tracers based on the shape analysis (Shape), a non-input analysis used for irreversible tracers. A Monte Carlo simulation study based on experimental monkey data with two actual PET tracers (a complete trapping irreversible tracer [(11)C]MP4A and an incomplete trapping irreversible tracer [(18)F]FEP-4MA) was performed to examine the effects of the environmental error and the tracer elimination rate on the estimation of the k3-parameter (corresponds to metabolic rate) using Shape (original) and modified Shape (M-Shape) analysis. The simulation results were also compared with the experimental results obtained with the two PET tracers. When the tracer β-value was over 0.03, the M-Shape method was superior to the Shape method for the estimation of the k3-parameter. The simulation results were also in reasonable agreement with the experimental ones. M-Shape can be used as the non-input analysis of incomplete trapping irreversible tracers for PET study. Copyright © 2013 Elsevier Inc. All rights reserved.

Quantifying irreversible movement in steep, fractured bedrock permafrost on Matterhorn (CH)

NASA Astrophysics Data System (ADS)

Weber, Samuel; Beutel, Jan; Faillettaz, Jérome; Hasler, Andreas; Krautblatter, Michael; Vieli, Andreas

2017-02-01

Understanding rock slope kinematics in steep, fractured bedrock permafrost is a challenging task. Recent laboratory studies have provided enhanced understanding of rock fatigue and fracturing in cold environments but were not successfully confirmed by field studies. This study presents a unique time series of fracture kinematics, rock temperatures and environmental conditions at 3500 m a. s. l. on the steep, strongly fractured Hörnligrat of the Matterhorn (Swiss Alps). Thanks to 8 years of continuous data, the longer-term evolution of fracture kinematics in permafrost can be analyzed with an unprecedented level of detail. Evidence for common trends in spatiotemporal pattern of fracture kinematics could be found: a partly reversible seasonal movement can be observed at all locations, with variable amplitudes. In the wider context of rock slope stability assessment, we propose separating reversible (elastic) components of fracture kinematics, caused by thermoelastic strains, from the irreversible (plastic) component due to other processes. A regression analysis between temperature and fracture displacement shows that all instrumented fractures exhibit reversible displacements that dominate fracture kinematics in winter. Furthermore, removing this reversible component from the observed displacement enables us to quantify the irreversible component. From this, a new metric - termed index of irreversibility - is proposed to quantify relative irreversibility of fracture kinematics. This new index can identify periods when fracture displacements are dominated by irreversible processes. For many sensors, irreversible enhanced fracture displacement is observed in summer and its initiation coincides with the onset of positive rock temperatures. This likely indicates thawing-related processes, such as meltwater percolation into fractures, as a forcing mechanism for irreversible displacements. For a few instrumented fractures, irreversible displacements were found at the

Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

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

Tamura, Akitoshi, E-mail: akitoshi-tamura@ds-pharma.co.jp; Miyawaki, Izuru; Yamada, Toru

It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination ofmore » serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

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

BYK191023 (2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3h-imidazo[4,5-b]pyridine) is an NADPH- and time-dependent irreversible inhibitor of inducible nitric-oxide synthase.

PubMed

Tiso, Mauro; Strub, Andreas; Hesslinger, Christian; Kenney, Claire T; Boer, Rainer; Stuehr, Dennis J

2008-04-01

Imidazopyridine derivates were recently shown to be a novel class of selective and arginine-competitive inhibitors of inducible nitric-oxide synthase (iNOS), and 2-[2-(4-methoxypyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine (BYK191023) was found to have very high selectivity in enzymatic and cellular models ( Mol Pharmacol 69: 328-337, 2006 ). Here, we show that BYK191023 irreversibly inactivates murine iNOS in an NADPH- and time-dependent manner, whereas it acts only as a reversible l-arginine-competitive inhibitor in the absence of NADPH or during anaerobic preincubation. Time-dependent irreversible inhibition by BYK191023 could also be demonstrated in intact cells using the RAW macrophage or iNOS-overexpressing human embryonic kidney 293 cell lines. The mechanism of BYK191023 inhibition in the presence of NADPH was studied using spectral, kinetic, chromatographic, and radioligand binding methods. BYK191023-bound iNOS was spectrally indistinguishable from l-arginine-bound iNOS, pointing to an interaction of BYK191023 with the catalytic center of the enzyme. [(3)H]BYK191023 was recovered quantitatively from irreversibly inactivated iNOS, and no inhibitor metabolite was detected by high-performance liquid chromatography (HPLC). Size exclusion chromatography revealed only about 20% iNOS dissociation into monomers. Furthermore, HPLC and spectrophotometric analysis showed that the irreversible inhibition was associated with loss of heme from iNOS and a reduced ability to form the distinctive ferrous heme-CO complex (cytochrome P450). Thus, enzyme inactivation is mainly caused by heme loss, and it occurs in the inhibitor-bound enzyme in the presence of electron flux from NADPH.

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

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.

Reversible and irreversible heat transfer by radiation

NASA Astrophysics Data System (ADS)

del Río, Fernando; de la Selva, Sara María Teresa

2015-05-01

The theme of heat transfer by radiation is absent from most textbooks on thermodynamics, and its treatment in the applied literature presents some basic discrepancies concerning the validity of the Clausius relation between the quantity of heat exchanged, δ Q, and the accompanying entropy change, dS. We review the reversible and irreversible heat transfers by radiation to clarify the validity of the Clausius relation, and we show that in both cases, the Clausius relation is obeyed, as it should be. We also deal with radiation diluted by the presence of matter, introducing a dilution coefficient, ϕ, and an irreversibility factor, χ (φ ). This treatment requires the use of the correct relation between energy and heat fluxes, the spectral fluxes of energy and entropy, and Planck’s equation for the entropy of monochromatic radiation. For the irreversible case of diluted radiation, we recover the ratio between the fluxes of heat and entropy that agree with Clausius’ inequality, including an irreversibility factor, (4/3)χ (φ ). An improved modification for the explicit function χ (φ ) is given. As an illustration, the fluxes of energy and entropy from the Sun to the Earth are obtained. We also calculate the fluxes re-emitted by the Earth, taking into account the greenhouse effect. We find the value of 1.258 W{{m}-2}{{K}-1} for the re-emitted entropy flux after the radiation has been thermalized, which is much larger than the incident flux, in agreement with other authors.

The SAT Protein of Porcine Parvovirus Accelerates Viral Spreading through Induction of Irreversible Endoplasmic Reticulum Stress.

PubMed

Mészáros, István; Tóth, Renáta; Olasz, Ferenc; Tijssen, Peter; Zádori, Zoltán

2017-08-15

The SAT protein (SATp) of porcine parvovirus (PPV) accumulates in the endoplasmic reticulum (ER), and SAT deletion induces the slow-spreading phenotype. The in vitro comparison of the wild-type Kresse strain and its SAT knockout (SAT - ) mutant revealed that prolonged cell integrity and late viral release are responsible for the slower spreading of the SAT - virus. During PPV infection, regardless of the presence or absence of SATp, the expression of downstream ER stress response proteins (Xbp1 and CHOP) was induced. However, in the absence of SATp, significant differences in the quantity and the localization of CHOP were detected, suggesting a role of SATp in the induction of irreversible ER stress in infected cells. The involvement of the induction of irreversible ER stress in porcine testis (PT) cell necrosis and viral egress was confirmed by treatment of infected cells by ER stress-inducing chemicals (MG132, dithiothreitol, and thapsigargin), which accelerated the egress and spreading of both the wild-type and the SAT - viruses. UV stress induction had no beneficial effect on PPV infection, underscoring the specificity of ER stress pathways in the process. However, induction of CHOP and its nuclear translocation cannot alone be responsible for the biological effect of SAT, since nuclear CHOP could not complement the lack of SAT in a coexpression experiment. IMPORTANCE SATp is encoded by an alternative open reading frame of the PPV genome. Earlier we showed that SATp of the attenuated PPV NADL-2 strain accumulates in the ER and accelerates virus release and spreading. Our present work revealed that slow spreading is a general feature of SAT - PPVs and is the consequence of prolonged cell integrity. PPV infection induced ER stress in infected cells regardless of the presence of SATp, as demonstrated by the morphological changes of the ER and expression of the stress response proteins Xbp1 and CHOP. However, the presence of SATp made the ER stress more severe and

The SAT Protein of Porcine Parvovirus Accelerates Viral Spreading through Induction of Irreversible Endoplasmic Reticulum Stress

PubMed Central

Tóth, Renáta; Olasz, Ferenc; Tijssen, Peter; Zádori, Zoltán

2017-01-01

ABSTRACT The SAT protein (SATp) of porcine parvovirus (PPV) accumulates in the endoplasmic reticulum (ER), and SAT deletion induces the slow-spreading phenotype. The in vitro comparison of the wild-type Kresse strain and its SAT knockout (SAT−) mutant revealed that prolonged cell integrity and late viral release are responsible for the slower spreading of the SAT− virus. During PPV infection, regardless of the presence or absence of SATp, the expression of downstream ER stress response proteins (Xbp1 and CHOP) was induced. However, in the absence of SATp, significant differences in the quantity and the localization of CHOP were detected, suggesting a role of SATp in the induction of irreversible ER stress in infected cells. The involvement of the induction of irreversible ER stress in porcine testis (PT) cell necrosis and viral egress was confirmed by treatment of infected cells by ER stress-inducing chemicals (MG132, dithiothreitol, and thapsigargin), which accelerated the egress and spreading of both the wild-type and the SAT− viruses. UV stress induction had no beneficial effect on PPV infection, underscoring the specificity of ER stress pathways in the process. However, induction of CHOP and its nuclear translocation cannot alone be responsible for the biological effect of SAT, since nuclear CHOP could not complement the lack of SAT in a coexpression experiment. IMPORTANCE SATp is encoded by an alternative open reading frame of the PPV genome. Earlier we showed that SATp of the attenuated PPV NADL-2 strain accumulates in the ER and accelerates virus release and spreading. Our present work revealed that slow spreading is a general feature of SAT− PPVs and is the consequence of prolonged cell integrity. PPV infection induced ER stress in infected cells regardless of the presence of SATp, as demonstrated by the morphological changes of the ER and expression of the stress response proteins Xbp1 and CHOP. However, the presence of SATp made the ER stress more

Vinpocetine attenuates neointimal hyperplasia in diabetic rat carotid arteries after balloon injury.

PubMed

Wang, Ke; Wen, Li; Peng, Wenhui; Li, Hailing; Zhuang, Jianhui; Lu, Yuyan; Liu, Baoxin; Li, Xiankai; Li, Weiming; Xu, Yawei

2014-01-01

Diabetes exacerbates abnormal vascular smooth muscle cell (VSMC) accumulation in response to arterial wall injury. Vinpocetine has been shown to improve vascular remolding; however, little is known about the direct effects of vinpocetine on vascular complications mediated by diabetes. The objective of this study was to determine the effects of vinpocetine on hyperglycemia-facilitated neointimal hyperplasia and explore its possible mechanism. Nondiabetic and diabetic rats were subjected to balloon injury of the carotid artery followed by 3-week treatment with either vinpocetine (10 mg/kg/day) or saline. Morphological analysis and proliferating cell nuclear antigen (PCNA) immunostaining were performed on day 21. Rat VSMCs proliferation was determined with 5-ethynyl-20-deoxyuridine cell proliferation assays. Chemokinesis was monitored with scratch assays, and production of reactive oxygen species (ROS) was assessed using a 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) flow cytometric assay. Apoptosis was detected by annexin V-FITC/PI flow cytometric assay. Cell signaling was assessed by immunblotting. Vinpocetine prevented intimal hyperplasia in carotid arteries in both normal (I/M ratio: 93.83 ± 26.45% versus 143.2 ± 38.18%, P<0.05) and diabetic animals (I/M ratio: 120.5 ± 42.55% versus 233.46 ± 33.98%, P<0.05) when compared to saline. The in vitro study demonstrated that vinpocetine significantly inhibited VSMCs proliferation and chemokinesis as well as ROS generation and apoptotic resistance, which was induced by high glucose (HG) treatment. Vinpocetine significantly abolished HG-induced phosphorylation of Akt and JNK1/2 without affecting their total levels. For downstream targets, HG-induced phosphorylation of IκBα was significantly inhibited by vinpocetine. Vinpocetine also attenuated HG-enhanced expression of PCNA, cyclin D1 and Bcl-2. Vinpocetine attenuated neointimal formation in diabetic rats and inhibited HG-induced VSMCs proliferation

Vinpocetine Attenuates Neointimal Hyperplasia in Diabetic Rat Carotid Arteries after Balloon Injury

PubMed Central

Peng, Wenhui; Li, Hailing; Zhuang, Jianhui; Lu, Yuyan; Liu, Baoxin; Li, Xiankai; Li, Weiming; Xu, Yawei

2014-01-01

Background Diabetes exacerbates abnormal vascular smooth muscle cell (VSMC) accumulation in response to arterial wall injury. Vinpocetine has been shown to improve vascular remolding; however, little is known about the direct effects of vinpocetine on vascular complications mediated by diabetes. The objective of this study was to determine the effects of vinpocetine on hyperglycemia-facilitated neointimal hyperplasia and explore its possible mechanism. Materials and Methods Nondiabetic and diabetic rats were subjected to balloon injury of the carotid artery followed by 3-week treatment with either vinpocetine (10 mg/kg/day) or saline. Morphological analysis and proliferating cell nuclear antigen (PCNA) immunostaining were performed on day 21. Rat VSMCs proliferation was determined with 5-ethynyl-20-deoxyuridine cell proliferation assays. Chemokinesis was monitored with scratch assays, and production of reactive oxygen species (ROS) was assessed using a 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) flow cytometric assay. Apoptosis was detected by annexin V-FITC/PI flow cytometric assay. Cell signaling was assessed by immunblotting. Results Vinpocetine prevented intimal hyperplasia in carotid arteries in both normal (I/M ratio: 93.83 ± 26.45% versus 143.2 ± 38.18%, P<0.05) and diabetic animals (I/M ratio: 120.5 ± 42.55% versus 233.46 ± 33.98%, P<0.05) when compared to saline. The in vitro study demonstrated that vinpocetine significantly inhibited VSMCs proliferation and chemokinesis as well as ROS generation and apoptotic resistance, which was induced by high glucose (HG) treatment. Vinpocetine significantly abolished HG-induced phosphorylation of Akt and JNK1/2 without affecting their total levels. For downstream targets, HG-induced phosphorylation of IκBα was significantly inhibited by vinpocetine. Vinpocetine also attenuated HG-enhanced expression of PCNA, cyclin D1 and Bcl-2. Conclusions Vinpocetine attenuated neointimal formation in diabetic

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.

Increased Expression of FoxM1 Transcription Factor in Respiratory Epithelium Inhibits Lung Sacculation and Causes Clara Cell Hyperplasia

PubMed Central

Wang, I-Ching; Zhang, Yufang; Snyder, Jonathan; Sutherland, Mardi J.; Burhans, Michael S.; Shannon, John M.; Park, Hyun Jung; Whitsett, Jeffrey A.; Kalinichenko, Vladimir V.

2010-01-01

Foxm1 is a member of the Forkhead Box (Fox) family of transcription factors. Foxm1 (previously called Foxm1b, HFH-11B, Trident, Win, or MPP2) is expressed in multiple cell types and plays important roles in cellular proliferation, differentiation and tumorigenesis. Genetic deletion of Foxm1 from mouse respiratory epithelium during initial stages of lung development inhibits lung maturation and causes respiratory failure after birth. However, the role of Foxm1 during postnatal lung morphogenesis remains unknown. In the present study, Foxm1 expression was detected in epithelial cells of conducting and peripheral airways and changing dynamically with lung maturation. To discern the biological role of Foxm1 in the prenatal and postnatal lung, a novel transgenic mouse line that expresses a constitutively active form of FoxM1 (FoxM1 N-terminal deletion mutant or FoxM1-ΔN) under the control of lung epithelial-specific SPC promoter was produced. Expression of the FoxM1-ΔN transgene during embryogenesis caused epithelial hyperplasia, inhibited lung sacculation and expression of the type II epithelial marker, pro-SPC. Expression of FoxM1-ΔN mutant during the postnatal period did not influence alveologenesis but caused focal airway hyperplasia and increased proliferation of Clara cells. Likewise, expression of FoxM1-ΔN mutant in conducting airways with Scgb1a1 promoter was sufficient to induce Clara cell hyperplasia. Furthermore, FoxM1-ΔN cooperated with activated K-Ras to induce lung tumor growth in vivo. Increased activity of Foxm1 altered lung sacculation, induced proliferation in the respiratory epithelium and accelerated lung tumor growth, indicating that precise regulation of Foxm1 is critical for normal lung morphogenesis and development of lung cancer. PMID:20816795

Inducible Transgenic Models of BRCA1 Function

DTIC Science & Technology

1998-10-01

development, and for signs of hyperplasia, dysplasia and neoplasia. Specific Aim 3. Inducibly abolish Brcal expression in the mammary epithelium of...abnormalities in mammary epithelial proliferation, differentiation and development, and for signs of hyperplasia, dysplasia and neoplasia. 6...Lyu MS, Kozak CA and Leder P. Expression of Brcal is associated with terminal differentiation of ectodermally and mesodermally derived tissues in mice

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.

Reversible Activation of Halophilic β-lactamase from Methanol-Induced Inactive Form: Contrast to Irreversible Inactivation of Non-Halophilic Counterpart.

PubMed

Tokunaga, Hiroko; Maeda, Junpei; Arakawa, Tsutomu; Tokunaga, Masao

2017-06-01

Effects of a water-miscible organic solvent, methanol, on the structure and activity of halophilic β-lactamase derived from Chromohalobacter sp.560 (HaBla), were investigated by means of circular dichroism (CD) measurement and enzymatic activity determination. Beta-lactamase activity was enhanced about 1.2-fold in the presence of 10-20% methanol. CD measurement of HaBla revealed different structures depending on the methanol concentration: native-like active form (Form I) in 10-20% methanol and methanol-induced inactive form at higher concentration (Form II in 40-60% and Form III in 75-80% methanol). Incubation of HaBla with 40% methanol led to the complete loss of activity within ~80 min accompanied by the formation of Form II, whose activity was recovered promptly up to ~80% of full activity upon dilution of the methanol concentration to 10%. In addition, when the protein concentration was sufficiently high (e.g., 0.7 mg/ml), HaBla activity of Form III in 75% methanol could be recovered in the same way (with slightly slower recovery rate), upon dilution of the methanol concentration. In contrast, non-halophilic β-lactamase from Escherichia coli K12 strain MG1655 (EcBla) was irreversibly denatured in the presence of 40% methanol. HaBla showed remarkable ability to renature from the methanol-induced inactive states.

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.

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

Peroxynitrite induces destruction of the tetrahydrobiopterin and heme in endothelial nitric oxide synthase: transition from reversible to irreversible enzyme inhibition†

PubMed Central

Chen, Weiguo; Druhan, Lawrence J.; Chen, Chun-An; Hemann, Craig; Chen, Yeong-Renn; Berka, Vladimir; Tsai, Ah-Lim; Zweier, Jay L.

2010-01-01

Endothelial nitric oxide synthase (eNOS) is an important regulator of vascular and cardiac function. Peroxynitrite (ONOO−) inactivates eNOS, but questions remain regarding the mechanisms of this process. It has been reported that inactivation is due to oxidation of the eNOS zinc-thiolate cluster, rather than the cofactor tetrahydrobiopterin (BH4); however, this remains highly controversial. Therefore, we investigated the mechanisms of ONOO−-induced eNOS dysfunction and their dose-dependence. Exposure of human eNOS to ONOO− resulted in a dose-dependent loss of activity with a marked destabilization of the eNOS dimer. HPLC analysis indicated that both free and eNOS-bound BH4 were oxidized during exposure to ONOO−; however, full oxidation of protein bound biopterin required higher ONOO− levels. Additionally, ONOO− triggered changes in UV/Visible spectrum and heme content of the enzyme. Pre-incubation of eNOS with BH4 decreased dimer destabilization and heme alteration. Addition of BH4 to the ONOO−-destabilized eNOS dimer only partially rescued enzyme function. In contrast to ONOO− treatment, incubation with the zinc chelator TPEN with removal of enzyme-bound zinc did not change the eNOS activity or stability of the SDS-resistant eNOS dimer, demonstrating that the dimer stabilization induced by BH4 does not require zinc occupancy of the zinc-thiolate cluster. While ONOO− treatment was observed to induce loss of Zn-binding this can not account for the loss of enzyme activity. Therefore, ONOO−-induced eNOS inactivation is primarily due to oxidation of BH4 and irreversible destruction of the heme/heme-center. PMID:20184376

Guinea pig ductus arteriosus. II - Irreversible closure after birth.

NASA Technical Reports Server (NTRS)

Fay, F. S.; Cooke, P. H.

1972-01-01

To investigate the mechanism underlying irreversibility of ductal closure after birth, studies were undertaken to determine the exact time course for the onset of irreversible closure of the guinea pig ductus arteriosus. Parallel studies of the reactivity of ductal smooth muscle to oxygen and studies of the postpartum cellular changes within the vessel were also carried out.

Antifreeze Protein Binds Irreversibly to Ice

NASA Astrophysics Data System (ADS)

Braslavsky, I.; Pertaya, N.; di Prinzio, C. L.; Wilen, L.; Thomson, E.; Wettlaufer, J. S.; Marshall, C. B.; Davies, P. L.

2006-03-01

Many organisms are protected from freezing by antifreeze proteins (AFPs), which bind to ice and prevent its growth by a mechanism not completely understood. Although it has been postulated that AFPs would have to bind irreversibly to arrest the growth of an ice crystal bathed in excess liquid water, the binding forces seem insufficient to support such a tight interaction. By putting a fluorescent tag on a fish AFP, we were able to visualize AFP binding to ice and demonstrate, by lack of recovery after photo-bleaching, that it is indeed irreversible. Because even the most avid protein/ligand interactions exhibit reversibility, this finding is key to understanding the mechanism of antifreeze proteins, which are becoming increasingly valuable in cryopreservation and improving the frost tolerance of crops.

Coagulative interstitial laser-induced thermotherapy of benign prostatic hyperplasia: online imaging with a T2-weighted fast spin-echo MR sequence--experience in six patients.

PubMed

Mueller-Lisse, U G; Thoma, M; Faber, S; Heuck, A F; Muschter, R; Schneede, P; Weninger, E; Hofstetter, A G; Reiser, M F

1999-02-01

To determine if hypointense lesions clearly outline on T2-weighted fast spin-echo (SE) magnetic resonance (MR) images obtained during coagulative interstitial laser-induced thermotherapy (LITT) of a prostate with benign hyperplasia. In six patients with benign prostatic hyperplasia (BPH), 12 LITT treatments were followed online with repetitive axial T2-weighted fast SE imaging (repetition time, 3,700 msec; echo time, 138 msec; acquisition time, 19 seconds). Development, time course, correlation with interstitial tissue temperature, and diameters of hypointense lesions around the laser diffusor tip were investigated. Lesion diameters on T2-weighted images acquired during LITT were compared with diameters of final lesions on T2-weighted images and unperfused lesions on enhanced T1-weighted SE images obtained at the end of therapy. Hypointense lesions developed within 20-40 seconds of LITT. Average correlation coefficients between interstitial temperature development and signal intensity development were 0.92 during LITT and 0.90 after LITT. Regression slopes were significantly steeper during LITT (0.67% signal intensity change per degree Celsius) than after LITT (0.47% per degree Celsius; P = .038). Lesions remained visible after LITT for all procedures. Average maximum diameters of lesions were 1-3 mm larger during LITT than after LITT (P = .0006-.019). Repetitive T2-weighted fast SE MR imaging during interstitial coagulative LITT of BPH demonstrates the development of permanent hypointense prostate lesions. However, posttherapeutic lesion diameters tend to be overestimated during LITT.

Case report: Irreversible electroporation for locally advanced pancreatic cancer.

PubMed

Orcutt, Sonia; Kis, Bela; Malafa, Mokenge

2017-01-01

For patients with pancreatic adenocarcinoma who are not candidates for surgical resection, long-term survival is poor, even with currently available systemic and radiation therapy options. However, for those with locally advanced disease who do not have distant metastasis, locoregional control of the tumor has the potential to improve long-term outcomes. A newly developed technology, irreversible electroporation, has advantages over traditional thermal ablation with unresectable cancers in this location. In our case report, we describe the first patient treated with irreversible electroporation at our institution for locally advanced pancreatic cancer. The patient is a 63-year-old man who had a partial response to standard chemotherapy and radiation, but was found on operative assessment to have persistently unresectable disease. He therefore underwent irreversible electroporation to the pancreatic mass. His postoperative course was complicated by delayed gastric emptying and wound infection. Three months after surgery, he had no evidence of distant or recurrent disease. Irreversible electroporation for locally advanced pancreatic cancer is an emerging technique which attempts to improve local control of locally advanced, non-metastatic pancreatic cancer. Early data have demonstrated the potential for improved long-term survival in these patients, although further studies are needed to confirm safety and efficacy of this technique. While there is a positive outlook for the use of irreversible electroporation for locally advanced pancreas cancer, there remain some uncertainties surrounding this therapy, which underscores the importance of future research in this area. Copyright © 2017. Published by Elsevier Ltd.

Intragenomic conflict in populations infected by Parthenogenesis Inducing Wolbachia ends with irreversible loss of sexual reproduction

PubMed Central

2010-01-01

Background The maternally inherited, bacterial symbiont, parthenogenesis inducing (PI) Wolbachia, causes females in some haplodiploid insects to produce daughters from both fertilized and unfertilized eggs. The symbionts, with their maternal inheritance, benefit from inducing the production of exclusively daughters, however the optimal sex ratio for the nuclear genome is more male-biased. Here we examine through models how an infection with PI-Wolbachia in a previously uninfected population leads to a genomic conflict between PI-Wolbachia and the nuclear genome. In most natural populations infected with PI-Wolbachia the infection has gone to fixation and sexual reproduction is impossible, specifically because the females have lost their ability to fertilize eggs, even when mated with functional males. Results The PI Wolbachia infection by itself does not interfere with the fertilization process in infected eggs, fertilized infected eggs develop into biparental infected females. Because of the increasingly female-biased sex ratio in the population during a spreading PI-Wolbachia infection, sex allocation alleles in the host that cause the production of more sons are rapidly selected. In haplodiploid species a reduced fertilization rate leads to the production of more sons. Selection for the reduced fertilization rate leads to a spread of these alleles through both the infected and uninfected population, eventually resulting in the population becoming fixed for both the PI-Wolbachia infection and the reduced fertilization rate. Fertilization rate alleles that completely interfere with fertilization ("virginity alleles") will be selected over alleles that still allow for some fertilization. This drives the final resolution of the conflict: the irreversible loss of sexual reproduction and the complete dependence of the host on its symbiont. Conclusions This study shows that dependence among organisms can evolve rapidly due to the resolution of the conflicts between

Performance Optimization of Irreversible Air Heat Pumps Considering Size Effect

NASA Astrophysics Data System (ADS)

Bi, Yuehong; Chen, Lingen; Ding, Zemin; Sun, Fengrui

2018-06-01

Considering the size of an irreversible air heat pump (AHP), heating load density (HLD) is taken as thermodynamic optimization objective by using finite-time thermodynamics. Based on an irreversible AHP with infinite reservoir thermal-capacitance rate model, the expression of HLD of AHP is put forward. The HLD optimization processes are studied analytically and numerically, which consist of two aspects: (1) to choose pressure ratio; (2) to distribute heat-exchanger inventory. Heat reservoir temperatures, heat transfer performance of heat exchangers as well as irreversibility during compression and expansion processes are important factors influencing on the performance of an irreversible AHP, which are characterized with temperature ratio, heat exchanger inventory as well as isentropic efficiencies, respectively. Those impacts of parameters on the maximum HLD are thoroughly studied. The research results show that HLD optimization can make the size of the AHP system smaller and improve the compactness of system.

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.

4-Nitrophenol induces Leydig cells hyperplasia, which may contribute to the differential modulation of the androgen receptor and estrogen receptor-α and -β expression in male rat testes.

PubMed

Zhang, Yonghui; Piao, Yuanguo; Li, Yansen; Song, Meiyan; Tang, Pingli; Li, Chunmei

2013-11-25

4-Nitrophenol (PNP) is generally regarded as an environmental endocrine disruptor capable of estrogenic and anti-androgenic activities. To investigate PNP-induced reproductive effects, immature male rats were injected subcutaneously with PNP (0.1, 1, 10mg/kg body weight or vehicle) daily for 4 weeks. We assessed reproductive tract alterations, sex hormone balance in the serum and estrogen receptor (ER)-α, -β and androgen receptor (AR) expression in testes. Although no significant difference was observed in body weight or testes weights of PNP-treated rats compared with the controls, the serum concentrations of testosterone in the 10mg/kg PNP-treated group were significantly elevated. This effect was accompanied by Leydig cells hyperplasia in the testes. Conversely, there was a significant decrease in estradiol concentration and aromatase expression in the testes of the 10mg/kg PNP-treated group. Furthermore, we observed a significant increase in ERα expression in the testes of the 10mg/kg PNP-treated group compared with the control group. Conversely, ERβ expression displayed a significant reduction. Moreover, AR expression was significantly increased in the 10mg/kg PNP-treated group compared with the control group. The existence of AR, ER-α and -β in the testes suggests that estradiol and testosterone directly affect germ cells and that differential modulation of AR, ER-α and -β in the testis may be involved in the direct effects of PNP or either the indirect effects of PNP-induced disruption of the estradiol-to-testosterone balance or the Leydig cells hyperplasia. Thus, the measurement of many endpoints is necessary for good risk assessment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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.

The Crataegus extract WS 1442 inhibits balloon catheter-induced intimal hyperplasia in the rat carotid artery by directly influencing PDGFR-beta.

PubMed

Fürst, Robert; Zirrgiebel, Ute; Totzke, Frank; Zahler, Stefan; Vollmar, Angelika M; Koch, Egon

2010-08-01

Effective systemic drugs against restenosis upon percutaneous transluminal coronary angioplasty (PTCA) are largely lacking. Polyphenols have been suggested to ameliorate post-angioplasty restenosis. Hawthorn (Crataegus spp.) extracts, which are among the most frequently used herbal medicinal products against mild forms of congestive heart failure, contain polyphenols, but have not been investigated in this context. We aimed to assess the potential of the hawthorn extract WS 1442 to prevent balloon catheter-induced intimal hyperplasia and to elucidate the underlying mechanisms. We analyzed the effects of WS 1442 on serum-induced vascular smooth muscle cell (VSMC) and endothelial cell (EC) growth and migration, growth factor-induced proliferation, growth factor receptor activity, and neointima formation in the rat carotid artery model. WS 1442 (100 microg/ml) decreased VSMC migration by 38% and proliferation by 44%, whereas EC migration and proliferation were unaltered. The extract inhibited VSMC DNA synthesis induced by platelet-derived growth factor (PDGF) (IC(50): 47 microg/ml), but not that of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). Along this line, WS 1442 blocked recombinant human PDGF receptor (PDGFR)-beta kinase activity (IC(50): 1.4 microg/ml) and decreased PDGFR-beta activation and extracellular signal-regulated kinase (ERK) activation in VSMCs. In rats, orally administered WS 1442 significantly reduced neointima formation after balloon catheter dilatation of the carotid artery. WS 1442 inhibits migration and proliferation of VSMCs, but not of ECs, and reduces balloon catheter-evoked neointima formation probably through inhibition of PDGFR-beta. Thus, the present study suggests a novel adjunct pharmacological strategy to prevent angioplasty-related restenosis. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

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

Ictal time-irreversible intracranial EEG signals as markers of the epileptogenic zone.

PubMed

Schindler, Kaspar; Rummel, Christian; Andrzejak, Ralph G; Goodfellow, Marc; Zubler, Frédéric; Abela, Eugenio; Wiest, Roland; Pollo, Claudio; Steimer, Andreas; Gast, Heidemarie

2016-09-01

To show that time-irreversible EEG signals recorded with intracranial electrodes during seizures can serve as markers of the epileptogenic zone. We use the recently developed method of mapping time series into directed horizontal graphs (dHVG). Each node of the dHVG represents a time point in the original intracranial EEG (iEEG) signal. Statistically significant differences between the distributions of the nodes' number of input and output connections are used to detect time-irreversible iEEG signals. In 31 of 32 seizure recordings we found time-irreversible iEEG signals. The maximally time-irreversible signals always occurred during seizures, with highest probability in the middle of the first seizure half. These signals spanned a large range of frequencies and amplitudes but were all characterized by saw-tooth like shaped components. Brain regions removed from patients who became post-surgically seizure-free generated significantly larger time-irreversibilities than regions removed from patients who still had seizures after surgery. Our results corroborate that ictal time-irreversible iEEG signals can indeed serve as markers of the epileptogenic zone and can be efficiently detected and quantified in a time-resolved manner by dHVG based methods. Ictal time-irreversible EEG signals can help to improve pre-surgical evaluation in patients suffering from pharmaco-resistant epilepsies. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Minimum energy dissipation required for a logically irreversible operation

NASA Astrophysics Data System (ADS)

Takeuchi, Naoki; Yoshikawa, Nobuyuki

2018-01-01

According to Landauer's principle, the minimum heat emission required for computing is linked to logical entropy, or logical reversibility. The validity of Landauer's principle has been investigated for several decades and was finally demonstrated in recent experiments by showing that the minimum heat emission is associated with the reduction in logical entropy during a logically irreversible operation. Although the relationship between minimum heat emission and logical reversibility is being revealed, it is not clear how much free energy is required to be dissipated for a logically irreversible operation. In the present study, in order to reveal the connection between logical reversibility and free energy dissipation, we numerically demonstrated logically irreversible protocols using adiabatic superconductor logic. The calculation results of work during the protocol showed that, while the minimum heat emission conforms to Landauer's principle, the free energy dissipation can be arbitrarily reduced by performing the protocol quasistatically. The above results show that logical reversibility is not associated with thermodynamic reversibility, and that heat is not only emitted from logic devices but also absorbed by logic devices. We also formulated the heat emission from adiabatic superconductor logic during a logically irreversible operation at a finite operation speed.

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.

Effect of Nitric Oxide on Neointimal Hyperplasia based on Sex and Hormone Status

PubMed Central

Hogg, Melissa E.; Varu, Vinit N.; Vavra, Ashley K.; Popowich, Daniel A.; Banerjee, Monisha N.; Martinez, Janet; Jiang, Qun; Saavedra, Joseph E.; Keefer, Larry K.; Kibbe, Melina R.

2011-01-01

Nitric oxide (NO)-based therapies decrease neointimal hyperplasia; however, studies have only been performed in male animal models. Thus, we sought to evaluate the effect of NO on vascular smooth muscle cells (VSMC) in vitro and neointimal hyperplasia in vivo based on sex and hormone status. In hormone-replete media, male VSMC proliferated at greater rates than female VSMC. In hormone-deplete media, female VSMC proliferated at greater rates than male VSMC. However, in both hormone environments, NO inhibited proliferation and migration to a greater extent in male versus female VSMC. These findings correlated with greater G0/G1 cell cycle arrest and changes in cell cycle protein expression in male versus female VSMC following exposure to NO. Next, the rat carotid artery injury model was performed to assess the effect of NO on neointimal hyperplasia in vivo. Consistent with the in vitro data, NO was significantly more effective at inhibiting neointimal hyperplasia in hormonally intact males versus females using weight-based dosing. An increased weight-based dose of NO in females was able to achieve efficacy equal to that in males. Surprisingly, NO was less effective at inhibiting neointimal hyperplasia in both sexes in castrated animals. In conclusion, these data suggest that NO inhibits neointimal hyperplasia more effectively in males than females and in hormonally-intact compared to castrated rats, indicating that the effect of NO in the vasculature may be sex- and hormone-dependent. PMID:21256959

Covalent modification of pericardial patches for sustained rapamycin delivery inhibits venous neointimal hyperplasia

PubMed Central

Bai, Hualong; Lee, Jung Seok; Chen, Elizabeth; Wang, Mo; Xing, Ying; Fahmy, Tarek M.; Dardik, Alan

2017-01-01

Prosthetic grafts and patches are commonly used in cardiovascular surgery, however neointimal hyperplasia remains a significant concern, especially under low flow conditions. We hypothesized that delivery of rapamycin from nanoparticles (NP) covalently attached to patches allows sustained site-specific delivery of therapeutic agents targeted to inhibit localized neointimal hyperplasia. NP were covalently linked to pericardial patches using EDC/NHS chemistry and could deliver at least 360 ng rapamycin per patch without detectable rapamycin in serum; nanoparticles were detectable in the liver, kidney and spleen but no other sites within 24 hours. In a rat venous patch angioplasty model, control patches developed robust neointimal hyperplasia on the patch luminal surface characterized by Eph-B4-positive endothelium and underlying SMC and infiltrating cells such as macrophages and leukocytes. Patches delivering rapamycin developed less neointimal hyperplasia, less smooth muscle cell proliferation, and had fewer infiltrating cells but retained endothelialization. NP covalently linked to pericardial patches are a novel composite delivery system that allows sustained site-specific delivery of therapeutics; NP delivering rapamycin inhibit patch neointimal hyperplasia. NP linked to patches may represent a next generation of tissue engineered cardiovascular implants. PMID:28071663

Covalent modification of pericardial patches for sustained rapamycin delivery inhibits venous neointimal hyperplasia

NASA Astrophysics Data System (ADS)

Bai, Hualong; Lee, Jung Seok; Chen, Elizabeth; Wang, Mo; Xing, Ying; Fahmy, Tarek M.; Dardik, Alan

2017-01-01

Prosthetic grafts and patches are commonly used in cardiovascular surgery, however neointimal hyperplasia remains a significant concern, especially under low flow conditions. We hypothesized that delivery of rapamycin from nanoparticles (NP) covalently attached to patches allows sustained site-specific delivery of therapeutic agents targeted to inhibit localized neointimal hyperplasia. NP were covalently linked to pericardial patches using EDC/NHS chemistry and could deliver at least 360 ng rapamycin per patch without detectable rapamycin in serum; nanoparticles were detectable in the liver, kidney and spleen but no other sites within 24 hours. In a rat venous patch angioplasty model, control patches developed robust neointimal hyperplasia on the patch luminal surface characterized by Eph-B4-positive endothelium and underlying SMC and infiltrating cells such as macrophages and leukocytes. Patches delivering rapamycin developed less neointimal hyperplasia, less smooth muscle cell proliferation, and had fewer infiltrating cells but retained endothelialization. NP covalently linked to pericardial patches are a novel composite delivery system that allows sustained site-specific delivery of therapeutics; NP delivering rapamycin inhibit patch neointimal hyperplasia. NP linked to patches may represent a next generation of tissue engineered cardiovascular implants.

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.

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.

An improvement of the measurement of time series irreversibility with visibility graph approach

NASA Astrophysics Data System (ADS)

Wu, Zhenyu; Shang, Pengjian; Xiong, Hui

2018-07-01

We propose a method to improve the measure of real-valued time series irreversibility which contains two tools: the directed horizontal visibility graph and the Kullback-Leibler divergence. The degree of time irreversibility is estimated by the Kullback-Leibler divergence between the in and out degree distributions presented in the associated visibility graph. In our work, we reframe the in and out degree distributions by encoding them with different embedded dimensions used in calculating permutation entropy(PE). With this improved method, we can not only estimate time series irreversibility efficiently, but also detect time series irreversibility from multiple dimensions. We verify the validity of our method and then estimate the amount of time irreversibility of series generated by chaotic maps as well as global stock markets over the period 2005-2015. The result shows that the amount of time irreversibility reaches the peak with embedded dimension d = 3 under circumstances of experiment and financial markets.

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.

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.

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

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.

Time in Science: Reversibility vs. Irreversibility

NASA Astrophysics Data System (ADS)

Pomeau, Yves

To discuss properly the question of irreversibility one needs to make a careful distinction between reversibility of the equations of motion and the choice of the initial conditions. This is also relevant for the rather confuse philosophy of the wave packet reduction in quantum mechanics. The explanation of this reduction requires also to make precise assumptions on what initial data are accessible in our world. Finally I discuss how a given (and long) time record can be shown in an objective way to record an irreversible or reversible process. Or: can a direction of time be derived from its analysis? This leads quite naturally to examine if there is a possible spontaneous breaking of the time reversal symmetry in many body systems, a symmetry breaking that would be put in evidence objectively by looking at certain specific time correlations.

Mechanisms of asbestos-induced squamous metaplasia in tracheobronchial epithelial cells.

PubMed Central

Cameron, G; Woodworth, C D; Edmondson, S; Mossman, B T

1989-01-01

Within 1 to 4 weeks after exposure to asbestos, differentiated rodent and human tracheobronchial epithelial cells in organ culture undergo squamous metaplasia, a putative preneoplastic lesion characterized by conversion of mucociliary cell types to keratinizing cells. The exogenous addition of retinal acetate (RA) to culture medium of hamster tracheal organ cultures reverses preestablished, asbestos-induced squamous metaplasia, although data suggest that the effectiveness of RA decreases as the length of time between exposure to asbestos and initial application of RA increases. alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), inhibits squamous metaplasia caused by asbestos or vitamin A deficiency, whereas addition of methylglyoxal bis(guanylhydrazone) (MGBG), a structural analog of spermidine and inhibitor of S-adenosylmethionine decarboxylase, causes an enhancement of metaplasia under both circumstances. Basal cell hyperplasia and increased incorporation of 3H-thymidine by tracheal epithelial cells also are seen after addition of the polyamines, putrescine or spermidine, to tracheal organ cultures, an observation supporting the importance of polyamines in the development of this lesion. The use of retinoids and inhibitors of ODC could be promising as preventive and/or therapeutic approaches for individuals at high risk for development of asbestos-associated diseases. PMID:2924752

Stromal adipocyte enhancer-binding protein (AEBP1) promotes mammary epithelial cell hyperplasia via proinflammatory and hedgehog signaling.

PubMed

Holloway, Ryan W; Bogachev, Oleg; Bharadwaj, Alamelu G; McCluskey, Greg D; Majdalawieh, Amin F; Zhang, Lei; Ro, Hyo-Sung

2012-11-09

Disruption of mammary stromal-epithelial communication leads to aberrant mammary gland development and induces mammary tumorigenesis. Macrophages have been implicated in carcinogenesis primarily by creating an inflammatory microenvironment, which promotes growth of the adjacent epithelial cells. Adipocyte enhancer-binding protein 1 (AEBP1), a novel proinflammatory mediator, promotes macrophage inflammatory responsiveness by inducing NF-κB activity, which has been implicated in tumor cell growth and survival by aberrant sonic hedgehog (Shh) expression. Here, we show that stromal macrophage AEBP1 overexpression results in precocious alveologenesis in the virgin AEBP1 transgenic (AEBP1(TG)) mice, and the onset of ductal hyperplasia was accelerated in AEBP1(TG) mice fed a high fat diet, which induces endogenous AEBP1 expression. Transplantation of AEBP1(TG) bone marrow cells into non-transgenic (AEBP1(NT)) mice resulted in alveolar hyperplasia with up-regulation of NF-κB activity and TNFα expression as displayed in the AEBP1(TG) mammary macrophages and epithelium. Shh expression was induced in AEBP1(TG) macrophages and RAW264.7 macrophages overexpressing AEBP1. The Shh target genes Gli1 and Bmi1 expression was induced in the AEBP1(TG) mammary epithelium and HC11 mammary epithelial cells co-cultured with AEBP1(TG) peritoneal macrophages. The conditioned AEBP1(TG) macrophage culture media promoted NF-κB activity and survival signal, Akt activation, in HC11 cells, whereas such effects were abolished by TNFα neutralizing antibody treatment. Furthermore, HC11 cells displayed enhanced proliferation in response to AEBP1(TG) macrophages and their conditioned media. Our findings highlight the role of AEBP1 in the signaling pathways regulating the cross-talk between mammary epithelium and stroma that could predispose the mammary tissue to tumorigenesis.

Stromal Adipocyte Enhancer-binding Protein (AEBP1) Promotes Mammary Epithelial Cell Hyperplasia via Proinflammatory and Hedgehog Signaling*

PubMed Central

Holloway, Ryan W.; Bogachev, Oleg; Bharadwaj, Alamelu G.; McCluskey, Greg D.; Majdalawieh, Amin F.; Zhang, Lei; Ro, Hyo-Sung

2012-01-01

Disruption of mammary stromal-epithelial communication leads to aberrant mammary gland development and induces mammary tumorigenesis. Macrophages have been implicated in carcinogenesis primarily by creating an inflammatory microenvironment, which promotes growth of the adjacent epithelial cells. Adipocyte enhancer-binding protein 1 (AEBP1), a novel proinflammatory mediator, promotes macrophage inflammatory responsiveness by inducing NF-κB activity, which has been implicated in tumor cell growth and survival by aberrant sonic hedgehog (Shh) expression. Here, we show that stromal macrophage AEBP1 overexpression results in precocious alveologenesis in the virgin AEBP1 transgenic (AEBP1TG) mice, and the onset of ductal hyperplasia was accelerated in AEBP1TG mice fed a high fat diet, which induces endogenous AEBP1 expression. Transplantation of AEBP1TG bone marrow cells into non-transgenic (AEBP1NT) mice resulted in alveolar hyperplasia with up-regulation of NF-κB activity and TNFα expression as displayed in the AEBP1TG mammary macrophages and epithelium. Shh expression was induced in AEBP1TG macrophages and RAW264.7 macrophages overexpressing AEBP1. The Shh target genes Gli1 and Bmi1 expression was induced in the AEBP1TG mammary epithelium and HC11 mammary epithelial cells co-cultured with AEBP1TG peritoneal macrophages. The conditioned AEBP1TG macrophage culture media promoted NF-κB activity and survival signal, Akt activation, in HC11 cells, whereas such effects were abolished by TNFα neutralizing antibody treatment. Furthermore, HC11 cells displayed enhanced proliferation in response to AEBP1TG macrophages and their conditioned media. Our findings highlight the role of AEBP1 in the signaling pathways regulating the cross-talk between mammary epithelium and stroma that could predispose the mammary tissue to tumorigenesis. PMID:22995915

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.

Effect of design variables on irreversible magnet demagnetization in brushless dc motor

NASA Astrophysics Data System (ADS)

Kim, Tae Heoung; Lee, Ju

2005-05-01

The large demagnetizing currents in brushless dc (BLdc) motor are generated by the short-circuited stator windings and the fault of a drive circuit. So, irreversible magnet demagnetization occurs due to the external demagnetizing field by these currents. In this paper, we deal with the effect of design variables on irreversible magnet demagnetization in BLdc motor through the modeling approach using a two-dimensional finite-element method (2D FEM). The nonlinear analysis of a permanent magnet is added to 2D FEM to consider irreversible demagnetization. As a result, it is shown that magnet thickness, teeth surface width, and rotor back yoke thickness are the most important geometrical dimensions of BLdc motor in terms of irreversible magnet demagnetization.

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.

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.

Influence of Panax ginseng on Alpha-Adrenergic Receptor of Benign Prostatic Hyperplasia

PubMed Central

Kim, Su Kang; Chung, Joo-Ho; Lee, Byung-Cheol; Lee, Sang Won; Lee, Kang Hyo

2014-01-01

Purpose Benign prostatic hyperplasia (BPH) is the most common prostate problem in older men. The present study aimed to investigate the inhibitory effect of Panax ginseng C.A. Meyer (P. ginseng) on a rat model of testosterone-induced BPH. Methods The rats were divided into 3 groups (each group, n=10): control, testosterone-induced BPH (20 mg/kg, subcutaneous injection), and P. ginseng (200 mg/kg, orally) groups. After 4 weeks, all animals were sacrificed to examine the blood biochemical profiles, prostate volume, weight, histopathological changes, alpha-1D adrenergic receptor (Adra1d) mRNA expression, and epidermal growth factor receptor (EGFR) and B-cell CLL/lymphoma 2 (BCL2) protein expression. Results The group treated with P. ginseng showed significantly lesser prostate size and weight than the testosterone-induced BPH group. In addition, P. ginseng decreased the mRNA expression of Adra1d as well as the expression of EGFR and BCL2 in prostate tissue. Conclusions These results suggest that P. ginseng may inhibit the alpha-1-adrenergic receptor to suppress the development of BPH. PMID:25558416

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

Multiscale Analysis of Time Irreversibility Based on Phase-Space Reconstruction and Horizontal Visibility Graph Approach

NASA Astrophysics Data System (ADS)

Zhang, Yongping; Shang, Pengjian; Xiong, Hui; Xia, Jianan

Time irreversibility is an important property of nonequilibrium dynamic systems. A visibility graph approach was recently proposed, and this approach is generally effective to measure time irreversibility of time series. However, its result may be unreliable when dealing with high-dimensional systems. In this work, we consider the joint concept of time irreversibility and adopt the phase-space reconstruction technique to improve this visibility graph approach. Compared with the previous approach, the improved approach gives a more accurate estimate for the irreversibility of time series, and is more effective to distinguish irreversible and reversible stochastic processes. We also use this approach to extract the multiscale irreversibility to account for the multiple inherent dynamics of time series. Finally, we apply the approach to detect the multiscale irreversibility of financial time series, and succeed to distinguish the time of financial crisis and the plateau. In addition, Asian stock indexes away from other indexes are clearly visible in higher time scales. Simulations and real data support the effectiveness of the improved approach when detecting time irreversibility.

[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.

A fingerprint encryption scheme based on irreversible function and secure authentication.

PubMed

Yang, Yijun; Yu, Jianping; Zhang, Peng; Wang, Shulan

2015-01-01

A fingerprint encryption scheme based on irreversible function has been designed in this paper. Since the fingerprint template includes almost the entire information of users' fingerprints, the personal authentication can be determined only by the fingerprint features. This paper proposes an irreversible transforming function (using the improved SHA1 algorithm) to transform the original minutiae which are extracted from the thinned fingerprint image. Then, Chinese remainder theorem is used to obtain the biokey from the integration of the transformed minutiae and the private key. The result shows that the scheme has better performance on security and efficiency comparing with other irreversible function schemes.

Measures of thermodynamic irreversibility in deterministic and stochastic dynamics

NASA Astrophysics Data System (ADS)

Ford, Ian J.

2015-07-01

It is generally observed that if a dynamical system is sufficiently complex, then as time progresses it will share out energy and other properties amongst its component parts to eliminate any initial imbalances, retaining only fluctuations. This is known as energy dissipation and it is closely associated with the concept of thermodynamic irreversibility, measured by the increase in entropy according to the second law. It is of interest to quantify such behaviour from a dynamical rather than a thermodynamic perspective and to this end stochastic entropy production and the time-integrated dissipation function have been introduced as analogous measures of irreversibility, principally for stochastic and deterministic dynamics, respectively. We seek to compare these measures. First we modify the dissipation function to allow it to measure irreversibility in situations where the initial probability density function (pdf) of the system is asymmetric as well as symmetric in velocity. We propose that it tests for failure of what we call the obversibility of the system, to be contrasted with reversibility, the failure of which is assessed by stochastic entropy production. We note that the essential difference between stochastic entropy production and the time-integrated modified dissipation function lies in the sequence of procedures undertaken in the associated tests of irreversibility. We argue that an assumed symmetry of the initial pdf with respect to velocity inversion (within a framework of deterministic dynamics) can be incompatible with the Past Hypothesis, according to which there should be a statistical distinction between the behaviour of certain properties of an isolated system as it evolves into the far future and the remote past. Imposing symmetry on a velocity distribution is acceptable for many applications of statistical physics, but can introduce difficulties when discussing irreversible behaviour.

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.

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.

Fundamental economic irreversibilities influence policies for enhancing international forest phytosanitary security

Treesearch

Thomas P. Holmes; Will Allen; Robert G. Haight; E. Carina H. Keskitalo; Mariella Marzano; Maria Pettersson; Christopher P. Quine; E. R. Langer

2017-01-01

National and international efforts to manage forest biosecurity create tension between opposing sources of ecological and economic irreversibility. Phytosanitary policies designed to protect national borders from biological invasions incur sunk costs deriving from economic and political irreversibilities that incentivizes wait-and-see decision-making. However, the...

Pressure-Induced Irreversible Phase Transition in the Energetic Material Urea Nitrate

NASA Astrophysics Data System (ADS)

Li, Shourui; Zou, Bo

2013-06-01

The behavior of energetic material Urea Nitrate ((NH2)2 COH+ . NO3-,UN) has been investigated up to the pressure of ~26 GPa. UN exhibits the typical supramolecular structure with uronium cation and nitrate anion held together by multiple hydrogen bonds in the layer. Both Raman and XRD data provide obvious evidence for the distorted phase transition in the pressure range ~9-15 GPa. Further analysis indicates phase II has Pc symmetry. The mechanism for the phase transition involves collapse of the initial 2D supramolecular structure to 3D hydrogen-bonded networks in phase Pc. Importantly, the transition is irreversible and leads to a large reduction in volume on release of pressure. The density in phase Pc has been increased by ~11.8% compared to the phase P21/ c under ambient conditions and therefore phase Pc is expected to have much higher detonation power. This study opens new opportunities for preparing energetic materials with high density combining supramolecular chemistry with high-pressure techniques. Corresponding author. E-mail: zoubo@jlu.edu.cn This work is supported by National Science Foundation of China (NSFC) (Nos. 91227202, and 21073071).

Induced expression of hepatic N-methyl-D-aspartate receptor 2C subunit gene during liver enlargement induced by lead nitrate, a hepatocellular mitogen.

PubMed

Nemoto, Kiyomitsu; Ikeda, Ayaka; Hikida, Tokihiro; Kojima, Misaki; Degawa, Masakuni

2013-02-01

We previously demonstrated the super-induced expression of the Grin2c gene encoding the N-methyl-D-aspartate receptor 2C subunit during the development of liver enlargement with hepatocellular hypertrophy induced by phenobarbital, clofibrate, or piperonyl butoxide. In the present study, we assessed whether or not Grin2c gene expression was induced during the development of chemically induced liver enlargement with hyperplasia. Male Sprague-Dawley (SD) rats, stroke-prone spontaneously hypertensive rats (SHRSPs), and SHRSP's normotensive control, Wistar-Kyoto (WKY) rats, were administered lead nitrate (LN) (0.1 mmol/kg, single i.v.), a direct inducer of liver hyperplasia, and changes in the level of Grin2c mRNA in the liver were assessed by real-time RT-PCR. The level of hepatic Grin2c mRNA was significantly higher 6-48 hr after the injection in SD rats (about 30~40- and 70-fold over the control at 6~24 hr and 48 hr, respectively) and in WKY rats (about 20-fold over the control only at 12 hr), but was not significantly higher in SHRSPs. Such differences in LN-induced levels of Grin2c mRNA among SD rats, WKY rats, and SHRSPs were closely correlated with those in the previously reported increase in liver weight 48 hr after LN administration. The present findings suggest that the increase in the level of hepatic Grin2c mRNA relates to development of chemically induced liver enlargement with hyperplasia.

The Impact of Uncertainty and Irreversibility on Investments in Online Learning

ERIC Educational Resources Information Center

Oslington, Paul

2004-01-01

Uncertainty and irreversibility are central to online learning projects, but have been neglected in the existing educational cost-benefit analysis literature. This paper builds some simple illustrative models of the impact of irreversibility and uncertainty, and shows how different types of cost and demand uncertainty can have substantial impacts…

Anderson localized state as a predissipative state: irreversible emission of thermalized quanta from a dynamically delocalized state.

PubMed

Yamada, Hiroaki; Ikeda, Kensuke S

2002-04-01

It was shown that localization in one-dimensional disordered (quantum) electronic system is destroyed against coherent harmonic perturbations and the delocalized electron exhibits an unlimited diffusive motion [Yamada and Ikeda, Phys. Rev. E 59, 5214 (1999)]. The appearance of diffusion implies that the system has potential for irreversibility and dissipation. In the present paper, we investigate dissipative property of the dynamically delocalized state, and we show that an irreversible quasistationary energy flow indeed appears in the form of a "heat" flow when we couple the system with another dynamical degree of freedom. In the concrete we numerically investigate dissipative properties of a one-dimensional tight-binding electronic system perturbed by time-dependent harmonic forces, by coupling it with a quantum harmonic oscillator or a quantum anharmonic oscillator. It is demonstrated that if the on-site potential is spatially irregular an irreversible energy transfer from the scattered electron to the test oscillator occurs. Moreover, the test oscillator promptly approaches a thermalized state characterized by a well-defined time-dependent temperature. On the contrary, such a relaxation process cannot be observed at all for periodic potential systems. Our system is one of the minimal quantum systems in which a distinct nonequilibrium statistical behavior is self-induced.

The Safety and Efficacy of Irreversible Electroporation for Large Hepatocellular Carcinoma.

PubMed

Zeng, Jianying; Liu, Guifeng; Li, Zhong-Hai; Yang, Yi; Fang, Gang; Li, Rong-Rong; Xu, Ke-Cheng; Niu, Lizhi

2017-02-01

This study aimed to investigate the safety and effectiveness of irreversible electroporation ablation for unresectable large liver cancer. Fourteen patients were enrolled: 8 with large hepatocellular carcinoma (tumor diameter: 5.1-11.5 cm) and 6 with medium hepatocellular carcinoma (tumor diameter: 3.0-4.1 cm). All patients received percutaneous irreversible electroporation ablation. Ablation time and the incidence of complications were assessed by a t test. Post-irreversible electroporation and regular contrast-enhanced computerized tomography scans were performed to investigate the effect of tumor size (large vs medium) on irreversible electroporation treatment efficacy; 4-table data were assessed using a Fisher exact test. The 14 patients completed irreversible electroporation ablation successfully. In the large hepatocellular carcinoma group, no major complications occurred in the perioperative period. Minor complications comprised bloating, hypokalemia, edema, low white blood cells, and blood clotting abnormalities. All complications were mild and improved after symptomatic treatment. The frequency of minor complications was not significantly different ( P > .05) compared with the medium hepatocellular carcinoma group. The average follow-up time was 2.8 ± 2.1 months and complete ablation was achieved in 25% (2/8; residual = 75%). For the patients with medium hepatocellular carcinoma, the mean follow-up time was 4.3 ± 3.2 months; the rate of complete ablation was 66.6% (4/6; residual rate = 33.3%). The complete ablation rate was not statistically different between the 2 groups ( P > .05). Irreversible electroporation ablation for unresectable large hepatocellular carcinoma is safe, with no major complications. Short-term efficacy is relatively good; however, long-term efficacy remains to be explored.

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

Irreversible Local Markov Chains with Rapid Convergence towards Equilibrium.

PubMed

Kapfer, Sebastian C; Krauth, Werner

2017-12-15

We study the continuous one-dimensional hard-sphere model and present irreversible local Markov chains that mix on faster time scales than the reversible heat bath or Metropolis algorithms. The mixing time scales appear to fall into two distinct universality classes, both faster than for reversible local Markov chains. The event-chain algorithm, the infinitesimal limit of one of these Markov chains, belongs to the class presenting the fastest decay. For the lattice-gas limit of the hard-sphere model, reversible local Markov chains correspond to the symmetric simple exclusion process (SEP) with periodic boundary conditions. The two universality classes for irreversible Markov chains are realized by the totally asymmetric SEP (TASEP), and by a faster variant (lifted TASEP) that we propose here. We discuss how our irreversible hard-sphere Markov chains generalize to arbitrary repulsive pair interactions and carry over to higher dimensions through the concept of lifted Markov chains and the recently introduced factorized Metropolis acceptance rule.

Irreversible Local Markov Chains with Rapid Convergence towards Equilibrium

NASA Astrophysics Data System (ADS)

Kapfer, Sebastian C.; Krauth, Werner

2017-12-01

We study the continuous one-dimensional hard-sphere model and present irreversible local Markov chains that mix on faster time scales than the reversible heat bath or Metropolis algorithms. The mixing time scales appear to fall into two distinct universality classes, both faster than for reversible local Markov chains. The event-chain algorithm, the infinitesimal limit of one of these Markov chains, belongs to the class presenting the fastest decay. For the lattice-gas limit of the hard-sphere model, reversible local Markov chains correspond to the symmetric simple exclusion process (SEP) with periodic boundary conditions. The two universality classes for irreversible Markov chains are realized by the totally asymmetric SEP (TASEP), and by a faster variant (lifted TASEP) that we propose here. We discuss how our irreversible hard-sphere Markov chains generalize to arbitrary repulsive pair interactions and carry over to higher dimensions through the concept of lifted Markov chains and the recently introduced factorized Metropolis acceptance rule.

Use of irreversible electroporation in unresectable pancreatic cancer

PubMed Central

2015-01-01

Irreversible electroporation is a non-thermal injury ablative modality that has been in clinical use since 2008 in the treatment of locally advanced soft tissue tumors. It has been reported to be utilized intraoperatively, laparoscopically or percutaneously. The method of action of IRE relies on a high voltage (maximum 3,000 volts) small microsecond pulse lengths (70 to 90 microseconds) to induce cell membrane porosity which leads to slow/protracted cell death over time. One of the largest unmet needs in oncology that IRE has been utilized is in locally advanced (stage III) pancreatic cancer. Recent studies have demonstrated the safety and palliation with encouraging improvement in overall survival. Its inherent limitation still remains tissue heterogeneity and the unique settings based on tumor histology and prior induction therapy. There remains a high technical demand of the end-user and the more extensive knowledge transfer which makes the learning curve longer in order to achieve appropriate and safe utilization. PMID:26151062

A Fingerprint Encryption Scheme Based on Irreversible Function and Secure Authentication

PubMed Central

Yu, Jianping; Zhang, Peng; Wang, Shulan

2015-01-01

A fingerprint encryption scheme based on irreversible function has been designed in this paper. Since the fingerprint template includes almost the entire information of users' fingerprints, the personal authentication can be determined only by the fingerprint features. This paper proposes an irreversible transforming function (using the improved SHA1 algorithm) to transform the original minutiae which are extracted from the thinned fingerprint image. Then, Chinese remainder theorem is used to obtain the biokey from the integration of the transformed minutiae and the private key. The result shows that the scheme has better performance on security and efficiency comparing with other irreversible function schemes. PMID:25873989

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.

Structure-activity relationship investigation for benzonaphthyridinone derivatives as novel potent Bruton's tyrosine kinase (BTK) irreversible inhibitors.

PubMed

Wang, Beilei; Deng, Yuanxin; Chen, Yongfei; Yu, Kailin; Wang, Aoli; Liang, Qianmao; Wang, Wei; Chen, Cheng; Wu, Hong; Hu, Chen; Miao, Weili; Hur, Wooyoung; Wang, Wenchao; Hu, Zhenquan; Weisberg, Ellen L; Wang, Jinhua; Ren, Tao; Wang, Yinsheng; Gray, Nathanael S; Liu, Qingsong; Liu, Jing

2017-09-08

Through a structure-based drug design approach, a tricyclic benzonaphthyridinone pharmacophore was used as a starting point for carrying out detailed medicinal structure-activity relationhip (SAR) studies geared toward characterization of a panel of proposed BTK inhibitors, including 6 (QL-X-138), 7 (BMX-IN-1) and 8 (QL47). These studies led to the discovery of the novel potent irreversible BTK inhibitor, compound 18 (CHMFL-BTK-11). Kinetic analysis of compound 18 revealed an irreversible binding efficacy (k inact /K i ) of 0.01 μM -1 s -1 . Compound 18 potently inhibited BTK kinase Y223 auto-phosphorylation (EC 50  < 100 nM), arrested cell cycle in G0/G1 phase, and induced apoptosis in Ramos, MOLM13 and Pfeiffer cells. We believe these features would make 18 a good pharmacological tool for studying BTK-related pathologies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

Brownian movement and microscopic irreversibility

NASA Astrophysics Data System (ADS)

Gordon, L. G. M.

1981-02-01

An extension of the hypothetical experiment of Szilard, which involved the action of a one-molecule gas in an isolated isothermal system, is developed to illustrate how irreversibility may arise out of Brownian motion. As this development requires a consideration of nonmolecular components such as wheels and pistons, the thought-experiment is remodeled in molecular terms and appears to function as a perpetuum mobile.

A minimal dissipation type-based classification in irreversible thermodynamics and microeconomics

NASA Astrophysics Data System (ADS)

Tsirlin, A. M.; Kazakov, V.; Kolinko, N. A.

2003-10-01

We formulate the problem of finding classes of kinetic dependencies in irreversible thermodynamic and microeconomic systems for which minimal dissipation processes belong to the same type. We show that this problem is an inverse optimal control problem and solve it. The commonality of this problem in irreversible thermodynamics and microeconomics is emphasized.

Macroscopic irreversibility and microscopic paradox: A Constructal law analysis of atoms as open systems

PubMed Central

Lucia, Umberto

2016-01-01

The relation between macroscopic irreversibility and microscopic reversibility is a present unsolved problem. Constructal law is introduced to develop analytically the Einstein’s, Schrödinger’s, and Gibbs’ considerations on the interaction between particles and thermal radiation (photons). The result leads to consider the atoms and molecules as open systems in continuous interaction with flows of photons from their surroundings. The consequent result is that, in any atomic transition, the energy related to the microscopic irreversibility is negligible, while when a great number of atoms (of the order of Avogadro’s number) is considered, this energy related to irreversibility becomes so large that its order of magnitude must be taken into account. Consequently, macroscopic irreversibility results related to microscopic irreversibility by flows of photons and amount of atoms involved in the processes. PMID:27762333

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.

Chronic Continuous Exenatide Infusion Does Not Cause Pancreatic Inflammation and Ductal Hyperplasia in Non-Human Primates

PubMed Central

Fiorentino, Teresa Vanessa; Owston, Michael; Abrahamian, Gregory; La Rosa, Stefano; Marando, Alessandro; Perego, Carla; Di Cairano, Eliana S.; Finzi, Giovanna; Capella, Carlo; Sessa, Fausto; Casiraghi, Francesca; Paez, Ana; Adivi, Ashwin; Davalli, Alberto; Fiorina, Paolo; Guardado Mendoza, Rodolfo; Comuzzie, Anthony G.; Sharp, Mark; DeFronzo, Ralph A.; Halff, Glenn; Dick, Edward J.; Folli, Franco

2016-01-01

In this study, we aimed to evaluate the effects of exenatide (EXE) treatment on exocrine pancreas of nonhuman primates. To this end, 52 baboons (Papio hamadryas) underwent partial pancreatectomy, followed by continuous infusion of EXE or saline (SAL) for 14 weeks. Histological analysis, immunohistochemistry, Computer Assisted Stereology Toolbox morphometry, and immunofluorescence staining were performed at baseline and after treatment. The EXE treatment did not induce pancreatitis, parenchymal or periductal inflammatory cell accumulation, ductal hyperplasia, or dysplastic lesions/pancreatic intraepithelial neoplasia. At study end, Ki-67–positive (proliferating) acinar cell number did not change, compared with baseline, in either group. Ki-67–positive ductal cells increased after EXE treatment (P = 0.04). However, the change in Ki-67–positive ductal cell number did not differ significantly between the EXE and SAL groups (P = 0.13). M-30–positive (apoptotic) acinar and ductal cell number did not change after SAL or EXE treatment. No changes in ductal density and volume were observed after EXE or SAL. Interestingly, by triple-immunofluorescence staining, we detected c-kit (a marker of cell transdifferentiation) positive ductal cells co-expressing insulin in ducts only in the EXE group at study end, suggesting that EXE may promote the differentiation of ductal cells toward a β-cell phenotype. In conclusion, 14 weeks of EXE treatment did not exert any negative effect on exocrine pancreas, by inducing either pancreatic inflammation or hyperplasia/dysplasia in nonhuman primates. PMID:25447052

A dioxin-like compound induces hyperplasia and branching morphogenesis in mouse mammary gland, through alterations in TGF-β1 and aryl hydrocarbon receptor signaling.

PubMed

Miret, Noelia; Rico-Leo, Eva; Pontillo, Carolina; Zotta, Elsa; Fernández-Salguero, Pedro; Randi, Andrea

2017-11-01

Hexachlorobenzene (HCB) is a widespread environmental pollutant and a dioxin-like compound that binds weakly to the aryl hydrocarbon receptor (AhR). Because AhR and transforming growth factor β1 (TGF-β1) converge to regulate common signaling pathways, alterations in this crosstalk might contribute to developing preneoplastic lesions. The aim of this study was to evaluate HCB action on TGF-β1 and AhR signaling in mouse mammary gland, through AhR+/+ and AhR-/- models. Results showed a differential effect in mouse mammary epithelial cells (NMuMG), depending on the dose: 0.05μM HCB induced cell migration and TGF-β1 signaling, whereas 5μM HCB reduced cell migration, promoted cell cycle arrest and stimulated the dioxin response element (DRE) -dependent pathway. HCB (5μM) enhanced α-smooth muscle actin expression and decreased TGF-β receptor II mRNA levels in immortalized mouse mammary fibroblasts AhR+/+, resembling the phenotype of transformed cells. Accordingly, their conditioned medium was able to enhance NMuMG cell migration. Assays in C57/Bl6 mice showed HCB (3mg/kg body weight) to enhance ductal hyperplasia, cell proliferation, estrogen receptor α nuclear localization, branch density, and the number of terminal end buds in mammary gland from AhR+/+ mice. Primary culture of mammary epithelial cells from AhR+/+ mice showed reduced AhR mRNA levels after HCB exposure (0.05 and 5μM). Interestingly, AhR-/- mice exhibited an increase in ductal hyperplasia and mammary growth in the absence of HCB treatment, thus revealing the importance of AhR in mammary development. Our findings show that environmental HCB concentrations modulate AhR and TGF-β1 signaling, which could contribute to altered mammary branching morphogenesis, likely leading to preneoplastic lesions and retaining terminal end buds. Copyright © 2017. Published by Elsevier Inc.

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.

Pilot Decision-Making in Irreversible Emergencies

ERIC Educational Resources Information Center

Winter, Scott R.

2013-01-01

The purpose of this study was to determine if a reflexive learning treatment utilizing select case studies could enhance the decision-making of pilots who encounter an irreversible emergency. Participants, who consisted of members of the subject university's professional pilot program, were divided into either a control or experimental group and…

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

Fluctuation theorems in feedback-controlled open quantum systems: Quantum coherence and absolute irreversibility

NASA Astrophysics Data System (ADS)

Murashita, Yûto; Gong, Zongping; Ashida, Yuto; Ueda, Masahito

2017-10-01

The thermodynamics of quantum coherence has attracted growing attention recently, where the thermodynamic advantage of quantum superposition is characterized in terms of quantum thermodynamics. We investigate the thermodynamic effects of quantum coherent driving in the context of the fluctuation theorem. We adopt a quantum-trajectory approach to investigate open quantum systems under feedback control. In these systems, the measurement backaction in the forward process plays a key role, and therefore the corresponding time-reversed quantum measurement and postselection must be considered in the backward process, in sharp contrast to the classical case. The state reduction associated with quantum measurement, in general, creates a zero-probability region in the space of quantum trajectories of the forward process, which causes singularly strong irreversibility with divergent entropy production (i.e., absolute irreversibility) and hence makes the ordinary fluctuation theorem break down. In the classical case, the error-free measurement ordinarily leads to absolute irreversibility, because the measurement restricts classical paths to the region compatible with the measurement outcome. In contrast, in open quantum systems, absolute irreversibility is suppressed even in the presence of the projective measurement due to those quantum rare events that go through the classically forbidden region with the aid of quantum coherent driving. This suppression of absolute irreversibility exemplifies the thermodynamic advantage of quantum coherent driving. Absolute irreversibility is shown to emerge in the absence of coherent driving after the measurement, especially in systems under time-delayed feedback control. We show that absolute irreversibility is mitigated by increasing the duration of quantum coherent driving or decreasing the delay time of feedback control.

Entropy production in a Glauber–Ising irreversible model with dynamical competition

NASA Astrophysics Data System (ADS)

Barbosa, Oscar A.; Tomé, Tânia

2018-06-01

An out of equilibrium Glauber–Ising model, evolving in accordance with an irreversible and stochastic Markovian dynamics, is analyzed in order to improve our comprehension concerning critical behavior and phase transitions in nonequilibrium systems. Therefore, a lattice model ruled by the competition between two Glauber dynamics acting on interlaced square lattices is proposed. Previous results have shown how the entropy production provides information about irreversibility and criticality. Mean-field approximations and Monte Carlo simulations were used in the analysis. The results obtained here show a continuous phase transition, reflected in the entropy production as a logarithmic divergence of its derivative, which suggests a shared universality class with the irreversible models invariant under the symmetry operations of the Ising model.

Goblet Cell Hyperplasia Requires High Bicarbonate Transport To Support Mucin Release.

PubMed

Gorrieri, Giulia; Scudieri, Paolo; Caci, Emanuela; Schiavon, Marco; Tomati, Valeria; Sirci, Francesco; Napolitano, Francesco; Carrella, Diego; Gianotti, Ambra; Musante, Ilaria; Favia, Maria; Casavola, Valeria; Guerra, Lorenzo; Rea, Federico; Ravazzolo, Roberto; Di Bernardo, Diego; Galietta, Luis J V

2016-10-27

Goblet cell hyperplasia, a feature of asthma and other respiratory diseases, is driven by the Th-2 cytokines IL-4 and IL-13. In human bronchial epithelial cells, we find that IL-4 induces the expression of many genes coding for ion channels and transporters, including TMEM16A, SLC26A4, SLC12A2, and ATP12A. At the functional level, we find that IL-4 enhances calcium- and cAMP-activated chloride/bicarbonate secretion, resulting in high bicarbonate concentration and alkaline pH in the fluid covering the apical surface of epithelia. Importantly, mucin release, elicited by purinergic stimulation, requires the presence of bicarbonate in the basolateral solution and is defective in cells derived from cystic fibrosis patients. In conclusion, our results suggest that Th-2 cytokines induce a profound change in expression and function in multiple ion channels and transporters that results in enhanced bicarbonate transport ability. This change is required as an important mechanism to favor release and clearance of mucus.

Goblet Cell Hyperplasia Requires High Bicarbonate Transport To Support Mucin Release

PubMed Central

Gorrieri, Giulia; Scudieri, Paolo; Caci, Emanuela; Schiavon, Marco; Tomati, Valeria; Sirci, Francesco; Napolitano, Francesco; Carrella, Diego; Gianotti, Ambra; Musante, Ilaria; Favia, Maria; Casavola, Valeria; Guerra, Lorenzo; Rea, Federico; Ravazzolo, Roberto; Di Bernardo, Diego; Galietta, Luis J. V.

2016-01-01

Goblet cell hyperplasia, a feature of asthma and other respiratory diseases, is driven by the Th-2 cytokines IL-4 and IL-13. In human bronchial epithelial cells, we find that IL-4 induces the expression of many genes coding for ion channels and transporters, including TMEM16A, SLC26A4, SLC12A2, and ATP12A. At the functional level, we find that IL-4 enhances calcium- and cAMP-activated chloride/bicarbonate secretion, resulting in high bicarbonate concentration and alkaline pH in the fluid covering the apical surface of epithelia. Importantly, mucin release, elicited by purinergic stimulation, requires the presence of bicarbonate in the basolateral solution and is defective in cells derived from cystic fibrosis patients. In conclusion, our results suggest that Th-2 cytokines induce a profound change in expression and function in multiple ion channels and transporters that results in enhanced bicarbonate transport ability. This change is required as an important mechanism to favor release and clearance of mucus. PMID:27786259

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.

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

Low dose oral desmopressin for nocturnal polyuria in patients with benign prostatic hyperplasia: a double-blind, placebo controlled, randomized study.

PubMed

Wang, Chung-Jing; Lin, Yu-Nan; Huang, Shi-Wei; Chang, Chien-Hsing

2011-01-01

We evaluated the long-term efficacy and safety of low dose oral desmopressin in elderly patients with benign prostatic hyperplasia with more than nocturnal voids and nocturnal polyuria more than 30% of total daily urine volume. Eligible patients with benign prostatic hyperplasia older than 65 years with nocturia, nocturnal polyuria and International Prostate Symptom Score 14 or greater were included in the study. All patients received placebo or 0.1 mg desmopressin orally at bedtime. Patients were required to visit the outpatient clinic from the first visit, and after 1, 3, 6 and 12 months of treatment. Patients maintained flow volume charts and used diaries to record voiding data throughout the study. During followup urinalysis, urine sodium, urine osmolality, serum electrolytes, prostate specific antigen, International Prostate Symptom Score, quality of life, transrectal ultrasonography of prostate, uroflowmetry and post-void residual urine volume were performed at each visit. A total of 115 patients were enrolled in the study and randomized as 58 in the placebo group and 57 in the desmopressin group. Desmopressin significantly decreased nocturnal urine output and the number of nocturia episodes, and prolonged the first sleep period (p < 0.01). Compared to before treatment desmopressin gradually decreased serum sodium and induced statistically but not clinically significant hyponatremia after 12 months of treatment. No serious systemic complications were found during medication. Low dose oral desmopressin is an effective and well tolerated treatment for nocturnal polyuria in the lower urinary tract symptoms of patients with benign prostatic hyperplasia. Long-term desmopressin therapy gradually decreases serum sodium and it might induce hyponatremia even in patients without initial hyponatremia. For long-term desmopressin administration serum sodium should be assessed carefully, at least at 1 week after treatment. Copyright © 2011 American Urological Association

[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.

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

Time irreversibility in reversible shell models of turbulence.

PubMed

De Pietro, Massimo; Biferale, Luca; Boffetta, Guido; Cencini, Massimo

2018-04-06

Turbulent flows governed by the Navier-Stokes equations (NSE) generate an out-of-equilibrium time irreversible energy cascade from large to small scales. In the NSE, the energy transfer is due to the nonlinear terms that are formally symmetric under time reversal. As for the dissipative term: first, it explicitly breaks time reversibility; second, it produces a small-scale sink for the energy transfer that remains effective even in the limit of vanishing viscosity. As a result, it is not clear how to disentangle the time irreversibility originating from the non-equilibrium energy cascade from the explicit time-reversal symmetry breaking due to the viscous term. To this aim, in this paper we investigate the properties of the energy transfer in turbulent shell models by using a reversible viscous mechanism, avoiding any explicit breaking of the [Formula: see text] symmetry. We probe time irreversibility by studying the statistics of Lagrangian power, which is found to be asymmetric under time reversal also in the time-reversible model. This suggests that the turbulent dynamics converges to a strange attractor where time reversibility is spontaneously broken and whose properties are robust for what concerns purely inertial degrees of freedoms, as verified by the anomalous scaling behavior of the velocity structure functions.

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.

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.

Variability of Irreversible Poleward Transport in the Lower Stratosphere

NASA Technical Reports Server (NTRS)

Olsen, Mark; Douglass, Anne; Newman, Paul; Nash, Eric; Witte, Jacquelyn; Ziemke, Jerry

2011-01-01

The ascent and descent of the Brewer-Dobson circulation plays a large role in determining the distributions of many constituents in the extratropical lower stratosphere. However, relatively fast, quasi-horizontal transport out of the tropics and polar regions also significantly contribute to determining these distributions. The tropical tape recorder signal assures that there must be outflow from the tropics into the extratropical lower stratosphere. The phase of the quasi-biennial oscillation (QBO) and state of the polar vortex are known to modulate the transport from the tropical and polar regions, respectively. In this study we examine multiple years of ozone distributions in the extratropical lower stratosphere observed by the Aura Microwave Limb Sounder (MLS) and the Aura High Resolution Dynamic Limb Sounder (HIRDLS). The distributions are compared with analyses of irreversible, meridional isentropic transport. We show that there is considerable year-to-year seasonal variability in the amount of irreversible transport from the tropics, which is related to both the phase of the QBO and the state of the polar vortex. The reversibility of the transport is consistent with the number of observed breaking waves. The variability of the atmospheric index of refraction in the lower stratosphere is shown to be significantly correlated with the wave breaking and amount of irreversible transport. Finally, we will show that the seasonal extratropical stratosphere to troposphere transport of ozone can be substantially modulated by the amount of irreversible meridional transport in the lower stratosphere and we investigate how observable these differences are in data of tropospheric ozone.

Effects of flavocoxid, a dual inhibitor of COX and 5-lipoxygenase enzymes, on benign prostatic hyperplasia

PubMed Central

Altavilla, D; Minutoli, L; Polito, F; Irrera, N; Arena, S; Magno, C; Rinaldi, M; Burnett, BP; Squadrito, F; Bitto, A

2012-01-01

BACKGROUND AND PURPOSE Inflammation plays a key role in the development of benign prostatic hyperplasia (BPH). Eicosanoids derived from the COX and 5-lipoxygenase (5-LOX) pathways are elevated in the enlarging prostate. Flavocoxid is a novel flavonoid–based ‘dual inhibitor’ of the COX and 5-LOX enzymes. This study evaluated the effects of flavocoxid in experimental BPH. EXPERIMENTAL APPROACH Rats were treated daily with testosterone propionate (3 mg·kg−1 s.c.) or its vehicle for 14 days to induce BPH. Animals receiving testosterone were randomized to receive vehicle (1 mL·kg−1, i.p.) or flavocoxid (20 mg·kg−1, i.p.) for 14 days. Histological changes, eicosanoid content and mRNA and protein levels for apoptosis-related proteins and growth factors were assayed in prostate tissue. The effects of flavocoxid were also tested on human prostate carcinoma PC3 cells. KEY RESULTS Flavocoxid reduced prostate weight and hyperplasia, blunted inducible expression of COX-2 and 5-LOX as well as the increased production of PGE2 and leukotriene B4 (LTB4), enhanced pro-apoptotic Bax and caspase-9 and decreased the anti-apoptotic Bcl-2 mRNA. Flavocoxid also reduced EGF and VEGF expression. In PC3 cells, flavocoxid stimulated apoptosis and inhibited growth factor expression. Flavocoxid-mediated induction of apoptosis was inhibited by the pan-caspase inhibitor, Z-VAD-FMK, in PC3 cells, suggesting an essential role of caspases in flavocoxid-mediated apoptosis during prostatic growth. CONCLUSION AND IMPLICATIONS Our results show that a ‘dual inhibitor’ of the COX and 5-LOX enzymes, such as flavocoxid, might represent a rational approach to reduce BPH through modulation of eicosanoid production and a caspase-induced apoptotic mechanism. PMID:22471974

Effects of flavocoxid, a dual inhibitor of COX and 5-lipoxygenase enzymes, on benign prostatic hyperplasia.

PubMed

Altavilla, D; Minutoli, L; Polito, F; Irrera, N; Arena, S; Magno, C; Rinaldi, M; Burnett, B P; Squadrito, F; Bitto, A

2012-09-01

Inflammation plays a key role in the development of benign prostatic hyperplasia (BPH). Eicosanoids derived from the COX and 5-lipoxygenase (5-LOX) pathways are elevated in the enlarging prostate. Flavocoxid is a novel flavonoid-based 'dual inhibitor' of the COX and 5-LOX enzymes. This study evaluated the effects of flavocoxid in experimental BPH. Rats were treated daily with testosterone propionate (3 mg·kg(-1)  s.c.) or its vehicle for 14 days to induce BPH. Animals receiving testosterone were randomized to receive vehicle (1 mL·kg(-1) , i.p.) or flavocoxid (20 mg·kg(-1) , i.p.) for 14 days. Histological changes, eicosanoid content and mRNA and protein levels for apoptosis-related proteins and growth factors were assayed in prostate tissue. The effects of flavocoxid were also tested on human prostate carcinoma PC3 cells. Flavocoxid reduced prostate weight and hyperplasia, blunted inducible expression of COX-2 and 5-LOX as well as the increased production of PGE(2) and leukotriene B(4) (LTB(4) ), enhanced pro-apoptotic Bax and caspase-9 and decreased the anti-apoptotic Bcl-2 mRNA. Flavocoxid also reduced EGF and VEGF expression. In PC3 cells, flavocoxid stimulated apoptosis and inhibited growth factor expression. Flavocoxid-mediated induction of apoptosis was inhibited by the pan-caspase inhibitor, Z-VAD-FMK, in PC3 cells, suggesting an essential role of caspases in flavocoxid-mediated apoptosis during prostatic growth. Our results show that a 'dual inhibitor' of the COX and 5-LOX enzymes, such as flavocoxid, might represent a rational approach to reduce BPH through modulation of eicosanoid production and a caspase-induced apoptotic mechanism. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

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

Life-threatening urethral hemorrhage after placement of a Foley catheter in a patient with uroseptic disseminated intravascular coagulation due to chronic urinary retention induced by untreated benign prostatic hyperplasia.

PubMed

Ikegami, Yukihiro; Yoshida, Keisuke; Imaizumi, Tsuyoshi; Isosu, Tsuyoshi; Kurosawa, Shin; Murakawa, Masahiro

2016-10-01

A 77-year-old man with severe septic disseminated intravascular coagulation following urinary infection was transported to our hospital. He had developed urinary retention induced by untreated prostatic hyperplasia. Immediate drainage with a Foley catheter was successfully carried out, but the hematuria progressed to life-threatening hemorrhage. Complete hemostasis was impossible by surgical treatment because the tissue around the prostatic urethra was very fragile and hemorrhagic. Organized treatments (continuous hemodiafiltration combined with polymyxin-B immobilized fiber column hemoperfusion and systemic treatment with antibiotics and coagulation factors) were commenced soon after the operation. The patient eventually recovered from the septic disseminated intravascular coagulation. This case report illustrates the risk of placement of Foley catheters in patients with severe septic disseminated intravascular coagulation.

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.

High regenerative capacity of the liver and irreversible injury of male reproductive system in carbon tetrachloride-induced liver fibrosis rat model.

PubMed

Bubnov, Rostyslav V; Drahulian, Maria V; Buchek, Polina V; Gulko, Tamara P

2018-03-01

Liver fibrosis (LF) is a chronic disease, associated with many collateral diseases including reproductive dysfunction. Although the normal liver has a large regenerative capacity the complications of LF could be severe and irreversible. Hormone and sex-related issues of LF development and interactions with male reproductive have not been finally studied. The aim was to study the reproductive function of male rats in experimental CCl 4 -induced liver fibrosis rat model, and the capability for restoration of both the liver and male reproduction system. Studies were conducted on 20 3-month old Wistar male rats. The experimental animals were injected with freshly prepared 50% olive oil solution of carbohydrate tetrachloride (CCl 4 ). On the 8th week after injection we noted the manifestations of liver fibrosis. The rats were left to self-healing of the liver for 8 weeks. All male rats underwent ultrasound and biopsy of the liver and testes on the 8th and 16th weeks. The male rats were mated with healthy females before CCl 4 injection, after modeling LF on the 8th week, and after self-healing of the liver. Pregnancy was monitored on ultrasound. On the 8th week of experiment we observed ultrasound manifestation of advanced liver fibrosis, including hepatosplenomegaly, portal hypertension. Ultrasound exam of the rat testes showed testicular degeneration, hydrocele, fibrosis, scarring, petrifications, size reduction, and restriction of testicular descent; testes size decreased from 1.24 ± 0.62 ml to 0.61 ± 0.13, p  < 0.01. Liver histology showed granular dystrophy of hepatocytes, necrotic areas, lipid inclusions in parenchyma. Rats with liver fibrosis demonstrated severe injury of the reproductive system and altering of fertility: the offspring of male rats with advanced LF was 4.71 ± 0.53 born alive vs 9.55 ± 0.47 born from mating with healthy males, p  < 0.001. Eight weeks after last CCl 4 injection, we revealed signs of liver regeneration, significant

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.

The connection between logical and thermodynamic irreversibility

NASA Astrophysics Data System (ADS)

Ladyman, James; Presnell, Stuart; Short, Anthony J.; Groisman, Berry

There has recently been a good deal of controversy about Landauer's Principle, which is often stated as follows: the erasure of one bit of information in a computational device is necessarily accompanied by a generation of kT ln 2 heat. This is often generalised to the claim that any logically irreversible operation cannot be implemented in a thermodynamically reversible way. Norton [2005. Eaters of the lotus: Landauer's principle and the return of Maxwell's demon. Studies in History and Philosophy of Modern Physics, 36, 375-411] and Maroney [2005. The (absence of a) relationship between thermodynamic and logical reversibility. Studies in History and Philosophy of Modern Physics, 36, 355-374] both argue that Landauer's Principle has not been shown to hold in general, and Maroney offers a method that he claims instantiates the operation Reset in a thermodynamically reversible way. In this paper we defend the qualitative form of Landauer's Principle, and clarify its quantitative consequences (assuming the second law of thermodynamics). We analyse in detail what it means for a physical system to implement a logical transformation L, and we make this precise by defining the notion of an L-machine. Then we show that logical irreversibility of L implies thermodynamic irreversibility of every corresponding L-machine. We do this in two ways. First, by assuming the phenomenological validity of the Kelvin statement of the second law, and second, by using information-theoretic reasoning. We illustrate our results with the example of the logical transformation 'Reset', and thereby recover the quantitative form of Landauer's Principle.

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.

Time irreversibility of financial time series based on higher moments and multiscale Kullback-Leibler divergence

NASA Astrophysics Data System (ADS)

Li, Jinyang; Shang, Pengjian

2018-07-01

Irreversibility is an important property of time series. In this paper, we propose the higher moments and multiscale Kullback-Leibler divergence to analyze time series irreversibility. The higher moments Kullback-Leibler divergence (HMKLD) can amplify irreversibility and make the irreversibility variation more obvious. Therefore, many time series whose irreversibility is hard to be found are also able to show the variations. We employ simulated data and financial stock data to test and verify this method, and find that HMKLD of stock data is growing in the form of fluctuations. As for multiscale Kullback-Leibler divergence (MKLD), it is very complex in the dynamic system, so that exploring the law of simulation and stock system is difficult. In conventional multiscale entropy method, the coarse-graining process is non-overlapping, however we apply a different coarse-graining process and obtain a surprising discovery. The result shows when the scales are 4 and 5, their entropy is nearly similar, which demonstrates MKLD is efficient to display characteristics of time series irreversibility.

Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 2, Insights into the Technical Rationale

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

Rationale of prostatic artery embolization (PAE) in the treatment of symptomatic benign prostatic hyperplasia is conventionally believed to include two parts: shrinkage of the enlarged prostate gland as a result of PAE-induced ischemic infarction and potential effects to relax the increased prostatic smooth muscle tone by reducing the number and density of α{sub 1}-adrenergic receptor in the prostate stroma. This review describes new insights into the likely mechanisms behind PAE, such as ischemia-induced apoptosis, apoptosis enhanced by blockage of androgens circulation to the embolized prostate, secondary denervation following PAE, and potential effect of nitric oxide pathway immediately after embolization. Studiesmore » on therapeutic mechanisms in PAE may shed light on potentially new treatment strategies and development of novel techniques.« less

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.

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

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

The natural outcome of melamine-induced bladder stones with bladder epithelial hyperplasia after the withdrawal of melamine in mice.

PubMed

Ren, Shu-Ting; Xu, Chang-Fu; Du, Yun-Xia; Gao, Xiao-Li; Sun, Ying; Jiang, Yi-Na

2012-07-01

The natural outcome of melamine-induced bladder stones (cystoliths) with bladder epithelial hyperplasia (BEH) after melamine withdrawn is unclear. Using an ideal dual-model system, three experiments were conducted in BALB/c mice. Each experiment included a control, model 1 and model 2 groups. The mice were fed a regular diet in controls or a 9373 ppm melamine diet in models, and the first day was designated as dosing day 1. The melamine diet was then replaced by the regular diet in the model 2 groups, and the first day was designated as post-dosing day 1. On dosing days 12, 35 and 49, the incidence of cystoliths and diffusely active BEH was 8/8 in the mice of three model 1 groups. On post-dosing days 1, 4 and 8, in the mice of three model 2 groups, the incidence of cystoliths was 2/8, 0/8 and 1/8, respectively, and the progressive regression of BEH was observed. In conclusion, both the stones and BEH have the natural property of rapid development and rapid regression, and melamine withdrawn plays a key role in the stone dissolution-discharge necessary for BEH regression. BEH may be reversible after the discharge of the stones. The conventionally conservative therapy is thus reasonable. Copyright © 2012 Elsevier Ltd. All rights reserved.

The immunohistochemical detection of involucrin in denture induced fibrous inflammatory hyperplasia of oral mucous membrane.

PubMed

Thomas, G A

1991-01-01

Involucrin is a major structural protein specific to the cross-linked cell envelope found in the stratum corneum of stratified squamous epithelium. This protein is considered to be an excellent immunohistochemical marker of normal squamous differentiation. Detection of variations to the patterns of immunostaining for involucrin may also be of value in the differential diagnosis between benign and malignant lesions. Previous studies of involucrin expression in oral mucosa have failed to clarify the effect of chronic inflammatory change upon the patterns of immunoreactivity. This study investigated involucrin staining patterns in fibrous inflammatory hyperplasia of oral mucous membrane (FIH). The results suggest that in FIH an altered pattern of involucrin immunostain occurs in areas of severe inflammatory change. This may reflect changes to the pattern of squamous differentiation in this tissue.

Changes in expression of cytokines in polyhexamethylene guanidine-induced lung fibrosis in mice: Comparison of bleomycin-induced lung fibrosis.

PubMed

Kim, Min-Seok; Kim, Sung-Hwan; Jeon, Doin; Kim, Hyeon-Young; Lee, Kyuhong

2018-01-15

Inhalation of polyhexamethylene guanidine (PHMG) causes irreversible pulmonary injury, such as pulmonary fibrosis. However, the mechanism underlying PHMG-induced lung injury is unclear. In this study, we compared the difference in time-dependent lung injury between PHMG- and bleomycin (BLM)-treated mice and determined cytokines involved in inducing lung injury by performing cytokine antibody array analysis. Mice were treated once with 1.8mg/kg BLM or 1.2mg/kg PHMG through intratracheal instillation and were sacrificed on days 7 and 28. Bronchoalveolar lavage fluid (BALF) analysis showed that the number of neutrophils was significantly higher in PHMG-treated mice than in BLM-treated mice on day 7. Histopathological analysis showed inflammatory cell infiltration and fibrosis mainly in the terminal bronchioles and alveoli in the lungs of PHMG- and BLM-treated mice. However, continuous macrophage infiltration in the alveolar space and bronchioloalveolar epithelial hyperplasia (BEH) were only observed in PHMG-treated mice. Cytokine antibody array analysis showed that 15 and eight cytokines were upregulated in PHMG- and BLM-treated mice, respectively, on day 7. On day 28, 13 and five cytokines were upregulated in PHMG and BLM-treated mice, respectively. In addition, the expressed cytokines between days 7 and 28 in BLM-treated mice were clearly different, but were similar in PHMG-treated mice. Consequently, between PHMG- and BLM-treated mice, we observed differences in the expression patterns and types of cytokines. These differences are considered to be a result of the inflammatory processes induced by both substances, which may mainly involve macrophage infiltration. Therefore, continuous induction of the inflammatory response by PHMG may play an important role in the development of pulmonary fibrosis. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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

Statistical Irreversible Thermodynamics in the Framework of Zubarev's Nonequilibrium Statistical Operator Method

NASA Astrophysics Data System (ADS)

Luzzi, R.; Vasconcellos, A. R.; Ramos, J. G.; Rodrigues, C. G.

2018-01-01

We describe the formalism of statistical irreversible thermodynamics constructed based on Zubarev's nonequilibrium statistical operator (NSO) method, which is a powerful and universal tool for investigating the most varied physical phenomena. We present brief overviews of the statistical ensemble formalism and statistical irreversible thermodynamics. The first can be constructed either based on a heuristic approach or in the framework of information theory in the Jeffreys-Jaynes scheme of scientific inference; Zubarev and his school used both approaches in formulating the NSO method. We describe the main characteristics of statistical irreversible thermodynamics and discuss some particular considerations of several authors. We briefly describe how Rosenfeld, Bohr, and Prigogine proposed to derive a thermodynamic uncertainty principle.

Re-analysis of experiments to quantify irreversibility of pesticide sorption-desorption in soil

USDA-ARS?s Scientific Manuscript database

Previously published research has used an isotope-exchange technique to measure irreversibility of pesticide adsorption-desorption in soil. Results have indicated significant irreversibility (6-51%) in the sorption in five pesticide-soil systems measured over 72 hours. Here, we propose a three-site ...

[Telangiectatic focal nodular hyperplasia accompanied with hemorrhage and necrosis during the course: report of a case].

PubMed

Machida, Takuro; Hirayama, Michiaki; Horita, Shoichi; Hagiwara, Seiya; Ikari, Shuji; Kato, Takashi; Sasaki, Kiyotaka; Kurose, Tatsuhiko; Nakamura, Hideaki; Kagaya, Hidetoshi; Meguro, Takashi; Abe, Motoki; Yamaguchi, Koji; Fujita, Miyoshi; Morita, Takayuki; Takahashi, Toshiyuki

2008-06-01

A tumor, which was 10 cm in diameter, was found in the lateral segment of the liver of a 42-year-old man in October, 2004. The lesion was clinically diagnosed as focal nodular hyperplasia (FNH). In March, 2006, the patient admitted our hospital complaining epigastralgia, back pain, and fever. Hemorrhage and necrotic region was revealed within the tumor, hence lateral segmentectomy was carried out. The lesion was pathologically diagnosed as a telangiectatic FNH (T-FNH). A possibility that hemorrhage or necrosis may be induced within a T-FNH during its progress should be taken into consideration.

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.

Time-Dependent Reversible-Irreversible Deformation Threshold Determined Explicitly by Experimental Technique

NASA Technical Reports Server (NTRS)

Castelli, Michael G.; Arnold, Steven M.

2000-01-01

Structural materials for the design of advanced aeropropulsion components are usually subject to loading under elevated temperatures, where a material's viscosity (resistance to flow) is greatly reduced in comparison to its viscosity under low-temperature conditions. As a result, the propensity for the material to exhibit time-dependent deformation is significantly enhanced, even when loading is limited to a quasi-linear stress-strain regime as an effort to avoid permanent (irreversible) nonlinear deformation. An understanding and assessment of such time-dependent effects in the context of combined reversible and irreversible deformation is critical to the development of constitutive models that can accurately predict the general hereditary behavior of material deformation. To this end, researchers at the NASA Glenn Research Center at Lewis Field developed a unique experimental technique that identifies the existence of and explicitly determines a threshold stress k, below which the time-dependent material deformation is wholly reversible, and above which irreversible deformation is incurred. This technique is unique in the sense that it allows, for the first time, an objective, explicit, experimental measurement of k. The underlying concept for the experiment is based on the assumption that the material s time-dependent reversible response is invariable, even in the presence of irreversible deformation.

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

Androgen receptor and immune inflammation in benign prostatic hyperplasia and prostate cancer

PubMed Central

Izumi, Kouji; Li, Lei; Chang, Chawnshang

2014-01-01

Both benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are frequent diseases in middle-aged to elderly men worldwide. While both diseases are linked to abnormal growth of the prostate, the epidemiological and pathological features of these two prostate diseases are different. BPH nodules typically arise from the transitional zone, and, in contrast, PCa arises from the peripheral zone. Androgen deprivation therapy alone may not be sufficient to cure these two prostatic diseases due to its undesirable side effects. The alteration of androgen receptor-mediated inflammatory signals from infiltrating immune cells and prostate stromal/epithelial cells may play key roles in those unwanted events. Herein, this review will focus on the roles of androgen/androgen receptor signals in the inflammation-induced progression of BPH and PCa. PMID:26594314

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

Statins and nitric oxide donors affect thrombospondin 1-induced chemotaxis.

PubMed

Seymour, Keri; Stein, Jeffrey; Han, Xuan; Maier, Kristopher G; Gahtan, Vivian

2014-01-01

Thrombospondin 1 (TSP-1) induces vascular smooth muscle cell (VSMC) migration and intimal hyperplasia. Statins and nitric oxide (NO) donors decrease intimal hyperplasia. We previously showed that statins (long-term exposure) and NO donors inhibit TSP-1-induced VSMC chemotaxis. (1) Pretreatment with short-term statin will inhibit TSP-1-induced VSMC chemotaxis and (2) NO donors will enhance statin inhibition of TSP-1-induced or platelet-derived growth factor (PDGF)-induced VSMC chemotaxis. We examined these treatment effects on TSP-1-induced VSMC chemotaxis: (1) long-term (20 hours) versus short-term (20 minutes) pravastatin, (2) diethylenetriamine NONOate (DETA/NO) or S-nitroso-N-acetylpenicillamine (SNAP) in combination with pravastatin, and (3) comparison of TSP-1 to PDGF as a chemoattractant. Pravastatin (long term or short term) inhibited TSP-1-induced chemotaxis. Diethylenetriamine NONOate and SNAP impeded statin inhibition of TSP-1-induced chemotaxis. Platelet-derived growth factor and TSP-1 had opposite effects on DETA/NO-pravastatin treatment. Short-term statin pretreatment inhibited TSP-1-induced VSMC chemotaxis, suggesting a pleiotropic effect. High-dose NO reversed statin inhibition of TSP-1-induced chemotaxis, suggesting NO and statin combination therapies warrant further study. © The Author(s) 2014.

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.

Irreversible impacts of heat on the emissions of monoterpenes, sesquiterpenes, phenolic BVOC and green leaf volatiles from several tree species

NASA Astrophysics Data System (ADS)

Kleist, E.; Mentel, T. F.; Andres, S.; Bohne, A.; Folkers, A.; Kiendler-Scharr, A.; Rudich, Y.; Springer, M.; Tillmann, R.; Wildt, J.

2012-12-01

Climate change will induce extended heat waves to parts of the vegetation more frequently. High temperatures may act as stress (thermal stress) on plants changing emissions of biogenic volatile organic compounds (BVOCs). As BVOCs impact the atmospheric oxidation cycle and aerosol formation, it is important to explore possible alterations of BVOC emissions under high temperature conditions. Applying heat to European beech, Palestine oak, Scots pine, and Norway spruce in a laboratory setup either caused the well-known exponential increases of BVOC emissions or induced irreversible changes of BVOC emissions. Considering only irreversible changes of BVOC emissions as stress impacts, we found that high temperatures decreased the de novo emissions of monoterpenes, sesquiterpenes and phenolic BVOC. This behaviour was independent of the tree species and whether the de novo emissions were constitutive or induced by biotic stress. In contrast, application of thermal stress to conifers amplified the release of monoterpenes stored in resin ducts of conifers and induced emissions of green leaf volatiles. In particular during insect attack on conifers, the plants showed de novo emissions of sesquiterpenes and phenolic BVOCs, which exceeded constitutive monoterpene emissions from pools. The heat-induced decrease of de novo emissions was larger than the increased monoterpene release caused by damage of resin ducts. For insect-infested conifers the net effect of thermal stress on BVOC emissions could be an overall decrease. Global change-induced heat waves may put hard thermal stress on plants. If so, we project that BVOC emissions increase is more than predicted by models only in areas predominantly covered with conifers that do not emit high amounts of sesquiterpenes and phenolic BVOCs. Otherwise overall effects of high temperature stress will be lower increases of BVOC emissions than predicted by algorithms that do not consider stress impacts.

Irreversible blockade of sigma-1 receptors by haloperidol and its metabolites in guinea pig brain and SH-SY5Y human neuroblastoma cells.

PubMed

Cobos, Enrique J; del Pozo, Esperanza; Baeyens, José M

2007-08-01

We evaluated the effect of haloperidol (HP) and its metabolites on [(3)H](+)-pentazocine binding to sigma(1) receptors in SH-SY5Y human neuroblastoma cells and guinea pig brain P(1), P(2) and P(3) subcellular fractions. Three days after a single i.p. injection in guinea pigs of HP (but not of other sigma(1) antagonists or (-)-sulpiride), [(3)H](+)-pentazocine binding to brain membranes was markedly decreased. Recovery of sigma(1) receptor density to steady state after HP-induced inactivation required more than 30 days. HP-metabolite II (reduced HP, 4-(4-chlorophenyl)-alpha-(4-fluorophenyl)-4-hydroxy-1-piperidinebutanol), but not HP-metabolite I (4-(4-chlorophenyl)-4-hydroxypiperidine), irreversibly blocked sigma(1) receptors in guinea pig brain homogenate and P(2) fraction in vitro. We found similar results in SH-SY5Y cells, which suggests that this process may also take place in humans. HP irreversibly inactivated sigma(1) receptors when it was incubated with brain homogenate and SH-SY5Y cells, but not when incubated with P(2) fraction membranes, which suggests that HP is metabolized to inactivate sigma(1) receptors. Menadione, an inhibitor of the ketone reductase activity that leads to the production of HP-metabolite II, completely prevented HP-induced inactivation of sigma(1) receptors in brain homogenates. These results suggest that HP may irreversibly inactivate sigma(1) receptors in guinea pig and human cells, probably after metabolism to reduced HP.

Patient-Specific, Multi-Scale Modeling of Neointimal Hyperplasia in Vein Grafts

PubMed Central

Donadoni, Francesca; Pichardo-Almarza, Cesar; Bartlett, Matthew; Dardik, Alan; Homer-Vanniasinkam, Shervanthi; Díaz-Zuccarini, Vanessa

2017-01-01

Neointimal hyperplasia is amongst the major causes of failure of bypass grafts. The disease progression varies from patient to patient due to a range of different factors. In this paper, a mathematical model will be used to understand neointimal hyperplasia in individual patients, combining information from biological experiments and patient-specific data to analyze some aspects of the disease, particularly with regard to mechanical stimuli due to shear stresses on the vessel wall. By combining a biochemical model of cell growth and a patient-specific computational fluid dynamics analysis of blood flow in the lumen, remodeling of the blood vessel is studied by means of a novel computational framework. The framework was used to analyze two vein graft bypasses from one patient: a femoro-popliteal and a femoro-distal bypass. The remodeling of the vessel wall and analysis of the flow for each case was then compared to clinical data and discussed as a potential tool for a better understanding of the disease. Simulation results from this first computational approach showed an overall agreement on the locations of hyperplasia in these patients and demonstrated the potential of using new integrative modeling tools to understand disease progression. PMID:28458640

Articaine for supplemental intraosseous anesthesia in patients with irreversible pulpitis.

PubMed

Bigby, Jason; Reader, Al; Nusstein, John; Beck, Mike; Weaver, Joel

2006-11-01

The purpose of this study was to determine the anesthetic efficacy and heart rate effect of 4% articaine with 1:100,000 epinephrine for supplemental intraosseous injection in mandibular posterior teeth diagnosed with irreversible pulpitis. Thirty-seven emergency patients, diagnosed with irreversible pulpitis of a mandibular posterior tooth, received an inferior alveolar nerve block and had moderate-to-severe pain upon endodontic access. The Stabident system was used to administer 1.8 ml of 4% articaine with 1:100,000 epinephrine. Success of the intraosseous injection was defined as none or mild pain upon endodontic access or initial instrumentation. The results demonstrated that anesthetic success was obtained in 86% (32 of 37) of the patients. Maximum mean heart rate was increased 32 beats/minute during the intraosseous injection. We can conclude that when the inferior alveolar nerve block fails to provide profound pulpal anesthesia, the intraosseous injection of 4% articaine with 1:100,000 epinephrine would be successful 86% of the time in achieving pulpal anesthesia in mandibular posterior teeth of patients presenting with irreversible pulpitis.

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.

Reversible and Irreversible Time-Dependent Behavior of GRCop-84

NASA Technical Reports Server (NTRS)

Lerch, Bradley A.; Arnold, Steven M.; Ellis, David L.

2017-01-01

A series of mechanical tests were conducted on a high-conductivity copper alloy, GRCop-84, in order to understand the time dependent response of this material. Tensile, creep, and stress relaxation tests were performed over a wide range of temperatures, strain rates, and stress levels to excite various amounts of time-dependent behavior. At low applied stresses the deformation behavior was found to be fully reversible. Above a certain stress, termed the viscoelastic threshold, irreversible deformation was observed. At these higher stresses the deformation was observed to be viscoplastic. Both reversible and irreversible regions contained time dependent deformation. These experimental data are documented to enable characterization of constitutive models to aid in design of high temperature components.

[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.

[Determination of irreversibility of clinical brain death. Electroencephalography and evoked potentials].

PubMed

Buchner, H; Ferbert, A

2016-02-01

Principally, in the fourth update of the rules for the procedure to finally determine the irreversible cessation of function of the cerebrum, the cerebellum and the brainstem, the importance of an electroencephalogram (EEG), somatosensory evoked potentials (SEP) and brainstem auditory evoked potentials (BAEP) are confirmed. This paper presents the reliability and validity of the electrophysiological diagnosis, discusses the amendments in the fourth version of the guidelines and introduces the practical application, problems and sources of error.An EEG is the best established supplementary diagnostic method for determining the irreversibility of clinical brain death syndrome. It should be noted that residual brain activity can often persist for many hours after the onset of brain death syndrome, particularly in patients with primary brainstem lesions. The derivation and analysis of an EEG requires a high level of expertise to be able to safely distinguish artefacts from primary brain activity. The registration of EEGs to demonstrate the irreversibility of clinical brain death syndrome is extremely time consuming.The BAEPs can only be used to confirm the irreversibility of brain death syndrome in serial examinations or in the rare cases of a sustained wave I or sustained waves I and II. Very often, an investigation cannot be reliably performed because of existing sound conduction disturbances or failure of all potentials even before the onset of clinical brain death syndrome. This explains why BAEPs are only used in exceptional cases.The SEPs of the median nerve can be very reliably derived, are technically simple and with few sources of error. A serial investigation is not required and the time needed for examination is short. For these reasons SEPs are given preference over EEGs and BAEPs for establishing the irreversibility of clinical brain death syndrome.

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.

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.

Theoretical foundations of apparent-damping phenomena and nearly irreversible energy exchange in linear conservative systems.

PubMed

Carcaterra, A; Akay, A

2007-04-01

This paper discusses a class of unexpected irreversible phenomena that can develop in linear conservative systems and provides a theoretical foundation that explains the underlying principles. Recent studies have shown that energy can be introduced to a linear system with near irreversibility, or energy within a system can migrate to a subsystem nearly irreversibly, even in the absence of dissipation, provided that the system has a particular natural frequency distribution. The present work introduces a general theory that provides a mathematical foundation and a physical explanation for the near irreversibility phenomena observed and reported in previous publications. Inspired by the properties of probability distribution functions, the general formulation developed here is based on particular properties of harmonic series, which form the common basis of linear dynamic system models. The results demonstrate the existence of a special class of linear nondissipative dynamic systems that exhibit nearly irreversible energy exchange and possess a decaying impulse response. In addition to uncovering a new class of dynamic system properties, the results have far-reaching implications in engineering applications where classical vibration damping or absorption techniques may not be effective. Furthermore, the results also support the notion of nearly irreversible energy transfer in conservative linear systems, which until now has been a concept associated exclusively with nonlinear systems.

Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes.

PubMed

Dubovsky, Jason A; Beckwith, Kyle A; Natarajan, Gayathri; Woyach, Jennifer A; Jaglowski, Samantha; Zhong, Yiming; Hessler, Joshua D; Liu, Ta-Ming; Chang, Betty Y; Larkin, Karilyn M; Stefanovski, Matthew R; Chappell, Danielle L; Frissora, Frank W; Smith, Lisa L; Smucker, Kelly A; Flynn, Joseph M; Jones, Jeffrey A; Andritsos, Leslie A; Maddocks, Kami; Lehman, Amy M; Furman, Richard; Sharman, Jeff; Mishra, Anjali; Caligiuri, Michael A; Satoskar, Abhay R; Buggy, Joseph J; Muthusamy, Natarajan; Johnson, Amy J; Byrd, John C

2013-10-10

Given its critical role in T-cell signaling, interleukin-2-inducible kinase (ITK) is an appealing therapeutic target that can contribute to the pathogenesis of certain infectious, autoimmune, and neoplastic diseases. Ablation of ITK subverts Th2 immunity, thereby potentiating Th1-based immune responses. While small-molecule ITK inhibitors have been identified, none have demonstrated clinical utility. Ibrutinib is a confirmed irreversible inhibitor of Bruton tyrosine kinase (BTK) with outstanding clinical activity and tolerability in B-cell malignancies. Significant homology between BTK and ITK alongside in silico docking studies support ibrutinib as an immunomodulatory inhibitor of both ITK and BTK. Our comprehensive molecular and phenotypic analysis confirms ITK as an irreversible T-cell target of ibrutinib. Using ibrutinib clinical trial samples along with well-characterized neoplastic (chronic lymphocytic leukemia), parasitic infection (Leishmania major), and infectious disease (Listeria monocytogenes) models, we establish ibrutinib as a clinically relevant and physiologically potent ITK inhibitor with broad therapeutic utility. This trial was registered at www.clinicaltrials.gov as #NCT01105247 and #NCT01217749.

Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes

PubMed Central

Dubovsky, Jason A.; Beckwith, Kyle A.; Natarajan, Gayathri; Woyach, Jennifer A.; Jaglowski, Samantha; Zhong, Yiming; Hessler, Joshua D.; Liu, Ta-Ming; Chang, Betty Y.; Larkin, Karilyn M.; Stefanovski, Matthew R.; Chappell, Danielle L.; Frissora, Frank W.; Smith, Lisa L.; Smucker, Kelly A.; Flynn, Joseph M.; Jones, Jeffrey A.; Andritsos, Leslie A.; Maddocks, Kami; Lehman, Amy M.; Furman, Richard; Sharman, Jeff; Mishra, Anjali; Caligiuri, Michael A.; Satoskar, Abhay R.; Buggy, Joseph J.; Muthusamy, Natarajan; Johnson, Amy J.

2013-01-01

Given its critical role in T-cell signaling, interleukin-2–inducible kinase (ITK) is an appealing therapeutic target that can contribute to the pathogenesis of certain infectious, autoimmune, and neoplastic diseases. Ablation of ITK subverts Th2 immunity, thereby potentiating Th1-based immune responses. While small-molecule ITK inhibitors have been identified, none have demonstrated clinical utility. Ibrutinib is a confirmed irreversible inhibitor of Bruton tyrosine kinase (BTK) with outstanding clinical activity and tolerability in B-cell malignancies. Significant homology between BTK and ITK alongside in silico docking studies support ibrutinib as an immunomodulatory inhibitor of both ITK and BTK. Our comprehensive molecular and phenotypic analysis confirms ITK as an irreversible T-cell target of ibrutinib. Using ibrutinib clinical trial samples along with well-characterized neoplastic (chronic lymphocytic leukemia), parasitic infection (Leishmania major), and infectious disease (Listeria monocytogenes) models, we establish ibrutinib as a clinically relevant and physiologically potent ITK inhibitor with broad therapeutic utility. This trial was registered at www.clinicaltrials.gov as #NCT01105247 and #NCT01217749. PMID:23886836

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

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.

Irreversible and reversible components in the genesis of hypertension by sodium chloride (salt).

PubMed

Tekol, Yalcin

2008-01-01

Despite the abundant studies and overwhelming evidences demonstrating the essential role of salt (sodium chloride) for developing "essential" hypertension (EH), the controversies about salt-hypertension (HT) relations are still continuing. One of important mistakes in this topic is assuming that the HT-producing effect of salt is reversible. The present paper explains the complex nature of salt-HT relations. The deduction was made basing on the studies which investigate the relations between salt and HT. Animal experiments show that HT-producing effect of salt contains irreversible and reversible components. The existence of irreversible component manifests itself in this way: the blood pressure (BP) does not recede to the natural values despite removing of salt exposure. The proportion of BP decreasing after salt exposure termination belongs to the reversible component. Available evidences indicate that the irreversible component is developed in utero, during suckling and, generally, in prepubertal period secondary to salt exposure, however, if the salt exposure extends over more than one period, the HT may be intensified. The consequences of salt exposure during early life of human beings have not been investigated as detailed as in experimental animals, however, there are some clinical trials and epidemiological observations indicating that, similar to experimental animals, irreversible and reversible components are also developed in man during the genesis of HT. By the introduction of irreversible and reversible components notion, some obscured items on salt-HT relations can be clarified. For example, some intervention studies could not find dramatic relations between salt and HT, because these interventions modify only the reversible component, but irreversible component remains unchanged. As a result, salt exposure is detrimental for each period of life. For eradication of HT, it is prerequisite to prevent all individuals (especially pregnant or lactating

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.

Partial purification of the mu opioid receptor irreversibly labeled with (/sup 3/H)b-funaltrexamine

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

Liu-Chen, L.Y.; Phillips, C.A.; Tam, S.W.

1986-03-01

The mu opioid receptor in bovine striatal membranes was specifically and irreversibly labeled by incubation with 5 nM (/sup 3/H)..beta..-funaltrexamine (approx.-FNA) at 37/sup 0/C for 90 min in the presence of 100 mM NaCl. The specific and irreversible binding of (/sup 3/H)..beta..-FNA as defined by that blocked by 1 /sup +/M naloxone was about 60% of total irreversible binding. The specific irreversible binding was saturable, stereospecific, time-, temperature, and tissue-dependent. Mu opioid ligands were much more potent than delta or kappa ligands in inhibiting the specific irreversible labeling. SDS polyacrylamide gel electrophoresis of solubilized membranes in the presence of 2-mercaptoethanolmore » yielded a major radiolabeled broad band of MW 68-97K daltons, characteristic of a glycoprotein band. This band was not observed in membranes labeled in the presence of excess unlabeled naloxone. The glycoprotein nature of the (/sup 3/H)..beta..-FNA-labeled opioid receptor was confirmed by its binding to a wheat germ agglutinin-Sepharose column and its elution with N-acetylglucosamine.« less

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.

Proliferation of Prostate Stromal Cell Induced by Benign Prostatic Hyperplasia Epithelial Cell Stimulated With Trichomonas vaginalis via Crosstalk With Mast Cell.

PubMed

Kim, Jung-Hyun; Kim, Sang-Su; Han, Ik-Hwan; Sim, Seobo; Ahn, Myoung-Hee; Ryu, Jae-Sook

2016-11-01

Chronic inflammation has a role in the pathogenesis of benign prostatic hyperplasia (BPH) and prostate cancer. Mast cells have been detected in chronic inflammatory infiltrate of the prostate, and it is possible that the interaction between prostate epithelial cells and Trichomonas vaginalis influences the activity of mast cells in the prostate stroma. Activated mast cells might influence the biological functions of nearby tissues and cells. In this study, we investigated whether mast cells reacted with the culture supernatant of BPH epithelial cells infected with T. vaginalis may induce the proliferation of prostate stromal cells. To measure the proliferation of prostate stromal cells in response to chronic inflammation caused by the infection of BPH-1 cells with T. vaginalis, the CCK-8 assay and wound healing assay were used. ELISAs, quantitative real-time PCR, western blotting and immunofluorescence were used to measure the production and expression of inflammatory cytokine and cytokine receptor. BPH-1 cells incubated with live trichomonads produced increased levels of CCL2, IL-1β, IL-6, and CXCL8, and induced the migration of mast cells and monocytes. When the culture supernatant of BPH-1 cells stimulated with trichomonads (TCM) was added to mast cells, they became activated, as confirmed by release of β-hexosaminidase and CXCL8. Prostate stromal cells incubated with the culture supernatant of mast cells activated with TCM (M-TCM) proliferated and expressed increased levels of CXCL8, CCL2, and the cytokine receptors CXCR1 and CCR2. Blocking the chemokine receptors reduced the proliferation of stromal cells and also decreased the production of CXCL8 and CCL2. Moreover, the expression of FGF2, cyclin D1, and Bcl-2 was increased in the proliferated stromal cells stimulated with M-TCM. Additionally, the M-TCM-treated stromal cells were more invasive than control cells. The inflammatory mediators released by BPH epithelial cells in response to infection by

[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.

Irreversible denaturation of maltodextrin glucosidase studied by differential scanning calorimetry, circular dichroism, and turbidity measurements.

PubMed

Goyal, Megha; Chaudhuri, Tapan K; Kuwajima, Kunihiro

2014-01-01

Thermal denaturation of Escherichia coli maltodextrin glucosidase was studied by differential scanning calorimetry, circular dichroism (230 nm), and UV-absorption measurements (340 nm), which were respectively used to monitor heat absorption, conformational unfolding, and the production of solution turbidity. The denaturation was irreversible, and the thermal transition recorded at scan rates of 0.5-1.5 K/min was significantly scan-rate dependent, indicating that the thermal denaturation was kinetically controlled. The absence of a protein-concentration effect on the thermal transition indicated that the denaturation was rate-limited by a mono-molecular process. From the analysis of the calorimetric thermograms, a one-step irreversible model well represented the thermal denaturation of the protein. The calorimetrically observed thermal transitions showed excellent coincidence with the turbidity transitions monitored by UV-absorption as well as with the unfolding transitions monitored by circular dichroism. The thermal denaturation of the protein was thus rate-limited by conformational unfolding, which was followed by a rapid irreversible formation of aggregates that produced the solution turbidity. It is thus important to note that the absence of the protein-concentration effect on the irreversible thermal denaturation does not necessarily means the absence of protein aggregation itself. The turbidity measurements together with differential scanning calorimetry in the irreversible thermal denaturation of the protein provided a very effective approach for understanding the mechanisms of the irreversible denaturation. The Arrhenius-equation parameters obtained from analysis of the thermal denaturation were compared with those of other proteins that have been reported to show the one-step irreversible thermal denaturation. Maltodextrin glucosidase had sufficiently high kinetic stability with a half-life of 68 days at a physiological temperature (37°C).

Irreversible evolution of angular-dependent coercivity in Fe80Ni20 nanowire arrays: Detection of a single vortex state

NASA Astrophysics Data System (ADS)

Alikhani, M.; Ramazani, A.; Almasi Kashi, M.; Samanifar, S.; Montazer, A. H.

2016-09-01

The irreversible evolution of magnetic coercivity in arrays of 75 nm diameter Fe80Ni20 nanowires (NWs) has been explored by means of first-order reversal curve (FORC) analysis as a function of the angle between the magnetic field and the NW axis (0°≤θ≤90°). The Fe80Ni20 NWs with lengths up to 60 μm were fabricated using a pulsed electrodeposition method into hard-anodic aluminum oxide templates with an interpore distance of 275 nm. Investigating the interwire and intrawire magnetostatic interactions, the angular FORC (AFORC) diagrams indicated enhanced intrawire interactions with increasing length and θ (<90°), induced by a magnetization reversal through vortex domain wall (VDW) propagation. Intriguingly, in addition to the VDW mode, a single vortex state with broad irreversible switching of nucleation and annihilation fields was detected at θ=83° for 60 μm long NWs. At θ=90°, the NWs reversed magnetization through transverse domain wall, involving a reversible component by a fraction of 95%. Furthermore, the transition angle between the reversal modes was found to decrease with increasing aspect ratio from 200 to 800. The irreversible angular-dependent coercivity (HcIrrev(θ)) of Fe80Ni20 NWs was extracted from the AFORC measurements and compared with the major angular dependence of coercivity (HcMajor(θ)) obtained from the conventional hysteresis loop measurements. While HcMajor(θ) showed a non-monotonic behavior, HcIrrev(θ) constantly increased with increasing θ (<90°). On the other hand, using analytical models, a 93% agreement was obtained between the theoretical angular-dependent nucleation field and experimental HcIrrev(θ) for irreversible switching of VDW when 0°≤θ≤86°.

The Anti-Inflammatory Effects of Matrix Metalloproteinase-3 on Irreversible Pulpitis of Mature Erupted Teeth

PubMed Central

Eba, Hisanori; Murasawa, Yusuke; Iohara, Koichiro; Isogai, Zenzo; Nakamura, Hiroshi; Nakamura, Hiroyuki; Nakashima, Misako

2012-01-01

Matrix metalloproteinases (MMPs) are involved in extracellular matrix degradation and the modulation of cell behavior. These proteinases have also been implicated in tissue repair and regeneration. Our previous studies have demonstrated that MMP-3 elicits stimulatory effects on the proliferation and the migration of endothelial cells as well as anti-apoptotic effects on these cells in vitro. In addition, we found that MMP-3 enhanced the regeneration of lost pulp tissue in a rat incisor pulp injury model. However, continuously erupting rodent incisors exhibit significantly different pulp organization compared with mature erupted teeth. Therefore, we have further extended these studies using a canine irreversible pulpitis model to investigate the effects of MMP-3. In this study, the crowns of the canine mature premolars were removed and the pulp tissues were amputated. The amputated pulp tissues remained exposed for 24 or 72 hours to induce mild or severe irreversible pulpitis, respectively, followed by sealing of the cavities. In both models, the whole pulp tissues became necrotic by day 14. In this mild pulpitis model, the regeneration of pulp tissue with vasculature and nerves was observed until 14 days after sealing with MMP-3, followed by extracellular matrix formation in the regenerated pulp tissues until day 28. The treatment with MMP-3 resulted in a decrease in the number of macrophage and antigen-presenting cells and a significant inhibition of IL-6 expression on day 3. The inhibition of MMP-3 activity abolished these anti-inflammatory effects. Immunofluorescence staining demonstrated that MMP-3 was involved in the modification of serum-derived hyaluronan-associated proteins and hyaluronan (SHAP-HA) complexes possibly through the degradation of versican. These results demonstrate that MMP-3 can act as an anti-inflammatory agent and suggest that MMP-3 might represent a useful therapy for the treatment of mild irreversible pulpitis. PMID:23285075

High expression of neutral endopeptidase in idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells.

PubMed

Cohen, A J; King, T E; Gilman, L B; Magill-Solc, C; Miller, Y E

1998-11-01

Idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells (IDHPNC) is a clinicopathological entity characterized by a diffuse hyperplasia of neuroendocrine cells involving distal bronchi and bronchioles. The pathogenesis of this syndrome remains unknown. The hyperplastic neuroendocrine (NE) cells contain multiple neuropeptides, including the bombesinlike peptides (BLP), which are likely important in the pathogenesis of the disorder by stimulating proliferation of fibroblasts in a paracrine fashion and the NE cells themselves in an autocrine manner. Neutral endopeptidase (NEP) is a cell-surface enzyme that hydrolyzes BLP and other bioactive peptides. Low or undetectable NEP is present in many primary lung cancers and cell lines. Low NEP expression could increase neuropeptide-induced autocrine effects by increasing local levels of neuropeptides. We hypothesized that IDHPNC was associated with low or absent NEP expression. NEP expression was assayed in patients with IDHPNC (n = 3) and was compared with expression in patients with idiopathic pulmonary fibrosis (n = 5), hypersensitivity pneumonitis (n = 5), and normal lung (n = 4) using immunohistochemistry, ELISA, activity assay, and Western blot analysis. By these assays, NEP expression was highest in lungs affected by IDHPNC. NEP mRNA, as assessed in IDHPNC lung tissue by RT-PCR, was the expected size and free of mutation between bp 238-2437. Therefore, IDHPNC is unlikely to be the result of a defect in NEP expression. The apparent increase in NEP expression in lung tissue from patients with IDHPNC may reflect a compensatory increase that partly counteracts abundant neuropeptides, including BLP, present in this disorder.

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.

Inertial effects during irreversible meniscus reconfiguration in angular pores

NASA Astrophysics Data System (ADS)

Ferrari, Andrea; Lunati, Ivan

2014-12-01

In porous media, the dynamics of the invading front between two immiscible fluids is often characterized by abrupt reconfigurations caused by local instabilities of the interface. As a prototype of these phenomena we consider the dynamics of a meniscus in a corner as it can be encountered in angular pores. We investigate this process in detail by means of direct numerical simulations that solve the Navier-Stokes equations in the pore space and employ the Volume of Fluid method (VOF) to track the evolution of the interface. We show that for a quasi-static displacement, the numerically calculated surface energy agrees well with the analytical solutions that we have derived for pores with circular and square cross sections. However, the spontaneous reconfigurations are irreversible and cannot be controlled by the injection rate: they are characterized by the amount of surface energy that is spontaneously released and transformed into kinetic energy. The resulting local velocities can be orders of magnitude larger than the injection velocity and they induce damped oscillations of the interface that possess their own time scales and depend only on fluid properties and pore geometry. In complex media (we consider a network of cubic pores) reconfigurations are so frequent and oscillations last long enough that increasing inertial effects leads to a different fluid distribution by influencing the selection of the next pore to be invaded. This calls into question simple pore-filling rules based only on capillary forces. Also, we demonstrate that inertial effects during irreversible reconfigurations can influence the work done by the external forces that is related to the pressure drop in Darcy's law. This suggests that these phenomena have to be considered when upscaling multiphase flow because local oscillations of the menisci affect macroscopic quantities and modify the constitutive relationships to be used in macro-scale models. These results can be extrapolated to other

Simplification of irreversible Markov chains by removal of states with fast leaving rates.

PubMed

Jia, Chen

2016-07-07

In the recent work of Ullah et al. (2012a), the authors developed an effective method to simplify reversible Markov chains by removal of states with low equilibrium occupancies. In this paper, we extend this result to irreversible Markov chains. We show that an irreversible chain can be simplified by removal of states with fast leaving rates. Moreover, we reveal that the irreversibility of the chain will always decrease after model simplification. This suggests that although model simplification can retain almost all the dynamic information of the chain, it will lose some thermodynamic information as a trade-off. Examples from biology are also given to illustrate the main results of this paper. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reversible and irreversible sorption of perfluorinated compounds (PFCs) by sediments of an urban reservoir.

PubMed

Chen, Huiting; Reinhard, Martin; Nguyen, Viet Tung; Gin, Karina Yew-Hoong

2016-02-01

Uncertainty about the extent to which contaminant sorption by suspended solids and bed sediments is irreversible is a major impediment for modeling and managing the water quality of surface water resources. This study examined reversible and irreversible sorption of several perfluorinated compounds (PFCs) to bed sediments from an urban reservoir. PFCs investigated include C4, C6, C8, C9 and C10 perfluoroalkanoate homologues (PFBA, PFHxA, PFOA, PFNA and PFDA, respectively) and perfluorooctane and hexane sulfonate (PFOS and PFHxS, respectively). Although sorption branches of the PFOS, PFNA and PFDA isotherms were nearly linear (implying a partitioning-like process), desorption experiments indicated that a fraction of the sorbed PFCs were entrapped and resistant to desorption. The hysteretic desorption branches were approximately linear. Irreversibility increased with chain length and was nearly complete for PFDA (thermodynamic irreversibility index (TII) 0.98). For the weakly sorbing PFOA and PFHxS, sorption was largely reversible. Data suggest that (1) for the strongly sorbing PFCs, e.g. PFNA, PFDA and PFOS, bed sediments acted predominantly as irreversible sinks, (2) aqueous concentrations of the moderately sorbing PFCs (PFOA and PFHxS) are buffered by reversibly sorbing suspended solids, and (3) the short-chain PFCs (PFBA and PFHxA) are not significantly sorbed and therefore not expected to be significantly influenced by sediment transport. Situations in which highly contaminated particles entering relatively clean water bodies, equilibrium is approached from the reverse (desorption) direction. For irreversibly sorbed contaminants field-based K(D) values will be higher than the K(D) values derived from laboratory sorption data obtained from forward sorption experiments. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hyperplasia of the submucosal glands of the columnar-lined oesophagus.

PubMed

Lörinc, Ester; Öberg, Stefan

2015-04-01

To evaluate the presence of multi-layered epithelium (ME) and to compare the distribution, size and morphology of the oesophageal submucosal glands (SMG) beneath reflux exposed metaplastic columnar mucosa with those of normal squamous epithelium in patients with columnar-lined oesophagus (CLO). In eight oesophageal resection specimens, the SMG of the metaplastic segments were significantly larger than those in the squamous segments of patients with CLO (0.81 versus 0.56 mm(2) , P = <0.001). There was an accumulation of SMG close to the neosquamocolumnar junction (NSCJ), as indicated by a higher median frequency of SMG (0.080 SMG/mm) compared with that of the squamous (0.013 SMG/mm) and metaplastic segments (0.031 SMG/mm) (P = 0.022). The frequency of ME was significantly higher in the metaplastic compared with the normal squamous segments (1/158 mm and 1/341 mm, respectively, P = 0.028) and ME was found almost exclusively (96%) in direct connection with the excretory ducts of SMG. Hyperplasia of SMG in the metaplastic segment, accumulation of SMG near the NSCJ, the presence of ME in connection with the excretory ducts of SMG and metaplasia are all reflux-induced morphological changes, possibly induced by stimulation of progenitors in the excretory ducts of the SMG. © 2014 John Wiley & Sons Ltd.

Irreversible Denaturation of Maltodextrin Glucosidase Studied by Differential Scanning Calorimetry, Circular Dichroism, and Turbidity Measurements

PubMed Central

Goyal, Megha; Chaudhuri, Tapan K.; Kuwajima, Kunihiro

2014-01-01

Thermal denaturation of Escherichia coli maltodextrin glucosidase was studied by differential scanning calorimetry, circular dichroism (230 nm), and UV-absorption measurements (340 nm), which were respectively used to monitor heat absorption, conformational unfolding, and the production of solution turbidity. The denaturation was irreversible, and the thermal transition recorded at scan rates of 0.5–1.5 K/min was significantly scan-rate dependent, indicating that the thermal denaturation was kinetically controlled. The absence of a protein-concentration effect on the thermal transition indicated that the denaturation was rate-limited by a mono-molecular process. From the analysis of the calorimetric thermograms, a one-step irreversible model well represented the thermal denaturation of the protein. The calorimetrically observed thermal transitions showed excellent coincidence with the turbidity transitions monitored by UV-absorption as well as with the unfolding transitions monitored by circular dichroism. The thermal denaturation of the protein was thus rate-limited by conformational unfolding, which was followed by a rapid irreversible formation of aggregates that produced the solution turbidity. It is thus important to note that the absence of the protein-concentration effect on the irreversible thermal denaturation does not necessarily means the absence of protein aggregation itself. The turbidity measurements together with differential scanning calorimetry in the irreversible thermal denaturation of the protein provided a very effective approach for understanding the mechanisms of the irreversible denaturation. The Arrhenius-equation parameters obtained from analysis of the thermal denaturation were compared with those of other proteins that have been reported to show the one-step irreversible thermal denaturation. Maltodextrin glucosidase had sufficiently high kinetic stability with a half-life of 68 days at a physiological temperature (37°C). PMID

Time irreversibility and multifractality of power along single particle trajectories in turbulence

NASA Astrophysics Data System (ADS)

Cencini, Massimo; Biferale, Luca; Boffetta, Guido; De Pietro, Massimo

2017-10-01

The irreversible turbulent energy cascade epitomizes strongly nonequilibrium systems. At the level of single fluid particles, time irreversibility is revealed by the asymmetry of the rate of kinetic energy change, the Lagrangian power, whose moments display a power-law dependence on the Reynolds number, as recently shown by Xu et al. [H. Xu et al., Proc. Natl. Acad. Sci. USA 111, 7558 (2014), 10.1073/pnas.1321682111]. Here Lagrangian power statistics are rationalized within the multifractal model of turbulence, whose predictions are shown to agree with numerical and empirical data. Multifractal predictions are also tested, for very large Reynolds numbers, in dynamical models of the turbulent cascade, obtaining remarkably good agreement for statistical quantities insensitive to the asymmetry and, remarkably, deviations for those probing the asymmetry. These findings raise fundamental questions concerning time irreversibility in the infinite-Reynolds-number limit of the Navier-Stokes equations.

Estimating Temperature Rise Due to Flashlamp Heating Using Irreversible Temperature Indicators

NASA Technical Reports Server (NTRS)

Koshti, Ajay M.

1999-01-01

One of the nondestructive thermography inspection techniques uses photographic flashlamps. The flashlamps provide a short duration (about 0.005 sec) heat pulse. The short burst of energy results in a momentary rise in the surface temperature of the part. The temperature rise may be detrimental to the top layer of the part being exposed. Therefore, it is necessary to ensure the nondestructive nature of the technique. Amount of the temperature rise determines whether the flashlamp heating would be detrimental to the part. A direct method for the temperature measurement is to use of an infrared pyrometer that has much shorter response time than the flash duration. In this paper, an alternative technique is given using the irreversible temperature 'indicators. This is an indirect technique and it measures the temperature rise on the irreversible temperature indicators and computes the incident heat flux. Once the heat flux is known, the temperature rise on the part can be computed. A wedge shaped irreversible temperature indicator for measuring the heat flux is proposed. A procedure is given to use the wedge indicator.

Reversing the irreversible: From limit cycles to emergent time symmetry

NASA Astrophysics Data System (ADS)

Cortês, Marina; Smolin, Lee

2018-01-01

In 1979 Penrose hypothesized that the arrows of time are explained by the hypothesis that the fundamental laws are time irreversible [R. Penrose, in General Relativity: An Einstein Centenary Survey (1979)]. That is, our reversible laws, such as the standard model and general relativity are effective, and emerge from an underlying fundamental theory which is time irreversible. In [M. Cortês and L. Smolin, Phys. Rev. D 90, 084007 (2014), 10.1103/PhysRevD.90.084007; 90, 044035 (2014), 10.1103/PhysRevD.90.044035; 93, 084039 (2016), 10.1103/PhysRevD.93.084039] we put forward a research program aiming at realizing just this. The aim is to find a fundamental description of physics above the Planck scale, based on irreversible laws, from which will emerge the apparently reversible dynamics we observe on intermediate scales. Here we continue that program and note that a class of discrete dynamical systems are known to exhibit this very property: they have an underlying discrete irreversible evolution, but in the long term exhibit the properties of a time reversible system, in the form of limit cycles. We connect this to our original model proposal in [M. Cortês and L. Smolin, Phys. Rev. D 90, 084007 (2014), 10.1103/PhysRevD.90.084007], and show that the behaviors obtained there can be explained in terms of the same phenomenon: the attraction of the system to a basin of limit cycles, where the dynamics appears to be time reversible. Further than that, we show that our original models exhibit the very same feature: the emergence of quasiparticle excitations obtained in the earlier work in the space-time description is an expression of the system's convergence to limit cycles when seen in the causal set description.

Irreversible Heavy Chain Transfer to Chondroitin*

PubMed Central

Lauer, Mark E.; Hascall, Vincent C.; Green, Dixy E.; DeAngelis, Paul L.; Calabro, Anthony

2014-01-01

We have recently demonstrated that the transfer of heavy chains (HCs) from inter-α-inhibitor, via the enzyme TSG-6 (tumor necrosis factor-stimulated gene 6), to hyaluronan (HA) oligosaccharides is an irreversible event in which subsequent swapping of HCs between HA molecules does not occur. We now describe our results of HC transfer experiments to chondroitin sulfate A, chemically desulfated chondroitin, chemoenzymatically synthesized chondroitin, unsulfated heparosan, heparan sulfate, and alginate. Of these potential HC acceptors, only chemically desulfated chondroitin and chemoenzymatically synthesized chondroitin were HC acceptors. The kinetics of HC transfer to chondroitin was similar to HA. At earlier time points, HCs were more widely distributed among the different sizes of chondroitin chains. As time progressed, the HCs migrated to lower molecular weight chains of chondroitin. Our interpretation is that TSG-6 swaps the HCs from the larger, reversible sites on chondroitin chains, which function as HC acceptors, onto smaller chondroitin chains, which function as irreversible HC acceptors. HCs transferred to smaller chondroitin chains were unable to be swapped off the smaller chondroitin chains and transferred to HA. HCs transferred to high molecular weight HA were unable to be swapped onto chondroitin. We also present data that although chondroitin was a HC acceptor, HA was the preferred acceptor when chondroitin and HA were in the same reaction mixture. PMID:25135638

Surface Detail Reproduction and Dimensional Stability of Contemporary Irreversible Hydrocolloid Alternatives after Immediate and Delayed Pouring.

PubMed

Kusugal, Preethi; Chourasiya, Ritu Sunil; Ruttonji, Zarir; Astagi, Preeti; Nayak, Ajay Kumar; Patil, Abhishekha

2018-01-01

To overcome the poor dimensional stability of irreversible hydrocolloids, alternative materials were introduced. The dimensional changes of these alternatives after delayed pouring are not well studied and documented in the literature. The purpose of the study is to evaluate and compare the surface detail reproduction and dimensional stability of two irreversible hydrocolloid alternatives with an extended-pour irreversible hydrocolloid at different time intervals. All testing were performed according to the ANSI/ADA specification number 18 for surface detail reproduction and specification number 19 for dimensional change. The test materials used in this study were newer irreversible hydrocolloid alternatives such as AlgiNot FS, Algin-X Ultra FS, and Kromopan 100 which is an extended pour irreversible hydrocolloid as control. The surface detail reproduction was evaluated using stereomicroscope. The dimensional change after storage period of 1 h, 24 h, and 120 h was assessed and compared between the test materials and control. The data were analyzed using one-way ANOVA and post hoc Bonferroni test. Statistically significant results ( P < 0.001) were seen when mean scores of the tested materials were compared with respect to reproduction of 22 μm line from the metal block. Kromopan 100 showed statistically significant differences between different time intervals ( P < 0.001) and exhibited more dimensional change. Algin-X Ultra FS proved to be more accurate and dimensionally stable. Newer irreversible hydrocolloid alternative impression materials were more accurate in surface detail reproduction and exhibited minimal dimensional change after storage period of 1 h, 24 h, and 120 h than extended-pour irreversible hydrocolloid impression material.

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

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.

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

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.

Liver-derived systemic factors drive β-cell hyperplasia in insulin resistant states

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

El Ouaamari, Abdelfattah; Kawamori, Dan; Dirice, Ercument

2013-02-21

Integrative organ cross-talk regulates key aspects of energy homeostasis and its dysregulation may underlie metabolic disorders such as obesity and diabetes. To test the hypothesis that cross-talk between the liver and pancreatic islets modulates β-cell growth in response to insulin resistance, we used the Liver-specific Insulin Receptor Knockout (LIRKO) mouse, a unique model that exhibits dramatic islet hyperplasia. Using complementary in vivo parabiosis and transplantation assays, and in vitro islet culture approaches, we demonstrate that humoral, non-neural, non-cell autonomous factor(s) induce β-cell proliferation in LIRKO mice. Furthermore, we report that a hepatocyte-derived factor(s) stimulates mouse and human β-cell proliferation inmore » ex vivo assays, independent of ambient glucose and insulin levels. These data implicate the liver as a critical source of β-cell growth factors in insulin resistant states.« less

Single cell imaging of Bruton's Tyrosine Kinase using an irreversible inhibitor

NASA Astrophysics Data System (ADS)

Turetsky, Anna; Kim, Eunha; Kohler, Rainer H.; Miller, Miles A.; Weissleder, Ralph

2014-04-01

A number of Bruton's tyrosine kinase (BTK) inhibitors are currently in development, yet it has been difficult to visualize BTK expression and pharmacological inhibition in vivo in real time. We synthesized a fluorescent, irreversible BTK binder based on the drug Ibrutinib and characterized its behavior in cells and in vivo. We show a 200 nM affinity of the imaging agent, high selectivity, and irreversible binding to its target following initial washout, resulting in surprisingly high target-to-background ratios. In vivo, the imaging agent rapidly distributed to BTK expressing tumor cells, but also to BTK-positive tumor-associated host cells.

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

Detailed Modeling and Irreversible Transfer Process Analysis of a Multi-Element Thermoelectric Generator System

NASA Astrophysics Data System (ADS)

Xiao, Heng; Gou, Xiaolong; Yang, Suwen

2011-05-01

Thermoelectric (TE) power generation technology, due to its several advantages, is becoming a noteworthy research direction. Many researchers conduct their performance analysis and optimization of TE devices and related applications based on the generalized thermoelectric energy balance equations. These generalized TE equations involve the internal irreversibility of Joule heating inside the thermoelectric device and heat leakage through the thermoelectric couple leg. However, it is assumed that the thermoelectric generator (TEG) is thermally isolated from the surroundings except for the heat flows at the cold and hot junctions. Since the thermoelectric generator is a multi-element device in practice, being composed of many fundamental TE couple legs, the effect of heat transfer between the TE couple leg and the ambient environment is not negligible. In this paper, based on basic theories of thermoelectric power generation and thermal science, detailed modeling of a thermoelectric generator taking account of the phenomenon of energy loss from the TE couple leg is reported. The revised generalized thermoelectric energy balance equations considering the effect of heat transfer between the TE couple leg and the ambient environment have been derived. Furthermore, characteristics of a multi-element thermoelectric generator with irreversibility have been investigated on the basis of the new derived TE equations. In the present investigation, second-law-based thermodynamic analysis (exergy analysis) has been applied to the irreversible heat transfer process in particular. It is found that the existence of the irreversible heat convection process causes a large loss of heat exergy in the TEG system, and using thermoelectric generators for low-grade waste heat recovery has promising potential. The results of irreversibility analysis, especially irreversible effects on generator system performance, based on the system model established in detail have guiding significance for

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

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

Irreversible atorvastatin-associated hearing loss.

PubMed

Liu, Michael; Alafris, Antonia; Longo, Anthony J; Cohen, Henry

2012-02-01

Drug-associated ototoxicity is a potentially irreversible adverse event. Among the several 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) available in the United States, only atorvastatin is associated with tinnitus, but none are associated with any forms of hearing loss. A search of the published literature (1950-August 2011) revealed no published case reports of ototoxicity associated with statins. To our knowledge, we describe the first case of progressive, irreversible hearing loss in a 32-year-old man 18 months after starting atorvastatin therapy. He began taking atorvastatin 20 mg every evening for treatment of hypercholesterolemia. Six months later, he complained of occasional episodes of tinnitus, which resolved spontaneously. An audiogram was obtained and was normal. By 18 months, the tinnitus became continuous. Another audiogram revealed bilateral "cookie-bite" middle-frequency hearing loss. Atorvastatin was immediately discontinued, and the patient was fitted with hearing aids. Four years after drug discontinuation, his hearing loss had neither progressed nor regressed. Use of the Naranjo adverse drug reaction probability scale indicated a possible (score of 2) temporal and causal relationship between the patient's hearing loss and atorvastatin. Causes of "cookie-bite" hearing loss include chronic exposure to loud noises, presbycusis, genetic predisposition, and drugs. The manufacturer of atorvastatin has received three unpublished cases of deafness, but claims that causal relationships were not established. Despite these claims by the manufacturer, based on this case report, we recommend that clinicians and patients be aware of the risk of atorvastatin-associated tinnitus and permanent hearing loss. Further research is needed to better understand the mechanism and frequency of this adverse event. © 2012 Pharmacotherapy Publications, Inc.

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.

Surface Detail Reproduction and Dimensional Stability of Contemporary Irreversible Hydrocolloid Alternatives after Immediate and Delayed Pouring

PubMed Central

Kusugal, Preethi; Chourasiya, Ritu Sunil; Ruttonji, Zarir; Astagi, Preeti; Nayak, Ajay Kumar; Patil, Abhishekha

2018-01-01

Purpose: To overcome the poor dimensional stability of irreversible hydrocolloids, alternative materials were introduced. The dimensional changes of these alternatives after delayed pouring are not well studied and documented in the literature. The purpose of the study is to evaluate and compare the surface detail reproduction and dimensional stability of two irreversible hydrocolloid alternatives with an extended-pour irreversible hydrocolloid at different time intervals. Materials and Methods: All testing were performed according to the ANSI/ADA specification number 18 for surface detail reproduction and specification number 19 for dimensional change. The test materials used in this study were newer irreversible hydrocolloid alternatives such as AlgiNot FS, Algin-X Ultra FS, and Kromopan 100 which is an extended pour irreversible hydrocolloid as control. The surface detail reproduction was evaluated using stereomicroscope. The dimensional change after storage period of 1 h, 24 h, and 120 h was assessed and compared between the test materials and control. The data were analyzed using one-way ANOVA and post hoc Bonferroni test. Results: Statistically significant results (P < 0.001) were seen when mean scores of the tested materials were compared with respect to reproduction of 22 μm line from the metal block. Kromopan 100 showed statistically significant differences between different time intervals (P < 0.001) and exhibited more dimensional change. Algin-X Ultra FS proved to be more accurate and dimensionally stable. Conclusions: Newer irreversible hydrocolloid alternative impression materials were more accurate in surface detail reproduction and exhibited minimal dimensional change after storage period of 1 h, 24 h, and 120 h than extended-pour irreversible hydrocolloid impression material. PMID:29599578

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

Antimicrobial activity and properties of irreversible hydrocolloid impression materials incorporated with silver nanoparticles.

PubMed

Ginjupalli, Kishore; Alla, Rama Krishna; Tellapragada, Chaitanya; Gupta, Lokendra; Upadhya Perampalli, Nagaraja

2016-06-01

Conventional spray and the immersion disinfection of irreversible hydrocolloid impression materials may lead to dimensional changes. The purpose of this in vitro study was to investigate the antimicrobial activity and properties of irreversible hydrocolloid impression materials incorporated with silver nanoparticles. The antimicrobial activity and properties of 2 commercially available irreversible hydrocolloid impression materials were evaluated after incorporating varying concentrations of silver nanoparticles. Antimicrobial activity was determined using the disk diffusion method. The gel strength, permanent deformation, flow, and gelation time were measured according to American Dental Association specification #18. Analysis of variance was used to identify the significant differences within and across the groups (α=.05). Adding silver nanoparticles to irreversible hydrocolloid impression materials resulted in superior antimicrobial activity without adversely affecting their properties. Adding silver nanoparticles to Zelgan significantly increased the gel strength compared with the control group, except at 5 wt%. However, the gel strength of Tropicalgin was unaffected except at 5 wt%. An increase in the permanent deformation was found with the incorporation of silver nanoparticles in both Zelgan and Tropicalgin. The flow of Zelgan increased with the incorporation of silver nanoparticles, whereas a decrease in the flow of Tropicalgin was observed at 1 wt% and 2 wt%. An increase in the gelation time of both Zelgan and Tropicalgin was observed with the incorporation of silver nanoparticles. Based on this in vitro study, silver nanoparticles can be incorporated into irreversible hydrocolloid impression materials as antimicrobial agents without adversely affecting their properties. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

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

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.

Microscopic theory for the time irreversibility and the entropy production

NASA Astrophysics Data System (ADS)

Chun, Hyun-Myung; Noh, Jae Dong

2018-02-01

In stochastic thermodynamics, the entropy production of a thermodynamic system is defined by the irreversibility measured by the logarithm of the ratio of the path probabilities in the forward and reverse processes. We derive the relation between the irreversibility and the entropy production starting from the deterministic equations of motion of the whole system consisting of a physical system and a surrounding thermal environment. The derivation assumes the Markov approximation that the environmental degrees of freedom equilibrate instantaneously. Our approach provides a guideline for the choice of the proper reverse process to a given forward process, especially when there exists a velocity-dependent force. We demonstrate our idea with an example of a charged particle in the presence of a time-varying magnetic field.

Prostaglandin E2 to diagnose between reversible and irreversible pulpitis.

PubMed

Petrini, M; Ferrante, M; Ciavarelli, L; Brunetti, L; Vacca, M; Spoto, G

2012-01-01

The aim of this work is to verify a correlation between the grade of inflammation and the concentration of PGE2 in human dental pulp. A total of 25 human dental pulps were examined by histological analysis and radioimmunologic dosage of PGE2. The pulps used in this experiment were from healthy and symptomatic teeth; the first ones were collected from teeth destined to be extracted for orthodontic reasons. An increase was observed of PGE2 in reversible pulpitis compared with healthy pulps and with the irreversible pulpitis and the clear decrease of these when NSAIDs are taken. This study demonstrates that PGE2 level is correlated to histological analysis thus allowing to distinguish symptomatic teeth in reversible and irreversible pulpitis.

Flux pinning characteristics and irreversibility line in high temperature superconductors

NASA Technical Reports Server (NTRS)

Matsushita, T.; Ihara, N.; Kiuchi, M.

1995-01-01

The flux pinning properties in high temperature superconductors are strongly influenced by thermally activated flux motion. The scaling relation of the pinning force density and the irreversibility line in various high temperature superconductors are numerically analyzed in terms of the flux creep model. The effect of two factors, i.e., the flux pinning strength and the dimensionality of the material, on these properties are investigated. It is speculated that the irreversibility line in Bi-2212 superconductors is one order of magnitude smaller than that in Y-123, even if the flux pinning strength in Bi-2212 is improved up to the level of Y-123. It is concluded that these two factors are equally important in determination of the flux pinning characteristics at high temperatures.

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.

Advanced Caries Microbiota in Teeth with Irreversible Pulpitis.

PubMed

Rôças, Isabela N; Lima, Kenio C; Assunção, Isauremi V; Gomes, Patrícia N; Bracks, Igor V; Siqueira, José F

2015-09-01

Bacterial taxa in the forefront of caries biofilms are candidate pathogens for irreversible pulpitis and are possibly the first ones to invade the pulp and initiate endodontic infection. This study examined the microbiota of the most advanced layers of dentinal caries in teeth with irreversible pulpitis. DNA extracted from samples taken from deep dentinal caries associated with pulp exposures was analyzed for the presence and relative levels of 33 oral bacterial taxa by using reverse-capture checkerboard hybridization assay. Quantification of total bacteria, streptococci, and lactobacilli was also performed by using real-time quantitative polymerase chain reaction. Associations between the target bacterial taxa and clinical signs/symptoms were also evaluated. The most frequently detected taxa in the checkerboard assay were Atopobium genomospecies C1 (53%), Pseudoramibacter alactolyticus (37%), Streptococcus species (33%), Streptococcus mutans (33%), Parvimonas micra (13%), Fusobacterium nucleatum (13%), and Veillonella species (13%). Streptococcus species, Dialister invisus, and P. micra were significantly associated with throbbing pain, S. mutans with pain to percussion, and Lactobacillus with continuous pain (P < .05). Quantitative polymerase chain reaction revealed a mean total bacterial load of 1 × 10(8) (range, 2.05 × 10(5) to 4.5 × 10(8)) cell equivalents per milligram (wet weight) of dentin. Streptococci and lactobacilli were very prevalent but comprised only 0.09% and 2% of the whole bacterial population, respectively. Several bacterial taxa were found in advanced caries lesions in teeth with exposed pulps, and some of them were significantly associated with symptoms. A role for these taxa in the etiology of irreversible pulpitis is suspected. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Direct and irreversible inhibition of cyclooxygenase-1 by nitroaspirin (NCX 4016).

PubMed

Corazzi, Teresa; Leone, Mario; Maucci, Raffaella; Corazzi, Lanfranco; Gresele, Paolo

2005-12-01

Benzoic acid, 2-(acetyl-oxy)-3-[(nitrooxy)methyl]phenyl ester (NCX 4016), a new drug made by an aspirin molecule linked, through a spacer, to a nitric oxide (NO)-donating moiety, is now under clinical testing for the treatment of atherothrombotic conditions. Aspirin exerts its antithrombotic activity by irreversibly inactivating platelet cyclooxygenase (COX)-1. NCX 4016 in vivo undergoes metabolism into deacetylated and/or denitrated metabolites, and it is not known whether NCX 4016 needs to liberate aspirin to inhibit COX-1, or whether it can block it as a whole molecule. The aim of our study was to evaluate the effects of NCX 4016 and its analog or metabolites on platelet COX-1 and whole blood COX-2 and on purified ovine COX (oCOX)-1 and oCOX-2. In particular, we have compared the mechanism by which NCX 4016 inhibits purified oCOX enzymes with that of aspirin using a spectrophotometric assay. All the NCX 4016 derivatives containing acetylsalicylic acid inhibited the activity of oCOX-1 and oCOX-2, whereas the deacetylated metabolites and the nitric oxide-donating moiety were inactive. Dialysis experiments showed that oCOX-1 inhibition by NCX 4016, similar to aspirin, is irreversible. Reversible COX inhibitors (indomethacin) or salicylic acid incubated with the enzyme before NCX 4016 prevent the irreversible inhibition of oCOX-1 by NCX 4016 as well as by aspirin. In conclusion, our data show that NCX 4016 acts as a direct and irreversible inhibitor of COX-1 and that the presence of a spacer and NO-donating moiety in the molecule slows the kinetics of COX-1 inhibition by NCX 4016, compared with aspirin.

Preventing Scars after Injury with Partial Irreversible Electroporation

PubMed Central

Golberg, Alexander; Villiger, Martin; Khan, Saiqa; Quinn, Kyle P.; Lo, William C. Y.; Bouma, Brett E.; Mihm, Martin C.; Austen, William G.; Yarmush, Martin L.

2017-01-01

Preventing the formation of hypertrophic scars, especially those that are a result of major trauma or burns, would have enormous impact in the fields of regenerative and trauma medicine. In this report, we introduce a non-invasive method to prevent scarring based on non-thermal partial irreversible electroporation. Contact burn injuries in rats were treated with varying treatment parameters to optimize the treatment protocol. Scar surface area and structural properties of the scar were assessed with histology and non-invasive, longitudinal imaging with polarization-sensitive optical coherence tomography. We found that partial irreversible electroporation using 200 pulses of 250 V and 70 μs duration, delivered at 3 Hz every 20 days during a total of five therapy sessions after the initial burn injury resulted in a 57.9% reduction of the scar area in comparison with untreated scars and structural features approaching those of normal skin. Noteworthy, unlike humans, rats do not develop hypertrophic scars. Therefore, the use of a rat animal model is the limiting factor of this work. PMID:27393126

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.

Irreversibility inversions in two-dimensional turbulence

NASA Astrophysics Data System (ADS)

Bragg, Andrew D.; De Lillo, Filippo; Boffetta, Guido

2018-02-01

In this paper, we consider a recent theoretical prediction [Bragg et al., Phys. Fluids 28, 013305 (2016), 10.1063/1.4939694] that for inertial particles in two-dimensional (2D) turbulence, the nature of the irreversibility of the particle-pair dispersion inverts when the particle inertia exceeds a certain value. In particular, when the particle Stokes number, St , is below a certain value, the forward-in-time (FIT) dispersion should be faster than the backward-in-time (BIT) dispersion, but for St above this value, this should invert so that BIT becomes faster than FIT dispersion. This nontrivial behavior arises because of the competition between two physically distinct irreversibility mechanisms that operate in different regimes of St . In three-dimensional (3D) turbulence, both mechanisms act to produce faster BIT than FIT dispersion, but in 2D turbulence, the two mechanisms have opposite effects because of the flux of energy from the small to the large scales. We supplement the qualitative argument given by Bragg et al. [Phys. Fluids 28, 013305 (2016), 10.1063/1.4939694] by deriving quantitative predictions of this effect in the short time limit. We confirm the theoretical predictions using results of inertial particle dispersion in a direct numerical simulation of 2D turbulence. A more general finding of this analysis is that in turbulent flows with an inverse energy flux, inertial particles may yet exhibit a net downscale flux of kinetic energy because of their nonlocal-in-time dynamics.

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

An in vitro investigation into the physical properties of irreversible hydrocolloid alternatives.

PubMed

Patel, Rishi D; Kattadiyil, Mathew T; Goodacre, Charles J; Winer, Myron S

2010-11-01

A number of manufacturers have introduced new products that are marketed as alternatives to irreversible hydrocolloid impression materials. However, there is a paucity of laboratory and clinical research on these products compared to traditional irreversible hydrocolloid. The purpose of this study was to evaluate the detail reproduction, gypsum compatibility, and linear dimensional change of 3 recently introduced impression materials designed as alternatives to irreversible hydrocolloid. The tested materials were Position Penta Quick, Silgimix, and AlgiNot. An irreversible hydrocolloid impression material, Jeltrate Plus Antimicrobial, served as the control. The parameters of detail reproduction, gypsum compatibility, and linear dimensional change were tested in accordance with ANSI/ADA Specifications No. 18 and 19. The gypsum compatibility was tested using a type III stone (Microstone Golden) and a type IV stone (Die-Keen Green). The data were analyzed using the Kruskal-Wallis rank test and the Mann-Whitney U test (α=.05). The test materials demonstrated significantly (P<.001) better detail reproduction than the control material. Silgimix exhibited the best compatibility with Microstone, whereas AlgiNot and Position Penta Quick exhibited the best gypsum compatibility with Die-Keen. An incompatibility was observed over time between the Jeltrate control material and the Microstone gypsum material. For linear dimensional change, the mean dimension of the control material most closely approximated the distance between the lines on the test die, but it exhibited the greatest variability in measurements. All of the test materials exhibited linear dimensional change within the ADA's accepted limit of 1.0%. The 3 new impression materials exhibited better detail reproduction and less variability in linear dimensional change than the irreversible hydrocolloid control. Gypsum compatibility varied with the brand of gypsum used, with an incompatibility identified between the

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.

Irreversible entropy production in two-phase flows with evaporating drops

NASA Technical Reports Server (NTRS)

Bellan, J.; Okong'o, N. A.

2002-01-01

A derivation of the irreversible entropy production, that is the dissipation, in two-phase flows is presented for the purpose of examining the effect of evaporative-drop modulation of flows having turbulent features.

Prepubertal exposure to bisphenol-A induces ERα upregulation and hyperplasia in adult gerbil female prostate

PubMed Central

Campos, Mônica S; Galvão, André L V; Rodríguez, Daniel A O; Biancardi, Manoel F; Marques, Mara R; Vilamaior, Patrícia S L; Santos, Fernanda C A; Taboga, Sebastião R

2015-01-01

Prostate physiology is highly dependent on oestrogenic and androgenic homeostasis. Interferences in this equilibrium, especially in early periods of life, may disrupt the prostate and increase the susceptibility to the development of diseases with ageing. Taking this into account, and considering the increase of environmental chemicals with endocrine-disrupting potential such as bisphenol-A (BPA), this study aimed to evaluate the prostates of adult female gerbils exposed to BPA and BPA plus testosterone from pubertal to adult periods. Morphological, stereological and chemical analyses revealed that long-term BPA exposure, even in environmental dosages, increases the proliferative status of the prostate, increases the number of ERα-positive stromal cells and elicits the development of prostatic hyperplasia in adult female gerbils. Moreover, we also observed that the association with testosterone did not increase the proliferative status of the gland, which shows that low levels of BPA are enough to cause an oestrogenic disruption of the prostate in young adults. This evidence suggests that this oestrogenic endocrine disruptor may increase the susceptibility to prostatic disorders with ageing. PMID:26098999

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.

Focal epithelial hyperplasia arising after delivery of metal-ceramic fixed dental prosthesis.

PubMed

Park, Min-Woo; Cho, Young-Ah; Kim, Soung-Min; Myoung, Hoon; Lee, Jong-Ho; Lee, Suk-Keun

2014-12-01

Focal epithelial hyperplasia (FEH) is a human papillomavirus (HPV)-induced alteration of the oral mucosa that presents with a clinically distinct appearance. While other HPV-infected lesions such as squamous papilloma, verruca vulgaris, and condyloma acuminatum involve the skin, oral mucosa, and genital mucosa, FEH occurs only in the oral mucosa. The affected oral mucosa exhibits multiple papules and nodules with each papule/nodule being flat-topped or sessile. The affected region resembles the normal color of oral mucosa rather than appearing as a white color since the epithelial surface is not hyperkeratinized. Almost all cases present with multiple sites of occurrence. This rare, benign epithelial proliferation is related to low-risk HPV, especially HPV-13 and -32, and is not transformed into carcinoma. We report a case of FEH that arose on the attached gingiva of an East Asian male adult related to prosthesis without detection of any HPV subtype in HPV DNA chip and sequencing.

Macrophages are related to goblet cell hyperplasia and induce MUC5B but not MUC5AC in human bronchus epithelial cells.

PubMed

Silva, Manuel A; Bercik, Premysl

2012-06-01

Airway goblet cell hyperplasia (GCH)--detectable by mucin staining--and abnormal macrophage infiltrate are pathological features present in many chronic respiratory disorders. However, it is unknown if both factors are associated. Using in-vivo and in-vitro models, we investigated whether macrophages are related with GCH and changes in mucin immunophenotypes. Lung sections from Sprague-Dawley rats treated for 48 h with one intra-tracheal dose of PBS or LPS (n=4-6 per group) were immunophenotyped for rat-goblet cells, immune, and proliferation markers. Human monocyte-derived macrophages (MDM) were pre-treated with or without LPS, immunophenotyped, and their supernatant, as well as cytokines at levels equivalent to supernatant were used to challenge primary culture of normal human bronchus epithelial cells (HBEC) in air-liquid interface, followed by MUC5B and MUC5AC mucin immunostaining. An association between increased bronchiolar goblet cells and terminal-bronchiolar proliferative epithelial cells confirmed the presence of GCH in our LPS rat model, which was related with augmented bronchiolar CD68 macrophage infiltration. The in-vitro experiments have shown that MUC5AC phenotype was inhibited when HBEC were challenged with supernatant from MDM pre-treated with or without LPS. In contrast, TNF-α and interleukin-1β at levels equivalent to supernatant from LPS-treated MDM increased MUC5AC. MUC5B was induced by LPS, supernatant from LPS-treated MDM, a mix of cytokines including TNF-α and TNF-α alone at levels present in supernatant from LPS-treated MDM. We demonstrated that macrophages are related with bronchiolar GCH, and that they induced MUC5B and inhibited MUC5AC in HBEC, suggesting a role for them in the pathogenesis of airway MUC5B-related GCH.

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.

Unreal perpetual motion machine, Rydberg constant and Carnot non-unitary efficiency as a consequence of the atomic irreversibility

NASA Astrophysics Data System (ADS)

Lucia, Umberto

2018-02-01

A perpetual motion machine is a completely ideal engine which cannot be realized. Carnot introduced the concept of the ideal engine which operates on a completely reversible cycle, without any dissipation, but with an upper limit in it. So, even in ideal condition without any dissipation, there is something that prevents the conversion of all the energy absorbed by an ideal reservoir into work. But what is the cause of irreversibility? Here we highlight the atomic nature of this irreversibility, proving that it is no more than the continuous interaction of the atoms with the surrounding field. The macroscopic irreversibility is the consequence of the microscopic irreversibility.

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.

Biotin Attachment Domain-Containing Proteins Irreversibly Inhibit Acetyl CoA Carboxylase

DOE PAGES

Keereetaweep, Jantana; Liu, Hui; Zhai, Zhiyang; ...

2018-04-06

The first committed step in fatty acid synthesis is mediated by Acetyl-CoA carboxylase (ACCase), a biotin-dependent enzyme that carboxylates acetyl-CoA to produce malonyl-CoA. ACCase can be feedback-regulated by short-term (reversible) and longer-term (irreversible) inhibition upon oversupply of fatty acids (FA) provided by Tween80 (predominantly containing oleic acid; 18:1). Biotin-Attachment-Domain-Containing (BADC) proteins are inactive analogs of biotin carboxyl transfer protein (BCCP) that lack biotin and their incorporation into ACCase downregulates it by displacing active (biotin-containing) BCCP subunits. Individual T-DNA insertion lines of BADC1, BADC2, and BADC3 were used to generate badc1badc2 and badc1badc3. The badc1badc3 mutant and wild-type exhibited normal growthmore » and development, however ACCase activity was 26% higher in badc1badc3 relative to wild-type and its seeds contained 30.1 %DW more FA and 32.6 %DW more TAG than wild-type. Cell suspension cultures were generated from leaves of badc1badc3 and wild-type plants to test whether BADC contributes to the irreversible phase of ACCase inhibition resulting from culture in medium containing 10mM Tween80. While the reversible phase of ACCase inhibition after two days of Tween80 feeding was equivalent for badc1badc3 and wild-type, the irreversible phase of inhibition following four days of Tween80 feeding was reduced by 50% in badc1badc3 relative to wild-type. In this work we present evidence for two important homeostatic roles for BADC proteins in downregulating ACCase activity: during normal growth and development, and by contributing to its long-term irreversible feedback inhibition resulting from oversupply of fatty acids.« less

Biotin Attachment Domain-Containing Proteins Irreversibly Inhibit Acetyl CoA Carboxylase

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

Keereetaweep, Jantana; Liu, Hui; Zhai, Zhiyang

The first committed step in fatty acid synthesis is mediated by Acetyl-CoA carboxylase (ACCase), a biotin-dependent enzyme that carboxylates acetyl-CoA to produce malonyl-CoA. ACCase can be feedback-regulated by short-term (reversible) and longer-term (irreversible) inhibition upon oversupply of fatty acids (FA) provided by Tween80 (predominantly containing oleic acid; 18:1). Biotin-Attachment-Domain-Containing (BADC) proteins are inactive analogs of biotin carboxyl transfer protein (BCCP) that lack biotin and their incorporation into ACCase downregulates it by displacing active (biotin-containing) BCCP subunits. Individual T-DNA insertion lines of BADC1, BADC2, and BADC3 were used to generate badc1badc2 and badc1badc3. The badc1badc3 mutant and wild-type exhibited normal growthmore » and development, however ACCase activity was 26% higher in badc1badc3 relative to wild-type and its seeds contained 30.1 %DW more FA and 32.6 %DW more TAG than wild-type. Cell suspension cultures were generated from leaves of badc1badc3 and wild-type plants to test whether BADC contributes to the irreversible phase of ACCase inhibition resulting from culture in medium containing 10mM Tween80. While the reversible phase of ACCase inhibition after two days of Tween80 feeding was equivalent for badc1badc3 and wild-type, the irreversible phase of inhibition following four days of Tween80 feeding was reduced by 50% in badc1badc3 relative to wild-type. In this work we present evidence for two important homeostatic roles for BADC proteins in downregulating ACCase activity: during normal growth and development, and by contributing to its long-term irreversible feedback inhibition resulting from oversupply of fatty acids.« less

Smoothed quantum-classical states in time-irreversible hybrid dynamics

NASA Astrophysics Data System (ADS)

Budini, Adrián A.

2017-09-01

We consider a quantum system continuously monitored in time which in turn is coupled to an arbitrary dissipative classical system (diagonal reduced density matrix). The quantum and classical dynamics can modify each other, being described by an arbitrary time-irreversible hybrid Lindblad equation. Given a measurement trajectory, a conditional bipartite stochastic state can be inferred by taking into account all previous recording information (filtering). Here, we demonstrate that the joint quantum-classical state can also be inferred by taking into account both past and future measurement results (smoothing). The smoothed hybrid state is estimated without involving information from unobserved measurement channels. Its average over recording realizations recovers the joint time-irreversible behavior. As an application we consider a fluorescent system monitored by an inefficient photon detector. This feature is taken into account through a fictitious classical two-level system. The average purity of the smoothed quantum state increases over that of the (mixed) state obtained from the standard quantum jump approach.

Assessing the role of feed water constituents in irreversible membrane fouling of pilot-scale ultrafiltration drinking water treatment systems.

PubMed

Peiris, R H; Jaklewicz, M; Budman, H; Legge, R L; Moresoli, C

2013-06-15

Fluorescence excitation-emission matrix (EEM) approach together with principal component analysis (PCA) was used for assessing hydraulically irreversible fouling of three pilot-scale ultrafiltration (UF) systems containing full-scale and bench-scale hollow fiber membrane modules in drinking water treatment. These systems were operated for at least three months with extensive cycles of permeation, combination of back-pulsing and scouring and chemical cleaning. The principal component (PC) scores generated from the PCA of the fluorescence EEMs were found to be related to humic substances (HS), protein-like and colloidal/particulate matter content. PC scores of HS- and protein-like matter of the UF feed water, when considered separately, showed reasonably good correlations with the rate of hydraulically irreversible fouling for long-term UF operations. In contrast, comparatively weaker correlations for PC scores of colloidal/particulate matter and the rate of hydraulically irreversible fouling were obtained for all UF systems. Since, individual correlations could not fully explain the evolution of the rate of irreversible fouling, multi-linear regression models were developed to relate the combined effect of HS-like, protein-like and colloidal/particulate matter PC scores to the rate of hydraulically irreversible fouling for each specific UF system. These multi-linear regression models revealed significant individual and combined contribution of HS- and protein-like matter to the rate of hydraulically irreversible fouling, with protein-like matter generally showing the greatest contribution. The contribution of colloidal/particulate matter to the rate of hydraulically irreversible fouling was not as significant. The addition of polyaluminum chloride, as coagulant, to UF feed appeared to have a positive impact in reducing hydraulically irreversible fouling by these constituents. The proposed approach has applications in quantifying the individual and synergistic

Time irreversibility of the statistics of a single particle in compressible turbulence

NASA Astrophysics Data System (ADS)

Grafke, Tobias; Frishman, Anna; Falkovich, Gregory

2015-04-01

We investigate time irreversibility from the point of view of a single particle in Burgers turbulence. Inspired by the recent work for incompressible flows [Xu et al., Proc. Natl. Acad. Sci. USA 111, 7558 (2014), 10.1073/pnas.1321682111], we analyze the evolution of the kinetic energy for fluid markers and use the fluctuations of the instantaneous power as a measure of time irreversibility. For short times, starting from a uniform distribution of markers, we find the scaling <[E(t ) -E (0 ) ] n>∝t and ∝Ren -1 for the power as a function of the Reynolds number. Both observations can be explained using the "flight-crash" model, suggested by Xu et al. Furthermore, we use a simple model for shocks that reproduces the moments of the energy difference, including the pre-factor for . To complete the single-particle picture for Burgers we compute the moments of the Lagrangian velocity difference and show that they are bifractal. This arises in a similar manner to the bifractality of Eulerian velocity differences. In the above setting, time irreversibility is directly manifest as particles eventually end up in shocks. We additionally investigate time irreversibility in the long-time limit when all particles are located inside shocks and the Lagrangian velocity statistics are stationary. We find the same scalings for the power and energy differences as at short times and argue that this is also a consequence of rare "flight-crash" events related to shock collisions.

Cardiac hypertrophy induced by active Raf depends on Yorkie-mediated transcription

PubMed Central

Yu, Lin; Daniels, Joseph P.; Wu, Huihui; Wolf, Matthew J.

2015-01-01

Organ hypertrophy can result from enlargement of individual cells or from cell proliferation or both. Activating mutations in the serine-threonine kinase Raf cause cardiac hypertrophy and contribute to Noonan syndrome in humans. Cardiac-specific expression of activated Raf also causes hypertrophy in Drosophila melanogaster. We found that Yorkie (Yki), a transcriptional coactivator in the Hippo pathway that regulates organ size, is required for Raf-induced cardiac hypertrophy in flies. Although aberrant activation of Yki orthologs stimulates cardiac hyperplasia in mice, cardiac-specific expression of an activated mutant form of Yki in fruit flies caused cardiac hypertrophy without hyperplasia. Knockdown of Yki caused cardiac dilation without loss of cardiomyocytes and prevented Raf-induced cardiac hypertrophy. In flies, Yki-induced cardiac hypertrophy required the TEA domain–containing transcription factor Scalloped, and, in mammalian cells, expression of mouse RafL613V, an activated form of Raf with a Noonan syndrome mutation, increased Yki-induced Scalloped activity. Furthermore, overexpression of Tgi (a Tondu domain–containing Scalloped-binding corepressor) in the fly heart abrogated Yki- or Raf-induced cardiac hypertrophy. Thus, crosstalk between Raf and Yki occurs in the heart and can influence Raf-mediated cardiac hypertrophy. PMID:25650441

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

Loschmidt echo in many-spin systems: a quest for intrinsic decoherence and emergent irreversibility

NASA Astrophysics Data System (ADS)

Zangara, Pablo R.; Pastawski, Horacio M.

2017-03-01

If a magnetic polarization excess is locally injected in a crystal of interacting spins in thermal equilibrium, this ‘excitation’ would spread as consequence of spin-spin interactions. Such an apparently irreversible process is known as spin diffusion and it can lead the system back to ‘equilibrium’. Even so, a unitary quantum dynamics would ensure a precise memory of the non-equilibrium initial condition. Then, if at a certain time, say t/2, an experimental protocol reverses the many-body dynamics by changing the sign of the effective Hamiltonian, it would drive the system back to the initial non-equilibrium state at time t. As a matter of fact, the reversal is always perturbed by small experimental imperfections and/or uncontrolled internal or environmental degrees of freedom. This limits the amount of signal M(t) recovered locally at time t. The degradation of M(t) accounts for these perturbations, which can also be seen as the sources of decoherence. This general idea defines the Loschmidt echo (LE), which embodies the various time-reversal procedures implemented in nuclear magnetic resonance. Here, we present an invitation to the study of the LE following the pathway induced by the experiments. With such a purpose, we provide a historical and conceptual overview that briefly revisits selected phenomena that underlie the LE dynamics including chaos, decoherence, localization and equilibration. This guiding thread ultimately leads us to the discussion of decoherence and irreversibility as an emergent phenomenon. In addition, we introduce the LE formalism by means of spin-spin correlation functions in a manner suitable for presentation in a broad scope physics journal. Last, but not least, we present new results that could trigger new experiments and theoretical ideas. In particular, we propose to transform an initially localized excitation into a more complex initial state, enabling a dynamically prepared LE. This induces a global definition of the LE in

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.

An Irreversible Constitutive Law for Modeling the Delamination Process using Interface Elements

NASA Technical Reports Server (NTRS)

Goyal, Vinay K.; Johnson, Eric R.; Davila, Carlos G.; Jaunky, Navin; Ambur, Damodar (Technical Monitor)

2002-01-01

An irreversible constitutive law is postulated for the formulation of interface elements to predict initiation and progression of delamination in composite structures. An exponential function is used for the constitutive law such that it satisfies a multi-axial stress criterion for the onset of delamination, and satisfies a mixed mode fracture criterion for the progression of delamination. A damage parameter is included to prevent the restoration of the previous cohesive state between the interfacial surfaces. To demonstrate the irreversibility capability of the constitutive law, steady-state crack growth is simulated for quasi-static loading-unloading cycle of various fracture test specimens.

An Irreversible Constitutive Law for Modeling the Delamination Process Using Interface Elements

NASA Technical Reports Server (NTRS)

Goyal, Vinay K.; Johnson, Eric R.; Davila, Carlos G.; Jaunky, Navin; Bushnell, Dennis M. (Technical Monitor)

2002-01-01

An irreversible constitutive law is postulated for the formulation of interface elements to predict initiation and progression of delamination in composite structures. An exponential function is used for the constitutive law such that it satisfies a multi-axial stress criterion for the onset of delamination, and satisfies a mixed mode fracture criterion for the progression of delamination. A damage parameter is included to prevent the restoration of the previous cohesive state between the interfacial surfaces. To demonstrate the irreversibility capability of the constitutive law, steady-state crack growth is simulated for quasi-static loading-unloading cycle of various fracture test specimens.

Temperature stability of proteins: Analysis of irreversible denaturation using isothermal calorimetry.

PubMed

Schön, Arne; Clarkson, Benjamin R; Jaime, Maria; Freire, Ernesto

2017-11-01

The structural stability of proteins has been traditionally studied under conditions in which the folding/unfolding reaction is reversible, since thermodynamic parameters can only be determined under these conditions. Achieving reversibility conditions in temperature stability experiments has often required performing the experiments at acidic pH or other nonphysiological solvent conditions. With the rapid development of protein drugs, the fastest growing segment in the pharmaceutical industry, the need to evaluate protein stability under formulation conditions has acquired renewed urgency. Under formulation conditions and the required high protein concentration (∼100 mg/mL), protein denaturation is irreversible and frequently coupled to aggregation and precipitation. In this article, we examine the thermal denaturation of hen egg white lysozyme (HEWL) under irreversible conditions and concentrations up to 100 mg/mL using several techniques, especially isothermal calorimetry which has been used to measure the enthalpy and kinetics of the unfolding and aggregation/precipitation at 12°C below the transition temperature measured by DSC. At those temperatures the rate of irreversible protein denaturation and aggregation of HEWL is measured to be on the order of 1 day -1 . Isothermal calorimetry appears a suitable technique to identify buffer formulation conditions that maximize the long term stability of protein drugs. © 2017 Wiley Periodicals, Inc.

Temperature stability of proteins: Analysis of irreversible denaturation using isothermal calorimetry

PubMed Central

Schön, Arne; Clarkson, Benjamin R; Jaime, Maria; Freire, Ernesto

2017-01-01

The structural stability of proteins has been traditionally studied under conditions in which the folding/unfolding reaction is reversible, since thermodynamic parameters can only be determined under these conditions. Achieving reversibility conditions in temperature stability experiments has often required performing the experiments at acidic pH or other nonphysiological solvent conditions. With the rapid development of protein drugs, the fastest growing segment in the pharmaceutical industry, the need to evaluate protein stability under formulation conditions has acquired renewed urgency. Under formulation conditions and the required high protein concentration (~100 mg/mL), protein denaturation is irreversible and frequently coupled to aggregation and precipitation. In this article, we examine the thermal denaturation of hen egg white lysozyme (HEWL) under irreversible conditions and concentrations up to 100 mg/mL using several techniques, especially isothermal calorimetry which has been used to measure the enthalpy and kinetics of the unfolding and aggregation/precipitation at 12°C below the transition temperature measured by DSC. At those temperatures the rate of irreversible protein denaturation and aggregation of HEWL is measured to be on the order of 1 day−1. Isothermal calorimetry appears a suitable technique to identify buffer formulation conditions that maximize the long term stability of protein drugs. PMID:28722205

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

Avoiding neuromuscular stimulation in liver irreversible electroporation using radiofrequency electric fields

NASA Astrophysics Data System (ADS)

Castellví, Quim; Mercadal, Borja; Moll, Xavier; Fondevila, Dolors; Andaluz, Anna; Ivorra, Antoni

2018-02-01

Electroporation-based treatments typically consist of the application of high-voltage dc pulses. As an undesired side effect, these dc pulses cause electrical stimulation of excitable tissues such as motor nerves. The present in vivo study explores the use of bursts of sinusoidal voltage in a frequency range from 50 kHz to 2 MHz, to induce irreversible electroporation (IRE) whilst avoiding neuromuscular stimulation. A series of 100 dc pulses or sinusoidal bursts, both with an individual duration of 100 µs, were delivered to rabbit liver through thin needles in a monopolar electrode configuration, and thoracic movements were recorded with an accelerometer. Tissue samples were harvested three hours after treatment and later post-processed to determine the dimensions of the IRE lesions. Thermal damage due to Joule heating was ruled out via computer simulations. Sinusoidal bursts with a frequency equal to or above 100 kHz did not cause thoracic movements and induced lesions equivalent to those obtained with conventional dc pulses when the applied voltage amplitude was sufficiently high. IRE efficacy dropped with increasing frequency. For 100 kHz bursts, it was estimated that the electric field threshold for IRE is about 1.4 kV cm-1 whereas that of dc pulses is about 0.5 kV cm-1.

Zinc irreversibly damages major enzymes of energy production and antioxidant defense prior to mitochondrial permeability transition.

PubMed

Gazaryan, Irina G; Krasinskaya, Inna P; Kristal, Bruce S; Brown, Abraham M

2007-08-17

Recent observations point to the role played by Zn2+ as an inducer of neuronal death. Two Zn2+ targets have been identified that result in inhibition of mitochondrial respiration: the bc1 center and, more recently, alpha-ketoglutarate dehydrogenase. Zn2+ is also a mediator of oxidative stress, leading to mitochondrial failure, release of apoptotic peptides, and neuronal death. We now present evidence, by means of direct biochemical assays, that Zn2+ is imported through the Ca2+ uniporter and directly targets major enzymes of energy production (lipoamide dehydrogenase) and antioxidant defense (thioredoxin reductase and glutathione reductase). We demonstrate the following. (a) These matrix enzymes are rapidly inhibited by application of Zn2+ to intact mitochondria. (b) Delayed treatment with membrane-impermeable chelators has no effect, indicating rapid transport of biologically relevant quantities of Zn2+ into the matrix. (c) Membrane-permeable chelators stop but do not reverse enzyme inactivation. (d) Enzyme inhibition is rapid and irreversible and precedes the major changes associated with the mitochondrial permeability transition (MPT). (e) The extent and rate of enzyme inactivation linearly correlates with the MPT onset and propagation. (f) The Ca2+ uniporter blocker, Ruthenium Red, protects enzyme activities and delays pore opening up to 2 microm Zn2+. An additional, unidentified import route functions at higher Zn2+ concentrations. (g) No enzyme inactivation is observed for Ca2+-induced MPT. These observations strongly suggest that, unlike Ca2+, exogenous Zn2+ interferes with mitochondrial NADH production and directly alters redox protection in the matrix, contributing to mitochondrial dysfunction. Inactivation of these enzymes by Zn2+ is irreversible, and thus only their de novo synthesis can restore function, which may underlie persistent loss of oxidative carbohydrate metabolism following transient ischemia.

N-acetylcysteine improves redox status, mitochondrial dysfunction, mucin-depleted crypts and epithelial hyperplasia in dextran sulfate sodium-induced oxidative colitis in mice.

PubMed

Amrouche-Mekkioui, Ilhem; Djerdjouri, Bahia

2012-09-15

The effect of N-acetylcysteine (NAC), a pharmacological antioxidant was investigated in a murine model of chronic colitis. Male NMRI mice were given 5% dextran sulfate sodium (DSS) in drinking water for 5 days followed by 10 days of water, three times. Compared to control mice given water, DSS-treated mice displayed severe imbalanced redox status with decreased glutathione and catalase, but increased malondialdehyde, protein carbonyls, nitric oxide and myeloperoxidase levels, at days 35th (active colitis) and 45th (recovery period). It also resulted in mitochondrial dysfunction, mucosal ulcers, mucin-depleted crypts and epithelial cell apoptosis. Crypt abscesses and glandular hyperplasia occurred selectively in distal colon. NAC (150 mg/kg) given in drinking water for 45 days along with 3 DSS cycles improved the hallmarks of DSS-colitis. Interestingly, the moderate impact of NAC on lipids and proteins oxidation correlated with myeloperoxidase and nitric oxide levels.NAC as a mucoregulator and a thiol restoring agent is protective on oxidative crypt alterations, mucin depletion, epithelial cell hyperplasia and apoptosis. Taken together, our results highlight the role of NAC as a scavenger of phagocytes-derived reactive oxygen species in mice DDS-colitis, suggesting that a long term NAC diet might be beneficial in inflammatory bowel diseases and colorectal cancer. Copyright © 2012 Elsevier B.V. All rights reserved.

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

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.

Anti-Proliferation Effects of Garlic (Allium sativum L.) on the Progression of Benign Prostatic Hyperplasia.

PubMed

Chung, Kyung-Sook; Shin, Su-Jin; Lee, Na Young; Cheon, Se-Yun; Park, Wansu; Sun, Seung-Ho; An, Hyo-Jin

2016-07-01

Benign prostatic hyperplasia (BPH) is a urologic disease that affects most of men over the age 50. But until now there is no such perfect cure without side effects. Because of diverse adverse effects, it is desirable to develop effective and long term-safety-herbal medicines to inhibit the progress of BPH. In spite of garlic's large use and a wide spectrum of studies, including anti-hyperlipidemic, cardio-protective, and anti-inflammatory activities, there was none to prove efficacy for BPH. In this study, we evaluated the efficacy of garlic to prove its suppressing effects on BPH. Garlic administration decreased relative prostate weight ratio, suppressed mRNA expression level of AR, DHT serum levels, and the growth of prostatic tissue in BPH-induced rats. Moreover, garlic administration decreased the levels of inflammatory proteins, iNOS, and COX-2 in prostatic tissue. Further investigation showed that garlic induced accumulation of death-inducing signal complex and activation of AMPK and decreased the levels of anti-apoptotic proteins, such as Bcl-2, Bcl-xL, and survivin. These results suggest that garlic may have suppressing effects on BPH and it has great potential to be developed as treatment for BPH. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Essays on oil price volatility and irreversible investment

NASA Astrophysics Data System (ADS)

Pastor, Daniel J.

In chapter 1, we provide an extensive and systematic evaluation of the relative forecasting performance of several models for the volatility of daily spot crude oil prices. Empirical research over the past decades has uncovered significant gains in forecasting performance of Markov Switching GARCH models over GARCH models for the volatility of financial assets and crude oil futures. We find that, for spot oil price returns, non-switching models perform better in the short run, whereas switching models tend to do better at longer horizons. In chapter 2, I investigate the impact of volatility on firms' irreversible investment decisions using real options theory. Cost incurred in oil drilling is considered sunk cost, thus irreversible. I collect detailed data on onshore, development oil well drilling on the North Slope of Alaska from 2003 to 2014. Volatility is modeled by constructing GARCH, EGARCH, and GJR-GARCH forecasts based on monthly real oil prices, and realized volatility from 5-minute intraday returns of oil futures prices. Using a duration model, I show that oil price volatility generally has a negative relationship with the hazard rate of drilling an oil well both when aggregating all the fields, and in individual fields.

Scaling and efficiency determine the irreversible evolution of a market

PubMed Central

Baldovin, F.; Stella, A. L.

2007-01-01

In setting up a stochastic description of the time evolution of a financial index, the challenge consists in devising a model compatible with all stylized facts emerging from the analysis of financial time series and providing a reliable basis for simulating such series. Based on constraints imposed by market efficiency and on an inhomogeneous-time generalization of standard simple scaling, we propose an analytical model which accounts simultaneously for empirical results like the linear decorrelation of successive returns, the power law dependence on time of the volatility autocorrelation function, and the multiscaling associated to this dependence. In addition, our approach gives a justification and a quantitative assessment of the irreversible character of the index dynamics. This irreversibility enters as a key ingredient in a novel simulation strategy of index evolution which demonstrates the predictive potential of the model.

Magnetic irreversibility: An important amendment in the zero-field-cooling and field-cooling method

NASA Astrophysics Data System (ADS)

Teixeira Dias, Fábio; das Neves Vieira, Valdemar; Esperança Nunes, Sabrina; Pureur, Paulo; Schaf, Jacob; Fernanda Farinela da Silva, Graziele; de Paiva Gouvêa, Cristol; Wolff-Fabris, Frederik; Kampert, Erik; Obradors, Xavier; Puig, Teresa; Roa Rovira, Joan Josep

2016-02-01

The present work reports about experimental procedures to correct significant deviations of magnetization data, caused by magnetic relaxation, due to small field cycling by sample transport in the inhomogeneous applied magnetic field of commercial magnetometers. The extensively used method for measuring the magnetic irreversibility by first cooling the sample in zero field, switching on a constant applied magnetic field and measuring the magnetization M(T) while slowly warming the sample, and subsequently measuring M(T) while slowly cooling it back in the same field, is very sensitive even to small displacement of the magnetization curve. In our melt-processed YBaCuO superconducting sample we observed displacements of the irreversibility limit up to 7 K in high fields. Such displacements are detected only on confronting the magnetic irreversibility limit with other measurements, like for instance zero resistance, in which the sample remains fixed and so is not affected by such relaxation. We measured the magnetic irreversibility, Tirr(H), using a vibrating sample magnetometer (VSM) from Quantum Design. The zero resistance data, Tc0(H), were obtained using a PPMS from Quantum Design. On confronting our irreversibility lines with those of zero resistance, we observed that the Tc0(H) data fell several degrees K above the Tirr(H) data, which obviously contradicts the well known properties of superconductivity. In order to get consistent Tirr(H) data in the H-T plane, it was necessary to do a lot of additional measurements as a function of the amplitude of the sample transport and extrapolate the Tirr(H) data for each applied field to zero amplitude.

Irreversible airway obstruction assessed by high-resolution computed tomography (HRCT), exhaled nitric oxide (FENO), and biological markers in induced sputum in patients with asthma.

PubMed

Zhang, Lanlan; Gang, Jin; Zhigang, Cao; Yali, Cui; Baozhong, Shen; Fangbiao, Zhang; Liu, Chuntao

2014-09-01

The objective of this study was to explore the significance of assessing irreversible airway obstruction (IAO) in asthma patients by high-resolution computed tomography (HRCT), biological markers in induced sputum, and exhaled nitric oxide (FENO). The study was conducted in 34 patients with IAO, 46 patients with reversible airway obstruction (RAO), 40 patients who did not have airway obstruction (NAO), and 40 healthy subjects serving as controls. These patients received a step therapy for at least 3 months based on the guidelines for the prevention and treatment of asthma. After achieving complete or partial control of asthma, HRCT, lung function, FENO, and chemokine levels in induced sputum were measured. The airway wall area (WA; %) correlated with forced expiratory volume-1 (FEV-1(L); r = -0.67, p < 0.0001), and significant differences in bronchial wall thickening (BWT) of the LEVEL E generation airways were observed between the asthma and control groups (p < 0.01). FENO levels correlated with FEV-1 (%) in the IAO group (r = 0.49, p = 0.01). The levels of matrix metalloproteases-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in asthma patients with IAO, RAO, and NAO were significantly higher than those in the controls (p < 0.05). The level of neutrophilia in the sputum from the IAO group was higher than that from the RAO, NAO and control groups. Asthma patients with IAO have an increased BWT. Airway measurements with HRCT scans appear to be valuable in the evaluation of airway remodeling in asthma patients with IAO.

The farnesyltransferase inhibitor, LB42708, inhibits growth and induces apoptosis irreversibly in H-ras and K-ras-transformed rat intestinal epithelial cells

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

Kim, Han-Soo; Kim, Ju Won; Gang, Jingu

2006-09-15

LB42708 (LB7) and LB42908 (LB9) are pyrrole-based orally active farnesyltransferase inhibitors (FTIs) that have similar structures. The in vitro potencies of these compounds against FTase and GGTase I are remarkably similar, and yet they display different activity in apoptosis induction and morphological reversion of ras-transformed rat intestinal epithelial (RIE) cells. Both FTIs induced cell death despite K-ras prenylation, implying the participation of Ras-independent mechanism(s). Growth inhibition by these two FTIs was accompanied by G1 and G2/M cell cycle arrests in H-ras and K-ras-transformed RIE cells, respectively. We identified three key markers, p21{sup CIP1/WAF1}, RhoB and EGFR, that can explain themore » differences in the molecular mechanism of action between two FTIs. Only LB7 induced the upregulation of p21{sup CIP1/WAF1} and RhoB above the basal level that led to the cell cycle arrest and to distinct morphological alterations of ras-transformed RIE cells. Both FTIs successfully inhibited the ERK and activated JNK in RIE/K-ras cells. While the addition of conditioned medium from RIE/K-ras reversed the growth inhibition of ras-transformed RIE cells by LB9, it failed to overcome the growth inhibitory effect of LB7 in both H-ras- and K-ras-transformed RIE cells. We found that LB7, but not LB9, decreased the expression of EGFRs that confers the cellular unresponsiveness to EGFR ligands. These results suggest that LB7 causes the induction of p21{sup CIP1/WAF1} and RhoB and downregulation of EGFR that may serve as critical steps in the mechanism by which FTIs trigger irreversible inhibitions on the cell growth and apoptosis in ras-transformed cells.« less

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.

50 CFR 402.09 - Irreversible or irretrievable commitment of resources.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.09 Irreversible or... proposed species or proposed critical habitat under section 7(a)(4) of the Act. ...

50 CFR 402.09 - Irreversible or irretrievable commitment of resources.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.09 Irreversible or... proposed species or proposed critical habitat under section 7(a)(4) of the Act. ...

50 CFR 402.09 - Irreversible or irretrievable commitment of resources.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.09 Irreversible or... proposed species or proposed critical habitat under section 7(a)(4) of the Act. ...

50 CFR 402.09 - Irreversible or irretrievable commitment of resources.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.09 Irreversible or... proposed species or proposed critical habitat under section 7(a)(4) of the Act. ...

50 CFR 402.09 - Irreversible or irretrievable commitment of resources.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.09 Irreversible or... proposed species or proposed critical habitat under section 7(a)(4) of the Act. ...

Histologic evaluation of human benign prostatic hyperplasia treated by dutasteride: a study by xenograft model with improved severe combined immunodeficient mice.

PubMed

Tsujimura, Akira; Fukuhara, Shinichiro; Soda, Tetsuji; Takezawa, Kentaro; Kiuchi, Hiroshi; Takao, Tetsuya; Miyagawa, Yasushi; Nonomura, Norio; Adachi, Shigeki; Tokita, Yoriko; Nomura, Taisei

2015-01-01

To evaluate histologic change in human prostate samples treated with dutasteride and to elucidate direct effects of dutasteride on human prostate tissue, the present study was conducted by using a xenograft model with improved severe combined immunodeficient (super-SCID) mice, although it is well known that dutasteride reduces prostate volume. After establishment of a xenograft model of human benign prostatic hyperplasia in morphology and function, samples implanted into super-SCID mice with and without dutasteride were evaluated pathohistologically at 2 and 6 months after initiation of dutasteride administration. The proliferative index evaluated by Ki-67 staining was significantly lower in the dutasteride group than the control at 2 and 6 months after administration. Apoptotic index evaluated by the terminal transferase TdT-mediated dUTP-biotin nick end labeling staining was higher in the dutasteride group than the control at 2 and 6 months after administration. Quick scores in the dutasteride group for staining of both cyclooxygenase-2 (Cox-2) and Ras homolog gene family, member A (RhoA) were significantly lower than those in the control group at 2 and 6 months after administration. Dutasteride inhibits cell proliferation and induces apoptosis of prostatic cells, causing a reduced prostate volume. Furthermore, decreased expression of Cox-2 and RhoA within benign prostatic hyperplasia tissue by dutasteride may induce an early effect on improvement of lower urinary tract symptoms, probably by attenuating inflammation reaction of the prostate and decreasing intraurethral pressure, other than the mechanism of reduced prostate volume. Copyright © 2015 Elsevier Inc. 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.

Subchronic inhalation of coal dust particulate matter 10 induces bronchoalveolar hyperplasia and decreases MUC5AC expression in male Wistar rats.

PubMed

Kania, Nia; Setiawan, Bambang; Widjadjanto, Edi; Nurdiana, Nurdiana; Widodo, M Aris; Kusuma, H M S Chandra

2014-10-01

Coal dust is a pollutant found in coal mines that are capable of inducing oxidative stress and inflammation, but the effects on lung metaplasia as an early step of carcinogenesis remain unknown. The purpose of the present study was to evaluate the effects of PM10 coal dust on lung histology, MUC5AC expression, epidermal growth factor (EGF) expression, and epidermal growth factor receptor (EGFR) expression. An experimental study was done on male Wistar rats, which were divided into the following groups: control groups exposed to coal dust for 14 days (at doses of 6.25 mg/m(3), 12.5 mg/m(3), and 25 mg/m(3)), and the groups exposed to coal dust for 28 days (at doses of 6.25 mg/m(3), 12.5 mg/m(3), and 25 mg/m(3)). EGF expressions in rat lungs were measured by ELISA. EGFR and MUC5AC were measured by a confocal laser scanning microscope. The bronchoalveolar epithelial image of the group exposed to coal dust for 14 and 28 days showed a epithelial rearrangement, hyperplastic (metaplastic) goblet cells, and scattered massive inflammatory cells. The pulmonary parenchymal image of the group of exposed to coal dust for 14 and 28 days showed scattered inflammatory cells filling up the pulmonary alveolar networks, leading to an appearance of thickened parenchymal alveoli until emphysema-like structure. There was no significant difference in MUC5AC, EGF, and EGFR expressions for 14-d exposure (p>0.05). There was no significant difference in EGF and EGFR expressions for 28-d exposure (p>0.05), but there was a significant difference in MUC5AC expression (p<0.05). We concluded that subchronic inhalation of coal dust particulate matter 10 induces bronchoalveolar reactive hyperplasia and rearrangement of epithelial cells which accompanied by decrease expression MUC5AC in male rats. Copyright © 2014 Elsevier GmbH. All rights reserved.

Role of Phosphatidylinositol 3-Kinase in Friend Spleen Focus-Forming Virus-Induced Erythroid Disease▿

PubMed Central

Umehara, Daigo; Watanabe, Shinya; Ochi, Haruyo; Anai, Yukari; Ahmed, Nursarat; Kannagi, Mari; Hanson, Charlotte; Ruscetti, Sandra; Nishigaki, Kazuo

2010-01-01

Infection of erythroid cells by Friend spleen focus-forming virus (SFFV) leads to acute erythroid hyperplasia in mice due to expression of its unique envelope glycoprotein, gp55. Erythroid cells expressing SFFV gp55 proliferate in the absence of their normal regulator, erythropoietin (Epo), because of interaction of the viral envelope protein with the erythropoietin receptor and a short form of the receptor tyrosine kinase Stk (sf-Stk), leading to constitutive activation of several signal transduction pathways. Our previous in vitro studies showed that phosphatidylinositol 3-kinase (PI3-kinase) is activated in SFFV-infected cells and is important in mediating the biological effects of the virus. To determine the role of PI3-kinase in SFFV-induced disease, mice deficient in the p85α regulatory subunit of class IA PI3-kinase were inoculated with different strains of SFFV. We observed that p85α status determined the extent of erythroid hyperplasia induced by the sf-Stk-dependent viruses SFFV-P (polycythemia-inducing strain of SFFV) and SFFV-A (anemia-inducing strain of SFFV) but not by the sf-Stk-independent SFFV variant BB6. Our data also indicate that p85α status determines the response of mice to stress erythropoiesis, consistent with a previous report showing that SFFV uses a stress erythropoiesis pathway to induce erythroleukemia. We further showed that sf-Stk interacts with p85α and that this interaction depends upon sf-Stk kinase activity and tyrosine 436 in the multifunctional docking site. Pharmacological inhibition of PI3-kinase blocked proliferation of primary erythroleukemia cells from SFFV-infected mice and the erythroleukemia cell lines derived from them. These results indicate that p85α may regulate sf-Stk-dependent erythroid proliferation induced by SFFV as well as stress-induced erythroid hyperplasia. PMID:20504929

Antibacterial efficacy and effect of Morinda citrifolia L. mixed with irreversible hydrocolloid for dental impressions: A randomized controlled trial.

PubMed

Ahmed, A Shafath; Charles, P David; Cholan, R; Russia, M; Surya, R; Jailance, L

2015-08-01

This study aimed to evaluate whether the extract of Morinda citrifolia L. mixed with irreversible hydrocolloid powder decreases microbial contamination during impression making without affecting the resulting casts. Twenty volunteers were randomly divided into two groups (n = 10). Group A 30 ml extract of M. citrifolia L diluted in 30 ml of water was mixed to make the impression with irreversible hydrocolloid material. Group B 30 ml deionized water was mixed with irreversible hydrocolloid material to make the impressions following which the surface roughness and dimensional stability of casts were evaluated. Extract of M. citrifolia L. mixed with irreversible hydrocolloid decreased the percentage of microorganisms when compared with water (P < 0.001) but did not affect the surface quality or dimensional stability of the casts. Mixing the extract of M. citrifolia L. with irreversible hydrocolloid powder is an alternative method to prevent contamination without sacrificing impression quality.

Effect of Benincasa hispida fruits on testosterone-induced prostatic hypertrophy in albino rats

PubMed Central

Nandecha, Chetan; Nahata, Alok; Dixit, Vinod Kumar

2010-01-01

Background: Benincasa hispida Cogn. has been used traditionally in India for the management of urinary disorders. The fruit of B hispida is used as a diuretic and the seeds have been reported to possess antiangiogenic effects in prostate cells. Objective: The aim of the present study was to examine the effect of petroleum ether extract, ethanolic extract, and B hispida seed oil on hyperplasia of the prostate induced by the subcutaneous administration of testosterone in rats. Methods: In vitro studies were performed to determine the 5α-reductase inhibitory potential of the extracts. The results of those studies paved the way for the pharmacologic screening of the extracts to assess their potential against testosterone-induced hyperplasia in rats. Nine groups containing 10 rats per group were created for this study. Hyperplasia was induced by administration of testosterone (3 mg/kg SC) for 14 days in all the groups except the vehicle-treated group. Simultaneous administration of petroleum ether extract (100 or 200 mg/kg PO), ethanolic extract (100 or 200 mg/kg PO), and B hispida seed oil (20 or 40 mg/kg PO) was conducted. A standard 5α-reductase inhibitor (ie, finasteride) was used as a positive control. The weight of the rats was recorded on day 0 (ie, day 1 of the study) and on day 14, and the influence of testosterone and test extracts on the weight of the rats was determined. On day 14, rats were euthanized; prostates were dissected out, and weighed. The rats' prostate/body weight (P/BW) ratio was then determined. Histologic examinations were performed on prostates from each group. Results: The petroleum ether extract as well as B hispida seed oil exhibited inhibition of 5α-reductase activity in in vitro studies. Ethanolic extract did not exhibit significant inhibitory potential in vitro. Further in vivo study found that testosterone treatment significantly increased the rats' P/BW ratio in all the groups except the vehicle-treated rats, and this increase in

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.

Using irreversible compression in digital radiology: a preliminary study of the opinions of radiologists

NASA Astrophysics Data System (ADS)

Seeram, Euclid

2006-03-01

The large volumes of digital images produced by digital imaging modalities in Radiology have provided the motivation for the development of picture archiving and communication systems (PACS) in an effort to provide an organized mechanism for digital image management. The development of more sophisticated methods of digital image acquisition (Multislice CT and Digital Mammography, for example), as well as the implementation and performance of PACS and Teleradiology systems in a health care environment, have created challenges in the area of image compression with respect to storing and transmitting digital images. Image compression can be reversible (lossless) or irreversible (lossy). While in the former, there is no loss of information, the latter presents concerns since there is a loss of information. This loss of information from diagnostic medical images is of primary concern not only to radiologists, but also to patients and their physicians. In 1997, Goldberg pointed out that "there is growing evidence that lossy compression can be applied without significantly affecting the diagnostic content of images... there is growing consensus in the radiologic community that some forms of lossy compression are acceptable". The purpose of this study was to explore the opinions of expert radiologists, and related professional organizations on the use of irreversible compression in routine practice The opinions of notable radiologists in the US and Canada are varied indicating no consensus of opinion on the use of irreversible compression in primary diagnosis, however, they are generally positive on the notion of the image storage and transmission advantages. Almost all radiologists are concerned with the litigation potential of an incorrect diagnosis based on irreversible compressed images. The survey of several radiology professional and related organizations reveals that no professional practice standards exist for the use of irreversible compression. Currently, the

Effect of disinfection on irreversible hydrocolloid and alternative impression materials and the resultant gypsum casts.

PubMed

Suprono, Montry S; Kattadiyil, Mathew T; Goodacre, Charles J; Winer, Myron S

2012-10-01

Many new products have been introduced and marketed as alternatives to traditional irreversible hydrocolloid materials. These alternative materials have the same structural formula as addition reaction silicone, also known as vinyl polysiloxane (VPS), impression materials. Currently, there is limited in vitro and in vivo research on these products, including on the effects of chemical disinfectants on the materials. The purpose of this study was to compare the effects of a spray disinfecting technique on a traditional irreversible hydrocolloid and 3 new alternative impression materials in vitro. The tests were performed in accordance with the American National Standards Institute/American Dental Association (ANSI/ADA) Specification Nos. 18 and 19. Under standardized conditions, 100 impressions were made of a ruled test block with an irreversible hydrocolloid and 3 alternative impression materials. Nondisinfected irreversible hydrocolloid was used as the control. The impressions were examined for surface detail reproduction before and after disinfection with a chloramine-T product. Type III and Type V dental stone casts were evaluated for linear dimensional change and gypsum compatibility. Comparisons of linear dimensional change were analyzed with 2-way ANOVA of mean ranks with the Scheffé post hoc comparisons (α=.05). Data for surface detail reproduction were analyzed with the Wilcoxon Signed-Rank procedure and gypsum compatibility with the Kruskal-Wallis Rank procedure (α=.05). The alternative impression materials demonstrated significantly better outcomes with all 3 parameters tested. Disinfection with chloroamine-T did not have any effect on the 3 alternative impression materials. The irreversible hydrocolloid groups produced the most variability in the measurements of linear dimensional change. All of the tested materials were within the ADA's acceptable limit of 1.0% for linear dimensional change, except for the disinfected irreversible hydrocolloid

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.

Antibacterial efficacy and effect of Morinda citrifolia L. mixed with irreversible hydrocolloid for dental impressions: A randomized controlled trial

PubMed Central

Ahmed, A. Shafath; Charles, P. David; Cholan, R.; Russia, M.; Surya, R.; Jailance, L.

2015-01-01

Aim: This study aimed to evaluate whether the extract of Morinda citrifolia L. mixed with irreversible hydrocolloid powder decreases microbial contamination during impression making without affecting the resulting casts. Materials and Methods: Twenty volunteers were randomly divided into two groups (n = 10). Group A 30 ml extract of M. citrifolia L diluted in 30 ml of water was mixed to make the impression with irreversible hydrocolloid material. Group B 30 ml deionized water was mixed with irreversible hydrocolloid material to make the impressions following which the surface roughness and dimensional stability of casts were evaluated. Results: Extract of M. citrifolia L. mixed with irreversible hydrocolloid decreased the percentage of microorganisms when compared with water (P < 0.001) but did not affect the surface quality or dimensional stability of the casts. Conclusion: Mixing the extract of M. citrifolia L. with irreversible hydrocolloid powder is an alternative method to prevent contamination without sacrificing impression quality. PMID:26538926

A Bovine Lymphosarcoma Cell Line Infected with Theileria annulata Exhibits an Irreversible Reconfiguration of Host Cell Gene Expression

PubMed Central

Durrani, Zeeshan; Pillai, Sreerekha S.; Baird, Margaret; Shiels, Brian R.

2013-01-01

Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner. PMID:23840536

The role of muscarinic receptor subtypes on carbachol-induced contraction of normal human detrusor and overactive detrusor associated with benign prostatic hyperplasia.

PubMed

Yamanishi, Tomonori; Kaga, Kanya; Fuse, Miki; Shibata, Chiharu; Kamai, Takao; Uchiyama, Tomoyuki

2015-06-01

The aim of this study was to compare the effect of antimuscarinic antagonists on carbachol-induced contraction of normal human bladder and detrusor overactivity associated with benign prostatic hyperplasia (DO/BPH). Samples of human bladder muscle were obtained from patients undergoing total cystectomy for bladder cancer (normal bladder), and those undergoing retropubic prostatectomy for BPH. All of the patients with DO/BPH had detrusor overactivity according to urodynamic studies. Detrusor muscle strips were mounted in 10-ml organ baths containing Krebs solution, and concentration-response curves for carbachol were obtained in the presence of antimuscarinic antagonists (4-DAMP, methoctramine, pirenzepine, tolterodine, solifenacin, trospium, propiverine, oxybutynin, and imidafenacin) or vehicle. All antagonists competitively antagonized concentration-response curves to carbachol with high affinities in normal bladder. The rank order of mean pA2 values was as follows: trospium (10.1) > 4-DAMP (9.87), imidafenacin (9.3) > solifenacin (8.8) > tolterodine (8.6) > oxybutynin (8.3) > propiverine (7.7) > pirenzepine (7.4) > methoctramine (6.6). The effects of these antimuscarinic antagonists did not change when tested with DO/BPH bladder, suggesting that each antimuscarinic antagonist has a similar effect in this condition. Schild plots showed a slope corresponding to unity, except for propiverine with DO/BPH detrusor. In conclusion, M3-receptors mainly mediate contractions in human bladder strips with normal state and DO/BPH. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Severe Intestinal Inflammation in the Small Intestine of Mice Induced by Controllable Deletion of Claudin-7.

PubMed

Li, Wen-Jing; Xu, Chang; Wang, Kun; Li, Teng-Yan; Wang, Xiao-Nan; Yang, Hui; Xing, Tiaosi; Li, Wen-Xia; Chen, Yan-Hua; Gao, Hong; Ding, Lei

2018-05-01

As a potential tumor suppressor gene, Claudin-7 (Cldn7), which is a component of tight junctions, may play an important role in colorectal cancer occurrence and development. To generate a knockout mouse model of inducible conditional Cldn7 in the intestine and analyze the phenotype of the mice after induction with tamoxifen. We constructed Cldn7-flox transgenic mice and crossed them with Villin-CreERT2 mice. The Cldn7 inducible conditional knockout mice appeared normal and were well developed at birth. We induced Cldn7 gene deletion by injecting different dosages of tamoxifen into the mice and then conducted a further phenotypic analysis. After induction for 5 days in succession at a dose of 200 µl tamoxifen in sunflower oil at 10 mg/ml per mouse every time, the mice appeared dehydrated, had a lower temperature, and displayed inactivity or death. The results of hematoxylin-eosin staining showed that the intestines of the Cldn7 inducible conditional knockout mice had severe intestinal defects that included epithelial cell sloughing, necrosis, inflammation and hyperplasia. Owing to the death of ICKO mice, we adjusted the dose of tamoxifen to a dose of 100 µl in sunflower oil at 10 mg/ml per mouse (aged more than 8 weeks old) every 4 days. And we could induce atypical hyperplasia and adenoma in the intestine. Immunofluorescent staining indicated that the intestinal epithelial structure was destroyed. Electron microscopy experimental analysis indicated that the intercellular gap along the basolateral membrane of Cldn7 inducible conditional knockout mice in the intestine was increased and that contact between the cells and matrix was loosened. We generated a model of intestinal Cldn7 inducible conditional knockout mice. Intestinal Cldn7 deletion induced by tamoxifen initiated inflammation and hyperplasia in mice.

When an Adiabatic Irreversible Expansion or Compression Becomes Reversible

ERIC Educational Resources Information Center

Anacleto, Joaquim; Ferreira, J. M.; Soares, A. A.

2009-01-01

This paper aims to contribute to a better understanding of the concepts of a "reversible process" and "entropy". For this purpose, an adiabatic irreversible expansion or compression is analysed, by considering that an ideal gas is expanded (compressed), from an initial pressure P[subscript i] to a final pressure P[subscript f], by being placed in…

Efficacy of a Dexamethasone-Eluting Nitinol Stent on the Inhibition of Pseudointimal Hyperplasia in a Transjugular Intrahepatic Portosystemic Shunt: An Experimental Study in a Swine Model

PubMed Central

Seo, Tae-Seok; Park, Young-Koo; Song, Ho-Young; Park, Sang Joon; Yuk, Sun-Hong

2005-01-01

Objective We wanted to evaluate the feasibility and efficacy of using a dexamethasone (DM)-eluting nitinol stent to inhibit the pseudointimal hyperplasia following stent placement in the transjugular intrahepatic portosystemic shunt tract (TIPS) of a swine. Materials and Methods Fifteen stents were constructed using 0.15 mm-thick nitinol wire; they were 60 mm in length and 10 mm in diameter. The metallic stents were then classified into three types; type 1 and 2 was coated with the mixture of 12% and 20%, respectively, of DM solution and polyurethane (PU), while type 3 was a bare stent that was used for control study. In fifteen swine, each type of stent was implanted in the TIPS tract of 5 swine, and each animal was sacrificed 2 weeks after TIPS creation. The proliferation of the pseudointima was evaluated both on follow-up portogram and pathologic examination. Results One TIPS case, using the type 1 stent, and two TIPS cases, using the type 2 stent, maintained their luminal patency while the others were all occluded. On the histopathologic analysis, the mean of the maximum pseudointimal hyperplasia was expressed as the percentage of the stent radius that was patent, and these values were 51.2%, 50% and 76% for the type 1, 2, and 3 stents, respectively. Conclusion The DM-eluting stent showed a tendency to reduce the development of pseudointimal hyperplasia in the TIPS tract of a swine model with induced-portal hypertension. PMID:16374082

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

Irreversible electroporation of stage 3 locally advanced pancreatic cancer: optimal technique and outcomes

PubMed Central

2015-01-01

Objective Irreversible electroporation (IRE) of stage 3 pancreatic adenocarcinoma has been used to provide quality of life time in patients who have undergone appropriate induction therapy. The optimal technique has been reported within the literature, but not in video form. IRE of locally advanced pancreatic cancer is technically demanding requiring precision ultrasound use for continuous imaging in multiple needle placements and during IRE energy delivery. Methods Appropriate patients with locally advanced pancreatic cancer should have undergone appropriate induction chemotherapy for a reasonable duration. The safe and effective technique for irreversible electroporation is preformed through an open approach with the emphasis on intra-operative ultrasound and intra-operative electroporation management. Results The technique of open irreversible electroporation of the pancreas involves bracketing the target tumor with IRE probes and any and all invaded vital structures including the celiac axis, superior mesenteric artery (SMA), superior mesenteric-portal vein, and bile duct with continuous intraoperative ultrasound imaging through a caudal to cranial approach. Optimal IRE delivery requires a change in amperage of at least 12 amps from baseline tissue conductivity in order to achieve technical success. Multiple pull-backs are necessary since the IRE ablation probe lengths are 1 cm and thus needed to achieve technical success along the caudal to cranial plane. Conclusions Irreversible electroporation in combination with multi-modality therapy for locally advanced pancreatic carcinoma is feasible for appropriate patients with locally advanced cancer. Technical demands are high and require the highest quality ultrasound for precise spacing measurements and optimal delivery to ensure adequate change in tissue resistance. PMID:29075594

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

Logic reversibility and thermodynamic irreversibility demonstrated by DNAzyme-based Toffoli and Fredkin logic gates.

PubMed

Orbach, Ron; Remacle, Françoise; Levine, R D; Willner, Itamar

2012-12-26

The Toffoli and Fredkin gates were suggested as a means to exhibit logic reversibility and thereby reduce energy dissipation associated with logic operations in dense computing circuits. We present a construction of the logically reversible Toffoli and Fredkin gates by implementing a library of predesigned Mg(2+)-dependent DNAzymes and their respective substrates. Although the logical reversibility, for which each set of inputs uniquely correlates to a set of outputs, is demonstrated, the systems manifest thermodynamic irreversibility originating from two quite distinct and nonrelated phenomena. (i) The physical readout of the gates is by fluorescence that depletes the population of the final state of the machine. This irreversible, heat-releasing process is needed for the generation of the output. (ii) The DNAzyme-powered logic gates are made to operate at a finite rate by invoking downhill energy-releasing processes. Even though the three bits of Toffoli's and Fredkin's logically reversible gates manifest thermodynamic irreversibility, we suggest that these gates could have important practical implication in future nanomedicine.

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.

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.

Organ differences in the impact of p27(kip1) deficiency on carcinogenesis induced by N-methyl-N-nitrosourea.

PubMed

Ogawa, Kumiko; Murasaki, Toshiya; Sugiura, Satoshi; Nakanishi, Makoto; Shirai, Tomoyuki

2013-06-01

To evaluate the impact of p27 on carcinogenesis in various organs, N-methyl-N-nitrosourea (MNU), a direct-acting alkylating agent, was given to p27 knock-out mice. Groups of 20-40 male and female mice with null, hetero- or wild-type p27 alleles were given drinking water containing 240 ppm MNU or distilled water every other week for five cycles. The incidence and multiplicity of the induced proliferative lesions were then histologically evaluated at weeks 14 and 20. MNU treatment induced various lesions including squamous hyperplasia and squamous cell carcinoma in the forestomach, atypical hyperplasia and adenocarcinomas in the fundic and pyloric glands, adenomas and adenocarcinomas in the duodenum, malignant lymphomas in the thymus, liver, kidney and spleen and alveolar hyperplasia, adenomas, adenocarcinomas and malignant lymphomas in the lung. Although the incidences of the lesions in the forestomach, fundic and pyloric glands did not differ among the p27 genotypes, those of alveolar hyperplasia of the lung and malignant lymphoma of the thymus were significantly increased in p27-null males as compared with both wild- and hetero-type animals. Moreover, in both p27(+/+) and p27(+/-) cases, the rates for p27-positive cells were obviously increased in proliferative lesions of the pyloric gland and the lung. However, an increased rate of p27-positive cells was not observed in malignant lymphoma of the thymus. These findings suggest that p27 does not control the cell cycle equally in all organs affected by MNU-induced carcinogenesis. Copyright © 2011 John Wiley & Sons, Ltd.

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.

Lagrangian formulation of irreversible thermodynamics and the second law of thermodynamics.

PubMed

Glavatskiy, K S

2015-05-28

We show that the equations which describe irreversible evolution of a system can be derived from a variational principle. We suggest a Lagrangian, which depends on the properties of the normal and the so-called "mirror-image" system. The Lagrangian is symmetric in time and therefore compatible with microscopic reversibility. The evolution equations in the normal and mirror-imaged systems are decoupled and describe therefore independent irreversible evolution of each of the systems. The second law of thermodynamics follows from a symmetry of the Lagrangian. Entropy increase in the normal system is balanced by the entropy decrease in the mirror-image system, such that there exists an "integral of evolution" which is a constant. The derivation relies on the property of local equilibrium, which states that the local relations between the thermodynamic quantities in non-equilibrium are the same as in equilibrium.

Propofol and sodium thiopental protect against MK-801-induced neuronal necrosis in the posterior cingulate/retrosplenial cortex.

PubMed

Jevtovic-Todorovic, V; Wozniak, D F; Powell, S; Olney, J W

2001-09-21

N-Methyl-D-aspartate (NMDA) antagonists act by an anti-excitotoxic action to provide neuroprotection against acute brain injury, but these agents can also cause toxic effects. In low doses they induce reversible neuronal injury, but in higher doses they cause irreversible degeneration of cerebrocortical neurons. GABAmimetic drugs protect against the reversible neurotoxic changes in rat brain. Here we show that two GABAmimetic anesthetic agents--propofol and sodium thiopental--protect against the irreversible neurodegenerative reaction induced by the powerful NMDA antagonist, MK-801.

Pressure-induced amorphization of La{sub 1/3}TaO{sub 3}

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

Noked, O., E-mail: noked@bgu.ac.il; Physics Department, Ben-Gurion University, Beer Sheva 84105; Melchior, A.

2013-06-15

La{sub 1/3}TaO{sub 3}, an A-site cation deficient perovskite, has been studied under pressure by synchrotron X-ray powder diffraction and Raman spectroscopy. It undergoes irreversible pressure induced amorphization at P=18.5 GPa. An almost linear unit cell volume decrease vs. pressure is observed from ambient pressure up to the phase transition. The Raman spectroscopy also shows amorphization at the same pressure, with positive shifts of all modes as a function of pressure. The pressure dependence of the E{sub g} and A{sub 1g} Raman modes arising from the octahedral oxygen network is discussed. - Graphical abstract: La{sub 1/3}Tao{sub 3} exhibits linear pressure–volume relationmore » until irreversible pressure induced amorphization at 18.5 Gpa. - Highlights: • La{sub 1/3}TaO{sub 3} has been studied under pressure by synchrotron XRD and Raman spectroscopy. • La{sub 1/3}TaO{sub 3} undergoes irreversible pressure induced amorphization around 18.5 GPa. • The transition is manifested in both XRD and Raman measurements. • A linear P–V relation is observed from ambient pressure up to the phase transition.« less