Assessment of temporal association of relapse of canine multicentric lymphoma with components of the CHOP protocol: Is cyclophosphamide the weakest link?

PubMed

Wang, Shang-Lin; Lee, Jih-Jong; Liao, Albert Taiching

2016-07-01

Combination chemotherapy, using cyclophosphamide, hydroxydaunorubicin, vincristine and prednisolone (CHOP), is the most commonly used treatment for canine lymphoma. Most affected dogs respond during the initial stages of chemotherapy, but many relapse. The aim of this study was to evaluate the relationship between the use of specific chemotherapy drugs and clinical relapse, using the modified Madison-Wisconsin, 25 week chemotherapy protocol. Forty-one of 68 dogs affected with multicentric lymphoma relapsed during the treatment period. Relapse occurred more frequently after the administration of cyclophosphamide (n = 24; P < 0.01), compared with vincristine (n = 9) or doxorubicin (n = 5). Therefore, the therapeutic outcome of traditional CHOP-based chemotherapy might be improved by replacing cyclophosphamide with other cytotoxic drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effect of long or chopped straw on pig behaviour.

PubMed

Lahrmann, H P; Oxholm, L C; Steinmetz, H; Nielsen, M B F; D'Eath, R B

2015-05-01

In the EU, pigs must have permanent access to manipulable materials such as straw, rope, wood, etc. Long straw can fulfil this function, but can increase labour requirements for cleaning pens, and result in problems with blocked slatted floors and slurry systems. Chopped straw might be more practical, but what is the effect on pigs' behaviour of using chopped straw instead of long straw? Commercial pigs in 1/3 slatted, 2/3 solid pens of 15 pigs were provided with either 100 g/pig per day of long straw (20 pens) or of chopped straw (19 pens). Behavioural observations were made of three focal pigs per pen (one from each of small, medium and large weight tertiles) for one full day between 0600 and 2300 h at each of ~40 and ~80 kg. The time spent rooting/investigating overall (709 s/pig per hour at 40 kg to 533 s/pig per hour at 80 kg), or directed to the straw/solid floor (497 s/pig per hour at 40 kg to 343 s/pig per hour at 80 kg), was not affected by straw length but reduced with age. Time spent investigating other pigs (83 s/pig per hour at 40 kg), the slatted floor (57 s/pig per hour) or pen fixtures (21 s/pig per hour) was not affected by age or straw length. Aggressive behaviour was infrequent, but lasted about twice as long in pens with chopped straw (2.3 s/pig per hour at 40 kg) compared with pens with long straw (1.0 s/pig per hour at 40 kg, P=0.060). There were no significant effects of straw length on tail or ear lesions, but shoulders were significantly more likely to have minor scratches with chopped straw (P=0.031), which may reflect the higher levels of aggression. Smaller pigs showed more rooting/investigatory behaviour, and in particular directed towards the straw/solid floor and the slatted floor than their larger pen-mates. Females exhibited more straw and pen fixture-directed behaviour than males. There were no effects of pig size or sex on behaviour directed towards other pigs. In summary, pigs spent similar amounts of time interacting with straw/solid floor when long and chopped straw were provided, and most aspects of pig-directed behaviour and injuries were not affected by straw length. There was an increase in pigs with minor shoulder lesions with chopped straw, perhaps because of increased aggression. The use of chopped straw as an enrichment material for pigs warrants further investigation in larger and more detailed studies.

Progesterone production is affected by unfolded protein response (UPR) signaling during the luteal phase in mice.

PubMed

Park, Hyo-Jin; Park, Sun-Ji; Koo, Deog-Bon; Lee, Sang-Rae; Kong, Il-Keun; Ryoo, Jae-Woong; Park, Young-Il; Chang, Kyu-Tae; Lee, Dong-Seok

2014-09-15

We examined whether the three unfolded protein response (UPR) signaling pathways, which are activated in response to endoplasmic reticulum (ER)-stress, are involved in progesterone production in the luteal cells of the corpus luteum (CL) during the mouse estrous cycle. The luteal phase of C57BL/6 female mice (8 weeks old) was divided into two stages: the functional stage (16, 24, and 48 h) and the regression stage (72 and 96 h). Western blotting and reverse transcription (RT)-PCR were performed to analyze UPR protein/gene expression levels in each stage. We investigated whether ER stress affects the progesterone production by using Tm (0.5 μg/g BW) or TUDCA (0.5 μg/g BW) through intra-peritoneal injection. Our results indicate that expressions of Grp78/Bip, p-eIF2α/ATF4, p50ATF6, and p-IRE1/sXBP1 induced by UPR activation were predominantly maintained in functional and early regression stages of the CL. Furthermore, the expression of p-JNK, CHOP, and cleaved caspase3 as ER-stress mediated apoptotic factors increased during the regression stage. Cleaved caspase3 levels increased in the late-regression stage after p-JNK and CHOP expression in the early-regression stage. Additionally, although progesterone secretion and levels of steroidogenic enzymes decreased following intra-peritoneal injection of Tunicamycin, an ER stress inducer, the expression of Grp78/Bip, p50ATF6, and CHOP dramatically increased. These results suggest that the UPR signaling pathways activated in response to ER stress may play important roles in the regulation of the CL function. Furthermore, our findings enhance the understanding of the basic mechanisms affecting the CL life span. Copyright © 2014 Elsevier Inc. All rights reserved.

Anthocyanin inhibits propidium iodide DNA fluorescence in Euphorbia pulcherrima: implications for genome size variation and flow cytometry.

PubMed

Bennett, Michael D; Price, H James; Johnston, J Spencer

2008-04-01

Measuring genome size by flow cytometry assumes direct proportionality between nuclear DNA staining and DNA amount. By 1997 it was recognized that secondary metabolites may affect DNA staining, thereby causing inaccuracy. Here experiments are reported with poinsettia (Euphorbia pulcherrima) with green leaves and red bracts rich in phenolics. DNA content was estimated as fluorescence of propidium iodide (PI)-stained nuclei of poinsettia and/or pea (Pisum sativum) using flow cytometry. Tissue was chopped, or two tissues co-chopped, in Galbraith buffer alone or with six concentrations of cyanidin-3-rutinoside (a cyanidin-3-rhamnoglucoside contributing to red coloration in poinsettia). There were large differences in PI staining (35-70 %) between 2C nuclei from green leaf and red bract tissue in poinsettia. These largely disappeared when pea leaflets were co-chopped with poinsettia tissue as an internal standard. However, smaller (2.8-6.9 %) differences remained, and red bracts gave significantly lower 1C genome size estimates (1.69-1.76 pg) than green leaves (1.81 pg). Chopping pea or poinsettia tissue in buffer with 0-200 microm cyanidin-3-rutinoside showed that the effects of natural inhibitors in red bracts of poinsettia on PI staining were largely reproduced in a dose-dependent way by this anthocyanin. Given their near-ubiquitous distribution, many suspected roles and known affects on DNA staining, anthocyanins are a potent, potential cause of significant error variation in genome size estimations for many plant tissues and taxa. This has important implications of wide practical and theoretical significance. When choosing genome size calibration standards it seems prudent to select materials producing little or no anthocyanin. Reviewing the literature identifies clear examples in which claims of intraspecific variation in genome size are probably artefacts caused by natural variation in anthocyanin levels or correlated with environmental factors known to induce variation in pigmentation.

Cyclophilin B is involved in p300-mediated degradation of CHOP in tumor cell adaptation to hypoxia.

PubMed

Jeong, K; Kim, H; Kim, K; Kim, S-J; Hahn, B-S; Jahng, G-H; Yoon, K-S; Kim, S S; Ha, J; Kang, I; Choe, W

2014-03-01

The regulation of CCAAT/enhancer-binding protein-homologous protein (CHOP), an endoplasmic reticulum (ER) stress-response factor, is key to cellular survival. Hypoxia is a physiologically important stress that induces cell death in the context of the ER, especially in solid tumors. Although our previous studies have suggested that Cyclophilin B (CypB), a molecular chaperone, has a role in ER stress, currently, there is no direct information supporting its mechanism under hypoxia. Here, we demonstrate for the first time that CypB is associated with p300 E4 ligase, induces ubiquitination and regulates the proteasomal turnover of CHOP, one of the well-known pro-apoptotic molecules under hypoxia. Our findings show that CypB physically interacts with the N-terminal α-helix domain of CHOP under hypoxia and cooperates with p300 to modulate the ubiquitination of CHOP. We also show that CypB is transcriptionally induced through ATF6 under hypoxia. Collectively, these findings demonstrate that CypB prevents hypoxia-induced cell death through modulation of ubiquitin-mediated CHOP protein degradation, suggesting that CypB may have an important role in the tight regulation of CHOP under hypoxia.

Cyclophilin B is involved in p300-mediated degradation of CHOP in tumor cell adaptation to hypoxia

PubMed Central

Jeong, K; Kim, H; Kim, K; Kim, S-J; Hahn, B-S; Jahng, G-H; Yoon, K-S; Kim, S S; Ha, J; Kang, I; Choe, W

2014-01-01

The regulation of CCAAT/enhancer-binding protein-homologous protein (CHOP), an endoplasmic reticulum (ER) stress-response factor, is key to cellular survival. Hypoxia is a physiologically important stress that induces cell death in the context of the ER, especially in solid tumors. Although our previous studies have suggested that Cyclophilin B (CypB), a molecular chaperone, has a role in ER stress, currently, there is no direct information supporting its mechanism under hypoxia. Here, we demonstrate for the first time that CypB is associated with p300 E4 ligase, induces ubiquitination and regulates the proteasomal turnover of CHOP, one of the well-known pro-apoptotic molecules under hypoxia. Our findings show that CypB physically interacts with the N-terminal α-helix domain of CHOP under hypoxia and cooperates with p300 to modulate the ubiquitination of CHOP. We also show that CypB is transcriptionally induced through ATF6 under hypoxia. Collectively, these findings demonstrate that CypB prevents hypoxia-induced cell death through modulation of ubiquitin-mediated CHOP protein degradation, suggesting that CypB may have an important role in the tight regulation of CHOP under hypoxia. PMID:24270407

Food processing and structure impact the metabolizable energy of almonds.

PubMed

Gebauer, Sarah K; Novotny, Janet A; Bornhorst, Gail M; Baer, David J

2016-10-12

The measured metabolizable energy (ME) of whole almonds has been shown to be less than predicted by Atwater factors. However, data are lacking on the effects of processing (roasting, chopping or grinding) on the ME of almonds. A 5-period randomized, crossover study in healthy individuals (n = 18) was conducted to measure the ME of different forms of almonds (42 g per day), as part of a controlled diet: whole, natural almonds; whole, roasted almonds; chopped almonds; almond butter; and control (0 g per day). After 9 days of adaptation to each diet, participants collected all urine and fecal samples for 9 days. Diets, urine, and feces were analyzed to determine ME. Fracture force and fracture properties of whole and chopped almonds were measured. Measured ME (kcal g -1 ) of whole natural almonds (4.42), whole roasted almonds (4.86), and chopped almonds (5.04) was significantly lower than predicted with Atwater factors (P < 0.001); ME of almond butter (6.53 kcal g -1 ) was similar to predicted (P = 0.08). The ME of whole roasted and chopped almonds was lower than almond butter (P < 0.0001). ME of whole natural almonds was lower than whole roasted almonds (P < 0.05). This may be due to lower hardness of whole roasted (298 ± 1.3 N) compared to whole natural almonds (345 ± 1.6 N) (P < 0.05), and to whole natural almonds fracturing into fewer, larger particles, thus inhibiting the release of lipids. Atwater factors overestimate the ME of whole (natural and roasted) and chopped almonds. The amount of calories absorbed from almonds is dependent on the form in which they are consumed.

Comparison of efficacy and toxicity of doxorubicin and mitoxantrone in combination chemotherapy for canine lymphoma

PubMed Central

Wang, Shang-Lin; Lee, Jih-Jong; Liao, Albert Taiching

2016-01-01

Forty-four dogs with multicentric lymphoma were treated using a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) induction protocol or treated using a cyclophosphamide, mitoxantrone, vincristine, and prednisolone (CMOP) induction protocol. There was no statistical difference in signalment and the presence of historical negative prognostic factors between the groups. The median progression-free survival (PFS) in the CHOP and CMOP groups were 222 d and 162 d, respectively (P = 0.75). The median survival time (MST) of dogs in CHOP and CMOP groups were 318 d and 242 d, respectively (P = 0.63). Anorexia and diarrhea episodes were significantly higher in the CHOP group than in the CMOP group (P = 0.02 and P = 0.01, respectively). These results suggest that the CMOP protocol provides similar PFS, MST and causes fewer side effects compared to the CHOP protocol. Therefore, the CMOP protocol may be another treatment choice for canine multicentric lymphoma. PMID:26933263

Comparison of efficacy and toxicity of doxorubicin and mitoxantrone in combination chemotherapy for canine lymphoma.

PubMed

Wang, Shang-Lin; Lee, Jih-Jong; Liao, Albert Taiching

2016-03-01

Forty-four dogs with multicentric lymphoma were treated using a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) induction protocol or treated using a cyclophosphamide, mitoxantrone, vincristine, and prednisolone (CMOP) induction protocol. There was no statistical difference in signalment and the presence of historical negative prognostic factors between the groups. The median progression-free survival (PFS) in the CHOP and CMOP groups were 222 d and 162 d, respectively (P = 0.75). The median survival time (MST) of dogs in CHOP and CMOP groups were 318 d and 242 d, respectively (P = 0.63). Anorexia and diarrhea episodes were significantly higher in the CHOP group than in the CMOP group (P = 0.02 and P = 0.01, respectively). These results suggest that the CMOP protocol provides similar PFS, MST and causes fewer side effects compared to the CHOP protocol. Therefore, the CMOP protocol may be another treatment choice for canine multicentric lymphoma.

Evaluation of factors associated with second remission in dogs with lymphoma undergoing retreatment with a cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy protocol: 95 cases (2000-2007).

PubMed

Flory, Andrea B; Rassnick, Kenneth M; Erb, Hollis N; Garrett, Laura D; Northrup, Nicole C; Selting, Kim A; Phillips, Brenda S; Locke, Jennifer E; Chretin, John D

2011-02-15

To evaluate factors associated with second remission in dogs with lymphoma retreated with a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) protocol after relapse following initial treatment with a first-line 6-month CHOP protocol. Retrospective case series. 95 dogs with lymphoma. Medical records were reviewed. Remission duration was estimated by use of the Kaplan-Meier method. Factors potentially associated with prognosis were examined. Median remission duration after the first-line CHOP protocol was 289 days (range, 150 to 1,457 days). Overall, 78% (95% confidence interval [CI], 69% to 86%) of dogs achieved a complete remission following retreatment, with a median second remission duration of 159 days (95% CI, 126 to 212 days). Duration of time off chemotherapy was associated with likelihood of response to retreatment; median time off chemotherapy was 140 days for dogs that achieved a complete remission after retreatment and 84 days for dogs that failed to respond to retreatment. Second remission duration was associated with remission duration after initial chemotherapy; median second remission duration for dogs with initial remission duration ≥ 289 days was 214 days (95% CI, 168 to 491 days), compared with 98 days (95% CI, 70 to 144 days) for dogs with initial remission duration < 289 days. Findings suggested that retreatment with the CHOP protocol can be effective in dogs with lymphoma that successfully complete an initial 6-month CHOP protocol.

Chop deletion reduces oxidative stress, improves β cell function, and promotes cell survival in multiple mouse models of diabetes

PubMed Central

Song, Benbo; Scheuner, Donalyn; Ron, David; Pennathur, Subramaniam; Kaufman, Randal J.

2008-01-01

The progression from insulin resistance to type 2 diabetes is caused by the failure of pancreatic β cells to produce sufficient levels of insulin to meet the metabolic demand. Recent studies indicate that nutrient fluctuations and insulin resistance increase proinsulin synthesis in β cells beyond the capacity for folding of nascent polypeptides within the endoplasmic reticulum (ER) lumen, thereby disrupting ER homeostasis and triggering the unfolded protein response (UPR). Chronic ER stress promotes apoptosis, at least in part through the UPR-induced transcription factor C/EBP homologous protein (CHOP). We assessed the effect of Chop deletion in multiple mouse models of type 2 diabetes and found that Chop–/– mice had improved glycemic control and expanded β cell mass in all conditions analyzed. In both genetic and diet-induced models of insulin resistance, CHOP deficiency improved β cell ultrastructure and promoted cell survival. In addition, we found that isolated islets from Chop–/– mice displayed increased expression of UPR and oxidative stress response genes and reduced levels of oxidative damage. These findings suggest that CHOP is a fundamental factor that links protein misfolding in the ER to oxidative stress and apoptosis in β cells under conditions of increased insulin demand. PMID:18776938

Factors Affecting Detection of Hepatitis E Virus on Canadian Retail Pork Chops and Pork Livers Assayed Using Real-Time RT-PCR.

PubMed

Wilhelm, B J; Leblanc, D; Avery, B; Pearl, D L; Houde, A; Rajić, A; McEwen, S A

2016-03-01

We collected 599 Canadian retail pork chops and 283 pork livers routinely (usually weekly) from April 2011 to March 2012 using the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) retail sampling platform. Samples were assayed using validated real-time (q) reverse transcriptase polymerase chain reaction (RT-PCR) and nested classical RT-PCR for the detection of hepatitis E virus (HEV), porcine enteric calicivirus (PEC) and rotavirus (RV). The presence of Escherichia coli, Salmonella spp. and Campylobacter spp. was measured on a subset of our samples. Exact logistic regression models were fitted for predictors for HEV detection, for each assay. For both assays, sample type (pork chop versus liver) was a significant predictor for HEV RNA detection. For nested classical RT-PCR but not qRT-PCR, region of sample collection was a significant predictor (P = 0.008) of HEV detection. Odds of HEV detection were greatest in spring relative to other seasons. E. coli was a significant predictor for HEV RNA detection using the qRT-PCR (P = 0.03). Overall, the prevalence of E. coli, Salmonella spp. and Campylobacter spp. was significantly greater than HEV, PEC or RV on our retail pork samples. Our sparse data set for the detection of PEC and RV precluded modelling of risk factors for the detection of these viruses. © 2015 Zoonoses and Public Health © 2015 Her Majesty the Queen in Right of Canada Reproduced with the permission of the Minister of the Public Health Agency of Canada.

Calculating the nutrient composition of recipes with computers.

PubMed

Powers, P M; Hoover, L W

1989-02-01

The objective of this research project was to compare the nutrient values computed by four commonly used computerized recipe calculation methods. The four methods compared were the yield factor, retention factor, summing, and simplified retention factor methods. Two versions of the summing method were modeled. Four pork entrée recipes were selected for analysis: roast pork, pork and noodle casserole, pan-broiled pork chops, and pork chops with vegetables. Assumptions were made about changes expected to occur in the ingredients during preparation and cooking. Models were designed to simulate the algorithms of the calculation methods using a microcomputer spreadsheet software package. Identical results were generated in the yield factor, retention factor, and summing-cooked models for roast pork. The retention factor and summing-cooked models also produced identical results for the recipe for pan-broiled pork chops. The summing-raw model gave the highest value for water in all four recipes and the lowest values for most of the other nutrients. A superior method or methods was not identified. However, on the basis of the capabilities provided with the yield factor and retention factor methods, more serious consideration of these two methods is recommended.

Improving tenderness of normal and callipyge lambs with calcium chloride.

PubMed

Clare, T L; Jackson, S P; Miller, M F; Elliott, C T; Ramsey, C B

1997-02-01

Effects of CaCl2 injection on meat quality traits of 10 normal and 10 callipyge phenotype crossbred lambs were studied. Primal cuts from one side of each carcass served as the control and cuts from the other side were injected. After storage for 14 d at 2 degrees C, chops were evaluated by Warner-Bratzler shear (WBS) force, trained sensory panel, and consumer sensory panel. Treatment of the muscles with 200 mM CaCl2 increased (P < .05) tenderness and lamb flavor intensity scores by the trained sensory panel and decreased (P < .05) WBS force in both normal and callipyge phenotypes. When callipyge muscles were not injected, consumers rated 94% of leg chops, 60% of loin chops, and 89.4% of shoulder chops acceptable in tenderness. However, when callipyge muscles were CaCl2-injected, consumers rated 96.5% of leg chops, 85.4% of loin chips, and 93.5% of shoulder chops acceptable in tenderness. Normal phenotype carcasses had more marbling (P < .05) in a firmer, finer-textured, brighter cherry red longissimus muscle. Injection of CaCl2 did not affect visual lean color or L, a or b values during retail display of the chops. However, CaCl2 injection decreased color uniformity, increased discoloration, and increased browning at d 2. Therefore, a 5% (wt/wt) injection of 200 mM CaCl2 solution can be applied to improve normal and callipyge lamb tenderness and reduce tenderness and juiciness variation without detrimental effects on other palatability traits when evaluated by trained sensory panelists or consumers.

CHOP chemotherapy for the treatment of canine multicentric T-cell lymphoma.

PubMed

Rebhun, R B; Kent, M S; Borrofka, S A E B; Frazier, S; Skorupski, K; Rodriguez, C O

2011-03-01

Dogs with multicentric T-cell lymphoma are commonly treated with CHOP chemotherapy protocols that include cyclophosphamide, doxorubicin, vincristine and prednisone. The purpose of this study was to evaluate the use of CHOP chemotherapy for dogs with multicentric T-cell lymphoma. Identification of prognostic factors in this specific subset of dogs was of secondary interest. Twenty-three out of 24 dogs responded to CHOP chemotherapy and these dogs remained on the protocol for a median of 146 days. No variable was associated with progression free survival (PFS) including stage, substage, hypercalcemia or radiographic evidence of a cranial mediastinal mass. The median overall survival time (OST) for all dogs was 235 days. Dogs that were thrombocytopenic at presentation experienced a significantly longer OST (323 versus 212 days, P=0.01). © 2010 Blackwell Publishing Ltd.

Influence of the chopped frequency of light on optical transport characteristics of human skin including at acupuncture points

NASA Astrophysics Data System (ADS)

Yang, Hong-qin; Xie, Shu-sen; Liu, Song-hao; Li, Hui; Wang, Yu-hua; Guo, Zhou-yi

2007-11-01

An experimental protocol was established for noninvasively measuring the optical transport characteristics of skin tissue along human meridian direction over body surface including at acupuncture points. The diffuse remittance for 658 nm light radiation along the pericardium meridian and non-meridian directions were measured respectively. The influence of the chopped frequency of light on the detected light signal was investigated. It is shown that the optical transport characteristics of skin tissue accords with the Beer's exponential attenuation law along the meridian including at acupuncture points and non-median directions. However there is an obvious difference between the propagations along the meridian direction and non-meridian direction (P<0.05). Furthermore, the chopped frequency can affect the detected signal. The diffuse remittance signal decreased with the chopped frequency's increase and it was different between the meridian and non-meridian directions. These findings are important and meaningful for interpreting the human meridian phenomena by biomedical optics.

Disease Characteristics, Patterns of Care, and Survival in Very Elderly Patients with Diffuse Large B-Cell Lymphoma

PubMed Central

Williams, Jessica N.; Rai, Ashish; Lipscomb, Joseph; Koff, Jean L.; Nastoupil, Loretta J.; Flowers, Christopher R.

2015-01-01

Background Although rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered standard therapy for diffuse large B-cell lymphoma (DLBCL), patterns of use and the impact of R-CHOP on survival in patients >80 years are less clear. Methods We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to characterize presentation, treatment, and survival patterns in DLBCL patients diagnosed from 2002–2009. Chi-squared tests compared characteristics and initial treatments of DLBCL patients >80 years and ≤80 years. Multivariable logistic regression models examined factors associated with treatment selection in patients >80 years; standard and propensity score-adjusted multivariable Cox proportional hazards models examined relationships between treatment regimen, treatment duration, and survival. Results Among 4,635 patients with DLBCL, 1,156 (25%) were >80 years. Patients >80 were less likely to receive R-CHOP and more likely to be observed or receive rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP); both p<0.0001. Marital status, stage, disease site, performance status, radiation therapy, and growth factor support were associated with initial R-CHOP in patients >80. In propensity score-matched multivariable Cox proportional hazards models examining relationships between treatment regimen and survival, R-CHOP was the only regimen associated with improved OS (hazard ratio (HR) = 0.45, 95% confidence interval (CI) = 0.33–0.62) and LRS (HR=0.58, 95% CI 0.38–0.88). Conclusions Although DLBCL patients >80 years were less likely to receive R-CHOP, this regimen conferred the longest survival and should be considered for this population. Further studies are needed to characterize the impact of DLBCL treatment on quality of life in this age group. PMID:25675909

A synthetic chalcone, 2'-hydroxy-2,3,5'-trimethoxychalcone triggers unfolded protein response-mediated apoptosis in breast cancer cells.

PubMed

Lee, Da Hyun; Jung Jung, You; Koh, Dongsoo; Lim, Yoongho; Lee, Young Han; Shin, Soon Young

2016-03-01

The primary aim of this study was to find novel chemopreventive agents effective against breast cancer. Endoplasmic reticulum (ER) stress can induce apoptosis through the unfolded protein response (UPR). 2'-Hydroxy-2,3,5'-trimethoxychalcone (DK143) is a synthetic flavonoid derivative. The present study provides evidence supporting the role of the UPR in mediating the apoptotic effect of DK143. Treatment with DK143 triggered apoptosis through the activation of the caspase pathway in MDA-MB-231 breast cancer cells without affecting viability of MCF10A non-transformed breast epithelial cells. Further analysis revealed that DK143 produced reactive oxygen species (ROS) in MDA-MB-231 cells, but not in MCF10A cells, and upregulated the expression of ER stress sensors, including GRP78/BiP, IRE1α, CHOP, and Bim in MDA-MB-231 cells. In addition, UPR-related transcription factors, XBP-1 and CHOP, were activated by DK143. Moreover, silencing of IRE1α or CHOP by corresponding siRNA molecules attenuated DK143-induced apoptosis. Furthermore, DK143 suppressed mouse tumor growth in vivo. These results demonstrate that promoting ER stress in breast cancer cells via UPR induction might be a promising strategy for developing new chemotherapeutic or chemopreventive agents for breast cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles.

PubMed

Cunningham, David; Hawkes, Eliza A; Jack, Andrew; Qian, Wendi; Smith, Paul; Mouncey, Paul; Pocock, Christopher; Ardeshna, Kirit M; Radford, John A; McMillan, Andrew; Davies, John; Turner, Deborah; Kruger, Anton; Johnson, Peter; Gambell, Joanna; Linch, David

2013-05-25

Dose intensification with a combination of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) every 2 weeks improves outcomes in patients older than 60 years with diffuse large B-cell lymphoma compared with CHOP every 3 weeks. We investigated whether this survival benefit from dose intensification persists in the presence of rituximab (R-CHOP) in all age groups. Patients (aged ≥18 years) with previously untreated bulky stage IA to stage IV diffuse large B-cell lymphoma in 119 centres in the UK were randomly assigned centrally in a one-to-one ratio, using minimisation, to receive six cycles of R-CHOP every 14 days plus two cycles of rituximab (R-CHOP-14) or eight cycles of R-CHOP every 21 days (R-CHOP-21). R-CHOP-21 was intravenous cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), vincristine 1·4 mg/m(2) (maximum dose 2 mg), and rituximab 375 mg/m(2) on day 1, and oral prednisolone 40 mg/m(2) on days 1-5, administered every 21 days for a total of eight cycles. R-CHOP-14 was intravenous cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), vincristine 2 mg, rituximab 375 mg/m(2) on day 1, and oral prednisolone 100 mg on days 1-5, administered every 14 days for six cycles, followed by two further infusions of rituximab 375 mg/m(2) on day 1 every 14 days. The trial was not masked. The primary outcome was overall survival (OS). This study is registered, number ISRCTN 16017947. 1080 patients were assigned to R-CHOP-21 (n=540) and R-CHOP-14 (n=540). With a median follow-up of 46 months (IQR 35-57), 2-year OS was 82·7% (79·5-85·9) in the R-CHOP-14 group and 80·8% (77·5-84·2) in the R-CHOP-21 (standard) group (hazard ratio 0·90, 95% CI 0·70-1·15; p=0·3763). No significant improvement was noted in 2-year progression-free survival (R-CHOP-14 75·4%, 71·8-79·1, and R-CHOP-21 74·8%, 71·0-78·4; 0·94, 0·76-1·17; p=0·5907). High international prognostic index, poor-prognosis molecular characteristics, and cell of origin were not predictive for benefit from either schedule. Grade 3 or 4 neutropenia was higher in the R-CHOP-21 group (318 [60%] of 534 vs 167 [31%] of 534), with no prophylactic use of recombinant human granulocyte-colony stimulating factor mandated in this group, whereas grade 3 or 4 thrombocytopenia was higher with R-CHOP-14 (50 [9%] vs 28 [5%]); other frequent grade 3 or 4 adverse events were febrile neutropenia (58 [11%] vs 28 [5%]) and infection (125 [23%] vs 96 [18%]). Frequencies of non-haematological adverse events were similar in the R-CHOP-21 and R-CHOP-14 groups. R-CHOP-14 is not superior to R-CHOP-21 chemotherapy for previously untreated diffuse large B-cell lymphoma; therefore, R-CHOP-21 remains the standard first-line treatment in patients with this haematological malignancy. No molecular or clinical subgroup benefited from dose intensification in this study. Chugai Pharmaceutical, Cancer Research UK, National Institute for Health Research Biomedical Research Centres scheme at both University College London and the Royal Marsden NHS Foundation Trust, and Institute of Cancer Research. Copyright © 2013 Elsevier Ltd. All rights reserved.

Prognostic importance of the soluble form of IL-2 receptorα (sIL-2Rα) and its relationship with surface expression of IL-2Rα (CD25) of lymphoma cells in diffuse large B-cell lymphoma treated with CHOP-like regimen with or without rituximab: a retrospective analysis of 338 cases.

PubMed

Hashimoto, Yoko; Yokohama, Akihiko; Saitoh, Akio; Nakahashi, Hirotaka; Toyama, Kohtaro; Mitsui, Takeki; Koiso, Hiromi; Saitoh, Takayuki; Handa, Hiroshi; Uchiumi, Hideki; Jinbo, Takahiro; Murayama, Kayoko; Matsumoto, Morio; Sawamura, Morio; Karasawa, Masamitsu; Murakami, Hirokazu; Hirato, Junko; Nojima, Yoshihisa; Kojima, Masaru; Tsukamoto, Norifumi

2013-01-01

We evaluated the prognostic significance of the serum level of the soluble form of interleukin-2 receptorα (sIL-2Rα) and investigated its association with CD25 expression on tumor cells in diffuse large B-cell lymphoma (DLBCL). Three hundred and thirty-eight adult patients with newly diagnosed DLBCL were eligible for this retrospective study. 32.2% of patients were treated with CHOP-like regimen and 67.8% with R-CHOP-like regimen. CD25 expression on the surface of tumor cells was evaluated in 143 cases and its relationship with sIL-2Rα level was also investigated. Both overall survival (OS) and progression-free survival (PFS) were poorer in patients with higher sIL-2Rα, in both R-CHOP and CHOP groups. sIL-2Rα > 1,000 U/mL and performance status (PS) ≥ 2 were independently associated with poorer OS, and sIL-2Rα > 1,000 U/mL, age > 60 years, and ≥ 2 extranodal sites were independently associated with poorer PFS in the R-CHOP group. The sIL-2Rα level was higher in the CD25-positive group than in the CD25-negative group in stage 3 or 4 disease (p = 0.010). Multiple linear regression analysis showed CD25 expression to be independently correlated with sIL-2Rα levels. High sIL-2Rα is an important risk factor for survival in DLBCL treated with not only CHOP-like, but also R-CHOP-like regimens, regardless of the tumor's expression of CD25.

CHOP or THP-COP regimens in the treatment of newly diagnosed peripheral T-cell lymphoma, not otherwise specified: a comparison of doxorubicin and pirarubicin.

PubMed

Shibata, Yuhei; Hara, Takeshi; Kasahara, Senji; Yamada, Toshiki; Sawada, Michio; Mabuchi, Ryoko; Matsumoto, Takuro; Nakamura, Nobuhiko; Nakamura, Hiroshi; Ninomiya, Soranobu; Kitagawa, Junichi; Kanemura, Nobuhiro; Kito, Yusuke; Goto, Naoe; Miyazaki, Tatsuhiko; Takami, Tsuyoshi; Takeuchi, Tamotsu; Shimizu, Masahito; Tsurumi, Hisashi

2017-06-01

The CHOP regimen consisting of cyclophosphamide, doxorubicin (DOX), vincristine and prednisolone has been the most used regimen for peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Pirarubicin [tetrahydropyranyladriamycin (THP)], a derivative of DOX, is an anthracycline with reportedly less cardiotoxicity than DOX. Here, we confirmed the efficacy of THP-COP using THP instead of DOX in the treatment of PTCL-NOS. The study protocol employed a retrospective, consecutive entry design. We retrospectively analysed 56 patients with PTCL-NOS who had received THP-COP or CHOP. These regimens were performed every 21 days. Twenty-nine patients received THP-COP, and 27 received CHOP. There were no significant differences in known prognostic factors, including in the International Prognostic Index (IPI) and the prognostic index for T-cell lymphoma (PIT), between the two groups. Complete remission rates in patients with THP-COP and CHOP were 52% in both groups; the 3-year overall survival (OS) rates were 67% and 52% (p = 0.074), and the 3-year progression-free survival (PFS) rates were 51% and 29% (p = 0.070), respectively. In patients with low IPI (low or low-intermediate), THP-COP had significantly better 3-year OS (100% vs. 64%; p < 0.001) and 3-year PFS (75% vs. 33%; p < 0.05) than CHOP. Similar differences between THP-COP and CHOP were observed in patients with a low PIT (groups 1 or 2). Our study showed that THP-COP produced results equivalent to CHOP regarding efficacy and safety in patients with PTCL-NOS. In patients with low IPI or PIT, THP-COP resulted in significantly better prognosis. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Community health outreach program of the Chad-Cameroon petroleum development and pipeline project.

PubMed

Utzinger, Jürg; Wyss, Kaspar; Moto, Daugla D; Tanner, Marcel; Singer, Burton H

2004-02-01

A critical appraisal has been presented of the CHOP for a large-scale energy infrastructure development project that was implemented in two of the world's poorest countries. The project is under close scrutiny from various independent monitoring groups, civil society organizations, and human rights groups. Reviewing the achievements and shortcomings permits the extraction of important lessons that will be critical for the future adoption of the CHOP in the current setting and for the implementation of additional CHOPs elsewhere in the developing world. The authors believe that the design must be flexible, efficient, and innovative so that a CHOP promptly can address pressing public health issues as they arise (eg, epidemic outbreak) and include the needs and demands of the concerned communities. An innovative feature of the current project is the high degree and mix of public-private partnerships. The project's CHOP also relies on partnerships. As elaborated elsewhere, public-private partnerships should be seen as a social experiment--they reveal promise but are not the solution for every problem. For this CHOP, the focus is on partnerships between a multinational consortium, government agencies, and international organizations. The partnerships also include civil society organizations for monitoring and evaluation and local NGOs designated for the implementation of the selected public health interventions within the CHOP. The governments and their respective health policies often form the umbrella under which the partnerships operate. With the increase in globalization, however, the importance and capacities of governments have diminished, and there is growing private-sector involvement. Private enterprise is seen as an efficient, innovative, pragmatic, and powerful means to achieve environmental and social sustainability. Experiences with the partnership configurations in the current CHOP are of importance for tackling grand challenges in global health by applying a systemic approach. Other innovations of the project in general, and the CHOP in particular, are the strong emphases on institutional-capacity building, integration, and sustainability. In countries like Chad and Cameroon, there are serious shortages of well-qualified health personnel. The CHOP described in this article provides leverage for initiating better healthcare that will reduce the high burden of disease in the developing world. Reducing mortality rates for infants and children younger than 5 years in sub-Saharan Africa requires massive scaling-up of malaria-control interventions (eg, large-scale distribution of ITNs to protect millions of African children), thereby approaching the Abuja targets (see Armstrong Schellenberg et al). The local NGOs that took a lead within the framework of the CHOP in the distribution of ITNs and accompanying health education messages can extend these activities to communities living outside the vicinity of the project area. Serious shortcomings of the current CHOP, consistently identified by the external monitoring groups, include the lack of a regional health plan, cumulative impact assessment, and provision of clean water and sanitation outside the narrowly defined project area. This point is of central importance, particularly for Chad, where access to clean water and improved sanitation facilities is low. Another limitation of the current CHOP is the insufficient amount of significance addressed to tuberculosis and the apparent lack of concerted control efforts against HIV infection, AIDS, and tuberculosis. These criticisms, however, must be balanced against the lack of clarity in international discourse about the proper extent of responsibility of the corporate sector for dealing with the health problems of countries in which they do business. In an elegant analysis, the environmental risk factor "unsafe water, sanitation and hygiene" was shown to be one of the major contributors to loss of healthy life, particularly in the developing world. Provision of clean water and sanitation is a key factor for sustainable control of schistosomiasis and soil-transmitted helminths. Reduction of helminth infections might have a beneficial effect on the HIV and AIDS pandemic. The question still remains: What is, or should be, the scope and limits of responsibility of the corporate sector in solving these problems? There is a critical need for the monitoring and evaluation of the long-term impact of a CHOP that develops in parallel with a large development project, emphasizing the broadest possible determinants of health and well-being. To become operational, it requires the establishment and running of a longitudinal demographic surveillance system in the area and in adjacent areas that are unlikely to be affected by the project. This approach, coupled with regular household surveys for in-depth appraisal of health-seeking and asset indices, is the most promising source of data for impact measurement of health, poverty, and equity-related issues. It will facilitate subtle monitoring and surveillance activities, fostering a truly systemic approach by inclusion of all stake holders on the basis of the existing but constantly evolving system.

Additional Survival Benefit of Involved-Lesion Radiation Therapy After R-CHOP Chemotherapy in Limited Stage Diffuse Large B-Cell Lymphoma

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

Kwon, Jeanny; Kim, Il Han, E-mail: ihkim@snu.ac.kr; Cancer Research Institute, Seoul National University College of Medicine, Seoul

Purpose: The purpose of this study was to evaluate the role of involved-lesion radiation therapy (ILRT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in limited stage diffuse large B-cell lymphoma (DLBCL) by comparing outcomes of R-CHOP therapy alone with R-CHOP followed by ILRT. Methods and Materials: We identified 198 patients treated with R-CHOP (median, 6 cycles) for pathologically confirmed DLBCL of limited stage from July 2004 to December 2012. Clinical characteristics of these patients were 33% with stage I and 66.7% with stage II; 79.8% were in the low or low-intermediate risk group; 13.6% had B symptoms; 29.8%more » had bulky tumors (≥7 cm); and 75.3% underwent ≥6 cycles of R-CHOP therapy. RT was given to 43 patients (21.7%) using ILRT technique, which included the prechemotherapy tumor volume with a median margin of 2 cm (median RT dose: 36 Gy). Results: After a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 85.8% and 88.9%, respectively. Multivariate analysis showed ≥6 cycles of R-CHOP (PFS, P=.004; OS, P=.004) and ILRT (PFS, P=.021; OS, P=.014) were favorable prognosticators of PFS and OS. A bulky tumor (P=.027) and response to R-CHOP (P=.012) were also found to be independent factors of OS. In subgroup analysis, the effect of ILRT was prominent in patients with a bulky tumor (PFS, P=.014; OS, P=.030) or an elevated level of serum lactate dehydrogenase (LDH; PFS, P=.004; OS, P=.012). Conclusions: Our results suggest that ILRT after R-CHOP therapy improves PFS and OS in patients with limited stage DLBCL, especially in those with bulky disease or an elevated serum LDH level.« less

The Novel Mechanisms Concerning the Inhibitions of Palmitate-Induced Proinflammatory Factor Releases and Endogenous Cellular Stress with Astaxanthin on MIN6 β-Cells.

PubMed

Kitahara, Atsuko; Takahashi, Kazuto; Morita, Naru; Murashima, Toshitaka; Onuma, Hirohisa; Sumitani, Yoshikazu; Tanaka, Toshiaki; Kondo, Takuma; Hosaka, Toshio; Ishida, Hitoshi

2017-06-20

Astaxanthin, an antioxidant agent, can protect pancreatic β-cells of db/db mice from glucotoxicity and resolve chronic inflammation in adipose tissue. Nonetheless, the effects of astaxanthin on free-fatty-acid-induced inflammation and cellular stress in β-cells remain to be demonstrated. Meanwhile, palmitate enhances the secretion of pro-inflammatory adipokines monocyte chemoattractant protein-1 (MCP-1) and VEGF 120 (vascular endothelial growth factor). We therefore investigated the influence of astaxanthin on palmitate-stimulated MCP-1 and VEGF 120 secretion in mouse insulinoma (MIN6) pancreatic β-cells. Furthermore, whether astaxanthin prevents cellular stress in MIN6 cells was also assessed. Pre-treatment with astaxanthin or with N -acetyl-cysteine (NAC) which is an antioxidant drug, significantly attenuated the palmitate-induced MCP-1 release through downregulation of phosphorylated c-Jun NH₂-terminal protein kinase (JNK) pathways, and suppressed VEGF 120 through the PI3K/Akt pathways relative to the cells stimulated with palmitate alone. In addition, palmitate significantly upregulated homologous protein (CHOP) and anti-glucose-regulated protein (GRP78), which are endoplasmic reticulum (ER) stress markers, in MIN6 cells. On the other hand, astaxanthin attenuated the increased CHOP content, but further up-regulated palmitate-stimulated GRP78 protein expression. By contrast, NAC had no effects on either CHOP or GRP78 enhancement induced by palmitate in MIN6 cells. In conclusion, astaxanthin diminishes the palmitate-stimulated increase in MCP-1 secretion via the downregulation of JNK pathways in MIN6 cells, and affects VEGF 120 secretion through PI3K/Akt pathways. Moreover, astaxanthin can prevent not only oxidative stress caused endogenously by palmitate but also ER stress, which NAC fails to attenuate, via upregulation of GRP78, an ER chaperon.

The Novel Mechanisms Concerning the Inhibitions of Palmitate-Induced Proinflammatory Factor Releases and Endogenous Cellular Stress with Astaxanthin on MIN6 β-Cells

PubMed Central

Kitahara, Atsuko; Takahashi, Kazuto; Morita, Naru; Murashima, Toshitaka; Onuma, Hirohisa; Sumitani, Yoshikazu; Tanaka, Toshiaki; Kondo, Takuma; Hosaka, Toshio; Ishida, Hitoshi

2017-01-01

Astaxanthin, an antioxidant agent, can protect pancreatic β-cells of db/db mice from glucotoxicity and resolve chronic inflammation in adipose tissue. Nonetheless, the effects of astaxanthin on free-fatty-acid-induced inflammation and cellular stress in β-cells remain to be demonstrated. Meanwhile, palmitate enhances the secretion of pro-inflammatory adipokines monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF120). We therefore investigated the influence of astaxanthin on palmitate-stimulated MCP-1 and VEGF120 secretion in mouse insulinoma (MIN6) pancreatic β-cells. Furthermore, whether astaxanthin prevents cellular stress in MIN6 cells was also assessed. Pre-treatment with astaxanthin or with N-acetyl-cysteine (NAC) which is an antioxidant drug, significantly attenuated the palmitate-induced MCP-1 release through downregulation of phosphorylated c-Jun NH2-terminal protein kinase (JNK) pathways, and suppressed VEGF120 through the PI3K/Akt pathways relative to the cells stimulated with palmitate alone. In addition, palmitate significantly upregulated homologous protein (CHOP) and anti-glucose-regulated protein (GRP78), which are endoplasmic reticulum (ER) stress markers, in MIN6 cells. On the other hand, astaxanthin attenuated the increased CHOP content, but further up-regulated palmitate-stimulated GRP78 protein expression. By contrast, NAC had no effects on either CHOP or GRP78 enhancement induced by palmitate in MIN6 cells. In conclusion, astaxanthin diminishes the palmitate-stimulated increase in MCP-1 secretion via the downregulation of JNK pathways in MIN6 cells, and affects VEGF120 secretion through PI3K/Akt pathways. Moreover, astaxanthin can prevent not only oxidative stress caused endogenously by palmitate but also ER stress, which NAC fails to attenuate, via upregulation of GRP78, an ER chaperon. PMID:28632169

Endoplasmic reticulum stress-mediated neuronal apoptosis by acrylamide exposure

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

Komoike, Yuta, E-mail: komoike@research.twmu.ac.jp

Acrylamide (AA) is a well-known neurotoxic compound in humans and experimental animals. However, intracellular stress signaling pathways responsible for the neurotoxicity of AA are still not clear. In this study, we explored the involvement of the endoplasmic reticulum (ER) stress response in AA-induced neuronal damage in vitro and in vivo. Exposure of SH-SY5Y human neuroblastoma cells to AA increased the levels of phosphorylated form of eukaryotic translation initiation factor 2α (eIF2α) and its downstream effector, activating transcription factor 4 (ATF4), indicating the induction of the unfolded protein response (UPR) by AA exposure. Furthermore, AA exposure increased the mRNA level ofmore » c/EBP homologous protein (CHOP), the ER stress-dependent apoptotic factor, and caused the accumulation of reactive oxygen species (ROS) in SH-SY5Y cells. Treatments of SH-SY5Y cells with the chemical chaperone, 4-phenylbutyric acid and the ROS scavenger, N-acetyl-cysteine reduced the AA-induced expression of ATF4 protein and CHOP mRNA, and resulted in the suppression of apoptosis. In addition, AA-induced eIF2α phosphorylation was also suppressed by NAC treatment. In consistent with in vitro study, exposure of zebrafish larvae at 6-day post fertilization to AA induced the expression of chop mRNA and apoptotic cell death in the brain, and also caused the disruption of brain structure. These findings suggest that AA exposure induces apoptotic neuronal cell death through the ER stress and subsequent eIF2α–ATF4–CHOP signaling cascade. The accumulation of ROS by AA exposure appears to be responsible for this ER stress-mediated apoptotic pathway. - Highlights: • Exposure of SH-SY5Y cells to AA activates the eIF2α–ATF4 pathway of the UPR. • Exposure of SH-SY5Y cells to AA induces the CHOP expression and apoptosis. • Exposure of zebrafish to AA induces the chop expression and apoptosis in the brain. • AA possibly induces apoptotic neuronal cell death through the ER stress response. • AA-induced ROS production is involved in this ER stress response.« less

Role of intrinsic search cues in the formation of consumer preferences and choice for pork chops.

PubMed

Verbeke, Wim; De Smet, Stefaan; Vackier, Isabelle; Van Oeckel, Monique J; Warnants, Nathalie; Van Kenhove, Patrick

2005-02-01

This study investigates the role of drip, colour, marbling and fat cover as intrinsic search cues in the formation of pork chop preferences and individual determinants. Data are collected from a sample of 443 pork consumers in Belgium through using repeated selection of chops from randomised photobooks and questionnaires including socio-demographic, attitudinal and behavioural variables. Data analysis includes mixture regression analysis, bivariate descriptive statistics and the estimation of multivariate probit models. Consumers sampled in this study prefer pork chops without fat cover. Preference for fat cover is stronger among male, 35+ aged consumers with lower levels of awareness of the relation between food and health and who like pork for other reasons than taste and nutritional value (all p<0.05). Preference for colour is equally consistent within an individual, though fifty-fifty light-dark, with dark chops being more preferred by 35+ aged consumers (p<0.05). Preferences for marbling and drip are not consistent and not determined by joint socio-demographic, attitudinal and behavioural factors. Preferences for cue levels are not correlated, except a weak relation between preference for dark chops without drip (r=0.116). Preferences are apparently formed by deductions with the use of single cues as key information, mainly based on fat cover or colour, and random choice on marbling and drip.

Effect of harvest time and physical form of alfalfa silage on chewing time and particle size distribution in boli, rumen content and faeces.

PubMed

Kornfelt, L F; Weisbjerg, M R; Nørgaard, P

2013-02-01

The study examined the effects of physical form and harvest time of alfalfa silage on eating and ruminating activity and particle size distribution in feed boli, rumen content and faeces in dry cows. The alfalfa crop was harvested at two stages of growth (early: NDF 37%, late: NDF 44% in dry matter (DM)), and from each harvest, a chopped (theoretical cutting length: 19 mm) and an unchopped crop was ensiled in bales. The silages were fed restrictively to four rumen cannulated non-lactating Jersey cows (391 ± 26 kg) in a 4 × 4 Latin square design. The cows were fed restrictively 80% of their ad libitum intake twice daily. Chewing activity was recorded for 96 h continuously. Swallowed boli, rumen content, rumen fluid and faeces samples were collected, washed in nylon bags (0.01 mm pore size) and freeze-dried before dry sieving through 4.750, 2.360, 1.000, 0.500 and 0.212 mm pore sizes into six fractions. The length (PL) and width (PW) of particles within each fraction was measured by the use of image analysis. The eating activity (min/kg dry matter intake (P < 0.01) and min/kg NDF (P < 0.05)) was affected by harvest time. The mean ruminating time (min/kg DM) was affected by harvest time (P < 0.01), physical form (P < 0.05) and NDF intake per kg BW (P < 0.01). The proportion of washed particle DM of total DM in boli, rumen content, rumen fluid and faeces was affected by harvest time (P < 0.01) and highest by feeding late-harvested alfalfa silage. Two peaks on the probability density distribution function (PDF) of PW and PL values of boli, rumen content and faeces were identified. Chopping of the silage decreased the mean PL and PW, the most frequent PL (mode) and 95% percentile PL and PW values in boli. In the rumen content, chopping increased the mean PW (P < 0.05). The dimension sizes of faeces particles were not significantly affected by chopping. The mode PW value was lower in rumen content and faeces than in boli (P < 0.001), and the mode PL value was higher in boli and lower in faeces compared with rumen contents (P < 0.001). In conclusion, the mean total chewing activity per kg NDF decreased due to chopping and early harvest time. The mean PL and PW in boli decreased due to chopping and late harvest. The two peak values on the PDF (PL) and PDF (PW) of boli, rumen content and faeces particles are most likely related to the leaf and the stem residues.

Bacteroides fragilis Enterotoxin Induces Formation of Autophagosomes in Endothelial Cells but Interferes with Fusion with Lysosomes for Complete Autophagic Flux through a Mitogen-Activated Protein Kinase-, AP-1-, and C/EBP Homologous Protein-Dependent Pathway.

PubMed

Ko, Su Hyuk; Jeon, Jong Ik; Myung, Hyun Soo; Kim, Young-Jeon; Kim, Jung Mogg

2017-10-01

Bacteroides fragilis enterotoxin (BFT), a virulence factor of enterotoxigenic B. fragilis (ETBF), plays an essential role in mucosal inflammation. Although autophagy contributes to the pathogenesis of diverse infectious diseases, little is known about autophagy in ETBF infection. This study was conducted to investigate the role of BFT in the autophagic process in endothelial cells (ECs). Stimulation of human umbilical vein ECs (HUVECs) with BFT increased light chain 3 protein II (LC3-II) conversion from LC3-I and protein expression of p62, Atg5, and Atg12. In addition, BFT-exposed ECs showed increased indices of autophagosomal fusion with lysosomes such as LC3-lysosome-associated protein 2 (LAMP2) colocalization and the percentage of red vesicles monitored by the expression of dual-tagged LC3B. BFT also upregulated expression of C/EBP homologous protein (CHOP), and inhibition of CHOP significantly increased indices of autophagosomal fusion with lysosomes. BFT activated an AP-1 transcription factor, in which suppression of AP-1 activity significantly downregulated CHOP and augmented autophagosomal fusion with lysosomes. Furthermore, suppression of Jun N-terminal protein kinase (JNK) mitogen-activated protein kinase (MAPK) significantly inhibited the AP-1 and CHOP signals, leading to an increase in autophagosomal fusion with lysosomes in BFT-stimulated ECs. These results suggest that BFT induced accumulation of autophagosomes in ECs, but activation of a signaling pathway involving JNK, AP-1, and CHOP may interfere with complete autophagy. Copyright © 2017 American Society for Microbiology.

Effects of dietary magnesium and duration of refrigerated storage on the quality of vacuum-packaged, boneless pork loins.

PubMed

Apple, J K; Davis, J R; Rakes, L K; Maxwell, C V; Stivarius, M R; Pohlman, F W

2001-01-01

Quality data were initially collected on 78 pork loins from crossbred pigs fed diets containing 0, 1.25 or 2.5% magnesium mica (MM). Loins were then vacuum-packaged, and randomly assigned to either 4 or 8 weeks of storage at 2°C. Dietary MM had no (P > 0.05) effect on moisture loss/retention or subjective and objective color measurements. Purge volume increased (P<0.05) and drip loss decreased (P<0.05) as storage time increased. Moreover, longissimus thoracis et lumborum (LM) chops became lighter (P<0.05), redder (P<0.05), and more yellow (P<0.05) during 8 weeks of storage. Although TBARS values increased linearly (P<0.001) during extended storage, LM chops from pigs fed 2.5% MM tended to have lower (P<0.07) TBARS values after 4 weeks of storage than chops from pigs fed 0 and 1.25% MM. After 8 weeks of storage, however, there was a tendency for TBARS values of chops from pigs fed 1.25% MM to be lower (P<0.07) than chops from pigs fed 2.5% MM. Even though feeding swine diets containing MM did not affect color and water-holding capacity of pork loins during storage, the data indicated inclusion of MM in swine diets may retard onset of oxidative rancidity in vacuum-packaged pork loins.

Retrospective analysis for treatment of naïve canine multicentric lymphoma with a 15-week, maintenance-free CHOP protocol.

PubMed

Curran, K; Thamm, D H

2016-08-01

Standard of care treatment of dogs with multicentric lymphoma includes combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP); however, owners may be hesitant to commit the resources necessary to complete a lengthy, multi-drug protocol. One hundred thirty-four client-owned dogs with multicentric lymphoma were treated with a 15-week CHOP chemotherapy protocol. The overall response rate was 98% with 104 dogs experiencing a complete response (CR). The median progression-free survival (PFS) time for all dogs was 176 days, and the median disease-specific overall survival time was 311 days. Prognostic factors identified on multivariate analysis as significant for PFS included substage, immunophenotype, hospitalization for adverse events, need for dose reduction, presence of neutrophilia at diagnosis, presence of anemia and experiencing a CR as best response to therapy. In conclusion, this protocol may be a viable alternative to CHOP protocols using a larger number of treatments. © 2015 John Wiley & Sons Ltd.

Sigmar1 regulates endoplasmic reticulum stress-induced C/EBP-homologous protein expression in cardiomyocytes.

PubMed

Alam, Shafiul; Abdullah, Chowdhury S; Aishwarya, Richa; Orr, A Wayne; Traylor, James; Miriyala, Sumitra; Panchatcharam, Manikandan; Pattillo, Christopher B; Bhuiyan, Md Shenuarin

2017-08-31

C/EBP-homologous protein (CHOP) is a ubiquitously expressed stress-inducible transcription factor robustly induced by maladaptive endoplasmic reticulum (ER) stresses in a wide variety of cells. Here, we examined a novel function of Sigma 1 receptor (Sigmar1) in regulating CHOP expression under ER stress in cardiomyocytes. We also defined Sigmar1-dependent activation of the adaptive ER-stress pathway in regulating CHOP expression. We used adenovirus-mediated Sigmar1 overexpression as well as Sigmar1 knockdown by siRNA in neonatal rat ventricular cardiomyocytes (NRCs); to induce ER stress, cardiomyocytes were treated with tunicamycin. Sigmar1-siRNA knockdown significantly increased the expression of CHOP and significantly induced cellular toxicity by sustained activation of ER stress in cardiomyocytes. Sigmar1 overexpression decreased the expression of CHOP and significantly decreased cellular toxicity in cells. Using biochemical and immunocytochemical experiments, we also defined the specific ER-stress pathway associated with Sigmar1-dependent regulation of CHOP expression and cellular toxicity. We found that Sigmar1 overexpression significantly increased inositol requiring kinase 1α (IRE1α) phosphorylation and increased spliced X-box-binding proteins (XBP1s) expression as well as nuclear localization. In contrast, Sigmar1 knockdown significantly decreased IRE1α phosphorylation and decreased XBP1s expression as well as nuclear transport. Taken together, these results indicate that Sigmar1-dependent activation of IRE1α-XBP1s ER-stress response pathways are associated with inhibition of CHOP expression and suppression of cellular toxicity. Hence, Sigmar1 is an essential component of the adaptive ER-stress response pathways eliciting cellular protection in cardiomyocytes. © 2017 The Author(s).

Sigmar1 regulates endoplasmic reticulum stress-induced C/EBP-homologous protein expression in cardiomyocytes

PubMed Central

Alam, Shafiul; Abdullah, Chowdhury S.; Aishwarya, Richa; Orr, A. Wayne; Traylor, James; Miriyala, Sumitra; Panchatcharam, Manikandan; Pattillo, Christopher B.

2017-01-01

C/EBP-homologous protein (CHOP) is a ubiquitously expressed stress-inducible transcription factor robustly induced by maladaptive endoplasmic reticulum (ER) stresses in a wide variety of cells. Here, we examined a novel function of Sigma 1 receptor (Sigmar1) in regulating CHOP expression under ER stress in cardiomyocytes. We also defined Sigmar1-dependent activation of the adaptive ER-stress pathway in regulating CHOP expression. We used adenovirus-mediated Sigmar1 overexpression as well as Sigmar1 knockdown by siRNA in neonatal rat ventricular cardiomyocytes (NRCs); to induce ER stress, cardiomyocytes were treated with tunicamycin. Sigmar1-siRNA knockdown significantly increased the expression of CHOP and significantly induced cellular toxicity by sustained activation of ER stress in cardiomyocytes. Sigmar1 overexpression decreased the expression of CHOP and significantly decreased cellular toxicity in cells. Using biochemical and immunocytochemical experiments, we also defined the specific ER-stress pathway associated with Sigmar1-dependent regulation of CHOP expression and cellular toxicity. We found that Sigmar1 overexpression significantly increased inositol requiring kinase 1α (IRE1α) phosphorylation and increased spliced X-box-binding proteins (XBP1s) expression as well as nuclear localization. In contrast, Sigmar1 knockdown significantly decreased IRE1α phosphorylation and decreased XBP1s expression as well as nuclear transport. Taken together, these results indicate that Sigmar1-dependent activation of IRE1α-XBP1s ER-stress response pathways are associated with inhibition of CHOP expression and suppression of cellular toxicity. Hence, Sigmar1 is an essential component of the adaptive ER-stress response pathways eliciting cellular protection in cardiomyocytes. PMID:28667101

Stronger proteasomal inhibition and higher CHOP induction are responsible for more effective induction of paraptosis by dimethoxycurcumin than curcumin

PubMed Central

Yoon, M J; Kang, Y J; Lee, J A; Kim, I Y; Kim, M A; Lee, Y S; Park, J H; Lee, B Y; Kim, I A; Kim, H S; Kim, S-A; Yoon, A-R; Yun, C-O; Kim, E-Y; Lee, K; Choi, K S

2014-01-01

Although curcumin suppresses the growth of a variety of cancer cells, its poor absorption and low systemic bioavailability have limited its translation into clinics as an anticancer agent. In this study, we show that dimethoxycurcumin (DMC), a methylated, more stable analog of curcumin, is significantly more potent than curcumin in inducing cell death and reducing the clonogenicity of malignant breast cancer cells. Furthermore, DMC reduces the tumor growth of xenografted MDA-MB 435S cells more strongly than curcumin. We found that DMC induces paraptosis accompanied by excessive dilation of mitochondria and the endoplasmic reticulum (ER); this is similar to curcumin, but a much lower concentration of DMC is required to induce this process. DMC inhibits the proteasomal activity more strongly than curcumin, possibly causing severe ER stress and contributing to the observed dilation. DMC treatment upregulates the protein levels of CCAAT-enhancer-binding protein homologous protein (CHOP) and Noxa, and the small interfering RNA-mediated suppression of CHOP, but not Noxa, markedly attenuates DMC-induced ER dilation and cell death. Interestingly, DMC does not affect the viability, proteasomal activity or CHOP protein levels of human mammary epithelial cells, suggesting that DMC effectively induces paraptosis selectively in breast cancer cells, while sparing normal cells. Taken together, these results suggest that DMC triggers a stronger proteasome inhibition and higher induction of CHOP compared with curcumin, giving it more potent anticancer effects on malignant breast cancer cells. PMID:24625971

Potential of pelleted wheat straw as an alternative bedding material for broilers.

PubMed

Kheravii, S K; Swick, R A; Choct, M; Wu, S-B

2017-06-01

Broiler chickens are commonly placed on wood shavings as litter, but alternative litter sources are required due to the scarcity of wood shavings in many parts of the world. This study aimed to compare pelleted straw, chopped wheat straw, wood shavings, rice hulls, and shredded paper as litter candidates. Three-hundred-sixty Ross 308 one-day-old male chicks were used in this study. There were 5 litter treatments with 6 replicate pens, each with 12 birds. The feed conversion ratio (FCR) of birds reared on pelleted straw was improved compared (P < 0.05) to that of birds raised on rice hulls, whereas it did not differ for birds placed on wood shavings, rice hulls, chopped straw, or shredded paper. It was observed that the birds reared on wood shavings had higher relative gizzard weight at d 24 compared to those reared on pelleted straw (P < 0.05). Gizzard pH and measured cecal bacterial groups were not affected by the type of bedding material. Cecal bacterial groups measured at d 10 were not affected by bedding material. Birds reared on pelleted wheat straw had a lower incidence of footpad lesions than those on chopped straw and shredded paper on d 24 (P < 0.001) and 29 (P < 0.01). Litter source did not affect the occurrence of breast blisters at d 24, 29, or 35. On d 24, 29, and 35, pelleted straw litter was less caked than chopped straw and shredded paper (P < 0.001) whereas no significant differences were observed among pelleted straw, wood shavings, and rice hulls. The study demonstrated the potential benefits to using pelleted wheat straw as a bedding material. Further assessment of pelleting of wheat straw and other materials on broiler health, performance, and welfare are needed to determine the economic benefits of pelleted litter. © 2017 Poultry Science Association Inc.

O-GlcNAcylation of eIF2α regulates the phospho-eIF2α-mediated ER stress response.

PubMed

Jang, Insook; Kim, Han Byeol; Seo, Hojoong; Kim, Jin Young; Choi, Hyeonjin; Yoo, Jong Shin; Kim, Jae-woo; Cho, Jin Won

2015-08-01

O-GlcNAcylation is highly involved in cellular stress responses including the endoplasmic reticulum (ER) stress response. For example, glucosamine-induced flux through the hexosamine biosynthetic pathway can promote ER stress and ER stress inducers can change the total cellular level of O-GlcNAcylation. However, it is largely unknown which component(s) of the unfolded protein response (UPR) is directly regulated by O-GlcNAcylation. In this study, eukaryotic translation initiation factor 2α (eIF2α), a major branch of the UPR, was O-GlcNAcylated at Ser 219, Thr 239, and Thr 241. Upon ER stress, eIF2α is phosphorylated at Ser 51 by phosphorylated PKR-like ER kinase and this inhibits global translation initiation, except for that of specific mRNAs, including activating transcription factor 4, that induce stress-responsive genes such as C/EBP homologous protein (CHOP). Hyper-O-GlcNAcylation induced by O-GlcNAcase inhibitor (thiamet-G) treatment or O-GlcNAc transferase (OGT) overexpression hindered phosphorylation of eIF2α at Ser 51. The level of O-GlcNAcylation of eIF2α was changed by dithiothreitol treatment dependent on its phosphorylation at Ser 51. Point mutation of the O-GlcNAcylation sites of eIF2α increased its phosphorylation at Ser 51 and CHOP expression and resulted in increased apoptosis upon ER stress. These results suggest that O-GlcNAcylation of eIF2α affects its phosphorylation at Ser 51 and influences CHOP-mediated cell death. This O-GlcNAcylation of eIF2α was reproduced in thiamet-G-injected mouse liver. In conclusion, proper regulation of O-GlcNAcylation and phosphorylation of eIF2α is important to maintain cellular homeostasis upon ER stress. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of ubiquilin 1 on the unfolded protein response.

PubMed

Lu, Alice; Hiltunen, Mikko; Romano, Donna M; Soininen, Hilkka; Hyman, Bradley T; Bertram, Lars; Tanzi, Rudolph E

2009-05-01

Previous studies have implicated the unfolded protein response (UPR) in the pathogenesis of Alzheimer's disease (AD). We previously reported that DNA variants in the ubiquilin 1 (UBQLN1) gene increase the risk for AD. Since UBQLN1 has been shown to play a role in the UPR, we assessed the effects of overexpression and downregulation of UBQLN1 splice variants during tunicamycin-induced ER stress. In addition to previously described transcript variants, TV1 and TV2, we identified two novel transcript variants of UBQLN1 in brain: TV3 (lacking exons 2-4) and TV4 (lacking exon 4). Overexpression of TV1-3, but not TV4 significantly decreased the mRNA induction of UPR-inducible genes, C/EBP homologous protein (CHOP), BiP/GRP78, and protein disulfide isomerase (PDI) during the UPR. Stable overexpression of TV1-3, but not TV4, also significantly decreased the induction of CHOP protein and increased cell viability during the UPR. In contrast, downregulation of UBQLN1 did not affect CHOP mRNA induction, but instead increased PDI mRNA levels. These findings suggest that overexpression UBQLN1 transcript variants TV1-3, but not TV4, exert a protective effect during the UPR by attenuating CHOP induction and potentially increasing cell viability.

Effect of the callipyge phenotype and cooking method on tenderness of several major lamb muscles.

PubMed

Shackelford, S D; Wheeler, T L; Koohmaraie, M

1997-08-01

We conducted three experiments to determine the effects of the callipyge phenotype on the tenderness of several major lamb muscles and to determine the effect of method of cookery on the tenderness of callipyge lamb at 7 d postmortem. In Exp. 1, chops from normal (n = 23) and callipyge (n = 16) carcasses were open-hearth-broiled. Warner-Bratzler shear force values of longissimus, gluteus medius, semimembranosus, biceps femoris, semitendinosus, adductor, and quadriceps femoris were 123, 44, 28, 26, 19, 16, and 13% greater, respectively, for callipyge (P < .05). In Exp. 2, muscles from normal (n = 18) and callipyge (n = 18) carcasses were oven-roasted. Shear force of triceps brachii was 11% greater for callipyge (P < .001); however, phenotype did not affect shear force of supraspinatus (P = .87) or psoas major (P = .64). In Exp. 3, a trained sensory panel evaluated leg roasts and open-hearth-broiled leg chops from normal (n = 60) and callipyge lamb carcasses (n = 60). Callipyge chops were less tender than normal chops (P < .05). Regardless of callipyge phenotype, muscles were more (P < .05) tender when roasted; however, the effect of method of cookery on tenderness scores was greater for callipyge muscles than for normal muscles. Callipyge roasts and normal roasts had similar tenderness (P = .58), and callipyge roasts were more tender than normal chops (P < .05). Regardless of cooking method, callipyge samples were less juicy than normal samples (P < .05). These data demonstrate that the callipyge phenotype will likely reduce consumer satisfaction due to reduced tenderness and juiciness; however, reduced tenderness in callipyge leg muscles could be prevented by ovenroasting.

Deliverability and efficacy of R-CHOP chemotherapy in very elderly patients with diffuse large B-cell lymphoma: an Australian retrospective analysis.

PubMed

Millar, A; Ellis, M; Mollee, P; Cochrane, T; Fletcher, J; Caudron, A; Webster, B; Trotman, J

2015-11-01

Elderly patients with diffuse large B-cell lymphoma (DLBCL) have an inferior prognosis, due in part to advanced age and pre-existing comorbidities, with reduced tolerability and deliverability of standard R-CHOP chemotherapy. To examine the deliverability, toxicity and efficacy of R-CHOP and the prevalence of the germinal and non-germinal phenotype DLBCL in an elderly Australian cohort. This retrospective analysis included patients ≥75 years diagnosed with DLBCL. Comprehensive chemotherapy and toxicity data were collected for patients treated with R-CHOP. Baseline demographics and chemotherapy characteristics were compared with progression-free (PFS) and overall survival (OS). Immunohistochemical staining identified the prevalence of the non-germinal centre (non-GCB) phenotype. Of the 111 patients, 92 (83%) commenced R-CHOP with 26/92 (28%) receiving ≤4 cycles. Median average relative dose (ARD) was 0.80 (0.07-1.17). Median average relative dose intensity (ARDI) was 0.89 (0.33-1.18). Serious adverse events occurred in 77% of patients with ≥Gd3 adverse events in 74%. Overall response rate was 85%. Two-year PFS was 63% and OS 74%. ARD and performance status ≥2 were significant prognostic factors for PFS and OS but not ARDI. Non-GCB-phenotype was identified in 44/72 (61%) of patients with immunohistochemical data. Despite high response rates and respectable survival estimates, the absence of standard therapy in 17% of patients, and dose reductions and serious toxicity of R-CHOP in this Australian cohort highlights the need for the development of less toxic yet efficacious treatments for very elderly patients with DLBCL. The high prevalence of the non-GCB phenotype highlights the potential value of targeted biological therapy for this demographic. © 2015 Royal Australasian College of Physicians.

Chopped or Long Roughage: What Do Calves Prefer? Using Cross Point Analysis of Double Demand Functions

PubMed Central

Webb, Laura E.; Bak Jensen, Margit; Engel, Bas; van Reenen, Cornelis G.; Gerrits, Walter J. J.; de Boer, Imke J. M.; Bokkers, Eddie A. M.

2014-01-01

The present study aimed to quantify calves'(Bos taurus) preference for long versus chopped hay and straw, and hay versus straw, using cross point analysis of double demand functions, in a context where energy intake was not a limiting factor. Nine calves, fed milk replacer and concentrate, were trained to work for roughage rewards from two simultaneously available panels. The cost (number of muzzle presses) required on the panels varied in each session (left panel/right panel): 7/35, 14/28, 21/21, 28/14, 35/7. Demand functions were estimated from the proportion of rewards achieved on one panel relative to the total number of rewards achieved in one session. Cross points (cp) were calculated as the cost at which an equal number of rewards was achieved from both panels. The deviation of the cp from the midpoint (here 21) indicates the strength of the preference. Calves showed a preference for long versus chopped hay (cp  = 14.5; P  = 0.004), and for hay versus straw (cp  = 38.9; P = 0.004), both of which improve rumen function. Long hay may stimulate chewing more than chopped hay, and the preference for hay versus straw could be related to hedonic characteristics. No preference was found for chopped versus long straw (cp  = 20.8; P = 0.910). These results could be used to improve the welfare of calves in production systems; for example, in systems where calves are fed hay along with high energy concentrate, providing long hay instead of chopped could promote roughage intake, rumen development, and rumination. PMID:24558426

Home food preparation techniques impacted the availability of natural antioxidants and bioactivities in kale and broccoli.

PubMed

Yu, Lu; Gao, Boyan; Li, Yanfang; Wang, Thomas T Y; Luo, Yinghua; Wang, Jing; Yu, Liangli Lucy

2018-01-24

This study evaluated the effects of grinding and chopping with/without microwaving on the health-beneficial components, and antioxidant, anti-inflammation and anti-proliferation capacities of commercial kale and broccoli samples. The availability of indole-3-carbinol (I3C) was evaluated using high-performance liquid chromatography. The total phenolic contents, the scavenging activities against DPPH, oxygen, hydroxyl and ABTS cation radicals, and cell-based antioxidant activities were determined for the antioxidant capacities. The results indicated that chopping released the least nutraceutical components and antioxidant compounds. Microwaving had no effect on the I3C release from kale, but resulted in an elevated (more than 2-fold) release of I3C from broccoli. In addition, the choice of a blender affected the availability of the anti-proliferative compounds from the vegetables, while it had no effect on the availability of their anti-inflammatory compounds. In summary, different food preparation methods could strongly impact the availability of bioactive factors in the selected vegetables. These findings suggest that choosing an appropriate food processing method for each vegetable might be critical to obtain desirable health-beneficial effects.

Effect of dietary zinc and ractopamine hydrochloride on pork chop muscle fiber type distribution, tenderness, and color characteristics.

PubMed

Paulk, C B; Tokach, M D; Nelssen, J L; Burnett, D D; Vaughn, M A; Phelps, K J; Dritz, S S; Derouchey, J M; Goodband, R D; Woodworth, J C; Houser, T A; Haydon, K D; Gonzalez, J M

2014-05-01

A total of 320 finishing pigs (PIC 327 × 1050; initially 98 kg) were used to determine the effects of adding Zn to diets containing ractopamine HCl (RAC) on muscle fiber type distribution, fresh chop color, and cooked meat characteristics. Dietary treatments were fed for approximately 35 d and consisted of a corn-soybean meal-based negative control (CON), a positive control diet with 10 mg/kg of RAC (RAC+), and the RAC+ diet plus 75, 150, or 225 mg/kg added Zn from either ZnO or Availa-Zn. Loins randomly selected from each treatment (n = 20) were evaluated using contrasts: CON vs. RAC+, interaction of Zn level × source, Zn level linear and quadratic polynomials, and Zn source. There were no Zn source effects or Zn source × level interactions throughout the study (P > 0.10). Pigs fed RAC+ had increased (P < 0.02) percentage type IIX and a tendency for increased (P = 0.10) percent type IIB muscle fibers. Increasing added Zn decreased (linear, P = 0.01) percentage type IIA and tended to increase (P = 0.09) IIX muscle fibers. On d 1, 2, 3, 4, and 5 of display, pork chops from pigs fed the RAC+ treatment had greater (P < 0.03) L* values compared to the CON. On d 0 and 3 of display, increasing added Zn tended to decrease (quadratic, P = 0.10) L* values and decreased (quadratic, P < 0.03) L* values on d 1, 2, 4, and 5. Pigs fed RAC+ had decreased (P < 0.05) a* values on d 1 and 4 of display and tended to have decreased (P < 0.10) a* values on d 0 and 2 compared to CON pork chops. Pork chops from the RAC+ treatment had a tendency for increased (P < 0.08) oxymyoglobin percentage compared to CON pork chops on d 1, 2, 4, and 5. On d 0, as dietary Zn increased in RAC+ diets, there was a decrease (linear, P < 0.01) in the formation of pork chop surface oxymyoglobin percentage. Metmyoglobin reducing ability (MRA) of pork chops on d 5 was decreased in the RAC+ group. Chops from pigs fed added Zn had increased (quadratic, P < 0.03) MRA on d 3 and 5 of the display period. There was a trend for increased (linear, P = 0.07) cooking loss with increasing Zn in RAC diets and treatments did not affect tenderness as measured by Warner-Bratzler shear force (P > 0.07). In conclusion, RAC+ diets produced chops that were lighter and less red but maintained a greater percentage of surface oxymyoglobin throughout a 5-d simulated retail display. Ractopamine reduced MRA at the end of the display period, but supplementing Zn to RAC diets restored MRA to near CON treatment levels at the end of the display period.

Graphite-reinforced bone cement

NASA Technical Reports Server (NTRS)

Knoell, A. C.

1976-01-01

Chopped graphite fibers added to surgical bone cement form bonding agent with mechanical properties closely matched to those of bone. Curing reaction produces less heat, resulting in reduced traumatization of body tissues. Stiffness is increased without affecting flexural strength.

Comparison between L-CHOP and an L-CHOP protocol with interposed treatments of CCNU and MOPP (L-CHOP-CCNU-MOPP) for lymphoma in dogs.

PubMed

Rassnick, K M; Bailey, D B; Malone, E K; Intile, J L; Kiselow, M A; Flory, A B; Barlow, L L; Balkman, C E; Barnard, S M; Waite, A H

2010-12-01

An L-CHOP protocol with interposed treatments of CCNU and MOPP (L-CHOP-CCNU-MOPP) was evaluated in 66 dogs with stages III-V lymphoma. Results were compared with a historical group of 71 dogs treated with an L-CHOP protocol. Complete remission (CR) rates (85 and 80%, respectively) did not differ significantly between protocols (P = 0.48). First CR duration for dogs treated with L-CHOP-CCNU-MOPP was significantly longer: median, 317 days; 2-year CR rate, 35% versus median, 298 days; 2-year CR rate, 13%, P = 0.05). For the L-CHOP-CCNU-MOPP protocol, dogs in substage-b had a 4.3 times greater hazard of having a relapse than dogs in substage-a (P = 0.002). Frequency of adverse chemotherapy-associated gastrointestinal effects did not differ between protocols (P = 0.77). Neutropenia (primarily after CCNU) occurred more frequently in dogs treated with L-CHOP-CCNU-MOPP (P < 0.001). In summary, the L-CHOP-CCNU-MOPP protocol showed an improved duration of first CR as compared with an L-CHOP protocol, but the relevance of this finding might be subject to clinical judgement. © 2010 Blackwell Publishing Ltd.

Inhibition of glioma growth by minocycline is mediated through endoplasmic reticulum stress-induced apoptosis and autophagic cell death

PubMed Central

Liu, Wei-Ting; Huang, Chih-Yuan; Lu, I-Chen; Gean, Po-Wu

2013-01-01

Background We have reported that minocycline (Mino) induced autophagic death in glioma cells. In the present study, we characterize the upstream regulators that control autophagy and switch cell death from autophagic to apoptotic. Methods Western blotting and immunofluorescence were used to detect the expressions of eukaryotic translation initiation factor 2α (eIF2α), transcription factor GADD153 (CHOP), and glucose-regulated protein 78 (GRP78). Short hairpin (sh)RNA was used to knock down eIF2α or CHOP expression. Autophagy was assessed by the conversion of light chain (LC)3-I to LC3-II and green fluorescent protein puncta formation. An intracranial mouse model and bioluminescent imaging were used to assess the effect of Mino on tumor growth and survival time of mice. Results The expression of GRP78 in glioma was high, whereas in normal glia it was low. Mino treatment increased GRP78 expression and reduced binding of GRP78 with protein kinase-like endoplasmic reticulum kinase. Subsequently, Mino increased eIF2α phosphorylation and CHOP expression. Knockdown of eIF2α or CHOP reduced Mino-induced LC3-II conversion and glioma cell death. When autophagy was inhibited, Mino induced cell death in a caspase-dependent manner. Rapamycin in combination with Mino produced synergistic effects on LC3 conversion, reduction of the Akt/mTOR/p70S6K pathway, and glioma cell death. Bioluminescent imaging showed that Mino inhibited the growth of glioma and prolonged survival time and that these effects were blocked by shCHOP. Conclusions Mino induced autophagy by eliciting endoplasmic reticulum stress response and switched cell death from autophagy to apoptosis when autophagy was blocked. These results coupled with clinical availability and a safe track record make Mino a promising agent for the treatment of malignant gliomas. PMID:23787763

A novel type of EWS-CHOP fusion gene in myxoid liposarcoma

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

Matsui, Yoshito; Ueda, Takafumi; Kubo, Takahiro

2006-09-22

The cytogenetic hallmark of myxoid type and round cell type liposarcoma consists of reciprocal translocation of t(12;16)(q13;p11) and t(12;22)(q13;q12), which results in fusion of TLS/FUS and CHOP, and EWS and CHOP, respectively. Nine structural variations of the TLS/FUS-CHOP chimeric transcript have been reported, however, only two types of EWS-CHOP have been described. We describe here a case of myxoid liposarcoma containing a novel EWS-CHOP chimeric transcript and identified the breakpoint occurring in intron 13 of EWS. Reverse transcription-polymerase chain reaction and direct sequence showed that exon 13 of EWS was in-frame fused to exon 2 of CHOP. Genomic analysis revealedmore » that the breaks were located in intron 13 of EWS and intron 1 of CHOP.« less

Addition of rituximab to chop does not increase the risk of cardiotoxicity in patients with non-Hodgkin's lymphoma.

PubMed

Kilickap, Saadettin; Yavuz, Bunyamin; Aksoy, Sercan; Sahiner, Levent; Dincer, Murat; Harputluoglu, Hakan; Erman, Mustafa; Aytemir, Kudret; Tokgozoglu, Lale; Barista, Ibrahim

2008-01-01

The addition of rituximab to doxorubicin-containing standard chemotherapy significantly improves response to therapy and reduces the risk of death in B-cell non-Hodgkin's lymphoma (NHL) patients. However, the impact of this approach on doxorubicin-induced cardiotoxicity has not been elucidated. Patients who had been planned to receive CHOP or rituximab plus CHOP (R-CHOP) combination chemotherapy with a diagnosis of NHL were included in the study. In all patients, systolic and diastolic parameters were measured by using conventional and pulsed-wave tissue Doppler echocardiography, which is more sensitive than conventional lead-dependent techniques, both before and in the sixth month of therapy. There were 28 (M/F; 14/14) patients on CHOP and 33 (M/F; 16/17) patients on R-CHOP. Median age in CHOP and R-CHOP was 49 and 50 years (P = 0.44), respectively. Cumulative doxorubicin doses were 280 and 286 mg/m(2) on CHOP and R-CHOP (P = 0.65), respectively. None of the patients developed clinically evident congestive heart failure. Parameters of systolic function such as LVEF and FS did not significantly change in any patients. In both arms, tissue Doppler parameters of diastolic function such as lateral E and septal E velocity of mitral annulus decreased significantly after therapy (P < 0.001). However, the decrease in diastolic function was similar in both arms (P > 0.05). Conventional Doppler echocardiography yielded consistent findings. Both CHOP and R-CHOP cause diastolic dysfunction in the early period following their administration. The addition of rituximab to CHOP chemotherapy does not significantly increase the risk of doxorubicin-induced cardiotoxicity during this period.

The regulation of cellular apoptosis by the ROS-triggered PERK/EIF2α/chop pathway plays a vital role in bisphenol A-induced male reproductive toxicity

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

Yin, Li

Bisphenol A (2,2-bis(4-hydroxyphenyl)propane, BPA) is ubiquitous in the environment, wildlife, and humans. Evidence from past studies suggests that BPA is associated with decreased semen quality. However, the molecular basis for the adverse effect of BPA on male reproductive toxicity remains unclear. We evaluated the effect of BPA on mouse spermatocytes GC-2 cells and adult mice, and we explored the potential mechanism of its action. The results showed that BPA inhibited cell proliferation and increased the apoptosis rate. The testes from BPA-treated mice showed fewer spermatogenic cells and sperm in the seminiferous tubules. In addition, BPA caused reactive oxygen species (ROS)more » accumulation. Previous study has verified that mitochondrion was the organelle affected by the BPA-triggered ROS accumulation. We found that BPA induced damage to the endoplasmic reticulum (ER) in addition to mitochondria, and most ER stress-related proteins were activated in cellular and animal models. Knocking down of the PERK/EIF2α/chop pathway, one of the ER stress pathways, partially recovered the BPA-induced cell apoptosis. In addition, an ROS scavenger attenuated the expression of the PERK/EIF2α/chop pathway-related proteins. Taken together, these data suggested that the ROS regulated PERK/EIF2α/chop pathway played a vital role in BPA-induced male reproductive toxicity. - Highlights: • BPA exposure caused the damage of the endoplasmic reticulum. • BPA exposure activated ER stress related proteins in male reproductive system. • ROS regulated PERK/EIF2α/chop pathway played a vital role in BPA-induced toxicity.« less

Cost-benefit analysis of prophylactic granulocyte colony-stimulating factor during CHOP antineoplastic therapy for non-Hodgkin's lymphoma.

PubMed

Dranitsaris, G; Altmayer, C; Quirt, I

1997-06-01

Several randomised comparative trials have shown that granulocyte colony-stimulating factor (G-CSF) reduces the duration of neutropenia, hospitalisation and intravenous antibacterial use in patients with cancer who are receiving high-dosage antineoplastic therapy. However, one area that has received less attention is the role of G-CSF in standard-dosage antineoplastic regimens. One such treatment that is considered to have a low potential for inducing fever and neutropenia is the CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) for non-Hodgkin's lymphoma. We conducted a cost-benefit analysis from a societal perspective in order to estimate the net cost or benefit of prophylactic G-CSF in this patient population. This included direct costs for hospitalisation with antibacterial support, as well as indirect societal costs, such as time off work and antineoplastic therapy delays secondary to neutropenia. The findings were then tested by a comprehensive sensitivity analysis. The administration of G-CSF at a dosage of 5 micrograms/kg/day for 11 doses following CHOP resulted in an overall net cost of $Can1257. In the sensitivity analysis, lowering the G-CSF dosage to 2 micrograms/kg/day generated a net benefit of $Can6564, indicating a situation that was cost saving to society. The results of the current study suggest that the use of G-CSF in patients receiving CHOP antineoplastic therapy produces a situation that is close to achieving cost neutrality. However, low-dosage (2 micrograms/kg/day) G-CSF is an economically attractive treatment strategy because it may result in overall savings to society.

Parkin regulation of CHOP modulates susceptibility to cardiac endoplasmic reticulum stress.

PubMed

Han, Kim; Hassanzadeh, Shahin; Singh, Komudi; Menazza, Sara; Nguyen, Tiffany T; Stevens, Mark V; Nguyen, An; San, Hong; Anderson, Stasia A; Lin, Yongshun; Zou, Jizhong; Murphy, Elizabeth; Sack, Michael N

2017-05-18

The regulatory control of cardiac endoplasmic reticulum (ER) stress is incompletely characterized. As ER stress signaling upregulates the E3-ubiquitin ligase Parkin, we investigated the role of Parkin in cardiac ER stress. Parkin knockout mice exposed to aortic constriction-induced cardiac pressure-overload or in response to systemic tunicamycin (TM) developed adverse ventricular remodeling with excessive levels of the ER regulatory C/EBP homologous protein CHOP. CHOP was identified as a Parkin substrate and its turnover was Parkin-dose and proteasome-dependent. Parkin depletion in cardiac HL-1 cells increased CHOP levels and enhanced susceptibility to TM-induced cell death. Parkin reconstitution rescued this phenotype and the contribution of excess CHOP to this ER stress injury was confirmed by reduction in TM-induced cell death when CHOP was depleted in Parkin knockdown cardiomyocytes. Isogenic Parkin mutant iPSC-derived cardiomyocytes showed exaggerated ER stress induced CHOP and apoptotic signatures and myocardium from subjects with dilated cardiomyopathy showed excessive Parkin and CHOP induction. This study identifies that Parkin functions to blunt excessive CHOP to prevent maladaptive ER stress-induced cell death and adverse cardiac ventricular remodeling. Additionally, Parkin is identified as a novel post-translational regulatory moderator of CHOP stability and uncovers an additional stress-modifying function of this E3-ubiquitin ligase.

Use of visible and near-infrared spectroscopy to predict pork longissimus lean color stability.

PubMed

King, D A; Shackelford, S D; Wheeler, T L

2011-12-01

This study evaluated the use of visible and near-infrared (VISNIR) spectroscopy to predict lean color stability in pork loin chops. Spectra were collected immediately after and approximately 1 h after rib removal on 1,208 loins. Loins were aged for 14 d before a 2.54-cm chop was placed in simulated retail display. Spectra were collected on aged loins immediately after removal from the vacuum package and on chops 10 min after cutting. Instrumental color measurements [L*, a*, b*, hue angle, chroma, and E (overall color change)] were determined on d 0, 1, 7, 11, and 14 of display. Principal components analysis of display d 0 and 14 values of these traits identified a factor (first principal component; PC1) explaining 67% of the variance that was related to color change. Partial least squares regression was used to develop 3 models to predict PC1 values by using VISNIR spectra collected in the plant, on aged loins, and on chops. Loins with predicted PC1 values less than 0 were classified as having a stable color, whereas values greater than 0 were classified as having a labile lean color. Loins classified as stable by the in-plant model had smaller (P < 0.05) L* values than those classified as labile. Hue angle and ΔE values were less (P < 0.05) and a* and chroma values were greater (P < 0.05) after d 7 of display in loins predicted to have a stable color than in loins predicted to have a labile lean color. Similarly, chops from loins classified as stable using the aged loin model had smaller (P < 0.05) L* values than those from loins classified as labile. Furthermore, loins predicted to be stable had smaller (P < 0.05) hue angle and ΔE values and greater (P < 0.05) a* and chroma values after d 7 of display than did loins predicted to be labile. Results for the chop model were similar to those from the 2 loin models. Chops predicted to have a stable lean color had smaller (P < 0.05) L* values than did those predicted to have a labile lean color. Chops classified as stable had smaller (P < 0.05) hue angle and ΔE values and greater (P < 0.05) a* and chroma values after d 7 of display compared with chops classified as labile. All 3 models effectively segregated chops based on color stability, particularly with regard to redness. Regardless of the model being used, d 14 display values for a*, hue angle, and ΔE in loins classified as stable were similar to the d 7 values of loins classified as labile. Thus, these results suggest that VISNIR spectroscopy would be an effective technology for sorting pork loins with regard to lean color stability.

Voltammetric detection of biological molecules using chopped carbon fiber.

PubMed

Sugawara, Kazuharu; Yugami, Asako; Kojima, Akira

2010-01-01

Voltammetric detection of biological molecules was carried out using chopped carbon fibers produced from carbon fiber reinforced plastics that are biocompatible and inexpensive. Because chopped carbon fibers normally are covered with a sizing agent, they are difficult to use as an electrode. However, when the surface of a chopped carbon fiber was treated with ethanol and hydrochloric acid, it became conductive. To evaluate the functioning of chopped carbon fibers, voltammetric measurements of [Fe(CN)(6)](3-) were carried out. Redoxes of FAD, ascorbic acid and NADH as biomolecules were recorded using cyclic voltammetry. The sizing agents used to bundle the fibers were epoxy, polyamide and polyurethane resins. The peak currents were the greatest when using the chopped carbon fibers that were created with epoxy resins. When the electrode response of the chopped carbon fibers was compared with that of a glassy carbon electrode, the peak currents and the reversibility of the electrode reaction were sufficient. Therefore, the chopped carbon fibers will be useful as disposable electrodes for the sensing of biomolecules.

Kaempferol induces apoptosis in HepG2 cells via activation of the endoplasmic reticulum stress pathway.

PubMed

Guo, Haiqing; Ren, Feng; Zhang, Li; Zhang, Xiangying; Yang, Rongrong; Xie, Bangxiang; Li, Zhuo; Hu, Zhongjie; Duan, Zhongping; Zhang, Jing

2016-03-01

Kaempferol is a flavonoid compound that has gained importance due to its antitumor properties; however, the underlying mechanisms remain to be fully understood. The present study aimed to investigate the molecular mechanisms of the antitumor function of kaempferol in HepG2 hepatocellular carcinoma cells. Kaempferol was determined to reduce cell viability, increase lactate dehydrogenase activity and induce apoptosis in a concentration‑ and time‑dependent manner in HepG2 cells. Additionally, kaempferol‑induced apoptosis possibly acts via the endoplasmic reticulum (ER) stress pathway, due to the significant increase in the protein expression levels of glucose‑regulated protein 78, glucose‑regulated protein 94, protein kinase R‑like ER kinase, inositol‑requiring enzyme 1α, partial activating transcription factor 6 cleavage, caspase‑4, C/EBP homologous protein (CHOP) and cleaved caspase‑3. The pro‑apoptotic activity of kaempferol was determined to be due to induction of the ER stress‑CHOP pathway, as: i) ER stress was blocked by 4‑phenyl butyric acid (4‑PBA) pretreatment and knockdown of CHOP with small interfering RNA, which resulted in alleviation of kaempferol‑induced HepG2 cell apoptosis; and ii) transfection with plasmid overexpressing CHOP reversed the protective effect of 4‑PBA in kaempferol‑induced HepG2 cells and increased the apoptotic rate. Thus, kaempferol promoted HepG2 cell apoptosis via induction of the ER stress‑CHOP signaling pathway. These observations indicate that kaempferol may be used as a potential chemopreventive treatment strategy for patients with hepatocellular carcinoma.

Molecular characterization of phosphorylcholine expression on the lipooligosaccharide of Histophilus somni.

PubMed

Elswaifi, Shaadi F; St Michael, Frank; Sreenivas, Avula; Cox, Andrew; Carman, George M; Inzana, Thomas J

2009-10-01

Histophilus somni (Haemophilus somnus) is an important pathogen of cattle that is responsible for respiratory disease, septicemia, and systemic diseases such as thrombotic meningoencephalitis, myocarditis, and abortion. A variety of virulence factors have been identified in H. somni, including compositional and antigenic variation of the lipooligosaccharide (LOS). Phosphorylcholine (ChoP) has been identified as one of the components of H. somni LOS that undergoes antigenic variation. In this study, five genes (lic1ABCD(Hs) and glpQ) with homology to genes responsible for ChoP expression in Haemophilus influenzae LOS were identified in the H. somni genome. An H. somni open reading frame (ORF) with homology to H. influenzae lic1A (lic1A(Hi)) contained a variable number of tandem repeats (VNTR). However, whereas the tetranucleotide repeat 5'-CAAT-3' is present in lic1A(Hi), the VNTR in H. somni lic1A (lic1A(Hs)) consisted of 5'-AACC-3'. Due to the propensity of VNTR to vary during replication and cause the ORF to shift in and out of frame with the upstream start codon, the VNTR were deleted from lic1A(Hs) to maintain the gene constitutively on. This construct was cloned into Escherichia coli, and functional enzyme assays confirmed that lic1A(Hs) encoded a choline kinase, and that the VNTR were not required for expression of a functional gene product. Variation in the number of VNTR in lic1A(Hs) correlated with antigenic variation of ChoP expression in H. somni strain 124P. However, antigenic variation of ChoP expression in strain 738 predominately occurred through variable extension/truncation of the LOS outer core. These results indicated that the lic1(Hs) genes controlled expression of ChoP on the LOS, but that in H. somni there are two potential mechanisms that account for antigenic variation of ChoP.

Molecular characterization of phosphorylcholine expression on the lipooligosaccharide of Histophilus somni

PubMed Central

Elswaifi, Shaadi F.; St. Michael, Frank; Sreenivas, Avula; Cox, Andrew; Carman, George M.; Inzana, Thomas J.

2013-01-01

Histophilus somni (Haemophilus somnus) is an important pathogen of cattle that is responsible for respiratory disease, septicemia, and systemic diseases such as thrombotic meningoencephalitis, myocarditis, and abortion. A variety of virulence factors have been identified in H. somni, including compositional and antigenic variation of the lipooligosaccharide (LOS). Phosphorylcholine (ChoP) has been identified as one of the components of H. somni LOS that undergoes antigenic variation. In this study, five genes (lic1ABCDHs and glpQ) with homology to genes responsible for ChoP expression in Haemophilus influenzae LOS were identified in the H. somni genome. An H. somni open reading frame (ORF) with homology to H. influenzae lic1A (lic1AHi) contained a variable number of tandem repeats (VNTR). However, whereas the tetranucleotide repeat 5′-CAAT-3′ is present in lic1AHi, the VNTR in H. somni lic1A (lic1AHs) consisted of 5′-AACC-3′. Due to the propensity of VNTR to vary during replication and cause the ORF to shift in and out of frame with the upstream start codon, the VNTR were deleted from lic1AHs to maintain the gene constitutively on. This construct was cloned into Escherichia coli, and functional enzyme assays confirmed that lic1AHs encoded a choline kinase, and that the VNTR were not required for expression of a functional gene product. Variation in the number of VNTR in lic1AHs correlated with antigenic variation of ChoP expression in H. somni strain 124P. However, antigenic variation of ChoP expression in strain 738 predominately occurred through variable extension/truncation of the LOS outer core. These results indicated that the lic1Hs genes controlled expression of ChoP on the LOS, but that in H. somni there are two potential mechanisms that account for antigenic variation of ChoP. PMID:19682567

ERK1/2-dependent bestrophin-3 expression prevents ER-stress-induced cell death in renal epithelial cells by reducing CHOP.

PubMed

Lee, Wing-Kee; Chakraborty, Prabir K; Roussa, Eleni; Wolff, Natascha A; Thévenod, Frank

2012-10-01

Upon endoplasmic reticulum (ER) stress induction, cells endeavor to survive by engaging the adaptive stress response known as the unfolded protein response or by removing aggregated proteins via autophagy. Chronic ER stress culminates in apoptotic cell death, which involves induction of pro-apoptotic CHOP. Here, we show that bestrophin-3 (Best-3), a protein previously associated with Ca(2+)-activated Cl(-) channel activity, is upregulated by the ER stressors, thapsigargin (TG), tunicamycin (TUN) and the toxic metal Cd(2+). In cultured rat kidney proximal tubule cells, ER stress, CHOP and cell death were induced after 6h by Cd(2+) (25μM), TG (3μM) and TUN (6μM), were associated with increased cytosolic Ca(2+) and downstream formation of reactive oxygen species and attenuated by the Ca(2+) chelator BAPTA-AM (10μM), the antioxidant α-tocopherol (100μM), or overexpression of catalase (CAT). Immunofluorescence staining showed Best-3 expression in the plasma membrane, nuclei and intracellular compartments, though not in the ER, in cultured cells and rat kidney cortex sections. Best-3 mRNA was augmented by ER stress and signaled through increased Ca(2+), oxidative stress and ERK1/2 phosphorylation, because it was attenuated by α-tocopherol, CAT expression, BAPTA-AM, calmodulin kinase inhibitor calmidazolium (40μM), ERK1/2 inhibitor U0126 (10μM), and ERK1/2 RNAi. Knockdown of Best-3 resulted in decreased cell number consequentially of cell death, as determined by nuclear staining and PARP-1 cleavage. Furthermore, reduced ER stress-cell death by Best-3 overexpression is attributed to diminished CHOP. Since Best-3 overexpression did not affect upstream signaling pathways, we hypothesize that Best-3 possibly interferes with CHOP transcription. From our novel observations, we conclude that ERK1/2-dependent Best-3 activation regulates cell fate decisions during ER stress by suppressing CHOP induction and death. Copyright © 2012 Elsevier B.V. All rights reserved.

Evaluation of chopped switchgrass and chopped bermudagrass as litter materials over multiple heavy broiler flocks

USDA-ARS?s Scientific Manuscript database

Chopped switchgrass (SG) and chopped bermudagrass (BG) were evaluated as alternatives to pine shavings (PS) for broiler litter over 3 flocks. Twenty-four pens were filled with the 3 litter types. Live performance parameters included mortality, BW, BW gain, feed consumption, and feed conversion. Mort...

Preclinical anti-tumor activity of antibody-targeted chemotherapy with CMC-544 (inotuzumab ozogamicin), a CD22-specific immunoconjugate of calicheamicin, compared with non-targeted combination chemotherapy with CVP or CHOP.

PubMed

DiJoseph, John F; Dougher, Maureen M; Evans, Deborah Y; Zhou, Bin-Bing; Damle, Nitin K

2011-04-01

CMC-544 (inotuzumab ozogamicin) is a CD22-specific immunoconjugate of calicheamicin currently being evaluated in patients with non-Hodgkin's B-cell lymphoma (BCL). CHOP and CVP represent untargeted combination chemotherapy comprised of cyclophosphamide, vincristine and prednisone with or without doxorubicin, commonly used in the treatment of NHL. Here, we describe anti-tumor efficacy of CMC-544, CHOP or CVP against human BCL xenografts. In vitro, human BCLs were cultured with CMC-544 or individual constituents of CHOP for inhibition of their growth. In vivo, immunocompromised mice with established BCL xenografts were administered CHOP, CVP or CMC-544 to monitor their survival and BCL growth. In vitro, CMC-544 was more potent in causing growth inhibition of various BCL than cyclophosphamide, doxorubicin, vincristine or dexamethasone. In vivo, treatment with CHOP or CVP inhibited growth of BCL xenografts for up to 40 days after which BCL relapsed. Tumor growth inhibition by CMC-544 (>100 days) lasted longer than that by CHOP or CVP. BCL xenografts that relapsed after the treatment with CHOP or CVP were far less responsive to CHOP or CVP re-treatment but regressed upon subsequent treatment with CMC-544. CVP could be co-administered with suboptimal doses of CMC-544, while CHOP could be administered on alternant days with CMC-544 to cause enhanced regression of established BCL xenografts. Preclinically, CMC-544 provides greater therapeutic benefit than CVP or CHOP against BCL xenografts. CMC-544 may also be co-administered with standard chemotherapeutic regimens in the treatment of B-NHL for superior anti-tumor activity.

CHOP Contributes to, But Is Not the Only Mediator of, IAPP Induced β-Cell Apoptosis.

PubMed

Gurlo, T; Rivera, J F; Butler, A E; Cory, M; Hoang, J; Costes, S; Butler, Peter C

2016-04-01

The islet in type 2 diabetes is characterized by β-cell loss, increased β-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). When protein misfolding protective mechanisms are overcome, human IAPP (h-IAPP) forms membrane permeant toxic oligomers that induce β-cell dysfunction and apoptosis. In humans with type 2 diabetes (T2D) and mice transgenic for h-IAPP, endoplasmic reticulum (ER) stress has been inferred from nuclear translocation of CCAAT/enhancer-binding protein homologous protein (CHOP), an established mediator of ER stress. To establish whether h-IAPP toxicity is mediated by ER stress, we evaluated diabetes onset and β-cell mass in h-IAPP transgenic (h-TG) mice with and without deletion of CHOP in comparison with wild-type controls. Diabetes was delayed in h-TG CHOP(-/-) mice, with relatively preserved β-cell mass and decreased β-cell apoptosis. Deletion of CHOP attenuates dysfunction of the autophagy/lysosomal pathway in β-cells of h-TG mice, uncovering a role for CHOP in mediating h-IAPP-induced dysfunction of autophagy. As deletion of CHOP delayed but did not prevent h-IAPP-induced β-cell loss and diabetes, we examined CHOP-independent stress pathways. JNK, a target of the IRE-1pTRAF2 complex, and the Bcl-2 family proapoptotic mediator BIM, a target of ATF4, were comparably activated by h-IAPP expression in the presence and absence of CHOP. Therefore, although these studies affirm that CHOP is a mediator of h-IAPP-induced ER stress, it is not the only one. Therefore, suppression of CHOP alone is unlikely to be a durable therapeutic strategy to protect against h-IAPP toxicity because multiple stress pathways are activated.

A prospective randomized study of Chop versus Chop plus alpha-2B interferon in patients with intermediate and high grade non-Hodgkin's lymphoma: the International Oncology Study Group NHL1 Study .

PubMed

Giles, F J; Shan, J; Advani, S H; Akan, H; Aydogdu, I; Aziz, Z; Azim, H A; Bapsy, P P; Buyukkececi, F; Chaimongkol, B; Chen, P M; Cheong, S K; Ferhanoglu, B; Hamza, R; Khalid, H M; Intragumtornchai, T; Kim, S W; Kim, S Y; Koc, H; Kumar, L; Kumar, R; Lei, K I; Lekhakula, A; Muthalib, A; Patel, M; Poovalingam, V P; Prayoonwiwat, W; Rana, F; Reksodiputro, A H; Ruff, P; Sagar, T G; Schwarer, A P; Song, H S; Suh, C W; Suharti, C; Supindiman, I; Tee, G Y; Thamprasit, T; Villalon, A H; Wickham, N R; Wong, J E; Yalcin, A; Jootar, S

2000-12-01

The addition of a brief alpha interferon regimen to each CHOP induction cycle, plus one year of alpha interferon thrice weekly maintenance therapy, has no early effect on response rates or survival in patients with Intermediate or High grade cell NHL. The CHOP (Cyclophosphamide, Adriamycin. Vincristine, Prednisone) regimen is the most widely used first-line therapy for patients with Intermediate or High Grade (IG/HG) non-Hodgkin's lymphoma (NHL). Alpha 2b interferon (INF) enhances response rates and improves survival in low-grade NHL. The International Oncology Study Group (IOSG) conducted a prospective randomized study comparing CHOP alone or combined with INF in patients with IG/HG-NHL. The primary study aim was to compare the objective response rates in these patient cohorts. Patients with a confirmed diagnosis of measurable NHL of International Working Formulation (IWF) groups D to H histology were randomized to receive CHOP alone or CHOP with 5Mu INF s.c. for 5 days on days 22 to 26 of each 28 day cycle with INF 5 million units (Mu) given three times per week subcutaneously for 52 weeks in those patients who responded to CHOP plus INF. The overall response rates were equivalent in both groups: CHOP alone (214 patients) 81% (complete 55%, partial 26%); CHOP plus INF (221 patients) 80% (complete 54%, partial 26%). At 36 months, the actuarial survival rate was equivalent in both groups. There is no apparent early advantage in terms of response or survival conferred by adding the study INF regimen to CHOP therapy for patients with IG/HG-NHL.

Endoplasmic reticulum stress signaling is involved in mitomycin C (MMC)-induced apoptosis in human fibroblasts via PERK pathway.

PubMed

Shi, Kun; Wang, Daode; Cao, Xiaojian; Ge, Yingbin

2013-01-01

Endoplasmic reticulum (ER) stress-mediated cell apoptosis has been implicated in various cell types, including fibroblasts. Previous studies have shown that mitomycin C (MMC)-induced apoptosis occurs in fibroblasts, but the effects of MMC on ER stress-mediated apoptosis in fibroblasts have not been examined. Here, MMC-induced apoptosis in human primary fibroblasts was investigated by exposing cells to a single dose of MMC for 5 minutes. Significant inhibition of cell proliferation and increased apoptosis were observed using a cell viability assay, Annexin V/propidium iodide double staining, cell cycle analysis, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining. Upregulation of proapoptotic factors, including cleaved caspase-3 and poly ADP-ribose polymerase (PARP), was detected by Western blotting. MMC-induced apoptosis was correlated with elevation of 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP), which are hallmarks of ER stress. Three unfolded protein response (UPR) sensors (inositol-requiring enzyme 1, IRE1; activating transcription factor 6, ATF6; and PKR-like ER kinase, PERK) and their downstream signaling pathways were also activated. Knockdown of CHOP attenuated MMC-induced apoptosis by increasing the ratio of BCL-2/BAX and decreasing BIM expression, suggesting that ER stress is involved in MMC-induced fibroblast apoptosis. Interestingly, knockdown of PERK significantly decreased ER stress-mediated apoptosis by reducing the expression of CHOP, BIM and cleaved caspase-3. Reactive oxygen species (ROS) scavenging also decreased the expression of GRP78, phospho-PERK, CHOP, and BIM. These results demonstrate that MMC-induced apoptosis is triggered by ROS generation and PERK activation.

Endoplasmic Reticulum Stress Signaling Is Involved in Mitomycin C(MMC)-Induced Apoptosis in Human Fibroblasts via PERK Pathway

PubMed Central

Cao, Xiaojian; Ge, Yingbin

2013-01-01

Endoplasmic reticulum (ER) stress-mediated cell apoptosis has been implicated in various cell types, including fibroblasts. Previous studies have shown that mitomycin C (MMC)-induced apoptosis occurs in fibroblasts, but the effects of MMC on ER stress-mediated apoptosis in fibroblasts have not been examined. Here, MMC-induced apoptosis in human primary fibroblasts was investigated by exposing cells to a single dose of MMC for 5 minutes. Significant inhibition of cell proliferation and increased apoptosis were observed using a cell viability assay, Annexin V/propidium iodide double staining, cell cycle analysis, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining. Upregulation of proapoptotic factors, including cleaved caspase-3 and poly ADP-ribose polymerase (PARP), was detected by Western blotting. MMC-induced apoptosis was correlated with elevation of 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP), which are hallmarks of ER stress. Three unfolded protein response (UPR) sensors (inositol-requiring enzyme 1, IRE1; activating transcription factor 6, ATF6; and PKR-like ER kinase, PERK) and their downstream signaling pathways were also activated. Knockdown of CHOP attenuated MMC-induced apoptosis by increasing the ratio of BCL-2/BAX and decreasing BIM expression, suggesting that ER stress is involved in MMC-induced fibroblast apoptosis. Interestingly, knockdown of PERK significantly decreased ER stress-mediated apoptosis by reducing the expression of CHOP, BIM and cleaved caspase-3. Reactive oxygen species (ROS) scavenging also decreased the expression of GRP78, phospho-PERK, CHOP, and BIM. These results demonstrate that MMC-induced apoptosis is triggered by ROS generation and PERK activation. PMID:23533616

Increased expression of 78 kD glucose-regulated protein promotes cardiomyocyte apoptosis in a rat model of liver cirrhosis

PubMed Central

Zhang, Lili; Zhang, Huiying; Lv, Minli; Jia, Jiantao; Fan, Yimin; Tian, Xiaoxia; Li, Xujiong; Li, Baohong; Ji, Jingquan; Wang, Limin; Zhao, Zhongfu; Han, Dewu; Ji, Cheng

2015-01-01

Aims: This study was to investigate the role and underlying mechanism of 78 kD glucose-regulated protein (GRP78) in cardiomyocyte apoptosis in a rat model of liver cirrhosis. Methods: A rat model of liver cirrhosis was established with multiple pathogenic factors. A total of 42 male SD rats were randomly divided into the liver cirrhosis group and control group. Cardiac structure analysis was performed to assess alterations in cardiac structure. Cardiomyocytes apoptosis was detected by TdT-mediated dUTP nick end labeling method. Expression of GRP78, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, nuclear factor kappa-light-chain-enhancer of activated B cells p65 subunit (NF-κB p65) and B cell lymphoma-2 (Bcl-2) was detected by immunohistochemical staining. Results: The ratios of left ventricular wall thickness to heart weight and heart weight to body weight were significantly increased with the progression of liver cirrhosis (P < 0.05). Apoptosis index of cardiomyocytes was significantly increased with the progression of liver cirrhosis (P < 0.05). The expression levels of GRP78, CHOP and caspase-12 were significantly increased in the progression of liver cirrhosis (P < 0.05). The expression levels of NF-κB p65 and Bcl-2 were highest in the 4-wk liver cirrhosis, and they were decreased in the 6-wk and 8-wk in the progression of liver cirrhosis. GRP78 expression levels were positively correlated with apoptosis index, CHOP and caspase-12 expression levels (P < 0.05). CHOP expression levels were negatively correlated with NF-κB p65 and Bcl-2 expression levels (P < 0.05). Conclusion: Increased expression of GRP78 promotes cardiomyocyte apoptosis in rats with cirrhotic cardiomyopathy. PMID:26464674

Selenium deficiency aggravates T-2 toxin-induced injury of primary neonatal rat cardiomyocytes through ER stress.

PubMed

Xu, Jing; Pan, Shengchi; Gan, Fang; Hao, Shu; Liu, Dandan; Xu, Haibin; Huang, Kehe

2018-04-01

Keshan disease is a potentially fatal cardiomyopathy in humans. Selenium deficiency, T-2 toxin, and myocarditis virus are thought to be the major factors contributing to Keshan disease. But the relationship among these three factors is poorly described. This study aims to explore whether selenium deficiency aggravates T-2 toxin-induced cardiomyocyte injury and its underlying mechanism. Cardiomyocytes were isolated from neonatal rat and cultured at the physiological (2.0 μM) or lower concentrations of selenium with different concentrations of T-2 toxin. Our results showed that selenium deficiencies aggravated T-2 toxin-induced cardiomyocyte injury in a concentration-dependent manner as demonstrated by MTT bioassay, LDH activity, reactive oxygen species levels and caspase 3 protein expressions. T-2 toxin treatment significantly increased mRNA expressions for stress proteins GRP78 and CHOP in cardiomyocytes compared with the control. Selenium deficiencies further promoted GRP78, CHOP and p-eIF2α expressions. Knockdown of CHOP by the specific small interfering RNA eliminated the effect of selenium deficiencies on T-2 toxin-induced injury. It could be concluded that selenium deficiency aggravates T-2 toxin-induced cardiomyocyte injury through initiating more aggressive endoplasmic reticulum stress. Copyright © 2018 Elsevier B.V. All rights reserved.

BRITE Constellation: data processing and photometry

NASA Astrophysics Data System (ADS)

Popowicz, A.; Pigulski, A.; Bernacki, K.; Kuschnig, R.; Pablo, H.; Ramiaramanantsoa, T.; Zocłońska, E.; Baade, D.; Handler, G.; Moffat, A. F. J.; Wade, G. A.; Neiner, C.; Rucinski, S. M.; Weiss, W. W.; Koudelka, O.; Orleański, P.; Schwarzenberg-Czerny, A.; Zwintz, K.

2017-09-01

Context. The BRIght Target Explorer (BRITE) mission is a pioneering space project aimed at the long-term photometric monitoring of the brightest stars in the sky by means of a constellation of nanosatellites. Its main advantage is high photometric accuracy and time coverage which are inaccessible from the ground. Its main drawback is the lack of cooling of the CCD detectors and the absence of good shielding that would protect them from energetic particles. Aims: The main aim of this paper is the presentation of procedures used to obtain high-precision photometry from a series of images acquired by the BRITE satellites in two modes of observing, stare and chopping. The other aim is a comparison of the photometry obtained with two different pipelines and a comparison of the real scatter with expectations. Methods: We developed two pipelines corresponding to the two modes of observing. They are based on aperture photometry with a constant aperture, circular for stare mode of observing and thresholded for chopping mode. Impulsive noise is a serious problem for observations made in the stare mode of observing and therefore in the pipeline developed for observations made in this mode, hot pixels are replaced using the information from shifted images in a series obtained during a single orbit of a satellite. In the other pipeline, the hot pixel replacement is not required because the photometry is made in difference images. Results: The assessment of the performance of both pipelines is presented. It is based on two comparisons, which use data from six runs of the UniBRITE satellite: (I) comparison of photometry obtained by both pipelines on the same data, which were partly affected by charge transfer inefficiency (CTI), (II) comparison of real scatter with theoretical expectations. It is shown that for CTI-affected observations, the chopping pipeline provides much better photometry than the other pipeline. For other observations, the results are comparable only for data obtained shortly after switching to chopping mode. Starting from about 2.5 years in orbit, the chopping mode of observing provides significantly better photometry for UniBRITE data than the stare mode. Conclusions: This paper shows that high-precision space photometry with low-cost nanosatellites is achievable. The proposed methods, used to obtain photometry from images affected by high impulsive noise, can be applied to data from other space missions or even to data acquired from ground-based observations. Based on data collected by the BRITE Constellation satellite mission, designed, built, launched, operated and supported by the Austrian Research Promotion Agency (FFG), the University of Vienna, the Technical University of Graz, the Canadian Space Agency (CSA), the University of Toronto Institute for Aerospace Studies (UTIAS), the Foundation for Polish Science & Technology (FNiTP MNiSW), and National Science Centre (NCN).

Zyflamend Sensitizes Tumor Cells to TRAIL-Induced Apoptosis Through Up-Regulation of Death Receptors and Down-Regulation of Survival Proteins: Role of ROS-Dependent CCAAT/Enhancer-Binding Protein-Homologous Protein Pathway

PubMed Central

Kim, Ji Hye; Park, Byoungduck; Gupta, Subash C.; Kannappan, Ramaswamy; Sung, Bokyung

2012-01-01

Abstract Aim: TNF (tumor necrosis factor)-related apoptosis-inducing ligand (TRAIL), is a selective killer of tumor cells, although its potential is limited by the development of resistance. In this article, we investigated whether the polyherbal preparation Zyflamend® can sensitize tumor cells to TRAIL. Results: We found that Zyflamend potentiated TRAIL-induced apoptosis in human cancer cells. Zyflamend manifested its effects through several mechanisms. First, it down-regulated the expression of cell survival proteins known to be linked to resistance to TRAIL. Second, Zyflamend up-regulated the expression of pro-apoptotic protein, Bax. Third, Zyflamend up-regulated the expression of death receptors (DRs) for TRAIL. Up-regulation of DRs was critical as gene-silencing of these receptors significantly reduced the effect of Zyflamend on TRAIL-induced apoptosis. The up-regulation of DRs was dependent on CCAAT/enhancer-binding protein-homologous protein (CHOP), as Zyflamend induced CHOP, its gene-silencing abolished the induction of receptors, and mutation of the CHOP binding site on DR5 promoter abolished Zyflamend-mediated DR5 transactivation. Zyflamend mediated its effects through reactive oxygen species (ROS), as ROS quenching reduced its effect. Further, Zyflamend induced DR5 and CHOP and down-regulated the expression of cell survival proteins in nude mice bearing human pancreatic cancer cells. Innovation: Zyflamend can sensitize tumor cells to TRAIL through modulation of multiple cell signaling mechanisms that are linked to ROS. Conclusion: Zyflamend potentiates TRAIL-induced apoptosis through the ROS-CHOP-mediated up-regulation of DRs, increase in pro-apoptotic protein and down-regulation of cell survival proteins. Antioxid. Redox Signal. 16, 413–427. PMID:22004570

Effects of alfalfa hay and its physical form (chopped versus pelleted) on performance of Holstein calves.

PubMed

Jahani-Moghadam, M; Mahjoubi, E; Hossein Yazdi, M; Cardoso, F C; Drackley, J K

2015-06-01

Inclusion of forage and its physical form in starter may affect rumen development, average daily gain (ADG), and dry matter intake (DMI) of dairy calves. To evaluate the effects of forage and its physical form (chopped vs. pelleted) on growth of calves under a high milk feeding regimen, 32 Holstein calves (38.8±1.1kg) were assigned at birth to 1 of 3 treatments in a completely randomized block design. Dietary treatments (% of dry matter) were (1) 100% semi-texturized starter (CON); (2) 90% semi-texturized starter + 10% chopped alfalfa hay (mean particle size=5.4mm) as a total mixed ration (TMR; CH); and (3) 90% semi-texturized starter + 10% pelleted alfalfa (mean=5.8mm) hay as a TMR (PH). Data were subjected to mixed model analysis with contrasts used to evaluate effect of forage inclusion. Calves were weaned at 76 d of age and the experiment finished 2 wk after weaning. Individual milk and solid feed consumption were recorded daily. Solid feed consumption and ADG increased as age increased (effect of week), but neither forage inclusion nor physical form of forage affected these variables pre- or postweaning. Plasma urea N was affected by treatments such that the CON group had a lower concentration than forage-fed groups. Forage inclusion, but not physical form, resulted in increased total protein in plasma. Although days with elevated rectal temperature, fecal score, and general appearance were not affected by dietary treatments, calves fed alfalfa hay during the first month of life had fewer days with respiratory issues, regardless of physical form of hay. We concluded that provision of forage does have some beneficial effects in calves fed large amounts of milk replacer, but pelleted alfalfa hay did not result in any improvement in calf performance or health. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Restoration of visual response in aged dystrophic RCS rats using AAV-mediated channelopsin-2 gene transfer.

PubMed

Tomita, Hiroshi; Sugano, Eriko; Yawo, Hiromu; Ishizuka, Toru; Isago, Hitomi; Narikawa, Satoko; Kügler, Sebastian; Tamai, Makoto

2007-08-01

To investigate whether the channelopsin-2 (Chop2) gene would restore visual responses in 10-month-old dystrophic Royal College of Surgeons (aged RCS; rdy/rdy) rats, the authors transferred the Chop2 gene into the retinal cells of aged RCS rats using the adenoassociated virus (AAV) vector. The N-terminal fragment (residues 1-315) of Chop2 was fused to a fluorescent protein, Venus, in frame at the end of the Chop2 coding fragment. The viral vector construct (AAV-Chop2V) for the expression of the Chop2V in the retina was made by subcloning into an adenoassociated virus vector, including the CAG promoter. To evaluate the expression profile of Chop2V in the retina, the rats were killed and the eyes were removed and fixed with 4% paraformaldehyde in 0.1 M phosphate-buffered saline. Retinal wholemount specimens and cryosections were made. Under anesthetized conditions, electrodes for the recording of visually evoked potentials (VEPs) were implanted onto the visual cortex in aged-RCS (rdy/rdy) rats. AAV-Chop2V vectors were then injected into the vitreous cavity of the left eyes. As a control, AAV-Venus vectors were applied to the right eyes. VEPs were evoked by the flash of a blue, white, or red light-emitting diode (LED) and were recorded from the visual cortex of the rats at various time points after the AAV vector injection. Chop2V fluorescence was predominantly observed in retinal ganglion cells (RGCs). Some fluorescence was observed in the inner nuclear layer and the inner plexiform layer neurites. A tendency of recovery was observed in the VEPs of aged RCS (rdy/rdy) rats after the AAV-Chop2V injection but not after the AAV-Venus injection. The visual response of AAV-Chop2V-injected aged RCS (rdy/rdy) rats was less sensitive to the blue LED flash than that of nondystrophic RCS (+/+) rats. The AAV-Chop2V-injected aged RCS (rdy/rdy) rats were insensitive to the red LED flash, which evoked a robust VEP in the RCS (+/+) rats. The visual response of aged RCS (rdy/rdy) rats was partially restored by transduction of the Chop2 gene through AAV into the inner retinal neurons, mainly RGCs. These results suggest that the transduction of Chop2 would provide a new strategy to treat some retinitis pigmentosa (RP) symptoms independent of their etiology.

Quinoa Black Bean Salad

MedlinePlus

... 2 cups tomato, chopped 1 medium red bell pepper, chopped 1 medium green bell pepper, chopped 2 fresh green chilis (or to taste), minced Black pepper (to taste) Directions Rinse the quinoa in cold ...

The antimicrobial effects of chopped garlic in ground beef and raw meatball (ciğ köfte).

PubMed

Aydin, Ali; Bostan, Kamil; Erkan, Mehmet Emin; Bingöl, Bariş

2007-03-01

This study was carried out to investigate the antimicrobial effects of chopped garlic in ground beef and raw meatball (çig köfte), which is a traditional food product eaten raw. Fresh minced ground beef and raw meatball batter prepared with traditional methods were separated into groups. Chopped and crushed garlic was added to each batch in order to reach various concentrations from 0% to 10%. The ground beef samples were stored at refrigerator and ambient temperatures. The raw meatball samples were only stored at room temperature. All samples were analyzed in order to determine the microbial counts at the 2(nd), 6(th), 12(th), and 24(th) hours of storage. Garlic addition decreased the microbial growth in some ground beef samples kept either at room temperature or in the refrigerator. However, microbial growth increased in some ground beef samples kept in similar conditions. The difference was found in samples kept in the refrigerator for 24 hours in terms of total aerobic mesophilic bacteria and coliform bacteria when garlic used at 10%. The effects of garlic on the microbial growth of both coliforms and Staphylococcus/Micrococcus in the samples kept at room temperature were increased. The yeast and mold counts in ground beef samples kept in any condition were not affected by garlic addition. However, the addition of garlic to the raw meatball mix decreased the microbial count, in terms of total aerobic mesophilic bacteria and yeast and mold counts, when the garlic was added at 5% or 10% (P < .05). The addition of 10% garlic to raw meatball caused a permanent decrease in yeast and mold count, unlike in ground beef. The results of this study indicate that the chopped garlic has a slowing-down effect on microbiological growth in ground meat depending on the garlic concentration, but this effect was not at an expected level even at the highest concentration, because potential antimicrobial agents in chopped garlic were probably insufficiently extracted.

CHOP mediates XBP1S-induced renal mesangial cell necrosis following high glucose treatment.

PubMed

Shao, Decui; Ni, Jun; Shen, Yang; Liu, Jia; Zhou, Li; Xue, Hong; Huang, Yu; Zhang, Wei; Lu, Limin

2015-07-05

High glucose (HG)-induced apoptosis in mesangial cells (MCs) is a critical determinant during the pathogenesis of diabetic nephropathy. The signaling cascade inducing MCs apoptosis by HG involves overproduction of reactive oxygen species. Our previous studies have demonstrated that HG-induced oxidative stress is mediated by suppression of spliced/active X-box binding protein 1 (XBP1S), suggesting the importance of XBP1S in HG-induced MCs apoptosis. CHOP, an endoplasmic reticulum stress-associated proapoptotic signal, is involved in downstream of XBP1S. In the present study, we explored the effect of XBP1S in modulating HG-induced apoptosis in renal MCs and then identified the role of CHOP in these processes. Apoptosis and necrosis were quantified by flow cytometry; protein levels of XBP1S, caspase3, Bax, Bcl2, BNIP3, and CHOP were analyzed by Western blotting. The cellular localization of XBP1S was determined by immunofluorescence histochemistry. The binding of XBP1 to CHOP promoter was determined by chromatin immunoprecipitation assays. In addition, adenoviruses harboring XBP1S gene (Ad-XBP1S) were used to overexpress XBP1S, whereas the knockdown of CHOP was achieved by small interference RNA. HG suppressed nuclear distribution of XBP1S and induced apoptosis and necrosis in MCs. Ad-XBP1S infection enhanced the nuclear translocation of XBP1S and reduced MCs apoptosis and necrosis. XBP1S bound to the promoter region of CHOP and upregulated CHOP expression. Conversely, CHOP expression was reduced upon HG exposure and knockdown of CHOP increased necrosis but not apoptosis in MCs. These results suggest that XBP1S protected MCs from HG-induced apoptosis and necrosis, and CHOP participates in XBP1S-regulated necrosis but not apoptosis. Copyright © 2015. Published by Elsevier B.V.

[Comparative study on the efficacy of Hyper CVAD/MA regimen and CHOP or CHOP like regimen in the treatment of primary peripheral T cell lymphoma].

PubMed

Wang, Jin; Gao, Lei; Qiu, Huiying; Zhang, Weiping; Yang, Jianmin; Song, Xianmin; Lyu, Shuqing; Chen, Jie; Wang, Jianmin

2014-10-01

To evaluate the curative efficacy and safety of two regimens, Hyper CVAD/MA and CHOP/CHOP, in the treatment of primary peripheral T cell lymphoma (PTCL). The clinical data of 80 primary PTCL patients were retrospectively analyzed, and the efficacy and safety of the two regimens, Hyper CVAD/MA and CHOP/CHOP, were evaluated. Of 80 patients with primary PTCL, 23 were treated with Hyper CVAD/MA regimen (HM group, experimental group) and 57 with CHOP or CHOP-like regimen (CC group, control group). The differences between overall response rate (ORR) among HM group and CC group (78.3% vs 54.4%, P = 0.047), ORR in patients with IPI score of 0-2 (86.7% vs 55.2%, P = 0.037), courses of chemotherapy to achieve remission (4 vs 6, P = 0.004), median progression-free survival (PFS) time (24 months vs 12 months, P = 0.039) and 1- year PFS rate (82.6% against 45.6%, P = 0.006) were statistically significant. The relapse rates were similar between 2 groups (50.0% vs 54.8%, P = 0.744). The 2-year and 3-year progression-free survivals and 3 year overall survival were not significantly different (P > 0.05). Patients in Hyper CVAD/MA group are more susceptible to neutropenia (<1.5 × 10⁹/L) (73.9% vs 38.6%, P=0.004). The curative effect of Hyper CVAD/MA regimen as induction therapy in treatment of PTCL patients except ALK positive PTCL patients was better than that of CHOP/CHOP-like regimen.

Amendments and mulches improve the biological quality of soils degraded by mining activities in SE Spain

NASA Astrophysics Data System (ADS)

Luna Ramos, Lourdes; Miralles Mellado, Isabel; Hernández Fernández, María Teresa; García Izquierdo, Carlos; Solé Benet, Albert

2014-05-01

Mining and quarrying activities generate negative visual impacts in the landscape and a loss of environmental quality. Substrate properties at the end of mining are in general not suitable for plant growth, even native ones. In an experimental soil restoration in limestone quarries from Sierra de Gádor (Almería), SE Spain, the effect of organic amendment (sewage sludge, compost from the organic fraction of domestic waste or non-amendment) combined or not with two different kind of mulches (fine gravel, chopped forest residue) was tested by triplicate in 5 x 5 m plots with the aim to improve soil/substrate properties and to reduce evaporation and erosion. In each experimental plot 75 native plants (Stipa tenacissima, Anthyllis terniflora and Anthyllis cytisoides) were planted. Effects of adding organic amendments and mulches on some soil microbiological and biochemical parameters (microbial biomass carbon, basal respiration and different enzymatic activities, such as dehydrogenase, phosphatase, β-glucosidase and urease) were analyzed 5 years after the start of the experiment. Vegetation growth was also monitored. The two-way ANOVA, using as factors amendment and mulch, showed a significant positive influence of organic amendments on microbial biomass (Cmic), basal respiration and some enzymatic activities related to the cycles of C and N. The highest values of these parameters were obtained with compost. The influence of the mulch factor and its interactions with the amendment factor on the measured variables did not follow a clear trend with respect the measured parameters. Mulching did not improved significantly (p<0.05) the positive effect of organic amendments on Cmic although Cmic values increased with the incorporation of "forest chopped residue" and decreased with gravel incorporation. In general, both type of mulch decreased or have no effect on the microbial activity detected in the amended soils, with the only exception of the forest chopped residue, which increased phosphatase activity in the compost amended soil. Plant growth was significantly higher in amended soils than in the control, but it is remarkable that the mulch type "forest chopped residue" had a negative effect on vegetation growth. The addition of organic amendments, especially compost from the organic fraction of domestic wastes, is beneficial to restore degraded or man-made soils from quarrying areas because they stimulate microbial growth and activity, resulting in mineralization of nutrients necessary for plants and increasing soil fertility and quality. However, after 5 years the effects of the mulch "forest chopped residue", on the improvement of soil or substrate quality are not clear.

Chicken Picadillo

MedlinePlus

... large yellow onion, finely chopped 1 medium green pepper, finely chopped 1 medium red pepper, finely chopped 3 cloves garlic, mashed 1/3 ... large skillet over medium heat. Add the onion, peppers, and garlic, and sauté until the vegetables are ...

Generation of the novel monoclonal antibody against TLS/EWS-CHOP chimeric oncoproteins that is applicable to one of the most sensitive assays for myxoid and round cell liposarcomas.

PubMed

Oikawa, Kosuke; Ishida, Tsuyoshi; Imamura, Tetsuo; Yoshida, Keiichi; Takanashi, Masakatsu; Hattori, Hiroyuki; Ishikawa, Akio; Fujita, Koji; Yamamoto, Kengo; Matsubayashi, Jun; Kuroda, Masahiko; Mukai, Kiyoshi

2006-03-01

The fusion oncoproteins, TLS-CHOP and EWS-CHOP, are characteristic markers for myxoid and round cell liposarcomas (MLS/RCLS). Especially, the peptide sequence of 26 amino acids corresponding to the normally untranslated CHOP exon 2 and parts of exon 3 (5'-UTR) is a unique structure for these chimeric proteins. In this report, we have generated monoclonal antibodies against the unique peptide sequence of TLS/EWS-CHOP oncoproteins. These antibodies reacted with TLS-CHOP fusion protein, but not reacted with normal TLS and CHOP proteins by Western blot analysis. In addition, one of the antibodies also recognized the chimeric oncoprotein in archival paraffin-embedded tissue samples of MLS/RCLS. The oncoprotein was detectable by the antibody even in the paraffin-embedded tissue samples whose mRNAs were too degraded to be detected by a nested reverse transcription-polymerase chain reaction-based assay. Thus, the molecular assay using the novel antibody is expected to be one of the most sensitive diagnostic assays for MLS/RCLS.

Nupr1/Chop signal axis is involved in mitochondrion-related endothelial cell apoptosis induced by methamphetamine

PubMed Central

Cai, D; Huang, E; Luo, B; Yang, Y; Zhang, F; Liu, C; Lin, Z; Xie, W-B; Wang, H

2016-01-01

Methamphetamine (METH) abuse has been a serious global public health problem for decades. Previous studies have shown that METH causes detrimental effects on the nervous and cardiovascular systems. METH-induced cardiovascular toxicity has been, in part, attributed to its destructive effect on vascular endothelial cells. However, the underlying mechanism of METH-caused endothelium disruption has not been investigated systematically. In this study, we identified a novel pathway involved in endothelial cell apoptosis induced by METH. We demonstrated that exposure to METH caused mitochondrial apoptosis in human umbilical vein endothelial cells and rat cardiac microvascular endothelial cells in vitro as well as in rat cardiac endothelial cells in vivo. We found that METH mediated endothelial cell apoptosis through Nupr1–Chop/P53–PUMA/Beclin1 signaling pathway. Specifically, METH exposure increased the expression of Nupr1, Chop, P53 and PUMA. Elevated p53 expression raised up PUMA expression, which initiated mitochondrial apoptosis by downregulating antiapoptotic Bcl-2, followed by upregulation of proapoptotic Bax, resulting in translocation of cytochrome c (cyto c), an apoptogenic factor, from the mitochondria to cytoplasm and activation of caspase-dependent pathways. Interestingly, increased Beclin1, upregulated by Chop, formed a ternary complex with Bcl-2, thereby decreasing the dissociative Bcl-2. As a result, the ratio of dissociative Bcl-2 to Bax was also significantly decreased, which led to translocation of cyto c and initiated more drastic apoptosis. These findings were supported by data showing METH-induced apoptosis was significantly inhibited by silencing Nupr1, Chop or P53, or by PUMA or Beclin1 knockdown. Based on the present data, a novel mechanistic model of METH-induced endothelial cell toxicity is proposed. Collectively, these results highlight that the Nupr1–Chop/P53–PUMA/Beclin1 pathway is essential for mitochondrion-related METH-induced endothelial cell apoptosis and may be a potential therapeutic target for METH-caused cardiovascular toxicity. Future studies using knockout animal models are warranted to substantiate the present findings. PMID:27031958

Baked Pork Chops With Apple Cranberry Sauce

MedlinePlus

... chops—try serving with a side of brown rice and steamed broccoli Ingredients For pork chops: 4 boneless pork chops (about 3 oz each) 1/4 tsp ground black pepper 1 medium orange, rinsed, for 1/4 ...

The γ-secretase cleavage product of Polycystin-1 regulates TCF and CHOP-mediated transcriptional activation through a p300-dependent mechanism

PubMed Central

Merrick, David; Chapin, Hannah; Baggs, Julie E.; Yu, Zhiheng; Somlo, Stefan; Sun, Zhaoxia; Hogenesch, John B.; Caplan, Michael

2011-01-01

Summary Mutations in Pkd1, encoding polycystin-1 (PC1), cause Autosomal Dominant Polycystic Kidney Disease (ADPKD). We show that the carboxy-terminal tail (CTT) of PC1 is released by γ-secretase-mediated cleavage and regulates the Wnt and CHOP pathways by binding the transcription factors TCF and CHOP, disrupting their interaction with the common transcriptional co-activator p300. Loss of PC1 causes increased proliferation and apoptosis, while reintroducing PC1-CTT into cultured Pkd1 null cells reestablishes normal growth rate, suppresses apoptosis, and prevents cyst formation. Inhibition of γ-secretase activity impairs the ability of PC1 to suppress growth and apoptosis, and leads to cyst formation in cultured renal epithelial cells. Expression of the PC1-CTT is sufficient to rescue the dorsal body curvature phenotype in zebrafish embryos resulting from either γ-secretase inhibition or suppression of Pkd1 expression. Thus, γ-secretase-dependent release of the PC1-CTT creates a protein fragment whose expression is sufficient to suppress ADPKD-related phenotypes in vitro and in vivo. PMID:22178500

Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in the treatment of stage IE/IIE extranodal natural killer/T cell lymphoma, nasal type: 13-year follow-up in 135 patients.

PubMed

Wang, Liang; Xia, Zhong-jun; Huang, Hui-qiang; Lu, Yue; Zhang, Yu-jing

2012-11-01

We conducted a retrospective study of 135 patients of stage IE/IIE extranodal natural killer/T cell lymphoma, nasal type (ENKTL) treated with CHOP as induction chemotherapy to find some valuable prognostic factors and analyze the usefulness of International Prognostic Index (IPI) and Korean Prognostic Index (KPI) in predicting prognosis. Most of the patients were in the low-risk group (IPI score 0-1). Complete remission (CR) after induction chemotherapy was achieved in 31.8 % of the patients, which increased to 69.6 % after radiotherapy. The 2-, 5-, and 10-year overall survival (OS) rates were 60, 48, and 43 %, respectively. Patients with better performance status (ECOG 0-1), normal serum LDH level, without local invasiveness, low KPI scores, and IPI score of 0 had significantly better overall survival (P < 0.05) in univariate analysis. Using multivariate analysis, we identified serum LDH level, ECOG PS score and local invasiveness to be independent prognostic factors. In conclusion, ENKTL is an aggressive lymphoma that shows heterogeneity. The IPI and KPI score systems should be improved further to classify patients into different groups, and should be validated in larger prospective trials. Due to the multi-drug resistance mechanism of ENKTL, CHOP is no longer the state of art and novel drugs should be incorporated into future treatments.

Prodigiosin activates endoplasmic reticulum stress cell death pathway in human breast carcinoma cell lines

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

Pan, Mu-Yun; Shen, Yuh-Chiang; National Research Institute of Chinese Medicine, Taipei, Taiwan

Prodigiosin is a bacterial tripyrrole pigment with potent cytotoxicity against diverse human cancer cell lines. Endoplasmic reticulum (ER) stress is initiated by accumulation of unfolded or misfolded proteins in the ER lumen and may induce cell death when irremediable. In this study, the role of ER stress in prodigiosin-induced cytotoxicity was elucidated for the first time. Comparable to the ER stress inducer thapsigargin, prodigiosin up-regulated signature ER stress markers GRP78 and CHOP in addition to activating the IRE1, PERK and ATF6 branches of the unfolded protein response (UPR) in multiple human breast carcinoma cell lines, confirming prodigiosin as an ERmore » stress inducer. Prodigiosin transcriptionally up-regulated CHOP, as evidenced by its promoting effect on the CHOP promoter activity. Of note, knockdown of CHOP effectively lowered prodigiosin's capacity to evoke PARP cleavage, reduce cell viability and suppress colony formation, highlighting an essential role of CHOP in prodigiosin-induced cytotoxic ER stress response. In addition, prodigiosin down-regulated BCL2 in a CHOP-dependent manner. Importantly, restoration of BCL2 expression blocked prodigiosin-induced PARP cleavage and greatly enhanced the survival of prodigiosin-treated cells, suggesting that CHOP-dependent BCL2 suppression mediates prodigiosin-elicited cell death. Moreover, pharmacological inhibition of JNK by SP600125 or dominant-negative blockade of PERK-mediated eIF2α phosphorylation impaired prodigiosin-induced CHOP up-regulation and PARP cleavage. Collectively, these results identified ER stress-mediated cell death as a mode-of-action of prodigiosin's tumoricidal effect. Mechanistically, prodigiosin engages the IRE1–JNK and PERK–eIF2α branches of the UPR signaling to up-regulate CHOP, which in turn mediates BCL2 suppression to induce cell death. Highlights: ► Prodigiosin is a bacterial tripyrrole pigment with potent anticancer effect. ► Prodigiosin is herein identified as an endoplasmic reticulum (ER) stress inducer. ► Prodigiosin-induced cytotoxicity involves ER stress-mediated cell death. ► Prodigiosin transcriptionally induces CHOP to suppress BCL2 for evoking cell death. ► Prodigiosin engages the IRE1–JNK and PERK–eIF2α pathways to up-regulate CHOP.« less

Rituximab in the treatment of diffuse large B-cell lymphoma primary of the lung.

PubMed

Aviles, Agustin; Nambo, Maria J; Huerta-Guzman, Judith; Silva, Luis; Neri, Natividad

2013-03-01

Diffuse large B-cell lymphoma primary of lung (DLBCL-PL) is a rare presentation of extranodal lymphoma, in most cases chemotherapy-based anthracyclines: CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has been the treatment, with excellent outcome. The addition of rituximab to CHOP (R-CHOP) has been considered the gold standard in the treatment of nodal DLBCL. Thus, we assess in a large number of cases of DLBCL-PL whether the use of R-CHOP could improve survival in this setting of patients. Forty-two patients with DLBCL-PL, stage IE, age 65 years or younger, were treated with standard R-CHOP, no consolidation radiotherapy or maintenance therapy were considered. They were matched with patients who received CHOP alone to assess efficacy and toxicity. Complete response was observed in 35 patients (83%), and 7 patients were considered failure (16%). The study has a median follow-up of 42.8 months. Actuarial curves at 5 years showed that progression-free survival was 88 % and overall survival was 70 %. The results were not statistically different when compared retrospectively with patients who received CHOP alone. Treatment was well tolerated. The addition of rituximab to chemotherapy did not improve outcome in patients with DLBCL-PL.

Consumer visual appraisal and shelf life of leg chops from suckling kids raised with natural milk or milk replacer.

PubMed

Ripoll, Guillermo; Alcalde, María J; Argüello, Anastasio; Córdoba, María G; Panea, Begoña

2018-05-01

The use of milk replacers to feed suckling kids could affect the shelf life and appearance of the meat. Leg chops were evaluated by consumers and the instrumental color was measured. A machine learning algorithm was used to relate them. The aim of this experiment was to study the shelf life of the meat of kids reared with dam's milk or milk replacers and to ascertain which illuminant and instrumental color variables are used by consumers as criteria to evaluate that visual appraisal. Meat from kids reared with milk replacers was more valuable and had a longer shelf life than meat from kids reared with natural milk. Consumers used the color of the whole surface of the leg chop to assess the appearance of meat. Lightness and hue angle were the prime cues used to evaluate the appearance of meat. Illuminant D65 was more useful for relating the visual appraisal with the instrumental color using a machine learning algorithm. The machine learning algorithms showed that the underlying rules used by consumers to evaluate the appearance of suckling kid meat are not at all linear and can be computationally schematized into a simple algorithm. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Phosphorylcholine Allows for Evasion of Bactericidal Antibody by Haemophilus influenzae

PubMed Central

Clark, Sarah E.; Snow, Julian; Li, Jianjun; Zola, Tracey A.; Weiser, Jeffrey N.

2012-01-01

The human pathogen Haemophilus influenzae has the ability to quickly adapt to different host environments through phase variation of multiple structures on its lipooligosaccharide (LPS), including phosphorylcholine (ChoP). During colonization with H. influenzae, there is a selection for ChoP+ phase variants. In a murine model of nasopharyngeal colonization, this selection is lost in the absence of adaptive immunity. Based on previous data highlighting the importance of natural antibody in limiting H. influenzae colonization, the effect of ChoP expression on antibody binding and its bactericidal activity was investigated. Flow cytometric analysis revealed that ChoP+ phase variants had decreased binding of antibody to LPS epitopes compared to ChoP− phase variants. This difference in antibody binding correlated with increased survival of ChoP+ phase variants in the presence of antibody-dependent, complement-mediated killing. ChoP+ phase variants were also more resistant to trypsin digestion, suggesting a general effect on the physical properties of the outer membrane. Moreover, ChoP-mediated protection against antibody binding correlated with increased resilience of outer membrane integrity. Collectively, these data suggest that ChoP expression provides a selective advantage during colonization through ChoP-mediated effects on the accessibility of bactericidal antibody to the cell surface. PMID:22396641

[In vitro drug release behavior of carrier made of porous glass ceramics].

PubMed

Wang, De-ping; Huang, Wen-hai; Zhou, Nai

2002-09-01

To conduct the in vitro test on drug release of rifampin encapsulated in a carrier made of porous phosphate glass ceramics and to analyze main factors which affect the drug release rate. A certain quantitative of rifampin was sealed in a hollow cylindrical capsule which consisted of chopped calcium phosphate crystal fiber obtained from glass crystallization. The rifampin concentration was measured in the simulated physiological solution in which the capsule soaked. Rifampin could be released in a constant rate from the porous glass ceramic carrier in a long time. The release rate was dependent on the size of crystal fiber and the wall thickness of the capsule. This kind of calcium phosphate glass ceramics can be a candidate of the carrier materials used as long term drug therapy after osteotomy surgery.

Effects of Feeding Purple Rice (Oryza sativa L. Var. Glutinosa) on the Quality of Pork and Pork Products

PubMed Central

Jaturasitha, Sanchai; Ratanapradit, Punnares; Piawong, Witapong; Kreuzer, Michael

2016-01-01

Purple rice is a strain of glutaneous rice rich in anthocyanins and γ-oryzanol. Both types of compounds are involved in antioxidant and lipid metabolism of mammals. Three experimental diet types were used which consisted approximately by half either of purple rice, white rice or corn. Diets were fed to 3×10 pigs growing from about 30 to 100 kg. Meat samples were investigated either as raw or cured loin chops or as smoked bacon produced from the belly. Various physicochemical traits were assessed and data were evaluated by analysis of variance. Traits describing water-holding capacity (drip, thaw, and cooking losses) and tenderness (sensory grading, shear force) of the meat were mostly not significantly affected by the diet type. However, purple rice feeding of pigs resulted in lower fat and cholesterol contents of loin and smoked bacon compared to white rice, but not compared to corn feeding except of the fat content of the loin. The shelf life of the raw loin chops was improved by purple rice as well. In detail, the occurrence of thiobarbituric acid reactive substances after 9 days of chilled storage was three to four times higher in the white rice and corn diets than with purple rice. The n-6:n-3 ratio in the raw loin chops was 9:1 with purple rice and clearly higher with 12:1 with the other diets, meat lipids. Level and kind of effect of purple rice found in raw meat was not always recovered in the cured loin chops and the smoked bacon. Still the impression of flavor and color, as well as overall acceptability were best in the smoked bacon from the purple-rice fed pigs, whereas this effect did not occur in the cured loin chops. These findings suggest that purple rice has a certain, useful, bioactivity in pigs concerning meat quality, but some of these effects are of low practical relevance. Further studies have to show ways how transiency and low recovery in meat products of some of the effects can be counteracted. PMID:26949957

Factors that influence baled silage fermentation

USDA-ARS?s Scientific Manuscript database

Baled silage is an attractive management option for many forage and livestock producers. Most principles involved in making well-preserved, baled silage are similar to those required for precision-chopped silages. Generally, the overall goal is identical: create an anaerobic environment in which pla...

Serum lactate dehydrogenase with a systemic inflammation score is useful for predicting response and survival in patients with newly diagnosed diffuse large B-cell lymphoma.

PubMed

Jung, Sung-Hoon; Yang, Deok-Hwan; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Kim, Hyeoung-Joon; Lee, Je-Jung

2015-01-01

We evaluated the relationship between serum lactate dehydrogenase (LDH) level with systemic inflammation score and survival in 213 patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP chemotherapy. The patients were classified into 3 groups based on LDH with the Glasgow Prognostic Score (L-GPS). A score of 2 was assigned to patients with elevated C-reactive protein, hypoalbuminemia and elevated LDH, a score of 1 to those with one or two abnormalities and a score of 0 to those with no abnormality. In multivariate analysis, independent poor prognostic factors for progression-free survival were L-GPS 2 [hazard ratio (HR) 5.415, p = 0.001], Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (HR 3.504, p = 0.001) and bulky lesion (HR 2.030, p = 0.039). Independent poor prognostic factors for overall survival were L-GPS 2 (HR 5.898, p = 0.001) and ECOG PS ≥2 (HR 3.525, p = 0.001). The overall response rate for the R-CHOP chemotherapy decreased according to the L-GPS; it was 96.7% at L-GPS 0, 87% at L-GPS 1 and 75% at L-GPS 2 (p = 0.009). L-GPS based on systemic inflammatory indicators may be a useful clinical prognostic indicator for survival, and predicts the response for R-CHOP chemotherapy in patients with newly diagnosed DLBCL. © 2014 S. Karger AG, Basel.

ISO Key Project: Exploring the full range of QUASAR/AGN properties

NASA Technical Reports Server (NTRS)

Wilkes, B.

1998-01-01

The PIA (PHOT Interactive Analysis) software was upgraded as new releases were made available by VILSPA. We have continued to analyze our data but, given the large number of still outstanding problems with the calibration and analysis (listed below), we remain unable to move forward on our scientific program. We have concentrated on observations with long (256 sec) exposure times to avoid the most extreme detector responsivity drift problems which occur with a change in observed flux level, ie. as one begins to observe a new target. There remain a significant number of problems with analyzing these data including: (1) the default calibration source (FCS) observations early in the mission were too short and affected by strong detector responsivity drifts; (2) the calibration of the FCS sources is not yet well-understood, particularly for chopped observations (which includes most of ours); (3) the detector responsivity drift is not well-understood and models are only now becoming available for fitting chopped data; (4) charged particle hits on the detector cause transient responsivity drifts which need to be corrected; (5) the "flat-field" calibration of the long-wavelength (array) detectors: C1OO, C200 leaves significant residual structure and so needs to be improved;(6) the vignetting correction, which affects detected flux levels in the array detectors, is not yet available; (7) the intra-filter calibrations are not yet available; and (8) the background above 60 microns has a significant gradient which results in spurious positive and negative "detections" in chopped observations. ISO Observation planning, conferences and talks, ground based observing and other grant related activities are also briefly discussed.

9 CFR 381.401 - Required nutrition labeling of ground or chopped poultry products.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Required nutrition labeling of ground or chopped poultry products. 381.401 Section 381.401 Animals and Animal Products FOOD SAFETY AND... Nutrition Labeling § 381.401 Required nutrition labeling of ground or chopped poultry products. Nutrition...

9 CFR 381.401 - Required nutrition labeling of ground or chopped poultry products.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Required nutrition labeling of ground or chopped poultry products. 381.401 Section 381.401 Animals and Animal Products FOOD SAFETY AND... Nutrition Labeling § 381.401 Required nutrition labeling of ground or chopped poultry products. Nutrition...

9 CFR 317.301 - Required nutrition labeling of ground or chopped meat products.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Required nutrition labeling of ground or chopped meat products. 317.301 Section 317.301 Animals and Animal Products FOOD SAFETY AND... Nutrition Labeling § 317.301 Required nutrition labeling of ground or chopped meat products. (a) Nutrition...

9 CFR 317.301 - Required nutrition labeling of ground or chopped meat products.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Required nutrition labeling of ground or chopped meat products. 317.301 Section 317.301 Animals and Animal Products FOOD SAFETY AND... Nutrition Labeling § 317.301 Required nutrition labeling of ground or chopped meat products. (a) Nutrition...

9 CFR 317.301 - Required nutrition labeling of ground or chopped meat products.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Required nutrition labeling of ground or chopped meat products. 317.301 Section 317.301 Animals and Animal Products FOOD SAFETY AND... Nutrition Labeling § 317.301 Required nutrition labeling of ground or chopped meat products. (a) Nutrition...

9 CFR 317.301 - Required nutrition labeling of ground or chopped meat products.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Required nutrition labeling of ground or chopped meat products. 317.301 Section 317.301 Animals and Animal Products FOOD SAFETY AND... Nutrition Labeling § 317.301 Required nutrition labeling of ground or chopped meat products. (a) Nutrition...

9 CFR 381.401 - Required nutrition labeling of ground or chopped poultry products.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Required nutrition labeling of ground or chopped poultry products. 381.401 Section 381.401 Animals and Animal Products FOOD SAFETY AND... Nutrition Labeling § 381.401 Required nutrition labeling of ground or chopped poultry products. Nutrition...

9 CFR 381.401 - Required nutrition labeling of ground or chopped poultry products.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Required nutrition labeling of ground or chopped poultry products. 381.401 Section 381.401 Animals and Animal Products FOOD SAFETY AND... Nutrition Labeling § 381.401 Required nutrition labeling of ground or chopped poultry products. Nutrition...

Combined chemoradiation for the management of nasal natural killer (NK)/T-cell lymphoma: elucidating the significance of systemic chemotherapy.

PubMed

Guo, Ye; Lu, Jiade J; Ma, Xuejun; Wang, Biyun; Hong, Xiaonan; Li, Xiaoqiu; Li, Jin

2008-01-01

The objective of this analysis was to evaluate the efficacy and treatment outcome of CHOP and CHOP combined with nitrosourea chemotherapy in natural killer (NK)/T-cell lymphoma of the nasal cavity. Sixty-three patients with NK/T-cell lymphoma of the nasal cavity were treated with CHOP or CHOP combined with oral nitrosourea chemotherapy between January 1997 and June 2005. By the Ann Arbor Lymphoma Staging Classification, 57 patients (90%) had Stage IE or IIE disease and six patients (10%) had Stage III or IV disease. All patients with Stage IE or IIE disease were intended to be treated curatively with combined chemoradiation; and patients who had Stage III or IV disease were treated with chemotherapy alone with curative intention. Chemotherapy consisted of: (1) up to six cycles of the standard CHOP based regimen, or (2) up to six cycles of the standard CHOP based regimen with oral Semustine dosed at 120 mg (or Lomustine dosed at 100mg) on day 1 of each chemotherapy cycle. External beam radiation therapy was delivered by daily conventional fractionation by Co-60 or 6MVx linear accelerator for patients with Stage IE or IIE disease. The radiation dose to the tumor bed was between 36 and 50 Gy with a median dose of 45 Gy. Fifty-three patients received chemotherapy prior to radiation, and four patients were treated with involved field radiation before chemotherapy. The median follow up for all 44 surviving patients was 31 months (range: 6-104 months). The 2-year progression-free survival (PFS) and overall survival (OS) rates were 60% and 70%, respectively. The PFS and OS of patients who were treated with or without oral nitrosourea in addition to CHOP were 73% vs. 44% (P=0.035) and 75% vs. 64% (P=0.276), respectively. Nine patients with Stage IE or IIE diseases developed disease progression during their planned treatment and died within 10 months after the initiation of treatment; Six patients who achieved complete response (CR) after planned chemoradiation developed systemic recurrence and died at 13-48 months despite salvage treatment; one patient died of Hemophagocytic Syndrome during radiotherapy after achieving CR from chemotherapy. Three patients with Stage III or IV disease died during chemotherapy or during salvage treatment at 2, 4, and 19 months, respectively. Among the 59 patients who received chemotherapy as their initial treatment, 29, 6, 12, and 12 patients had complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) respectively after chemotherapy. The 2-year overall survival rates for these four groups of patients were 100%, 75%, 60%, and 17%, respectively (P<0.0001). Multivariate analysis revealed that International Prognostic Index (IPI) for Lymphoma, perforation of nasal septum as a presenting symptom, "B" symptoms, ECOG performance, as well as response after chemotherapy, were significant independent prognostic factors for this group of patients. The extent of response after induction chemotherapy is significantly related to the treatment outcome of patients with nasal NK/T-cell lymphoma. CHOP based chemotherapy combined with oral nitrosourea followed by involved field radiotherapy may provide improved treatment results compared to conventional CHOP chemotherapy and radiation. This strategy needs to be optimized and tested in a prospective trial for its efficacy.

Involved Field Radiation After Autologous Stem Cell Transplant for Diffuse Large B-Cell Lymphoma in the Rituximab Era

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

Biswas, Tithi; Dhakal, Sughosh; Chen Rui

2010-05-01

Purpose: For patients with recurrent or refractory large B-cell non-Hodgkin's lymphoma, high-dose chemotherapy and autologous stem cell transplant (ASCT) is the treatment of choice. We evaluated the role of involved field radiation therapy (IFRT) post-ASCT for patients initially induced with cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) or, more recently, rituximab-CHOP (R-CHOP). Materials and Methods: Between May 1992 and April 2005, 176 patients underwent ASCT for recurrent or refractory large B-cell non-Hodgkin's lymphoma; 164 patients were evaluable for endpoint analysis. Fifty percent of the CHOP group (n = 131), and 39% of the R-CHOP group (n = 33), received IFRT. Follow-upmore » from the time of transplant was a median/mean of 1.7/3 years (range, 0.03-13 years). Results: The 5-year overall survival (OS) and disease-specific survival (DSS) improved with IFRT in both the R-CHOP (p = 0.006 and 0.02, respectively) and CHOP (p = 0.02 and p = 0.04, respectively) groups. IFRT was associated with a 10% (p = 0.17) reduction in local failure, alone or with a distant site. On univariate analysis, IFRT was associated with superior OS (hazard ratio [HR] = 0.50 [95% CI 0.32, 0.78]; p = 0.002) and DSS (HR = 0.53 [95% CI 0.33, 0.86]; p = 0.009). Presence of B symptoms was adverse (p = 0.03). On multivariate analysis, only IFRT was associated with significant improvement in OS (HR = 0.35 [0.18, 0.68]; p = 0.002) and DSS (HR = 0.39 [95% CI 0.18, 0.84]; p = 0.01). Conclusions: Recognizing that positive and negative patient selection bias exists for the use of IFRT post-ASCT, patients initially treated with CHOP or R-CHOP and who undergo ASCT for recurrent or refractory disease may benefit from subsequent IFRT presumably due to enhanced local control that can translate into a survival advantage.« less

Comparison between Antiemetic Effects of Palonosetron and Granisetron on Chemotherapy-Induced Nausea and Vomiting in Japanese Patients Treated with R-CHOP.

PubMed

Uchida, Mayako; Mori, Yasuo; Nakamura, Tsutomu; Kato, Koji; Kamezaki, Kenjiro; Takenaka, Katsuto; Shiratsuchi, Motoaki; Kadoyama, Kaori; Miyamoto, Toshihiro; Akashi, Koichi

2017-01-01

In the present study, the antiemetic effect of palonosetron, not combined with dexamethasone and aprepitant, on chemotherapy-induced nausea and vomiting was evaluated in patients with malignant lymphoma receiving first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy, and was compared to that of granisetron. A total of 74 patients with non-Hodgkin lymphoma were included in this study (April 2007 to December 2015). Palonosetron (0.75 mg) or granisetron (3 mg) was intravenously administered before R-CHOP therapy. The proportions of patients with complete response (CR) during the overall (0-120 h after the start of R-CHOP therapy), acute (0-24 h) and delayed (24-120 h) phases were evaluated. CR was defined as no vomiting and no use of antiemetic rescue medication. A total of 32 and 42 patients were treated with palonosetron and granisetron, respectively. The CR rate in the palonosetron group was significantly higher than that in the granisetron group during the delayed phase (90.6 and 61.9%, respectively; p=0.007). Logistic regression analysis showed that use of palonosetron improved the CR rate during the delayed phase, compared to use of granisetron. Female sex, age less than 60 years, no habitual alcohol intake, and Eastern Cooperative Oncology Group performance status (ECOG-PS) score of 1 were significant risk factors associated with non-CR. The findings of this study suggested the superiority of palonosetron to granisetron, without accompanying dexamethasone and aprepitant, for chemotherapy-induced nausea and vomiting in patients with malignant lymphoma.

Clinical Significance of Non-neutropenic Fever in the Management of Diffuse Large B-Cell Lymphoma Patients Treated with Rituximab-CHOP: Comparison with Febrile Neutropenia and Risk Factor Analysis.

PubMed

Park, Silvia; Kang, Cheol-In; Chung, Doo Ryeon; Peck, Kyong Ran; Kim, Won Seog; Kim, Seok Jin

2015-07-01

Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard chemotherapy in diffuse large B-cell lymphoma (DLBCL) patients. Although febrile neutropenia (FN) is the major toxicity of this regimen, non-neutropenic fever (NNF) becomes an emerging issue. We analyzed clinical features and outcomes of febrile complications from 397 patients with newly diagnosed DLBCL who were registered in the prospective cohort study. They had completed R-CHOP between September 2008 and January 2013. Thirty-nine patients (9.8%) had NNF whereas 160 patients (40.3%) had FN. Among them, 24 patients (6.0%) had both during their treatment. Compared to frequent occurrence of initial FN after the first cycle (> 50% of total events), more than 80% of NNF cases occurred after the third cycle. Interstitial pneumonitis comprised the highest proportion of NNF cases (54.8%), although the causative organism was not identified in the majority of cases. Thus, pathogen was identified in a limited number of patients (n=9), and Pneumocystis jiroveci pneumonia (PJP) was the most common. Considering that interstitial pneumonitis without documented pathogen could be clinically diagnosed with PJP, the overall rate of PJP including probable cases was 4.5% (18 cases from 397 patients). The NNF-related mortality rate was 10.3% (four deaths from 39 patients with NNF) while the FN-related mortality rate was only 1.3%. NNF was observed with incidence of 10% during R-CHOP treatment, and showed different clinical manifestations with respect to the time of initial episode and causes.

Comparison of gemcitabin, cisplatin, and dexamethasone (GDP), CHOP, and CHOPE in the first-line treatment of peripheral T-cell lymphomas.

PubMed

Jia, Bo; Hu, Shaoxuan; Yang, Jianliang; Zhou, Shengyu; Liu, Peng; Qin, Yan; Gui, Lin; Yang, Sheng; Lin, Hua; Zhang, Changgong; Xing, Puyuan; Wang, Lin; Dong, Mei; Zhou, Liqiang; Sun, Yan; He, Xiaohui; Shi, Yuankai

2016-10-01

Optimal chemotherapy regimen for peripheral T-cell lymphomas (PTCL) has not been fully defined. This study aimed to evaluate the optimal chemotherapy regimen in the first-line treatment for PTCL patients. Between 2003 and 2014, 93 consecutive patients with PTCL were enrolled in this study. Of 93 patients, 42 patients received CHOPE, 40 patients with CHOP, and 11 patients with GDP regimen. Response could be evaluated in 88 of 93 patients at the end of primary treatment. The CR rate for patients received CHOP (n = 38), CHOPE (n = 39), and GDP (n = 11) were 28.9, 51.3, and 45.5%, respectively, (P = 0.132) with an ORR of 65.8, 76.9, and 90.9%, respectively, (P = 0.210). The median follow-up time was 17.1 (1.4-108.3) months. Median progression-free survival (PFS) in CHOP (n = 40), CHOPE (n = 42), and GDP (n = 11) groups were 6.0, 15.3, and 9.7 months (P = 0.094) with 1-year PFS of 35.0, 54.8, and 45.5%, respectively, (P = 0.078). One-year OS for patients received CHOP (n = 40), CHOPE (n = 42), and GDP (n = 11) were 65.0, 83.3, and 100%, respectively, (P = 0.013) (CHOP vs CHOPE, P = 0.030; CHOP vs GDP, P = 0.024; CHOPE vs GDP, P = 0.174). CHOPE has a trend to improve CR rate, 1-year PFS and OS compared with CHOP alone. GDP shows promising efficacy which worth further exploration in large cohort studies. Clinical experience presented in this study may serve as reference for future large cohort studies.

Search for potent attractants of onion flies.

PubMed

Miller, J R; Harris, M O; Breznak, J A

1984-10-01

Of various chopped vegetables tested,Allium spp. high in propyl-containing alkyl sulfides (e.g.,cepa group) caught the most onion flies in trapping tests in the field. Fly catches to chopped onion increased with bait quantity. Attractancy of chopped onion changed dramatically during aging in the field; catch increased over the first few days, peaked at ca. fivefold over fresh material by 3-5 days, and then declined sharply. This age-dependent increase in attraction was not seen for garlic (known to have antimicrobial properties) nor with chopped onion mixed with chopped garlic. These data suggested that attraction of onion flies to onions was strongly influenced by microbial activity associated with decomposing onions. The bacteriumKlebsiella pneumoniae was identified as a major colonizer of onions maximally attractive to onion flies. This increased attraction is not due to the previously reported microbially produced volatiles ethyl acetate and tetramethyl pyrazine.

Identification of residues within the African swine fever virus DP71L protein required for dephosphorylation of translation initiation factor eIF2α and inhibiting activation of pro-apoptotic CHOP

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

Barber, Claire; Netherton, Chris; Goatley, Lynnett

The African swine fever virus DP71L protein recruits protein phosphatase 1 (PP1) to dephosphorylate the translation initiation factor 2α (eIF2α) and avoid shut-off of global protein synthesis and downstream activation of the pro-apoptotic factor CHOP. Residues V16 and F18A were critical for binding of DP71L to PP1. Mutation of this PP1 binding motif or deletion of residues between 52 and 66 reduced the ability of DP71L to cause dephosphorylation of eIF2α and inhibit CHOP induction. The residues LSAVL, between 57 and 61, were also required. PP1 was co-precipitated with wild type DP71L and the mutant lacking residues 52- 66 ormore » the LSAVL motif, but not with the PP1 binding motif mutant. The residues in the LSAVL motif play a critical role in DP71L function but do not interfere with binding to PP1. Instead we propose these residues are important for DP71L binding to eIF2α. - Highlights: •The African swine fever virus DP71L protein recruits protein phosphatase 1 (PP1) to dephosphorylate translation initiation factor eIF2α (eIF2α). •The residues V{sup 16}, F{sup 18} of DP71L are required for binding to the α, β and γ isoforms of PP1 and for DP71L function. •The sequence LSAVL downstream from the PP1 binding site (residues 57–61) are also important for DP71L function. •DP71L mutants of the LSAVL sequence retain ability to co-precipitate with PP1 showing these sequences have a different role to PP1 binding.« less

Microbial modulation of host immunity with the small molecule phosphorylcholine.

PubMed

Clark, Sarah E; Weiser, Jeffrey N

2013-02-01

All microorganisms dependent on persistence in a host for survival rely on either hiding from or modulating host responses to infection. The small molecule phosphorylcholine, or choline phosphate (ChoP), is used for both of these purposes by a wide array of bacterial and parasitic microbes. While the mechanisms underlying ChoP acquisition and expression are diverse, a unifying theme is the use of ChoP to reduce the immune response to infection, creating an advantage for ChoP-expressing microorganisms. In this minireview, we discuss several benefits of ChoP expression during infection as well as how the immune system fights back against ChoP-expressing pathogens.

Association between quality of response and outcomes in patients with newly diagnosed mantle cell lymphoma receiving VR-CAP versus R-CHOP in the phase 3 LYM-3002 study.

PubMed

Verhoef, Gregor; Robak, Tadeusz; Huang, Huiqiang; Pylypenko, Halyna; Siritanaratkul, Noppadol; Pereira, Juliana; Drach, Johannes; Mayer, Jiri; Okamoto, Rumiko; Pei, Lixia; Rooney, Brendan; Cakana, Andrew; van de Velde, Helgi; Cavalli, Franco

2017-05-01

In the phase 3 LYM-3002 study comparing intravenous VR-CAP with R-CHOP in patients with newly-diagnosed, measurable stage II-IV mantle cell lymphoma, not considered or ineligible for transplant, the median progression-free survival was significantly improved with VR-CAP (24.7 versus 14.4 months with R-CHOP; P <0.001). This post-hoc analysis evaluated the association between the improved outcomes and quality of responses achieved with VR-CAP versus R-CHOP in LYM-3002. Patients were randomized to six to eight 21-day cycles of VR-CAP or R-CHOP. Outcomes included progression-free survival, duration of response (both assessed by an independent review committee), and time to next anti-lymphoma treatment, evaluated by response (complete response/unconfirmed complete response and partial response), MIPI risk status, and maximum reduction of lymph-node measurements expressed as the sum of the product of the diameters. Within each response category, the median progression-free survival was longer for patients given VR-CAP than for those given R-CHOP (complete response/unconfirmed complete response: 40.9 versus 19.8 months; partial response: 17.1 versus 11.7 months, respectively); similarly, the median time to next anti-lymphoma treatment was longer among the patients given VR-CAP than among those treated with R-CHOP (complete response/unconfirmed complete response: not evaluable versus 26.6 months; partial response: 35.3 versus 24.3 months). Within the complete/unconfirmed complete and partial response categories, improvements in progression-free survival, duration of response and time to next anti-lymphoma treatment were more pronounced in patients with low-and intermediate-risk MIPI treated with VR-CAP than with R-CHOP. In each response category, more VR-CAP than R-CHOP patients had a sum of the product of the diameters nadir of 0 during serial radiological assessments. Results of this post-hoc analysis suggest a greater duration and quality of response in patients treated with VR-CAP in comparison with those treated with R-CHOP, with the improvements being more evident in patients with low- and intermediate-risk MIPI. LYM-3002 ClinicalTrials.gov: NCT00722137 . Copyright© Ferrata Storti Foundation.

The Many Facets of Lipooligosaccharide as a Virulence Factor for Histophilus somni.

PubMed

Inzana, Thomas J

2016-01-01

The lipooligosaccharide (LOS) of Histophilus somni is a multifaceted molecule that provides critical protection to the bacterium against host defenses, may act as an adhesin, and like similar molecules of gram-negative bacteria, is an endotoxin that signals through toll-like receptor 4 and NF-κB to cause inflammation. The lipid A component is responsible for the endotoxic and apoptotic activity of the LOS. The H. somni LOS lacks O-side chains typically characteristic of gram-negative bacteria that have lipopolysaccharide, but has a complex, microheterogeneous outer core. The LOS of disease isolates is capable of undergoing structural and antigenic phase variation of its outer core due to slip-strand mispairing of glycosyltransferase genes that contain repetitive sequences of DNA base pairs. Such variation enables the bacteria to evade bactericidal antibodies made to oligosaccharide antigens. In addition, the LOS can be decorated with phase-variable phosphorylcholine (ChoP), which binds to platelet-activating factor receptor on host cells, thereby aiding in colonization of the upper respiratory tract. However, ChoP is likely not expressed when the bacteria are in systemic sites because ChoP also binds to C-reactive protein, resulting in activation of host complement and promoting bactericidal activity. The structure of some LOS outer core chains is identical to oligosaccharides on host glycosphingolipids of red blood cells, other cells, and merconium (lacto-N-neotetraose, lacto-N-biose, N-acetyllactosamine, etc.). Furthermore, terminal galactose residues on LOS and elsewhere are decorated with sialic acid, which blocks antibody binding, activation of complement, phagocytosis, and intracellular killing. Therefore, antigenic mimicry of host antigens is an important defense mechanism provided by the oligosaccharide component of the LOS to avoid innate and adaptive host defense mechanisms. However, some strains of H. somni isolated from the bovine genital tract, particularly the normal bovine prepuce, are incapable of LOS phase variation, sialylation of the LOS, and expression of ChoP. At least 1 such strain has been shown to be avirulent, underscoring the importance of the LOS as a virulence factor, although this strain is deficient in other factors as well. The structure and arrangement of the inner core glycoses (heptose and 3-deoxy-D-manno-2-octulosnic acid) is remarkably similar to the inner core oligosaccharide on some strains of Neisseria spp., and mutants that contain a truncated LOS oligosaccharide are considerably more serum-sensitive than the parent strain. Therefore, the LOS is a critical component that enables H. somni to resist host defenses and cause disease.

Fruiting of browse plants affected by pine site preparation in east Texas

Treesearch

John J. Stransky; Douglas Richardson

1977-01-01

Pine planting sites prepared by burning yielded 120 kg/ha of browse fruits the third growing season after site treatment. Control plots yielded 74, KG-bladed plots 57, and chopped plots 41 kg/ha. Blackberries, American beautyberry, sumac, Sebastian bush, muscadine grape, blueberries, and southern wax-myrtle were the principal species. Most fruit was available in summer...

Cotton Chopping to Administrative Chairperson: The Changing Role of Women on Small Farms.

ERIC Educational Resources Information Center

Smith, Joyce L.; Jenkins, Quentin A. L.

The objectives of this case study are to determine the personal, family, and community interactions of women on small farms, to determine how women on small farms are affected by social and cultural change, and to determine the influence of significant and generalized others on the behavior of women on small farms. The theoretical framework…

Effect of the type of frying culinary fat on volatile compounds isolated in fried pork loin chops by using SPME-GC-MS.

PubMed

Ramírez, María Rosario; Estévez, Mario; Morcuende, David; Cava, Ramón

2004-12-15

The effect of the type of frying culinary fat (olive oil, sunflower oil, butter, and pig lard) on volatile compounds isolated from fried pork loin chops (m. Longissimus dorsi) was measured by SPME-GC-MS. Frying modified the fatty acid composition of lipids from pork loin chops, which tended to be similar to that of the culinary fat used to fry. Volatile compounds formed from the oxidation of fatty acids increased, such as aldehydes, ketones, alcohols, and hydrocarbons. Besides, each culinary fat used modified the volatile profiles in fried meat differently. Sunflower oil-fried pork loin chops presented the highest aldehyde aliphatic content, probably due to their highest content of polyunsaturated acids. Hexanal, the most abundant aldehyde in fried samples, presented the most elevated content in sunflower oil-fried pork loin chops. In addition, these samples presented more heterocyclic compounds from the Maillard reaction than other fried samples. Volatiles detected in olive oil-fried pork loin chops were mainly lipid-derived compounds such as pentan-1-ol, hexanal, hept-2-enal, nonanal, decanal, benzaldehyde, and nonan-2-one. Butter-fried pork loins were abundant in ketones with a high number of carbons (heptan-2-one, nonan-2-one, undecan-2-one, tridecanone, and heptadecan-2-one). Pig lard-fried pork loin chops presented some Strecker aldehydes isolated in only these samples, such as 2-methylbutanal and 3-(methylthio)propanal, and a sulfur compound (dimethyl disulfide) related to Strecker aldehydes.

Enrichment, isolation, and virulence of freeze-stressed plasmid-bearing virulent strains of Yersinia enterocolitica on pork.

PubMed

Bhaduri, Saumya

2006-08-01

The influence of freeze stress at -20 degrees C on the enrichment, isolation, detection, presence of virulence plasmid, and expression of virulence of plasmid-bearing Yersinia enterocolitica (YEP+) inoculated on pork chop medallions was assessed. Pork chop medallions (10 cm2) artificially contaminated with 10, 1, and 0.5 CFU/cm2 of YEP+ strains (serotype O:3) were placed in sterile petri dishes at -20 degrees C for 24 h. The medallions were swabbed when frozen, after thawing at room temperature for 1.5 h and after thawing at 4 degrees C for 18 h. Swabs were enriched and YEP+ were detected and isolated using the Congo red-binding and low-calcium-response assays. The YEP+ were isolated under all conditions on pork chop medallions inoculated with 10 CFU/cm2 and at a level of 1 CFU/cm2 when thawed at room temperature and at 4 degrees C but not from frozen pork chop medallions. The YEP+ were not isolated from pork chop medallions inoculated with 0.5 CFU/cm2 and then frozen, whereas YEP+ were recovered when inoculated at this level from pork chop medallions not subjected to freezing. Virulence of the strains isolated from frozen pork chop medallions was confirmed by PCR and the expression of plasmid-associated phenotypes. These results indicate that YEP+ subjected to freezing on pork are potentially capable of causing foodborne illness and that freezing is not a substitute for safe handling and proper cooking of pork.

Protein Oxidation and Sensory Quality of Brine-Injected Pork Loins Added Ascorbate or Extracts of Green Tea or Maté during Chill-Storage in High-Oxygen Modified Atmosphere.

PubMed

Jongberg, Sisse; Tørngren, Mari Ann; Skibsted, Leif H

2018-01-15

Background: Ascorbate is often applied to enhance stability and robustness of brine-injected pork chops sold for retail, but may affect protein oxidation, while plant extracts are potential substitutes. Methods: Brine-injected pork chops (weight-gain ~12%, NaCl ~0.9%) prepared with ascorbate (225 ppm), green tea extract (25 ppm gallic acid equivalents (GAE)), or maté extract (25 ppm GAE) stored (5 °C, seven days) in high-oxygen atmosphere packaging (MAP: 80% O₂ and 20% CO₂) were analyzed for color changes, sensory quality, and protein oxidation compared to a control without antioxidant. Results: No significant differences were observed for green tea and maté extracts as compared to ascorbate when evaluated based on lipid oxidation derived off-flavors, except for stale flavor, which maté significantly reduced. All treatments increased the level of the protein oxidation product, α-aminoadipic semialdehyde as compared to the control, and ascorbate was further found to increase thiol loss and protein cross-linking, with a concomitant decrease in the sensory perceived tenderness. Conclusions: Green tea and maté were found to equally protect against lipid oxidation derived off-flavors, and maté showed less prooxidative activity towards proteins as compared to ascorbate, resulting in more tender meat. Maté is a valuable substitute for ascorbate in brine-injected pork chops.

Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL): A Multicenter, Randomized Phase III Trial.

PubMed

Dührsen, Ulrich; Müller, Stefan; Hertenstein, Bernd; Thomssen, Henrike; Kotzerke, Jörg; Mesters, Rolf; Berdel, Wolfgang E; Franzius, Christiane; Kroschinsky, Frank; Weckesser, Matthias; Kofahl-Krause, Dorothea; Bengel, Frank M; Dürig, Jan; Matschke, Johannes; Schmitz, Christine; Pöppel, Thorsten; Ose, Claudia; Brinkmann, Marcus; La Rosée, Paul; Freesmeyer, Martin; Hertel, Andreas; Höffkes, Heinz-Gert; Behringer, Dirk; Prange-Krex, Gabriele; Wilop, Stefan; Krohn, Thomas; Holzinger, Jens; Griesshammer, Martin; Giagounidis, Aristoteles; Raghavachar, Aruna; Maschmeyer, Georg; Brink, Ingo; Bernhard, Helga; Haberkorn, Uwe; Gaska, Tobias; Kurch, Lars; van Assema, Daniëlle M E; Klapper, Wolfram; Hoelzer, Dieter; Geworski, Lilli; Jöckel, Karl-Heinz; Scherag, André; Bockisch, Andreas; Rekowski, Jan; Hüttmann, Andreas

2018-05-11

Purpose Interim positron emission tomography (PET) using the tracer, [ 18 F]fluorodeoxyglucose, may predict outcomes in patients with aggressive non-Hodgkin lymphomas. We assessed whether PET can guide therapy in patients who are treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Patients and Methods Newly diagnosed patients received two cycles of CHOP-plus rituximab (R-CHOP) in CD20-positive lymphomas-followed by a PET scan that was evaluated using the ΔSUV max method. PET-positive patients were randomly assigned to receive six additional cycles of R-CHOP or six blocks of an intensive Burkitt's lymphoma protocol. PET-negative patients with CD20-positive lymphomas were randomly assigned or allocated to receive four additional cycles of R-CHOP or the same treatment with two additional doses rituximab. The primary end point was event-free survival time as assessed by log-rank test. Results Interim PET was positive in 108 (12.5%) and negative in 754 (87.5%) of 862 patients treated, with statistically significant differences in event-free survival and overall survival. Among PET-positive patients, 52 were randomly assigned to R-CHOP and 56 to the Burkitt protocol, with 2-year event-free survival rates of 42.0% (95% CI, 28.2% to 55.2%) and 31.6% (95% CI, 19.3% to 44.6%), respectively (hazard ratio, 1.501 [95% CI, 0.896 to 2.514]; P = .1229). The Burkitt protocol produced significantly more toxicity. Of 754 PET-negative patients, 255 underwent random assignment (129 to R-CHOP and 126 to R-CHOP with additional rituximab). Event-free survival rates were 76.4% (95% CI, 68.0% to 82.8%) and 73.5% (95% CI, 64.8% to 80.4%), respectively (hazard ratio, 1.048 [95% CI, 0.684 to 1.606]; P = .8305). Outcome prediction by PET was independent of the International Prognostic Index. Results in diffuse large B-cell lymphoma were similar to those in the total group. Conclusion Interim PET predicted survival in patients with aggressive lymphomas treated with R-CHOP. PET-based treatment intensification did not improve outcome.

Food processing and structure impact the metabolizable energy of almonds

USDA-ARS?s Scientific Manuscript database

The measured metabolizable energy (ME) of whole almonds has been shown to be less than predicted by Atwater factors. However, data are lacking on the effects of processing (roasting, chopping or grinding) on the ME of almonds. A 5-period randomized, crossover study in healthy individuals (n=18) was ...

A crosstalk between p21 and UPR-induced transcription factor C/EBP homologous protein (CHOP) linked to type 2 diabetes.

PubMed

Mihailidou, Chrysovalantou; Papavassiliou, Athanasios G; Kiaris, Hippokratis

2014-04-01

Type 2 diabetes (T2D) is a disease that is characterized by raised levels of glucose in the blood combined with insulin resistance and relative insulin deficiency. The pathogenesis of type 2 diabetes is associated with the induction of the unfolded protein response (UPR). While UPR aims to restore tissue homeostasis following stress of the endoplasmic reticulum (ER), prolonged ER stress triggers apoptosis at least in part through the unfolded protein response (UPR)-activated transcription factor C/EBP (CCAAT/enhancer binding protein) homologous protein (CHOP). CHOP has elevated as a critical mediator connecting accumulation and aggregation of unfolded proteins in the ER and oxidative stress and also contributes to the induction of apoptosis in β-cell (beta-cell) - cells under conditions of increased insulin demand. p21 is a cell cycle regulator that is implicated in the regulation of the UPR by various mechanisms involving inhibition of apoptosis and facilitation of the regeneration capacity of the β cells. In this review we summarize the role of ER stress in the pathogenesis of type 2 diabetes which is associated with the induction of the unfolded protein response (UPR). We also review recent evidence associating p21 activity with β cell health and regenerative capacity by mechanisms that may interfere with the effects of p21 in the UPR or operate independently of ER stress. Most likely understanding the molecular details of the pathogenesis of type 2 diabetes will be beneficial for the management of the disease. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Effect of packaging type during postmortem aging and degree of doneness on pork chop sensory traits of loins selected to vary in color and marbling.

PubMed

Klehm, B J; King, D A; Dilger, A C; Shackelford, S D; Boler, D D

2018-05-04

The objective was to determine the interactions between packaging type and degree of doneness on sensory traits of pork loins classified based on the newly proposed USDA quality grades. A total of 144 loins were selected from 2 groups of pigs (lean growth or meat quality production focus) to represent as much variation in visual color and marbling as possible. Selection was achieved with a VQG grading camera. The ventral surface of the loins was evaluated for loin quality traits at 1 d postmortem. At 2 d postmortem loins were sliced into 28-mm-thick chops. Chop within each loin was randomly assigned to either individual vacuum packages or to individual Styrofoam trays and overwrapped in polyvinyl chloride (PVC) oxygen permeable film. Overwrapped PVC packages were then placed in bulk packages and flushed with a gas mixture that contained approximately 0.4% carbon monoxide, 30% carbon dioxide, and 80% nitrogen. Vacuum-packaged chops were aged until 14 d postmortem. Chops packaged in PVC overwrap were aged until 9 d postmortem in the bulk packages, then placed on simulated retail display until 14 d postmortem. Chops from each packaging type were cooked to an internal temperature of either 63 °C or 71 °C for the evaluation of slice shear force (SSF) or for evaluation of tenderness, juiciness, and flavor by a trained panel. Data were analyzed as split-split plot design with production focus of the pigs, proposed USDA quality grade, packaging type, and degree of doneness as fixed effects. While there were main effect differences between production focuses, there were no interactions with production focus. There were also no 3-way (P ≥ 0.19) interactions and only one 2-way interaction among quality grade, packaging type, or degree of doneness. There were no differences in sensory tenderness (P = 0.30), juiciness (P = 0.49), flavor (P = 0.89), SSF (P = 0.13), or cook loss (P = 0.06) among USDA quality grades. There were no differences in sensory tenderness (P = 0.06), juiciness (P = 0.32), flavor (P = 0.74), SSF (P = 0.99), or cook loss (P = 0.12) between chops aged in vacuum packages or PVC packages. Chops cooked to 63 °C were 4.6% more tender (P < 0.0001), 10.1% juicier (P < 0.0001), and 2.9% less flavorful (P = 0.01) than chops cooked to 71 °C. These data suggest that cooking chops to 63 °C rather than 71 °C was a more effective way to improve tenderness and juiciness than selecting chops of a certain quality grade or altering packaging postmortem.

Role of Unfolded Protein Response Dysregulation in Oxidative Injury of Retinal Pigment Epithelial Cells

PubMed Central

Chen, Chen; Cano, Marisol; Wang, Joshua J.; Li, Jingming; Huang, Chuangxin; Yu, Qiang; Herbert, Terence P.; Handa, James T.

2014-01-01

Abstract Aims: Age-related macular degeneration (AMD), a major cause of legal blindness in the elderly, is associated with genetic and environmental risk factors, such as cigarette smoking. Recent evidence shows that cigarette smoke (CS) that contains high levels of potent oxidants preferably targets retinal pigment epithelium (RPE) leading to oxidative damage and apoptosis; however, the mechanisms are poorly understood. The present study aimed to investigate the role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in CS-related RPE apoptosis. Results: ER stress and proapoptotic gene C/EBP homologous protein (CHOP) were induced in the RPE/choroid complex from mice exposed to CS for 2 weeks and in human RPE cells treated with hydroquinone, a potent oxidant found at high concentrations in CS. Suppressing ER stress or inhibiting CHOP activation by pharmacological chaperones or genetic approaches attenuated hydroquinone-induced RPE cell apoptosis. In contrast to enhanced CHOP activation, protein level of active X-box binding protein 1 (XBP1), a major regulator of the adaptive UPR, was reduced in hydroquinone-treated cells. Conditional knockout of XBP1 gene in the RPE resulted in caspase-12 activation, increased CHOP expression, and decreased antiapoptotic gene Bcl-2. Furthermore, XBP1-deficient RPE cells are more sensitive to oxidative damage induced by hydroquinone or NaIO3, a CS-unrelated chemical oxidant. Conversely, overexpressing XBP1 protected RPE cells and attenuated oxidative stress-induced RPE apoptosis. Innovation and Conclusion: These findings provide strong evidence suggesting an important role of ER stress and the UPR in CS-related oxidative injury of RPE cells. Thus, the modulation of the UPR signaling may provide a promising target for the treatment of AMD. Antioxid. Redox Signal. 20, 2091–2106. PMID:24053669

Down-regulation of 14-3-3β exerts anti-cancer effects through inducing ER stress in human glioma U87 cells: Involvement of CHOP–Wnt pathway

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

Cao, Lei; Lei, Hui; Chang, Ming-Ze

We previously identified 14-3-3β as a tumor-specific isoform of 14-3-3 protein in astrocytoma, but its functional role in glioma cells and underlying mechanisms are poorly understood. In the present study, we investigated the effects of 14-3-3β inhibition in human glioma U87 cells using specific targeted small interfering RNA (siRNA). The results showed that 14-3-3β is highly expressed in U87 cells but not in normal astrocyte SVGp12 cells. Knockdown of 14-3-3β by Si-14-3-3β transfection significantly decreased the cell viability but increased the LDH release in a time-dependent fashion in U87 cells, and these effects were accompanied with G0/G1 cell cycle arrestmore » and apoptosis. In addition, 14-3-3β knockdown induced ER stress in U87 cells, as evidenced by ER calcium release, increased expression of XBP1S mRNA and induction of ER related pro-apoptotic factors. Down-regulation of 14-3-3β significantly decreased the nuclear localization of β-catenin and inhibited Topflash activity, which was shown to be reversely correlated with CHOP. Furthermore, Si-CHOP and sFRP were used to inhibit CHOP and Wnt, respectively. The results showed that the anti-cancer effects of 14-3-3β knockdown in U87 cells were mediated by increased expression of CHOP and followed inhibition of Wnt/β-catenin pathway. In summary, the remarkable efficiency of 14-3-3β knockdown to induce apoptotic cell death in U87 cells may find therapeutic application for the treatment of glioma patients. - Highlights: • Knockdown of 14-3-3β leads to cytotoxicity in human glioma U87 cells. • Knockdown of 14-3-3β induces cell cycle arrest and apoptosis in U87 cells. • Knockdown of 14-3-3β results in ER stress in U87 cells. • Knockdown of 14-3-3β inhibits Wnt/β-catenin pathway via CHOP activation.« less

Correlation between compressive strength and ultrasonic pulse velocity of high strength concrete incorporating chopped basalt fibre

NASA Astrophysics Data System (ADS)

Shafiq, Nasir; Fadhilnuruddin, Muhd; Elshekh, Ali Elheber Ahmed; Fathi, Ahmed

2015-07-01

Ultrasonic pulse velocity (UPV), is considered as the most important test for non-destructive techniques that are used to evaluate the mechanical characteristics of high strength concrete (HSC). The relationship between the compressive strength of HSC containing chopped basalt fibre stands (CBSF) and UPV was investigated. The concrete specimens were prepared using a different ratio of CBSF as internal strengthening materials. The compressive strength measurements were conducted at the sample ages of 3, 7, 28, 56 and 90 days; whilst, the ultrasonic pulse velocity was measured at 28 days. The result of HSC's compressive strength with the chopped basalt fibre did not show any improvement; instead, it was decreased. The UPV of the chopped basalt fibre reinforced concrete has been found to be less than that of the control mix for each addition ratio of the basalt fibre. A relationship plot is gained between the cube compressive strength for HSC and UPV with various amounts of chopped basalt fibres.

Evaluation of a 15-week CHOP protocol for the treatment of canine multicentric lymphoma.

PubMed

Burton, J H; Garrett-Mayer, E; Thamm, D H

2013-12-01

Dose intense CHOP protocols have been shown to improve outcome for people with non-Hodgkin's lymphoma, but evaluation of dose intense CHOP protocols for canine lymphoma is currently limited. The hypothesis of this retrospective study was that a 15-week dose intense CHOP protocol would have shorter treatment duration with similar efficacy to other doxorubicin-based multidrug protocols. Thirty-one client owned dogs with multicentric lymphoma were treated with a 15-week CHOP chemotherapy protocol with an overall response rate of 100% and a median progression-free interval (PFI) of 140 days [95% confidence interval (CI) 91-335 days]. Dogs that had two or more treatment delays had significantly prolonged PFI and overall survival in multivariate analysis. Dose intensity did not correlate with patient outcome. Dogs experiencing multiple treatment delays secondary to adverse events may receive their individual maximally tolerated dose while dogs with no adverse events may be underdosed. Future studies should focus on individual patient dose optimization. © 2012 Blackwell Publishing Ltd.

Chopped molecular beam multiplexing system

NASA Technical Reports Server (NTRS)

Adams, Billy R. (Inventor)

1986-01-01

The integration of a chopped molecular beam mass spectrometer with a time multiplexing system is described. The chopping of the molecular beam is synchronized with the time intervals by a phase detector and a synchronous motor. Arithmetic means are generated for phase shifting the chopper with respect to the multiplexer. A four channel amplifier provides the capacity to independently vary the baseline and amplitude in each channel of the multiplexing system.

Sensory and Nutritional Evaluation of Meat Loaves with and without Granular Soy Concentrate

DTIC Science & Technology

1982-05-01

garlic , sweet chopped peppers, eggs, milk, water, and Onions, dry, finely I lb ..... 3 cups ............ tomato juice. Mix lightly but chopped ...thoroughly. Avoid overmixing if Garlic , dry, minced ......... 2 tsp (2 ......... using mixer. (optional) cloves) Pepper, sweet, 8 oz ..... I % cups...fresh, chopped (option l) 9gs, whole, 2 lb 8 oz. 1% qt (24 ......... slightly beaten eggs) Milknonfat, dry .. Soz ..... 1% ups ......... Water

Competition After Windrowing or Single-Roller Chopping For Site Preparation in the Southern Piedmont

Treesearch

James H. Miller

1980-01-01

For two years, post-treatment regrowth of herbaceous and woody species was sampled on two adjoining areas in the southern Piedmont where they had been either sheared and piled into windrows or chopped by a single pass of a single-drum roller-chopper. Windrowing yielded 55% less total standing crop of woody trees, shrubs, and vines after 2 years than chopping did. But...

Strengthening behavior of chopped multi-walled carbon nanotube reinforced aluminum matrix composites

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

Shin, S.E.; Bae, D.H., E-mail: donghyun@yonsei.ac.kr

2013-09-15

Strengthening behavior of the aluminum composites reinforced with chopped multi-walled carbon nanotubes (MWCNTs) or aluminum carbide formed during annealing at 500 °C has been investigated. The composites were fabricated by hot-rolling the powders which were ball-milled under various conditions. During the early annealing process, aluminum atoms can cluster inside the tube due to the diffusional flow of aluminum atoms into the tube, providing an increase of the strength of the composite. Further annealing induces the formation of the aluminum carbide phase, leading to an overall drop in the strength of the composites. While the strength of the composites can bemore » evaluated according to the rule of mixture, a particle spacing effect can be additionally imparted on the strength of the composites reinforced with the chopped MWCNTs or the corresponding carbides since the reinforcing agents are smaller than the submicron matrix grains. - Highlights: • Strengthening behavior of chopped CNT reinforced Al-based composites is investigated. • Chopped CNTs have influenced the strength and microstructures of the composites. • Chopped CNTs are created under Ar- 3% H2 atmosphere during mechanical milling. • Strength can be evaluated by the rule of the mixture and a particle spacing effect.« less

Significant improvement in the thermal annealing process of optical resonators

NASA Astrophysics Data System (ADS)

Salzenstein, Patrice; Zarubin, Mikhail

2017-05-01

Thermal annealing performed during process improves the quality of the roughness of optical resonators reducing stresses at the periphery of their surface thus allowing higher Q-factors. After a preliminary realization, the design of the oven and the electronic method were significantly improved thanks to nichrome resistant alloy wires and chopped basalt fibers for thermal isolation during the annealing process. Q-factors can then be improved.

Controlling Brochothrix thermosphacta as a spoilage risk using in-package atmospheric cold plasma.

PubMed

Patange, Apurva; Boehm, Daniela; Bueno-Ferrer, Carmen; Cullen, P J; Bourke, Paula

2017-09-01

Brochothrix thermosphacta is the predominant spoilage microorganism in meat and its control in processing environments is important to maintain meat product quality. Atmospheric cold plasma is of interest for control of pathogenic and spoilage microorganisms in foods. This study ascertained the potential of dielectric barrier discharge atmospheric cold plasma (DBD-ACP) for control of B. thermosphacta, taking microbial and food environment factors into consideration, and investigated the shelf-life of lamb chop after in-package plasma treatment in modified atmosphere. Community profiling was used to assess the treatment effects on the lamb microflora. ACP treatment (80 kV) for 30s inactivated B. thermosphacta populations below detection levels in PBS, while 5 min treatment achieved a 2 Log cycle reduction using a complex meat model medium and attached cells. The antimicrobial efficacy of plasma was reduced but still apparent on lamb chop surface-inoculated with high concentrations of B. thermosphacta. Lamb chop treated under modified atmosphere exhibited reduced microbial growth over the product shelf-life and community profiling showed no evident changes to the microbial populations after the treatment. The overall results indicated potential of ACP to enhance microbial control leading to meat storage life extension through adjusting the modality of treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sensory characteristics and carcass traits of boars, barrows, and gilts fed high- or adequate-protein diets and slaughtered at 100 or 110 kilograms.

PubMed

Nold, R A; Romans, J R; Costello, W J; Henson, J A; Libal, G W

1997-10-01

The objective of this study was to determine consumer reaction to boar (BO), barrow (BA), and gilt (G) meat from pigs grown and finished on high- (HI) and low- (LO) protein diets and slaughtered at 100 and 110 kg BW. Within each of two trials, 54 BO, BA, and G were allotted within sexes to HI or LO protein sequences for growing and finishing: 19 and 17% (BOHI), 18 and 16% (BOLO), 17 and 15% (GHI), 16 and 14% (GLO), 15 and 13% (BAHI), and 14 and 12% (BALO). Backfat skatole and salivary gland 16-androstene concentrations were measured from samples taken at slaughter. Longissimus (LM) and semitendinosus (ST) chops from 24 pigs (with equal representation across diet and sex groups) were evaluated by trained panelists for tenderness, juiciness, and off-flavor. Consumer panelists evaluated acceptability of LM chops. In the 100-kg trial, HI diets improved (P < .05) carcass leanness in BO and BA but not in G. In both trials, BO were leaner (P < .05) than G, and both were leaner (P < .05) than BA. Skatole and 16-androstene concentrations were similar (P > .05) among sexes in both trials. In the 100-kg trial, trained panelists found BOLO chops had more (P < .05) off-flavor. In the 110-kg trial, all BO had more off-flavor (P < .05) than BAHI, BALO, and GHI but were similar (P > .05) to GLO. In both trials, BA chops were more tender (P < .05) than G and BO chops and LM chops had less off-flavor (P < .05) than ST chops. In the 110-kg trial, skatole was correlated (r = .28, P < .001) to off-flavor. A relationship may exist among diet, skatole deposition, and off-flavor. Untrained consumers reported all chops were equally acceptable (P > .05).

Soil properties and pine growth affected by site preparation after clearcutting

Treesearch

John J. Stransky; John H. Roese; K.G. Watterson

1985-01-01

A pine-hardwood sawtimber stand in southeast Texas was clearcut in September 1972. Random plots were burned, chopped, KG-bladed, or left untreated. In the spring of 1974, 1-0 loblolly pine seedlings (Pinus taeda L.) were handplanted at 8 by 10 foot spacing. Data from soil samples, taken from the 0-5 inch depth before clearcutting and 1, 3, and 5...

The Association Between Liver and Tumor [18F]FDG Uptake in Patients with Diffuse Large B Cell Lymphoma During Chemotherapy.

PubMed

Wu, Xingchen; Bhattarai, Abhisek; Korkola, Pasi; Pertovaara, Hannu; Eskola, Hannu; Kellokumpu-Lehtinen, Pirkko-Liisa

2017-10-01

The aim of this study was to explore the association between liver, mediastinum and tumor 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) uptake during chemotherapy in diffuse large B cell lymphoma (DLBCL). Nineteen patients with proven DLBCL underwent positron emission tomography (PET)/X-ray computed tomography scan at baseline, 1 week and 2 cycles after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy, and again after chemotherapy completion. The mean and maximal standardized uptake value (SUVmean and SUVmax) of the liver and mediastinum were measured and correlated with the tumor SUVmax, SUVsum, whole-body metabolic tumor volume (MTVwb), and total lesion glycolysis (TLG). At baseline, both the liver and mediastinum SUVmean and SUVmax correlated inversely with the tumor MTVwb or TLG (p < 0.01 or 0.001). The liver SUVmean and SUVmax increased significantly after 1 week of R-CHOP therapy and remained at the high level until chemotherapy completion. The mediastinum SUVmean and SUVmax remained stable during chemotherapy. The tumor SUVmax, SUVsum, MTVwb, and TLG decreased significantly after 1 week of R-CHOP therapy. The change of the liver SUVmean correlated inversely with the change of tumor MTVwb and TLG after 1 week of chemotherapy (p < 0.05, respectively). The intersubject variability of liver and mediastinum [ 18 F]FDG uptake ranged from 11 to 26 %. The liver [ 18 F]FDG uptake increased significantly after R-CHOP therapy. One of the possible reasons is the distribution of a greater fraction of the tracer to healthy tissues rather than tumor after effective chemotherapy. The variability of the liver [ 18 F]FDG uptake during chemotherapy might affect the visual analysis of the interim PET scan and this needs to be confirmed in future studies with a large patient cohort. In addition, the intersubject variability of the liver and mediastinum [ 18 F]FDG uptake should be considered.

Brain glucose metabolism in diffuse large B-cell lymphoma patients as assessed with FDG-PET: impact on outcome and chemotherapy effects.

PubMed

Adams, Hugo Ja; de Klerk, John Mh; Fijnheer, Rob; Heggelman, Ben Gf; Dubois, Stefan V; Nievelstein, Rutger Aj; Kwee, Thomas C

2016-06-01

There is a lack of data on the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy on brain glucose metabolism of diffuse large B-cell lymphoma (DLBCL) patients, as measured by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, the prognostic value of brain glucose metabolism measurements is currently unknown. To investigate the use of FDG-PET for measurement of brain glucose metabolism in R-CHOP-treated DLBCL patients, and to assess its prognostic value. This retrospective study included DLBCL patients who underwent FDG-PET including the brain. FDG-PET metabolic volume products (MVPs) of the entire brain, cerebral cortex, basal ganglia, and cerebellum were measured, before and after R-CHOP therapy. Whole-body total lesion glycolysis (TLG) was also measured. Thirty-eight patients were included, of whom 18 had an appropriate end-of-treatment FDG-PET scan. There were no significant differences (P > 0.199) between pre- and post-treatment brain glucose metabolism metrics. Low basal ganglia MVP was associated with a significantly worse progression-free survival (PFS) and overall survival (OS) (P = 0.020 and P = 0.032), and low cerebellar MVP was associated with a significantly worse OS (P = 0.034). There were non-significant very weak correlations between pretreatment brain glucose metabolism metrics and TLG. In the multivariate Cox regression, only the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) remained an independent predictor of PFS (hazard ratio 3.787, P = 0.007) and OS (hazard ratio 2.903, P = 0.0345). Brain glucose metabolism was not affected by R-CHOP therapy. Low pretreatment brain glucose metabolism was associated with a worse outcome, but did not surpass the predictive value of the NCCN-IPI. © The Foundation Acta Radiologica 2015.

What We Learn About Process Specification Languages from Studying Recipes

DTIC Science & Technology

1987-08-01

minutes or until very lightly browned. Add carrot, shallots, onion, celery root, mushrooms, and garlic ,· *I I* stir well *I add_to( chop ...a computer program. Most recipes require that each ingredient receives a preprocessing treatment (eg. peel, chop ) before being used. Thus, we found...named operations that must be performed by a cook such as chop , set_heat, ... (see section 7 for more details on these), "active operations

Study Techniques for Controlling Flavor Intensity in Compressed Foods (Phase 2)

DTIC Science & Technology

1976-06-10

and gravies were prepared as cooked materials, freeze- dried and chopped . The mushroom soup ingredients were all used as procured in their dry...This material, after blending with the soup base, was free£e= dried and chopped prior to blending with the re- maining components in preparation of...Exec- utive Chef, using the following formula: TABLE XII Onion Gravy Formula Ingredients % Onions, Chopped Tomato Paste Hard Wheat Flour Beef

Glucose Deprivation Induces ATF4-Mediated Apoptosis through TRAIL Death Receptors

PubMed Central

Iurlaro, Raffaella; Püschel, Franziska; León-Annicchiarico, Clara Lucía; O'Connor, Hazel; Martin, Seamus J.; Palou-Gramón, Daniel; Lucendo, Estefanía

2017-01-01

ABSTRACT Metabolic stress occurs frequently in tumors and in normal tissues undergoing transient ischemia. Nutrient deprivation triggers, among many potential cell death-inducing pathways, an endoplasmic reticulum (ER) stress response with the induction of the integrated stress response transcription factor ATF4. However, how this results in cell death remains unknown. Here we show that glucose deprivation triggered ER stress and induced the unfolded protein response transcription factors ATF4 and CHOP. This was associated with the nontranscriptional accumulation of TRAIL receptor 1 (TRAIL-R1) (DR4) and with the ATF4-mediated, CHOP-independent induction of TRAIL-R2 (DR5), suggesting that cell death in this context may involve death receptor signaling. Consistent with this, the ablation of TRAIL-R1, TRAIL-R2, FADD, Bid, and caspase-8 attenuated cell death, although the downregulation of TRAIL did not, suggesting ligand-independent activation of TRAIL receptors. These data indicate that stress triggered by glucose deprivation promotes the ATF4-dependent upregulation of TRAIL-R2/DR5 and TRAIL receptor-mediated cell death. PMID:28242652

The prednisone dosage in the CHOP chemotherapy regimen for non-Hodgkin's lymphomas (NHL): is there a standard?

PubMed

Moreno, A; Colon-Otero, G; Solberg, L A

2000-01-01

Discrepancies in the quoted prednisone dosages in the regimens reported as the only standard CHOP regimen stimulated our interest in reviewing the medical literature regarding this issue and to assess whether practicing hematologists and oncologists in the U.S. are aware of the different dose schedules of prednisone in the published CHOP programs. Sixteen textbooks and chemotherapy reference books were reviewed. A MEDLINE search of English-language articles published between January 1970 and December 1998 was performed. An eight-point questionnaire was sent via e-mail with responses obtained from 421 hematology/oncology physicians in the U.S. Sixteen textbooks and chemotherapy reference books reviewed quoted only one prednisone dosage as part of the standard CHOP regimen; the prednisone dosages quoted as standard varied between publications. More than 4,000 eligible non-Hodgkin's lymphoma patients have been treated with the CHOP chemotherapy as part of 43 different clinical trials reviewed. The dosages of prednisone and prednisolone used varied among six different levels. Thirty percent (127/421) of practicing U.S. physicians were not aware of the existence of more than one prednisone dose schedule as part of the CHOP regimen. The three most frequently used dosages are 100 mg/days 1-5 (67%), 100 mg/m(2)/days 1-5 (17%), and 60 mg/m(2)/days 1-5 (13%). Discrepancies in steroid dosages used as part of the reported standard CHOP regimens are common and not well recognized in the medical literature nor by practicing U.S. hematologists/oncologists. Based on this study, a prednisone dose of 100 mg/day for five days should be considered the standard dose.

Excessive L-cysteine induces vacuole-like cell death by activating endoplasmic reticulum stress and mitogen-activated protein kinase signaling in intestinal porcine epithelial cells.

PubMed

Ji, Yun; Wu, Zhenlong; Dai, Zhaolai; Sun, Kaiji; Zhang, Qing; Wu, Guoyao

2016-01-01

High intake of dietary cysteine is extremely toxic to animals and the underlying mechanism remains largely unknown. This study was conducted to test the hypothesis that excessive L-cysteine induces cell death by activating endoplasmic reticulum (ER) stress and mitogen-activated protein kinase (MAPK) signaling in intestinal porcine epithelial cells. Jejunal enterocytes were cultured in the presence of 0-10 mmol/L L-cysteine. Cell viability, morphologic alterations, mRNA levels for genes involved in ER stress, protein abundances for glucose-regulated protein 78, C/EBP homologous protein (CHOP), alpha subunit of eukaryotic initiation factor-2 (eIF2α), extracellular signal-regulated kinase (ERK1/2), p38 MAPK, and c-Jun N-terminal protein kinase (JNK1/2) were determined. The results showed that L-cysteine (5-10 mmol/L) reduced cell viability (P < 0.05) and led to vacuole-like cell death in intestinal porcine epithelial cells. These adverse effects of L-cysteine were not affected by the autophagy inhibitor 3-methyladenine. The protein abundances for CHOP, phosphorylated (p)-eIF2α, p-JNK1/2, p-p38 MAPK, and the spliced form of XBP-1 mRNA were enhanced (P < 0.05), whereas those for p-ERK1/2 were reduced (P < 0.05). Collectively, excessive L-cysteine induces vacuole-like cell death via the activation of ER stress and MAPK signaling in small intestinal epithelial cells. These signaling pathways may be potential targets for developing effective strategies to prevent the toxicity of dietary cysteine.

High precision moving magnet chopper for variable operation conditions

NASA Technical Reports Server (NTRS)

Aicher, Winfried; Schmid, Manfred

1994-01-01

In the context of an ESTEC technology contract, a Chopping Mechanism was developed and built with the Far Infrared and Submillimeter Telescope (FIRST) astronomy mission as a reference. The task of the mechanism is to tilt the subreflector of the telescope with an assumed mass of 2.5 kg about one chopping axis at nominal frequencies of up to 5 Hz and chopping angles of up to +/- 11.25 mrad with high efficiency (minimum time for position change). The chopping axis is required to run through the subreflector vertex. After performing a concept trade-off also considering the low operational temperatures in the 130 K range, a design using moving magnet actuators was found to be the favorite one. In addition, a bearing concept using flexible pivots was chosen to meet the high chopping accuracy required. With this approach, a very reliable design could be realized, since the actuators work without any mechanical contact between its moving and fixed parts, and the only bearings used are two flexible pivots supporting the subreflector mounting interface. The mechanism was completely built in titanium in a lightweight and stiff design. The moving magnet actuators were designed to meet the stringent requirements for minimum risetime (time necessary to move from one angular position to a new one) in the 20 msec range. The angular position and the corresponding chopping frequency as well can be arbitrarily selected by the user.

CHOP plus etoposide and gemcitabine (CHOP-EG) as front-line chemotherapy for patients with peripheral T cell lymphomas.

PubMed

Kim, Jong Gwang; Sohn, Sang Kyun; Chae, Yee Soo; Kim, Dong Hwan; Baek, Jin Ho; Lee, Kyu Bo; Lee, Je-Jung; Chung, Ik-Joo; Kim, Hyeoung-Joon; Yang, Deok-Hwan; Lee, Won-Sik; Joo, Young-Don; Sohn, Chang-Hak

2006-07-01

The present study evaluated the feasibility of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus etoposide and gemcitabine (CHOP-EG) as front-line chemotherapy in patients with peripheral T cell lymphomas (PTCLs). Twenty-six patients with newly diagnosed PTCLs were enrolled into the pilot study. Treatment consisted of classical CHOP plus etoposide 100 mg/m(2) intravenously (i.v.) on day 1 and gemcitabine 600 mg/m(2) i.v. on day 1 in a 3 week interval. Fifteen complete responses (CR, 57.7%) or one unconfirmed complete response (uCR, 3.8%) and four partial responses (PR, 15.4%) were confirmed, giving an overall response rate of 76.9% (95% CI, 58.3-96.3%). Median survival has not yet been reached, while median event free survival was 215 days at a median follow-up duration of 383 days. Estimated overall survival at 1 year was 69.6%. The most severe haematological adverse event was neutropaenia, which occurred with a grade 4 intensity in 14 patients (53.8%). Additionally, febrile neutropaenia was observed in four patients (15.4%). However, there was no treatment-related death. The CHOP-EG regimen was found to be feasible in patients with PTCLs. For further investigation on the role of gemcitabine in the treatment of PTCLs, a more large scale phase II or phase III study is warranted.

Diffraction effects in mechanically chopped laser pulses

NASA Astrophysics Data System (ADS)

Gambhir, Samridhi; Singh, Mandip

2018-06-01

A mechanical beam chopper consists of a rotating disc of regularly spaced wide slits which allow light to pass through them. A continuous light beam, after passing through the rotating disc, is switched-on and switched-off periodically, and a series of optical pulses are produced. The intensity of each pulse is expected to rise and fall smoothly with time. However, a careful study has revealed that the edges of mechanically chopped laser light pulses consist of periodic intensity undulations which can be detected with a photo detector. In this paper, it is shown that the intensity undulations in mechanically chopped laser pulses are produced by diffraction of light from the rotating disc, and a detailed explanation is given of the intensity undulations in mechanically chopped laser pulses. An experiment presented in this paper provides an efficient method to capture a one dimensional diffraction profile of light from a straight sharp-edge in the time domain. In addition, the experiment accurately measures wavelengths of three different laser beams from the undulations in mechanically chopped laser light pulses.

Intrarenal renin-angiotensin system mediates fatty acid-induced ER stress in the kidney

PubMed Central

Li, Chunling; Lin, Yu; Luo, Renfei; Chen, Shaoming; Zheng, Peili; Levi, Moshe; Yang, Tianxin; Wang, Weidong

2015-01-01

Obesity-related kidney disease is related to caloric excess promoting deleterious cellular responses. Accumulation of saturated free fatty acids in tubular cells produces lipotoxicity involving significant cellular dysfunction and injury. The objectives of this study were to elucidate the role of renin-angiotensin system (RAS) activation in saturated fatty acid-induced endoplasmic reticulum (ER) stress in cultured human proximal tubule epithelial cells (HK2) and in mice fed with a high-fat diet. Treatment with saturated fatty acid palmitic acid (PA; 0.8 mM) for 24 h induced ER stress in HK2, leading to an unfolded protein response as reflected by increased expressions of the ER chaperone binding immunoglobulin protein (BiP) and proapoptotic transcription factor C/EBP homologous protein (CHOP) protein as evaluated by immunoblotting. PA treatment also induced increased protein expression of inositol requiring protein 1α (IRE1α), phosphorylated eukaryotic initiation factor-α (eIF2α), and activating transcription factor 4 (ATF4) as well as activation of caspase-3. PA treatment was associated with increased angiotensin II levels in cultured medium. The angiotensin II type 1 receptor (AT1R) blocker valsartan or renin inhibitor aliskiren dramatically suppressed PA-induced upregulation of BiP, CHOP, IRE1α, p-eIF2α, and ATF4 in HK2 cells. In contrast, valsartan or aliskiren did not prevent ER stress induced by tunicamycin. C57BL/6 mice fed with a high-fat diet for 14 wk exhibited increased protein expressions of BiP and CHOP compared with control mice, which were significantly attenuated by the valsartan treatment. Increased angiotensin II levels in serum and urine were observed in mice fed with a high-fat diet when compared with controls. It is suggested that the intrarenal RAS activation may play an important role in diabetic kidney injury via mediating ER stress induced by saturated fatty acid. PMID:26672616

Chicken Stew

MedlinePlus

... 2 tsp salt 1/2 tsp ground black pepper 3 medium tomatoes, chopped 1 tsp chopped parsley ... combine the chicken, water, garlic, onion, salt, black pepper, tomatoes, and parsley. Tightly cover and cook over ...

Protein Oxidation and Sensory Quality of Brine-Injected Pork Loins Added Ascorbate or Extracts of Green Tea or Maté during Chill-Storage in High-Oxygen Modified Atmosphere

PubMed Central

Tørngren, Mari Ann

2018-01-01

Background: Ascorbate is often applied to enhance stability and robustness of brine-injected pork chops sold for retail, but may affect protein oxidation, while plant extracts are potential substitutes. Methods: Brine-injected pork chops (weight-gain ~12%, NaCl ~0.9%) prepared with ascorbate (225 ppm), green tea extract (25 ppm gallic acid equivalents (GAE)), or maté extract (25 ppm GAE) stored (5 °C, seven days) in high-oxygen atmosphere packaging (MAP: 80% O2 and 20% CO2) were analyzed for color changes, sensory quality, and protein oxidation compared to a control without antioxidant. Results: No significant differences were observed for green tea and maté extracts as compared to ascorbate when evaluated based on lipid oxidation derived off-flavors, except for stale flavor, which maté significantly reduced. All treatments increased the level of the protein oxidation product, α-aminoadipic semialdehyde as compared to the control, and ascorbate was further found to increase thiol loss and protein cross-linking, with a concomitant decrease in the sensory perceived tenderness. Conclusions: Green tea and maté were found to equally protect against lipid oxidation derived off-flavors, and maté showed less prooxidative activity towards proteins as compared to ascorbate, resulting in more tender meat. Maté is a valuable substitute for ascorbate in brine-injected pork chops. PMID:29342928

Inhibition of endoplasmic reticulum stress by intermedin1-53 attenuates angiotensin II-induced abdominal aortic aneurysm in ApoE KO Mice.

PubMed

Ni, Xian-Qiang; Lu, Wei-Wei; Zhang, Jin-Sheng; Zhu, Qing; Ren, Jin-Ling; Yu, Yan-Rong; Liu, Xiu-Ying; Wang, Xiu-Jie; Han, Mei; Jing, Qing; Du, Jie; Tang, Chao-Shu; Qi, Yong-Fen

2018-06-26

Endoplasmic reticulum stress (ERS) is involved in the development of abdominal aortic aneurysm (AAA). Since bioactive peptide intermedin (IMD)1-53 protects against AAA formation, here we investigated whether IMD1-53 attenuates AAA by inhibiting ERS. AAA model was induced by angiotensin II (AngII) in ApoE KO mouse background. AngII-treated mouse aortas showed increased ERS gene transcription of caspase12, eukaryotic translation initiation factor 2a (eIf2a) and activating transcription factor 4(ATF4).The protein level of ERS marker glucose regulated protein 94(GRP94), ATF4 and C/EBP homologous protein 10(CHOP) was also up-regulated by AngII. Increased ERS levels were accompanied by severe VSMC apoptosis in human AAA aorta. In vivo administration of IMD1-53 greatly reduced AngII-induced AAA and abrogated the activation of ERS. To determine whether IMD inhibited AAA by ameliorating ERS, we used 2 non-selective ERS inhibitors phenyl butyrate (4-PBA) and taurine (TAU). Similar to IMD, PBA, and TAU significantly reduced the incidence of AAA and AAA-related pathological disorders. In vitro, AngII infusion up-regulated CHOP, caspase12 expression and led to VSMC apoptosis. IMD siRNA aggravated the CHOP, caspase12-mediated VSMC apoptosis, which was abolished by ATF4 silencing. IMD infusion promoted the phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) in aortas in ApoE KO mice, and the AMPK inhibitor compound C abolished the protective effect of IMD on VSMC ERS and apoptosis induced by AngII. In conclusion, IMD may protect against AAA formation by inhibiting ERS via activating AMPK phosphorylation.

A new prognostic model identifies patients aged 80 years and older with diffuse large B-cell lymphoma who may benefit from curative treatment: A multicenter, retrospective analysis by the Spanish GELTAMO group.

PubMed

Pardal, Emilia; Díez Baeza, Eva; Salas, Queralt; García, Tomás; Sancho, Juan M; Monzón, Encarna; Moraleda, José M; Córdoba, Raúl; de la Cruz, Fátima; Queizán, José A; Rodríguez, María J; Navarro, Belén; Hernández, José A; Díez, Rosana; Vahi, María; Viguria, María C; Canales, Miguel; Peñarrubia, María J; González-López, Tomás J; Montes-Moreno, Santiago; González-Barca, Eva; Caballero, Dolores; Martín, Alejandro

2018-04-15

The means of optimally managing very elderly patients with diffuse large B-cell lymphoma (DLBCL) has not been established. We retrospectively analyzed 252 patients aged 80-100 years, diagnosed with DLBCL or grade 3B follicular lymphoma, treated in 19 hospitals from the GELTAMO group. Primary objective was to analyze the influence of the type of treatment and comorbidity scales on progression-free survival (PFS) and overall survival (OS). One hundred sixty-three patients (63%) were treated with chemotherapy that included anthracyclines and/or rituximab, whereas 15% received no chemotherapeutic treatment. With a median follow-up of 44 months, median PFS and OS were 9.5 and 12.5 months, respectively. In an analysis restricted to the 205 patients treated with any kind of chemotherapy, comorbidity scales did not influence the choice of treatment type significantly. Independent factors associated with better PFS and OS were: age < 86 years, cumulative illness rating scale (CIRS) score < 6, intermediate risk (1-2) R-IPI, and treatment with R-CHOP at full or reduced doses. We developed a prognostic model based on the multivariate analysis of the 108 patients treated with R-CHOP-like: median OS was 45 vs. 12 months (P = .001), respectively, for patients with 0-1 vs. 2-3 risk factors (age > 85 years, R-IPI 3-5 or CIRS > 5). In conclusion, treatment with R-CHOP-like is associated with good survival in a significant proportion of patients. We have developed a simple prognostic model that may aid the selection patients who could benefit from a curative treatment, although it needs to be validated in larger series. © 2018 Wiley Periodicals, Inc.

Protective Effects of Hericium erinaceus Mycelium and Its Isolated Erinacine A against Ischemia-Injury-Induced Neuronal Cell Death via the Inhibition of iNOS/p38 MAPK and Nitrotyrosine

PubMed Central

Lee, Kam-Fai; Chen, Jiann-Hwa; Teng, Chih-Chuan; Shen, Chien-Heng; Hsieh, Meng-Chiao; Lu, Chien-Chang; Lee, Ko-Chao; Lee, Li-Ya; Chen, Wan-Ping; Chen, Chin-Chu; Huang, Wen-Shih; Kuo, Hsing-Chun

2014-01-01

Hericium erinaceus, an edible mushroom, has been demonstrated to potentiate the effects of numerous biological activities. The aim of this study was to investigate whether H. erinaceus mycelium could act as an anti-inflammatory agent to bring about neuroprotection using a model of global ischemic stroke and the mechanisms involved. Rats were treated with H. erinaceus mycelium and its isolated diterpenoid derivative, erinacine A, after ischemia reperfusion brain injuries caused by the occlusion of the two common carotid arteries. The production of inflammatory cytokines in serum and the infracted volume of the brain were measured. The proteins from the stroke animal model (SAM) were evaluated to determine the effect of H. erinaceus mycelium. H. erinaceus mycelium reduced the total infarcted volumes by 22% and 44% at a concentration of 50 and 300 mg/kg, respectively, compared to the SAM group. The levels of acute inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor á, were all reduced by erinacine A. Levels of nitrotyrosine-containing proteins, phosphorylation of p38 MAPK and CCAAT enhancer-binding protein (C/EBP) and homologous protein (CHOP) expression were attenuated by erinacine A. Moreover, the modulation of ischemia injury factors present in the SAM model by erinacine A seemed to result in the suppression of reactive nitrogen species and the downregulation of inducible NO synthase (iNOS), p38 MAPK and CHOP. These findings confirm the nerve-growth properties of Hericium erinaceus mycelium, which include the prevention of ischemic injury to neurons; this protective effect seems to be involved in the in vivo activity of iNOS, p38 MAPK and CHOP. PMID:25167134

Protective effects of Hericium erinaceus mycelium and its isolated erinacine A against ischemia-injury-induced neuronal cell death via the inhibition of iNOS/p38 MAPK and nitrotyrosine.

PubMed

Lee, Kam-Fai; Chen, Jiann-Hwa; Teng, Chih-Chuan; Shen, Chien-Heng; Hsieh, Meng-Chiao; Lu, Chien-Chang; Lee, Ko-Chao; Lee, Li-Ya; Chen, Wan-Ping; Chen, Chin-Chu; Huang, Wen-Shih; Kuo, Hsing-Chun

2014-08-27

Hericium erinaceus, an edible mushroom, has been demonstrated to potentiate the effects of numerous biological activities. The aim of this study was to investigate whether H. erinaceus mycelium could act as an anti-inflammatory agent to bring about neuroprotection using a model of global ischemic stroke and the mechanisms involved. Rats were treated with H. erinaceus mycelium and its isolated diterpenoid derivative, erinacine A, after ischemia reperfusion brain injuries caused by the occlusion of the two common carotid arteries. The production of inflammatory cytokines in serum and the infracted volume of the brain were measured. The proteins from the stroke animal model (SAM) were evaluated to determine the effect of H. erinaceus mycelium. H. erinaceus mycelium reduced the total infarcted volumes by 22% and 44% at a concentration of 50 and 300 mg/kg, respectively, compared to the SAM group. The levels of acute inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor á, were all reduced by erinacine A. Levels of nitrotyrosine-containing proteins, phosphorylation of p38 MAPK and CCAAT enhancer-binding protein (C/EBP) and homologous protein (CHOP) expression were attenuated by erinacine A. Moreover, the modulation of ischemia injury factors present in the SAM model by erinacine A seemed to result in the suppression of reactive nitrogen species and the downregulation of inducible NO synthase (iNOS), p38 MAPK and CHOP. These findings confirm the nerve-growth properties of Hericium erinaceus mycelium, which include the prevention of ischemic injury to neurons; this protective effect seems to be involved in the in vivo activity of iNOS, p38 MAPK and CHOP.

Impact of dietary fiber and physical form on performance of lactating dairy cows.

PubMed

Woodford, J A; Jorgensen, N A; Barrington, G P

1986-04-01

Two trials were conducted to study the effects of forage intake and physical form on lactating cow performance. In trial 1, four cows in a 4 X 4 Latin square were fed long alfalfa hay at 28, 36, 45, and 53% of total dry matter plus concentrate. Total dry matter intake was not affected by forage percent. Total chewing time and milk fat percentage increased linearly with increasing forage consumption. Maximum 4% fat-corrected milk production occurred when diets contained 27% neutral detergent fiber and 18% acid detergent fiber. In trial 2, four cows in a 4 X 4 Latin square were fed diets of chopped alfalfa hay and concentrate in proportions to supply 27.4% total ration neutral detergent fiber. Mean particle length measured with an oscillating screen particle separator of the chopped hay was .26, .46, .64, and .90 cm. Total dry matter and forage dry matter intakes and total chewing were not influenced by forage mean particle length. Mean particle length did not affect actual milk or 4% fat-corrected milk production. Depression of milk fat percentage was prevented when forage mean particle length was greater than or equal .64 cm. Apparent digestibility of dietary constituents and rate of passage of hay and concentrate was not influenced by forage intake or physical form.

Center for the Evaluation of Biomarkers for the Early Detection of Breast Cancer

DTIC Science & Technology

2005-10-01

4 servings 1 1/2 pounds boneless, skinless salmon fillet 1/4 cup chopped shallots 2 teaspoons chopped fresh dill 1 tablespoon fresh lemon juice 2...yogurt 1 tablespoon lemon juice To find out more information about women’s cancers, contact: 2 teaspoons minced garlic 1/2 teaspoon salt 1-800...4CANCER 1/4 teaspoon black pepper 1 tablespoon chopped fresh dill www.cancergov.gov-National Cancer Institute 1/4 cup grated, and squeezed dry, English

R-THP-COP versus R-CHOP in patients younger than 70 years with untreated diffuse large B cell lymphoma: A randomized, open-label, noninferiority phase 3 trial.

PubMed

Hara, Takeshi; Yoshikawa, Takeshi; Goto, Hideko; Sawada, Michio; Yamada, Toshiki; Fukuno, Kenji; Kasahara, Senji; Shibata, Yuhei; Matsumoto, Takuro; Mabuchi, Ryoko; Nakamura, Nobuhiko; Nakamura, Hiroshi; Ninomiya, Soranobu; Kitagawa, Junichi; Kanemura, Nobuhiro; Nannya, Yasuhito; Katsumura, Naoki; Takahashi, Takeshi; Kito, Yusuke; Takami, Tsuyoshi; Miyazaki, Tatsuhiko; Takeuchi, Tamotsu; Shimizu, Masahito; Tsurumi, Hisashi

2018-06-08

Pirarubicin (tetrahydropyranyl adriamycin [THP]) is an anthracyclin with less cardiotoxicity than doxorubicin (DOX). We previously reported the efficacy and safety of R-THP-COP consisting of rituximab (R), THP, cyclophosphamide (CPA), vincristine (VCR), and prednisolone (PSL) for diffuse large B cell lymphoma (DLBCL) in phase 2 studies. Here, we prospectively compared the efficacy and safety of the R-THP-COP and standard R-CHOP regimen (consisting of R, CPA, DOX, VCR, and PSL) in a noninferiority phase 3 trial. This prospective, randomized phase 3 study included patients younger than 70 years of age with previously untreated DLBCL. The regimen consisted of R (day 1), DOX, or THP (day 3), CPA (day 3), VCR (day 3), and PSL for 5 days every 3 weeks for 6 to 8 cycles. Between July 5, 2006 and June 11, 2013, 81 patients were randomly assigned to the treatment groups (R-CHOP group, 40 patients; R-THP-COP group, 41 patients). R-THP-COP was noninferior to R-CHOP, as assessed by the primary endpoint of complete response rate (85% vs 85% respectively). With a median follow-up of 75.2 months, the 5-year overall survival was 87% in the R-CHOP group and 82% in the R-THP-COP group (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.31-2.49; P = .82). The 5-year progression-free survival was 74% in the R-CHOP group and 79% in the R-THP-COP group (HR: 1.37, 95% CI: 0.56-3.55; P = .49). No grade 3 cardiac side effects were observed in either group. No serious late adverse reactions were observed in either group, with the exception of therapy-related acute myeloid leukemia in the R-THP-COP group. These data indicate that R-THP-COP is noninferior to R-CHOP with regard to clinical response, and has an acceptable safety profile. Thus, this regimen may be an alternative therapy to R-CHOP. Copyright © 2018 John Wiley & Sons, Ltd.

Control of Aeromonas on minimally processed vegetables by decontamination with lactic acid, chlorinated water, or thyme essential oil solution.

PubMed

Uyttendaele, M; Neyts, K; Vanderswalmen, H; Notebaert, E; Debevere, J

2004-02-01

Aeromonas is an opportunistic pathogen, which, although in low numbers, may be present on minimally processed vegetables. Although the intrinsic and extrinsic factors of minimally processed prepacked vegetable mixes are not inhibitory to the growth of Aeromonas species, multiplication to high numbers during processing and storage of naturally contaminated grated carrots, mixed lettuce, and chopped bell peppers was not observed. Aeromonas was shown to be resistant towards chlorination of water, but was susceptible to 1% and 2% lactic acid and 0.5% and 1.0% thyme essential oil treatment, although the latter provoked adverse sensory properties when applied for decontamination of chopped bell peppers. Integration of a decontamination step with 2% lactic acid in the processing line of grated carrots was shown to have the potential to control the overall microbial quality of the grated carrots and was particularly effective towards Aeromonas.

A low power low noise analog front end for portable healthcare system

NASA Astrophysics Data System (ADS)

Yanchao, Wang; Keren, Ke; Wenhui, Qin; Yajie, Qin; Ting, Yi; Zhiliang, Hong

2015-10-01

The presented analog front end (AFE) used to process human bio-signals consists of chopping instrument amplifier (IA), chopping spikes filter and programmable gain and bandwidth amplifier. The capacitor-coupling input of AFE can reject the DC electrode offset. The power consumption of current-feedback based IA is reduced by adopting capacitor divider in the input and feedback network. Besides, IA's input thermal noise is decreased by utilizing complementary CMOS input pairs which can offer higher transconductance. Fabricated in Global Foundry 0.35 μm CMOS technology, the chip consumes 3.96 μA from 3.3 V supply. The measured input noise is 0.85 μVrms (0.5-100 Hz) and the achieved noise efficient factor is 6.48. Project supported by the Science and Technology Commission of Shanghai Municipality (No. 13511501100), the State Key Laboratory Project of China (No. 11MS002), and the State Key Laboratory of ASIC & System, Fudan University.

CHOP versus GEM-P in previously untreated patients with peripheral T-cell lymphoma (CHEMO-T): a phase 2, multicentre, randomised, open-label trial.

PubMed

Gleeson, Mary; Peckitt, Clare; To, Ye Mong; Edwards, Laurice; Oates, Jacqueline; Wotherspoon, Andrew; Attygalle, Ayoma D; Zerizer, Imene; Sharma, Bhupinder; Chua, Sue; Begum, Ruwaida; Chau, Ian; Johnson, Peter; Ardeshna, Kirit M; Hawkes, Eliza A; Macheta, Marian P; Collins, Graham P; Radford, John; Forbes, Adam; Hart, Alistair; Montoto, Silvia; McKay, Pamela; Benstead, Kim; Morley, Nicholas; Kalakonda, Nagesh; Hasan, Yasmin; Turner, Deborah; Cunningham, David

2018-05-01

Outcomes with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like chemotherapy in peripheral T-cell lymphoma are poor. We investigated whether the regimen of gemcitabine, cisplatin, and methylprednisolone (GEM-P) was superior to CHOP as front-line therapy in previously untreated patients. We did a phase 2, parallel-group, multicentre, open-label randomised trial in 47 hospitals: 46 in the UK and one in Australia. Participants were patients aged 18 years and older with bulky (tumour mass diameter >10 cm) stage I to stage IV disease (WHO performance status 0-3), previously untreated peripheral T-cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, enteropathy-associated T-cell lymphoma, or hepatosplenic γδ T-cell lymphoma. We randomly assigned patients (1:1) stratified by subtype of peripheral T-cell lymphoma and international prognostic index to either CHOP (intravenous cyclophosphamide 750 mg/m 2 , doxorubicin 50 mg/m 2 , and vincristine 1·4 mg/m 2 [maximum 2 mg] on day 1, and oral prednisolone 100 mg on days 1-5) every 21 days for six cycles; or GEM-P (intravenous gemcitabine 1000 mg/m 2 on days 1, 8, and 15, cisplatin 100 mg/m 2 on day 15, and oral or intravenous methylprednisolone 1000 mg on days 1-5) every 28 days for four cycles. The primary endpoint was the proportion of patients with a CT-based complete response or unconfirmed complete response on completion of study chemotherapy, to detect a 20% superiority of GEM-P compared with CHOP, assessed in all patients who received at least one cycle of treatment and had an end-of-treatment CT scan or reported clinical progression as the reason for stopping trial treatment. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov (NCT01719835) and the European Clinical Trials Database (EudraCT 2011-004146-18). Between June 18, 2012, and Nov 16, 2016, we randomly assigned 87 patients to treatment, 43 to CHOP and 44 to GEM-P. A planned unmasked review of efficacy data by the independent data monitoring committee in November, 2016, showed that the number of patients with a confirmed or unconfirmed complete response with GEM-P was non-significantly inferior compared with CHOP and the trial was closed early. At a median follow-up of 27·4 months (IQR 16·6-38·4), 23 patients (62%) of 37 assessable patients assigned to CHOP had achieved a complete response or unconfirmed complete response compared with 17 (46%) of 37 assigned to GEM-P (odds ratio 0·52, 95% CI 0·21-1·31; p=0·164). The most common adverse events of grade 3 or worse in both groups were neutropenia (17 [40%] with CHOP and nine [20%] with GEM-P), thrombocytopenia (4 [10%] with CHOP and 13 [30%] with GEM-P, and febrile neutropenia (12 [29%] with CHOP and 3 [7%] with GEM-P). Two patients (5%) died during the study, both in the GEM-P group, from lung infections. The number of patients with a complete response or unconfirmed complete response did not differ between the groups, indicating that GEM-P was not superior for this outcome. CHOP should therefore remain the reference regimen for previously untreated peripheral T-cell lymphoma. Bloodwise and the UK National Institute of Health Research. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Effects of chopping time, meat source and storage temperature on the colour of New Zealand type fresh beef sausages.

PubMed

Boles, J A; Mikkelsen, V L; Swan, J E

1998-05-01

The colour stability of finely chopped fresh sausages made from post-rigor, pre-rigor salt added (1.5% w/w) or pre-rigor no salt added beef mince was evaluated using a Hunter Miniscan (L (∗) a (∗) b (∗)) and sensory colour panel. Batters were chopped for various times and sausages stored at -1.5 °, + 4.0 ° and + 8.0 °C. Regardless of meat source or chopping time, colour stability was greatest at -1.5 °C. Panellists found the colour of all sausages stored at -1.5 °C acceptable for at least six days. Sausages made from unsalted pre-rigor mince had markedly better colour stability than those made from the other meats, especially when stored at 4 °C or 8 °C.

Outcomes of a hospital-based employee lactation program.

PubMed

Spatz, Diane L; Kim, Gabriella S; Froh, Elizabeth B

2014-12-01

Little has been published about employee lactation support in hospitals and other healthcare facilities. The Children's Hospital of Philadelphia (CHOP), Philadelphia, PA, has a comprehensive employee lactation program. The objective of this study was to describe the breastfeeding practices of our employees and compare these results with national Centers for Disease Control and Prevention (CDC) data. The human resources department generated a list of all employees who filed for maternity leave between 2007 and 2011. These employees were contacted confidentially via e-mail to complete an electronic-based (SurveyMonkey.com) questionnaire. An initial message and three reminder messages were sent over a 3-month period during the last quarter of 2012, with 545 women completing the survey (response rate, 40%). Women who responded to the survey had significantly higher breastfeeding initiation rates compared with national CDC data (94.5% vs. 76.9%; p<0.0001). At 6 months, significantly more CHOP employees were breastfeeding (78.6% vs. 47.2%; p<0.0001). At 12 months 32.4% of CHOP employees were still breastfeeding compared with CDC data of 25.5% (p=0.0003). Additionally, over 20% of CHOP employees breastfed their infants for over 12 months (no national data for comparison). Within CHOP's comprehensive employee lactation program, women achieved breastfeeding milestones that well exceeded national data and the Healthy People 2020 targets for breastfeeding initiation and duration. CHOP's employee lactation program can serve as a model for other institutions.

A Host-Dependent Prognostic Model for Elderly Patients with Diffuse Large B-Cell Lymphoma.

PubMed

Miura, Katsuhiro; Konishi, Jun; Miyake, Takaaki; Makita, Masanori; Hojo, Atsuko; Masaki, Yasufumi; Uno, Masatoshi; Ozaki, Jun; Yoshida, Chikamasa; Niiya, Daigo; Kitazume, Koichi; Maeda, Yoshinobu; Takizawa, Jun; Sakai, Rika; Yano, Tomofumi; Yamamoto, Kazuhiko; Sunami, Kazutaka; Hiramatsu, Yasushi; Aoyama, Kazutoshi; Tsujimura, Hideki; Murakami, Jun; Hatta, Yoshihiro; Kanno, Masatoshi

2017-05-01

Decision-making models for elderly patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) are in great demand. The Society of Lymphoma Treatment in Japan (SoLT-J), in collaboration with the West-Japan Hematology and Oncology Group (West-JHOG), collected and retrospectively analyzed the clinical records of ≥65-year-old patients with DLBCL treated with R-CHOP from 19 sites across Japan to build an algorithm that can stratify adherence to R-CHOP. A total of 836 patients with a median age of 74 years (range, 65-96 years) were analyzed. In the SoLT-J cohort ( n  = 555), age >75 years, serum albumin level <3.7 g/dL, and Charlson Comorbidity Index score ≥3 were independent adverse risk factors and were defined as the Age, Comorbidities, and Albumin (ACA) index. Based on their ACA index score, patients were categorized into "excellent" (0 points), "good" (1 point), "moderate" (2 points), and "poor" (3 points) groups. This grouping effectively discriminated the 3-year overall survival rates, mean relative total doses (or relative dose intensity) of anthracycline and cyclophosphamide, unanticipated R-CHOP discontinuance rates, febrile neutropenia rates, and treatment-related death rates. Additionally, the ACA index showed comparable results for these clinical parameters when it was applied to the West-JHOG cohort ( n  = 281). The ACA index has the ability to stratify the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of elderly patients with DLBCL treated with R-CHOP. The Oncologist 2017;22:554-560 IMPLICATIONS FOR PRACTICE: Currently, little is known regarding how to identify elderly patients with diffuse large B-cell lymphoma who may tolerate a full dose of chemotherapy or to what extent cytotoxic drugs should be reduced in some specific conditions. The Society of Lymphoma Treatment in Japan developed a host-dependent prognostic model consisting of higher age (>75 years), hypoalbuminemia (<3.7 g/dL), and higher Charlson Comorbidity Index score (≥3) for such elderly patients. This model can stratify the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of these patients and thus help clinicians in formulating personalized treatment strategies for this growing patient population. © AlphaMed Press 2017.

A Host‐Dependent Prognostic Model for Elderly Patients with Diffuse Large B‐Cell Lymphoma

PubMed Central

Konishi, Jun; Miyake, Takaaki; Makita, Masanori; Hojo, Atsuko; Masaki, Yasufumi; Uno, Masatoshi; Ozaki, Jun; Yoshida, Chikamasa; Niiya, Daigo; Kitazume, Koichi; Maeda, Yoshinobu; Takizawa, Jun; Sakai, Rika; Yano, Tomofumi; Yamamoto, Kazuhiko; Sunami, Kazutaka; Hiramatsu, Yasushi; Aoyama, Kazutoshi; Tsujimura, Hideki; Murakami, Jun; Hatta, Yoshihiro; Kanno, Masatoshi

2017-01-01

Abstract Background. Decision‐making models for elderly patients with diffuse large B‐cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) are in great demand. Patients and Methods. The Society of Lymphoma Treatment in Japan (SoLT‐J), in collaboration with the West‐Japan Hematology and Oncology Group (West‐JHOG), collected and retrospectively analyzed the clinical records of ≥65‐year‐old patients with DLBCL treated with R‐CHOP from 19 sites across Japan to build an algorithm that can stratify adherence to R‐CHOP. Results. A total of 836 patients with a median age of 74 years (range, 65–96 years) were analyzed. In the SoLT‐J cohort (n = 555), age >75 years, serum albumin level <3.7 g/dL, and Charlson Comorbidity Index score ≥3 were independent adverse risk factors and were defined as the Age, Comorbidities, and Albumin (ACA) index. Based on their ACA index score, patients were categorized into “excellent” (0 points), “good” (1 point), “moderate” (2 points), and “poor” (3 points) groups. This grouping effectively discriminated the 3‐year overall survival rates, mean relative total doses (or relative dose intensity) of anthracycline and cyclophosphamide, unanticipated R‐CHOP discontinuance rates, febrile neutropenia rates, and treatment‐related death rates. Additionally, the ACA index showed comparable results for these clinical parameters when it was applied to the West‐JHOG cohort (n = 281). Conclusion. The ACA index has the ability to stratify the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of elderly patients with DLBCL treated with R‐CHOP. The Oncologist 2017;22:554–560 Implications for Practice. Currently, little is known regarding how to identify elderly patients with diffuse large B‐cell lymphoma who may tolerate a full dose of chemotherapy or to what extent cytotoxic drugs should be reduced in some specific conditions. The Society of Lymphoma Treatment in Japan developed a host‐dependent prognostic model consisting of higher age (>75 years), hypoalbuminemia (<3.7 g/dL), and higher Charlson Comorbidity Index score (≥3) for such elderly patients. This model can stratify the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of these patients and thus help clinicians in formulating personalized treatment strategies for this growing patient population. PMID:28408622

Emissions from cold heavy oil production with sands (CHOPS) facilities in Alberta, Canada

NASA Astrophysics Data System (ADS)

Roscioli, J. R.; Herndon, S. C.; Yacovitch, T. I.; Knighton, W. B.; Zavala-Araiza, D.; Johnson, M. R.; Tyner, D. R.

2017-12-01

Cold heavy oil production with sands (CHOPS) is generally characterized as a pump driven oil extraction method producing a mixture of sand, water, and heavy oil to heated liquid storage tanks. In addition to fluids, CHOPS sites also produce solution gas, primarily composed of methane, through the well annulus. Depending on formation and well production characteristics, large volumes of this solution gas are frequently vented to the atmosphere without flaring or conservation. To better understand these emission we present measurements of methane, ethane, propane and aromatic emission rates from CHOPS sites using dual tracer flux ratio methodology. The use of two tracers allowed on-site emission sources to be accurately identified and in one instance indicated that the annular vent was responsible for >75% of emissions at the facility. Overall, a measurement survey of five CHOPS sites finds that the methane emissions are in general significantly under-reported by operators. This under-reporting may arise from uncertainties associated with measured gas-to-oil ratios upon which the reported vent volume is based. Finally, measurements of ethane, propane and aromatics from these facilities indicates surprisingly low non-methane hydrocarbon content.

Evaluation of alkaline electrolyzed water to replace traditional phosphate enhancement solutions: Effects on water holding capacity, tenderness, and sensory characteristics.

PubMed

Rigdon, Macc; Hung, Yen-Con; Stelzleni, Alexander M

2017-01-01

Sixty-four pork loins were randomly assigned to one of four treatments to evaluate the use of alkaline electrolyzed reduced water as a replacement for traditional enhancement solutions. Treatments included: alkaline electrolyzed reduced water (EOH; pH≈11.5), EOH plus 2.5% potassium-lactate (EOK), industry standard (IS; 0.35% sodium tri-polyphosphate, 0.14% sodium chloride, 2.5% potassium-lactate), and no enhancement (CON). After enhancement (targeting 110%) and rest period, chops were cut (2.54-cm) to test treatment effects on water holding capacity, Warner-Bratzler shear force (WBSF), and sensory attributes. Despite its alkaline nature EOH chops exuded more water (P<0.05) than EOK, IS, or CON chops. Control chops were similar (P>0.05) to EOK, however CON and EOK both lost more moisture (P<0.05) than IS. The use of alkaline electrolyzed reduced water did not improve WBSF or sensory characteristics compared to IS treated chops. As a stand-alone enhancement solution alkaline electrolyzed reduced water was not a suitable replacement for industry standard solutions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Method of Fabricating Chopped-Fiber Composite Piston

NASA Technical Reports Server (NTRS)

Rivers, H. Kevin (Inventor); Ransone, Philip O. (Inventor); Northam, G. Burton (Inventor)

1999-01-01

A three-dimensional piston molding is fabricated from a mixture of chopped, carbon tow filaments of variable length, which are prepregged with carbonaceous organic resins and/or pitches and molded by conventional molding processes into a near net shape, to form a carbon-fiber reinforced organic-matrix composite part. Continuous reinforcement in the form of carbon-carbon composite tapes or pieces of fabric can be also laid in the mold before or during the charging of the mold with the chopped-fiber mixture, to enhance the strength in the crown and wrist-pin areas. The molded chopped-fiber reinforced organic-matrix composite parts are then pyrolized in an inert atmosphere, to convert the organic matrix materials to carbon. These pyrolized parts are then densified by reimpregnation with resins or pitches, which are subsequently carbonized. Densification is also accomplished by direct infiltration with carbon by vapor deposition processes. Once the desired density has been achieved, the piston molds are machined to final piston dimensions, and piston ring grooves are added. To prevent oxidation and/or to seal the piston surface or near surface, the chopped-fiber piston is coated with ceramic and/or metallic sealants: and/or coated with a catalyst.

Straight and chopped DC performance data for a reliance EV-250AT motor with a General Electric EV-1 controller

NASA Technical Reports Server (NTRS)

Edie, P. C.

1981-01-01

Straight and chopped DC motor performances for a Reliance EV-250AT motor with an EV-1 controller were examined. Effects of motor temperature and operating voltage are shown. It is found that the maximum motor efficiency is approximately 85% at low operating temperatures in the straight DC mode. Chopper efficiency is 95% under all operating conditions. For equal speeds, the motor operated in the chopped mode develops slightly more torque and draws more current than it does in the straight DC mode.

Macrolide Antibiotics Exhibit Cytotoxic Effect under Amino Acid-Depleted Culture Condition by Blocking Autophagy Flux in Head and Neck Squamous Cell Carcinoma Cell Lines

PubMed Central

Hirasawa, Kazuhiro; Moriya, Shota; Miyahara, Kana; Kazama, Hiromi; Hirota, Ayako; Takemura, Jun; Abe, Akihisa; Inazu, Masato; Hiramoto, Masaki; Tsukahara, Kiyoaki

2016-01-01

Autophagy, a self-digestive system for cytoplasmic components, is required to maintain the amino acid pool for cellular homeostasis. We previously reported that the macrolide antibiotics azithromycin (AZM) and clarithromycin (CAM) have an inhibitory effect on autophagy flux, and they potently enhance the cytocidal effect of various anticancer reagents in vitro. This suggests that macrolide antibiotics can be used as an adjuvant for cancer chemotherapy. Since cancer cells require a larger metabolic demand than normal cells because of their exuberant growth, upregulated autophagy in tumor cells has now become the target for cancer therapy. In the present study, we examined whether macrolides exhibit cytotoxic effect under an amino acid-starving condition in head and neck squamous cancer cell lines such as CAL 27 and Detroit 562 as models of solid tumors with an upregulated autophagy in the central region owing to hypovascularity. AZM and CAM induced cell death under the amino acid-depleted (AAD) culture condition in these cell lines along with CHOP upregulation, although they showed no cytotoxicity under the complete culture medium. CHOP knockdown by siRNA in the CAL 27 cells significantly suppressed macrolide-induced cell death under the AAD culture condition. CHOP-/- murine embryonic fibroblast (MEF) cell lines also attenuated AZM-induced cell death compared with CHOP+/+ MEF cell lines. Using a tet-off atg5 MEF cell line, knockout of atg5, an essential gene for autophagy, also induced cell death and CHOP in the AAD culture medium but not in the complete culture medium. This suggest that macrolide-induced cell death via CHOP induction is dependent on autophagy inhibition. The cytotoxicity of macrolide with CHOP induction was completely cancelled by the addition of amino acids in the culture medium, indicating that the cytotoxicity is due to the insufficient amino acid pool. These data suggest the possibility of using macrolides for “tumor-starving therapy”. PMID:27977675

Cost-Effectiveness Analysis of Bendamustine Plus Rituximab as a First-Line Treatment for Patients with Follicular Lymphoma in Spain.

PubMed

Sabater, Eliazar; López-Guillermo, Armando; Rueda, Antonio; Salar, Antonio; Oyagüez, Itziar; Collar, Juan Manuel

2016-08-01

Follicular lymphoma (FL) is the second most common type of lymphoid cancer in Western Europe. The aim of this study was to evaluate the cost utility of rituximab-bendamustine treatment compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) treatment as a first-line therapy for patients with advanced FL in Spain. A Markov model was developed to estimate the cost effectiveness of rituximab-bendamustine compared with R-CHOP as first-line treatment for patients with advanced FL in the Spanish National Health System (NHS). Transitions between health states (progression-free, including induction and maintenance; first relapse; second relapse; and death) were allowed for the patient cohort in 4-week-long cycles. Clinical data for the extrapolation of progression-free survival curves were obtained from randomized trials. Mortality rates and utilities were obtained from the literature. Outcomes were measured as quality-adjusted life-years (QALYs). The total costs (€, 2013) included drug costs (ex-factory prices with mandatory deductions), disease management costs and adverse event-associated costs. Costs and outcomes were discounted at a 3 % annual rate. Probabilistic sensitivity analysis was performed using 10,000 Monte Carlo simulations to assess the model robustness. Treatment and administration costs during the induction phase were higher for rituximab-bendamustine (€17,671) than for R-CHOP (€11,850). At the end of the 25-year period, the rituximab-bendamustine first-line strategy had a total cost of €68,357 compared with €69,528 for R-CHOP. Health benefits were higher for rituximab-bendamustine treatment (10.31 QALYs) than for R-CHOP treatment (9.82 QALYs). In the probabilistic analysis, rituximab-bendamustine was the dominant strategy over treatment with R-CHOP in 53.4 % of the simulations. First-line therapy with rituximab-bendamustine in FL patients was the dominant strategy over treatment with R-CHOP; it showed cost savings and higher health benefits for the Spanish NHS.

Characterization of methane emissions from five cold heavy oil production with sands (CHOPS) facilities.

PubMed

Roscioli, Joseph R; Herndon, Scott C; Yacovitch, Tara I; Knighton, W Berk; Zavala-Araiza, Daniel; Johnson, Matthew R; Tyner, David R

2018-03-07

Cold heavy oil production with sands (CHOPS) is a common oil extraction method in the Canadian provinces of Alberta and Saskatchewan that can result in significant methane emissions due to annular venting. Little is known about the magnitude of these emissions, nor their contributions to the regional methane budget. Here the authors present the results of field measurements of methane emissions from CHOPS wells and compare them with self-reported venting rates. The tracer ratio method was used not only to analyze total site emissions but at one site it was also used to locate primary emission sources and quantify their contributions to the facility-wide emission rate, revealing the annular vent to be a dominant source. Emissions measured from five different CHOPS sites in Alberta showed large discrepancies between the measured and reported rates, with emissions being mainly underreported. These methane emission rates are placed in the context of current reporting procedures and the role that gas-oil ratio (GOR) measurements play in vented volume estimates. In addition to methane, emissions of higher hydrocarbons were also measured; a chemical "fingerprint" associated with CHOPS wells in this region reveals very low emission ratios of ethane, propane, and aromatics versus methane. The results of this study may inform future studies of CHOPS sites and aid in developing policy to mitigate regional methane emissions. Methane measurements from cold heavy oil production with sand (CHOPS) sites identify annular venting to be a potentially major source of emissions at these facilities. The measured emission rates are generally larger than reported by operators, with uncertainty in the gas-oil ratio (GOR) possibly playing a large role in this discrepancy. These results have potential policy implications for reducing methane emissions in Alberta in order to achieve the Canadian government's goal of reducing methane emissions by 40-45% below 2012 levels within 8 yr.

What do preweaned and weaned calves need in the diet: a high fiber content or a forage source?

PubMed

Terré, M; Pedrals, E; Dalmau, A; Bach, A

2013-08-01

The objective of this study was to determine whether the improvement of performance of young calves associated with the supplementation of chopped grass hay reported in some studies is due to an increase in the total neutral detergent fiber (NDF) content of the consumed diet or to the provision of chopped grass hay. Sixty-three Holstein calves [9±4.4 d old; mean ± standard deviation (SD)] were randomly distributed in 4 treatments resulting from the combination of 2 levels of NDF content of a pelleted starter and the supply or absence of forage provision: low-NDF starter (18%) with or without chopped oat hay, and high-NDF starter (27%) with or without chopped oat hay. All animals were fed the same milk replacer (21% crude protein and 19.2% fat) at the rate of 4 L/d at 15% dry matter from d 1 to 34, and 2 L/d at 15% dry matter from d 35 to 42 (weaning). The study finished 2 wk after weaning. Body weight was measured weekly and individual calf starter and hay intake was recorded daily. On d 50, blood samples were drawn 2h after the morning concentrate offer to determine serum glucose and insulin concentrations. On d 52, samples of ruminal fluid were obtained via an esophageal tube, and pH was measured immediately. During the preweaning period, pelleted starter intake was similar among treatments, but average daily gain tended to be greater in low- than in high-NDF treatments (0.69 vs. 0.63±0.020 kg/d, respectively; mean ± SD). However, during the 2 wk after weaning, supplementation of forage improved pelleted starter intake and average daily gain without affecting the gain-to-feed ratio. Probably, the greater pelleted starter intake observed in forage-supplemented calves was mainly due to the greater ruminal pH found in forage-supplemented calves compared with forage-deprived calves (5.81 vs. 5.05±0.063, respectively). Blood insulin-to-glucose ratio was greater in forage-supplemented compared with unsupplemented calves [mean ± SD; 6.53 vs. 4.24±0.125 insulin (ng/L)-to-glucose (mg/dL) ratio, respectively]. In conclusion, a low-NDF pelleted starter is recommended during the preweaning period, and the provision of chopped hay is necessary right after weaning to improve calf performance. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Airborne vs. Inventory Measurements of Methane Emissions in the Alberta Upstream Oil and Gas Sector

NASA Astrophysics Data System (ADS)

Johnson, M.; Tyner, D. R.; Conley, S.; Schwietzke, S.; Zavala Araiza, D.

2017-12-01

Airborne measurements of methane emission rates were directly compared with detailed, spatially-resolved inventory estimates for different oil and gas production regions in Alberta, Canada. For a 50 km × 50 km region near Red Deer, Alberta, containing 2700 older gas and oil wells, measured methane emissions were 16 times higher than reported venting and flaring volumes would suggest, but consistent with regional inventory estimates (which include estimates for additional emissions from pneumatic equipment, fugitive leaks, gas migration, etc.). This result highlights how 94% of methane emissions in this region are attributable to sources missing from current reporting requirements. The comparison was even more stark for a 60 km × 60 km region near Lloydminster, dominated by 2300 cold heavy oil with sand (CHOPS) production sites. Aircraft measured methane emissions in this region were 5 times larger than that expected from reported venting and flaring volumes, and more than 3 times greater than regional inventory estimates. This significant discrepancy is most likely attributable to underreported intentional venting of casing gas at CHOPS sites, which is generally estimated based on the product of the measured produced oil volume and an assumed gas to oil ratio (GOR). GOR values at CHOPS sites can be difficult to measure and can be notoriously variable in time. Considering the implications for other CHOPS sites across Alberta only, the present results suggest that total reported venting in Alberta is low by a factor of 2.4 (range of 2.0-2.7) and total methane emissions from the conventional oil and gas sector (excluding mined oil sands) are likely at least 25-41% greater than currently estimated. This work reveals critical gaps in current measurement and reporting, while strongly supporting the need for urgent mitigation efforts in the context of newly proposed federal methane regulations in Canada, and separate regulatory development efforts in the province of Alberta.

Gene regulatory network of unfolded protein response genes in endoplasmic reticulum stress.

PubMed

Takayanagi, Sayuri; Fukuda, Riga; Takeuchi, Yuuki; Tsukada, Sakiko; Yoshida, Kenichi

2013-01-01

In the endoplasmic reticulum (ER), secretory and membrane proteins are properly folded and modified, and the failure of these processes leads to ER stress. At the same time, unfolded protein response (UPR) genes are activated to maintain homeostasis. Despite the thorough characterization of the individual gene regulation of UPR genes to date, further investigation of the mutual regulation among UPR genes is required to understand the complex mechanism underlying the ER stress response. In this study, we aimed to reveal a gene regulatory network formed by UPR genes, including immunoglobulin heavy chain-binding protein (BiP), X-box binding protein 1 (XBP1), C/EBP [CCAAT/enhancer-binding protein]-homologous protein (CHOP), PKR-like endoplasmic reticulum kinase (PERK), inositol-requiring 1 (IRE1), activating transcription factor 6 (ATF6), and ATF4. For this purpose, we focused on promoter-luciferase reporters for BiP, XBP1, and CHOP genes, which bear an ER stress response element (ERSE), and p5 × ATF6-GL3, which bears an unfolded protein response element (UPRE). We demonstrated that the luciferase activities of the BiP and CHOP promoters were upregulated by all the UPR genes, whereas those of the XBP1 promoter and p5 × ATF6-GL3 were upregulated by all the UPR genes except for BiP, CHOP, and ATF4 in HeLa cells. Therefore, an ERSE- and UPRE-centered gene regulatory network of UPR genes could be responsible for the robustness of the ER stress response. Finally, we revealed that BiP protein was degraded when cells were treated with DNA-damaging reagents, such as etoposide and doxorubicin; this finding suggests that the expression level of BiP is tightly regulated at the post-translational level, rather than at the transcriptional level, in the presence of DNA damage.

Egg Products for Use in a Cook-Freeze System

DTIC Science & Technology

1976-08-01

ounces) of water„ Peppers, green, finely chopped 4.56 1,65 748.4 3. Saute onions Oil, vegetable 1.98 0.72 326.6 and peppers in oil Butter 1^9 8 2...chestnuts, canned 6.84 2.48 1,124.9 5. Blend egg chopped white/methocel, Soy sauce 1.82 0.66 299.4 sauteed onions and Monosodium glutamate 0.05 0.02 9.1...black pepper, smoke Egg, yolk, blended 30.68 11.11 5,039.5 salt, nonfat dry 12 «PMP Ingredients Intage Pounds Grama Procedure Ham, chopped 15.21

Impact of inadequate doses of rituximab in the treatment of diffuse large B cell lymphoma in Malaysian patients.

PubMed

Gan, Gin Gin; Subramaniam, Rajaletchumy; Bee, Ping Chong; Chin, Edmund Fui Min; Abdul-Halim, Habibah; Tai, Mei Chee

2014-01-01

The current standard treatment for patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) is rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). A significant number of patients were not treated with recommended dose of rituximab due to limited financial resources in Malaysia. This study evaluates the efficacy of R-CHOP like chemotherapy in Malaysian patients with DLBCL. The study comprised a retrospective analysis of patients with DLBCL treated at a single centre. The outcome was compared with patients who were treated with R-CHOP like and CHOP like chemotherapy. Patients who were treated with lower dose of rituximab was subanalysed for outcome. A total of 86 patients who had CHOP-like chemotherapy were included. Only 39 (45%) patients had rituximab and only 12 (29%) patients had the recommended dose. The overall response (OR) and complete response (CR) rates were 88% and 81% respectively. There was no significant difference in OR and CR in patients who had rituximab and those without rituxmab. Those with International Prognostic Index (IPI) score of ≤ 2 had significant higher CR rate, progression free survival (PFS) and overall survival (p<0.001). The lack of significant improvement in CR and DFS in our patients may be due to an inadequate dose of rituximab.

Baicalin Protects the Cardiomyocytes from ER Stress-Induced Apoptosis: Inhibition of CHOP through Induction of Endothelial Nitric Oxide Synthase

PubMed Central

Wang, Bo; Guo, Xiaowang; Zeng, Chao; Xu, Yong; Shen, Liangliang; Cheng, Ke; Xia, Yuesheng; Li, Xiumin; Wang, Haichang; Fan, Li; Wang, Xiaoming

2014-01-01

Baicalin, the main active ingredient of the Scutellaria root, exerts anti-oxidant and anti-apoptotic effects in cardiovascular diseases. However, the therapeutic mechanism of baicalin remains unknown. Cultured neonatal rat cardiomyocytes were pre-treated with baicalin (0–50 µM) for 24 h, and subsequently treated with tunicamycin (100 ng/ml). Cell viability was detected by MTT assay, and cell damage was determined by LDH release and TUNEL assay. The expression of CHOP, JNK, caspase-3, eNOS was analyzed by western blot. NO was measured by DAF-FM staining. As a result, treatment with baicalin significantly reduced apoptosis induced by ER stress inducer tunicamycin in cardiomyocytes. Molecularly, baicalin ameliorated tunicamycin-induced ER stress by downregulation of CHOP. In addition, baicalin inverted tunicamycin-induced decreases of eNOS mRNA and protein levels, phospho eNOS and NO production through CHOP pathway. However, the protective effects of baicalin were significantly decreased in cardiomyocytes treated with L-NAME, which suppressed activation of nitric oxide synthase. In conclusion, our results implicate that baicalin could protect cardiomyocytes from ER stress-induced apoptosis via CHOP/eNOS/NO pathway, and suggest the therapeutic values of baicalin against ER stress-associated cardiomyocyte apoptosis. PMID:24520378

Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial.

PubMed

Rummel, Mathias J; Niederle, Norbert; Maschmeyer, Georg; Banat, G Andre; von Grünhagen, Ulrich; Losem, Christoph; Kofahl-Krause, Dorothea; Heil, Gerhard; Welslau, Manfred; Balser, Christina; Kaiser, Ulrich; Weidmann, Eckhart; Dürk, Heinz; Ballo, Harald; Stauch, Martina; Roller, Fritz; Barth, Juergen; Hoelzer, Dieter; Hinke, Axel; Brugger, Wolfram

2013-04-06

Rituximab plus chemotherapy, most often CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), is the first-line standard of care for patients with advanced indolent lymphoma, and for elderly patients with mantle-cell lymphoma. Bendamustine plus rituximab is effective for relapsed or refractory disease. We compared bendamustine plus rituximab with CHOP plus rituximab (R-CHOP) as first-line treatment for patients with indolent and mantle-cell lymphomas. We did a prospective, multicentre, randomised, open-label, non-inferiority trial at 81 centres in Germany between Sept 1, 2003, and Aug 31, 2008. Patients aged 18 years or older with a WHO performance status of 2 or less were eligible if they had newly diagnosed stage III or IV indolent or mantle-cell lymphoma. Patients were stratified by histological lymphoma subtype, then randomly assigned according to a prespecified randomisation list to receive either intravenous bendamustine (90 mg/m(2) on days 1 and 2 of a 4-week cycle) or CHOP (cycles every 3 weeks of cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), and vincristine 1.4 mg/m(2) on day 1, and prednisone 100 mg/day for 5 days) for a maximum of six cycles. Patients in both groups received rituximab 375 mg/m(2) on day 1 of each cycle. Patients and treating physicians were not masked to treatment allocation. The primary endpoint was progression-free survival, with a non-inferiority margin of 10%. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00991211, and the Federal Institute for Drugs and Medical Devices of Germany, BfArM 4021335. 274 patients were assigned to bendamustine plus rituximab (261 assessed) and 275 to R-CHOP (253 assessed). At median follow-up of 45 months (IQR 25-57), median progression-free survival was significantly longer in the bendamustine plus rituximab group than in the R-CHOP group (69.5 months [26.1 to not yet reached] vs 31.2 months [15.2-65.7]; hazard ratio 0.58, 95% CI 0.44-0.74; p<0.0001). Bendamustine plus rituximab was better tolerated than R-CHOP, with lower rates of alopecia (0 patients vs 245 (100%) of 245 patients who recieved ≥3 cycles; p<0.0001), haematological toxicity (77 [30%] vs 173 [68%]; p<0.0001), infections (96 [37%] vs 127 [50%]); p=0.0025), peripheral neuropathy (18 [7%] vs 73 [29%]; p<0.0001), and stomatitis (16 [6%] vs 47 [19%]; p<0.0001). Erythematous skin reactions were more common in patients in the bendamustine plus rituximab group than in those in the R-CHOP group (42 [16%] vs 23 [9%]; p=0.024). In patients with previously untreated indolent lymphoma, bendamustine plus rituximab can be considered as a preferred first-line treatment approach to R-CHOP because of increased progression-free survival and fewer toxic effects. Roche Pharma AG, Ribosepharm/Mundipharma GmbH. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dengue Virus Modulates the Unfolded Protein Response in a Time-dependent Manner*

PubMed Central

Peña, José; Harris, Eva

2011-01-01

Flaviviruses, such as dengue virus (DENV), depend on the host endoplasmic reticulum for translation, replication, and packaging of their genomes. Here we report that DENV-2 infection modulates the unfolded protein response in a time-dependent manner. We show that early DENV-2 infection triggers and then suppresses PERK-mediated eIF2α phosphorylation and that in mid and late DENV-2 infection, the IRE1-XBP1 and ATF6 pathways are activated, respectively. Activation of IRE1-XBP1 correlated with induction of downstream targets GRP78, CHOP, and GADD34. Furthermore, induction of CHOP did not induce apoptotic markers, such as suppression of anti-apoptotic protein Bcl-2, activation of caspase-9 or caspase-3, and cleavage of poly(ADP-ribose) polymerase. Finally, we show that DENV-2 replication is affected in PERK−/− and IRE1−/− mouse embryo fibroblasts when compared with wild-type mouse embryo fibroblasts. These results demonstrate that time-dependent activation of the unfolded protein response by DENV-2 can override inhibition of translation, prevent apoptosis, and prolong the viral life cycle. PMID:21385877

Prognostic Value of the Pretreatment Advanced Lung Cancer Inflammation Index (ALI) in Diffuse Large B Cell Lymphoma Patients Treated with R-CHOP Chemotherapy.

PubMed

Park, Young Hoon; Yi, Hyeon Gyu; Lee, Moon Hee; Kim, Chul Soo; Lim, Joo Han

2017-01-01

The Advanced Lung Cancer Inflammation Index (ALI, body mass index × albumin/neutrophil-to-lymphocyte ratio) has been demonstrated to be a prognostic factor of survival in some solid cancers. We retrospectively investigated the usefulness of the ALI to predict chemotherapy response and survival in 212 patients with diffuse large B cell lymphoma (DLBCL) treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. Patients were allocated to a low ALI group (n = 82, 38.7%) or a high ALI group (n = 130, 61.3%) according to an optimal pretreatment ALI cut-off value of 15.5 as determined by receiver operating curve analysis. The low ALI group displayed more adverse clinical characteristics, lower rates of complete remission (54.9 vs. 75.4%, p = 0.008), and poorer 5-year progression-free (PFS, 58.1 vs. 77.3%, p = 0.006) and overall (OS, 64.2 vs. 80.2%, p = 0.008) survival. Multivariate analysis showed that low ALI was found to independently predict shorter PFS and OS. Interestingly, a low ALI reverted to a high ALI during treatment in 58 patients (27.4%), and the 5-year OS of these patients was better than that of patients whose ALI remained low (n = 24, 72.5 vs. 24%, p < 0.001). ALI might be an easily available marker for predicting clinical outcomes in DLBCL patients treated with R-CHOP chemotherapy. © 2017 S. Karger AG, Basel.

Whole-brain radiotherapy and high-dose methylprednisolone for elderly patients with primary central nervous system lymphoma: Results of North Central Cancer Treatment Group (NCCTG) 96-73-51

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

Laack, Nadia N.; Ballman, Karla V.; Mayo Clinic Cancer Center, Rochester, MN

Purpose: The aim of this study was to evaluate the efficacy, toxicity, and survival of whole-brain radiotherapy-treated (WBRT) and high-dose methylprednisolone (HDMP)-treated in elderly patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Patients with PCNSL who were 70 years and older received 1 g of methylprednisolone daily for 5 days, 30 days after WBRT. Patients then received 1 g of methylprednisolone every 28 days until progression. The primary endpoint was overall survival (OS) at 6 months. Results were compared with those in patients on the previous North Central Cancer Treatment Group (NCCTG) trial who received pre-WBRT cytoxan,more » adriamycin, vincristine, prednisone (CHOP) and high-dose cytarabine (CHOP-WBRT). A planned interim analysis was performed. The current regimen would be considered inactive if survival was not improved from patients treated with CHOP-WBRT. Results: Nineteen patients were accrued between 1998 and 2003. Median age was 76 years. Interim analysis revealed a 6-month survival of 33%, resulting in closure of the trial. Toxicity, OS, and event-free survival (EFS) were similar to those in patients more than 70 years of age who received CHOP-WBRT. The subgroup of patients who received HDMP had longer OS (12.1 vs. 7.0 months, p = 0.76) and EFS (11.7 vs. 4.0 months, p = 0.04) compared with the CHOP-WBRT patients alive 60 days after the start of treatment. Conclusions: Patients on-study long enough to receive HDMP had prolongation of OS and EFS compared to patients receiving CHOP-WBRT. Although the numbers of patients are too small for statistical conclusions, the HDMP regimen deserves further study.« less

Frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL.

PubMed

Offner, Fritz; Samoilova, Olga; Osmanov, Evgenii; Eom, Hyeon-Seok; Topp, Max S; Raposo, João; Pavlov, Viacheslav; Ricci, Deborah; Chaturvedi, Shalini; Zhu, Eugene; van de Velde, Helgi; Enny, Christopher; Rizo, Aleksandra; Ferhanoglu, Burhan

2015-10-15

This phase 2 study evaluated whether substituting bortezomib for vincristine in frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy could improve efficacy in non-germinal center B-cell-like diffuse large B-cell lymphoma (non-GCB DLBCL), centrally confirmed by immunohistochemistry (Hans method). In total, 164 patients were randomized 1:1 to receive six 21-day cycles of rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2), and doxorubicin 50 mg/m(2), all IV day 1, prednisone 100 mg/m(2) orally days 1-5, plus either bortezomib 1.3 mg/m(2) IV days 1, 4, 8, 11 (rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib [VR-CAP]; n = 84) or vincristine 1.4 mg/m(2) (maximum 2 mg) IV day 1 (R-CHOP; n = 80). There were no significant differences between VR-CAP and R-CHOP in complete response rate (64.5%, 66.2%; odds ratio [OR], 0.91; P = .80), overall response rate (93.4%, 98.6%; OR, 0.21; P = .11), progression-free survival (hazard ratio [HR], 1.12; P = .76), or overall survival (HR, 0.89; P = .75). Rates of grade ≥3 adverse events (AEs; 88%, 89%), serious AEs (38%, 34%), discontinuations due to AEs (7%, 3%), and deaths due to AEs (2%, 5%) were similar with VR-CAP and R-CHOP. Grade ≥3 peripheral neuropathy rates were 6% and 3%, respectively. VR-CAP did not improve efficacy vs R-CHOP in non-GCB DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT01040871. © 2015 by The American Society of Hematology.

Method of making a continuous ceramic fiber composite hot gas filter

DOEpatents

Hill, Charles A.; Wagner, Richard A.; Komoroski, Ronald G.; Gunter, Greg A.; Barringer, Eric A.; Goettler, Richard W.

1999-01-01

A ceramic fiber composite structure particularly suitable for use as a hot gas cleanup ceramic fiber composite filter and method of making same from ceramic composite material has a structure which provides for increased strength and toughness in high temperature environments. The ceramic fiber composite structure or filter is made by a process in which a continuous ceramic fiber is intimately surrounded by discontinuous chopped ceramic fibers during manufacture to produce a ceramic fiber composite preform which is then bonded using various ceramic binders. The ceramic fiber composite preform is then fired to create a bond phase at the fiber contact points. Parameters such as fiber tension, spacing, and the relative proportions of the continuous ceramic fiber and chopped ceramic fibers can be varied as the continuous ceramic fiber and chopped ceramic fiber are simultaneously formed on the porous vacuum mandrel to obtain a desired distribution of the continuous ceramic fiber and the chopped ceramic fiber in the ceramic fiber composite structure or filter.

Influence of fresh alfalfa supplementation on fat skatole and indole concentration and chop odour and flavour in lambs grazing a cocksfoot pasture.

PubMed

Devincenzi, T; Prunier, A; Meteau, K; Nabinger, C; Prache, S

2014-12-01

We investigated the influence of the level of fresh alfalfa supplementation on fat skatole and indole concentration and chop sensory attributes in grazing lambs. Four groups of nine male Romane lambs grazing a cocksfoot pasture were supplemented with various levels of alfalfa for at least 60days before slaughter. Perirenal fat skatole concentration was higher for lambs that consumed alfalfa than for those that consumed only cocksfoot. The intensity of 'animal' odour in the lean part of the chop and of 'animal' flavour in both the lean and fat parts of the chop, evaluated by a trained sensory panel, increased from the lowest level of alfalfa supplementation onwards and did not increase further with increasing levels of alfalfa supplementation. The outcome of this study therefore suggests that these sensory attributes may reach a plateau when perirenal fat skatole concentration is in the range 0.16-0.24μg/g of liquid fat. Copyright © 2014. Published by Elsevier Ltd.

EFFECTS OF TEMPERATURE AND ENVIRONMENT ON MECHANICAL PROPERTIES OF TWO CHOPPED-FIBER AUTOMOTIVE STRUCTURAL COMPOSITES

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

Ruggles-Wrenn, M.B.

2003-10-06

The Durability of Lightweight Composite Structures Project was established at Oak Ridge National Laboratory (ORNL) by the U.S. Department of Energy to provide the experimentally-based, durability-driven design guidelines necessary to assure long-term structural integrity of automotive composite components. The initial focus of the ORNL Durability Project was on composite materials consisting of polyurethane reinforced with E-glass. Current focus of the project is on composite materials reinforced with carbon fibers. The primary purpose of this report is to provide the individual specimen test date. Basic mechanical property testing and results for two chopped-fiber composite materials, one reinforced with glass- and themore » other with carbon fiber are provided. Both materials use the same polyurethane matrix. Preforms for both materials were produced using the P4 process. Behavioral trends, effects of temperature and environment, and corresponding design knockdown factors are established for both materials. Effects of prior short-time loads and of prior thermal cycling are discussed.« less

Diffraction, chopping, and background subtraction for LDR

NASA Technical Reports Server (NTRS)

Wright, Edward L.

1988-01-01

The Large Deployable Reflector (LDR) will be an extremely sensitive infrared telescope if the noise due to the photons in the large thermal background is the only limiting factor. For observations with a 3 arcsec aperture in a broadband at 100 micrometers, a 20-meter LDR will emit 10(exp 12) per second, while the photon noise limited sensitivity in a deep survey observation will be 3,000 photons per second. Thus the background subtraction has to work at the 1 part per billion level. Very small amounts of scattered or diffracted energy can be significant if they are modulated by the chopper. The results are presented for 1-D and 2-D diffraction calculations for the lightweight, low-cost LDR concept that uses an active chopping quaternary to correct the wavefront errors introduced by the primary. Fourier transforms were used to evaluate the diffraction of 1 mm waves through this system. Unbalanced signals due to dust and thermal gradients were also studied.

Profile based image analysis for identification of chopped biomass stem nodes and internodes

USDA-ARS?s Scientific Manuscript database

Because of their significant variation in chemical composition, segregation of chopped biomass into nodes and internodes helps in efficient utilization of these feedstocks. Stem internodes having low ash content are a better feedstock for bioenergy and biofuel applications than nodes. However, separ...

Phaco chop technique for cataract surgery in the dog.

PubMed

Warren, Christi

2004-01-01

Phaco chop is a bimanual phacoemulsification technique to remove cataracts. The technique was first presented at the 1993 3rd American-International Congress on Cataract, IOL, and Refractive Surgery in Seattle by Dr Kunihiro Nagahara. He compared the lens with a block of wood and by applying chopping forces parallel to the natural planes of the lens lamellae, as one does in splitting wood, a nucleus can be cleaved with surprisingly little force and time. Dr Nagahara used the phaco tip to impale and high vacuum to hold the nucleus while a second instrument, or chopper, hooked the equator and was pulled centrally, splitting the nucleus along its natural cleavage planes. This was a breakthrough for surgeons who had been utilizing several minutes of phaco energy sculpting grooves and bowls in a lens. Studies have shown that compared with four-quadrant 'divide and conquer', the phaco chop technique uses less phaco time and energy, significantly reducing endothelial cell damage. Other advantages of phaco chop include reduction of zonular and capsular stress because forces are directed toward an opposing instrument and the phaco tip is kept in a central 'safe zone' in the middle of the pupil. This technique has also been successfully adapted to the canine phacoemulsification procedure. The larger canine lens requires some modifications, and lenses with hard nuclear and cortical material may not be amenable to this procedure.

Effect of stachydrine on endoplasmic reticulum stress-induced apoptosis in rat kidney after unilateral ureteral obstruction.

PubMed

Zhang, Cui; Lu, Ying; Tong, Qian-Qian; Zhang, Lan; Guan, Yu-Fei; Wang, Shu-Jing; Xing, Zhi-Hua

2013-01-01

Our study aimed at determining the effect of stachydrine on the PERK, CHOP, and caspase-3 in rat kidney with RIF. Rats were randomly divided into control group, model group, enalapril group, high stachydrine group, medium stachydrine group, and low stachydrine group. RIF models of five groups were developed by unilateral ureteral obstruction except the control group. The rats were sacrificed 12 days after surgery and blood samples were collected. Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were detected. Renal tubular damage index was determined by HE staining. The area percentage of RIF was determined by the Masson method. Expressions of PERK, CHOP, and caspase-3 in kidney were determined by immunohistochemistry. Tubulointerstitial injury index, RIF, serum Scr, BUN level, and expressions of PERK, CHOP, and caspase-3 were different between the model and treatment groups (P < 0.05; P < 0.01). The expressions of PERK, CHOP, and caspase-3 in nephridial tissue were reduced (P < 0.05), tubulointerstitial injury and RIF were reduced (P < 0.05), and Scr and BUN were lower (P < 0.05) in the high stachydrine group than those in the enalapril group. The expressions of PERK, CHOP, and caspase-3 were reduced in the endoplasmic reticulum stress-related apoptosis pathway after stachydrine treatment. Consequently, apoptosis was prevented, and RIF was inhibited.

CGK733-induced LC3 II formation is positively associated with the expression of cyclin-dependent kinase inhibitor p21Waf1/Cip1 through modulation of the AMPK and PERK/CHOP signaling pathways.

PubMed

Wang, Yufeng; Kuramitsu, Yasuhiro; Baron, Byron; Kitagawa, Takao; Tokuda, Kazuhiro; Akada, Junko; Nakamura, Kazuyuki

2015-11-24

Microtubule-associated protein 1A/1B-light chain 3 (LC3)-II is essential for autophagosome formation and is widely used to monitor autophagic activity. We show that CGK733 induces LC3 II and LC3-puncta accumulation, which are not involved in the activation of autophagy. The treatment of CGK733 did not alter the autophagic flux and was unrelated to p62 degradation. Treatment with CGK733 activated the AMP-activated protein kinase (AMPK) and protein kinase RNA-like endoplasmic reticulum kinase/CCAAT-enhancer-binding protein homologous protein (PERK/CHOP) pathways and elevated the expression of p21Waf1/Cip1. Inhibition of both AMPK and PERK/CHOP pathways by siRNA or chemical inhibitor could block CGK733-induced p21Waf1/Cip1 expression as well as caspase-3 cleavage. Knockdown of LC3 B (but not LC3 A) abolished CGK733-triggered LC3 II accumulation and consequently diminished AMPK and PERK/CHOP activity as well as p21Waf1/Cip1 expression. Our results demonstrate that CGK733-triggered LC3 II formation is an initial event upstream of the AMPK and PERK/CHOP pathways, both of which control p21Waf1/Cip1 expression.

Salmonella Immunotherapy Improves the Outcome of CHOP Chemotherapy in Non-Hodgkin Lymphoma-Bearing Mice

PubMed Central

Bascuas, Thais; Moreno, María; Grille, Sofía; Chabalgoity, José A.

2018-01-01

We have previously shown that Salmonella immunotherapy is effective to treat B-cell non-Hodgkin lymphoma (B-NHL) in mice. However, this model involves animals with high tumor burden, whereas in the clinics B-NHL patients are usually treated with chemotherapy (CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone) as first-line therapy prior to immunotherapy. Recently, we have described a NHL-B preclinical model using CHOP chemotherapy to achieve MRD in immunocompetent animals that closely resemble patients’ conditions. In this work, we assessed the efficacy of Salmonella immunotherapy in B-NHL-bearing mice undergoing chemotherapy. Salmonella administration significantly delayed tumor growth and prolonged survival of chemotherapy-treated NHL-bearing animals. Mice receiving the CHOP–Salmonella combined therapy showed increased numbers of tumor-infiltrating leukocytes and a different profile of cytokines and chemokines expressed in the tumor microenvironment. Further, Salmonella immunotherapy in CHOP-treated animals also enhanced NK cells cytotoxic activity as well as induced systemic lymphoma-specific humoral and cellular responses. Chemotherapy treatment profoundly impacted on the general health status of recipient animals, but those receiving Salmonella showed significantly better overall body condition. Altogether, the results clearly demonstrated that Salmonella immunotherapy could be safely used in individuals under CHOP treatment, resulting in a better prognosis. These results give strong support to consider Salmonella as a neoadjuvant therapy in a clinical setting. PMID:29410666

9 CFR 319.15 - Miscellaneous beef products.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Miscellaneous beef products. 319.15 Section 319.15 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Miscellaneous beef products. (a) Chopped beef, ground beef. “Chopped Beef” or “Ground Beef” shall consist of...

9 CFR 319.15 - Miscellaneous beef products.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Miscellaneous beef products. 319.15 Section 319.15 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Miscellaneous beef products. (a) Chopped beef, ground beef. “Chopped Beef” or “Ground Beef” shall consist of...

9 CFR 319.15 - Miscellaneous beef products.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Miscellaneous beef products. 319.15 Section 319.15 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Miscellaneous beef products. (a) Chopped beef, ground beef. “Chopped Beef” or “Ground Beef” shall consist of...

9 CFR 319.15 - Miscellaneous beef products.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Miscellaneous beef products. 319.15 Section 319.15 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Miscellaneous beef products. (a) Chopped beef, ground beef. “Chopped Beef” or “Ground Beef” shall consist of...

9 CFR 319.15 - Miscellaneous beef products.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Miscellaneous beef products. 319.15 Section 319.15 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Miscellaneous beef products. (a) Chopped beef, ground beef. “Chopped Beef” or “Ground Beef” shall consist of...

Effects of phenylethanolamine N-methyltransferase inhibitors on uptake and release of norepinephrine and dopamine from rat brain

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

Liang, N.Y.; Hower, J.A.; Borchardt, R.T.

1985-09-01

Inhibitors of phenylethanolamine N-methyltransferase (PNMT) and amphetamine were evaluated for their effects on the uptake of (TH)-norepinephrine (TH-NE) and the release of endogenous NE and dopamine (DA) from chopped rat brain tissues. Unlike amphetamine, all of PNMT inhibitors tested produced only slight inhibition of (TH)-NE uptake into chopped cerebral cortex. 2,3-Dichloro-alpha-methylbenzylamine (DCMB) and 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline (SKF64139), but not 2-cyclooctyl-2-hydroxyethylamine (CONH) and 1-aminomethylcycloundecanol (CUNH) produced slight release of endogenous NE and DA from chopped hypothalami, but their effects were less pronounced than those produced by amphetamine.

Straight and chopped DC performance data for a General Electric 5BY436A1 DC shunt motor with a General Electric EV-1 controller

NASA Technical Reports Server (NTRS)

Edie, P. C.

1981-01-01

Both straight and chopped dc motor performance data for a General Electric 5BY436A1 motor with a General Electric EV-1 controller is presented in tabular and graphical formats. Effects of motor temperature and operating voltage are also shown. The maximum motor efficiency is approximately 85% at low operating temperatures in the straight dc mode. Chopper efficiency can be assumed to be 95% under all operating conditions. For equal speeds, the motor operated in the chopped mode develops slightly more torque and draws more current than it does in the straight mode.

A new prognostic score for elderly patients with diffuse large B-cell lymphoma treated with R-CHOP: the prognostic role of blood monocyte and lymphocyte counts is absent.

PubMed

Procházka, Vít; Pytlík, Robert; Janíková, Andrea; Belada, David; Sálek, David; Papajík, Tomáš; Campr, Vít; Fürst, Tomáš; Furstova, Jana; Trněný, Marek

2014-01-01

Absolute lymphocyte count (ALC) and absolute monocyte count (AMC) have been documented as independent predictors of survival in patients with newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL). Analysis of the prognostic impact of ALC and AMC in the context of International Prognostic Index (IPI) and other significant variables in elderly population treated in the R-CHOP regime has not been carried out yet. In this retrospective study, a cohort of 443 newly diagnosed DLBCL patients with age ≥ 60 was analyzed. All patients were treated with the R-CHOP therapy. An extensive statistical analysis was performed to identify risk factors of 3-year overall survival (OS). In multivariate analysis, only three predictors proved significant: Eastern Cooperative Oncology Group performance status (ECOG), age and bulky disease presence. These predictors were dichotomized (ECOG ≥ 1, age ≥ 70, bulk ≥ 7.5) to create a novel four-level score. This score predicted 3-year OS of 94.0%, 77.4%, 62.7% and 35.4% in the low-, low-intermediate, high-intermediate and high-risk groups, respectively (P<0.001). Further, a three-level score was tested which stratifies the population better (3-year OS: 91.9%, 67.2%, 36.2% in the low, intermediate and high-risk groups, respectively) but is more difficult to interpret. Both the 3- and 4-level scores were compared to standard scoring systems and, in our population, were shown to be superior in terms of patients risk stratification with respect to 3-year OS prediction. The results were successfully validated on an independent cohort of 162 patients of similar group characteristics. The prognostic role of baseline ALC, AMC or their ratio (LMR) was not confirmed in the multivariate context in elderly population with DLBCL treated with R-CHOP. The newly proposed age-specific index stratifies the elderly population into risk groups more precisely than the conventional IPI and its existing variants.

Physics teacher use of the history of science

NASA Astrophysics Data System (ADS)

Winrich, Charles

The School of Education and the Department of Physics at Boston University offer a sequence of 10 two-credit professional development courses through the Improving the Teaching of Physics (ITOP) project. The ITOP courses combine physics content, readings from the physics education research (PER) literature, and the conceptual history of physics (CHOP). ITOP participants self-report changes to their teaching practices as a result of their participation in ITOP. The purpose of this study was to verify and characterize those changes in the specific area of the participants' use of history after their study of CHOP. Ten recent ITOP participants were observed, interviewed, and asked to provide lesson plans and samples of student work from their classes. Case studies of each participant's teaching were constructed from the data. The individual cases were synthesized to characterize the impact of CHOP on the ITOP participants. The results show that the participants integrate CHOP into their pedagogical content knowledge (PCK) to inform their understanding of: (1) the relationship between physics and other disciplines, (2) the relationship between specific physics concepts, (3) student understanding of physics concepts, (4) student difficulties in learning physics concepts, and (5) methods for teaching physics concepts. The participants use history to teach a variety of topics, although the most common were mechanics and electromagnetism. All of the participants used history to teach aspects of the nature of science (NOS) and to increase student interest in physics, while eight participants taught physics concepts through history. The predominant mode of incorporating history was through adding anecdotes about the scientists who worked on the concepts, but seven participants had their students study the historical development of physical concepts. All the participants discussed a lack of time as a factor that inhibits a greater use of history in their courses. Eight participants discussed a lack of appropriate resources for using history in high school physics classes. Two participants said they did not feel that explicit study of the history of physics would benefit their students until they had better mastery of physics concepts.

Cyproterone acetate enhances TRAIL-induced androgen-independent prostate cancer cell apoptosis via up-regulation of death receptor 5.

PubMed

Chen, Linjie; Wolff, Dennis W; Xie, Yan; Lin, Ming-Fong; Tu, Yaping

2017-03-07

Virtually all prostate cancer deaths occur due to obtaining the castration-resistant phenotype after prostate cancer cells escaped from apoptosis and/or growth suppression initially induced by androgen receptor blockade. TNF-related apoptosis-inducing ligand (TRAIL) was an attractive cancer therapeutic agent due to its minimal toxicity to normal cells and remarkable apoptotic activity in tumor cells. However, most localized cancers including prostate cancer are resistant to TRAIL-induced apoptosis, thereby creating a therapeutic challenge of inducing TRAIL sensitivity in cancer cells. Herein the effects of cyproterone acetate, an antiandrogen steroid, on the TRAIL-induced apoptosis of androgen receptor-negative prostate cancer cells are reported. Cell apoptosis was assessed by both annexin V/propidium iodide labeling and poly (ADP-ribose) polymerase cleavage assays. Gene and protein expression changes were determined by quantitative real-time PCR and western blot assays. The effect of cyproterone acetate on gene promoter activity was determined by luciferase reporter assay. Cyproterone acetate but not AR antagonist bicalutamide dramatically increased the susceptibility of androgen receptor-negative human prostate cancer PC-3 and DU145 cells to TRAIL-induced apoptosis but no effects on immortalized human prostate stromal PS30 cells and human embryonic kidney HEK293 cells. Further investigation of the TRAIL-induced apoptosis pathway revealed that cyproterone acetate exerted its effect by selectively increasing death receptor 5 (DR5) mRNA and protein expression. Cyproterone acetate treatment also increased DR5 gene promoter activity, which could be abolished by mutation of a consensus binding domain of transcription factor CCAAT-enhancer-binding protein homologous protein (CHOP) in the DR5 gene promoter. Cyproterone acetate increases CHOP expression in a concentration and time-dependent manner and endoplasmic reticulum stress reducer 4-phenylbutyrate could block cyproterone acetate-induced CHOP and DR5 up-regulation. More importantly, siRNA silencing of CHOP significantly reduced cyproterone acetate-induced DR5 up-regulation and TRAIL sensitivity in prostate cancer cells. Our study shows a novel effect of cyproterone acetate on apoptosis pathways in prostate cancer cells and raises the possibility that a combination of TRAIL with cyproterone acetate could be a promising strategy for treating castration-resistant prostate cancer.

The "Tomahawk Chop": The Continuous Struggle of Unlearning "Indian" Stereotypes.

ERIC Educational Resources Information Center

Pewewardy, Cornel D.

"Indian" mascots of athletic teams can be offensive to Native Americans when they portray negative and stereotypical images. The notion of the "tomahawk chop" invented by Atlanta Braves fans and all the antics that go along with such images prevent millions of Americans from understanding the authentic Indian America, both long…

9 CFR 319.311 - Chow mein vegetables with meat, and chop suey vegetables with meat.

Code of Federal Regulations, 2010 CFR

2010-01-01

... chop suey vegetables with meat. 319.311 Section 319.311 Animals and Animal Products FOOD SAFETY AND... PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Canned, Frozen, or Dehydrated Meat Food Products § 319.311 Chow mein vegetables with meat, and...

9 CFR 319.311 - Chow mein vegetables with meat, and chop suey vegetables with meat.

Code of Federal Regulations, 2011 CFR

2011-01-01

... chop suey vegetables with meat. 319.311 Section 319.311 Animals and Animal Products FOOD SAFETY AND... PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Canned, Frozen, or Dehydrated Meat Food Products § 319.311 Chow mein vegetables with meat, and...

Preparing sites for pine plantings in South Florida

Treesearch

James W. McMinn

1969-01-01

Typical slash pine and South Florida slash pine were planted on prepared flatwoods sites at three Florida locations. Site preparation treatments were burning, strip-chopping, double-chopping, clearing, and bedding. Results through the fifth year show that bedding provided the most favorable site for early growth, and that properly planted seedlings survived no better...

Geopolymer Porous Nanoceramics for Structural Smart and Thermal Shock Resistant Applications

DTIC Science & Technology

2011-02-02

porous membranes and foams, ceramic armor composites , iron-based geopolymer analogues, geopolymer composites reinforced with chopped polypropylene... geopolymers and geopolymer composites , as fabricated and upon conversion to ceramics with heating. The microstucture consisted of nanoporous...ceramic armore composites , iron-based geopolymer analogues, geopolymer composites reinforced with chopped polypropylene or basalt fibers and

"Slow-scanning" in Ground-based Mid-infrared Observations

NASA Astrophysics Data System (ADS)

Ohsawa, Ryou; Sako, Shigeyuki; Miyata, Takashi; Kamizuka, Takafumi; Okada, Kazushi; Mori, Kiyoshi; Uchiyama, Masahito S.; Yamaguchi, Junpei; Fujiyoshi, Takuya; Morii, Mikio; Ikeda, Shiro

2018-04-01

Chopping observations with a tip-tilt secondary mirror have conventionally been used in ground-based mid-infrared observations. However, it is not practical for next generation large telescopes to have a large tip-tilt mirror that moves at a frequency larger than a few hertz. We propose an alternative observing method, a "slow-scanning" observation. Images are continuously captured as movie data, while the field of view is slowly moved. The signal from an astronomical object is extracted from the movie data by a low-rank and sparse matrix decomposition. The performance of the "slow-scanning" observation was tested in an experimental observation with Subaru/COMICS. The quality of a resultant image in the "slow-scanning" observation was as good as in a conventional chopping observation with COMICS, at least for a bright point-source object. The observational efficiency in the "slow-scanning" observation was better than that in the chopping observation. The results suggest that the "slow-scanning" observation can be a competitive method for the Subaru telescope and be of potential interest to other ground-based facilities to avoid chopping.

Use of the chop hook to stabilize the capsular bag in patients with crystalline lens dislocations and cataracts.

PubMed

Zeng, Yanfeng; Fan, Licheng; Lu, Peirong

2017-04-01

Objective To observe the treatment effects of chop hook-assisted phacoemulsification surgery in patients with crystalline lens dislocation. Methods Thirty-seven eyes with cataracts and crystalline lens dislocations underwent cataract surgery. An L-shaped chop hook was introduced into the anterior chamber, and the tip was pushed or pulled to the centre of the anterior capsular edge of the zonular dialysis during the cataract operation. Postoperative follow-up was conducted for ≥ 1 month. Results All patients' postoperative visual abilities improved except one patient with glaucoma. One patient who underwent -5D intraocular lens implantation exhibited vision of 1/50. Visual acuity was less than 6/20 in 6 eyes, 6/20 to 10/20 in 7 eyes, and greater than 10/20 in 22 eyes. Conclusions L-shaped chop hooks can be used to push or pull the anterior capsular edge of the zonular dialysis for protection and avoidance of further zonular damage. This strategy provides satisfactory effects and reduces use of additional instruments.

Etching radical controlled gas chopped deep reactive ion etching

DOEpatents

Olynick, Deidre; Rangelow, Ivo; Chao, Weilun

2013-10-01

A method for silicon micromachining techniques based on high aspect ratio reactive ion etching with gas chopping has been developed capable of producing essentially scallop-free, smooth, sidewall surfaces. The method uses precisely controlled, alternated (or chopped) gas flow of the etching and deposition gas precursors to produce a controllable sidewall passivation capable of high anisotropy. The dynamic control of sidewall passivation is achieved by carefully controlling fluorine radical presence with moderator gasses, such as CH.sub.4 and controlling the passivation rate and stoichiometry using a CF.sub.2 source. In this manner, sidewall polymer deposition thicknesses are very well controlled, reducing sidewall ripples to very small levels. By combining inductively coupled plasmas with controlled fluorocarbon chemistry, good control of vertical structures with very low sidewall roughness may be produced. Results show silicon features with an aspect ratio of 20:1 for 10 nm features with applicability to nano-applications in the sub-50 nm regime. By comparison, previous traditional gas chopping techniques have produced rippled or scalloped sidewalls in a range of 50 to 100 nm roughness.

Microbiological quality of fish grown in wastewater-fed and non-wastewater-fed fishponds in Hanoi, Vietnam: influence of hygiene practices in local retail markets.

PubMed

Lan, Nguyen Thi Phong; Dalsgaard, Anders; Cam, Phung Dac; Mara, Duncan

2007-06-01

Mean water quality in two wastewater-fed ponds and one non-wastewater-fed pond in Hanoi, Vietnam was approximately 10(6) and approximately 10(4) presumptive thermotolerant coliforms (pThC) per 100 ml, respectively. Fish (common carp, silver carp and Nile tilapia) grown in these ponds were sampled at harvest and in local retail markets. Bacteriological examination of the fish sampled at harvest from both types of pond showed that they were of very good quality (2 - 3 pThC g(-1) fresh muscle weight), despite the skin and gut contents being very contaminated (10(2) - 10(3) pThC g(-1) fresh weight and 10(4) - 10(6) pThC g(-1) fresh weight, respectively). These results indicate that the WHO guideline quality of < or = 1000 faecal coliforms per 100 ml of pond water in wastewater-fed aquaculture is quite restrictive and represents a safety factor of approximately 3 orders of magnitude. However, when the fish from both types of pond were sampled at the point of retail sale, quality deteriorated to 10(2) - 10(5) pThC g(-1) of chopped fresh fish (mainly flesh and skin contaminated with gut contents); this was due to the practice of the local fishmongers in descaling and chopping up the fish from both types of pond with the same knife and on the same chopping block. Fishmonger education is required to improve their hygienic practices; this should be followed by regular hygiene inspections.

MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy: a report from the International DLBCL Rituximab-CHOP Consortium Program

PubMed Central

Xu-Monette, Zijun Y.; Møller, Michael B.; Tzankov, Alexander; Montes-Moreno, Santiago; Hu, Wenwei; Manyam, Ganiraju C.; Kristensen, Louise; Fan, Lei; Visco, Carlo; Dybkær, Karen; Chiu, April; Tam, Wayne; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W. L.; van Krieken, J. Han; Huang, Qin; Huh, Jooryung; Ai, Weiyun; Ponzoni, Maurilio; Ferreri, Andrés J. M.; Wu, Lin; Zhao, Xiaoying; Bueso-Ramos, Carlos E.; Wang, Sa A.; Go, Ronald S.; Li, Yong; Winter, Jane N.; Medeiros, L. Jeffrey

2013-01-01

MDM2 is a key negative regulator of the tumor suppressor p53, however, the prognostic significance of MDM2 overexpression in diffuse large B-cell lymphoma (DLBCL) has not been defined convincingly. In a p53 genetically–defined large cohort of de novo DLBCL patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R-CHOP) chemotherapy, we assessed MDM2 and p53 expression by immunohistochemistry (n = 478), MDM2 gene amplification by fluorescence in situ hybridization (n = 364), and a single nucleotide polymorphism in the MDM2 promoter, SNP309, by SNP genotyping assay (n = 108). Our results show that MDM2 overexpression, unlike p53 overexpression, is not a significant prognostic factor in overall DLBCL. Both MDM2 and p53 overexpression do not predict for an adverse clinical outcome in patients with wild-type p53 but predicts for significantly poorer survival in patients with mutated p53. Variable p53 activities may ultimately determine the survival differences, as suggested by the gene expression profiling analysis. MDM2 amplification was observed in 3 of 364 (0.8%) patients with high MDM2 expression. The presence of SNP309 did not correlate with MDM2 expression and survival. This study indicates that evaluation of MDM2 and p53 expression correlating with TP53 genetic status is essential to assess their prognostic significance and is important for designing therapeutic strategies that target the MDM2-p53 interaction. PMID:23982177

Ablation of the Proapoptotic Genes Chop or Ask1 Does Not Prevent or Delay Loss of Visual Function in a P23H Transgenic Mouse Model of Retinitis Pigmentosa

PubMed Central

Adekeye, Adeseye; Haeri, Mohammad; Solessio, Eduardo; Knox, Barry E.

2014-01-01

The P23H mutation in rhodopsin (RhoP23H) is a prevalent cause of autosomal dominant retinitis pigmentosa. We examined the role of the ER stress proteins, Chop and Ask1, in regulating the death of rod photoreceptors in a mouse line harboring the RhoP23H rhodopsin transgene (GHL+). We used knockout mice models to determine whether Chop and Ask1 regulate rod survival or retinal degeneration. Electrophysiological recordings showed similar retinal responses and sensitivities for GHL+, GHL+/Chop−/− and GHL+/Ask1−/− animals between 4–28 weeks, by which time all three mouse lines exhibited severe loss of retinal function. Histologically, ablation of Chop and Ask1 did not rescue photoreceptor loss in young animals. However, in older mice, a regional protective effect was observed in the central retina of GHL+/Chop−/− and GHL+/Ask1−/−, a region that was severely degenerated in GHL+ mice. Our results show that in the presence of the RhoP23H transgene, the rate of decline in retinal sensitivity is similar in Chop or Ask1 ablated and wild-type retinas, suggesting that these proteins do not play a major role during the acute phase of photoreceptor loss in GHL+ mice. Instead they may be involved in regulating secondary pathological responses such as inflammation that are upregulated during later stages of disease progression. PMID:24523853

R-hyper-CVAD versus R-CHOP/cytarabine with high-dose therapy and autologous haematopoietic stem cell support in fit patients with mantle cell lymphoma: 20 years of single-center experience.

PubMed

Widmer, Fabienne; Balabanov, Stefan; Soldini, Davide; Samaras, Panagiotis; Gerber, Bernhard; Manz, Markus G; Goede, Jeroen S

2018-02-01

Standard of care for untreated mantle cell lymphoma (MCL) is still debated. At the University Hospital Zurich, advanced MCL in physically fit patients is treated either with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone induction followed by consolidating high-dose chemotherapy and autologous stem cell support (R-CHOP/HD-ASCT), or with rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate-cytarabine (R-hyper-CVAD/MTX-AraC) without consolidating HD-ASCT upon physicians' and patients' choice. We retrospectively analysed the outcome and therapy tolerance in patients with MCL treated with R-CHOP/HD-ASCT or R-hyper-CVAD/MTX-AraC at the University Hospital Zurich between January 1996 and January 2016. Forty-three patients were included; 29 patients received R-CHOP/HD-ASCT and 14 patients R-hyper-CVAD/MTX-AraC. Mean age at diagnosis was 54.4 years (range 38-68 years). Thirty-five patients (81.4%) completed the entire first-line therapy (n = 24 in the R-CHOP/HD-ASCT group, n = 11 in the R-hyper-CVAD group). Of those, all patients responded and 97% achieved a complete remission (CR). With a mean follow-up of 5.7 years 10-year progression-free survival (PFS) for all patients was 32% and overall survival (OS) was 76%, with no difference between the two therapy groups. Complication-induced hospitalisation rate, haematological toxicity and economic burden were significantly higher in the R-hyper-CVAD therapy group. In contrast, quality of life and global health state were better in the R-hyper-CVAD therapy group. Both first-line therapies showed similar outcome with a median OS longer than 10 years. Due to significantly lower haematological toxicity and lower economic burden, we recommend R-CHOP/HD-ASCT as first-line therapy in fit adult patients with advanced MCL.

Brentuximab Vedotin in the Front-Line Treatment of Patients With CD30+ Peripheral T-Cell Lymphomas: Results of a Phase I Study

PubMed Central

Fanale, Michelle A.; Horwitz, Steven M.; Forero-Torres, Andres; Bartlett, Nancy L.; Advani, Ranjana H.; Pro, Barbara; Chen, Robert W.; Davies, Andrew; Illidge, Tim; Huebner, Dirk; Kennedy, Dana A.; Shustov, Andrei R.

2014-01-01

Purpose Front-line treatment of peripheral T-cell lymphomas (PTCL) involves regimens such as cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and results in a 5-year overall survival (OS) rate of less than 50%. This phase I open-label study evaluated the safety and activity of brentuximab vedotin administered sequentially with CHOP or in combination with CHP (CHOP without vincristine) as front-line treatment in patients with CD30+ PTCL. Patients and Methods Patients received sequential treatment (once every 3 weeks) with brentuximab vedotin 1.8 mg/kg (two cycles) followed by CHOP (six cycles) or brentuximab vedotin 1.8 mg/kg plus CHP (BV+CHP) for six cycles (once every 3 weeks). Responders received single-agent brentuximab vedotin for eight to 10 additional cycles (for a total of 16 cycles). The primary objective was assessment of safety; secondary end points included objective response rate, complete remission (CR) rate, progression-free survival rate (PFS), and OS. There were no prespecified comparisons of the two treatment approaches. Results After sequential treatment, 11 (85%) of 13 patients achieved an objective response (CR rate, 62%; estimated 1-year PFS rate, 77%). Grade 3/4 adverse events occurred in eight (62%) of 13 patients. At the end of combination treatment, all patients (n = 26) achieved an objective response (CR rate, 88%; estimated 1-year PFS rate, 71%). All seven patients without anaplastic large-cell lymphoma achieved CR. Grade 3/4 adverse events (≥ 10%) in the combination-treatment group were febrile neutropenia (31%), neutropenia (23%), anemia (15%), and pulmonary embolism (12%). Conclusion Brentuximab vedotin, administered sequentially with CHOP or in combination with CHP, had a manageable safety profile and exhibited substantial antitumor activity in newly diagnosed patients with CD30+ PTCL. A randomized phase III trial is under way, comparing BV+CHP with CHOP (clinical trial No. NCT01777152). PMID:25135998

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 accelerated cell death during infection, as shown by the higher rate of expression of CHOP and alteration of the localization of CHOP. The beneficial effect of irreversible ER stress on PPV spread was confirmed by treatment of infected cells with ER stress-inducing chemicals. Copyright © 2017 American Society for Microbiology.

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 severe and accelerated cell death during infection, as shown by the higher rate of expression of CHOP and alteration of the localization of CHOP. The beneficial effect of irreversible ER stress on PPV spread was confirmed by treatment of infected cells with ER stress-inducing chemicals. PMID:28566374

Magnetic nanoparticles trigger cell proliferation arrest of neuro-2a cells and ROS-mediated endoplasmic reticulum stress response

NASA Astrophysics Data System (ADS)

Wang, Pingping; Chen, Chuanfang; Zeng, Kun; Pan, Weidong; Song, Tao

2014-11-01

Magnetic nanoparticles (MNPs) have been increasingly applied in various areas, such as the biomedical and electronic industries. The unique properties of MNPs are beneficial to their applications, but concerns about their safety to human health along with the growing applications and production also arise. In this study, the cytotoxicity of superparamagnetic MNPs, with an average diameter of 10 nm and typical diameter range between 5 and 30 nm, was investigated using neuro-2a cells. The MNPs internalized into the cytoplasm of neuro-2a cells and inhibited the cell viability in a dose-dependent manner at concentrations ranging from 100 to 500 μg/mL. The cell growth inhibition would be partly attributed to the MNP-induced cell cycle arrest in the G0/G1 phase. MNPs triggered the endoplasmic reticulum (ER) stress response, as indicated by the up-regulated expression of the classical ER stress genes, binding immunoglobulin protein, activating transcription factor 6, and CCAAT-enhancer-binding protein homologous protein (CHOP). The induced production of cellular reactive oxygen species (ROS) and increased expression of heme oxygenase 1 and nuclear factor erythroid two-related factor two genes demonstrated that oxidative stress was also induced. Furthermore, the clearance of ROS by free radical scavenger N-acetylcysteine reduced the up-regulation of MNP-induced CHOP mRNA expressions, thereby suggesting that ROS was involved in the process of ER stress response induced by MNPs.

76 FR 76890 - Nutrition Labeling of Single-Ingredient Products and Ground or Chopped Meat and Poultry Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-09

.... FSIS-2005-0018] Nutrition Labeling of Single-Ingredient Products and Ground or Chopped Meat and Poultry... (FSIS) is delaying the effective date of the final regulations that require nutrition labeling of the... December 29, 2010, FSIS published the final rule, ``Nutrition Labeling of Single-Ingredient Products and...

A Biomechanical Analysis of the Karate Chop.

ERIC Educational Resources Information Center

Cavanagh, Peter R.; Landa, Jean

Although the sport of karate has been somewhat neglected by scientists, the following two isolated biomechanical studies exist in literature: (1) tracings of a karate chop in two planes were presented, but no data was given concerning the rates of movement of the limb segments, and (2) pre- and postimpact phenomena of five subjects were studied,…

Geopolymer Porous Nanoceramics for Structural, for Smart and Thermal Shock Resistant Applications

DTIC Science & Technology

2011-02-02

porous membranes and foams, ceramic armor composites , iron-based geopolymer analogues, geopolymer composites reinforced with chopped polypropylene...the microstructure of geopolymers and geopolymer composites , as fabricated and upon conversion to ceramics with heating. The microstructure consisted...porous membranes and foams, ceramic armor composites , iron-based geopolymer analogues, geopolymer composites reinforced with chopped polypropylene or

Successful management with CHOP for pulmonary lymphomatoid granulomatosis in a dog.

PubMed

Hatoya, Singo; Kumagai, Daijiro; Takeda, Seiko; Yamamoto, Emi; Nakanishi, Masako; Kuwamura, Mitsuru; Sugiura, Kikuya; Sasai, Hiroshi; Yamate, Jyoji; Inaba, Toshio

2011-04-01

A 3-year-old, spayed female miniature dachshund was presented for vomiting and anorexia. Thoracic radiographs and CT scan revealed abnormal pulmonary opacities at bilateral caudal lobe. Cytological analysis of the pulmonary mass revealed the presence of large lymphohistiocytic cells and small lymphocytes with occasional neutrophils and plasma cells. An open lung biopsy was performed and a diagnosis of pulmonary lymphomatoid granulomatosis (LYG) was made. The dog was administered CHOP based therapy (modified UW-25), and it survived for 1,022 days after admission. Immunohistochemistry revealed pulmonary lesions consisted of many CD79a positive B cells aggregation and proliferation with prominent angiocentric pattern. This was the first case of canine pulmonary LYG managed by CHOP chemotherapy.

Performance of a 14.9-kW laminated-frame dc series motor with chopper controller

NASA Technical Reports Server (NTRS)

Schwab, J. R.

1979-01-01

Traction motor using two types of excitation: ripple free dc from a motor generator set for baseline data and chopped dc as supplied by a battery and chopper controller was tested. For the same average values of input voltage and current, the power output was independent of the type of excitation. At the same speeds, motor efficiency at low power output (corresponding to low duty cycle of the controller) was 5 to 10 percentage points less on chopped dc than on ripple-free dc. This illustrates that for chopped waveforms, it is incorrect to calculate input power as the product of average voltage and average current. Locked-rotor torque, no load losses, and magnetic saturation data were so determined.

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

Madrak, R.; Wildman, D.

The key elements have been constructed for a fast chopper system capable of removing single 2.5 MeV proton bunches spaced at 325 MHz. The average chopping rate is ~ 1 MHz. The components include a pulse delaying microstrip structure for deflecting the beam, high voltage (1.2 kV) fast (ns rise time) pulsers, and an associated wideband combiner. Various designs for the deflecting structures have been studied. Measurements of the microstrip structures' coverage factors and pulse shapes are presented.

Advanced Concepts for Composite Structure Joints and Attachment Fittings. Volume I. Design and Evaluation.

DTIC Science & Technology

1981-11-01

interlaminar tension). The analysis is also influenced by other factors such as bolt location, washer/bolt size, fastener pattern, laminate thickness, corner...to reduce the cost of tooling were also studied. These include: * Pultrusion dies for under $5, 000 * Stable, accurate, low-cost chopped-fiber phenolic ...fittings were state-of- the-art methods developed for laminated composite plates, shells, beams, and columns as used in analyses of discontinuities, edge

Bio-composites based on cellulose acetate and kenaf fibers: Processing and properties

NASA Astrophysics Data System (ADS)

Pang, C.; Shanks, R. A.; Daver, F.

2014-05-01

Research on bio-composites is important because of its positive environmental impact. In this study, bio-composites based on plasticised cellulose acetate and kenaf fibers were prepared by solution casting and compression moulding methods. The fibers were chemically treated to remove lignin, hemicellulose and impurities. Mechanical, morphological and thermal properties of the bio-composites were studied. Introduction of chopped kenaf fibers increased the storage modulus. The flexural storage modulus of the composite was affected with the introduction of moisture. Moisture behaved similar to the effect of plasticiser, it reduced the modulus.

Reliability model for ductile hybrid FRP rebar using randomly dispersed chopped fibers

NASA Astrophysics Data System (ADS)

Behnam, Bashar Ramzi

Fiber reinforced polymer composites or simply FRP composites have become more attractive to civil engineers in the last two decades due to their unique mechanical properties. However, there are many obstacles such as low elasticity modulus, non-ductile behavior, high cost of the fibers, high manufacturing costs, and absence of rigorous characterization of the uncertainties of the mechanical properties that restrict the use of these composites. However, when FRP composites are used to develop reinforcing rebars in concrete structural members to replace the conventional steel, a huge benefit can be achieved since FRP materials don't corrode. Two FRP rebar models are proposed that make use of multiple types of fibers to achieve ductility, and chopped fibers are used to reduce the manufacturing costs. In order to reach the most optimum fractional volume of each type of fiber, to minimize the cost of the proposed rebars, and to achieve a safe design by considering uncertainties in the materials and geometry of sections, appropriate material resistance factors have been developed, and a Reliability Based Design Optimization (RBDO), has been conducted for the proposed schemes.

Monensin, a polyether ionophore antibiotic, overcomes TRAIL resistance in glioma cells via endoplasmic reticulum stress, DR5 upregulation and c-FLIP downregulation.

PubMed

Yoon, Mi Jin; Kang, You Jung; Kim, In Young; Kim, Eun Hee; Lee, Ju Ahn; Lim, Jun Hee; Kwon, Taeg Kyu; Choi, Kyeong Sook

2013-08-01

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) is preferentially cytotoxic to cancer cells over normal cells. However, many cancer cells, including malignant glioma cells, tend to be resistant to TRAIL. Monensin (a polyether ionophore antibiotic that is widely used in veterinary medicine) and salinomycin (a compound that is structurally related to monensin and shows cancer stem cell-inhibiting activity) are currently recognized as anticancer drug candidates. In this study, we show that monensin effectively sensitizes various glioma cells, but not normal astrocytes, to TRAIL-mediated apoptosis; this occurs at least partly via monensin-induced endoplasmic reticulum (ER) stress, CHOP-mediated DR5 upregulation and proteasome-mediated downregulation of c-FLIP. Interestingly, other polyether antibiotics, such as salinomycin, nigericin, narasin and lasalocid A, also stimulated TRAIL-mediated apoptosis in glioma cells via ER stress, CHOP-mediated DR5 upregulation and c-FLIP downregulation. Taken together, these results suggest that combined treatment of glioma cells with TRAIL and polyether ionophore antibiotics may offer an effective therapeutic strategy.

Chronic Intermittent Hypobaric Hypoxia Improves Cardiac Function through Inhibition of Endoplasmic Reticulum Stress.

PubMed

Yuan, Fang; Zhang, Li; Li, Yan-Qing; Teng, Xu; Tian, Si-Yu; Wang, Xiao-Ran; Zhang, Yi

2017-08-11

We investigated the role of endoplasmic reticulum stress (ERS) in chronic intermittent hypobaric hypoxia (CIHH)-induced cardiac protection. Adult male Sprague-Dawley rats were exposed to CIHH treatment simulating 5000 m altitude for 28 days, 6 hours per day. The heart was isolated and perfused with Langendorff apparatus and subjected to 30-min ischemia followed by 60-min reperfusion. Cardiac function, infarct size, and lactate dehydrogenase (LDH) activity were assessed. Expression of ERS molecular chaperones (GRP78, CHOP and caspase-12) was assayed by western blot analysis. CIHH treatment improved the recovery of left ventricular function and decreased cardiac infarct size and activity of LDH after I/R compared to control rats. Furthermore, CIHH treatment inhibited over-expression of ERS-related factors including GRP78, CHOP and caspase-12. CIHH-induced cardioprotection and inhibition of ERS were eliminated by application of dithiothreitol, an ERS inducer, and chelerythrine, a protein kinase C (PKC) inhibitor. In conclusion CIHH treatment exerts cardiac protection against I/R injury through inhibition of ERS via PKC signaling pathway.

Treatment of feline intermediate- to high-grade lymphoma with a modified university of Wisconsin-Madison protocol: 119 cases (2004-2012).

PubMed

Collette, S A; Allstadt, S D; Chon, E M; Vernau, W; Smith, A N; Garrett, L D; Choy, K; Rebhun, R B; Rodriguez, C O; Skorupski, K A

2016-08-01

CHOP-based (cyclophosphamide, doxorubicin, vinca alkaloid, prednisolone) chemotherapy protocols are often recommended for treatment of feline lymphoma. While maintenance-free CHOP-based protocols have been published and readily used in dogs, there is limited literature regarding similar maintenance-free protocols in cats. The purpose of this study was to describe the outcome of cats with intermediate- to high-grade lymphoma that were prescribed a modified 25-week University of Wisconsin-Madison (UW-25) chemotherapy protocol. A secondary objective was examination of potential prognostic factors. One hundred and nineteen cats from five institutions treated with a UW-25-based protocol were included. The Kaplan-Meier median progression-free interval (PFI) and survival time (MST) were 56 and 97 (range 2-2019) days, respectively. Cats assessed as having a complete response (CR) to therapy had significantly longer PFI and MST than those with partial or no response (PFI 205 versus 54 versus 21 days, respectively, P < 0.0001 and MST 318 versus 85 versus 27 days, respectively, P < 0.0001). © 2015 John Wiley & Sons Ltd.

Diffuse thyroid 18F-FDG uptake after R-CHOP therapy predicts favorable outcome in patients with DLBCL.

PubMed

Song, Moo-Kon; Chung, Joo-Seop; Kim, Seong-Jang; Kim, Sang-Soo; Shin, Ho-Jin

2015-06-01

Therapy-induced autoimmunity may mediate the destruction of cancer cells. Previous studies have demonstrated that presence of autoimmune thyroid disorder is associated with favorable outcome in patients with solid cancer. Patients with diffuse large B cell lymphoma (DLBCL) who achieved complete response on positron emission tomography/computed tomography (PET/CT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy were enrolled in this study. The patients with and without diffuse thyroid uptake (DTU) were classified by PET/CT. A total of 270 patients were enrolled in this study. DTU related to autoimmune thyroiditis was present in 61 patients. The median time to DTU detection was 5.7 months (range, 0-21.3 months). High International Prognostic Index (IPI) score (progression-free survival [PFS], p = 0.001; overall survival [OS], p = 0.008), bulky mass ≥10 cm (PFS, p = 0.001; OS, p = 0.001), bone marrow involvement (PFS, p < 0.001; OS, p = 0.001), and DTU after R-CHOP therapy (PFS, p < 0.001; OS, p = 0.001) were significantly associated with PFS and OS. High IPI score (PFS, p = 0.003; OS, p = 0.014), BM involvement (PFS, p = 0.009; OS, p = 0.039), and DTU after R-CHOP therapy (PFS, p = 0.002; OS, p = 0.002) were independently associated with PFS and OS. DTU after R-CHOP therapy independently predicted favorable outcomes in patients with DLBCL.

Cost-effectiveness of rituximab (MabThera) in diffuse large B-cell lymphoma in The Netherlands.

PubMed

Groot, M T; Lugtenburg, P J; Hornberger, J; Huijgens, P C; Uyl-de Groot, C A

2005-03-01

To determine the incremental cost-effectiveness ratio (ICER) of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) vs. CHOP plus rituximab (R-CHOP) in diffuse large B-cell lymphoma (DLBCL) patients in the Netherlands. A state transition model was developed to estimate the clinical course, costs and quality of life of patients with stage II, III or IV DLBCL receiving initial treatment with CHOP or R-CHOP to arrive at the ICER. The base year for the cost analysis was 2002 and was performed from the societal perspective. Only direct medical costs were included. The time horizon of the model was 15 yr and both costs and effects were discounted at 4%. Sensitivity analyses were performed to determine the effect of varying base-line assumptions of the model. The incremental gain in quality adjusted life years (QALYs) was 0.88 in both the younger and the older patient groups. The costs were 12 343 higher in the younger group of patients and 15 860 in the older patients. This resulted in an ICER of 13 983 for the younger and 17 933 for the older patients per QALY gained. These results were sensitive to the time horizon of the model, other variations had a marginal impact on the outcome. The addition of rituximab to standard therapy for DLBCL results in a gain of 0.88 QALYs. The ICER of 13 983 for younger and 17 933 for older patients per QALY gained should, seen in the light of disease severity, be considered acceptable by most policy makers in priority setting for budget allocation.

Treatment of AIDS related non-Hodgkin's lymphoma with combination mitoguazone dihydrochloride and low dose CHOP chemotherapy: results of a phase II study.

PubMed

Tulpule, Anil; Espina, Byron M; Pedro Santabarbara, A B; Palmer, Maria; Schiflett, Joanne; Boswell, William; Smith, Susan; Levine, Alexandra M

2004-01-01

To evaluate the response and side effects of combination therapy with low dose CHOP chemotherapy and mitoguazone dihydrochloride in patients with non-Hodgkin's lymphoma associated with the acquired immunodeficiency syndrome (AIDS-NHL). Eighteen patients newly diagnosed with intermediate or high-grade AIDS-NHL were treated with low dose CHOP as follows: day 1, cyclophosphamide 350 mg/m(2), intravenously (IV); doxorubicin 25mg/m(2) IV; vincristine 2mg IV; and prednisone 100mg given orally on days 1 through 5. In addition, mitoguazone dihydrochloride was given at a dose of 600 mg/m(2) IV on days 1 and 15 of each 28-day treatment cycle. Seventeen males and one female patient were accrued. Twelve patients had high-grade pathologies while the remainder had an intermediate grade pathology (diffuse large cell). The median CD4+ lymphocyte count was 98/dl (range 1-924). Three patients (17%) reported an AIDS-defining illness prior to lymphoma diagnosis. Of 14 evaluable patients, 6 (43%) achieved a complete remission and 5 (35%) a partial remission. The median failure free and overall survival times were 6.5 and 8.4 months, respectively. Major toxicity was hematologic with grade 3 or 4 neutropenia in 72%; two patients died of neutropenic sepsis. Mitoguazone in combination with low dose CHOP is a safe regimen, associated with a response rate of 79% (CR 43%, PR 36%, 95% CI=49-95%). These preliminary results suggest no major improvement in terms of response over use of CHOP without mitoguazone.

The effect of Vine Kill Method on Vine Kill, Tuber Skinning Injury, Tuber yield and size distribution, and tuber nutrients and phytonutrients in two potato cultivars grown for early potato production

USDA-ARS?s Scientific Manuscript database

Sixteen vine kill programs were tested on Bintje and Ciklamen potato cultivars grown for early potato production over a three year period near Paterson, Washington. Mechanical (flail chopping, flail chopping and undercutting), chemical (glufosinate, diquat, sulfuric acid, carfentrazone, pyraflufen-...

Chemistry Outreach Project to High Schools Using a Mobile Chemistry Laboratory, ChemKits, and Teacher Workshops

ERIC Educational Resources Information Center

Long, Gary L.; Bailey, Carol A.; Bunn, Barbara B.; Slebodnick, Carla; Johnson, Michael R.; Derozier, Shad

2012-01-01

The Chemistry Outreach Program (ChOP) of Virginia Tech was a university-based outreach program that addressed the needs of high school chemistry classes in underfunded rural and inner-city school districts. The primary features of ChOP were a mobile chemistry laboratory (MCL), a shipping-based outreach program (ChemKits), and teacher workshops.…

ROMI 4.0: Rough mill simulator 4.0 users manual

Treesearch

R. Edward Thomas; Timo Grueneberg; Urs Buehlmann

2015-01-01

The Rough MIll simulator (ROMI Version 4.0) is a computer software package for personal computers (PCs) that simulates current industrial practices for rip-first, chop-first, and rip and chop-first lumber processing. This guide shows how to set up the software; design, implement, and execute simulations; and examine the results. ROMI 4.0 accepts cutting bills with as...

Chopping and webbing control saw-palmetto in south Florida

Treesearch

Clifford E. Lewis

1972-01-01

Saw-palmetto is one of the more troublesome plants growing in south Florida, and its control is often desirable in programs of range and timber management. Both cross-chopping and webbing (root plowing) proved to be effective control measures, but webbing appeared to be less effective on a moist site. Many other shrubs were also effectively reduced by these treatments...

The role of 3DCT for the evaluation of chop injuries in clinical forensic medicine.

PubMed

Wittschieber, Daniel; Beck, Laura; Vieth, Volker; Hahnemann, Maria L

2016-09-01

As hatchet blows to the human head frequently cause fatal injuries, the forensic examination of survivors with cranial chop injuries is a rare phenomenon in forensic casework. Besides evaluation of clinical records, photographs, and medico-legal physical examination, the analysis and 3-dimensional reconstruction of pre-treatment computed tomography data (3DCT) must be considered an important and indispensable tool for the assessment of those cases because the characteristics of chopping trauma often appear masked or changed by clinical treatment. In the present article, the role of 3DCT for the evaluation of chop wounds in clinical forensic medicine is demonstrated by an illustrative case report of a young man who was attacked with a hatchet. 3DCT provides additional possibilities for supplementing missing information, such as number and direction of blows as well as weapon identification. Furthermore, 3DCT facilitates demonstration in court and understanding of medical lay people. We conclude that 3DCT is of particular value for the evaluation of survivors of life-threatening head and face injury. An increasing significance of this technique may be expected. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Successful Prophylactic Minocycline Treatment for Recurrent Helicobacter Cinaedi Sepsis during Chemotherapy in a Patient with Follicular Lymphoma].

PubMed

Aota, Yasuo; Gotoh, Akihiko; Nakamura, Itaru; Motoya, Kazuki; Okuda, Yuko; Hanyu, Naofumi; Honma, Toshihiro; Udou, Ryutaro; Yokoyama, Tomohisa; Kitagawa, Naoyuki; Komatsu, Norio

2017-05-01

A 63-year-old man with follicular lymphoma was administered standard R-CHOP chemotherapy. Six days after the second course of chemotherapy, the patient developed fever and chills. Blood cultures yielded rod-shaped gram-negative bacteria, but no further identification was obtained. High fever and chills returned on the fifth and sixth days after the third and fourth courses of R-CHOP, respectively. These blood cultures were also positive. Since we detected spiral-shaped gram-negative rods, we performed a prolonged culture during the febrile period after the fourth course of R-CHOP. This revealed the formation of characteristic film-like colonies, and Helicobacter cinaedi(H. cinaedi)bacteria was identified. After final identification, the patient was administered prophylactic minocycline treatment. Subsequent blood cultures were negative, fever did not recur, and we were able to complete 6 courses of R-CHOP. Although H. cinaedi has been reported to be a cause of sepsis in immunocompromised patients, standard correlation has not been established. Our case suggests that H. cinaedi should be considered when recurrent fever is observed after chemotherapy. Prophylactic antibiotic treatment with minocycline may prevent sepsis, as observed in our case.

Effect of borage and green tea aqueous extracts on the quality of lamb leg chops displayed under retail conditions.

PubMed

Bellés, M; Alonso, V; Roncalés, P; Beltrán, J A

2017-07-01

Different concentrations of two aqueous extracts from green tea leaves and borage seeds with potential antioxidant activity were evaluated in lamb leg chops. Chops were sprayed with 0.005, 0.05, 0.5, 5% (p/v) green tea extracts (T) and 0.5, 5 and 10% (p/v) borage seed extracts (B) and displayed under retail conditions for 13days. Total polyphenols, TBARS, colour, microbial and sensory analyses were performed. The extracts showed a concentration-dependent action; the minimum concentration of polyphenols which significantly reduced lipid oxidation was 2.08mgGAE/100cm 2 of meat. Both 0.5% T and 10% B limited colour deterioration, reducing also metmyoglobin formation. The extracts showed no antimicrobial effect, exceeding microbial counts of 7logCFU/cm 2 at 13days of display. Sensory analyses determined that none of the extracts added herb odours or flavours to lamb. In conclusion, 0.5% T or 10% B extracts extended lamb shelf life from 8 to 11days, so both would be recommended for lamb chops preservation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mutagenicity of basic fractions derived from lamb and beef cooked by common household methods.

PubMed

Barrington, P J; Baker, R S; Truswell, A S; Bonin, A M; Ryan, A J; Paulin, A P

1990-03-01

Mutagen production was examined in lamb and beef in relation to certain common household cooking methods. Mutagenicity was assessed, after extraction of the basic fraction of cooked meat samples, using Salmonella typhimurium strain TA1538 with added rat-liver S-9 homogenate. Little or no mutagenicity was found in barbecued lamb chops, in microwave-cooked lamb chops, sirloin steak, leg of lamb, or rolled beef loaf, in roasted leg of lamb or rolled beef loaf, in stewed blade steak or in boiled chuck steak. However, the basic fraction from well-done, edible fried or grilled meat contained mutagenic activity equivalent to approximately 30,000 TA1538 revertants/100 g cooked meat. It was found tht the mutagenic activity of grilled lamb chops, sirloin and rump steaks was directly related to the average surface temperatures attained during cooking. Use of butter as a frying medium was particularly associated with higher mutagenicity in meat samples. Fried meats (rump and fillet steaks) generally yielded higher mutagenic activity than did grilled meats (rump steak, lamb chops) at comparable temperatures of the cooking medium. Using similar cooking procedures, lamb did not differ markedly from beef in mutagenic activity.

Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: Subset analysis of randomized trial intergroup SWOG S9704

PubMed Central

Puvvada, Soham D.; Stiff, Patrick J.; Leblanc, Michael; Cook, James R.; Couban, Stephen; Leonard, John P.; Kahl, Brad; Marcellus, Deborah; Shea, Thomas C.; Winter, Jane N.; Li, Hongli; Rimsza, Lisa M.; Friedberg, Jonathan W.; Smith, Sonali M.

2016-01-01

Summary Double hit lymphoma (DHL) and double protein-expressing (MYC and BCL2) lymphomas (DPL) fare poorly with R-CHOP; consolidative autologous stem cell transplant (ASCT) may improve outcomes. S9704, a phase III randomized study of CHOP +/−R with or without ASCT allows evaluation of intensive consolidation. Immunohistochemical analysis identified 27 of 198 patients (13.6%) with MYC IHC overexpression and 20 (74%) harboring concurrent BCL2 overexpression. Four had DHL and 16 had DPL only. With median follow-up 127 months, there is a trend favoring outcomes after consolidative ASCT in DPL and MYC protein overexpressing patients, whereas all DHL patients have died irrespective of ASCT. PMID:27072903

Algorithms for the prediction of retinopathy of prematurity based on postnatal weight gain.

PubMed

Binenbaum, Gil

2013-06-01

Current ROP screening guidelines represent a simple risk model with two dichotomized factors, birth weight and gestational age at birth. Pioneering work has shown that tracking postnatal weight gain, a surrogate for low insulin-like growth factor 1, may capture the influence of many other ROP risk factors and improve risk prediction. Models including weight gain, such as WINROP, ROPScore, and CHOP ROP, have demonstrated accurate ROP risk assessment and a potentially large reduction in ROP examinations, compared to current guidelines. However, there is a need for larger studies, and generalizability is limited in countries with developing neonatal care systems. Copyright © 2013 Elsevier Inc. All rights reserved.

Curcumin induces apoptotic cell death of activated human CD4+ T cells via increasing endoplasmic reticulum stress and mitochondrial dysfunction.

PubMed

Zheng, Min; Zhang, Qinggao; Joe, Yeonsoo; Lee, Bong Hee; Ryu, Do Gon; Kwon, Kang Beom; Ryter, Stefan W; Chung, Hun Taeg

2013-03-01

Curcumin, a natural polyphenolic antioxidant compound, exerts well-known anti-inflammatory and immunomodulatory effects, the latter which can influence the activation of immune cells including T cells. Furthermore, curcumin can inhibit the expression of pro-inflammatory cytokines and chemokines, through suppression of the NF-κB signaling pathway. The beneficial effects of curcumin in diseases such as arthritis, allergy, asthma, atherosclerosis, diabetes and cancer may be due to its immunomodulatory properties. We studied the potential of curcumin to modulate CD4+ T cells-mediated autoimmune disease, by examining the effects of this compound on human CD4+ lymphocyte activation. Stimulation of human T cells with PHA or CD3/CD28 induced IL-2 mRNA expression and activated the endoplasmic reticulum (ER) stress response. The treatment of T cells with curcumin induced the unfolded protein response (UPR) signaling pathway, initiated by the phosphorylation of PERK and IRE1. Furthermore, curcumin increased the expression of the ER stress associated transcriptional factors XBP-1, cleaved p50ATF6α and C/EBP homologous protein (CHOP) in human CD4+ and Jurkat T cells. In PHA-activated T cells, curcumin further enhanced PHA-induced CHOP expression and reduced the expression of the anti-apoptotic protein Bcl-2. Finally, curcumin treatment induced apoptotic cell death in activated T cells via eliciting an excessive ER stress response, which was reversed by the ER-stress inhibitor 4-phenylbutyric acid or transfection with CHOP-specific siRNA. These results suggest that curcumin can impact both ER stress and mitochondria functional pathways, and thereby could be used as a promising therapy in the context of Th1-mediated autoimmune diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

Influence of feed intake, forage physical form, and forage fiber content on particle size of masticated forage, ruminal digesta, and feces of dairy cows.

PubMed

Shaver, R D; Nytes, A J; Satter, L D; Jorgensen, N A

1988-06-01

Two trials were conducted to determine particle size of masticates, ruminal digesta, and feces of dairy cows. In Trial 1, three Holstein cows with ruminal cannulae were fed prebloom alfalfa hay in long, chopped, or pelleted form in a Latin square design (21-d periods) conducted in early lactation (wk 3 to 11) and again during the dry period to attain high (3.75) and low (1.95% of BW) feed consumption. In trial 2, prebloom, midbloom, and full bloom alfalfa hay, mature bromegrass hay, and corn silage were fed to early lactation (wk 5 to 15) Holsteins in a 5 X 5 Latin square design (15-d periods). All diets (Trials 1 and 2) were formulated to 17% CP and contained forage:grain in a 60:40 ratio (DM basis). Similar particle distributions of digesta from long and chopped hay diets suggest little influence of chopping forage on particle size reduction when high quality forage is fed. The large proportion of DM in the small particle (less than .6 mm) pool in the rumen in both trials suggests that rate of escape of small particles from the rumen is an important factor influencing ruminal retention time. Increased proportion of coarse (greater than or equal to 2.36-mm screen) fecal particles at high intake and with fine grinding appears related to a reduction in chewing per unit feed consumed. Soluble DM and particulate matter passing a .063-mm screen made up a significant portion (30 to 50%) of the total DM sieved from all sampling sites in both trials.

The novel phloroglucinol derivative BFP induces apoptosis of glioma cancer through reactive oxygen species and endoplasmic reticulum stress pathways.

PubMed

Lu, Dah-Yuu; Chang, Chih-Shiang; Yeh, Wei-Lan; Tang, Chih-Hsin; Cheung, Chi-Wai; Leung, Yuk-Man; Liu, Ju-Fang; Wong, Kar-Lok

2012-09-15

Prenyl-phloroglucinol derivatives from hop plants have been shown to have anticancer activities. This study is the first to investigate the anticancer effects of the new phloroglucinol derivative (2,4-bis(4-fluorophenylacetyl)phloroglucinol; BFP). BFP induced cell death and anti-proliferation in three glioma, U251, U87 and C6 cells, but not in primary human astrocytes. BFP-induced concentration-dependently cell death in glioma cells was determined by MTT and SRB assay. Moreover, BFP-induced apoptotic cell death in glioma cells was measured by Hochest 33258 staining and fluorescence-activated cell sorter (FACS) of propidine iodine (PI) analysis. Treatment of U251 human glioma cells with BFP was also found to induce reactive oxygen species (ROS) generation, which was detected by a fluorescence dye used FACS analysis. Treatment of BFP also increased a number of signature endoplasmic reticulum (ER) stress markers glucose-regulated protein (GRP)-78, GRP-94, IRE1, phosphorylation of eukaryotic initiation factor-2α (eIF-2α) and up-regulation of CAAT/enhancer-binding protein homologous protein (CHOP). Moreover, treatment of BFP also increased the down-stream caspase activation, such as pro-caspase-7 and pro-caspase-12 degradation, suggesting the induction of ER stress. Furthermore, BFP also induced caspase-9 and caspase-3 activation as well as up-regulation of cleaved PARP expression. Treatment of antioxidants, or pre-transfection of cells with GRP78 or CHOP siRNA reduced BFP-mediated apoptotic-related protein expression. Taken together, the present study provides evidences to support that ROS generation, GRP78 and CHOP activation are mediating the BFP-induced human glioma cell apoptosis. Copyright © 2012 Elsevier GmbH. All rights reserved.

Remote Ischemic Preconditioning Enhances the Expression of Genes Encoding Antioxidant Enzymes and Endoplasmic Reticulum Stress-Related Proteins in Rat Skeletal Muscle.

PubMed

Park, Ui Jun; Kim, Hyoung Tae; Cho, Won Hyun; Park, Jae Hyoung; Jung, Hye Ra; Kim, Min Young

2016-12-01

Ischemic preconditioning (IPC), including remote IPC (rIPC) and direct IPC (dIPC), is a promising method to decrease ischemia-reperfusion (IR) injury. This study tested the effect of both rIPC and dIPC on the genes for antioxidant enzymes and endoplasmic reticulum (ER) stress-related proteins. Twenty rats were randomly divided into the control and study groups. In the control group (n=10), the right hind limb was sham-operated. The left hind limb (IscR) of the control group underwent IR injury without IPC. In the study group (n=10), the right hind limb received IR injury after 3 cycles of rIPC. The IscR received IR injury after 3 cycles of dIPC. Gene expression was analyzed by Quantitative real-time polymerase chain reaction from the anterior tibialis muscle. The expression of the antioxidant enzyme genes including glutathione peroxidase (GPx), superoxide dismutase (SOD) 1 and catalase (CAT) were significantly reduced in IscR compared with sham treatment. In comparison with IscR, rIPC enhanced the expression of GPx, SOD2, and CAT genes. dIPC enhanced the expression of SOD2 and CAT genes. The expression of SOD2 genes was consistently higher in rIPC than in dIPC, but the difference was only significant for SOD2. The expression of genes for ER stress-related proteins tended to be reduced in IscR in comparison with sham treatment. However, the difference was only significant for C/EBP homologous protein (CHOP). In comparison with IscR, rIPC significantly up-regulated activating transcription factor 4 and CHOP, whereas dIPC up-regulated CHOP. Both rIPC and dIPC enhanced expression of genes for antioxidant enzymes and ER stress-related proteins.

Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study

PubMed Central

Casulo, Carla; Byrtek, Michelle; Dawson, Keith L.; Zhou, Xiaolei; Farber, Charles M.; Flowers, Christopher R.; Hainsworth, John D.; Maurer, Matthew J.; Cerhan, James R.; Link, Brian K.; Zelenetz, Andrew D.; Friedberg, Jonathan W.

2015-01-01

Purpose Twenty percent of patients with follicular lymphoma (FL) experience progression of disease (POD) within 2 years of initial chemoimmunotherapy. We analyzed data from the National LymphoCare Study to identify whether prognostic FL factors are associated with early POD and whether patients with early POD are at high risk for death. Patients and Methods In total, 588 patients with stage 2 to 4 FL received first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Two groups were defined: patients with early POD 2 years or less after diagnosis and those without POD within 2 years, the reference group. An independent validation set, 147 patients with FL who received first-line R-CHOP, was analyzed for reproducibility. Results Of 588 patients, 19% (n = 110) had early POD, 71% (n = 420) were in the reference group, 8% (n = 46) were lost to follow-up, and 2% (n = 12) died without POD less than 2 years after diagnosis. Five-year overall survival was lower in the early-POD group than in the reference group (50% v 90%). This trend was maintained after we adjusted for FL International Prognostic Index (hazard ratio, 6.44; 95% CI, 4.33 to 9.58). Results were similar for the validation set (FL International Prognostic Index–adjusted hazard ratio, 19.8). Conclusion In patients with FL who received first-line R-CHOP, POD within 2 years after diagnosis was associated with poor outcomes and should be further validated as a standard end point of chemoimmunotherapy trials of untreated FL. This high-risk FL population warrants further study in directed prospective clinical trials. PMID:26124482

A new biologic prognostic model based on immunohistochemistry predicts survival in patients with diffuse large B-cell lymphoma.

PubMed

Perry, Anamarija M; Cardesa-Salzmann, Teresa M; Meyer, Paul N; Colomo, Luis; Smith, Lynette M; Fu, Kai; Greiner, Timothy C; Delabie, Jan; Gascoyne, Randy D; Rimsza, Lisa; Jaffe, Elaine S; Ott, German; Rosenwald, Andreas; Braziel, Rita M; Tubbs, Raymond; Cook, James R; Staudt, Louis M; Connors, Joseph M; Sehn, Laurie H; Vose, Julie M; López-Guillermo, Armando; Campo, Elias; Chan, Wing C; Weisenburger, Dennis D

2012-09-13

Biologic factors that predict the survival of patients with a diffuse large B-cell lymphoma, such as cell of origin and stromal signatures, have been discovered by gene expression profiling. We attempted to simulate these gene expression profiling findings and create a new biologic prognostic model based on immunohistochemistry. We studied 199 patients (125 in the training set, 74 in the validation set) with de novo diffuse large B-cell lymphoma treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like therapies, and immunohistochemical stains were performed on paraffin-embedded tissue microarrays. In the model, 1 point was awarded for each adverse prognostic factor: nongerminal center B cell-like subtype, SPARC (secreted protein, acidic, and rich in cysteine) < 5%, and microvascular density quartile 4. The model using these 3 biologic markers was highly predictive of overall survival and event-free survival in multivariate analysis after adjusting for the International Prognostic Index in both the training and validation sets. This new model delineates 2 groups of patients, 1 with a low biologic score (0-1) and good survival and the other with a high score (2-3) and poor survival. This new biologic prognostic model could be used with the International Prognostic Index to stratify patients for novel or risk-adapted therapies.

Non-Hodgkin's lymphomas in Turkey: eighteen years' experience at the Hacettepe University.

PubMed

Barista, I; Tekuzman, G; Firat, D; Baltali, E; Kansu, E; Kars, A; Ozisik, Y; Ruacan, S; Uzunalimoğlu, B; Karaağaoğlu, E

1994-12-01

In this retrospective study, 470 patients with non-Hodgkin's lymphoma (NHL) who had been followed in the Hacettepe University Medical Oncology Department between 1973 and 1990, were evaluated to establish their epidemiologic, clinical and therapeutic characteristics. Out of 470 patients, 302 (62.2%) were male and 168 (37.8%) were female. The ages ranged from 16 to 85, with a median of 44 years. Constitutional symptoms were present in 46.4% of the patients. According to the Working Formulation, low, intermediate, and high-grade lymphomas comprised 33.4%, 54.9%, and 12.7%, respectively. The most common extranodal presentation was gastrointestinal. The chemotherapy regimens most commonly used were CVP (cyclophosphamide, vincristine, prednisone), BCNOP (bleomycin, cyclophosphamide, mitoxantrone, vincristine, prednisone), CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and CHOP-Bleo (cyclophosphamide, doxorubicin, vincristine, prednisone, bleomycin). The response rates and the survival figures attained with these regimens were not statistically significantly different (P > 0.05). In the Cox multivariate model, pathologic grade, leukopenia, responsiveness to chemotherapy, bone marrow involvement and age were the important factors influencing the disease-free survival, while responsiveness to chemotherapy, age, presence of constitutional symptoms, pathologic grade, extranodal presentation and stage were the important factors influencing the overall survival. The distribution of NHL according to grade and stage was similar to that in western societies, while constitutional symptoms and lymphomas of the small intestine including immunoproliferative small intestinal disease were more common in Turkey.

miR-211 Plays a Critical Role in Cnidium officinale Makino Extract-Induced, ROS/ER Stress-Mediated Apoptosis in U937 and U266 Cells

PubMed Central

Cha, Jin Ah; Song, Hyo-Sook; Kang, Beomku; Park, Moon Nyeo; Park, Kyoung Sun; Shim, Bum-Sang

2018-01-01

Though Cnidium officinale Makino (COM) was known to have anti-angiogenic, anti-oxidant, neuroprotective, and anti-cancer effects, the underlying anticancer mechanism of COM using endoplasmic reticulum (ER) stress and miRNA remained unclear until now. Thus, in the current study, the inhibitory mechanism of COM in lymphoma and multiple myeloma (MM) cells was elucidated. COM exerted cytotoxicity in U937 and U266 but not Raw264.7 cells. COM treatment increased the expression of ER stress-related proteins such as p-protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), p-eukaryotic initiation factor (p-eIF2α), and activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP). COM also cleaved poly (ADP-ribose) polymerase (PARP) in a dose-dependent manner in both cells. Also, reactive oxygen species (ROS) generation was elevated by COM treatment. Conversely, the apoptotic effect of COM treatment was blocked by N-acetyl-l-cysteine (NAC) pretreatment. Also, the pro-survival miRNA, miR-211 was decreased by COM treatment in U937 and U266 cells. miR-211 mimic attenuated COM-induced apoptosis. Taken together, these results support the scientific evidence that COM induces apoptosis via ROS generation/CHOP activation and miR-211 suppression in U937 and U266 cells. PMID:29543750

Effects of selection for decreased residual feed intake on composition and quality of fresh pork.

PubMed

Smith, R M; Gabler, N K; Young, J M; Cai, W; Boddicker, N J; Anderson, M J; Huff-Lonergan, E; Dekkers, J C M; Lonergan, S M

2011-01-01

The objectives of this study were to determine the extent to which selection for decreased residual feed intake (RFI) affects pork composition and quality. Pigs from the fifth generation of selection for decreased RFI (select) and a randomly selected line (control) were utilized. Two experiments were conducted. In Exp. 1, barrows (22.6 ± 3.9 kg) from select and control lines were paired based on age and BW. The test was conducted in 8 replicates of pairs for the test period of 6 wk. Calpastatin activity and myosin isoforms profile were determined on samples from the LM. Control barrows were heavier (59.1 vs. 55.0 kg; P < 0.01) at the end of the test period. Calpastatin activity was greater (P < 0.01) in LM of select barrows than control barrows. In Exp. 2, composition and quality of gilts (114 kg) from control and select lines were determined. The model included fixed effects of line, slaughter date, melanocortin-4 receptor (MC4R) genotype, barn group, line × slaughter date, genotype × line interactions, a covariate of off-test BW, and sire, pen, and litter fitted as random effects. The select line (n = 80) had 0.043 kg less (P < 0.05) RFI per day than the control line (n = 89). Loin quality and composition were determined at 2 d postmortem. Desmin degradation was measured at 2 and 7 d postmortem. Purge, cook loss, sensory traits, and star probe texture were measured at 7 to 10 d postmortem on cooked chops. Residual correlations between RFI and composition and quality traits were calculated. Compared with the control line, carcasses from the select line tended to have less (P = 0.09) backfat, greater (P < 0.05) loin depth, and greater (P < 0.05) fat free lean. Loin chops from the select line had less (P < 0.01) intramuscular lipid content than loin chops from control line. Significant residual correlations between RFI and both tenderness (r = 0.24, P < 0.01) and star probe (r = -0.26, P < 0.01) were identified. Selection for decreased RFI has the potential to improve carcass composition with few effects on pH and water-holding capacity. However, decreased RFI could negatively affect tenderness and texture because of decreased lipid content and decreased postmortem protein degradation.

Choline kinase inhibition induces exacerbated endoplasmic reticulum stress and triggers apoptosis via CHOP in cancer cells

PubMed Central

Sanchez-Lopez, E; Zimmerman, T; Gomez del Pulgar, T; Moyer, M P; Lacal Sanjuan, J C; Cebrian, A

2013-01-01

Endoplasmic reticulum (ER) is a central organelle in eukaryotic cells that regulates protein synthesis and maturation. Perturbation of ER functions leads to ER stress, which has been previously associated with a broad variety of diseases. ER stress is generally regarded as compensatory, but prolonged ER stress has been involved in apoptosis induced by several cytotoxic agents. Choline kinase α (ChoKα), the first enzyme in the Kennedy pathway, is responsible for the generation of phosphorylcholine (PCho) that ultimately renders phosphatidylcholine. ChoKα overexpression and high PCho levels have been detected in several cancer types. Inhibition of ChoKα has demonstrated antiproliferative and antitumor properties; however, the mechanisms underlying these activities remain poorly understood. Here, we demonstrate that ChoKα inhibitors (ChoKIs), MN58b and RSM932A, induce cell death in cancer cells (T47D, MCF7, MDA-MB231, SW620 and H460), through the prolonged activation of ER stress response. Evidence of ChoKIs-induced ER stress includes enhanced production of glucose-regulated protein, 78 kDa (GRP78), protein disulfide isomerase, IRE1α, CHOP, CCAAT/enhancer-binding protein beta (C/EBPβ) and TRB3. Although partial reduction of ChoKα levels by small interfering RNA was not sufficient to increase the production of ER stress proteins, silencing of ChoKα levels also show a decrease in CHOP overproduction induced by ChoKIs, which suggests that ER stress induction is due to a change in ChoKα protein folding after binding to ChoKIs. Silencing of CHOP expression leads to a reduction in C/EBPβ, ATF3 and GRP78 protein levels and abrogates apoptosis in tumor cells after treatment with ChoKIs, suggesting that CHOP maintains ER stress responses and triggers the pro-apoptotic signal. Consistent with the differential effect of ChoKIs in cancer and primary cells previously described, ChoKIs only promoted a transient and moderated ER stress response in the non-tumorogenic cells MCF10A. In conclusion, pharmacological inhibition of ChoKα induces cancer cell death through a mechanism that involves the activation of exaggerated and persistent ER stress supported by CHOP overproduction. PMID:24287694

Sevoflurane-Induced Endoplasmic Reticulum Stress Contributes to Neuroapoptosis and BACE-1 Expression in the Developing Brain: The Role of eIF2α.

PubMed

Liu, Bin; Xia, Junming; Chen, Yali; Zhang, Jun

2017-02-01

Neonatal exposure to volatile anesthetics causes apoptotic neurodegeneration in the developing brain, possibly leading to neurocognitive deficits in adulthood. Endoplasmic reticulum (ER) stress might be associated with sevoflurane (sevo)-induced neuroapoptosis. However, the signaling pathway regulating sevo-induced neuroapoptosis is not understood. We investigated the effects of neonatal sevo exposure on ER signaling pathway activation. Seven-day-old mouse pups were divided into control (C) and sevo (S; 3 % sevo exposure, 6 h) groups. ER stress marker [protein kinase RNA-like ER kinase (PERK), eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), CHOP, and caspase-12] levels were determined by western blotting. To understand the role of eIF2α in sevo-induced ER stress and caspase-3 activation, pups were pretreated with an eIF2α dephosphorylation inhibitor, salubrinal, and a potent and selective inhibitor of PERK, GSK2656157, before sevo exposure, and the effects on ER stress signaling and neuroapoptosis were examined. We investigated whether neonatal exposure to sevo increased β-site APP-cleaving enzyme 1 (BACE-1) expression. Neonatal sevo exposure elevated caspase-3 activation. ER stress signaling was activated, along with increased PERK and eIF2α phosphorylation, and upregulation of proapoptotic proteins (ATF4 and CHOP) in the cerebral cortex of the developing brain. Pretreatment with salubrinal augmented sevo-induced eIF2α phosphorylation, which inhibited ER stress-mediated ATF4 and caspase-3 activation. Inhibition of PERK phosphorylation due to GSK2656157 pretreatment reduced the sevo-induced increase in eIF2α phosphorylation. Sevo increased BACE-1 expression, which was attenuated by GSK2656157 and salubrinal pretreatment. Our data suggested that neonatal sevo exposure-induced neuroapoptosis is mediated via the PERK-eIF2α-ATF4-CHOP axis of the ER stress signaling pathway. Modulation of eIF2α phosphorylation may play a key role in sevo-induced neurotoxicity in the developing brain.

CHOPPI: A Web Tool for the Analysis of Immunogenicity Risk from Host Cell Proteins in CHO-Based Protein Production

PubMed Central

Bailey-Kellogg, Chris; Gutiérrez, Andres H; Moise, Leonard; Terry, Frances; Martin, William D; De Groot, Anne S

2014-01-01

Despite high quality standards and continual process improvements in manufacturing, host cell protein (HCP) process impurities remain a substantial risk for biological products. Even at low levels, residual HCPs can induce a detrimental immune response compromising the safety and efficacy of a biologic. Consequently, advanced-stage clinical trials have been cancelled due to the identification of antibodies against HCPs. To enable earlier and rapid assessment of the risks in Chinese Hamster Ovary (CHO)-based protein production of residual CHO protein impurities (CHOPs), we have developed a web tool called CHOPPI, for CHO Protein Predicted Immunogenicity. CHOPPI integrates information regarding the possible presence of CHOPs (expression and secretion) with characterizations of their immunogenicity (T cell epitope count and density, and relative conservation with human counterparts). CHOPPI can generate a report for a specified CHO protein (e.g., identified from proteomics or immunoassays) or characterize an entire specified subset of the CHO genome (e.g., filtered based on confidence in transcription and similarity to human proteins). The ability to analyze potential CHOPs at a genomic scale provides a baseline to evaluate relative risk. We show here that CHOPPI can identify clear differences in immunogenicity risk among previously validated CHOPs, as well as identify additional “risky” CHO proteins that may be expressed during production and induce a detrimental immune response upon delivery. We conclude that CHOPPI is a powerful tool that provides a valuable computational complement to existing experimental approaches for CHOP risk assessment and can focus experimental efforts in the most important directions. Biotechnol. Bioeng. 2014;111: 2170–2182. PMID:24888712

Modulation of Pancreatic Islets' Function and Survival During Aging Involves the Differential Regulation of Endoplasmic Reticulum Stress by p21 and CHOP

PubMed Central

Mihailidou, Chrysovalantou; Chatzistamou, Ioulia; Papavassiliou, Athanasios G.

2017-01-01

Abstract Aims: Although endoplasmic reticulum (ER) stress is recognized as a major mechanism causing pancreatic dysfunction in diabetes, little is known on how aging modulates the process. Here, we compared the response with ER stress, viability, and insulin release from pancreatic islets of young (6 weeks) or aged (14 months) mice. Results: Islets from aged mice were more sensitive to ER stress than their younger counterparts; they exhibited more pronounced unfolded protein response (UPR) and caspase activation and displayed compromised insulin release after high-glucose stimulation. Genetic ablation of p21 sensitized the islets to ER stress, especially in the aged group, whereas CHOP ablation was protective for islets from both aged and younger animals. Ciclopirox (CPX), an iron chelator that stimulates p21 expression, protected islets from glucotoxicity and mice from diet-induced diabetes, especially in the aged group in a manner that was both p21 and CHOP dependent. Innovation: For the first time, the study shows that age-dependent susceptibility to diet-induced diabetes is associated with the activity of p21 and CHOP in pancreatic islets and that CPX protects islets from glucotoxicity and mice from diabetes in an age-dependent manner. Conclusions: Our results identify ER stress as an age-dependent modifier of islet survival and function by mechanisms implicating enhancement of CHOP activity and inhibition of the protective activity of p21. These findings suggest that interventions restoring the homeostatic activity of ER stress, by agents such as CPX, may be particularly beneficial for the management of diabetes in the elderly. Antioxid. Redox Signal. 27, 185–200. PMID:27931122

NCRI phase II study of CHOP in combination with ofatumumab in induction and maintenance in newly diagnosed Richter syndrome.

PubMed

Eyre, Toby A; Clifford, Ruth; Bloor, Adrian; Boyle, Lucy; Roberts, Corran; Cabes, Maite; Collins, Graham P; Devereux, Stephen; Follows, George; Fox, Christopher P; Gribben, John; Hillmen, Peter; Hatton, Chris S; Littlewood, Tim J; McCarthy, Helen; Murray, Jim; Pettitt, Andrew R; Soilleux, Elizabeth; Stamatopoulos, Basile; Love, Sharon B; Wotherspoon, Andrew; Schuh, Anna

2016-10-01

Richter syndrome (RS) is associated with chemotherapy resistance and a poor historical median overall survival (OS) of 8-10 months. We conducted a phase II trial of standard CHOP-21 (cyclophosphamide, doxorubicin, vincristine, prednisolone every 21 d) with ofatumumab induction (Cycle 1: 300 mg day 1, 1000 mg day 8, 1000 mg day 15; Cycles 2-6: 1000 mg day 1) (CHOP-O) followed by 12 months ofatumumab maintenance (1000 mg given 8-weekly for up to six cycles). Forty-three patients were recruited of whom 37 were evaluable. Seventy-three per cent were aged >60 years. Over half of the patients received a fludarabine and cyclophosphamide-based regimen as prior CLL treatment. The overall response rate was 46% (complete response 27%, partial response 19%) at six cycles. The median progression-free survival was 6·2 months (95% confidence interval [CI] 4·9-14·0 months) and median OS was 11·4 months (95% CI 6·4-25·6 months). Treatment-naïve and TP53-intact patients had improved outcomes. Fifteen episodes of neutropenic fever and 46 non-neutropenic infections were observed. There were no treatment-related deaths. Seven patients received platinum-containing salvage at progression, with only one patient obtaining an adequate response to proceed to allogeneic transplantation. CHOP-O with ofatumumab maintenance provides minimal benefit beyond CHOP plus rutuximab. Standard immunochemotherapy for RS remains wholly inadequate for unselected RS. Multinational trials incorporating novel agents are urgently needed. © 2016 John Wiley & Sons Ltd.

Prognostic value of interim FDG-PET in R-CHOP-treated diffuse large B-cell lymphoma: Systematic review and meta-analysis.

PubMed

Adams, Hugo J A; Kwee, Thomas C

2016-10-01

This study aimed to systematically review and meta-analyze the prognostic value of interim (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). MEDLINE and EMBASE were systematically searched for suitable studies. Included studies were methodologically appraised, and results were summarized both descriptively and meta-analytically. Nine studies, comprising a total of 996 R-CHOP-treated DLBCL patients, were included. Overall, studies were of moderate methodological quality. The area under the summary receiver operating curve (AUC) of interim FDG-PET in predicting treatment failure and death were 0.651 and 0.817, respectively. There was no heterogeneity in diagnostic odds ratios across available studies (I(2)=0.0%). At multivariable analysis, 2 studies reported interim FDG-PET to have independent prognostic value in addition to the International Prognostic Index (IPI) in predicting treatment failure, whereas 3 studies reported that this was not the case. One study reported interim FDG-PET to have independent prognostic value in addition to the IPI in predicting death, whereas 2 studies reported that this was not the case. In conclusion, interim FDG-PET in R-CHOP-treated DLBCL has some correlation with outcome, but its prognostic value is homogeneously suboptimal across studies and it has not consistently proven to surpass the prognostic potential of the IPI. Moreover, there is a lack of studies that compared interim FDG-PET to the recently developed and superior National Comprehensive Cancer Network-IPI. Therefore, at present there is no scientific base to support the clinical use of interim FDG-PET in R-CHOP-treated DLBCL. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A prospective study of reduced-dose three-course CHOP followed by involved-field radiotherapy for patients 70 years old or more with localized aggressive non-Hodgkin's lymphoma

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

Shikama, Naoto; Oguchi, Masahiko; Isobe, Koichi

2006-09-01

Purpose: We conducted a multicenter prospective study to evaluate the efficacy and safety of reduced-dose three-course CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) followed by involved-field radiotherapy for elderly patients with localized aggressive non-Hodgkin's lymphoma. The primary endpoint was compliance with the combined modality. Methods and Materials: This study included untreated patients, {>=}70 years old, with diffuse aggressive lymphoma, Stage IA or contiguous nonbulky Stage IIA. 80%-CHOP (cyclophosphamide 600 mg/m{sup 2}, doxorubicin 40 mg/m{sup 2}, vincristine 1.1 mg/m{sup 2}, and prednisolone at 80 mg/day for 5 days) was repeated every 3 weeks. After three cycles of chemotherapy, involved-field radiotherapy was performedmore » with a radiation dose of 30-50 Gy in 15-28 fractions. Results: Twenty-four patients with a median age of 75 years (range, 70-84 years) were enrolled. The compliance rate of the protocol study was 87.5% (95% confidence interval [CI], 67.6-97.3). Three patients received only two cycles of chemotherapy because of toxicity or second neoplasm. There were no deaths caused by severe toxicity. The 3-year progression-free and overall survival rates were 83.1% (95% CI, 75.4-90.8) and 82.9% (95% CI, 75.1-90.6), respectively. Conclusion: Three-course 80%-CHOP followed by involved-field radiotherapy may be safe for administration to elderly patients over 70 years old. The next step is to evaluate three-course 80%-CHOP and rituximab followed by radiotherapy in elderly patients with localized disease.« less

Modulation of Pancreatic Islets' Function and Survival During Aging Involves the Differential Regulation of Endoplasmic Reticulum Stress by p21 and CHOP.

PubMed

Mihailidou, Chrysovalantou; Chatzistamou, Ioulia; Papavassiliou, Athanasios G; Kiaris, Hippokratis

2017-08-01

Although endoplasmic reticulum (ER) stress is recognized as a major mechanism causing pancreatic dysfunction in diabetes, little is known on how aging modulates the process. Here, we compared the response with ER stress, viability, and insulin release from pancreatic islets of young (6 weeks) or aged (14 months) mice. Islets from aged mice were more sensitive to ER stress than their younger counterparts; they exhibited more pronounced unfolded protein response (UPR) and caspase activation and displayed compromised insulin release after high-glucose stimulation. Genetic ablation of p21 sensitized the islets to ER stress, especially in the aged group, whereas CHOP ablation was protective for islets from both aged and younger animals. Ciclopirox (CPX), an iron chelator that stimulates p21 expression, protected islets from glucotoxicity and mice from diet-induced diabetes, especially in the aged group in a manner that was both p21 and CHOP dependent. For the first time, the study shows that age-dependent susceptibility to diet-induced diabetes is associated with the activity of p21 and CHOP in pancreatic islets and that CPX protects islets from glucotoxicity and mice from diabetes in an age-dependent manner. Our results identify ER stress as an age-dependent modifier of islet survival and function by mechanisms implicating enhancement of CHOP activity and inhibition of the protective activity of p21. These findings suggest that interventions restoring the homeostatic activity of ER stress, by agents such as CPX, may be particularly beneficial for the management of diabetes in the elderly. Antioxid. Redox Signal. 27, 185-200.

Biology and trapping of stable flies (Diptera: Muscidae) developing in pineapple residues (Ananas comosus) in Costa Rica.

PubMed

Solórzano, José-Arturo; Gilles, Jeremie; Bravo, Oscar; Vargas, Cristina; Gomez-Bonilla, Yannery; Bingham, Georgina V; Taylor, David B

2015-01-01

Pineapple production in Costa Rica increased nearly 300-fold during the last 30 yr, and >40,000 hectares of land are currently dedicated to this crop. At the end of the pineapple cropping cycle, plants are chopped and residues incorporated into the soil in preparation for replanting. Associated with increased pineapple production has been a large increase in stable fly, Stomoxys calcitrans (L.), populations. Stable flies are attracted to, and oviposit in, the decomposing, chopped pineapple residues. In conjunction with chemical control of developing larvae, adult trapping is an important control strategy. In this study, four blue-black fabric traps, Nzi, Vavoua, Model H, and Ngu, were compared with a white sticky trap currently used for stable fly control in Costa Rica. Overall, the white sticky trap caught the highest number of stable flies, followed by the Nzi, Vavoua, Model H, and Ngu. Collections on the white sticky trap increased 16 d after residues were chopped; coinciding with the expected emergence of flies developing in the pineapple residues. During this same time period, collections in the blue-black fabric traps decreased. Sex ratio decreased from >7:1 (females:males) 3-7 d after chopping to 1:1 at 24-28 d. White sticky, Nzi and Vavoua traps collected similar numbers of colonizing flies 3-7 d after residues were chopped. However, white sticky traps collected more flies once emergence from the pineapple residues began. Although white sticky traps collected more flies than fabric traps, they remain labor intensive and environmentally unsound because of their disposable and nonbiodegradable nature. Published by Oxford University Press on behalf of the Entomological Society of America 2015. This work is written by US Government employees and is in the public domain in the US.

Biology and Trapping of Stable Flies (Diptera: Muscidae) Developing in Pineapple Residues (Ananas comosus) in Costa Rica

PubMed Central

Solórzano, José-Arturo; Gilles, Jeremie; Bravo, Oscar; Vargas, Cristina; Gomez-Bonilla, Yannery; Bingham, Georgina V.; Taylor, David B.

2015-01-01

Pineapple production in Costa Rica increased nearly 300-fold during the last 30 yr, and >40,000 hectares of land are currently dedicated to this crop. At the end of the pineapple cropping cycle, plants are chopped and residues incorporated into the soil in preparation for replanting. Associated with increased pineapple production has been a large increase in stable fly, Stomoxys calcitrans (L.), populations. Stable flies are attracted to, and oviposit in, the decomposing, chopped pineapple residues. In conjunction with chemical control of developing larvae, adult trapping is an important control strategy. In this study, four blue-black fabric traps, Nzi, Vavoua, Model H, and Ngu, were compared with a white sticky trap currently used for stable fly control in Costa Rica. Overall, the white sticky trap caught the highest number of stable flies, followed by the Nzi, Vavoua, Model H, and Ngu. Collections on the white sticky trap increased 16 d after residues were chopped; coinciding with the expected emergence of flies developing in the pineapple residues. During this same time period, collections in the blue-black fabric traps decreased. Sex ratio decreased from >7:1 (females:males) 3–7 d after chopping to 1:1 at 24–28 d. White sticky, Nzi and Vavoua traps collected similar numbers of colonizing flies 3–7 d after residues were chopped. However, white sticky traps collected more flies once emergence from the pineapple residues began. Although white sticky traps collected more flies than fabric traps, they remain labor intensive and environmentally unsound because of their disposable and nonbiodegradable nature. PMID:26454479

Low incidence of pneumocystis pneumonia utilizing PCR-based diagnosis in patients with B-cell lymphoma receiving rituximab-containing combination chemotherapy.

PubMed

Barreto, Jason N; Ice, Lauren L; Thompson, Carrie A; Tosh, Pritish K; Osmon, Douglas R; Dierkhising, Ross A; Plevak, Matthew F; Limper, Andrew H

2016-11-01

Recent literature has demonstrated concern over the risk of Pneumocystis jirovecii pneumonia (PJP) when administering rituximab with combination chemotherapy such as in R-CHOP; however, the exact risk and potential need for prophylaxis is unknown. We sought to determine the incidence of PJP infection following R-CHOP administration in patients with B-cell lymphoma. Consecutive patients diagnosed with B-cell lymphoma receiving R-CHOP were evaluated from chemotherapy initiation until 180 days after the last administration. The primary outcome was cumulative incidence of PJP infection. Secondary endpoints included the association of rituximab, prednisone and subsequent chemotherapy with PJP infection risk. A total of 689 patients (53% male, median age 66 years) were included. Seventy-three percent of patients completed at least 6 cycles of R-CHOP treatment. Median rituximab and prednisone cumulative doses were 3950 mg and 5325 mg, respectively. Median daily prednisone dose through end of treatment was 45 mg (range 7.6 mg to 119 mg). The cumulative incidence of PJP was 1.51% (95% CI 0.57-2.43, at maximum follow-up of 330 days), below 3.5%, the conventional threshold for prophylaxis. Univariate analysis did not detect a statistically significant association between PJP and rituximab, steroids, or receipt of additional chemotherapy in this patient population. Our results demonstrate a low occurrence of Pneumocystis pneumonia during R-CHOP treatment of B-cell lymphoma and argue against universal anti-Pneumocystis prophylaxis in this setting. Further investigations should focus on targeted anti-Pneumocystis prophylaxis for patients presenting with high-risk baseline characteristics or when receiving rituximab-inclusive intensive combination chemotherapy regimens as treatment for other aggressive lymphoma subtypes. Am. J. Hematol. 91:1113-1117, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Methodology of clinical trials evaluating the incorporation of new drugs in the first-line treatment of patients with diffuse large B-cell lymphoma (DLBCL): a critical review.

PubMed

Iacoboni, G; Zucca, E; Ghielmini, M; Stathis, A

2018-05-01

The first-line treatment of diffuse large B-cell lymphoma (DLBCL) is the combination of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, curing approximately 60% of patients. Many clinical trials have been carried out over the last 10 years trying to improve the results of this treatment, but the appropriateness of their planning strategies could be rediscussed. Reports of phase III trials evaluating the addition of molecularly targeted agents or new monoclonal antibodies to the classic R-CHOP backbone in first-line induction or maintenance treatment were reviewed. The trial design, primary end point, number of patients enrolled, patient selection criteria, treatment schedule and results were registered for each one. In addition, the phases I and II trials which preceded these phase III trials were also reviewed. Among six phase III trials with results, only one trial evaluating lenalidomide maintenance after response to R-CHOP induction was positive and reached its primary end point. The other five trials did not show an improved outcome with the addition of the new agent. The preceding phases I and II trials were very heterogeneous in their end points and design. Even though most of these trials were considered positive, thus encouraging further investigation, so far they failed to predict the results of the subsequent phase III trials. The standard of care for DLBCL is still R-CHOP. Phase I/II trials failed to predict the results of subsequent phase III trials evaluating non-chemotherapeutic agents added to R-CHOP. The methodology of phase II trials evaluating new agents in DLBCL needs to be better defined in the future.

B-machine polarimeter: A telescope to measure the polarization of the cosmic microwave background

NASA Astrophysics Data System (ADS)

Williams, Brian Dean

The B-Machine Telescope is the culmination of several years of development, construction, characterization and observation. The telescope is a departure from standard polarization chopping of correlation receivers to a half wave plate technique. Typical polarimeters use a correlation receiver to chop the polarization signal to overcome the 1/f noise inherent in HEMT amplifiers. B-Machine uses a room temperature half wave plate technology to chop between polarization states and measure the polarization signature of the CMB. The telescope has a demodulated 1/f knee of 5 mHz and an average sensitivity of 1.6 mK s . This document examines the construction, characterization, observation of astronomical sources, and data set analysis of B-Machine. Preliminary power spectra and sky maps with large sky coverage for the first year data set are included.

Joining and reinforcing a composite bumper beam and a composite crush can for a vehicle

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

Berger, Elisabeth; Decker, Leland; Armstrong, Dale

A front bumper beam and crush can (FBCC) system is provided for a vehicle. A bumper beam has an interior surface with a plurality of ribs extending therefrom. The ribs and the interior surface are made of a chopped fiber composite and cooperate to engage a crush can. The chopped fiber composite reinforces the engaging surfaces of the crush can and the interior surface of the bumper beam. The crush can has a tubular body made of a continuous fiber composite. The crush can has outwardly-extending flanges at an end spaced away from the bumper beam. The flanges are atmore » least partially provided with a layer of chopped fiber composite to reinforce a joint between the outwardly-extending flange and the vehicle frame.« less

Comparison of three site preparation techniques on growth of planted loblolly pine 6 years after a southern pine beetle epidemic

Treesearch

Wayne K. Clatterbuck; Michael Carr

2013-01-01

Three site preparation treatments: (1) complete removal of woody debris—drum chopped, raked, and disked; (2) drum chopping leaving woody debris; and (3) no site preparation—planting among dead standing trees were compared by evaluating the growth and survival of planted loblolly pine (Pinus taeda L.) after six growing seasons following a southern...

Effects of varying particle size of forage on digestion and chewing behavior of dairy heifers.

PubMed

Jaster, E H; Murphy, M R

1983-04-01

Eighteen Holstein heifers were fed long and chopped coarse and fine alfalfa hay ad libitum to evaluate effects of physical form on digestion and chemical composition of feed and fecal particles and to examine the applicability of a sinusoidal model to chewing behavior. Recordings of jaw movement were divided into 1-h segments for analysis. Least square mean size of fecal particles from coarse and finely chopped diets were 290 and 297 micrometers as compared to 227 micrometers on long hay. Intakes of dry matter were greater an digestibilities lower for chopped as compared to long hay. Crude protein content of separated feed and fecal particles increased as particle size decreased. Neural and acid detergent fiber concentrations decreased in feed and feces with decreasing particle size. Lignin content of feed particles decreased as particle size decreased, whereas for fecal particles lignin as a percent of cell wall followed a "U" shaped pattern of declining then increasing as size decreased. Patterns were sinusoidal for eating and ruminating long and chopped hays and total chewing (eating and ruminating) of long hay. Our results suggest a gradual effect on chemical degradation and physical detrition of digesta particles and chewing behavior as forage particle size decreased.

Efficacy and safety of frontline rituximab, cyclophosphamide, doxorubicin and prednisone plus bortezomib (VR-CAP) or vincristine (R-CHOP) in a subset of newly diagnosed mantle cell lymphoma patients medically eligible for transplantation in the randomized, phase 3 LYM-3002 study.

PubMed

Drach, Johannes; Huang, Huiqiang; Samoilova, Olga; Belch, Andrew; Farber, Charles; Bosly, André; Novak, Jan; Zaucha, Jan; Dascalescu, Angela; Bunworasate, Udomsak; Masliak, Zvenyslava; Vilchevskaya, Kateryna; Robak, Tadeusz; Pei, Lixia; Rooney, Brendan; van de Velde, Helgi; Cavalli, Franco

2018-04-01

This post-hoc subanalysis of the LYM-3002 phase 3 study assessed the efficacy and safety of substituting vincristine in rituximab, cyclophosphamide, doxorubicin and prednisone (R-CHOP; n = 42) for bortezomib (VR-CAP; n = 38) in a subgroup of 80 mantle cell lymphoma (MCL) patients aged <60 years who did not receive stem cell transplantation (SCT) despite medical eligibility. Complete response (CR)/unconfirmed CR (CRu) rates were 67 vs. 39% (odds ratio 3.69 [95% CI(confidence interval): 1.31, 10.41]; p = .012). After 40 months median follow-up, median progression-free survival by independent radiology committee with VR-CAP vs. R-CHOP was 32.6 vs. 12.0 months (hazard ratio (HR) 0.59 [95% CI: 0.31, 1.13]; p = .108); median overall survival was not reached vs. 47.3 months (HR 0.81 [95% CI: 0.33, 1.96]; p = .634). Adverse events included neutropenia (92/76%), thrombocytopenia (70/10%) and leukopenia (65/50%). VR-CAP represents a potential alternative to R-CHOP in combined and/or alternating regimens for younger, SCT-eligible MCL patients.

An evaluation of the effectiveness of FreshCase technology to extend the storage life of whole-muscle pork and ground pork sausage.

PubMed

Yang, X; Woerner, D R; McCullough, K R; Hasty, J D; Geornaras, I; Smith, G C; Sofos, J N; Belk, K E

2016-11-01

The objective of this study was to identify the maximum time of refrigerated storage before aerobic psychrotrophic bacteria grew to a level indicative of spoilage (7 log cfu/g) or other indicators of spoilage were observed for whole-muscle pork and ground pork sausage packaged using FreshCase technology. Pork chops and pork sausage were packaged using conventional vacuum packaging without nitrite in film (Control) or using FreshCase technology and were compared with respect to microbial counts, pH, instrumental color measurements, lipid oxidation level, and sensory properties. The storage life was 45 d for pork chops stored in FreshCase packages at 1°C and 19 d for ground pork sausage stored under the same condition. Results indicated that both pork chops and sausage stored in FreshCase packages retained redder color ( < 0.05) than those stored in Control packages. No differences ( > 0.05) existed between Control and FreshCase packaged samples for any off-odor detection for either pork chops or sausage. Moreover, levels of oxidative rancidity in all packages had low thiobarbituric acid reactive substances values. The results indicated that FreshCase technology can be used to extend storage life of pork products without having adverse effects on pork quality.

Emergency Preparedness for a Mass Gathering: the 2015 Papal Visit to Philadelphia.

PubMed

Paras, Emma; Butler, Matthew; Maguire, Brian F; Scarfone, Rich

2017-04-01

In September 2015, Pope Francis visited Philadelphia, Pennsylvania, and led outdoor events over the course of 2 days. As a result, The Children's Hospital of Philadelphia (CHOP) was faced with the challenge of planning for and responding to a mass gathering that was anticipated to be one of the largest in US history. As a result of unprecedented traffic restrictions, it was anticipated that patients, staff, and vendors would have severe challenges accessing the hospital, along with impaired communications from widespread cell phone service disruption. Previous mass gatherings have proven a need for early, detailed planning with multidisciplinary stakeholders, but little has been published on the impact of mass gatherings on area hospitals. This lack of data makes it difficult to predict the extent to which demand for hospital services would be increased and which services would be most affected. Early, coordinated planning allowed CHOP leaders to delegate responsibilities to those with specific expertise, prioritize needs, prevent duplication of efforts, and ensure engagement and accountability from key stakeholders. Emergency preparedness-led efforts including housing almost 1000 employees for 3 consecutive nights and assisting families with access allowed our hospital to maintain operations. The planning strategies shared here will provide emergency preparedness planners with a blueprint for future mass gathering preparedness. (Disaster Med Public Health Preparedness. 2017;11:267-276).

Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study.

PubMed

Chiappella, Annalisa; Martelli, Maurizio; Angelucci, Emanuele; Brusamolino, Ercole; Evangelista, Andrea; Carella, Angelo Michele; Stelitano, Caterina; Rossi, Giuseppe; Balzarotti, Monica; Merli, Francesco; Gaidano, Gianluca; Pavone, Vincenzo; Rigacci, Luigi; Zaja, Francesco; D'Arco, Alfonso; Cascavilla, Nicola; Russo, Eleonora; Castellino, Alessia; Gotti, Manuel; Congiu, Angela Giovanna; Cabras, Maria Giuseppina; Tucci, Alessandra; Agostinelli, Claudio; Ciccone, Giovannino; Pileri, Stefano A; Vitolo, Umberto

2017-08-01

The prognosis of young patients with diffuse large B-cell lymphoma at high risk (age-adjusted International Prognostic Index [aa-IPI] score 2 or 3) treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone) is poor. The aim of this study was to investigate the possible benefit of intensification with high-dose chemotherapy and autologous stem-cell transplantation as part of first-line treatment in these patients. We did a multicentre, open-label, randomised, controlled, phase 3 trial with a 2 × 2 factorial design to compare, at two different R-CHOP dose levels, a full course of rituximab-dose-dense chemotherapy (no transplantation group) versus an abbreviated course of rituximab-dose-dense chemotherapy followed by consolidation with R-MAD (rituximab plus high-dose cytarabine plus mitoxantrone plus dexamethasone) and high-dose BEAM chemotherapy (carmustine, etoposide, cytarabine, and melphalan) plus autologous stem-cell transplantation (transplantation group) in young patients (18-65 years) with untreated high-risk diffuse large B-cell lymphoma (aa-IPI score 2-3). At enrolment, patients were stratified according to aa-IPI score and randomly assigned (1:1:1:1) to receive R-CHOP (intravenous rituximab 375 mg/m 2 , cyclophosphamide 750 mg/m 2 , doxorubicin 50 mg/m 2 , and vincristine 1·4 mg/m 2 on day 1, plus oral prednisone 100 mg on days 1-5) delivered in a 14-day cycle (R-CHOP-14) for eight cycles; high-dose R-CHOP-14 (R-MegaCHOP-14; R-CHOP-14 except for cyclophosphamide 1200 mg/m 2 and doxorubicin 70 mg/m 2 ) for six cycles; R-CHOP-14 for four cycles followed by R-MAD (intravenous rituximab 375 mg/m 2 on day 1 or 4 plus intravenous cytarabine 2000 mg/m 2 and dexamethasone 4 mg/m 2 every 12 h on days 1-3 plus intravenous mitoxantrone 8 mg/m 2 on days 1-3) plus BEAM (intravenous carmustine 300 mg/m 2 on day -7, intravenous cytarabine 200 mg/m 2 twice a day on days -6 to -3, intravenous etoposide 100 mg/m 2 twice a day on days -6 to -3, plus intravenous melphalan 140 mg/m 2 on day -2) and autologous stem-cell transplantation (day 0); or R-MegaCHOP-14 for four cycles followed by R-MAD plus BEAM and autologous stem-cell transplantation. The primary endpoint was failure-free survival at 2 years in the intention-to-treat population. This study is registered with EudraCT (2005-002181-14; 2007-000275-42) and with ClinicalTrials.gov, number NCT00499018. Between Jan 10, 2006, and Sept 8, 2010, 399 patients were randomly assigned to receive transplantation (n=199) or no transplantation (n=200); 203 patients were assigned to receive R-CHOP-14 and 196 were assigned to receive R-MegaCHOP-14. With a median follow-up of 72 months (IQR 57-88), 2-year failure-free survival was 71% (95% CI 64-77) in the transplantation group versus 62% (95% CI 55-68) in the no transplantation group (hazard ratio [HR] 0·65 [95% CI 0·47-0·91]; stratified log-rank test p=0·012). No difference in 5-year overall survival was observed between these groups (78% [95% CI 71-83] versus 77% [71-83]; HR 0·98 [0·65-1·48]; stratified log-rank test p=0·91). Grade 3 or worse haematological adverse events were reported in 183 (92%) of 199 patients in the transplantation group versus 135 (68%) of 200 patients in the no transplantation group. Grade 3 or worse non-haematological adverse events were reported in 90 (45%) versus 31 (16%); the most common grade 3 or worse non-haematological adverse event was gastrointestinal (49 [25%] vs 19 [10%]). Treatment-related deaths occurred in 13 (3%) patients; eight in the transplantation group and five in the no transplantation group. Abbreviated rituximab-dose-dense chemotherapy plus R-MAD plus BEAM and autologous stem-cell transplantation reduced the risk of treatment failure compared with full course rituximab-dose-dense chemotherapy in young patients with diffuse large B-cell lymphoma at high risk. However, these results might not be clinically meaningful, since this improvement did not reflect an improvement in overall survival. These results do not support further consideration of the use of intensification of R-CHOP as an upfront strategy in patients with diffuse large B-cell lymphoma with poor prognosis. Fondazione Italiana Linfomi. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mars Science Laboratory Launch-Arrival Space Study: A Pork Chop Plot Analysis

NASA Technical Reports Server (NTRS)

Cianciolo, Alicia Dwyer; Powell, Richard; Lockwood, Mary Kae

2006-01-01

Launch-Arrival, or "pork chop", plot analysis can provide mission designers with valuable information and insight into a specific launch and arrival space selected for a mission. The study begins with the array of entry states for each pair of selected Earth launch and Mars arrival dates, and nominal entry, descent and landing trajectories are simulated for each pair. Parameters of interest, such as maximum heat rate, are plotted in launch-arrival space. The plots help to quickly identify launch and arrival regions that are not feasible under current constraints or technology and also provide information as to what technologies may need to be developed to reach a desired region. This paper provides a discussion of the development, application, and results of a pork chop plot analysis to the Mars Science Laboratory mission. This technique is easily applicable to other missions at Mars and other destinations.

Examining Racial Differences in Diffuse Large B-Cell Lymphoma Presentation and Survival

PubMed Central

Flowers, Christopher R.; Shenoy, Pareen J.; Borate, Uma; Bumpers, Kevin; Douglas-Holland, Tanyanika; King, Nassoma; Brawley, Otis W.; Lipscomb, Joseph; Lechowicz, Mary Jo; Sinha, Rajni; Grover, Rajinder S.; Bernal-Mizrachi, Leon; Kowalski, Jeanne; Donnellan, Will; The, Angelina; Reddy, Vishnu; Jaye, David L.; Foran, James

2014-01-01

We performed a retrospective cohort analysis of 701 (533 White and 144 Black) patients with DLBCL treated at two referral centers in southern United States between 1981-2010. Median age of diagnosis for Blacks was 50 years vs. 57 years for Whites (p<0.001). A greater percentage of Blacks presented with elevated lactate dehydrogenase levels, B-symptoms, and performance status≥2. More Whites (8%) than Blacks (3%) had positive family history of lymphoma (p=0.048). There were no racial differences in the use of R-CHOP (52% Black vs. 47% White, p=0.73). While black race predicted worse survival among patients treated with CHOP (Hazard ratio [HR] 1.8, p<0.001), treatment with R-CHOP was associated with improved survival irrespective of race (HR 0.61, p=0.01). Future studies should examine biological differences that may underlie the observed racial differences in presentation and outcome. PMID:22800091

Structural changes evaluation with Raman spectroscopy in meat batters prepared by different processes.

PubMed

Kang, Zhuang-Li; Li, Xiang; He, Hong-Ju; Ma, Han-Jun; Song, Zhao-Jun

2017-08-01

A comprehensive study was conducted to evaluate the structural changes of meat and protein of pork batters produced by chopping or beating process through the phase-contrast micrograph, laser light scattering analyzer, scanning electronic microscopy and Raman spectrometer. The results showed that the shattered myofibrilla fragments were shorter and particle-sizes were smaller in the raw batter produced by beating process than those in the chopping process. Compared with the raw and cooked batters produced by chopping process, modifications in amide I and amide III bands revealed a significant decrease of α -helix content and an increase of β -sheet, β -turn and random coils content in the beating process. The changes in secondary structure of protein in the batter produced by beating process was thermally stable. Moreover, more tyrosine residues were buried, and more gauche-gauche-trans disulfide bonds conformations and hydrophobic interactions were formed in the batter produced by beating process.

A Comparative study of two RVE modelling methods for chopped carbon fiber SMC

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

Chen, Zhangxing; Li, Yi; Shao, Yimin

To achieve vehicle light-weighting, the chopped carbon fiber sheet molding compound (SMC) is identified as a promising material to replace metals. However, there are no effective tools and methods to predict the mechanical property of the chopped carbon fiber SMC due to the high complexity in microstructure features and the anisotropic properties. In this paper, the Representative Volume Element (RVE) approach is used to model the SMC microstructure. Two modeling methods, the Voronoi diagram-based method and the chip packing method, are developed for material RVE property prediction. The two methods are compared in terms of the predicted elastic modulus andmore » the predicted results are validated using the Digital Image Correlation (DIC) tensile test results. Furthermore, the advantages and shortcomings of these two methods are discussed in terms of the required input information and the convenience of use in the integrated processing-microstructure-property analysis.« less

Effects of replacing maize silage with lucerne silage and lucerne silage chop length on rumen function and milk fatty acid composition.

PubMed

Thomson, A L; Humphries, D J; Kliem, K E; Dittmann, M T; Reynolds, C K

2017-09-01

The objective of this study was to investigate whether higher lucerne (Medicago sativa; alfalfa) silage inclusion rate and longer lucerne chop length improves rumen function through increased provision of physically effective fiber, when included in a maize and lucerne silage-based total mixed ration. Diets were formulated to contain a 50:50 forage:concentrate ratio [dry matter (DM) basis] and be isonitrogenous and contain equal levels of neutral detergent fiber (320 g/kg). The forage portion of the offered diets was composed of maize and lucerne silage DM in proportions (wt/wt) of either 25:75 (high lucerne; HL) or 75:25 (low lucerne; LL). Second-cut lucerne was harvested and conserved as silage at either a long (L) or a short (S) chop length (geometric mean particle lengths of 9.0 and 14.3 mm, respectively). These variables were combined in a 2 × 2 factorial arrangement to give 4 treatments (HLL, HLS, LLL, LLS), which were fed in a 4 × 4 Latin square design study to 4 rumen-cannulated, multiparous, Holstein dairy cows in mid lactation. Effects on DM intake, chewing behavior, rumen volatile fatty acid concentration, rumen pH, rumen and fecal particle size, milk production, and milk fatty acid profile were measured. Longer chop length increased rumination times per kilogram of DM intake (+2.8 min/kg) relative to the S chop length, with HLL diets resulting in the most rumination chews. Rumen concentrations of total volatile fatty acids, acetate, and n-valerate were higher for the HLS diet than the other 3 diets, whereas rumen propionate concentration was lowest for the HLL diet. Physically effective fiber (particles >4 mm) percentage in the rumen mat was increased when L chop length was fed regardless of lucerne inclusion rate. No effect of treatment was observed for milk yield, although milk protein concentration was increased by L for the LL diet (+1.6 g/kg) and decreased by L for the HLL diet (-1.4 g/kg). Milk fat concentrations of total cis-18:1 (+3.7 g/100 g of fatty acids) and 18:3 n-3 (+0.2 g/100 g of fatty acids) were greater with HL. In conclusion, longer lucerne silage chop length increased time spent ruminating per kilogram of DM intake, but had no effect on rumen pH in the present study. Increasing dietary lucerne inclusion rate had no effects on rumination activity or rumen pH, but decreased the ratio of n-6:n-3 polyunsaturated fatty acid concentrations in milk fat. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Therapeutic trials for a rabbit model of EBV-associated Hemophagocytic Syndrome (HPS): effects of vidarabine or CHOP, and development of Herpesvirus papio (HVP)-negative lymphomas surrounded by HVP-infected lymphoproliferative disease.

PubMed

Hayashi, K; Joko, H; Koirala, T R; Onoda, S; Jin, Z-S; Munemasa, M; Ohara, N; Oda, W; Tanaka, T; Oka, T; Kondo, E; Yoshino, T; Takahashi, K; Yamada, M; Akagi, T

2003-10-01

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS), which is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD), is a distinct disease characterized by high mortality. Treatment of patients with EBV-AHS has proved challenging. To develop some therapeutic interventions for EBV-AHS, we examined the effectiveness of an antiviral agent (vidarabine) or chemotherapy (CHOP), using a rabbit model for EBV-AHS. Fourteen untreated rabbits were inoculated intravenously with cell-free virions of the EBV-like virus Herpesvirus papio (HVP). All of the rabbits died of HVP-associated (LPD) and hemophagocytic syndrome (HPS) between 21 and 31 days after inoculation. Furthermore, three HVP-infected rabbits treated with vidarabine died between days 23 and 28 after inoculation, and their clinicopathological features were no different from those of untreated rabbits, indicating that this drug is not effective at all to treat HVP-induced rabbit LPD and HPS. Three of the infected rabbits that were treated with one course, with an incomplete set of three courses, or with three full courses of CHOP treatment died of HVP-induced LPD and HPS with a bleeding tendency and/or with opportunistic infections. They died on the 26th, 62nd and 105th day after virus inoculation, respectively. CHOP treatment transiently suppressed the HVP-induced LPD and contributed to the prolonged survival time of two infected rabbits. However, it did not remove all of the HVP-infected cells from the infected rabbits, and residual HVP-infected lymphocytes caused recurrences of rabbit LPD and HPS. The most interesting finding of this experiment was observed in the infected rabbit with the longest survival time of 105 days: HVP-negative lymphomas surrounded by HVP-induced LPD developed in the larynx and ileum of this rabbit, causing an obstruction of the lumen. We concluded that these were not secondary lymphomas caused by CHOP treatment, because no suspicious lesions were detected in three uninfected rabbits that were treated with three courses of CHOP for 120 days. It is therefore necessary to clarify the mechanism by which HVP-negative lymphomas associated with HVP-induced LPD can develop. Our data from therapeutic trials using EBV-AHS animal models indicate that vidarabine is not effective as an agent to treat HVP-infected rabbits, and even the cytotoxic chemotherapy of CHOP is not sufficient to cure the HVP-infected rabbits or to prolong the survival time of infected rabbits. Further studies will therefore be required to develop better therapies to treat EBV-AHS.

Inhibition of endoplasmic reticulum stress is involved in the neuroprotective effects of candesartan cilexitil in the rotenone rat model of Parkinson's disease.

PubMed

Wu, Liang; Tian, You-Yong; Shi, Jing-Ping; Xie, Wei; Shi, Jian-Quan; Lu, Jie; Zhang, Ying-Dong

2013-08-26

Recent studies indicated that angiotensin II (Ang II) receptor blockers could reduce neurotoxins-induced dopaminergic (DA) cell death, but the underlying mechanisms are still unclear. Given that endoplasmic reticulum (ER) stress plays a major role in rotenone-induced neuronal apoptosis, we investigated whether candesartan cilexetil, a selective and high-affinity Ang II receptor antagonist, could protect the DA neuron via reducing ER stress in a chronic rotenone rat model for Parkinson's disease (PD). Our data showed that candesartan cilexetil could ameliorate the descent latency in catalepsy tests, and decrease rotenone-induced DA neuron apoptosis. Moreover, candesartan cilexetil has been found to play a protective role via down-regulating the expression of activating transcription factor 4 (ATF4), the CCAAT-enhancer-binding protein (C/EBP) homologous protein (CHOP), and p53 upregulated modulator of apoptosis (Puma). Thus, our experiments strongly suggest that administration of candesartan cilexetil protects DA neuron involving blocking ER stress, possibly via inhibiting activation of the ATF4-CHOP-Puma pathway, which could provide new insight into clinical therapeutics for PD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Utilization of the cellular stress response to sensitize cancer cells to TRAIL-mediated apoptosis.

PubMed

Siegelin, Markus David

2012-08-01

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a promising death ligand who has received significant attention due to its specific anti-cancer activity. Recently, a number of clinical trials involving either recombinant soluble TRAIL or agonistic death receptor (DR) antibodies have even been initiated. One major caveat in TRAIL-based anti-cancer therapies is that a considerable number of cancer cells are notorious resistant to apoptosis induction by TRAIL. Overcoming this primary or secondary evolved resistance is an utmost important goal of present cancer research. The current literature suggests that TRAIL resistance is mediated by a number of endogenous factors. According to recent research, stress-related transcription factors have acquired a pivotal role in the sensitization of highly resistant cancer cells, for example, pancreatic cancer and glioblastoma cells, to TRAIL-mediated cell death. Out of this transcription factor family, C/EBP-homologous protein (CHOP) is linked to the control of DR-mediated apoptosis by modulation of several apoptotic and anti-apoptotic factors. Stress responses in certain organelles, such as endoplasmic reticulum (ER) and mitochondria, are potent inductors of CHOP expression. This report focuses on the influence of stress responses on endogenous or acquired resistance to extrinsic apoptosis in tumor cells and summarizes recent findings and results. The Medline and ClinicalTrials database with key words were used for this review. A potential novel treatment strategy for highly treatment-resistant tumors is the induction of a cellular stress response in cancer cells. The induction of an organelle-related stress response, such as nuclear, ER and mitochondrial stress, leads to a dramatic sensitization of a broad variety of cancer cells of different tumor entities to the apoptotic ligand, TRAIL. Importantly, non-neoplastic cells are not sensitized to TRAIL-mediated cell death through the unfolded protein response in most instances, suggesting that this treatment is not only of high efficacy, but even more less of unwanted toxicity in patients.

Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.

PubMed

Khor, Sara; Beca, Jaclyn; Krahn, Murray; Hodgson, David; Lee, Linda; Crump, Michael; Bremner, Karen E; Luo, Jin; Mamdani, Muhammad; Bell, Chaim M; Sawka, Carol; Gavura, Scott; Sullivan, Terrence; Trudeau, Maureen; Peacock, Stuart; Hoch, Jeffrey S

2014-08-12

Current treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice. We performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG). Rituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of $61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and $110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age. Our results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was potentially cost-effective by standard thresholds for patients <60 years old. However, cost-effectiveness decreased significantly with age, suggesting that rituximab may be not as economically attractive in the very elderly on average. This has important clinical implications regarding age-related use and funding decisions on this drug.

[The effect of size reduction of corn silage on feed intake, milk production and milk composition of cows].

PubMed

Preissinger, W; Schwarz, F J; Kirchgessner, M

1998-01-01

In three experiments (E1, E2, E3) maize silage of different physical structure and of different stage of maturity at harvest were fed to 24 (E1), 36 (E2) or 28 (E3) dairy cows. The cows were fed individually over an experimental period of five or six weeks. The maize silages had a mean DM content of 28% (E1), 32% (E2) or 36% (E3). At the stage of harvest, the stovers and the cobs had a mean DM content of < 22% (E1, E2) or 27% (E3), 40% (E1), 46% (E2) or 57% (E3), respectively. The maize was harvested with a chopping length of 4 and 8 mm (E1, E3) and of 6 and 8 mm (E2), without corn cracking (E1) or with and without corn cracking (E2, E3). The daily feed ration consisted of ad libitum offered maize silage, 1.7 kg DM hay, soya bean meal (E2, E3) and concentrate. The different chopping length of 4 mm, 6 mm or 8 mm had no effect on the maize silage intake in E1 and E2. In E3 the daily maize silage intake increased by about 1.2 kg DM per cow at a chopping length of 4 mm in comparison to 8 mm, whereas only the treatment with the combination of 4 mm chopping length and corn cracking showed a significant increase in DMI. The corn cracking improved the milk yield significantly (E2) or in a tendency (E3) at 2.0 kg (E2) or at 1.6 kg (E2), while the variation of chopping length had no effect on milk yield. The different physical structure did not influence the milk fat content with mean values of 4.65% (E1), 4.15% (E2) and 4.10% (E3), respectively. The milk protein content decreased in E2 feeding maize silage with a chopping length of 8 mm and corn cracking; but in E1 and E3 no effect was seen on protein content with mean values of 3.66% (E1) or 3.51% (E2).

3,3'-diindolylmethane potentiates tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of gastric cancer cells.

PubMed

Ye, Yang; Miao, Shuhan; Wang, Yan; Zhou, Jianwei; Lu, Rongzhu

2015-05-01

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) specifically kills cancer cells without destroying the majority of healthy cells. However, numerous types of cancer cell, including gastric cancer cells, tend to be resistant to TRAIL. The bioactive product 3,3'-diindolylmethane (DIM), which is derived from cruciferous vegetables, is also currently recognized as a candidate anticancer agent. In the present study, a Cell Counting Kit 8 cell growth assay and an Annexin V-fluorescein isothiocyanate apoptosis assay were performed to investigate the potentiating effect of DIM on TRAIL-induced apoptosis in gastric cancer cells, and the possible mechanisms of this potentiation. The results obtained demonstrated that, compared with TRAIL or DIM treatment alone, co-treatment with TRAIL (25 or 50 ng/ml) and DIM (10 µmol/l) induced cytotoxic and apoptotic effects in BGC-823 and SGC-7901 gastric cancer cells. Furthermore, western blot analysis revealed that the protein expression levels of death receptor 5 (DR5), CCAAT/enhancer binding protein homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) were upregulated in the co-treated gastric cancer cells. To the best of our knowledge, the present study is the first to provide evidence that DIM sensitizes TRAIL-induced inhibition of proliferation and apoptosis in gastric cancer cells, accompanied by the upregulated expression of DR5, CHOP and GRP78 proteins, which may be involved in endoplasmic reticulum stress mechanisms.

Modeling and Simulation of Compression Molding Process for Sheet Molding Compound (SMC) of Chopped Carbon Fiber Composites

DOE PAGES

Li, Yang; Chen, Zhangxing; Xu, Hongyi; ...

2017-01-02

Compression molded SMC composed of chopped carbon fiber and resin polymer which balances the mechanical performance and manufacturing cost presents a promising solution for vehicle lightweight strategy. However, the performance of the SMC molded parts highly depends on the compression molding process and local microstructure, which greatly increases the cost for the part level performance testing and elongates the design cycle. ICME (Integrated Computational Material Engineering) approaches are thus necessary tools to reduce the number of experiments required during part design and speed up the deployment of the SMC materials. As the fundamental stage of the ICME workflow, commercial softwaremore » packages for SMC compression molding exist yet remain not fully validated especially for chopped fiber systems. In this study, SMC plaques are prepared through compression molding process. The corresponding simulation models are built in Autodesk Moldflow with the same part geometry and processing conditions as in the molding tests. The output variables of the compression molding simulations, including press force history and fiber orientation of the part, are compared with experimental data. Influence of the processing conditions to the fiber orientation of the SMC plaque is also discussed. It is found that generally Autodesk Moldflow can achieve a good simulation of the compression molding process for chopped carbon fiber SMC, yet quantitative discrepancies still remain between predicted variables and experimental results.« less

Modeling and Simulation of Compression Molding Process for Sheet Molding Compound (SMC) of Chopped Carbon Fiber Composites

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

Li, Yang; Chen, Zhangxing; Xu, Hongyi

Compression molded SMC composed of chopped carbon fiber and resin polymer which balances the mechanical performance and manufacturing cost presents a promising solution for vehicle lightweight strategy. However, the performance of the SMC molded parts highly depends on the compression molding process and local microstructure, which greatly increases the cost for the part level performance testing and elongates the design cycle. ICME (Integrated Computational Material Engineering) approaches are thus necessary tools to reduce the number of experiments required during part design and speed up the deployment of the SMC materials. As the fundamental stage of the ICME workflow, commercial softwaremore » packages for SMC compression molding exist yet remain not fully validated especially for chopped fiber systems. In this study, SMC plaques are prepared through compression molding process. The corresponding simulation models are built in Autodesk Moldflow with the same part geometry and processing conditions as in the molding tests. The output variables of the compression molding simulations, including press force history and fiber orientation of the part, are compared with experimental data. Influence of the processing conditions to the fiber orientation of the SMC plaque is also discussed. It is found that generally Autodesk Moldflow can achieve a good simulation of the compression molding process for chopped carbon fiber SMC, yet quantitative discrepancies still remain between predicted variables and experimental results.« less

Chaetocin induces endoplasmic reticulum stress response and leads to death receptor 5-dependent apoptosis in human non-small cell lung cancer cells.

PubMed

Liu, Xianfang; Guo, Sen; Liu, Xiangguo; Su, Ling

2015-11-01

Epigenetic abnormalities are associated with non-small cell lung cancer (NSCLC) initiation and progression. Epigenetic drugs are being studied and in clinical trials. However, the molecular mechanism underlying the apoptosis by the epigenetic agents remains unclear. SUV39H1 is an important methyl-transferase for lysine 9 on histone H3 and usually related to gene transcriptional suppression, and chaetocin acts as the inhibitor of SUV39H1. We demonstrated here that chaetocin effectively suppressed the growth of multiple lung cancer cells through inducing apoptosis in a death receptor 5 (DR5)-dependent manner. Chaetocin treatment activated endoplasmic reticulum (ER) stress which gave rise to the up-regulation of ATF3 and CHOP. Furthermore, ATF3 and CHOP contributed to the induction of DR5 and subsequent apoptosis. When SUV39H1 was silenced with siRNA, the expression of ATF3, CHOP and DR5 was elevated. Thereafter, knockdown of SUV39H1 induced apoptosis in NSCLC cells. In summary, chaetocin pharmacologically inhibits the activity of SUV39H1 which provokes ER stress and results in up-regulation of ATF3 and CHOP, leading to DR5-dependent apoptosis eventually. These findings provide a novel interpretation on the anti-neoplastic activity of epigenetic drugs as a new therapeutic approach in NSCLC.

Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL.

PubMed

Plaisance, Valérie; Brajkovic, Saška; Tenenbaum, Mathie; Favre, Dimitri; Ezanno, Hélène; Bonnefond, Amélie; Bonner, Caroline; Gmyr, Valéry; Kerr-Conte, Julie; Gauthier, Benoit R; Widmann, Christian; Waeber, Gérard; Pattou, François; Froguel, Philippe; Abderrahmani, Amar

2016-01-01

Elevated plasma concentration of the pro-atherogenic oxidized low density lipoprotein cholesterol (LDL) triggers adverse effects in pancreatic beta-cells and is associated with type 2 diabetes. Here, we investigated whether the endoplasmic reticulum (ER) stress is a key player coupling oxidative stress to beta-cell dysfunction and death elicited by human oxidized LDL. We found that human oxidized LDL activates ER stress as evidenced by the activation of the inositol requiring 1α, and the elevated expression of both DDIT3 (also called CHOP) and DNAJC3 (also called P58IPK) ER stress markers in isolated human islets and the mouse insulin secreting MIN6 cells. Silencing of Chop and inhibition of ER stress markers by the chemical chaperone phenyl butyric acid (PBA) prevented cell death caused by oxidized LDL. Finally, we found that oxidative stress accounts for activation of ER stress markers induced by oxidized LDL. Induction of Chop/CHOP and p58IPK/P58IPK by oxidized LDL was mimicked by hydrogen peroxide and was blocked by co-treatment with the N-acetylcystein antioxidant. As a conclusion, the harmful effects of oxidized LDL in beta-cells requires ER stress activation in a manner that involves oxidative stress. This mechanism may account for impaired beta-cell function in diabetes and can be reversed by antioxidant treatment.

Contemporary issues: diseases with a food vector.

PubMed

Archer, D L; Young, F E

1988-10-01

Foodborne disease has become a contemporary issue. Several large, well-publicized outbreaks of foodborne disease have heightened public awareness that harmful microorganisms may be present in food and that chronic as well as acute disease may be caused by foodborne microbes. The field of food microbiology has likewise experienced a resurgence of interest. New tools, such as recombinant deoxyribonucleic acid technology and monoclonal antibody production, used to elucidate microbial virulence factors have facilitated identification of disease-causing microbes once thought to be harmless and demonstrated the complexity of individual virulence mechanisms previously considered to be well understood. Foodborne pathogens are also causing disease via some surprising food vectors, such as chopped, bottled garlic and sauteed onions. In addition to acute gastrointestinal disturbances, certain microorganisms may, through complex interactions with the human immune response, cause chronic diseases that affect several major organ systems. These microbes are serving as models in studies of molecular mimicry and genetic interrelatedness of procaryotes and eucaryotes. Other recently recognized attributes of foodborne microorganisms, such as the heat shock phenomenon and the possible nonculturability of some bacteria, may affect their ability to cause disease in humans. Because foodborne disease is a major cause of morbidity and mortality, the study of these diseases and their causative microorganisms presents a unique challenge to many professionals in the subdisciplines of microbiology, epidemiology, and clinical medicine.

Contemporary issues: diseases with a food vector.

PubMed Central

Archer, D L; Young, F E

1988-01-01

Foodborne disease has become a contemporary issue. Several large, well-publicized outbreaks of foodborne disease have heightened public awareness that harmful microorganisms may be present in food and that chronic as well as acute disease may be caused by foodborne microbes. The field of food microbiology has likewise experienced a resurgence of interest. New tools, such as recombinant deoxyribonucleic acid technology and monoclonal antibody production, used to elucidate microbial virulence factors have facilitated identification of disease-causing microbes once thought to be harmless and demonstrated the complexity of individual virulence mechanisms previously considered to be well understood. Foodborne pathogens are also causing disease via some surprising food vectors, such as chopped, bottled garlic and sauteed onions. In addition to acute gastrointestinal disturbances, certain microorganisms may, through complex interactions with the human immune response, cause chronic diseases that affect several major organ systems. These microbes are serving as models in studies of molecular mimicry and genetic interrelatedness of procaryotes and eucaryotes. Other recently recognized attributes of foodborne microorganisms, such as the heat shock phenomenon and the possible nonculturability of some bacteria, may affect their ability to cause disease in humans. Because foodborne disease is a major cause of morbidity and mortality, the study of these diseases and their causative microorganisms presents a unique challenge to many professionals in the subdisciplines of microbiology, epidemiology, and clinical medicine. PMID:3069199

Randomized Trial Comparing R-CHOP Versus High-Dose Sequential Chemotherapy in High-Risk Patients With Diffuse Large B-Cell Lymphomas.

PubMed

Cortelazzo, Sergio; Tarella, Corrado; Gianni, Alessandro Massimo; Ladetto, Marco; Barbui, Anna Maria; Rossi, Andrea; Gritti, Giuseppe; Corradini, Paolo; Di Nicola, Massimo; Patti, Caterina; Mulé, Antonino; Zanni, Manuela; Zoli, Valerio; Billio, Atto; Piccin, Andrea; Negri, Giovanni; Castellino, Claudia; Di Raimondo, Francesco; Ferreri, Andrés J M; Benedetti, Fabio; La Nasa, Giorgio; Gini, Guido; Trentin, Livio; Frezzato, Maurizio; Flenghi, Leonardo; Falorio, Simona; Chilosi, Marco; Bruna, Riccardo; Tabanelli, Valentina; Pileri, Stefano; Masciulli, Arianna; Delaini, Federica; Boschini, Cristina; Rambaldi, Alessandro

2016-11-20

Purpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT. Patients and Methods From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat. The primary efficacy end point of the study was 3-year event-free survival, and results were analyzed on an intent-to-treat basis. Results Clinical response (complete response, 78% v 76%; partial response, 5% v 9%) and failures (no response, 15% v 11%; and early treatment-related mortality, 2% v 3%) were similar after R-CHOP versus R-HDS, respectively. After a median follow-up of 5 years, the 3-year event-free survival was 62% versus 65% ( P = .83). At 3 years, compared with the R-CHOP arm, the R-HDS arm had better disease-free survival (79% v 91%, respectively; P = .034), but this subsequently vanished because of late-occurring treatment-related deaths. No difference was detected in terms of progression-free survival (65% v 75%, respectively; P = .12), or overall survival (74% v 77%, respectively; P = .64). Significantly higher hematologic toxicity ( P < .001) and more infectious complications ( P < .001) were observed in the R-HDS arm. Conclusion In this study, front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas.

Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis.

PubMed

Howlett, Christina; Snedecor, Sonya J; Landsburg, Daniel J; Svoboda, Jakub; Chong, Elise A; Schuster, Stephen J; Nasta, Sunita Dwivedy; Feldman, Tatyana; Rago, Allison; Walsh, Kristy M; Weber, Scott; Goy, Andre; Mato, Anthony

2015-08-01

'Double-hit lymphomas' (DHL), defined by concurrent MYC and BCL2 (or, alternatively, BCL6) rearrangements, have a very poor outcome compared to standard-risk, diffuse large B-cell lymphomas (DLBCL). Consequently, dose-intensive (DI) therapies and/or consolidation with high-dose therapy and transplant have been explored in DHL, although benefit has been debated. This meta-analysis compared survival outcomes in DHL patients receiving dose-escalated regimens [DI: R-Hyper-CVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) or R-CODOX-M/IVAC (rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high dose cytarabine); or intermediate-dose: R-EPOCH (rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone)] versus standard-dose regimens (R-CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) in the first-line setting. Data were synthesized to estimate hazard ratios of dose-escalated treatments versus R-CHOP using a Weibull proportional hazards model within a Bayesian meta-analysis framework. Eleven studies examining 394 patients were included. Patients were treated with either front-line R-CHOP (n = 180), R-EPOCH (n = 91), or R-Hyper-CVAD/rituximab, methotrexate, cytarabine (R-M/C), R-CODOX-M/R-IVAC (DI) (n = 123). Our meta-analysis revealed that median progression-free survival (n = 350) for the R-CHOP, R-EPOCH and DI groups was 12·1, 22·2, and 18·9 months, respectively. First-line treatment with R-EPOCH significantly reduced the risk of a progression compared with R-CHOP (relative risk reduction of 34%; P = 0·032); however, overall survival (n = 374) was not significantly different across treatment approaches. A subset of patients might benefit from intensive induction with/without transplant. Further investigation into the role of transplant and novel therapy combinations is necessary. © 2015 John Wiley & Sons Ltd.

Predictive algorithms for early detection of retinopathy of prematurity.

PubMed

Piermarocchi, Stefano; Bini, Silvia; Martini, Ferdinando; Berton, Marianna; Lavini, Anna; Gusson, Elena; Marchini, Giorgio; Padovani, Ezio Maria; Macor, Sara; Pignatto, Silvia; Lanzetta, Paolo; Cattarossi, Luigi; Baraldi, Eugenio; Lago, Paola

2017-03-01

To evaluate sensitivity, specificity and the safest cut-offs of three predictive algorithms (WINROP, ROPScore and CHOP ROP) for retinopathy of prematurity (ROP). A retrospective study was conducted in three centres from 2012 to 2014; 445 preterms with gestational age (GA) ≤ 30 weeks and/or birthweight (BW) ≤ 1500 g, and additional unstable cases, were included. No-ROP, mild and type 1 ROP were categorized. The algorithms were analysed for infants with all parameters (GA, BW, weight gain, oxygen therapy, blood transfusion) needed for calculation (399 babies). Retinopathy of prematurity (ROP) was identified in both eyes in 116 patients (26.1%), and 44 (9.9%) had type 1 ROP. Gestational age and BW were significantly lower in ROP group compared with no-ROP subjects (GA: 26.7 ± 2.2 and 30.2 ± 1.9, respectively, p < 0.0001; BW: 839.8 ± 287.0 and 1288.1 ± 321.5 g, respectively, p = 0.0016). Customized alarms of ROPScore and CHOP ROP correctly identified all infants having any ROP or type 1 ROP. WINROP missed 19 cases of ROP, including three type 1 ROP. ROPScore and CHOP ROP provided the best performances with an area under the receiver operating characteristic curve for the detection of severe ROP of 0.93 (95% CI, 0.90-0.96, and 95% CI, 0.89-0.96, respectively), and WINROP obtained 0.83 (95% CI, 0.77-0.87). Median time from alarm to treatment was 11.1, 5.1 and 9.1 weeks, for WINROP, ROPScore and CHOP ROP, respectively. ROPScore and CHOP ROP showed 100% sensitivity to identify sight-threatening ROP. Predictive algorithms are a reliable tool for early identification of infants requiring referral to an ophthalmologist, for reorganizing resources and reducing stressful procedures to preterm babies. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Extremely compact secondary mirror unit for the SOFIA Telescope capable of 6-degree-of-freedom alignment plus chopping

NASA Astrophysics Data System (ADS)

Zago, Lorenzo; Genequand, Pierre M.; Moerschell, Joseph

1998-08-01

SOFIA is a 2.5-m telescope to be carried on a special Boeing 747 for airborne observations at about 15'000 m. The paper describes the main features of the secondary mirror unit. The SOFIA secondary mirror needs active control for alignment along five degrees of freedom as well as for very fast chopping with a frequency up to 20 Hz. Moreover the general optical concept and the housing of the telescope inside a Boeing 747 have required the design of a very compact mechanism: indeed while the secondary mirror has a diameter of 350 mm the entire height of the secondary mirror unit (including the mirror) cannot be greater than 300 mm, which makes the SOFIA design much more compact than any other similar project. The objective is achieved by a very tight integration between a novel hexapod mechanism, in charge of tilt offsets and alignment along 3 axes, and a fast chopping mechanism based on advanced flexure structure technology. In the hexapod mechanism (which is in fact capable of 6-dof), the six linear actuators are arranged in an original geometry in order to leave as much space as possible to the overlying chopping system. Also, the actuators' `hinges' are here materialized by flexure elements. Three motorized levers are linked by flexure elements to the mirror isostatic interface as well as to a reaction ring for compensating angular momentum, which is mechanically driven together with the mirror. This a major difference from other designs (e.g. Keck or VLT) where the compensation mass is driven and controlled separately. The SOFIA solution obtains thus various advantages in term of used volume and has a simpler control system. Various details of the chopping mechanism are provided in the paper. Simulation preliminary results are also given.

A reinterpretation of millimeter observations of nearby IRAS excess stars

NASA Technical Reports Server (NTRS)

Weintraub, David A.; Stern, S. Alan

1994-01-01

We analyze new and previously published 1300, 870, and 800 micrometers, single-element bolometer observations of Vega (alpha Lyr), Formalhaut (alpha PsA), epsilon Eri, tau(sup1) Eri, and Beta Leo. We show that these data are consistent with models in which the dust disks around these stars are larger than the radio telescope beams with which they were observed; thus, these disks may be many hundreds of AU in radius or larger. Our interpretation of submillimeter/millimeter measurements of these stars also indicates that for some Infrared Astronomy Satellite (IRAS) IR excess stars the assumption that there is no astrophysical flux in the OFF beams, when using the standard ON-minus-OFF chopping technique and the chop distance is less than 1000AU, may be incorrect. Therefore, for IRAS IR excess stars within approximately 20 pc, virtually all submillimeter/millimeter chopping observations with chop throws less than 100" may have subtracted away some or most of the flux associated with their circumstellar disks. Finally, we present new 1300 micrometers continuum observations of Vega made with chop throws of 500 and 1000 AU. These data are consistent with an interpretation in which Vega has a disk that is at least 1000AU in radius; this disk could have a region with much less material per beam area near 500 AU than at both 100 AU and 1000 AU, corresponding to a gap at the orbital distance of alpha Lyr B. The observations of Vega are also consistent with the assumption that the circumVega dust structure is unresolved. Thus, these new data very effectively illustrate that the 'standard' model of small, unresolved, dust structures around main-sequence IRAS IR excess stars is not unique. Maps of IRAS IR excess stars, which soon will be available from submillimeter/millimeter array detectors, will determine whether the paradigm shift we propose will occur.

An Experimental Evaluation of the Internal Flow Field of an Automotive Heating, Ventilating and Air Conditioning System

DTIC Science & Technology

1990-07-01

HVAC) was conducted. This study consisted of four primary experiments designed to provide a fairly complete description of the governing flow mechanisms...interest. In order to generate the 28 required optical characteristics, the laser beam was directed through a mechanical beam chopper and a series of...lenses. The beam chopper operated at a frequency of 75 chops per second to create series of laser pulses 1/75s in duration. Once chopped, the beam was

Chopped random-basis quantum optimization

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

Caneva, Tommaso; Calarco, Tommaso; Montangero, Simone

2011-08-15

In this work, we describe in detail the chopped random basis (CRAB) optimal control technique recently introduced to optimize time-dependent density matrix renormalization group simulations [P. Doria, T. Calarco, and S. Montangero, Phys. Rev. Lett. 106, 190501 (2011)]. Here, we study the efficiency of this control technique in optimizing different quantum processes and we show that in the considered cases we obtain results equivalent to those obtained via different optimal control methods while using less resources. We propose the CRAB optimization as a general and versatile optimal control technique.

Draft Whole-Genome Sequences of Escherichia fergusonii Strains Isolated from Beef Trim (GTA-EF02), Ground Beef (GTA-EF03), and Chopped Kale (GTA-EF04).

PubMed

Manninger, Paul; Koziol, Adam; Carrillo, Catherine D

2016-04-14

Escherichia fergusoniiis a Gram-negative, rod-shaped, non-spore-forming member of theEnterobacteriaceaefamily and is a bacterium with both biotechnological applications and implication in human clinical disease. Here, we report the draft genome sequences of three isolates ofE. fergusoniifrom beef trim (GTA-EF02), ground beef (GTA-EF03), and chopped kale (GTA-EF04). Copyright © 2016 Manninger et al.

Sodium 4-phenylbutyrate protects against liver ischemia reperfusion injury by inhibition of endoplasmic reticulum-stress mediated apoptosis.

PubMed

Vilatoba, Mario; Eckstein, Christopher; Bilbao, Guadalupe; Smyth, Cheryl A; Jenkins, Stacie; Thompson, J Anthony; Eckhoff, Devin E; Contreras, Juan L

2005-08-01

Evidence is emerging that the endoplasmic reticulum (ER) participates in initiation of apoptosis induced by the unfolded protein response and by aberrant Ca(++) signaling during cellular stress such as ischemia/reperfusion injury (I/R injury). ER-induced apoptosis involves the activation of caspase-12 and C/EBP homologous protein (CHOP), and the shutdown of translation initiated by phosphorylation of eIF2alpha. Sodium 4-phenylbutyrate (PBA) is a low molecular weight fatty acid that acts as a chemical chaperone reducing the load of mutant or unfolded proteins retained in the ER during cellular stress and also exerting anti-inflammatory activity. It has been used successfully for treatment of urea cycle disorders and sickle cell disease. Thus, we hypothesized that PBA may reduce ER-induced apoptosis triggered by I/R injury to the liver. Groups of male C57BL/6 mice were subjected to warm ischemia (70% of the liver mass, 45 minutes). Serum aspartate aminotransferase was assessed 6 hours after reperfusion; apoptosis was evaluated by enzyme-linked immunosorbent assays of caspase-12 and plasma tumor necrosis factor alpha, Western blot analyses of eIF2alpha, and reverse transcriptase-polymerase chain reaction of CHOP expression. A dose-dependent decrease in aspartate aminotransferase was demonstrated in mice given intraperitoneal PBA (1 hour before and 12 hours after reperfusion), compared with vehicle-treated controls; this effect was associated with reduced pyknosis, parenchymal hemorrhages, and neutrophil infiltrates in PBA-treated mice, compared with controls. In a lethal model of total liver I/R injury, all vehicle-treated controls died within 3 days after reperfusion. In contrast, 50% survival (>30 days) was observed in animals given PBA. The beneficial effects of PBA were associated with a greater than 45% reduction in apoptosis, decreased ER-mediated apoptosis characterized by significant reduction in caspase-12 activation, and reduced levels of both phosphorylated eIF2alpha and CHOP. Significant reductions in plasma levels of tumor necrosis factor alpha and liver myeloperoxidase content were demonstrated after PBA treatment. Reduction in ER stress-induced hepatocellular injury was achieved by the administration of PBA. Targeting the ER-associated cell death pathway might offer a novel approach to reduce I/R injury to the liver.

Thermal expansion behavior of graphite/glass and graphite/magnesium

NASA Technical Reports Server (NTRS)

Tompkins, Stephen S.; Ard, K. E.; Sharp, G. Richard

1986-01-01

The thermal expansion behavior of n (+/- 8)s graphite fiber reinforced magnesium laminate and four graphite reinforced glass-matrix laminates (a unidirectional laminate, a quasi-isotropic laminate, a symmetric low angle-ply laminate, and a random chopped-fiber mat laminate) was determined, and was found, in all cases, to not be significantly affected by thermal cycling. Specimens were cycled up to 100 times between -200 F and 100 F, and the thermal expansion coefficients determined for each material as a function of temperature were found to be low. Some dimensional changes as a function of thermal cycling, and some thermal-strain hysteresis, were observed.

Mechanical characterization of glass fiber (woven roving/chopped strand mat E-glass fiber) reinforced polyester composites

NASA Astrophysics Data System (ADS)

Bhaskar, V. Vijaya; Srinivas, Kolla

2017-07-01

Polymer reinforced composites have been replacing most of the engineering material and their applications become more and more day by day. Polymer composites have been analyzing from past thirty five years for their betterment for adapting more applications. This paper aims at the mechanical properties of polyester reinforced with glass fiber composites. The glass fiber is reinforced with polyester in two forms viz Woven Rovings (WRG) and Chopped Strand Mat (CSMG) E-glass fibers. The composites are fabricated by hand lay-up technique and the composites are cut as per ASTM Standard sizes for corresponding tests like flexural, compression and impact tests, so that flexural strength, compression strength, impact strength and inter laminar shear stress(ILSS) of polymer matrix composites are analyzed. From the tests and further calculations, the polyester composites reinforced with Chopped Strand Mat glass fiber have shown better performance against flexural load, compression load and impact load than that of Woven Roving glass fiber.

BCL2 and MYC are expressed at high levels in canine diffuse large B-cell lymphoma but are not predictive for outcome in dogs treated with CHOP chemotherapy.

PubMed

Curran, K M; Schaffer, P A; Frank, C B; Lana, S E; Hamil, L E; Burton, J H; Labadie, J; Ehrhart, E J; Avery, P R

2017-12-01

Diffuse large B-cell lymphoma (DLBCL) is the most common haematopoietic malignancy in dogs. Recently, MYC and BCL2 expression levels determined with immunohistochemistry (IHC) were found to be prognostic in people with DLBCL. We hypothesized that canine DLBCL can be similarly subdivided into prognostic subtypes based on expression of MYC and BCL2. Cases of canine DLBCL treated with CHOP chemotherapy were retrospectively collected and 43 dogs had available histologic tissue and complete clinical follow-up. Median values of percent immunoreactive versus immunonegative cells were used to determine positive or negative expression status. Completion of CHOP was significantly associated with a positive outcome. Compared with human patients, our canine DLBCL patients had high IHC expression of both MYC and BCL2, and relative expression levels of one or both markers were not associated with clinical outcome. © 2016 John Wiley & Sons Ltd.

Successful treatment with biweekly CHOP for bone marrow relapse of blastic plasmacytoid dendritic cell neoplasm.

PubMed

Ono, Keiko; Ise, Mikiko; Ikebe, Dai; Sato, Akiyasu; Wang, Xiaofei; Sugawara, Takeaki; Tsujimura, Hideki; Itami, Makiko; Kumagai, Kyoya

2017-01-01

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological malignancy derived from precursors of plasmacytoid dendritic cells. The majority of patients initially respond to multi-agent chemotherapy, though most relapse within a year and the prognosis is very poor. We report a 67-year-old man with erythema on the right chest and a nasopharyngeal mass. Histological examination revealed a mass of tumor cells expressing CD4, CD56, and CD123, but neither CD3 nor CD20. He was diagnosed with BPDCN. Bone marrow involvement was not seen at diagnosis. He achieved complete remission (CR) with CHOP-like chemotherapy. After 1 year, he relapsed with a cutaneous tumor on the head, a nasopharyngeal tumor, and massive bone marrow involvement. Relapsed BPDCN is generally resistant to chemotherapy and the prognosis is dismal. However, he was successfully treated with biweekly CHOP therapy and achieved a second CR lasting 16 months.

Effect of length of chopped pristine and intercalated graphite fibers on the resistivity of fiber networks

NASA Technical Reports Server (NTRS)

Gaier, James R.; Stahl, Mark

1988-01-01

Samples of Amoco P-100 fibers were chopped to lengths of 3.14, 2.53, 1.90, 1.27, 0.66 mm, or milled for 2 hours. The two-point resistivity of compacts of these fibers were measured as a function of pressure from 34 kPa to 143 MPa. Samples of each fiber length were intercalated with bromine at room temperature and similarly measured. The low pressure resistivity of the compacts decreased with increasing fiber length. Intercalation lowered the resistivity of each of the chopped length compacts, but raised the resistivity of the milled fiber compacts. Bulk resistivity of all samples decreased with increasing pressure at similar rates. Even though fiber volumes were as low as 5 percent, all measurements exhibited measurable resistivity. A greater change with pressure in the resistance was observed for shorter fibers than for longer, probably an indication of tighter fiber packing. Intercalation appeared to have no effect on the fiber to fiber contact resistance.

Inconspicuous Insertion 22;12 in Myxoid/Round Cell Liposarcoma Accompanied by the Secondary Structural Abnormality der(16)t(1;16)

PubMed Central

Birch, Nathan C.; Antonescu, Cristina R.; Nelson, Marilu; Sarran, Lisa; Neff, James R.; Seemayer, Thomas; Bridge, Julia A.

2003-01-01

In myxoid/round cell liposarcoma, the t(12;16)(q13;p11) and its associated fusion transcript, FUS-CHOP, characterize greater than 95% of cases. The variant translocation t(12;22)(q13;q12) and associated EWS-CHOP fusion transcript are rare. A second non-random aberration observed in roughly 20% of Ewing’s sarcomas, and to a lesser extent other select sarcomas, is the unbalanced 1;16 translocation. Recognition of this secondary aberration in the absence of an obvious primary karyotypic abnormality strongly suggests that the use of other genetic approaches will be informative in uncovering a clinically suspected primary anomaly. The following case illustrates the utility of molecular cytogenetic and reverse transcriptase-polymerase chain reaction techniques in diagnosing an ins(22;12)(q12;q13q14) and associated EWS-CHOP fusion transcript in a myxoid/round cell liposarcoma exhibiting a der(16)t(1;16)(q11;q11). PMID:12876210

Inconspicuous insertion 22;12 in myxoid/round cell liposarcoma accompanied by the secondary structural abnormality der(16)t(1;16).

PubMed

Birch, Nathan C; Antonescu, Cristina R; Nelson, Marilu; Sarran, Lisa; Neff, James R; Seemayer, Thomas; Bridge, Julia A

2003-08-01

In myxoid/round cell liposarcoma, the t(12;16)(q13;p11) and its associated fusion transcript, FUS-CHOP, characterize greater than 95% of cases. The variant translocation t(12;22)(q13;q12) and associated EWS-CHOP fusion transcript are rare. A second non-random aberration observed in roughly 20% of Ewing's sarcomas, and to a lesser extent other select sarcomas, is the unbalanced 1;16 translocation. Recognition of this secondary aberration in the absence of an obvious primary karyotypic abnormality strongly suggests that the use of other genetic approaches will be informative in uncovering a clinically suspected primary anomaly. The following case illustrates the utility of molecular cytogenetic and reverse transcriptase-polymerase chain reaction techniques in diagnosing an ins(22;12)(q12;q13q14) and associated EWS-CHOP fusion transcript in a myxoid/round cell liposarcoma exhibiting a der(16)t(1;16)(q11;q11).

Endoplasmic Reticulum Stress Mediates Methamphetamine-Induced Blood–Brain Barrier Damage

PubMed Central

Qie, Xiaojuan; Wen, Di; Guo, Hongyan; Xu, Guanjie; Liu, Shuai; Shen, Qianchao; Liu, Yi; Zhang, Wenfang; Cong, Bin; Ma, Chunling

2017-01-01

Methamphetamine (METH) abuse causes serious health problems worldwide, and long-term use of METH disrupts the blood–brain barrier (BBB). Herein, we explored the potential mechanism of endoplasmic reticulum (ER) stress in METH-induced BBB endothelial cell damage in vitro and the therapeutic potential of endoplasmic reticulum stress inhibitors for METH-induced BBB disruption in C57BL/6J mice. Exposure of immortalized BMVEC (bEnd.3) cells to METH significantly decreased cell viability, induced apoptosis, and diminished the tightness of cell monolayers. METH activated ER stress sensor proteins, including PERK, ATF6, and IRE1, and upregulated the pro-apoptotic protein CHOP. The ER stress inhibitors significantly blocked the upregulation of CHOP. Knockdown of CHOP protected bEnd.3 cells from METH-induced cytotoxicity. Furthermore, METH elevated the production of reactive oxygen species (ROS) and induced the dysfunction of mitochondrial characterized by a Bcl2/Bax ratio decrease, mitochondrial membrane potential collapse, and cytochrome c. ER stress release was partially reversed by ROS inhibition, and cytochrome c release was partially blocked by knockdown of CHOP. Finally, PBA significantly attenuated METH-induced sodium fluorescein (NaFluo) and Evans Blue leakage, as well as tight junction protein loss, in C57BL/6J mice. These data suggest that BBB endothelial cell damage was caused by METH-induced endoplasmic reticulum stress, which further induced mitochondrial dysfunction, and that PBA was an effective treatment for METH-induced BBB disruption. PMID:28959203

Estrogen receptor α protects pancreatic β-cells from apoptosis by preserving mitochondrial function and suppressing endoplasmic reticulum stress.

PubMed

Zhou, Zhenqi; Ribas, Vicent; Rajbhandari, Prashant; Drew, Brian G; Moore, Timothy M; Fluitt, Amy H; Reddish, Britany R; Whitney, Kate A; Georgia, Senta; Vergnes, Laurent; Reue, Karen; Liesa, Marc; Shirihai, Orian; van der Bliek, Alexander M; Chi, Nai-Wen; Mahata, Sushil K; Tiano, Joseph P; Hewitt, Sylvia C; Tontonoz, Peter; Korach, Kenneth S; Mauvais-Jarvis, Franck; Hevener, Andrea L

2018-03-30

Estrogen receptor α (ERα) action plays an important role in pancreatic β-cell function and survival; thus, it is considered a potential therapeutic target for the treatment of type 2 diabetes in women. However, the mechanisms underlying the protective effects of ERα remain unclear. Because ERα regulates mitochondrial metabolism in other cell types, we hypothesized that ERα may act to preserve insulin secretion and promote β-cell survival by regulating mitochondrial-endoplasmic reticulum (EndoRetic) function. We tested this hypothesis using pancreatic islet-specific ERα knockout (PERαKO) mice and Min6 β-cells in culture with Esr1 knockdown (KD). We found that Esr1-KD promoted reactive oxygen species production that associated with reduced fission/fusion dynamics and impaired mitophagy. Electron microscopy showed mitochondrial enlargement and a pro-fusion phenotype. Mitochondrial cristae and endoplasmic reticulum were dilated in Esr1-KD compared with ERα replete Min6 β-cells. Increased expression of Oma1 and Chop was paralleled by increased oxygen consumption and apoptosis susceptibility in ERα-KD cells. In contrast, ERα overexpression and ligand activation reduced both Chop and Oma1 expression, likely by ERα binding to consensus estrogen-response element sites in the Oma1 and Chop promoters. Together, our findings suggest that ERα promotes β-cell survival and insulin secretion through maintenance of mitochondrial fission/fusion-mitophagy dynamics and EndoRetic function, in part by Oma1 and Chop repression.

Treatment factors affecting outcomes in HIV-associated non-Hodgkin lymphomas: a pooled analysis of 1546 patients

PubMed Central

Xue, Xiaonan; Wang, Dan; Tamari, Roni; Lee, Jeannette Y.; Mounier, Nicolas; Kaplan, Lawrence D.; Ribera, Josep-Maria; Spina, Michele; Tirelli, Umberto; Weiss, Rudolf; Galicier, Lionel; Boue, Francois; Wilson, Wyndham H.; Wyen, Christoph; Oriol, Albert; Navarro, José-Tomás; Dunleavy, Kieron; Little, Richard F.; Ratner, Lee; Garcia, Olga; Morgades, Mireia; Remick, Scot C.; Noy, Ariela; Sparano, Joseph A.

2013-01-01

Limited comparative data exist for the treatment of HIV-associated non-Hodgkin lymphoma. We analyzed pooled individual patient data for 1546 patients from 19 prospective clinical trials to assess treatment-specific factors (type of chemotherapy, rituximab, and concurrent combination antiretroviral [cART] use) and their influence on the outcomes complete response (CR), progression free survival (PFS), and overall survival (OS). In our analysis, rituximab was associated with a higher CR rate (odds ratio [OR] 2.89; P < .001), improved PFS (hazard ratio [HR] 0.50; P < .001), and OS (HR 0.51; P < .0001). Compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), initial therapy with more dose-intense regimens resulted in better CR rates (ACVBP [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisolone]: OR 1.70; P < .04), PFS (ACVBP: HR 0.72; P = .049; “intensive regimens”: HR 0.35; P < .001) and OS (“intensive regimens”: HR 0.54; P < .001). Infusional etoposide, prednisone, infusional vincristine, infusional doxorubicin, and cyclophosphamide (EPOCH) was associated with significantly better OS in diffuse large B-cell lymphoma (HR 0.33; P = .03). Concurrent use of cART was associated with improved CR rates (OR 1.89; P = .005) and trended toward improved OS (HR 0.78; P = .07). These findings provide supporting evidence for current patterns of care where definitive evidence is unavailable. PMID:24014242

Exocrine pancreas ER stress is differentially induced by different fatty acids.

PubMed

Danino, Hila; Ben-Dror, Karin; Birk, Ruth

2015-12-10

Exocrine pancreas acinar cells have a highly developed endoplasmic reticulum (ER), accommodating their high protein production rate. Overload of dietary fat (typical to obesity) is a recognized risk factor in pancreatitis and pancreatic cancer. Dietary fat, especially saturated fat, has been suggested by others and us to induce an acinar lipotoxic effect. The effect of different dietary fatty acids on the ER stress response is unknown. We studied the effect of acute (24h) challenge with different fatty acids (saturated, mono and poly-unsaturated) at different concentrations (between 200 and 500µM, typical to normal and obese states, respectively), testing fat accumulation, ER stress indicators, X-box binding protein 1 (Xbp1) splicing and nuclear translocation, as well as unfolded protein response (UPR) transcripts and protein levels using exocrine pancreas acinar AR42J and primary cells. Acute exposure of AR42J cells to different fatty acids caused increased accumulation of triglycerides, dependent on the type of fat. Different FAs had different effects on ER stress: most notably, saturated palmitic acid significantly affected the UPR response, as demonstrated by altered Xbp1 splicing, elevation in transcript levels of UPR (Xbp, CHOP, Bip) and immune factors (Tnfα, Tgfβ), and enhanced Xbp1 protein levels and Xbp1 time-dependent nuclear translocation. Poly-unsaturated FAs caused milder elevation of ER stress markers, while mono-unsaturated oleic acid attenuated the ER stress response. Thus, various fatty acids differentially affect acinar cell fat accumulation and, apart from oleic acid, induce ER stress. The differential effect of the various fatty acids could have potential nutritional and therapeutic implications. Copyright © 2015 Elsevier Inc. All rights reserved.

Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma

PubMed Central

Zode, Gulab S.; Sharma, Arti B.; Lin, Xiaolei; Searby, Charles C.; Bugge, Kevin; Kim, Gun Hee; Clark, Abbot F.; Sheffield, Val C.

2014-01-01

Administration of glucocorticoids induces ocular hypertension in some patients. If untreated, these patients can develop a secondary glaucoma that resembles primary open-angle glaucoma (POAG). The underlying pathology of glucocorticoid-induced glaucoma is not fully understood, due in part to lack of an appropriate animal model. Here, we developed a murine model of glucocorticoid-induced glaucoma that exhibits glaucoma features that are observed in patients. Treatment of WT mice with topical ocular 0.1% dexamethasone led to elevation of intraocular pressure (IOP), functional and structural loss of retinal ganglion cells, and axonal degeneration, resembling glucocorticoid-induced glaucoma in human patients. Furthermore, dexamethasone-induced ocular hypertension was associated with chronic ER stress of the trabecular meshwork (TM). Similar to patients, withdrawal of dexamethasone treatment reduced elevated IOP and ER stress in this animal model. Dexamethasone induced the transcriptional factor CHOP, a marker for chronic ER stress, in the anterior segment tissues, and Chop deletion reduced ER stress in these tissues and prevented dexamethasone-induced ocular hypertension. Furthermore, reduction of ER stress in the TM with sodium 4-phenylbutyrate prevented dexamethasone-induced ocular hypertension in WT mice. Our data indicate that ER stress contributes to glucocorticoid-induced ocular hypertension and suggest that reducing ER stress has potential as a therapeutic strategy for treating glucocorticoid-induced glaucoma. PMID:24691439

Salubrinal protects cardiomyocytes against apoptosis in a rat myocardial infarction model via suppressing the dephosphorylation of eukaryotic translation initiation factor 2α

PubMed Central

LI, RUI-JUN; HE, KUN-LUN; LI, XIN; WANG, LI-LI; LIU, CHUN-LEI; HE, YUN-YUN

2015-01-01

The aim of the present study was to examine the role of eIF2α in cardiomyocyte apoptosis and evaluate the cardioprotective role of salubrinal in a rat myocardial infarction (MI) model. Rat left anterior descending coronary arteries were ligated and the classical proteins involved in the endoplasmic reticulum stress (ERS)-induced apoptotic pathway were analyzed using quantitative polymerase chain reaction and western blot analysis. Salubrinal was administered to the rats and cardiomyocyte apoptosis and infarct size were evaluated by a specific staining method. Compared with the sham surgery group, the rate of cardiomyocyte apoptosis in the MI group was increased with the development of the disease. It was also demonstrated that the mRNA and protein levels of GRP78, caspase-12, CHOP and the protein expression of p-eIF2α were increased in the MI group. Furthermore, the results showed that treatment with salubrinal can decrease cardiomyocyte apoptosis and infarct size by increasing eIF2α phosphorylation and decreasing the expression of caspase-12 and CHOP. The present study suggests that salubrinal protects against ER stress-induced rat cadiomyocyte apoptosis via suppressing the dephosphorylation of eIF2α in the ERS-associated pathway. PMID:25816071

ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2α kinases.

PubMed

Kline, C Leah B; Van den Heuvel, A Pieter J; Allen, Joshua E; Prabhu, Varun V; Dicker, David T; El-Deiry, Wafik S

2016-02-16

ONC201 (also called TIC10) is a small molecule that inactivates the cell proliferation- and cell survival-promoting kinases Akt and ERK and induces cell death through the proapoptotic protein TRAIL. ONC201 is currently in early-phase clinical testing for various malignancies. We found through gene expression and protein analyses that ONC201 triggered an increase in TRAIL abundance and cell death through an integrated stress response (ISR) involving the transcription factor ATF4, the transactivator CHOP, and the TRAIL receptor DR5. ATF4 was not activated in ONC201-resistant cancer cells, and in ONC201-sensitive cells, knockdown of ATF4 or CHOP partially abrogated ONC201-induced cytotoxicity and diminished the ONC201-stimulated increase in DR5 abundance. The activation of ATF4 in response to ONC201 required the kinases HRI and PKR, which phosphorylate and activate the translation initiation factor eIF2α. ONC201 rapidly triggered cell cycle arrest, which was associated with decreased abundance of cyclin D1, decreased activity of the kinase complex mTORC1, and dephosphorylation of the retinoblastoma (Rb) protein. The abundance of X-linked inhibitor of apoptosis protein (XIAP) negatively correlated with the extent of apoptosis in response to ONC201. These effects of ONC201 were independent of whether cancer cells had normal or mutant p53. Thus, ONC201 induces cell death through the coordinated induction of TRAIL by an ISR pathway. Copyright © 2016, American Association for the Advancement of Science.

ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2α kinases

PubMed Central

Kline, C. Leah B.; Van den Heuvel, A. Pieter J.; Allen, Joshua E.; Prabhu, Varun V.; Dicker, David T.; El-Deiry, Wafik S.

2016-01-01

ONC201 (also called TIC10) is a small molecule that inactivates the cell proliferation- and cell survival-promoting kinases AKT and ERK and induces cell death through the pro-apoptotic protein TRAIL. ONC201 is currently in early phase clinical testing for various malignancies. Here, we found through gene expression and protein analyses that ONC201 triggered an increase in TRAIL abundance and cell death through an integrated stress response (ISR) involving the transcription factor ATF4, the transactivator CHOP, and the TRAIL receptor DR5. ATF4 was not activated in ONC201-resistant cancer cells, and in ONC201-sensitive cells, knockdown of ATF4 or CHOP partially abrogated ONC201-induced cytotoxicity and diminished the ONC201-stimulated increase in DR5 abundance. The activation of ATF4 in response to ONC201 required the kinases HRI and PKR, which phosphorylate and activate the translation initiation factor eIF2α. ONC201 rapidly triggered cell cycle arrest, which was associated with decreased abundance of cyclin D1, decreased activity of the kinase complex mTORC1, and dephosphorylation of the retinoblastoma (Rb) protein. The abundance of X-linked inhibitor of apoptosis protein (XIAP) negatively correlated with the extent of apoptosis in response to ONC201. These effects of ONC201 were independent of whether cancer cells had normal or mutant p53. Thus, ONC201 induces cell death through the coordinated induction of TRAIL by an ISR pathway. PMID:26884600

Systemic effects of AGEs in ER stress induction in vivo.

PubMed

Adamopoulos, Christos; Mihailidou, Chrysovalantou; Grivaki, Christofora; Papavassiliou, Kostas A; Kiaris, Hippokratis; Piperi, Christina; Papavassiliou, Athanasios G

2016-08-01

Emerging evidence indicates that accumulation of advanced glycation end products (AGEs) in human tissues may contribute to cell injury, inflammation and apoptosis through induction of endoplasmic reticulum (ER) stress. Human metabolism relies on ER homeostasis for the coordinated response of all metabolic organs by controlling the synthesis and catabolism of various nutrients. In vitro studies have demonstrated AGE-induced enhancement of unfolded protein response (UPR) in different cell types including endothelial, neuronal, pancreatic cells and podocytes, suggesting this crosstalk as an underlying pathological mechanism that contributes to metabolic diseases. In this minireview, we describe in vivo studies undertaken by our group and others that demonstrate the diverse systemic effects of AGEs in ER stress induction in major metabolic tissues such as brain, kidney, liver and pancreas of normal mice. Administration of high-AGEs content diet to normal mice for the period of 4 weeks upergulates the mRNA and protein levels of ER chaperone Bip (GRP78) indicative of UPR initiation in all major metabolic organs and induces activation of the pivotal transcription factor XBP1 that regulates glucose and lipid metabolism. Furthermore, animals with genetic ablation of UPR-activated transcription factor C/EBP homologous protein CHOP allocated in high-AGEs diet, exhibited relative resistance to UPR induction (BiP levels) and XBP1 activation in major metabolic organs. Since CHOP presents a critical mediator that links accumulation and aggregation of unfolded proteins with induction of oxidative stress and ER stress-related apoptosis, it is revealed as an important molecular target for the management of metabolic diseases.

Sarcopenia is an independent prognostic factor in elderly patients with diffuse large B-cell lymphoma treated with immunochemotherapy.

PubMed

Lanic, Hélène; Kraut-Tauzia, Jerôme; Modzelewski, Romain; Clatot, Florian; Mareschal, Sylvain; Picquenot, Jean Michel; Stamatoullas, Aspasia; Leprêtre, Stéphane; Tilly, Hervé; Jardin, Fabrice

2014-04-01

Approximately 25-35% of patients with diffuse large B-cell lymphoma (DLBCL) are older than 70 years. The aim of this study was to investigate the prognostic impact of depletion of skeletal muscle (sarcopenia) in elderly patients with DLBCL. This retrospective analysis included 82 patients with DLBCL older than 70 years and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, Oncovin, prednisone) or R-miniCHOP. Sarcopenia was measured by the analysis of stored computed tomography (CT) images at the L3 level at baseline. The surface of the muscular tissues was selected according to the CT Hounsfield unit. This value was normalized for stature in order to calculate the lumbar L3 skeletal muscle index (LSMI, in cm(2)/m(2)). The mean age of the population was 78 years. According to the defined cut-offs for LSMI, 45 patients with DLBCL were considered sarcopenic. Sarcopenic patients displayed a higher revised International Prognostic Index (R-IPI) compared with patients without sarcopenia, and were older, with a mean age of 80 years and 77 years, respectively (p = 0.006). With a median follow-up of 39 months, the 2-year overall survival in the sarcopenic population was 46% compared with 84% in the non-sarcopenic group (HR = 3.22; 95% CI = 1.73-5.98; p = 0.0002). In a multivariate analysis, sarcopenia remained predictive of outcome (p = 0.005). Sarcopenia is a relevant and predictive factor in elderly patients with DLBCL treated with rituximab plus chemotherapy.

A star-and-sky chopping polarimeter - Design and performance

NASA Astrophysics Data System (ADS)

Jain, S. K.; Srinivasulu, G.

1991-09-01

A star-and-sky chopping polarimeter is developed for accurate measurements of linear polarization of starlight in the standard astronomical photometric U, B, V, R, and I bands. The instrumental polarization, as determined by observing the standard unpolarized stars, is 0.04 percent. It is possible to use the instrument for the measurements of circular polarization as well. A Unicorn microcomputer controls the various operations of the instrument, acquires the data, and does the on-line data reduction. This paper describes the design and performance of the polarimeter.

Note: Voltage and intensity dependence of the saturation curves of free-air ionization chambers irradiated with chopped synchrotron radiation beams

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

Nariyama, Nobuteru

2012-01-15

Current saturation characteristics of free-air ionization chambers with electrode gaps of 4.2 and 8.4 mm were investigated using pulsed photon beam obtained by periodically interrupting synchrotron radiation beams with a chopper. Pulsed photon beams of 10 and 15 keV with pulse duration of 2.5 {mu}s and a frequency of 230 Hz were produced by chopping the beam. The measured recombination rate was found to be proportional to the intensity and inversely proportional to the applied voltage.

Chopping Time of the FPU {α }-Model

NASA Astrophysics Data System (ADS)

Carati, A.; Ponno, A.

2018-03-01

We study, both numerically and analytically, the time needed to observe the breaking of an FPU α -chain in two or more pieces, starting from an unbroken configuration at a given temperature. It is found that such a "chopping" time is given by a formula that, at low temperatures, is of the Arrhenius-Kramers form, so that the chain does not break up on an observable time-scale. The result explains why the study of the FPU problem is meaningful also in the ill-posed case of the α -model.

Influence of intramuscular fat content on the quality of pig meat - 2. Consumer acceptability of m. longissimus lumborum.

PubMed

Fernandez, X; Monin, G; Talmant, A; Mourot, J; Lebret, B

1999-09-01

The present study is part of a project which aimed to examine the influence of intramuscular fat (IMF) content on sensory attributes and consumer acceptability of pork. Two experiments were conducted to evaluate consumer acceptability of pork chops with varying IMF level in muscle Longissimus lumborum (LL). Each experiment used 32 castrated male pigs selected after slaughter either from 125 Duroc × Landrace (Experiment 1) or 102 Tia Meslan × Landrace (Experiment 2) crossbred animals, and showing large variability in LL IMF content: from <1.5 to >3.5% in Experiment 1 and from 1.25 to 3.25% in Experiment 2. A group of 56 consumers evaluated various items on rib-eye (LL muscle trimmed of backfat) (Experiment 1) and on entire chops trimmed of backfat (Experiment 2). Data from Experiment 1 indicate that an increase in IMF level is associated with an increase in visual perception of fat and a corresponding decrease in the willingness to eat and purchase the meat, when expressed before tasting. The latter effect disappeared after the consumers had tasted the meat, probably due to a positive effect of increase IMF, up to 3.5%, on the perception of texture and taste. In Experiment 2, where entire chops were evaluated, the perception of visible fat was not affected by IMF level, probably due to the lack of variation in the level of intermuscular fat between the four IMF groups. The willingness to eat and purchase the meat were unaffected by IMF level, whereas the perception of texture and taste was enhanced with increased IMF levels up to 3.25%. The present data suggest that the acceptability of pork may be improved by increasing IMF level but: (1) this effect disappeared for IMF levels higher than 3.5%, which are associated with a high risk of meat rejection due to visible fat and (2) the positive effect of increased IMF probably holds true as long as it is not associated with an increase in the level of intermuscular fat.

Validation of time and temperature values as critical limits for Salmonella and background flora growth during the production of fresh ground and boneless pork products.

PubMed

Mann, J E; Smith, L; Brashears, M M

2004-07-01

To provide pork processors with valuable data to validate the critical limits set for temperature during pork fabrication and grinding, a study was conducted to determine the growth of Salmonella serotypes and background flora at various temperatures. Growth of Salmonella Typhimurium and Salmonella Enteritidis and of background flora was monitored in ground pork and boneless pork chops held at various temperatures to determine growth patterns. Case-ready modified atmosphere packaged ground pork and fresh whole pork loins were obtained locally. Boneless chops and ground pork were inoculated with a cocktail mixture of streptomycin-resistant Salmonella to facilitate recovery in the presence of background flora. Samples were held at 4.4, 7.2C, and 10 degrees C and at room temperature (22.2 to 23.3 degrees C) to mimic typical processing and holding temperatures observed in pork processing environments. Salmonella counts were determined at regular intervals over 12 and 72 h for both room and refrigeration temperatures. No significant growth of Salmonella (P < 0.05) was observed in boneless pork chops held at refrigeration temperatures. However, Salmonella in boneless pork chops held at room temperature had grown significantly by 8 h. Salmonella grew at faster rates in ground pork. Significant growth was observed at 6, 24. and 72 h when samples were held at room temperature, 10 degrees C, and 7.2 degrees C, respectively. No significant growth was observed at 4.4 degrees C. Background flora in ground pork samples increased significantly after 10 h at room temperature and after 12 h for samples held at 10 and 7.2 degrees C. Background flora in samples held at refrigeration temperatures did not increase until 72 h. Background flora in the boneless chops increased significantly after 6 h at room temperature and after 24 h when held at 10 and 4.4 degrees C. These results illustrate that meat processors can utilize a variety of time and temperature combinations as critical limits to minimize Salmonella growth during production and storage of raw pork products.

Taraxacum mongolicum extract induced endoplasmic reticulum stress associated-apoptosis in triple-negative breast cancer cells.

PubMed

Li, Xiao-Hong; He, Xi-Ran; Zhou, Yan-Yan; Zhao, Hai-Yu; Zheng, Wen-Xian; Jiang, Shan-Tong; Zhou, Qun; Li, Ping-Ping; Han, Shu-Yan

2017-07-12

Triple-negative breast cancer (TNBC) is an aggressive and deadly breast cancer subtype with limited treatment options. It is necessary to seek complementary strategies for TNBC management. Taraxacum mongolicum, commonly named as dandelion, is a herb medicine with anti-cancer activity and has been utilized to treat mammary abscess, hyperplasia of mammary glands from ancient time in China, but the scientific evidence and action mechanisms still need to be studied. This study was intended to investigate the therapeutic effect and molecular mechanisms of dandelion extract in TNBC cell line. Dandelion extract was prepared and purified, and then its chemical composition was determined. Cell viability was evaluated by MTT assay. Analysis of cell apoptosis and cell cycle was assessed by flow cytometry. The expression levels of mRNA and proteins were determined by real-time PCR and Western blotting, respectively. Caspase inhibitor Z-VAD-FMK and CHOP siRNA were used to confirm the cell apoptosis induced by dandelion extract. Dandelion extract significantly decreased MDA-MB-231cell viability, triggered G2/M phase arrest and cell apoptosis. Concurrently, it caused a markedly increase of cleaved caspase-3 and PARP proteins. Caspase inhibitor Z-VAD-FMK abolished the apoptosis triggered by dandelion extract. The three ER stress-related signals were strongly induced after dandelion treatment, including increased mRNA expressions of ATF4, ATF6, XBP1s, GRP78 and CHOP genes, elevated protein levels of phosphorylated PERK, eIF-2α, IRE1, as well as the downstream molecules of CHOP and GRP78. MDA-MB-231 cells transfected with CHOP siRNA significantly reduced apoptosis induced by dandelion extract. The underlying mechanisms at least partially ascribe to the strong activation of PERK/p-eIF2α/ATF4/CHOP axis. ER stress related cell apoptosis accounted for the anti-cancer effect of dandelion extract, and these findings support dandelion extract might be a potential therapeutic approach to treat TNBC. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Effectiveness of three bulking agents for food waste composting

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

Adhikari, Bijaya K.; Barrington, Suzelle; Martinez, Jose

2009-01-15

Rather than landfilling, composting the organic fraction of municipal solid wastes recycles the waste as a safe and nutrient enriched soil amendment, reduces emissions of greenhouse gases and generates less leachate. The objective of this project was to investigate the composting effectiveness of three bulking agents, namely chopped wheat (Triticum) straw, chopped mature hay consisting of 80% timothy (milium) and 20% clover (triphullum) and pine (pinus) wood shavings. These bulking agents were each mixed in duplicates at three different ratios with food waste (FW) and composted for 10 days using prototype in-vessel composters to observe their temperature and pH trends.more » Then, each mixture was matured in vertical barrels for 56 days to measure their mass loss and final nutrient content and to visually evaluate their level of decomposition. Chopped wheat straw (CWS) and chopped hay (CH) were the only two formulas that reached thermophilic temperatures during the 10 days of active composting when mixed with FW at a wet mass ratio of 8.9 and 8.6:1 (FW:CWS and FW:CH), respectively. After 56 days of maturation, these two formulas were well decomposed with no or very few recognizable substrate particles, and offered a final TN exceeding the original. Wood shavings (WS) produced the least decomposed compost at maturation, with wood particles still visible in the final product, and with a TN lower than the initial. Nevertheless, all bulking agents produced compost with an organic matter, TN, TP and TK content suitable for use as soil amendment.« less

Glistening-region model for multipath studies

NASA Astrophysics Data System (ADS)

Groves, Gordon W.; Chow, Winston C.

1998-07-01

The goal is to achieve a model of radar sea reflection with improved fidelity that is amenable to practical implementation. The geometry of reflection from a wavy surface is formulated. The sea surface is divided into two components: the smooth `chop' consisting of the longer wavelengths, and the `roughness' of the short wavelengths. Ordinary geometric reflection from the chop surface is broadened by the roughness. This same representation serves both for forward scatter and backscatter (sea clutter). The `Road-to-Happiness' approximation, in which the mean sea surface is assumed cylindrical, simplifies the reflection geometry for low-elevation targets. The effect of surface roughness is assumed to make the sea reflection coefficient depending on the `Deviation Angle' between the specular and the scattering directions. The `specular' direction is that into which energy would be reflected by a perfectly smooth facet. Assuming that the ocean waves are linear and random allows use of Gaussian statistics, greatly simplifying the formulation by allowing representation of the sea chop by three parameters. An approximation of `low waves' and retention of the sea-chop slope components only through second order provides further simplification. The simplifying assumptions make it possible to take the predicted 2D ocean wave spectrum into account in the calculation of sea-surface radar reflectivity, to provide algorithms for support of an operational system for dealing with target tracking in the presence of multipath. The product will be of use in simulated studies to evaluate different trade-offs in alternative tracking schemes, and will form the basis of a tactical system for ship defense against low flyers.

Feasibility of abbreviated cycles of immunochemotherapy for completely resected limited-stage CD20+ diffuse large B-cell lymphoma (CISL 12-09).

PubMed

Yoon, Dok Hyun; Sohn, Byeong Seok; Oh, Sung Yong; Lee, Won-Sik; Lee, Sang Min; Yang, Deok-Hwan; Huh, Jooryung; Suh, Cheolwon

2017-02-21

The appropriate number of chemotherapy cycles for limited stage diffuse large B-cell lymphoma (DLBCL) patients without gross residual lesions after complete resection, has not been specifically questioned. We performed a multicenter, single-arm, phase 2 study to investigate the feasibility of 3 cycles of abbreviated R-CHOP chemotherapy in low-risk patients with completely resected localized CD20+ DLBCL. Between December 2010 and May 2013, we recruited 23 patients. One was excluded due to ineligibility, and hence, 22 were included in the final analysis. The primary sites comprised the intestine (n = 15), cervical lymph nodes (n = 4), stomach (n = 1), tonsil (n = 1), and spleen (n = 1). All patients successfully completed the 3 cycles of planned R-CHOP chemotherapy. Over a median follow-up of 39.5 months (95% confidence interval, 29.9-47.1 months), both the estimated 2-year disease-free survival and overall survival rates was 95% confidence interval, 85.9-104.1%. Only one patient with an international prognostic index of 2 experienced relapse and died. The most common grade 3 or 4 toxicity condition included neutropenia (n = 8, 36.4%). Three patients experienced grade 3 febrile neutropenia, but no grade 3 or 4 non-hematologic toxicity was observed. DLBCL patients without residual lesions after resection were enrolled and R-CHOP chemotherapy was repeated at 3-week-intervals over 3 cycles. The primary endpoint was 2-year disease-free survival. Three cycles of abbreviated R-CHOP immunochemotherapy is feasible for completely resected low risk localized DLBCL.

Penfluridol induces endoplasmic reticulum stress leading to autophagy in pancreatic cancer.

PubMed

Ranjan, Alok; German, Nadezhda; Mikelis, Constantinos; Srivenugopal, Kalkunte; Srivastava, Sanjay K

2017-06-01

Pancreatic cancer is one of the most aggressive and difficult to treat cancers. Experimental and clinical evidence suggests that high basal state autophagy in pancreatic tumors could induce resistance to chemotherapy. Recently, we have demonstrated that penfluridol suppresses pancreatic tumor growth by autophagy-mediated apoptosis both in vitro and in vivo; however, the mechanism of autophagy induction by penfluridol was not clear. Several studies have established that endoplasmic reticulum stress could lead to autophagy and inhibit tumor progression. In this study, we demonstrated that penfluridol induced endoplasmic reticulum stress in BxPC-3, AsPC-1, and Panc-1 pancreatic cancer cell lines as indicated by upregulation of endoplasmic reticulum stress markers such as binding protein (BIP), C/EBP homologous protein (CHOP) and inositol requiring 1α (IRE1α) after treatment with penfluridol in a concentration-dependent manner. Inhibiting endoplasmic reticulum stress by pretreatment with pharmacological inhibitors such as sodium phenylbutyrate and mithramycin or by silencing CHOP using CHOP small interfering RNA, blocked penfluridol-induced autophagy. These results clearly indicate that penfluridol-induced endoplasmic reticulum stress lead to autophagy in our model. Western blot analysis of subcutaneously implanted AsPC-1 and BxPC-3 tumors as well as orthotopically implanted Panc-1 tumors demonstrated upregulation of BIP, CHOP, and IRE1α expression in the tumor lysates from penfluridol-treated mice as compared to tumors from control mice. Altogether, our study establishes that penfluridol-induced endoplasmic reticulum stress leads to autophagy resulting in reduced pancreatic tumor growth. Our study opens a new therapeutic target for advanced chemotherapies against pancreatic cancer.

Effects of chronic social defeat stress on behavior and choline acetyltransferase, 78-kDa glucose-regulated protein, and CCAAT/enhancer-binding protein (C/EBP) homologous protein in adult mice.

PubMed

Zhao, Tong; Huang, Guang-Biao; Muna, Sushma Shrestha; Bagalkot, Tarique Rajasaheb; Jin, Hong-Mei; Chae, Han-Jung; Chung, Young-Chul

2013-07-01

Social defeat stress induces physiological and behavioral symptoms, including anxiety, anhedonia, immune deficits, and altered expression of key brain genes. The present study investigated the effects of social defeat stress on the behaviors and expressions of Chat, Grp78, and chop in the brains of adult mice. Adult mice were divided into susceptible and unsusceptible groups after 10 days of social defeat stress. In experiment 1, behavioral tests were conducted, and brains were processed for Western blotting at day 27 after stress. In experiment 2, social avoidance tests were conducted, and brains were processed for Western blotting at day 12 after stress. The results indicate decreased and increased locomotion and anxiety behavior in all defeated mice. Decrease in social interaction, increased immobility, and impaired memory performance were only observed in susceptible mice. A decrease in the Chat level at days 12 and 27 was noted in the prefrontal cortex (PFC), amygdala (Amyg), and dorsal hippocampus (HIP) in defeated mice. The expression levels of Grp78 and chop measured on days 12 and 27 were significantly greater in the Amyg of susceptible mice. In the PFC and HIP, defeated mice displayed different patterns in the levels of Grp78 and chop expressions measured on days 12 and 27. The present study demonstrated that chronic social defeat stress in mice produces stress-related behaviors. Different response patterns were noted for Grp78 and chop expression among the groups in terms of brain regions and time-course effects.

Germline Gain-of-Function Mutations in AFF4 Cause a Developmental Syndrome Functionally Linking the Super Elongation Complex and Cohesin

PubMed Central

Izumi, Kosuke; Nakato, Ryuichiro; Zhang, Zhe; Edmondson, Andrew C.; Noon, Sarah; Dulik, Matthew C.; Rajagopalan, Ramkakrishnan; Venditti, Charles P.; Gripp, Karen; Samanich, Joy; Zackai, Elaine H.; Deardorff, Matthew A.; Clark, Dinah; Allen, Julian L.; Dorsett, Dale; Misulovin, Ziva; Komata, Makiko; Bando, Masashige; Kaur, Maninder; Katou, Yuki; Shirahige, Katsuhiko; Krantz, Ian D.

2015-01-01

Transcriptional elongation is critical for gene expression regulation during embryogenesis. The super elongation complex (SEC) governs this process by mobilizing paused RNA polymerase II (RNAP2). Using exome sequencing, we discovered missense mutations in AFF4, a core component of the SEC in three unrelated probands with a novel syndrome that phenotypically overlaps Cornelia de Lange syndrome (CdLS), that we have named CHOPS syndrome (C for Cognitive impairment and Coarse facies, H for Heart defects, O for Obesity, P for Pulmonary involvement and S for Short stature and Skeletal dysplasia). Transcriptome and chromatin immunoprecipitation sequencing (ChIP-seq) analyses demonstrated similar alterations of genome-wide binding of AFF4, cohesin and RNAP2 between CdLS and CHOPS syndrome. Direct molecular interaction between SEC, cohesin and RNAP2 was demonstrated. This data supports a common molecular pathogenesis for CHOPS syndrome and CdLS caused by disturbance of transcriptional elongation due to alterations in genome-wide binding of AFF4 and cohesin. PMID:25730767

First Performance Results of the PIP2IT MEBT 200 Ohm Kicker Prototype

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

Saewert, G.; Awida, M. H.; Chase, B. E.

The PIP-II project is a program to upgrade the Fermilab accelerator complex. The PIP-II linac includes a 2.1 MeV Medium Energy Beam Transport (MEBT) section that incorporates a unique chopping system to perform arbitrary, bunch-by-bunch removal of 162.5 MHz structured beam. The MEBT chopping system will consist of two identical kickers working together and a beam absorber. One design of two having been proposed has been a 200 Ohm characteristic impedance traveling wave dual-helix kicker driven with custom designed high-speed switches. This paper reports on the first performance results of one prototype kicker built, installed and tested with beam at the PIP-II Injector Test (PIP2IT) facility. The helix deflector design details are discussed. The electrical performance of the high-speed switch driver operating at 500 V bias is presented. Tests performed were chopping beam at 81.25 MHz for microseconds as well as with a truly arbitrary pattern for 550more » $$\\mu$$s bursts having a 45 MHz average switching rate and repeating at 20 Hz.« less

Archaeal community dynamics and abiotic characteristics in a mesophilic anaerobic co-digestion process treating fruit and vegetable processing waste sludge with chopped fresh artichoke waste.

PubMed

Ros, M; Franke-Whittle, I H; Morales, A B; Insam, H; Ayuso, M; Pascual, J A

2013-05-01

This study evaluated the feasibility of obtaining methane in anaerobic digestion (AD) from the waste products generated by the processing of fruit and vegetables. During the first phase (0-55 d) of the AD using sludge from fruit and vegetable processing, an average value of 244±88 L kg(-1) dry matter d(-1)of biogas production was obtained, and methane content reached 65% of the biogas. Co-digestion with chopped fresh artichoke wastes in a second phase (55-71 d) enhanced biogas production, and resulted in an average value of 354±68 L kg(-1) dry matter d(-1), with higher methane content (more than 70%). The archaeal community involved in methane production was studied using the ANAEROCHIP microarray and real-time PCR. Results indicated that species of Methanosaeta and Methanosarcina were important during the AD process. Methanosarcina numbers increased after the addition of chopped fresh artichoke, while Methanosaeta numbers decreased. Copyright © 2013 Elsevier Ltd. All rights reserved.

The chalcone 2'-hydroxy-4',5'-dimethoxychalcone activates death receptor 5 pathway and leads to apoptosis in human nonsmall cell lung cancer cells.

PubMed

Yang, Lina; Su, Ling; Cao, Congmei; Xu, Linyan; Zhong, Diansheng; Xu, Lijia; Liu, Xiangguo

2013-06-01

Natural chalcones have been proved to inhibit cancer cells with therapeutic potential, but the underlying molecular mechanism is still largely unexplored. Here, we identified a novel chalcone, 2'-hydroxy-4',5'-dimethoxychalcone (HDMC) and demonstrated that HDMC induced apoptosis in various nonsmall cell lung cancer cells. Further study showed that HDMC elevated cellular reactive oxygen species (ROS) levels, thus inducing expressions of ATF4 and C/EBP homologous protein (CHOP). Then, death receptor 5 (DR5) was upregulated through ATF4-CHOP axis and eventually resulted in apoptosis. We also found that downregulation of c-FLIPL contributed to HDMC-induced apoptosis. In conclusion, HDMC induces apoptosis in human nonsmall cell lung cancer cells via activation of DR5 signaling pathway, and ROS-mediated ATF4-CHOP axis is involved in the process. Our results further supported the potential for HDMC to be developed as a new antitumor agent for cancer therapy or chemoprevention. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

Shelf life of fresh meat products under LED or fluorescent lighting.

PubMed

Steele, K S; Weber, M J; Boyle, E A E; Hunt, M C; Lobaton-Sulabo, A S; Cundith, C; Hiebert, Y H; Abrolat, K A; Attey, J M; Clark, S D; Johnson, D E; Roenbaugh, T L

2016-07-01

Enhanced pork loin chops, beef longissimus lumborum steaks, semimembranosus steaks (superficial and deep portions), ground beef, and ground turkey were displayed under light emitting diode (LED) and fluorescent (FLS) lighting in two multi-shelf, retail display cases with identical operating parameters. Visual and instrumental color, internal product temperature, case temperature, case cycling, thiobarbituric acid reactive substances (TBARS), and Enterobacteriaceae and aerobic plate counts were evaluated. Under LED, beef products (except the deep portion of beef semimembranosus steaks) showed less (P<0.05) visual discoloration. Pork loin chops had higher (P<0.05) L* values for LED lighting. Other than beef longissimus lumborum steaks, products displayed under LED lights had colder internal temperatures than products under FLS lights (P<0.05). Under LED, pork loin chops, ground turkey, and beef semimembranosus steaks had higher (P<0.05) values for TBARS. LED provides colder case and product temperatures, more case efficiency, and extended color life by at least 0.5d for longissimus and semimembranosus steaks; however, some LED cuts showed increased lipid oxidation. Copyright © 2016. Published by Elsevier Ltd.

Optical chopper for the HIRDLS instrument

NASA Astrophysics Data System (ADS)

Opyd, Walter G.; Loewenthal, Stuart

2003-12-01

Requirements, performance and life-test results are presented for the optical chopper installed in the High-Resolution Dynamics Limb Sounder (HIRDLS) to be flown on the AURA mission of the NASA Earth Observing System (EOS). Optical chopping is essential in order to achieve the required sensitivity and accuracy in measurement of infrared emission from various chemical species in the earth's atmosphere. Chopping of the optical input as far forward in the telescope as practical minimizes calibration errors arising from variations in emission from warm optics and due to electronic drifts in the infrared detecting system. At 500 Hz, a reflective chopper blade is used to alternate the instrument view between the atmospheric limb and cold space. The HIRDLS chopper is a six-toothed, mirrored wheel driven by a brushless DC motor. Chopper design was driven by requirements of 1) continuous operation at 5000 RPM for 50,000 hours in space vacuum, 2) chopping amplitude stability of one part in 100,000, 3) lubricant loss control for both bearing reliability and prevention of optics contamination, 4) compact size to fit in the folded telescope, and 5) survival in the launch environment.

Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials

PubMed Central

Mourad, Nathalie; Mounier, Nicolas; Brière, Josette; Raffoux, Emmanuel; Delmer, Alain; Feller, Alfred; Meijer, Chris J. L. M.; Emile, Jean-François; Bouabdallah, Réda; Bosly, André; Diebold, Jacques; Haioun, Corinne; Coiffier, Bertrand; Gisselbrecht, Christian

2008-01-01

To evaluate the prognostic significance of clinicobiologic and pathological features in angioimmunoblastic T-cell lymphoma (AITL), 157 AITL patients were retrieved from the GELA LNH87-LNH93 randomized clinical trials. One hundred forty-seven patients received a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)–like regimen with intensified courses in half of them. Histologically, 41 cases were classified as “rich in large cells” and 116 as “classic” (including 19 rich in epithelioid cells, 14 rich in clear cells, and 4 with hyperplastic germinal centers). Sixty-two cases were scored for CD10 and CXCL13 expression according to the abundance of positive lymphoid cells. Median age was 62 years, with 81% advanced stage, 72% B symptoms, 65% anemia, 50% hypergammaglobulinemia, and 66% elevated LDH. Overall 7-year survival was 30%. In multivariate analysis, only male sex (P = .004), mediastinal lymphadenopathy (P = .041), and anemia (P = .042) adversely affected overall survival. Increase in large cells and high level of CD10 and CXCL13 did not affect survival. Intensive regimen did not improve survival. In conclusion, AITL is a morphologically heterogeneous T-cell lymphoma commonly expressing CXCL13 and CD10 and carrying few prognostic factors. It portends a poor prognosis even when treated intensively. However, AITL is not always lethal with 30% of patients alive at 7 years. PMID:18292286

Responding to the recruiting call. How Children's Hospital of Philadelphia seeks healthcare pros.

PubMed

Botvin, J D

2001-01-01

The global shortage of healthcare professionals has touched every healthcare institution, and despite its renown, Children's Hospital of Philadelphia (CHOP) is no exception. In fact, the hospital's strategic addition of suburban facilities has exacerbated the situation. The recruitment plan builds on a strong new image campaign, and sharpens the focus on nurses, student nurses and allied health professionals. Direct mail is used--a first for recruitment at CHOP. The hospital's Web site is used as well as postings on numerous Internet job boards. Finally, the campaign also uses more traditional methods, such as print advertising.

Validation of the Children's Hospital of Philadelphia Retinopathy of Prematurity (CHOP ROP) Model.

PubMed

Binenbaum, Gil; Ying, Gui-Shuang; Tomlinson, Lauren A

2017-08-01

The Children's Hospital of Philadelphia Retinopathy of Prematurity (CHOP ROP) model uses birth weight (BW), gestational age at birth (GA), and weight gain rate to predict the risk of severe retinopathy of prematurity (ROP). In a model development study, it predicted all infants requiring treatment, while greatly reducing the number of examinations compared with current screening guidelines. To validate the CHOP ROP model in a multicenter cohort that is large enough to obtain a precise estimate of the model's sensitivity for treatment-requiring ROP. This investigation was a secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study. The setting was 30 hospitals in the United States and Canada between January 1, 2006, and June 30, 2012. The dates of analysis were September 28 to October 5, 2015. Participants were premature infants at risk for ROP with a known ROP outcome. Sensitivity for Early Treatment of Retinopathy of Prematurity type 1 ROP and potential reduction in the number of infants requiring examinations. In the primary analysis, the CHOP ROP model was applied weekly to predict the risk of ROP. If the risk was above a cut-point level (high risk), examinations were indicated, while low-risk infants received no examinations. In a secondary analysis, low-risk infants received fewer examinations rather than no examinations. Participants included 7483 premature infants at risk for ROP with a known ROP outcome. Their median BW was 1070 g (range, 310-3000 g), and their median GA was 28 weeks (range, 22-35 weeks). Among them, 3575 (47.8%) were female, and their race/ethnicity was 3615 white (48.3%), 2310 black (30.9%), 233 Asian (3.1%), 93 Pacific Islander (1.2%), and 40 American Indian/Alaskan native (0.5%). The original CHOP ROP model correctly predicted 452 of 459 infants who developed type 1 ROP (sensitivity, 98.5%; 95% CI, 96.9%-99.3%), reducing the number of infants requiring examinations by 34.3% if only high-risk infants received examinations. Lowering the cut point to capture all type 1 ROP cases (sensitivity, 100%; 95% CI, 99.2%-100%) resulted in only 6.8% of infants not requiring examinations. However, if low-risk infants were examined at 37 weeks' postmenstrual age and followed up only if ROP was present at that examination, all type 1 ROP cases would be captured, and the number of examinations performed among infants with GA exceeding 27 weeks would be reduced by 28.4%. The CHOP ROP model demonstrated high but not 100% sensitivity and may be better used to reduce examination frequency. The model might be used reliably to guide a modified ROP screening schedule and decrease the number of examinations performed.

Melatonin protects brain against ischemia/reperfusion injury by attenuating endoplasmic reticulum stress.

PubMed

Lin, Yu Wen; Chen, Tsung Ying; Hung, Chia Yang; Tai, Shih Huang; Huang, Sheng Yang; Chang, Che Chao; Hung, Hsin Yi; Lee, E Jian

2018-07-01

Endoplasmic reticulum (ER) stress plays a vital role in mediating ischemic reperfusion damage in brain. In this study, we evaluated whether melatonin inhibits ER stress in cultured neurons exposed to oxygen and glucose deprivation (OGD) and in rats subjected to transient focal cerebral ischemia. Sprague-Dawley rats were treated with melatonin (5 mg/kg) or control at reperfusion onset after transient occlusion of the right middle cerebral artery (MCA) for 90 min. Brain infarction and hemorrhage within infarcts were measured. The expression of ER stress proteins of phosphorylation of PRKR‑like endoplasmic reticulum kinase (p-PERK), phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α), activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) were detected by western blotting and immunohistochemistry analysis. The terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) method, cleaved caspase-3 and cytochrome c were used to investigate cell apoptosis in OGD-induced cultured neurons. Our results demonstrated that animals treated with melatonin had significantly reduced infarction volumes and individual cortical lesion sizes as well as increased numbers of surviving neurons. Melatonin can significantly modulate protein levels by decreasing both p-PERK and p-eIF2α in the ischemic core and penumbra. Moreover, the expressions of ATF4 and CHOP were restrained in the ischemic core and penumbra, respectively. Furthermore, pretreatment with melatonin at 10-100 µM effectively reduced the levels of p-PERK and p-eIF2α in cultured neurons after OGD injury. Melatonin treatment also effectively decreased neuron apoptosis resulting from OGD-induced neuron injury. These results indicate that melatonin effectively attenuated post-ischemic ER stress after ischemic stroke.

Linear models for calculating digestibile energy for sheep diets.

PubMed

Fonnesbeck, P V; Christiansen, M L; Harris, L E

1981-05-01

Equations for estimating the digestible energy (DE) content of sheep diets were generated from the chemical contents and a factorial description of diets fed to lambs in digestion trials. The diet factors were two forages (alfalfa and grass hay), harvested at three stages of maturity (late vegetative, early bloom and full bloom), fed in two ingredient combinations (all hay or a 50:50 hay and corn grain mixture) and prepared by two forage texture processes (coarsely chopped or finely chopped and pelleted). The 2 x 3 x 2 x 2 factorial arrangement produced 24 diet treatments. These were replicated twice, for a total of 48 lamb digestion trials. In model 1 regression equations, DE was calculated directly from chemical composition of the diet. In model 2, regression equations predicted the percentage of digested nutrient from the chemical contents of the diet and then DE of the diet was calculated as the sum of the gross energy of the digested organic components. Expanded forms of model 1 and model 2 were also developed that included diet factors as qualitative indicator variables to adjust the regression constant and regression coefficients for the diet description. The expanded forms of the equations accounted for significantly more variation in DE than did the simple models and more accurately estimated DE of the diet. Information provided by the diet description proved as useful as chemical analyses for the prediction of digestibility of nutrients. The statistics indicate that, with model 1, neutral detergent fiber and plant cell wall analyses provided as much information for the estimation of DE as did model 2 with the combined information from crude protein, available carbohydrate, total lipid, cellulose and hemicellulose. Regression equations are presented for estimating DE with the most currently analyzed organic components, including linear and curvilinear variables and diet factors that significantly reduce the standard error of the estimate. To estimate De of a diet, the user utilizes the equation that uses the chemical analysis information and diet description most effectively.

A randomized controlled trial of the effect of prednisone omission from a multidrug chemotherapy protocol on treatment outcome in dogs with peripheral nodal lymphomas.

PubMed

Childress, Michael O; Ramos-Vara, José A; Ruple, Audrey

2016-11-01

OBJECTIVE To determine the effect of prednisone omission from a multidrug chemotherapy protocol on outcome in dogs with peripheral nodal lymphomas. DESIGN Single-center, nonblinded, parallel-group, randomized, controlled trial. ANIMALS 40 client-owned dogs with a histopathologically confirmed diagnosis of peripheral nodal lymphoma and an expected survival time of > 4 weeks with treatment. PROCEDURES Treatment consisted of a combination of L-asparaginase, cyclophosphamide, doxorubicin, vincristine, and prednisone (L-CHOP) or an identical protocol except for the omission of prednisone (L-CHO). The primary outcome of interest was progression-free survival time. Veterinary caregivers and assessors of outcome were not blinded to treatment assignment. Treatment assignment was concealed from the owners of study dogs prior to enrollment, but was revealed after written informed consent was provided. RESULTS The trial was terminated early because of slow enrollment. The 40 dogs successfully enrolled in the study were randomly assigned to the L-CHOP (n = 18) or L-CHO (22) group; results for all 40 dogs were analyzed with respect to the primary outcome. Median progression-free survival time was 142.5 days for dogs receiving L-CHO and 292 days for dogs receiving L-CHOP (hazard ratio, 1.79; 95% confidence interval, 0.85 to 3.75). Serious adverse events were more common among dogs receiving L-CHO. However, this difference was not significant. CONCLUSIONS AND CLINICAL RELEVANCE The exclusion of prednisone from the L-CHOP protocol did not appear to result in improved progression-free survival time for dogs with peripheral nodal lymphomas. However, the present trial was likely underpowered to detect a clinically meaningful difference in progression-free survival time between groups.

Treatment option of bendamustine in combination with rituximab in elderly and frail patients with aggressive B-non-Hodgkin lymphoma: rational, efficacy, and tolerance.

PubMed

Horn, Julia; Kleber, Martina; Hieke, Stefanie; Schmitt-Gräff, Annette; Wäsch, Ralph; Engelhardt, Monika

2012-10-01

We analyzed the safety and efficacy of rituximab plus bendamustine (R-B) in elderly and frail patients with aggressive B-non-Hodgkin lymphoma (a-B-NHL). Few reports have as yet reported on R-B in a-B-NHL, albeit its value for indolent lymphoma vs. R-CHOP has impressively been shown. We assessed 20 consecutive patients with a-B-NHL receiving R-B as first-line or relapse treatment after (R)-CHOP in our department. Besides patient- and lymphoma-specific characteristics, comorbidity indices were determined. The median patient age was 72 years (51-86), the median Karnofsky performance status was 55 % (40-90 %), and according to the international prognostic index, 15 had high-intermediate or high-risk disease. The comorbidity indices revealed a median Kaplan-Feinstein index of 3 (range 1-3), Charlson comorbidity index of 4 (range 0-9), hematopoietic cell transplantation-specific comorbidity index of 3 (range 0-11), and Freiburg comorbidity index of 2 (range 0-2). Moreover, eight patients had echocardiographic and laboratory signs of cardiac insufficiency, all leading to R-B rather than R-CHOP treatment. The overall response rate was 55 %, with complete response and partial response rates of 20 and 35 %, respectively. In our frail and elderly patient cohort, R-B therapy was well-tolerated. Median progression free survival and overall survival were 8.3 months (95 % confidence interval [CI], 2.8--not reached [n.r.]) and 19.4 months (95 % CI, 4.6--n.r.), respectively. We conclude that R-B is a feasible and safe therapy option in a-B-NHL patients not qualifying for R-CHOP but needs to be further assessed in larger subsequent trials, these currently being under way.

Effects of first-line chemotherapy on natural killer cells in adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma.

PubMed

Ogura, Michinori; Ishida, Takashi; Tsukasaki, Kunihiro; Takahashi, Takeshi; Utsunomiya, Atae

2016-07-01

Natural killer (NK) cells are well known to be the most important effector cells mediating antibody-dependent cellular cytotoxicity (ADCC) which is an important mechanism of action of antibody drugs. We evaluated the effects of chemotherapy on the cell number and activity of NK cells from patients who received the vincristine-cyclophosphamide-doxorubicin-prednisone (VCAP), doxorubicin-ranimustine-prednisone (AMP), and vindesine-etoposide-carboplatin-prednisone (VECP) (mLSG15) or mLSG15-like (-L) regimen, which is one of the standard of cares for newly diagnosed adult T-cell leukemia-lymphoma (ATL), or the cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) or CHOP-L regimen which is another standard of care for ATL and peripheral T-cell lymphoma (PTCL). The number of lymphocytes and NK cells, and NK cell activity, were assessed using flow cytometry and a (51)Cr release assay, respectively. A total of 26 patients with untreated ATL or PTCL were enrolled, and blood samples from 25 patients were evaluable. NK cell number in ATL decreased after mLSG15/-L treatment, and the degree of decrease in the NK cell number was more prominent just before VECP therapy (Day 15-17 of each cycle) than just before VCAP therapy (Day 1 of each cycle). The NK cell number in ATL after CHOP/-L treatment also decreased. Interestingly, the NK cell activity showed a tendency to increase after the treatment. NK cell number in PTCL did not decrease by CHOP/-L regimen, but the activity was slightly decreased after the treatment. These results indicate that the effects of chemotherapeutic agents on NK cells vary according to the disease type and intensity of chemotherapy.

4-Phenylbutyrate Inhibits Tunicamycin-Induced Acute Kidney Injury via CHOP/GADD153 Repression

PubMed Central

Carlisle, Rachel E.; Brimble, Elise; Werner, Kaitlyn E.; Cruz, Gaile L.; Ask, Kjetil; Ingram, Alistair J.; Dickhout, Jeffrey G.

2014-01-01

Different forms of acute kidney injury (AKI) have been associated with endoplasmic reticulum (ER) stress; these include AKI caused by acetaminophen, antibiotics, cisplatin, and radiocontrast. Tunicamycin (TM) is a nucleoside antibiotic known to induce ER stress and is a commonly used inducer of AKI. 4-phenylbutyrate (4-PBA) is an FDA approved substance used in children who suffer from urea cycle disorders. 4-PBA acts as an ER stress inhibitor by aiding in protein folding at the molecular level and preventing misfolded protein aggregation. The main objective of this study was to determine if 4-PBA could protect from AKI induced by ER stress, as typified by the TM-model, and what mechanism(s) of 4-PBA's action were responsible for protection. C57BL/6 mice were treated with saline, TM or TM plus 4-PBA. 4-PBA partially protected the anatomic segment most susceptible to damage, the outer medullary stripe, from TM-induced AKI. In vitro work showed that 4-PBA protected human proximal tubular cells from apoptosis and TM-induced CHOP expression, an ER stress inducible proapoptotic gene. Further, immunofluorescent staining in the animal model found similar protection by 4-PBA from CHOP nuclear translocation in the tubular epithelium of the medulla. This was accompanied by a reduction in apoptosis and GRP78 expression. CHOP−/− mice were protected from TM-induced AKI. The protective effects of 4-PBA extended to the ultrastructural integrity of proximal tubule cells in the outer medulla. When taken together, these results indicate that 4-PBA acts as an ER stress inhibitor, to partially protect the kidney from TM-induced AKI through the repression of ER stress-induced CHOP expression. PMID:24416259

A fermented bean flour extract downregulates LOX-1, CHOP and ICAM-1 in HMEC-1 stimulated by ox-LDL.

PubMed

Gabriele, Morena; Pucci, Laura; La Marca, Margherita; Lucchesi, Daniela; Della Croce, Clara Maria; Longo, Vincenzo; Lubrano, Valter

2016-01-01

This study focused on an extract from fermented flour from the Lady Joy variety of the common bean Phaseolus vulgaris . The extract, Lady Joy lysate (Lys LJ), is enriched in antioxidant compounds during the fermentation. We assessed it for its protective effect on endothelial cells treated with oxidized-LDL (ox-LDL). The oxidative stress was determined by measuring the contents of thiobarbituric acid-reactive substances and reactive oxygen metabolites. ICAM-1, ET-1 and IL-6 concentrations were assessed using ELISA. LOX-1 and CHOP expression were analyzed using both quantitative RT-PCR and ELISA or western blotting. Ox-LDL treatment induced significant oxidative stress, which was strongly reduced by pre-treatment with the extract. The ox-LDL exposure significantly enhanced ICAM-1, IL-6 and ET-1 levels over basal levels. Lys LJ pre-treatment exerted an inhibitory effect on ox-LDL-induced endothelial activation with ICAM-1 levels comparable to those for the untreated cells. IL-6 and ET-1 production, although reduced, was still significantly higher than for the control. Both LOX-1 and CHOP expression were upregulated after ox-LDL exposure, but this effect was significantly decreased after Lys LJ pre-treatment. Lys LJ alone did not alter the ICAM-1, IL-6 and ET-1 concentrations or CHOP expression, but it did significantly lower the LOX-1 protein level. Our data suggest that Lys LJ is an effective antioxidant that is able to inhibit the oxidation process, but that it is only marginally active against inflammation and ET-1 production in HMEC-1 exposed to ox-LDL.

Parecoxib suppresses CHOP and Foxo1 nuclear translocation, but increases GRP78 levels in a rat model of focal ischemia.

PubMed

Ye, Zhi; Wang, Na; Xia, Pingping; Wang, E; Liao, Juan; Guo, Qulian

2013-04-01

Parecoxib, a novel COX-2 inhibitor, functions as a neuroprotective agent and rescues neurons from cerebral ischemic reperfusion injury-induced apoptosis. However, the molecular mechanisms underlying parecoxib neuroprotection remain to be elucidated. There is growing evidence that endoplasmic reticulum (ER) stress plays an important role in neuronal death caused by brain ischemia. However, very little is known about the role of parecoxib in mediating pathophysiological reactions to ER stress induced by ischemic reperfusion injury. Therefore, in the present study, we investigated whether delayed administration of parecoxib attenuates brain damage via suppressing ER stress-induced cell death. Adult male Sprague-Dawley rats were administered parecoxib (10 or 30 mg kg(-1), IP) or isotonic saline twice a day starting 24 h after middle cerebral artery occlusion (MCAO) for three consecutive days. The expressions of glucose-regulated protein 78 (GRP78) and oxygen-regulated protein 150 (ORP150) and C/EBP-homologous protein (CHOP) and forkhead box protein O 1 (Foxo1) in cytoplasmic and nuclear fraction were determined by Western blotting. The levels of caspase-12 expression were checked by immunohistochemistry analysis, served as a marker for ER stress-induced apoptosis. Parecoxib significantly suppressed cerebral ischemic injury-induced nuclear translocation of CHOP and Foxo1 and attenuated the immunoreactivity of caspase-12 in ischemic penumbra. Furthermore, the protective effect of delayed administration of parecoxib was accompanied by an increased GRP78 and ORP150 expression. Therefore, our study suggested that elevation of GRP78 and ORP150, and suppression of CHOP and Foxo1 nuclear translocation may contribute to parecoxib-mediated neuroprotection during ER stress responses.

Tensile Properties of Unsaturated Polyester and Epoxy Resin Reinforced with Recycled Carbon-Fiber-Reinforced Plastic

NASA Astrophysics Data System (ADS)

Okayasu, Mitsuhiro; Kondo, Yuta

2018-06-01

To better understand the mechanical properties of recycled carbon-fiber-reinforced plastic (rCFRP), CFRP crushed into small pieces was mixed randomly in different proportions (0-30 wt%) with two different resins: unsaturated polyester and epoxy resin. Two different sizes of crushed CFRP were used: 0.1 mm × 0.007 mm (milled CFRP) and 30 mm × 2 mm (chopped CFRP). The tensile strength of rCFRP was found to depend on both the proportion and the size of the CFRP pieces. It increased with increasing proportion of chopped CFRP, but decreased with increasing proportion of milled CFRP. There was no clear dependence of the tensile strength on the resin that was used. A low fracture strain was found for rCFRP samples made with chopped CFRP, in contrast to those made with milled CFRP. The fracture strain was found to increase with increasing content of milled CFRP up to 20 wt%, at which point, coalescence of existing microvoids occurred. However, there was a reduction in fracture strain for rCFRP with 30 wt% of milled CFRP, owing to the formation of defects (blow holes). Overall, the fracture strain was higher for rCFRPs based on epoxy resin than for those based on unsaturated polyester with the same CFRP content, because of the high ductility of the epoxy resin. The different tensile properties reflected different failure characteristics, with the use of chopped CFRP leading to a complicated rough fracture surface and with milled CFRP causing ductile failure through the presence of tiny dimple-like fractures. However, for a high content of milled CFRP (30 wt%), large blow holes were observed, leading to low ductility.

Effects of chronic social defeat stress on behaviour, endoplasmic reticulum proteins and choline acetyltransferase in adolescent mice.

PubMed

Huang, Guang-Biao; Zhao, Tong; Muna, Sushma Shrestha; Bagalkot, Tarique Rajasaheb; Jin, Hong-Mei; Chae, Han-Jung; Chung, Young-Chul

2013-08-01

The present study investigated the effects of social defeat stress on the behaviours and expressions of 78-kDa glucose-regulated protein (Grp78), CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) and choline acetyltransferase (Chat) in the brains of adolescent mice. Adolescent male C57BL/6J mice were divided into two groups (susceptible and unsusceptible) after 10 d social defeat stress. In expt 1, behavioural tests were conducted and brains were processed for Western blotting on day 21 after stress. In expt 2, social avoidance tests were conducted and brains were subsequently processed for Western blotting on day 12 after stress. Chronic social defeat stress produced more pronounced depression-like behaviours such as decreased locomotion and social interaction, increased anxiety-like behaviours and immobility, and impaired memory performance in susceptible mice. Moreover, susceptible mice showed greater expression of Grp78 and CHOP in the amygdala (Amyg) on days 12 and 21 compared with the other groups. Susceptible and unsusceptible groups showed significant increases in Grp78 and CHOP expression in the prefrontal cortex (PFC) and hippocampus (Hipp) on day 12 compared with the control group; this persisted until day 21. The levels of Chat measured on days 12 and 21 were significantly lower in the PFC, Amyg and Hipp of all defeated mice compared with controls. The findings of the behavioural tests indicate that chronic social defeat in adolescents produces anxiety-like behaviours, social withdrawal, despair-like behaviours and cognitive impairment. The Grp78, CHOP and Chat results suggest that the selective response of endoplasmic reticulum stress proteins in the Amyg plays an important role in the vulnerability-stress model of depression.

Tensile Properties of Unsaturated Polyester and Epoxy Resin Reinforced with Recycled Carbon-Fiber-Reinforced Plastic

NASA Astrophysics Data System (ADS)

Okayasu, Mitsuhiro; Kondo, Yuta

2017-08-01

To better understand the mechanical properties of recycled carbon-fiber-reinforced plastic (rCFRP), CFRP crushed into small pieces was mixed randomly in different proportions (0-30 wt%) with two different resins: unsaturated polyester and epoxy resin. Two different sizes of crushed CFRP were used: 0.1 mm × 0.007 mm (milled CFRP) and 30 mm × 2 mm (chopped CFRP). The tensile strength of rCFRP was found to depend on both the proportion and the size of the CFRP pieces. It increased with increasing proportion of chopped CFRP, but decreased with increasing proportion of milled CFRP. There was no clear dependence of the tensile strength on the resin that was used. A low fracture strain was found for rCFRP samples made with chopped CFRP, in contrast to those made with milled CFRP. The fracture strain was found to increase with increasing content of milled CFRP up to 20 wt%, at which point, coalescence of existing microvoids occurred. However, there was a reduction in fracture strain for rCFRP with 30 wt% of milled CFRP, owing to the formation of defects (blow holes). Overall, the fracture strain was higher for rCFRPs based on epoxy resin than for those based on unsaturated polyester with the same CFRP content, because of the high ductility of the epoxy resin. The different tensile properties reflected different failure characteristics, with the use of chopped CFRP leading to a complicated rough fracture surface and with milled CFRP causing ductile failure through the presence of tiny dimple-like fractures. However, for a high content of milled CFRP (30 wt%), large blow holes were observed, leading to low ductility.

Seawater inhalation induces acute lung injury via ROS generation and the endoplasmic reticulum stress pathway

PubMed Central

Li, Cong-Cong; Lu, Xi; Qian, Wei-Sheng; Li, Yu-Juan; Jin, Fa-Guang; Mu, De-Guang

2018-01-01

Seawater (SW) inhalation can induce acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In the present study, SW induced apoptosis of rat alveolar epithelial cells and histopathological alterations to lung tissue. Furthermore, SW administration increased generation of reactive oxygen species (ROS), whereas pretreatment with the ROS scavenger, N-acetyl-L-cysteine (NAC), significantly decreased ROS generation, apoptosis and histopathological alterations. In addition, SW exposure upregulated the expression levels of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP), which are critical proteins in the endoplasmic reticulum (ER) stress response, thus indicating that SW may activate ER stress. Conversely, blocking ER stress with 4-phenylbutyric acid (4-PBA) significantly improved SW-induced apoptosis and histopathological alterations, whereas an ER stress inducer, thapsigargin, had the opposite effect. Furthermore, blocking ROS with NAC inhibited SW-induced ER stress, as evidenced by the downregulation of GRP78, phosphorylated (p)-protein kinase R-like ER kinase (PERK), p-inositol-requiring kinase 1α (IRE1α), p-50 activating transcription factor 6α and CHOP. In addition, blocking ER stress with 4-PBA decreased ROS generation. In conclusion, the present study indicated that ROS and ER stress pathways, which are involved in alveolar epithelial cell apoptosis, are important in the pathogenesis of SW-induced ALI. PMID:29436612

Astaxanthin attenuates glutamate-induced apoptosis via inhibition of calcium influx and endoplasmic reticulum stress.

PubMed

Lin, Xiaotong; Zhao, Yan; Li, Shanhe

2017-07-05

Astaxanthin (AST) is a carotenoid that has been shown to have neuroprotective effects. In this study, it was found that AST significantly inhibited glutamate-induced loss of cell viability and apoptosis. AST pretreatment attenuated glutamate-induced activation of caspase-3, reduction of anti-apoptotic protein Bcl-2, and increase of pro-apoptotic protein Bak. In addition, AST pretreatment suppressed the production of intracellular reactive oxygen species. AST treatment also prevented glutamate-induced increase of the level of activated p38 mitogen-activated protein kinase (MAPK), which has been shown to promote apoptotic events. Furthermore, AST treatment greatly reduced the elevation of intracellular calcium level induced by glutamate and inhibited the activity of calpain, a calcium-dependent protease that plays an important role in mediating apoptosis stimulated by calcium overload in cytoplasm. Both oxidative stress and calcium overload can lead to endoplasmic reticulum (ER) stress. C/EBP-homologous protein (CHOP) is a bZIP transcription factor that can be activated by ER stress and promotes apoptosis. Here we found that AST attenuated glutamate-induced elevation of CHOP and ER chaperone glucose-regulated protein (GRP78). Overall, these results suggested that AST might protect cells against glutamate-induced apoptosis through maintaining redox balance and inhibiting glutamate-induced calcium influx and ER stress. Copyright © 2017 Elsevier B.V. All rights reserved.

Ankylosing spondylitis M-CSF-derived macrophages are undergoing unfolded protein response (UPR) and express higher levels of interleukin-23.

PubMed

Rezaiemanesh, Alireza; Mahmoudi, Mahdi; Amirzargar, Ali Akbar; Vojdanian, Mahdi; Jamshidi, Ahmad Reza; Nicknam, Mohammad Hossein

2017-09-01

Interleukin (IL)-23/IL-17 pathway involves in the pathogenesis of ankylosing spondylitis (AS). The exact mechanism implicated in overexpression of IL-23 and activation of the IL-23/IL-17 axis is not clear. The aim of the study was to clarify whether macrophages of AS patients undergo unfolded protein response (UPR) and secret increased IL-23. Peripheral blood monocyte isolated from 10 HLA-B27 + patients and five HLA-B27 + normal subjects were differentiated to macrophages by macrophage-colony stimulating factor (M-CSF) for seven days. Flow cytometry was used to detect monocyte purity and expression of macrophage markers. Analysis of mRNA expression for HLA-B and B27, UPR-associated proteins (BiP, CHOP, MDG1, and XBP1) and IL-23 was performed by RT-qPCR. RT-qPCR data showed a significant overexpression of HLA-B27, UPR genes (BiP, CHOP, and XBP1), and IL-23 in M-CSF-derived macrophages from AS patients compared to healthy controls. Increased expression of MDG1 was not significant. Our data suggest that UPR activation occurs in M-CSF-derived macrophages of AS patients and is accompanied by overexpression of HLA-B27. UPR appears to be associated with overproduction of IL-23 in AS macrophages.

Initiation and execution of lipotoxic ER stress in pancreatic β-cells

PubMed Central

Cunha, Daniel A.; Hekerman, Paul; Ladrière, Laurence; Bazarra-Castro, Angie; Ortis, Fernanda; Wakeham, Marion C.; Moore, Fabrice; Rasschaert, Joanne; Cardozo, Alessandra K.; Bellomo, Elisa; Overbergh, Lutgart; Mathieu, Chantal; Lupi, Roberto; Hai, Tsonwin; Herchuelz, Andre; Marchetti, Piero; Rutter, Guy A.; Eizirik, Décio L.; Cnop, Miriam

2013-01-01

Summary Free fatty acids (FFA) cause apoptosis of pancreatic β-cells and might contribute to β-cell loss in type 2 diabetes via the induction of endoplasmic reticulum (ER) stress. We studied here the molecular mechanisms implicated in FFA-induced ER stress initiation and apoptosis in INS-1E cells, FACS-purified primary β-cells and human islets exposed to oleate and/or palmitate. Treatment with saturated and/or unsaturated FFA led to differential ER stress signaling. Palmitate induced more apoptosis and markedly activated the IRE1, PERK and ATF6 pathways, owing to a sustained depletion of ER Ca2+ stores, whereas the unsaturated FFA oleate led to milder PERK and IRE1 activation and comparable ATF6 signaling. Non-metabolizable methyl-FFA analogs induced neither ER stress nor β-cell apoptosis. The FFA-induced ER stress response was not modified by high glucose concentrations, suggesting that ER stress in primary β-cells is primarily lipotoxic, and not glucolipotoxic. Palmitate, but not oleate, activated JNK. JNK inhibitors reduced palmitate-mediated AP-1 activation and apoptosis. Blocking the transcription factor CHOP delayed palmitate-induced β-cell apoptosis. In conclusion, saturated FFA induce ER stress via ER Ca2+ depletion. The IRE1 and resulting JNK activation contribute to β-cell apoptosis. PERK activation by palmitate also contributes to β-cell apoptosis via CHOP. PMID:18559892

Endoplasmic reticulum stress mediates withaferin A-induced apoptosis in human renal carcinoma cells.

PubMed

Choi, Min Jung; Park, Eun Jung; Min, Kyoung Jin; Park, Jong-Wook; Kwon, Taeg Kyu

2011-04-01

The accumulation of misfolded proteins in the lumen of the endoplasmic reticulum (ER) results in cellular stress that initiates a specialized response designated as the unfolded protein response. ER stress has been implicated in a variety of common diseases, such as diabetes, ischemia and neurodegenerative disorders. Withaferin A, a major chemical constituent of Withania somnifera, has been reported to inhibit tumor cell growth. We show that withaferin A induced a dose-dependent apoptotic cell death in several types of human cancer cells, as measured by FACS analysis and PARP cleavage. Treatment of Caki cells with withaferin A induced a number of signature ER stress markers, including phosphorylation of eukaryotic initiation factor-2α (eIF-2 α), ER stress-specific XBP1 splicing, and up-regulation of glucose-regulated protein (GRP)-78. In addition, withaferin A caused up-regulation of CAAT/enhancer-binding protein-homologous protein (CHOP), suggesting the induction of ER stress. Pretreatment with N-acetyl cysteine (NAC) significantly inhibited withaferin A-mediated ER stress proteins and cell death, suggesting that reactive oxygen species (ROS) mediate withaferin A-induced ER stress. Furthermore, CHOP siRNA or inhibition of caspase-4 activity attenuated withaferin A-induced apoptosis. Taken together, the present study provides strong evidence supporting an important role of the ER stress response in mediating withaferin A-induced apoptosis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Chronic restraint stress promotes learning and memory impairment due to enhanced neuronal endoplasmic reticulum stress in the frontal cortex and hippocampus in male mice.

PubMed

Huang, Rong-Rong; Hu, Wen; Yin, Yan-Yan; Wang, Yu-Chan; Li, Wei-Ping; Li, Wei-Zu

2015-02-01

Chronic stress has been implicated in many types of neurodegenerative diseases, such as Alzheimer's disease (AD). In our previous study, we demonstrated that chronic restraint stress (CRS) induced reactive oxygen species (ROS) overproduction and oxidative damage in the frontal cortex and hippocampus in mice. In the present study, we investigated the effects of CRS (over a period of 8 weeks) on learning and memory impairment and endoplasmic reticulum (ER) stress in the frontal cortex and hippocampus in male mice. The Morris water maze was used to investigate the effects of CRS on learning and memory impairment. Immunohistochemistry and immunoblot analysis were also used to determine the expression levels of protein kinase C α (PKCα), 78 kDa glucose-regulated protein (GRP78), C/EBP-homologous protein (CHOP) and mesencephalic astrocyte-derived neurotrophic factor (MANF). The results revealed that CRS significantly accelerated learning and memory impairment, and induced neuronal damage in the frontal cortex and hippocampus CA1 region. Moreover, CRS significantly increased the expression of PKCα, CHOP and MANF, and decreased that of GRP78 in the frontal cortex and hippocampus. Our data suggest that exposure to CRS (for 8 weeks) significantly accelerates learning and memory impairment, and the mechanisms involved may be related to ER stress in the frontal cortex and hippocampus.

Gefitinib enhances human colon cancer cells to TRAIL-induced apoptosis of via autophagy- and JNK-mediated death receptors upregulation.

PubMed

Chen, Lei; Meng, Yue; Guo, Xiaoqing; Sheng, Xiaotong; Tai, Guihua; Zhang, Fenglei; Cheng, Hairong; Zhou, Yifa

2016-11-01

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a potent cancer cell-specific apoptosis-inducing cytokine with little toxicity to most normal cells. Here, we report that gefitinib and TRAIL in combination produce a potent synergistic effect on TRAIL-sensitive human colon cancer HCT116 cells and an additive effect on TRAIL-resistant HT-29 cells. Interestingly, gefitinib increases the expression of cell surface receptors DR4 and DR5, possibly explaining the synergistic effect. Knockdown of DR4 and DR5 by siRNA significantly decreases gefitinib- and TRAIL-mediated cell apoptosis, supporting this idea. Because the inhibition of gefitinib-induced autophagy by 3-MA significantly decreases DR4 and DR5 upregulation, as well as reduces gefitinib- and TRAIL-induced apoptosis, we conclude that death receptor upregulation is autophagy mediated. Furthermore, our results indicate that death receptor expression may also be regulated by JNK activation, because pre-treatment of cells with JNK inhibitor SP600125 significantly decreases gefitinib-induced death receptor upregulation. Interestingly, SP600125 also inhibits the expression CHOP, yet CHOP has no impact on death receptor expressions. We also find here that phosphorylation of Akt and ERK might also be required for TRAIL sensitization. In summary, our results indicate that gefitinib effectively enhances TRAIL-induced apoptosis, likely via autophagy and JNK- mediated death receptor expression and phosphorylation of Akt and ERK.

Chronology of UPR activation in skeletal muscle adaptations to chronic contractile activity

PubMed Central

Memme, Jonathan M.; Oliveira, Ashley N.

2016-01-01

The mitochondrial and endoplasmic reticulum unfolded protein responses (UPRmt and UPRER) are important for cellular homeostasis during stimulus-induced increases in protein synthesis. Exercise triggers the synthesis of mitochondrial proteins, regulated in part by peroxisome proliferator activator receptor-γ coactivator 1α (PGC-1α). To investigate the role of the UPR in exercise-induced adaptations, we subjected rats to 3 h of chronic contractile activity (CCA) for 1, 2, 3, 5, or 7 days followed by 3 h of recovery. Mitochondrial biogenesis signaling, through PGC-1α mRNA, increased 14-fold after 1 day of CCA. This resulted in 10–32% increases in cytochrome c oxidase activity, indicative of mitochondrial content, between days 3 and 7, as well as increases in the autophagic degradation of p62 and microtubule-associated proteins 1A/1B light chain 3A (LC3)-II protein. Before these adaptations, the UPRER transcripts activating transcription factor-4, spliced X-box-binding protein 1, and binding immunoglobulin protein were elevated (1.3- to 3.8-fold) at days 1–3, while CCAAT/enhancer-binding protein homologous protein (CHOP) and chaperones binding immunoglobulin protein and heat shock protein (HSP) 70 were elevated at mRNA and protein levels (1.5- to 3.9-fold) at days 1–7 of CCA. The mitochondrial chaperones 10-kDa chaperonin, HSP60, and 75-kDa mitochondrial HSP, the protease ATP-dependent Clp protease proteolytic subunit, and the regulatory protein sirtuin-3 of the UPRmt were concurrently induced 10–80% between days 1 and 7. To test the role of the UPR in CCA-induced remodeling, we treated animals with the endoplasmic reticulum stress suppressor tauroursodeoxycholic acid and subjected them to 2 or 7 days of CCA. Tauroursodeoxycholic acid attenuated CHOP and HSP70 protein induction; however, this failed to impact mitochondrial remodeling. Our data indicate that signaling to the UPR is rapidly activated following acute contractile activity, that this is attenuated with repeated bouts, and that the UPR is involved in chronic adaptations to CCA; however, this appears to be independent of CHOP signaling. PMID:27122157

Cetuximab enhances cisplatin-induced endoplasmic reticulum stress-associated apoptosis in laryngeal squamous cell carcinoma cells by inhibiting expression of TXNDC5.

PubMed

Peng, Fusen; Zhang, Hailin; Du, Youhong; Tan, Pingqing

2018-03-01

Cisplatin and cetuximab, an anti‑epidermal growth factor receptor (EGFR) monoclonal humanized antibody, have been used for treatment of laryngeal squamous cell carcinoma (LSCC). It has been demonstrated that cisplatin and inhibition of EGFR signaling may induce endoplasmic reticulum (ER) stress‑associated apoptosis. However, ER protein thioredoxin domain‑containing protein 5 (TXNDC5) reportedly protects cells from ER stress‑associated apoptosis. The present study investigated the interaction between cisplatin, cetuximab and TXNDC5 on ER stress‑associated apoptosis in LSCC cells. AMC‑HN‑8 human LSCC cells with or without TXNDC5 overexpression or knockdown were treated with cisplatin (5, 10, 20 and 40 µM) and/or cetuximab (10, 50, 100 and 150 µg/ml), for 12, 24, 36 and 48 h. Cisplatin and cetuximab concentration‑ and time‑dependently increased and decreased the expression of TXNDC5 in AMC‑HN‑8 cells, respectively. Knockdown of TXNDC5 markedly augmented cisplatin‑induced levels of CCAAT/enhancer‑binding protein homologous protein (CHOP), caspase‑3 activity and apoptosis; while overexpression of TXNDC5 largely eliminated cetuximab‑induced levels of CHOP, caspase‑3 activity and apoptosis. Cisplatin and cetuximab demonstrated a combinatorial effect on increasing the levels of CHOP, caspase‑3 activity and apoptosis, which was largely eliminated by overexpression of TXNDC5 or a reactive oxygen species (ROS) scavenger/antagonist. In addition, promoter/luciferase reporter assays revealed that cisplatin and cetuximab regulated the expression of TXNDC5 at the gene transcription/promoter level. In conclusion, the findings suggested that ER stress‑associated apoptosis is a major mechanism underlying the apoptotic effect of cisplatin and cetuximab on LSCC cells; cetuximab enhanced cisplatin‑induced ER stress‑associated apoptosis in LSCC cells largely by inhibiting the expression of TXNDC5 and thereby increasing ROS production; cisplatin and cetuximab had stimulatory and inhibitory effects on the TXNDC5 gene promoter, respectively. The present study offered novel insights into the pharmacological effects of cisplatin and cetuximab on LSCC. It also suggested that TXNDC5 may be a potential therapeutic target for LSCC.

The Unfolded Protein Response Plays a Predominant Homeostatic Role in Response to Mitochondrial Stress in Pancreatic Stellate Cells

PubMed Central

Su, Hsin-Yuan; Waldron, Richard T.; Gong, Raymond; Ramanujan, V. Krishnan; Pandol, Stephen J.; Lugea, Aurelia

2016-01-01

Activated pancreatic stellate cells (PaSC) are key participants in the stroma of pancreatic cancer, secreting extracellular matrix proteins and inflammatory mediators. Tumors are poorly vascularized, creating metabolic stress conditions in cancer and stromal cells that necessitate adaptive homeostatic cellular programs. Activation of autophagy and the endoplasmic reticulum unfolded protein response (UPR) have been described in hepatic stellate cells, but the role of these processes in PaSC responses to metabolic stress is unknown. We reported that the PI3K/mTOR pathway, which AMPK can regulate through multiple inputs, modulates PaSC activation and fibrogenic potential. Here, using primary and immortalized mouse PaSC, we assess the relative contributions of AMPK/mTOR signaling, autophagy and the UPR to cell fate responses during metabolic stress induced by mitochondrial dysfunction. The mitochondrial uncoupler rottlerin at low doses (0.5–2.5 μM) was added to cells cultured in 10% FBS complete media. Mitochondria rapidly depolarized, followed by altered mitochondrial dynamics and decreased cellular ATP levels. This mitochondrial dysfunction elicited rapid, sustained AMPK activation, mTOR pathway inhibition, and blockade of autophagic flux. Rottlerin treatment also induced rapid, sustained PERK/CHOP UPR signaling. Subsequently, high doses (>5 μM) induced loss of cell viability and cell death. Interestingly, AMPK knock-down using siRNA did not prevent rottlerin-induced mTOR inhibition, autophagy, or CHOP upregulation, suggesting that AMPK is dispensable for these responses. Moreover, CHOP genetic deletion, but not AMPK knock-down, prevented rottlerin-induced apoptosis and supported cell survival, suggesting that UPR signaling is a major modulator of cell fate in PaSC during metabolic stress. Further, short-term rottlerin treatment reduced both PaSC fibrogenic potential and IL-6 mRNA expression. In contrast, expression levels of the angiogenic factors HGF and VEGFα were unaffected, and the immune modulator IL-4 was markedly upregulated. These data imply that metabolic stress-induced PaSC reprogramming differentially modulates neighboring cells in the tumor microenvironment. PMID:26849807

Electron-beam induced current characterization of back-surface field solar cells using a chopped scanning electron microscope beam

NASA Technical Reports Server (NTRS)

Luke, K. L.; Cheng, L.-J.

1984-01-01

A chopped electron beam induced current (EBIC) technique for the chacterization of back-surface field (BSF) solar cells is presented. It is shown that the effective recombination velocity of the low-high junction forming the back-surface field of BSF cells, in addition to the diffusion length and the surface recombination velocity of the surface perpendicular to both the p-n and low-high junctions, can be determined from the data provided by a single EBIC scan. The method for doing so is described and illustrated. Certain experimental considerations taken to enhance the quality of the EBIC data are also discussed.

Pointing control for LDR

NASA Technical Reports Server (NTRS)

Yam, Y.; Briggs, C.

1988-01-01

One important aspect of the LDR control problem is the possible excitations of structural modes due to random disturbances, mirror chopping, and slewing maneuvers. An analysis was performed to yield a first order estimate of the effects of such dynamic excitations. The analysis involved a study of slewing jitters, chopping jitters, disturbance responses, and pointing errors, making use of a simplified planar LDR model which describes the LDR dynamics on a plane perpendicular to the primary reflector. Briefly, the results indicate that the command slewing profile plays an important role in minimizing the resultant jitter, even to a level acceptable without any control action. An optimal profile should therefore be studied.

Frequency-dependent photothermal measurement of transverse thermal diffusivity of organic semiconductors

NASA Astrophysics Data System (ADS)

Brill, J. W.; Shahi, Maryam; Payne, Marcia M.; Edberg, Jesper; Yao, Y.; Crispin, Xavier; Anthony, J. E.

2015-12-01

We have used a photothermal technique, in which chopped light heats the front surface of a small (˜1 mm2) sample and the chopping frequency dependence of thermal radiation from the back surface is measured with a liquid-nitrogen-cooled infrared detector. In our system, the sample is placed directly in front of the detector within its dewar. Because the detector is also sensitive to some of the incident light, which leaks around or through the sample, measurements are made for the detector signal that is in quadrature with the chopped light. Results are presented for layered crystals of semiconducting 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS-pn) and for papers of cellulose nanofibrils coated with semiconducting poly(3,4-ethylene-dioxythiophene):poly(styrene-sulfonate) (NFC-PEDOT). For NFC-PEDOT, we have found that the transverse diffusivity, smaller than the in-plane value, varies inversely with thickness, suggesting that texturing of the papers varies with thickness. For TIPS-pn, we have found that the interlayer diffusivity is an order of magnitude larger than the in-plane value, consistent with previous estimates, suggesting that low-frequency optical phonons, presumably associated with librations in the TIPS side groups, carry most of the heat.

Trinitrotoluene Induces Endoplasmic Reticulum Stress and Apoptosis in HePG2 Cells.

PubMed

Song, Li; Wang, Yue; Wang, Jun; Yang, Fan; Li, Xiaojun; Wu, Yonghui

2015-11-09

This study aims to describe trinitrotoluene (TNT)-induced endoplasmic reticulum stress (ERS) and apoptosis in HePG2 cells. HePG2 cells were cultured in vitro with 0, 6, 12, or 24 μg/ml TNT solution for 12, 24, and 48 h. Western blotting was performed to detect intracellular ERS-related proteins, including glucose-regulated protein (GRP) 78, GRP94, Caspase 4, p-Jun N-terminal kinase (JNK), and C/EBP homologous protein (CHOP). Real-time PCR was used to measure mRNA expression from the respective genes. The expressions of ERS-related proteins GRP78 and GRP94 as well as mRNA and protein expression of ERS signaling apoptotic CHOP in the TNT treatment group were significantly increased. In addition, the mRNA and protein expression levels of ERS-induced apoptotic protein Caspase-4 were significantly increased. Flow cytometry revealed that after TNT treatment, the apoptosis rate also significantly increased. TNT could increase the expression levels of GRP78, GRP94, Caspase-4, and CHOP in HePG2 cells; this increase in protein expression might be involved in HePG2 apoptosis through the induction of the ERS pathway.

Trinitrotoluene Induces Endoplasmic Reticulum Stress and Apoptosis in HePG2 Cells

PubMed Central

Song, Li; Wang, Yue; Wang, Jun; Yang, Fan; Li, Xiaojun; Wu, Yonghui

2015-01-01

Background This study aims to describe trinitrotoluene (TNT)-induced endoplasmic reticulum stress (ERS) and apoptosis in HePG2 cells. Material/Methods HePG2 cells were cultured in vitro with 0, 6, 12, or 24 μg/ml TNT solution for 12, 24, and 48 h. Western blotting was performed to detect intracellular ERS-related proteins, including glucose-regulated protein (GRP) 78, GRP94, Caspase 4, p-Jun N-terminal kinase (JNK), and C/EBP homologous protein (CHOP). Real-time PCR was used to measure mRNA expression from the respective genes. Results The expressions of ERS-related proteins GRP78 and GRP94 as well as mRNA and protein expression of ERS signaling apoptotic CHOP in the TNT treatment group were significantly increased. In addition, the mRNA and protein expression levels of ERS-induced apoptotic protein Caspase-4 were significantly increased. Flow cytometry revealed that after TNT treatment, the apoptosis rate also significantly increased. Conclusions TNT could increase the expression levels of GRP78, GRP94, Caspase-4, and CHOP in HePG2 cells; this increase in protein expression might be involved in HePG2 apoptosis through the induction of the ERS pathway. PMID:26551326

Lipid and protein oxidation of α-linolenic acid-enriched pork during refrigerated storage as influenced by diet supplementation with olive leaves (Olea europea L.) or α-tocopheryl acetate.

PubMed

Botsoglou, Evropi; Govaris, Alexander; Ambrosiadis, Ioannis; Fletouris, Dimitrios

2012-12-01

The objective of this study was to evaluate the effect of diet supplementation with olive leaves or α-tocopheryl acetate on lipid and protein oxidation of raw and cooked n-3 enriched-pork during refrigerated storage. Enrichment of pork with α-linolenic acid through diet supplementation with linseed oil enhanced (p≤0.05) lipid oxidation in both raw and cooked chops but had no effect (p>0.05) on protein oxidation during refrigerated storage while decreasing (p≤0.05) the sensory attributes of cooked pork. Diet supplementation with olive leaves or α-tocopheryl acetate had no effect (p>0.05) on the fatty acid composition of pork but decreased (p≤0.05) lipid oxidation while exerting no effect (p>0.05) on protein oxidation in both raw and cooked α-linolenic acid-enriched chops stored and chilled for 9 days. Moreover, olive leaves and α-tocopheryl acetate supplemented at 10 g/kg and 200mg/kg diet, respectively, exerted (p≤0.05) a beneficial effect on the sensory attributes of cooked α-linolenic acid-enriched pork chops. Copyright © 2012 Elsevier Ltd. All rights reserved.

Optical chopper for the HIRDLS instrument

NASA Astrophysics Data System (ADS)

Opyd, Walter G.; Rudolf, Wayne; Loewenthal, Stuart; Heal, Thomas

1998-11-01

Test chipper performance, as well as mechanical design and electronic control concepts, are presented for the optical chopper developed for the High-Resolution Dynamics Limb Sounder (HIRDLS) to be flown on the CHEM-1 satellite of the NASA Earth Observing System (EOS). Optical chopping is essential in order to achieve the required sensitivity and accuracy in measurement of infrared emission from various chemical species in the earth's atmosphere. Chopping of the optical input as far forward in the telescope as practical minimizes calibration errors arising from variations in emission from warm optics and due to electronic drifts in the infrared detecting system. At 500 Hz, the reflective chopper blade switches between the atmospheric limb view and reference radiation from cold space. The HIRDLS chopper is a six- toothed, mirrored wheel driven by a three-phase, permanent- magnet, brushless DC motor with trapezoidal excitation synchronized to motor back-emf. Chopper design was driven by requirements of (1) continuous operation at 5000 RPM for 50,000 hours in space vacuum, (2) chopping amplitude stability of one part in 100,000, (3) lubricant loss control for both bearing reliability and prevention of optics contamination, (4) compact size to fit in the folded telescope, and (5) survival in the launch environment.

Chemotherapy for management of localised high-grade gastric B-cell lymphoma: how much is necessary?

PubMed

Raderer, M; Chott, A; Drach, J; Montalban, C; Dragosics, B; Jäger, U; Püspök, A; Osterreicher, C; Zielinski, C C

2002-07-01

Recent data suggest that chemotherapy with the cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen is a highly effective treatment for localised primary gastric lymphoma of diffuse large B-cell histology (DLBCL). We have reported that the large majority of patients achieve complete remission (CR) following three cycles of treatment, and now provide an updated series with special emphasis on patients receiving only short-term chemotherapy. All patients with a histologically verified diagnosis of gastric DLBCL in stages EI and EII(1) undergoing chemotherapy with the CHOP regimen were evaluated. Data analysed included clinical stage, histology [presence of an additional mucosa-associated lymphoid tissue (MALT) component], evidence of Helicobacter pylori infection, H. pylori eradication, time to CR, survival and regular restaging (i.e. after three and six cycles, respectively). A total of 37 patients with DLBCL of the stomach with localised disease were identified, five of whom also had a MALT component. Twenty-two patients presented with stage EI and 15 with stage EII(1) disease. All patients were given chemotherapy as sole management of their lymphoma; 36 patients received CHOP, while one patient was given CHOP along with rituximab. Thirty-two (86%) achieved a CR after a maximum of three cycles, while only four patients had to be given six cycles for CR. In total, nine of 37 patients (24%) discontinued therapy earlier than scheduled: one patient received one cycle, two received two, six received three and one patient received four cycles. Two of these patients stopped treatment due to toxicity, i.e. protracted thrombocytopenia or chemotherapy extravasation. One additional patient died after one cycle of treatment; autopsy disclosed no signs of remaining lymphoma. Three patients have died after a median follow-up of 39 months (including the one patient who discontinued therapy after one cycle of treatment), while the remaining 34 patients are alive without evidence of disease. Twenty-four out of 37 patients (65%) had also undergone H. pylori eradication (including six of nine patients receiving only short-term treatment). DLBCL of the stomach appears to be a highly chemosensitive disease. Our data question the need for full-term CHOP treatment in patients achieving CR upon first follow-up. However, recent data suggest that additional H. pylori eradication might have contributed to the excellent results achieved in our series.

Evaluation of sampling, cookery, and shear force protocols for objective evaluation of lamb longissimus tenderness.

PubMed

Shackelford, S D; Wheeler, T L; Koohmaraie, M

2004-03-01

Experiments were conducted to compare the effects of two cookery methods, two shear force procedures, and sampling location within non-callipyge and callipyge lamb LM on the magnitude, variance, and repeatability of LM shear force data. In Exp. 1, 15 non-callipyge and 15 callipyge carcasses were sampled, and Warner-Bratzler shear force (WBSF) was determined for both sides of each carcass at three locations along the length (anterior to posterior) of the LM, whereas slice shear force (SSF) was determined for both sides of each carcass at only one location. For approximately half the carcasses within each genotype, LM chops were cooked for a constant amount of time using a belt grill, and chops of the remaining carcasses were cooked to a constant endpoint temperature using open-hearth electric broilers. Regardless of cooking method and sampling location, repeatability estimates were at least 0.8 for LM WBSF and SSF. For WBSF, repeatability estimates were slightly higher at the anterior location (0.93 to 0.98) than the posterior location (0.88 to 0.90). The difference in repeatability between locations was probably a function of a greater level of variation in shear force at the anterior location. For callipyge LM, WBSF was higher (P < 0.001) at the anterior location than at the middle or posterior locations. For non-callipyge LM, WBSF was lower (P < 0.001) at the anterior location than at the middle or posterior locations. Consequently, the difference in WBSF between callipyge and non-callipyge LM was largest at the anterior location. Experiment 2 was conducted to obtain an estimate of the repeatability of SSF for lamb LM chops cooked with the belt grill using a larger number of animals (n = 87). In Exp. 2, LM chops were obtained from matching locations of both sides of 44 non-callipyge and 43 callipyge carcasses. Chops were cooked with a belt grill and SSF was measured, and repeatability was estimated to be 0.95. Repeatable estimates of lamb LM tenderness can be achieved either by cooking to a constant endpoint temperature with electric broilers or cooking for a constant amount of time with a belt grill. Likewise, repeatable estimates of lamb LM tenderness can be achieved with WBSF or SSF. However, use of belt grill cookery and the SSF technique could decrease time requirements which would decrease research costs.

Short communication: Effect of straw inclusion rate in a dry total mixed ration on the behavior of weaned dairy calves.

PubMed

Groen, M J; Steele, M A; DeVries, T J

2015-04-01

The primary objective of this study was to determine the effect of straw inclusion levels on the feeding behavior of young, weaned calves adapted to a dry total mixed ration (TMR) composed of a multitextured concentrate and chopped straw. A secondary objective was to determine how developed feeding patterns persist after calves were switched to a conventional silage-based diet. Ten Holstein bull calves (91 ± 2.4d of age, weighing 136 ± 12.3 kg) were assigned to 1 of 2 treatments: a TMR containing [dry matter (DM) basis] either (1) 85% concentrate and 15% chopped straw for 10 wk (wk 1 to 10) or (2) 85% concentrate and 15% chopped straw for 5 wk (wk 1 to 5), then 70% concentrate and 30% chopped straw for 5 wk (wk 6 to 10). After 10 wk, all animals were transitioned to a TMR containing (DM basis) 42.3% corn silage and 57.7% haylage for 2 wk (wk 11 to 12). During wk 1 to 5, all calves had similar DMI (5.5 kg/d), average daily gain (1.7 kg/d), feed efficiency (3.5 kg of DM/kg of gain), and eating time (151.9 min/d). During wk 6 to 10, calves transitioned to the 70% diet ate less DM (5.5 vs. 7.4 kg/d), grew more slowly (1.3 vs. 1.6 kg/d), sorted more against long forage particles (62.8 vs. 103.8%), and had greater feeding times (194.9 vs. 102.6 min/d). The difference in feeding time occurred only during the first 8 h after feed delivery. Despite similar DMI (5.2 kg/d) and average daily gain (1.1 kg/d) in wk 11 to 12, differences in behavior were observed resulting from previous diets. In wk 11 to 12, calves previously fed the 70% diet continued to have a longer meal immediately after feed delivery. Overall, the results indicate that diluting a dry TMR containing a multitextured concentrate and chopped straw with more straw resulted in calves spending more time feeding and having longer meals immediately after feed delivery; this feeding pattern carried over after calves were transitioned to a silage-based ration. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Monoclonal antibodies in the treatment of non-Hodgkin's lymphoma.

PubMed

Fanale, Michelle A; Younes, Anas

2007-01-01

Antibody-based therapeutic approaches have had a significant impact in the treatment of non-Hodgkin's lymphoma (NHL). Rituximab's development as an anti-CD20 antibody heralded a new era in treatment approaches for NHL. While rituximab was first shown to be effective in the treatment of relapsed follicular lymphoma, it is now standard monotherapy for front-line treatment of follicular lymphoma, and is also used in conjunction with chemotherapy for other indolent, intermediate and aggressive B-cell lymphomas. The development of rituximab has led to intense interest in this type of therapeutic approach and to development and approval of the radioimmunoconjugates of rituximab, (90)Y-ibritumomab tiuxetan and (131)I-tositumomab, which have added to the repertoire of treatments for relapsed follicular lymphoma and increased interest in developing other conjugated antibodies. Since rituximab is a chimeric antibody, there is a need to develop fully humanised antibodies, such as IMMU-106 (hA20), in order to minimise infusion reactions and eliminate the development of human antibodies against the drug. Further clinical evaluation of antibodies has been based largely on our knowledge of antigen expression on the surface of lymphoma cells and has led to the development of antibodies against CD22 (unconjugated epratuzumab and calicheamicin conjugated CMC-544 [inotuzumab ozogamicin]), CD80 (galiximab), CD52 (alemtuzumab), CD2 (MEDI-507 [siplizumab]), CD30 (SGN-30 and MDX-060 [iratumumab]), and CD40 (SGN-40). Furthermore, the VEGF (vascular endothelial growth factor) inhibitor bevacizumab, which was first approved for the treatment of colon cancer is currently under investigation in NHL, and agonists rather than antibodies to TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) [rApo2L/TRAIL, HGS-ETR1{mapatumumab}, HGS-ETR2] are currently being investigated as treatments for both advanced solid tumours and NHL. Knowledge of the ability of cancer cells to become resistant to a targeted therapy by activating an alternative pathway to evade apoptosis has driven studies that combine antibodies such as epratuzumab plus rituximab (ER) or ER plus chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) [ER-CHOP], inotuzumab ozogamicin plus rituximab, alemtuzumab plus CHOP (CHOP-C), bevacizumab plus rituximab, and now the combination of rApo2L/TRAIL plus rituximab. As a result of the expansion of research in this area, several treatment-specific adverse effects have been noted, including infusion-related reactions for rituximab, myelosuppression secondary to (90)Y-ibritumomab tiuxetan and (131)I-tositumomab, and immunosuppression leading to infectious complications for alemtuzumab. Also, soluble forms of the antigens (sCD30) are now being investigated as potential mechanisms of resistance to antibody treatments by binding the antibody before the drug can bind to the lymphoma cell. In addition, it has also become apparent that these antibodies often have a dose-dependent half-life (rituximab) or long half-lives of up to 2-3 weeks (epratuzumab and galiximab) with a consequent delay to a response, thus influencing how long we should wait for a response before declaring an antibody to be ineffective. Antibody-based therapeutic approaches have already had a profound impact on the treatment of NHL, and it is almost certain that, as their clinical development progresses, we will continue to refine the optimum methods of incorporating these drugs in NHL treatment in order to offer our patients the best clinical benefits.

Effects of residual feed intake classification and method of alfalfa processing on ewe intake and growth.

PubMed

Redden, R R; Surber, L M M; Grove, A V; Kott, R W

2014-02-01

The objective of this research was to evaluate the effects of residual feed intake (RFI) determined under ad libitum feeding conditions on DMI and performance of yearling ewes fed either chopped or pelleted alfalfa hay. In Exp. 1, 45 ewe-lambs had ad libitum access to a pelleted grower diet for 63 d and individual DMI was determined using an electronic feed delivery system. Residual feed intake values were assigned to each ewe-lamb as a measure of feed efficiency. Sixteen ewe-lambs with the most positive RFI values were classified as high RFI (inefficient) and 16 ewe-lambs with the most negative RFI values were classified as low RFI (efficient). In Exp. 2, half of the ewes from each efficiency group were placed into 1 of 2 pens and provided ad libitum access to either pelleted or chopped alfalfa hay. Individual DMI was again determined using an electronic feed delivery system. Body weight, LM area (LMA), and 12th-rib back fat thickness (BF) were measured at the beginning and end of both experiments. In Exp. 1, DMI by ewe-lambs in the low RFI group was 9% less (P = 0.01) than by ewe-lambs in the high RFI group (2.21 vs. 2.43 kg/d); however, ADG and initial and final BW, LMA, and BF did not differ (P > 0.27) among RFI groups. In Exp. 2, there were no feed processing × RFI group interactions (P > 0.14) for any trait. By design, RFI values were lower (P < 0.01) by yearling ewes in the low than high RFI group (-0.27 vs. 0.27); however, RFI values did not differ (P = 1.0) between yearling ewes fed chopped versus pelleted alfalfa. Dry matter intake was 22% less (P < 0.01) by yearling ewes in the low than high RFI group (2.5 vs. 3.2 kg/d) and 59% less (P < 0.01) by yearling ewes fed chopped versus pelleted alfalfa (2.2 vs. 3.5 kg/d). Initial and final BW, ADG, and G:F did not differ (P > 0.45) between RFI groups but were greater (P < 0.01) by yearling ewes fed pelleted alfalfa compared to chopped alfalfa. Final LMA did not differ (P = 0.77) between RFI groups, but final BF tended to be greater (P = 0.06) for high than low RFI yearling ewes (0.63 vs. 0.57 cm). Final LMA and BF were greater (P < 0.01) by yearling ewes fed pelleted than chopped alfalfa. Low RFI ewes had lower DMI and BF compared to high RFI ewes. Ewe efficiency as determined by RFI was repeatable on subsequent forage based diets; however, differences in intake and efficiency were more apparent when alfalfa was pelleted.

Heme Oxygenase Inhibition Sensitizes Neuroblastoma Cells to Carfilzomib.

PubMed

Barbagallo, Ignazio; Giallongo, Cesarina; Volti, Giovanni Li; Distefano, Alfio; Camiolo, Giuseppina; Raffaele, Marco; Salerno, Loredana; Pittalà, Valeria; Sorrenti, Valeria; Avola, Roberto; Di Rosa, Michelino; Vanella, Luca; Di Raimondo, Francesco; Tibullo, Daniele

2018-06-10

Neuroblastoma (NB) is an embryonic malignancy affecting the physiological development of adrenal medulla and paravertebral sympathetic ganglia in early infancy. Proteasome inhibitors (PIs) (i.e., carfilzomib (CFZ)) may represent a possible pharmacological treatment for solid tumors including NB. In the present study, we tested the effect of a novel non-competitive inhibitor of heme oxygenase-1 (HO-1), LS1/71, as a possible adjuvant therapy for the efficacy of CFZ in neuroblastoma cells. Our results showed that CFZ increased both HO-1 gene expression (about 18-fold) and HO activity (about 8-fold), following activation of the ER stress pathway. The involvement of HO-1 in CFZ-mediated cytotoxicity was further confirmed by the protective effect of pharmacological induction of HO-1, significantly attenuating cytotoxicity. In addition, HO-1 selective inhibition by a specific siRNA increased the cytotoxic effect following CFZ treatment in NB whereas SnMP, a competitive pharmacological inhibitor of HO, showed no changes in cytotoxicity. Our data suggest that treatment with CFZ produces ER stress in NB without activation of CHOP-mediated apoptosis, whereas co-treatment with CFZ and LS1/71 led to apoptosis activation and CHOP expression induction. In conclusion, our study showed that treatment with the non-competitive inhibitor of HO-1, LS1 / 71, increased cytotoxicity mediated by CFZ, triggering apoptosis following ER stress activation. These results suggest that PIs may represent a possible pharmacological treatment for solid tumors and that HO-1 inhibition may represent a possible strategy to overcome chemoresistance and increase the efficacy of chemotherapic regimens.

Reforming the household registration system: a preliminary glimpse of the blue chop household registration system in Shanghai and Shenzhen.

PubMed

Wong, L; Wai-po, H

1998-01-01

"For decades, the household registration system has functioned as a powerful device in halting rural influxes into Chinese cities. The exigencies of the reform call for reform of the hukou system [China's household registration]. One of the many attempts is the blue chop household registration system. Both Shanghai and Shenzhen have introduced this practice. In addition to promotion of real estate and investment, it creams off those more desirable migrants into the permanent population of the two cities. In view of the present situation of linking welfare provision with household registration status, this selective migration policy seems to be a sensible step forward." excerpt

Continental Rifts

NASA Astrophysics Data System (ADS)

Rosendahl, B. R.

Continental Rifts, edited by A. M. Quennell, is a new member of the Benchmark Papers in Geology Series, edited in toto by R. W. Fairbridge. In this series the individual volume editors peruse the literature on a given topic, select a few dozen papers of ostensibly benchmark quality, and then reorder them in some sensible fashion. Some of the original papers are republished intact, but many are chopped into “McNuggets™” of information. Depending upon the volume editor, the chopping process can range from a butchering job to careful and prudent pruning. The collecting, sifting, and reorganizing tasks are, of course, equally editor-sensitive. The end product of this series is something akin to a set of Reader's Digest of Geology.

Synergistic Anti-Tumor Activity of EZH2 Inhibitors and Glucocorticoid Receptor Agonists in Models of Germinal Center Non-Hodgkin Lymphomas

PubMed Central

Klaus, Christine R.; Wigle, Tim J.; Iwanowicz, Dorothy; Littlefield, Bruce A.; Porter-Scott, Margaret; Smith, Jesse J.; Moyer, Mikel P.; Copeland, Robert A.; Pollock, Roy M.; Kuntz, Kevin W.; Raimondi, Alejandra; Keilhack, Heike

2014-01-01

Patients with non-Hodgkin lymphoma (NHL) are treated today with a cocktail of drugs referred to as CHOP (Cyclophosphamide, Hydroxyldaunorubicin, Oncovin, and Prednisone). Subsets of patients with NHL of germinal center origin bear oncogenic mutations in the EZH2 histone methyltransferase. Clinical testing of the EZH2 inhibitor EPZ-6438 has recently begun in patients. We report here that combining EPZ-6438 with CHOP in preclinical cell culture and mouse models results in dramatic synergy for cell killing in EZH2 mutant germinal center NHL cells. Surprisingly, we observe that much of this synergy is due to Prednisolone – a glucocorticoid receptor agonist (GRag) component of CHOP. Dramatic synergy was observed when EPZ-6438 is combined with Prednisolone alone, and a similar effect was observed with Dexamethasone, another GRag. Remarkably, the anti-proliferative effect of the EPZ-6438+GRag combination extends beyond EZH2 mutant-bearing cells to more generally impact germinal center NHL. These preclinical data reveal an unanticipated biological intersection between GR-mediated gene regulation and EZH2-mediated chromatin remodeling. The data also suggest the possibility of a significant and practical benefit of combining EZH2 inhibitors and GRag that warrants further investigation in a clinical setting. PMID:25493630

Synergistic Anti-Tumor Activity of EZH2 Inhibitors and Glucocorticoid Receptor Agonists in Models of Germinal Center Non-Hodgkin Lymphomas.

PubMed

Knutson, Sarah K; Warholic, Natalie M; Johnston, L Danielle; Klaus, Christine R; Wigle, Tim J; Iwanowicz, Dorothy; Littlefield, Bruce A; Porter-Scott, Margaret; Smith, Jesse J; Moyer, Mikel P; Copeland, Robert A; Pollock, Roy M; Kuntz, Kevin W; Raimondi, Alejandra; Keilhack, Heike

2014-01-01

Patients with non-Hodgkin lymphoma (NHL) are treated today with a cocktail of drugs referred to as CHOP (Cyclophosphamide, Hydroxyldaunorubicin, Oncovin, and Prednisone). Subsets of patients with NHL of germinal center origin bear oncogenic mutations in the EZH2 histone methyltransferase. Clinical testing of the EZH2 inhibitor EPZ-6438 has recently begun in patients. We report here that combining EPZ-6438 with CHOP in preclinical cell culture and mouse models results in dramatic synergy for cell killing in EZH2 mutant germinal center NHL cells. Surprisingly, we observe that much of this synergy is due to Prednisolone - a glucocorticoid receptor agonist (GRag) component of CHOP. Dramatic synergy was observed when EPZ-6438 is combined with Prednisolone alone, and a similar effect was observed with Dexamethasone, another GRag. Remarkably, the anti-proliferative effect of the EPZ-6438+GRag combination extends beyond EZH2 mutant-bearing cells to more generally impact germinal center NHL. These preclinical data reveal an unanticipated biological intersection between GR-mediated gene regulation and EZH2-mediated chromatin remodeling. The data also suggest the possibility of a significant and practical benefit of combining EZH2 inhibitors and GRag that warrants further investigation in a clinical setting.

Frequency-dependent photothermal measurement of transverse thermal diffusivity of organic semiconductors

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

Brill, J. W.; Shahi, Maryam; Yao, Y.

2015-12-21

We have used a photothermal technique, in which chopped light heats the front surface of a small (∼1 mm{sup 2}) sample and the chopping frequency dependence of thermal radiation from the back surface is measured with a liquid-nitrogen-cooled infrared detector. In our system, the sample is placed directly in front of the detector within its dewar. Because the detector is also sensitive to some of the incident light, which leaks around or through the sample, measurements are made for the detector signal that is in quadrature with the chopped light. Results are presented for layered crystals of semiconducting 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS-pn)more » and for papers of cellulose nanofibrils coated with semiconducting poly(3,4-ethylene-dioxythiophene):poly(styrene-sulfonate) (NFC-PEDOT). For NFC-PEDOT, we have found that the transverse diffusivity, smaller than the in-plane value, varies inversely with thickness, suggesting that texturing of the papers varies with thickness. For TIPS-pn, we have found that the interlayer diffusivity is an order of magnitude larger than the in-plane value, consistent with previous estimates, suggesting that low-frequency optical phonons, presumably associated with librations in the TIPS side groups, carry most of the heat.« less

Autologous transplantation in CLL patients with B and C Binet stages: final results of the prospective randomized GOELAMS LLC 98 trial.

PubMed

Brion, A; Mahé, B; Kolb, B; Audhuy, B; Colombat, P; Maisonneuve, H; Foussard, C; Bureau, A; Ferrand, C; Lesesve, J F; Béné, M C; Feugier, P

2012-04-01

The relevance of high-dose chemotherapy followed by auto-SCT in CLL remains to be defined. The aim of the prospective, randomized, GOELAMS LLC 98 trial was to compare two strategies in previously untreated CLL patients aged <60 years. Conventional chemotherapy (Arm A) consisted of six monthly courses of CHOP followed by six CHOP courses in every 3 months in those achieving a complete or PR. Arm A was compared with high-dose therapy with auto-SCT (Arm B), used as consolidation after three CHOP courses in case of CR or very good PR. A total of 86 patients were enrolled, of which 39 and 43 patients were evaluable in arm A and arm B, respectively. The primary endpoint was PFS. On an intent-to-treat basis and with a median follow-up time of 77.1 (range 1-135.5) months, the median PFS was 22 months in Arm A and 53 months in Arm B (P<0.0001). Median survival time was 104.7 months in arm A and 107.4 months in arm B. This trial demonstrates that frontline high-dose therapy with auto-SCT prolongs PFS but does not translate into a survival advantage in advanced CLL patients in the pre-rituximab era.

Endoplasmic reticulum stress and IRE-1 signaling cause apoptosis in colon cancer cells in response to andrographolide treatment.

PubMed

Banerjee, Aditi; Ahmed, Hafiz; Yang, Peixin; Czinn, Steven J; Blanchard, Thomas G

2016-07-05

The plant metabolite andrographolide induces cell cycle arrest and apoptosis in cancer cells. The mechanism(s) by which andrographolide induces apoptosis however, have not been elucidated. The present study was performed to determine the molecular events that promote apoptosis in andrographolide treated cells using T84, HCT116 and COLO 205 colon cancer cell lines. Andrographolide was determined to limit colony formation and Ki67 expression, alter nuclear morphology, increase cytoplasmic histone-associated-DNA-fragments, and increase cleaved caspase-3 levels. Andrographolide also induced significantly higher expression of endoplasmic reticulum (ER) stress proteins GRP-78 and IRE-1 by 48 h but not PERK or ATF6. Apoptosis signaling molecules BAX, spliced XBP-1 and CHOP were also significantly increased. Moreover, chemical inhibition of ER stress or IRE-1 depletion with siRNA in andrographolide treated cells significantly limited expression of IRE-1 and CHOP as determined by immunofluorescence staining, real time PCR, or immunobloting. This was accompanied by a decreased BAX/Bcl-2 ratio. Andrographolide significantly promotes cancer cell death compared to normal cells. These data demonstrate that andrographolide associated ER stress contributes to apoptosis through the activation of a pro-apoptotic GRP-78/IRE-1/XBP-1/CHOP signaling pathway.

Vertical bloch line memory

NASA Technical Reports Server (NTRS)

Katti, Romney R. (Inventor); Stadler, Henry L. (Inventor); Wu, Jiin-chuan (Inventor)

1995-01-01

A new read gate design for the vertical Bloch line (VBL) memory is disclosed which offers larger operating margin than the existing read gate designs. In the existing read gate designs, a current is applied to all the stripes. The stripes that contain a VBL pair are chopped, while the stripes that do not contain a VBL pair are not chopped. The information is then detected by inspecting the presence or absence of the bubble. The margin of the chopping current amplitude is very small, and sometimes non-existent. A new method of reading Vertical Bloch Line memory is also disclosed. Instead of using the wall chirality to separate the two binary states, the spatial deflection of the stripe head is used. Also disclosed herein is a compact memory which uses vertical Bloch line (VBL) memory technology for providing data storage. A three-dimensional arrangement in the form of stacks of VBL memory layers is used to achieve high volumetric storage density. High data transfer rate is achieved by operating all the layers in parallel. Using Hall effect sensing, and optical sensing via the Faraday effect to access the data from within the three-dimensional packages, an even higher data transfer rate can be achieved due to parallel operation within each layer.

Techno-economic analysis of using corn stover to supply heat and power to a corn ethanol plant - Part 1: Cost of feedstock supply logistics

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

Sokhansanj, Shahabaddine; Mani, Sudhagar; Togore, Sam

2010-01-01

Supply of corn stover to produce heat and power for a typical 170 dam3 dry mill ethanol plant is proposed. The corn ethanol plant requires 5.6 MW of electricity and 52.3 MW of process heat, which creates the annual stover demand of as much as 140 Gg. The corn stover supply system consists of collection, preprocessing, transportation and on-site fuel storage and preparation to produce heat and power for the ethanol plant. Economics of the entire supply system was conducted using the Integrated Biomass Supply Analysis and Logistics (IBSAL) simulation model. Corn stover was delivered in three formats (square bales,more » dry chops and pellets) to the combined heat and power plant. Delivered cost of biomass ready to be burned was calculated at 73 $ Mg-1 for bales, 86 $ Mg-1 for pellets and 84 $ Mg-1 for field chopped biomass. Among the three formats of stover supply systems, delivered cost of pelleted biomass was the highest due to high pelleting cost. Bulk transport of biomass in the form of chops and pellets can provide a promising future biomass supply logistic system in the US, if the costs of pelleting and transport are minimized.« less

Effects of size and thermophilic pre-hydrolysis of banana peel during anaerobic digestion, and biomethanation potential of key tropical fruit wastes.

PubMed

Odedina, Mary Jesuyemi; Charnnok, Boonya; Saritpongteeraka, Kanyarat; Chaiprapat, Sumate

2017-10-01

Methane production potential of tropical fruit wastes, namely lady-finger banana peel, rambutan waste and longan waste were compared using BMP assay and stoichiometric modified Buswell and Mueller equation. Methane yields based on volatile solid (VS) were in the order of ground banana peel, chopped banana peel, chopped longan waste, and chopped rambutan waste (330.6, 268.3, 234.6 and 193.2 mLCH 4 /gVS) that corresponded to their calculated biodegradability. In continuous operations of banana peel digestion at feed concentrations based on total solid (TS) 1-2%, mesophilic single stage digester run at 20-day hydraulic retention time (20-day HRT) failed at 2%TS, but successfully recovered at 1.5%TS. Pre-hydrolysis thermophilic reactor (4-d HRT) was placed as pre-treatment to mesophilic reactor (20-d HRT). Higher biogas (with an evolution of H 2 ) and energy yields were obtained and greater system stability was achieved over the single stage digestion, particularly at higher solid feedstock. The best performance of two stage digestion was 68.5% VS destruction and energy yield of 2510.9kJ/kgVS added at a feed concentration of 2%TS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oyster mushroom cultivation with rice and wheat straw.

PubMed

Zhang, Ruihong; Li, Xiujin; Fadel, J G

2002-05-01

Cultivation of the oyster mushroom, Pleurotus sajor-caju, on rice and wheat straw without nutrient supplementation was investigated. The effects of straw size reduction method and particle size, spawn inoculation level, and type of substrate (rice straw versus wheat straw) on mushroom yield, biological efficiency, bioconversion efficiency, and substrate degradation were determined. Two size reduction methods, grinding and chopping, were compared. The ground straw yielded higher mushroom growth rate and yield than the chopped straw. The growth cycles of mushrooms with the ground substrate were five days shorter than with the chopped straw for a similar particle size. However, it was found that when the straw was ground into particles that were too small, the mushroom yield decreased. With the three spawn levels tested (12%, 16% and 18%), the 12% level resulted in significantly lower mushroom yield than the other two levels. Comparing rice straw with wheat straw, rice straw yielded about 10% more mushrooms than wheat straw under the same cultivation conditions. The dry matter loss of the substrate after mushroom growth varied from 30.1% to 44.3%. The straw fiber remaining after fungal utilization was not as degradable as the original straw fiber, indicating that the fungal fermentation did not improve the feed value of the straw.

Influence of genotype and ensiling of corn grain on in situ degradation of starch in the rumen.

PubMed

Philippeau, C; Michalet-Doreau, B

1998-08-01

This trial was conducted to determine the influence of genotype and ensiling of corn grain on the rate and extent of ruminal starch degradation. Two cultivars of corn that differed in texture of the endosperm, dent (Zea mays ssp. indentata) or flint (Zea mays ssp. indentura) were harvested at 30% whole-plant dry matter (DM). After separation from stover and cob, the kernels were coarsely chopped and ensiled or not ensiled. Grains were oven-dried at 40 degrees C and either ground through a 3-mm sieve or left unground. Ruminal DM and starch degradabilities were determined using the in situ technique. The proportion of starch lost through the pores of the bag without degradation was also determined. Mean ruminal DM and starch degradabilities were higher for ground grains than for chopped grains, which could be related to the proportion of DM and starch lost through the pores of the bag. For unensiled, chopped grain, ruminal starch degradability was higher for dent corn than for flint corn (72.3% vs. 61.6%). The ensiling process increased ruminal starch degradability, averaging 5.8 percentage units. The difference in ruminal starch degradability between dent corn and flint corn remained constant whether the corn was unensiled or ensiled (10.7 vs. 11.6 percentage units).

Reduction of Endoplasmic Reticulum Stress Improves Angiogenic Progenitor Cell function in a Mouse Model of Type 1 Diabetes.

PubMed

Bhatta, Maulasri; Chatpar, Krishna; Hu, Zihua; Wang, Joshua J; Zhang, Sarah X

2018-04-27

Persistent vascular injury and degeneration in diabetes are attributed in part to defective reparatory function of angiogenic cells. Our recent work implicates endoplasmic reticulum (ER) stress in high-glucose-induced bone marrow (BM) progenitor dysfunction. Herein, we investigated the in vivo role of ER stress in angiogenic abnormalities of streptozotocin-induced diabetic mice. Our data demonstrate that ER stress markers and inflammatory gene expression in BM mononuclear cells and hematopoietic progenitor cells increase dynamically with disease progression. Increased CHOP and cleaved caspase- 3 levels were observed in BM--derived early outgrowth cells (EOCs) after 3 months of diabetes. Inhibition of ER stress by ex vivo or in vivo chemical chaperone treatment significantly improved the generation and migration of diabetic EOCs while reducing apoptosis of these cells. Chemical chaperone treatment also increased the number of circulating angiogenic cells in peripheral blood, alleviated BM pathology, and enhanced retinal vascular repair following ischemia/reperfusion in diabetic mice. Mechanistically, knockdown of CHOP alleviated high-glucose-induced EOC dysfunction and mitigated apoptosis, suggesting a pivotal role of CHOP in mediating ER stress-associated angiogenic cell injury in diabetes. Together, our study suggests that targeting ER signaling may provide a promising and novel approach to enhancing angiogenic function in diabetes.

Seawater inhalation induces acute lung injury via ROS generation and the endoplasmic reticulum stress pathway.

PubMed

Li, Peng-Cheng; Wang, Bo-Rong; Li, Cong-Cong; Lu, Xi; Qian, Wei-Sheng; Li, Yu-Juan; Jin, Fa-Guang; Mu, De-Guang

2018-05-01

Seawater (SW) inhalation can induce acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In the present study, SW induced apoptosis of rat alveolar epithelial cells and histopathological alterations to lung tissue. Furthermore, SW administration increased generation of reactive oxygen species (ROS), whereas pretreatment with the ROS scavenger, N‑acetyl‑L‑cysteine (NAC), significantly decreased ROS generation, apoptosis and histopathological alterations. In addition, SW exposure upregulated the expression levels of glucose‑regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP), which are critical proteins in the endoplasmic reticulum (ER) stress response, thus indicating that SW may activate ER stress. Conversely, blocking ER stress with 4‑phenylbutyric acid (4‑PBA) significantly improved SW‑induced apoptosis and histopathological alterations, whereas an ER stress inducer, thapsigargin, had the opposite effect. Furthermore, blocking ROS with NAC inhibited SW‑induced ER stress, as evidenced by the downregulation of GRP78, phosphorylated (p)‑protein kinase R‑like ER kinase (PERK), p‑inositol‑requiring kinase 1α (IRE1α), p‑50 activating transcription factor 6α and CHOP. In addition, blocking ER stress with 4‑PBA decreased ROS generation. In conclusion, the present study indicated that ROS and ER stress pathways, which are involved in alveolar epithelial cell apoptosis, are important in the pathogenesis of SW‑induced ALI.

Grinding energy and physical properties of chopped and hammer-milled barley, wheat, oat, and canola straws

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

J.S. Tumuluru; L.G. Tabil; Y. Song

2014-01-01

In the present study, specific energy for grinding and physical properties of wheat, canola, oat and barley straw grinds were investigated. The initial moisture content of the straw was about 0.13–0.15 (fraction total mass basis). Particle size reduction experiments were conducted in two stages: (1) a chopper without a screen, and (2) a hammer mill using three screen sizes (19.05, 25.4, and 31.75 mm). The lowest grinding energy (1.96 and 2.91 kWh t-1) was recorded for canola straw using a chopper and hammer mill with 19.05-mm screen size, whereas the highest (3.15 and 8.05 kWh t-1) was recorded for barleymore » and oat straws. The physical properties (geometric mean particle diameter, bulk, tapped and particle density, and porosity) of the chopped and hammer-milled wheat, barley, canola, and oat straw grinds measured were in the range of 0.98–4.22 mm, 36–80 kg m-3, 49–119 kg m-3, 600–1220 kg m-3, and 0.9–0.96, respectively. The average mean particle diameter was highest for the chopped wheat straw (4.22-mm) and lowest for the canola grind (0.98-mm). The canola grinds produced using the hammer mill (19.05-mm screen size) had the highest bulk and tapped density of about 80 and 119 kg m-3; whereas, the wheat and oat grinds had the lowest of about 58 and 88–90 kg m-3. The results indicate that the bulk and tapped densities are inversely proportional to the particle size of the grinds. The flow properties of the grinds calculated are better for chopped straws compared to hammer milled using smaller screen size (19.05 mm).« less

The dynamic changes of endoplasmic reticulum stress pathway markers GRP78 and CHOP in the hippocampus of diabetic mice.

PubMed

Zhao, Yongmei; Yan, Ying; Zhao, Zhiwei; Li, Sen; Yin, Jie

2015-02-01

Diabetic encephalopathy has recently been recognized late complication of diabetes resulting in progressive cognitive deficits. Emerging evidence has indicated that endoplasmic reticulum (ER) stress-mediated apoptosis is involved in the pathogenesis of diabetic eye and kidney as well as non-diabetic neurodegeneration. However, there was little direct evidence for the involvement of ER stress in diabetic encephalopathy up to now. In the present work, we investigated the role of ER stress in the pathogenesis of diabetic encephalopathy. Our results have demonstrated the existence of ER stress in the hippocampus of streptozotocin (STZ)-induced diabetic mice. STZ injection i.p. rapidly induced up-regulation of the ER stress marker, the prosurvival chaperone glucose-regulated protein 78 (GRP78), as early as 6-24h and persisted at least for up to 72h in the hippocampus of mice, indicating the UPR activation soon after STZ administration. The increased expression of GRP78 in hippocampal cells is to relieve the ER stress. With the development of diabetes, the expression of GRP78 decreases while the expression of UPR-associated proapoptotic transcriptional regulator C/EBP homologous protein (CHOP) increases significantly in the hippocampal neurons of diabetic mice from 1 week after STZ administration to 12 weeks/the end of the study. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells in the hippocampus of diabetic mice were largely colocalized with NeuN- and CHOP-positive cells, indicating that the up-regulation of CHOP in hippocampal neurons of diabetic mice may promote neuronal apoptosis and account for the damaged learning and memory ability of diabetic mice. Therefore, our study provides evidence that ER stress may play an important role in the pathogenesis of neuronal degeneration and may contribute to cognitive dysfunction of diabetic encephalopathy. Copyright © 2014 Elsevier Inc. All rights reserved.

Transatlantic medical consultation and second opinion in pediatric cardiology has benefit past patient care: A case study in videoconferencing.

PubMed

Kovacikova, Lubica; Zahorec, Martin; Skrak, Peter; Hanna, Brian D; Lee Vogel, R

2017-07-01

Telemedicine is a rapidly evolving form of modern information and communication technology used to deliver clinical services and educational activities. The aim of this article is to report and analyze our experience with transatlantic consultation via videoconferencing in pediatric cardiology. In February, 2013, videoconferencing project was launched between a medium-volume pediatric cardiac center in Bratislava, Slovakia and subspecialty experts from a high-volume pediatric cardiac program at The Children's Hospital of Philadelphia (CHOP), USA. During 1.5-2 hours videoconferences, 2-3 patients with similar complex clinical scenarios were presented to CHOP experts. The main goal of the project was consultation on individual patients to validate, alter or radically change clinical management plans. From February, 2013 to January, 2017, 25 videoconferences occurred and 73 cases were discussed. The median patient age was 52 months (range; 1 day-30 years). Forty-six discussed cases were outpatients, 21 patients were in the intensive care unit and 6 patients were discussed post mortem. Thirty-one CHOP experts from different subspecialties participated actively in patient consultations. The most frequent recommendations were related to single ventricle, pulmonary hypertension or heart failure patients and intervention in complex and/or rare cardiac diseases. Specialists from CHOP agreed completely with the original care plan in 16% of cases. In 52% cases, adjustments to original plan were suggested. Radical changes were recommended in 30% of cases. Receiving institution adopted recommendations to the patient care fully in 79% and partially in 13% of patients. Based on our 4-year experience we consider videoconferencing between medium-size pediatric cardiac center and subspecialty experts from a high-volume pediatric cardiac program a suitable form of medical consultations. Videoconferencing assists in clinical decision making for complex patient cases and serves as an effective educational tool to gain knowledge and experience "without borders." © 2017 Wiley Periodicals, Inc.

Nupr1 Modulates Methamphetamine-Induced Dopaminergic Neuronal Apoptosis and Autophagy through CHOP-Trib3-Mediated Endoplasmic Reticulum Stress Signaling Pathway

PubMed Central

Xu, Xiang; Huang, Enping; Tai, Yunchun; Zhao, Xu; Chen, Xuebing; Chen, Chuanxiang; Chen, Rui; Liu, Chao; Lin, Zhoumeng; Wang, Huijun; Xie, Wei-Bing

2017-01-01

Methamphetamine (METH) is an illegal and widely abused psychoactive stimulant. METH exposure causes detrimental effects on multiple organ systems, primarily the nervous system, especially dopaminergic pathways, in both laboratory animals and humans. In this study, we hypothesized that Nuclear protein 1 (Nupr1/com1/p8) is involved in METH-induced neuronal apoptosis and autophagy through endoplasmic reticulum (ER) stress signaling pathway. To test this hypothesis, we measured the expression levels of Nupr1, ER stress protein markers CHOP and Trib3, apoptosis-related protein markers cleaved-caspase3 and PARP, as well as autophagy-related protein markers LC3 and Beclin-1 in brain tissues of adult male Sprague-Dawley (SD) rats, rat primary cultured neurons and the rat adrenal pheochromocytoma cells (PC12 cells) after METH exposure. We also determined the effects of METH exposure on the expression of these proteins after silencing Nupr1, CHOP, or Trib3 expression with synthetic small hairpin RNA (shRNA) or siRNA in vitro, and after silencing Nupr1 in the striatum of rats by injecting lentivirus containing shRNA sequence targeting Nupr1 gene to rat striatum. The results showed that METH exposure increased Nupr1 expression that was accompanied with increased expression of ER stress protein markers CHOP and Trib3, and also led to apoptosis and autophagy in rat primary neurons and in PC12 cells after 24 h exposure (3.0 mM), and in the prefrontal cortex and striatum of rats after repeated intraperitoneal injections (15 mg/kg × 8 injections at 12 h intervals). Silencing of Nupr1 expression partly reduced METH-induced apoptosis and autophagy in vitro and in vivo. These results suggest that Nupr1 plays an essential role in METH-caused neuronal apoptosis and autophagy at relatively higher doses and may be a potential therapeutic target in high-dose METH-induced neurotoxicity. PMID:28694771

Impact of salvage treatment modalities in patients with positive FDG-PET/CT after R-CHOP chemotherapy for aggressive B-cell non-Hodgkin lymphoma.

PubMed

Chin, Vicky; Fulham, Michael; Hertzberg, Mark; Jackson, Michael; Lindeman, Robert; Brighton, Timothy; Kidson-Gerber, Giselle; Wegner, Eva A; Cheung, Carol; MacCallum, Susan; Williams, Janet; Thompson, Stephen R

2018-06-01

To compare outcomes of different salvage treatment modalities in patients with aggressive B-cell non-Hodgkin lymphoma (NHL) who remain FDG-PET positive after R-CHOP chemotherapy. Existing data on these patients with FDG-PET primary refractory disease are limited. Patients with diffuse large B-cell lymphoma or grade 3 follicular lymphoma were retrospectively reviewed from the Prince of Wales Hospital databases. Eligibility criteria were: age≥18 years, treated with R-CHOP, with positive post-chemotherapy FDG-PET. Salvage treatment modalities were: radical radiotherapy (RT, dose≥30 Gy), high dose chemotherapy and autologous stem cell transplant (ASCT), or non-radical management. Survival was calculated from date of post-chemotherapy FDG-PET to last follow-up. Twenty-six patients from 2003-2015 met the inclusion criteria. Median age was 60 (range 19-84). Most had adverse baseline features: 21 (81%) stage III-IV, 24 (92%) bulky disease and nine (35%) skeletal involvement. Characteristics of PET-positivity post-chemotherapy were single site in 16 (62%), sites of prior bulk in 24 of 24, skeletal sites in five of nine, and able to be encompassed by RT in 21 (81%). Salvage treatment was: radical RT in 17 (65%), ASCT in four (15%) and non-radical in five (20%). Median follow-up of surviving patients was 31 months. Kaplan-Meier estimates of 3-year PFS and OS were 41% and 52%, respectively. By salvage modality, 3-year PFS was 51% for RT, 25% for ASCT and 20% for non-radical treatment, (P = 0.453); 3-year OS was respectively 65%, 25% and 40% (P = 0.173). Patients with FDG-PET positive disease after R-CHOP for aggressive B-cell NHL are salvageable with radiotherapy. © 2018 The Royal Australian and New Zealand College of Radiologists.

Availability of illicit tobacco in small retail outlets before and after the implementation of Australian plain packaging legislation.

PubMed

Scollo, Michelle; Bayly, Megan; Wakefield, Melanie

2015-03-01

We aimed to assess change in the availability of illicit tobacco in small mixed business retail outlets following the December 2012 introduction of plain packaging in Australia. 303 small retail outlets were visited in June and September 2012 (baseline months), and in December 2012 and February, April and July 2013. Fieldworkers requested a particular low-cost brand of cigarettes and then pressed the retailer for an 'even cheaper' brand. The cheapest pack of cigarettes offered was purchased and later examined to assess any divergence from prescribed Australian packaging regulations. The price paid was compared with tax liability and recommended retail price for the particular brand and pack size. In a sub-set of 179 stores, fieldworkers then asked the retailer about availability of unbranded (chop-chop) tobacco. Thirteen (2.2%) of 598 packs purchased pre-plain packaging were either non-compliant with Australian health warnings and/or suspiciously priced. Four packs (1.3%) of 297 met either or both criteria in the December implementation month, and five (0.6%) of 878 did so in the three collection months following implementation. Chop-chop was offered upon enquiry on 0.6% (n=2) of 338 occasions prior to implementation, 0.6% (n=1) of 170 occasions in the December 2012 implementation month, and 0.6% (n=3) of 514 occasions postimplementation. The likelihood of a 'positive' response (either an offer to sell or information about where unbranded tobacco may be purchased) did not differ across preimplementation, during-implementation and postimplementation waves. Overall, packs judged likely to be illicit were sold in response to requests for cheapest available packs on fewer than one percent of occasions. Offers to sell unbranded tobacco were rare. No change in availability of illicit tobacco was observed following implementation of plain packaging. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Micro EEG/ECG signal’s chopper-stabilization amplifying chip for novel dry-contact electrode

NASA Astrophysics Data System (ADS)

Sun, Jianhui; Wang, Chunxing; Wang, Gongtang; Wang, Jinhui; Hua, Qing; Cheng, Chuanfu; Cai, Xinxia; Yin, Tao; Yu, Yang; Yang, Haigang; Li, Dengwang

2017-02-01

Facing the body’s EEG (electroencephalograph, 0.5–100 Hz, 5–100 μV) and ECG’s (electrocardiogram, < 100 {Hz}, 0.01–5 mV) micro signal detection requirement, this paper develops a pervasive application micro signal detection ASIC chip with the chopping modulation/demodulation method. The chopper-stabilization circuit with the RRL (ripple reduction loop) circuit is to suppress the ripple voltage, which locates at the single-stage amplifier’s outputting terminal. The single-stage chopping core’s noise has been suppressed too, and it is beneficial for suppressing noises of post-circuit. The chopping core circuit uses the PFB (positive feedback loop) to increase the inputting resistance, and the NFB (negative feedback loop) to stabilize the 40 dB intermediate frequency gain. The cascaded switch-capacitor sample/hold circuit has been used for deleting spike noises caused by non-ideal MOS switches, and the VGA/BPF (voltage gain amplifier/band pass filter) circuit is used to tune the chopper system’s gain/bandwidth digitally. Assisted with the designed novel dry-electrode, the real test result of the chopping amplifying circuit gives some critical parameters: 8.1 μW/channel, 0.8 μVrms (@band-width = 100 Hz), 4216–11220 times digitally tuning gain range, etc. The data capture system uses the NI CO’s data capturing DAQmx interface, and the captured micro EEG/ECG’s waves are real-time displayed with the PC-Labview. The proposed chopper system is a unified EEG/ECG signal’s detection instrument and has a critical real application value. Project supported by the National Natural Science Foundation of China (Nos. 61527815, 31500800, 61501426, 61471342), the National Key Basic Research Plan (No. 2014CB744600), the Beijing Science and Technology Plan (No. Z141100000214002), and the Chinese Academy of Sciences’ Key Project (No. KJZD-EW-L11-2).

c-FLIP and the NOXA/Mcl-1 axis participate in the synergistic effect of pemetrexed plus cisplatin in human choroidal melanoma cells.

PubMed

Zhao, Xiaofei; Kong, Feng; Wang, Lei; Zhang, Han

2017-01-01

Choroidal melanoma is the most common primary malignant intraocular tumor, and very few effective therapies are available to treat it. Our study aimed to understand whether pemetrexed plus cisplatin exerts a beneficial synergistic effect in human choroidal melanoma cells and to delineate the underlying molecular mechanism. To accomplish these aims, we treated choroidal melanoma cells with pemetrexed and cisplatin and assessed cell survival with SRB and MTT assays. Proteins were detected using western blotting analysis. NOXA and CHOP were knocked down with siRNA. We found that pemetrexed or cisplatin alone inhibited survival and induced apoptosis in human choroidal melanoma cells. Furthermore, the expression levels of c-FLIP, an anti-apoptotic protein in the extrinsic apoptosis pathway, and Mcl-1, an anti-apoptotic protein in the intrinsic apoptosis pathway, were decreased by pemetrexed or cisplatin respectively, while the expression of a pro-apoptotic protein in the intrinsic apoptosis pathway, NOXA, was up-regulated. Moreover, pemetrexed or cisplatin alone increased the protein expression of the endoplasmic reticulum stress markers IRE1α, Bip and CHOP. Silencing CHOP expression reduced NOXA expression. These findings suggest that the pemetrexed or cisplatin induced intrinsic apoptosis via activation of the ER stress response. Importantly, combining the two compounds more strongly induced apoptosis. Following the cotreatment, CHOP and NOXA expression increased, while c-FLIP and Mcl-1 expression decreased, and these effects were more pronounced than when using either compound alone. This result suggests that pemetrexed and cisplatin synergistically activate ER stress response-induced apoptosis in choroidal melanoma cells. To summarize, the c-FLIP and NOXA/Mcl-1 axis participated in the synergistic effect of pemetrexed plus cisplatin in human choroidal melanoma cells. Intrinsic apoptosis was induced via activation of the ER stress response. Our study provides important mechanistic insights into potential cancer treatment with pemetrexed plus cisplatin and enriches our understanding of human choroidal melanoma.

Further development of the dynamic gas temperature measurement system. Volume 1: Technical efforts

NASA Technical Reports Server (NTRS)

Elmore, D. L.; Robinson, W. W.; Watkins, W. B.

1986-01-01

A compensated dynamic gas temperature thermocouple measurement method was experimentally verified. Dynamic gas temperature signals from a flow passing through a chopped-wheel signal generator and an atmospheric pressure laboratory burner were measured by the dynamic temperature sensor and other fast-response sensors. Compensated data from dynamic temperature sensor thermoelements were compared with fast-response sensors. Results from the two experiments are presented as time-dependent waveforms and spectral plots. Comparisons between compensated dynamic temperature sensor spectra and a commercially available optical fiber thermometer compensated spectra were made for the atmospheric burner experiment. Increases in precision of the measurement method require optimization of several factors, and directions for further work are identified.

A to Z List of Cancer Drugs

MedlinePlus

... T) Purinethol (Mercaptopurine) Purixan (Mercaptopurine) Q [No Entries] R Radium 223 Dichloride Raloxifene Hydrochloride Ramucirumab Rasburicase R-CHOP R-CVP Recombinant Human Papillomavirus (HPV) Bivalent ...

Colony-Stimulating Factors for Febrile Neutropenia during Cancer Therapy

PubMed Central

Bennett, Charles L.; Djulbegovic, Benjamin; Norris, LeAnn B.; Armitage, James O.

2014-01-01

A 55-year-old, previously healthy woman received a diagnosis of diffuse large-B-cell lymphoma after the evaluation of an enlarged left axillary lymph node obtained on biopsy. She had been asymptomatic except for the presence of enlarged axillary lymph nodes, which she had found while bathing. She was referred to an oncologist, who performed a staging evaluation. A complete blood count and test results for liver and renal function and serum lactate dehydrogenase were normal. Positron-emission tomography and computed tomography (PET–CT) identified enlarged lymph nodes with abnormal uptake in the left axilla, mediastinum, and retroperitoneum. Results on bone marrow biopsy were normal. The patient’s oncologist recommends treatment with six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab (CHOP-R) at 21-day intervals. Is the administration of prophylactic granulocyte colony-stimulating factor (G-CSF) with the first cycle of chemotherapy indicated? PMID:23514290

Effect of reducing dietary forage in lower starch diets on performance, ruminal characteristics, and nutrient digestibility in lactating Holstein cows.

PubMed

Farmer, E R; Tucker, H A; Dann, H M; Cotanch, K W; Mooney, C S; Lock, A L; Yagi, K; Grant, R J

2014-09-01

This experiment evaluated the effect of feeding a lower starch diet (21% of dry matter) with different amounts of forage (52, 47, 43, and 39% of dry matter) on lactational performance, chewing activity, ruminal fermentation and turnover, microbial N yield, and total-tract nutrient digestibility. Dietary forage consisted of a mixture of corn and haycrop silages, and as dietary forage content was reduced, chopped wheat straw (0-10% of dry matter) was added in an effort to maintain chewing activity. Dietary concentrate was adjusted (corn meal, nonforage fiber sources, and protein sources) to maintain similar amounts of starch and other carbohydrate and protein fractions among the diets. Sixteen lactating Holstein cows were used in replicated 4×4 Latin squares with 21-d periods. Dry matter intake increased while physically effective neutral detergent fiber (peNDF1.18) intake was reduced as forage content decreased from 52 to 39%. However, reducing dietary forage did not influence milk yield or composition, although we observed changes in dry matter intake. Time spent chewing, eating, and ruminating (expressed as minutes per day or as minutes per kilogram of NDF intake) were not affected by reducing dietary forage. However, addition of chopped wheat straw to the diets resulted in greater time spent chewing and eating per kilogram of peNDF1.18 consumed. Reducing dietary forage from 52 to 39% did not affect ruminal pH, ruminal digesta volume and mass, ruminal pool size of NDF or starch, ruminal digesta mat consistency, or microbial N yield. Ruminal acetate-to-propionate ratio was reduced, ruminal turnover rates of NDF and starch were greater, and total-tract digestibility of fiber diminished as dietary forage content decreased. Reducing the dietary forage content from 52 to 39% of dry matter, while increasing wheat straw inclusion to maintain chewing and rumen function, resulted in similar milk yield and composition although feed intake increased. With the lower starch diets in this short-term study, the minimal forage content to maintain lactational performance was between 39 and 43%. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The effect of wide swathing on wilting times and nutritive value of alfalfa haylage.

PubMed

Kung, L; Stough, E C; McDonell, E E; Schmidt, R J; Hofherr, M W; Reich, L J; Klingerman, C M

2010-04-01

On 3 consecutive cuttings, alfalfa from a single field was mowed with a John Deere 946 mower-conditioner (4-m cut width; Moline, IL) to leave narrow swaths (NS) ranging from 1.2 to 1.52 m wide (30-37% of cutter bar width) and wide swaths (WS) ranging from 2.44 to 2.74 m wide (62-67% of cutter bar width). Samples were collected from windrows and dry matter (DM) was monitored during wilting until a target of 43 to 45% DM was obtained. Forage from random windrows (n=4-6) was harvested by hand, chopped through a forage harvester before being packed in replicated vacuum-sealed bags, and allowed to ensile for 65 d. There was no swath width x cutting interaction for any parameter tested. Over all cuttings, the resulting silage DM was not different between the NS silage (43.8%) and the WS silage (44.9%). However, wide swathing greatly reduced the time of wilting before making silage. The hours of wilting time needed to reach the targeted DM for the NS silage compared with the WS silage at cuttings 1, 2, and 3 were 50 versus 29, 54 versus 28, and 25 versus 6, respectively. At the time of ensiling, the WS silage had more water-soluble carbohydrates (5.1%) than did the NS silage (3.7%). The WS silage had a lower pH (4.58) than did the NS silage (4.66), but swath width did not affect fermentation end products (lactic acid, acetic acid, and ethanol). The NS silage had more NH(3)-N (0.26%) than did the WS silage (0.21%). Wide swathing did not affect the concentration of ash or the digestibility of NDF, but it lowered the N content (NS=3.45%; WS=3.23%) and increased the ADF content (NS=39.7%; WS=40.9%) of the resulting silage. Wide swathing can markedly reduce the time that alfalfa must wilt before it can be chopped for silage, but under good conditions, as in this study, the resulting silage quality was generally not improved. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

High fat-diet and saturated fatty acid palmitate inhibits IGF-1 function in chondrocytes.

PubMed

Nazli, S A; Loeser, R F; Chubinskaya, S; Willey, J S; Yammani, R R

2017-09-01

Insulin-like growth factor-1 (IGF-1) promotes matrix synthesis and cell survival in cartilage. Chondrocytes from aged and osteoarthritic cartilage have a reduced response to IGF-1. The purpose of this study was to determine the effect of free fatty acids (FFA) present in a high-fat diet on IGF-1 function in cartilage and the role of endoplasmic reticulum (ER) stress. C57BL/6 male mice were maintained on either a high-fat (60% kcal from fat) or a low-fat (10% kcal from fat) diet for 4 months. Mice were then sacrificed; femoral head cartilage caps were collected and treated with IGF-1 to measure proteoglycan (PG) synthesis. Cultured human chondrocytes were treated with 500 μM FFA palmitate or oleate, followed by stimulation with (100 ng/ml) IGF-1 overnight to measure CHOP (a protein marker for ER stress) and PG synthesis. Human chondrocytes were pre-treated with palmitate or 1 mM 4-phenyl butyric acid (PBA) or 1 μM C-Jun N terminal Kinase (JNK) inhibitor, and IGF-1 function (PG synthesis and signaling) was measured. Cartilage explants from mice on the high fat-diet showed reduced IGF-1 mediated PG synthesis compared to a low-fat group. Treatment of human chondrocytes with palmitate induced expression of CHOP, activated JNK and inhibited IGF-1 function. PBA, a small molecule chemical chaperone that alleviates ER stress rescued IGF-1 function and a JNK inhibitor rescued IGF-1 signaling. Palmitate-induced ER stress inhibited IGF-1 function in chondrocytes/cartilage via activating the mitogen-activated protein (MAP) kinase JNK. This is the first study to demonstrate that ER stress is metabolic factor that regulates IGF-1 function in chondrocytes. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Regulation of eIF2α phosphorylation in hindlimb-unloaded and STS-135 space-flown mice

NASA Astrophysics Data System (ADS)

Zhao, Liming; Tanjung, Nancy; Swarnkar, Gaurav; Ledet, Eric; Yokota, Hiroki

2012-09-01

Various environmental stresses elevate the phosphorylation level of eukaryotic translation initiation factor 2 alpha (eIF2α) and induce transcriptional activation of a set of stress responsive genes such as activating transcription factors 3 and 6 (ATF3 and ATF6), CCAAT/enhancer-binding protein homologous protein (CHOP), and Xbp1 (X-box binding protein 1). These stress sources include radiation, oxidation, and stress to the endoplasmic reticulum, and it is recently reported that unloading by hindlimb unloading is such a stress source. No studies, however, have examined the phosphorylation level of eIF2α (eIF2α-p) using skeletal samples that have experienced microgravity in space. In this study we addressed a question: Does a mouse tibia flown in space show altered levels of eIF2α-p? To address this question, we obtained STS-135 flown samples that were harvested 4-7 h after landing. The tibia and femur isolated from hindlimb unloaded mice were employed as non-flight controls. The effects of loading were also investigated in non- flight controls. Results indicate that the level of eIF2α-p of the non-flight controls was elevated during hindlimb unloading and reduced after being released from unloading. Second, the eIF2α-p level of space-flown samples was decreased, and mechanical loading to the tibia caused the reduction of the eIF2α-p level. Third, the mRNA levels of ATF3, ATF6, and CHOP were lowered in space-flown samples as well as in the non-flight samples 4-7 h after being released from unloading. Collectively, the results herein indicated that a release from hindlimb unloading and a return to normal weight environment from space provided a suppressive effect to eIF2α-linked stress responses and that a period of 2-4 h is sufficient to induce this suppressive outcome.

Diffuse large B-cell lymphoma: 10 years' real-world clinical experience with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone.

PubMed

Horvat, Matej; Zadnik, Vesna; Južnič Šetina, Tanja; Boltežar, Lučka; Pahole Goličnik, Jana; Novaković, Srdjan; Jezeršek Novaković, Barbara

2018-03-01

Treatment with rituximab plus a regimen of cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) for patients with diffuse large B-cell lymphoma (DLBCL) has proven efficacy in clinical trials. The present study investigated its application in clinical practice. This single-center, retrospective database analysis included patients with DLBCL treated at the Slovenian Institute of Oncology Ljubljana between 2004 and 2013. Overall survival (OS) and progression-free survival (PFS) were assessed according to International Prognostic Index (IPI) and revised IPI (R-IPI) categories. Overall, 573 patients with DLBCL were included in the study (median follow-up, 45.3 months; range, 0.1-143.0). Patients were categorized as IPI 'low' (n=170; 30%), 'low-intermediate' (n=134; 23%), 'high-intermediate' (n=129; 23%) and 'high' (n=140; 24%) risk. R-IPI groups were indicated with 'very good' (n=59; 10%), 'good' (n=245; 43%) and 'poor' (n=269; 47%) prognosis. Ten-year OS and PFS rates were 51 and 72%, respectively; median OS was 124 months and median PFS was not reached. Ten-year OS rates were 80 and 87% in low-risk and 'very good' prognosis groups, respectively, and 30 and 37% in high-risk and poor prognosis patients, respectively. This analysis of patients with DLBCL indicated that many patients treated with R-CHOP and R-CHOP-like regimens in the real-world setting have excellent outcomes.

Fabrication of porous calcite using chopped nylon fiber and its evaluation using rats.

PubMed

Ishikawa, Kunio; Tram, Nguyen Xuan Thanh; Tsuru, Kanji; Toita, Riki

2015-02-01

Although porous calcite has attracted attention as bone substitutes, limited studies have been made so far. In the present study, porous calcite block was fabricated by introducing chopped nylon fiber as porogen. Ca(OH)2 powder containing 10 wt% chopped nylon fiber was compacted at 150 MPa, and sintered to burn out the fiber and to carbonate the Ca(OH)2 under stream of 1:2 O2-CO2. Sintering of Ca(OH)2 at 750 °C or lower temperature resulted in incomplete burning out of the fiber whereas sintering at 800 °C or higher temperature resulted in the formation of CaO due to the thermal decomposition of Ca(OH)2. However, sintering at 770 °C resulted in complete burning out of the fiber and complete carbonation of Ca(OH)2 to calcite without forming CaO. Macro- and micro-porosities of the porous calcite were approximately 23 and 16%, respectively. Diameter of the macropores was approximately 100 μm which is suitable for bone tissue penetration. Porous calcite block fabricated by this method exhibited good tissue response when implanted in the bone defect in femur of 12-weeks-old rat. Four weeks after implantation, bone bonded on the surface of calcite. Furthermore, bone tissue penetrated interior to the macropore at 8 weeks. These results demonstrated the good potential value of porous calcite as artificial bone substitutes.

SOFIA pointing and chopping: performance and prospect

NASA Astrophysics Data System (ADS)

Reinacher, Andreas; Lammen, Yannick; Graf, Friederike; Jakob, Holger

2016-09-01

The Stratospheric Observatory for Infrared Astronomy (SOFIA) is a 2.5m infrared telescope built into a Boeing 747 SP. In 2014 SOFIA reached its Full Operational Capability milestone and nowadays takes off about three times a week to observe the infrared sky from altitudes above most of the atmosphere's water vapor content. Despite reaching this major milestone the work to improve the observatory's performance is continuing in many areas. This paper focuses on the telescope's current pointing and chopping performance and gives an overview over the ongoing and foreseen work to further improve in those two areas. Pointing performance as measured with the fast focal plane camera in flight is presented and based on that data it is elaborated how and in which frequency bands a further reduction of image jitter might be achieved. One contributor to the remaining jitter as well as the major actuator to reduce jitter with frequencies greater than 5 Hz is SOFIA's Secondary Mirror Assembly (SMA) or Chopper. As-is SMA jitter and chopping performance data as measured in flight is presented as well as recent improvements to the position sensor cabling and calibration and their effect on the SMA's pointing accuracy. Furthermore a brief description of a laboratory mockup of the SMA is given and the intended use of this mockup to test major hardware changes for further performance improvement is explained.

Fibrates upregulate TRB3 in lymphocytes independent of PPAR alpha by augmenting CCAAT/enhancer-binding protein beta (C/EBP beta) expression.

PubMed

Selim, Erin; Frkanec, Julie T; Cunard, Robyn

2007-02-01

Fibrates, which function by binding and activating peroxisome proliferator-activated receptor alpha (PPARalpha), have been used successfully to treat hyperlipidemia and atherosclerosis. Increasing evidence suggests that in addition to their lipid lowering activities these medications also function as immunosuppressive agents. Tribbles is a Drosophila protein that slows cell cycle progression, and its mammalian homolog, TRB3 interferes with insulin-induced activation of AKT. In these studies we demonstrate that fibrates upregulate TRB3 expression in mitogen-activated lymphocytes. Interestingly, in lymphocytes fibrates augment TRB3 expression in both PPARalpha wildtype and knockout mice, suggesting that upregulation of this protein occurs in a PPARalpha-independent manner. Fibrates activate a proximal TRB3 promoter construct and mutation or partial deletion of a potential PPAR response element does not alter the ability of fibrates to drive TRB3 expression. Subsequent studies reveal that fibrates upregulate C/EBPbeta and CHOP in lymphocytes and mutation of potential C/EBPbeta and CHOP consensus sequences abrogates the ability of fibrates to upregulate TRB3 promoter activity. Accordingly, fibrates enhance the recruitment of C/EBPbeta and CHOP to the proximal TRB3 promoter. Finally, TRB3 expression in lymphocytes induces G2 cell cycle delay and cellular depletion. These studies outline a novel PPARalpha-independent mechanism of action of fibrates and document for the first time the expression of TRB3 in activated lymphocytes.

AAV delivery of GRP78/BiP promotes adaptation of human RPE cell to ER stress.

PubMed

Ghaderi, Shima; Ahmadian, Shahin; Soheili, Zahra-Soheila; Ahmadieh, Hamid; Samiei, Shahram; Kheitan, Samira; Pirmardan, Ehsan R

2018-02-01

Adeno associated virus (AAV)-mediated gene delivery of GRP78 (78 kDa glucose-regulated protein) attenuates the condition of endoplasmic reticulum (ER) stress and prevents apoptotic loss of photoreceptors in Retinitis pigmentosa (RP) rats. In the current study we overexpressed Grp78 with the help of AAV-2 in primary human retinal pigmented epithelium (hRPE) cell cultures and examined its effect on cell response to ER stress. The purpose of this work was studying potential stimulating effect of GRP78 on adaptation/pro-survival of hRPE cells under ER stress, as an in vitro model for RPE degeneration. To investigate the effect of Grp78 overexpression on unfolded protein response (UPR) markers under ER stress, hRPE primary cultures were transduced by recombinant virus rAAV/Grp78, and treated with ER stressor drug, tunicamycin. Expression changes of four UPR markers including GRP78, PERK, ATF6α, and GADD153/CHOP, were assessed by real-time PCR and western blotting. We found that GRP78 has a great contribution in modulation of UPR markers to favor adaptive response in ER-stressed hRPE cells. In fact, GRP78 overexpression affected adaptation and apoptotic phases of early UPR, through enhancement of two master regulators/ER stress sensors (PERK and ATF6α) and down-regulation of a key pro-apoptotic cascade activator (GADD153/CHOP). Together these findings demonstrate the promoting effect of GRP78 on adaptation/pro-survival of hRPE cells under ER stress. This protein with anti-apoptotic actions in the early UPR and important role in cell fate regulation, can be recruited as a useful candidate for future investigations of RPE degenerative diseases. © 2017 Wiley Periodicals, Inc.

Exogenous FABP4 induces endoplasmic reticulum stress in HepG2 liver cells.

PubMed

Bosquet, Alba; Guaita-Esteruelas, Sandra; Saavedra, Paula; Rodríguez-Calvo, Ricardo; Heras, Mercedes; Girona, Josefa; Masana, Lluís

2016-06-01

Fatty acid binding protein 4 (FABP4) is an intracellular fatty acid (FA) carrier protein that is, in part, secreted into circulation. Circulating FABP4 levels are increased in obesity, diabetes and other insulin resistance (IR) diseases. FAs contribute to IR by promoting endoplasmic reticulum stress (ER stress) and altering the insulin signaling pathway. The effect of FABP4 on ER stress in the liver is not known. The aim of this study was to investigate whether exogenous FABP4 (eFABP4) is involved in the lipid-induced ER stress in the liver. HepG2 cells were cultured with eFABP4 (40 ng/ml) with or without linoleic acid (LA, 200 μM) for 18 h. The expression of ER stress-related markers was determined by Western blotting (ATF6, EIF2α, IRE1 and ubiquitin) and real-time PCR (ATF6, CHOP, EIF2α and IRE1). Apoptosis was studied by flow cytometry using Annexin V-FITC and propidium iodide staining. eFABP4 increased the ER stress markers ATF6 and IRE1 in HepG2 cells. This effect led to insulin resistance mediated by changes in AKT and JNK phosphorylation. Furthermore, eFABP4 significantly induced both apoptosis, as assessed by flow cytometry, and CHOP expression, without affecting necrosis and ubiquitination. The presence of LA increased the ER stress response induced by eFABP4. eFABP4, per se, induces ER stress and potentiates the effect of LA in HepG2 cells, suggesting that FABP4 could be a link between obesity-associated metabolic abnormalities and hepatic IR mechanisms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Botulism

MedlinePlus

... potatoes cooked in foil, carrot juice, and chopped garlic in oil. Infant botulism occurs when a baby ... the refrigerator, not at room temperature. Oils with garlic or other herbs should also be refrigerated as ...

Chopping Copy.

ERIC Educational Resources Information Center

Bush, Don

1994-01-01

Discusses ways an editor can cut out words to help the reader understand quickly. Discusses dead wood, redundancy, redundancy in thought, smothered verbs, false precision, editing and academia, and making copy smoother. (SR)

10 CFR 75.4 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... uranium or enriching uranium in the isotope 235, zirconium tubes, heavy water or deuterium, nuclear-grade..., irradiated fuel element chopping machines, and hot cells. Nuclear fuel cycle-related research and development...

10 CFR 75.4 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

...); (3) A fuel fabrication plant; (4) An enrichment plant or isotope separation plant for the separation..., irradiated fuel element chopping machines, and hot cells. Nuclear fuel cycle-related research and development...

10 CFR 75.4 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

...); (3) A fuel fabrication plant; (4) An enrichment plant or isotope separation plant for the separation..., irradiated fuel element chopping machines, and hot cells. Nuclear fuel cycle-related research and development...

Jumpin' Jambalaya

MedlinePlus

... 2 tsp cayenne pepper 3 Tbsp finely chopped parsley Directions Wash chicken and pat dry. Cut the ... will take less time to cook). Stir in parsley and serve warm. Find more delicious heart healthy ...

Golfer's Elbow

MedlinePlus

... your elbow can cause golfer's elbow. This includes painting, raking, hammering, chopping wood, using a computer, doing ... using older golfing irons, consider upgrading to lighter graphite clubs. If you play tennis, a racket with ...

Design and analysis of optically pumped submillimeter waveguide maser amplifiers and oscillators

NASA Technical Reports Server (NTRS)

Galantowicz, T. A.

1975-01-01

The design and experimental measurements are described of an optically pumped far-infrared (FIR) waveguide maser; preliminary measurements on a FIR waveguide amplifier are presented. The FIR maser was found to operate satisfactorily in a chopped CW mode using either methanol (CH3OH) or acetonitrile (CH3CN) as the active molecule. Two other gases, difluoroethane and difluoroethylene, produced an unstable output with high threshold and low output power when operated in the chopped CW mode. Experimental measurements include FIR output versus cavity length, output beam pattern, output power versus pressure, and input power. The FIR output was the input to an amplifier which was constructed similar to the oscillator. An increase of 10% in output power was noted on the 118.8 microns line of methanol.

The Use of Basalt, Basalt Fibers and Modified Graphite for Nuclear Waste Repository - 12150

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

Gulik, V.I.; Biland, A.B.

2012-07-01

New materials enhancing the isolation of radioactive waste and spent nuclear fuel are continuously being developed.. Our research suggests that basalt-based materials, including basalt roving chopped basalt fiber strands, basalt composite rebar and materials based on modified graphite, could be used for enhancing radioactive waste isolation during the storage and disposal phases and maintaining it during a significant portion of the post-closure phase. The basalt vitrification process of nuclear waste is a viable alternative to glass vitrification. Basalt roving, chopped basalt fiber strands and basalt composite rebars can significantly increase the strength and safety characteristics of nuclear waste and spentmore » nuclear fuel storages. Materials based on MG are optimal waterproofing materials for nuclear waste containers. (authors)« less

Power converter

NASA Technical Reports Server (NTRS)

Black, J. M. (Inventor)

1981-01-01

A dc-to-dc converter employs four transistor switches in a bridge to chop dc power from a source, and a voltage multiplying diode rectifying ladder network to rectify and filter the chopped dc power for delivery to a load. The bridge switches are cross coupled in order for diagonally opposite pairs to turn on and off together using RC networks for the cross coupling to achieve the mode of operation of a free running multivibrator, and the diode rectifying ladder is configured to operate in a push-pull mode driven from opposite sides of the multivibrator outputs of the ridge switches. The four transistor switches provide a square-wave output voltage which as a peak-to-peak amplitude that is twice the input dc voltage, and is thus useful as a dc-to-ac inverter.

High-fructose diet is as detrimental as high-fat diet in the induction of insulin resistance and diabetes mediated by hepatic/pancreatic endoplasmic reticulum (ER) stress.

PubMed

Balakumar, M; Raji, L; Prabhu, D; Sathishkumar, C; Prabu, P; Mohan, V; Balasubramanyam, M

2016-12-01

In the context of high human consumption of fructose diets, there is an imperative need to understand how dietary fructose intake influence cellular and molecular mechanisms and thereby affect β-cell dysfunction and insulin resistance. While evidence exists for a relationship between high-fat-induced insulin resistance and metabolic disorders, there is lack of studies in relation to high-fructose diet. Therefore, we attempted to study the effect of different diets viz., high-fat diet (HFD), high-fructose diet (HFS), and a combination (HFS + HFD) diet on glucose homeostasis and insulin sensitivity in male Wistar rats compared to control animals fed with normal pellet diet. Investigations include oral glucose tolerance test, insulin tolerance test, histopathology by H&E and Masson's trichrome staining, mRNA expression by real-time PCR, protein expression by Western blot, and caspase-3 activity by colorimetry. Rats subjected to high-fat/fructose diets became glucose intolerant, insulin-resistant, and dyslipidemic. Compared to control animals, rats subjected to different combination of fat/fructose diets showed increased mRNA and protein expression of a battery of ER stress markers both in pancreas and liver. Transcription factors of β-cell function (INSIG1, SREBP1c and PDX1) as well as hepatic gluconeogenesis (FOXO1 and PEPCK) were adversely affected in diet-induced insulin-resistant rats. The convergence of chronic ER stress towards apoptosis in pancreas/liver was also indicated by increased levels of CHOP mRNA & increased activity of both JNK and Caspase-3 in rats subjected to high-fat/fructose diets. Our study exposes the experimental support in that high-fructose diet is equally detrimental in causing metabolic disorders.

Combination of romidepsin with cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated patients with peripheral T-cell lymphoma: a non-randomised, phase 1b/2 study.

PubMed

Dupuis, Jehan; Morschhauser, Franck; Ghesquières, Hervé; Tilly, Hervé; Casasnovas, Olivier; Thieblemont, Catherine; Ribrag, Vincent; Bossard, Céline; Le Bras, Fabien; Bachy, Emmanuel; Hivert, Bénédicte; Nicolas-Virelizier, Emmanuelle; Jardin, Fabrice; Bastie, Jean-Noel; Amorim, Sandy; Lazarovici, Julien; Martin, Antoine; Coiffier, Bertrand

2015-04-01

Romidepsin is a histone deacetylase inhibitor approved in the USA for patients with recurrent or refractory peripheral T-cell lymphoma and has shown activity in this setting with mainly haematological and gastrointestinal toxicity. Although it has limited efficacy, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy is widely used for treatment of de-novo peripheral T-cell lymphoma. We aimed to assess the safety, tolerability, and activity of romidepsin combined with CHOP in patients with previously untreated disease. We enrolled patients aged 18-80 years with histologically proven, previously untreated, peripheral T-cell lymphoma (Eastern Cooperative Oncology Group performance status ≤2) into a dose-escalation (phase 1b) and expansion (phase 2) study at nine Lymphoma Study Association centres in France. In the dose-escalation phase, we allocated consecutive blocks of three participants to receive eight 3 week cycles of CHOP (intravenous cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), and vincristine 1.4 mg/m(2) [maximum 2 mg] on day 1 and oral prednisone 40 mg/m(2) on days 1-5) in association with varying doses of romidepsin. The starting dose was 10 mg/m(2) intravenously on days 1 and 8 of each cycle, and we used a 3 + 3 design. We assessed dose-limiting toxicities only during the first two cycles. The primary endpoint was to determine the recommended dose for the combination. For the phase 2 study, we aimed to increase the cohort of patients receiving the recommended dose to a total of 25 patients. Patients were assessed for safety outcomes at least twice per cycle according to the Common Terminology Criteria for Adverse Events, version 4.0. Safety analyses included all patients who received at least one dose of romidepsin and CHOP. This trial is registered at the European Clinical Trials Database (EudraCT), number 2010-020962-91 and ClinicalTrials.gov, number NCT01280526. Between Jan 13, 2011, and May 21, 2013, we enrolled 37 patients (18 treated in phase 1b and 19 patients in phase 2). Three of six patients initially treated at 10 mg/m(2) had a dose-limiting toxicity. The dose-escalation committee decided to modify the study protocol to redefine dose-limiting toxicities with regard to haematological toxicity. Three patients were treated with 8 mg/m(2) of romidepsin, an additional three at 10 mg/m(2) (one dose-limiting toxicity), and six patients at 12 mg/m(2) (three dose-limiting toxicities). We chose romidepsin 12 mg/m(2) as the recommended dose for phase 2. Of the 37 patients treated, three had early cardiac events (two myocardial infarctions and one acute cardiac failure). No deaths were attributable to toxicity. 25 (68%) of 37 patients had at least one serious adverse event. Overall, the most frequent serious adverse events were febrile neutropenia (five [14%] of 37 patients), physical health deterioration (five [14%]), lung infection (four [11%]), and vomiting (three [8%]). 33 (89%) of patients had grade 3-4 neutropenia, and 29 (78%) had grade 3-4 thrombocytopenia. Romidepsin can be combined with CHOP but this combination should now be tested in comparison to CHOP alone in a randomised trial. Celgene. Copyright © 2015 Elsevier Ltd. All rights reserved.

VizieR Online Data Catalog: PACS photometry of FIR faint stars (Klaas+, 2018)

NASA Astrophysics Data System (ADS)

Klaas, U.; Balog, Z.; Nielbock, M.; Mueller, T. G.; Linz, H.; Kiss, Cs.

2018-01-01

70, 100 and 160um photometry of FIR faint stars from PACS scan map and chop/nod measurements. For scan maps also the photometry of the combined scan and cross-scan maps (at 160um there are usually two scan and cross-scan maps each as complements to the 70 and 100um maps) is given. Note: Not all stars have measured fluxes in all three filters. Scan maps: The main observing mode was the point-source mini-scan-map mode; selected scan map parameters are given in column mparam. An outline of the data processing using the high-pass filter (HPF) method is presented in Balog et al. (2014ExA....37..129B). Processing proceeded from Herschel Science Archive SPG v13.1.0 level 1 products with HIPE version 15 build 165 for 70 and 100um maps and from Herschel Science Archive SPG v14.2.0 level 1 products with HIPE version 15 build 1480 for 160um maps. Fluxes faper were obtained by aperture photometry with aperture radii of 5.6, 6.8 and 10.7 arcsec for the 70, 100 and 160um filter, respectively. Noise per pixel sigpix was determined with the histogram method, described in this paper, for coverage values greater than or equal to 0.5*maximum coverage. The number of map pixels (1.1, 1.4, and 2.1 arcsec pixel size, respectively) inside the photometric aperture is Naper = 81.42, 74.12, and 81.56, respectively. The corresponding correction factors for correlated noise are fcorr = 3.13, 2.76, and 4.12, respectively. The noise for the photometric aperture is calculated as sig_aper=sqrt(Naper)*fcorr*sigpix. Signal-to-noise ratios are determined as S/N=faper/sigaper. Aperture-correction factors to derive the total flux are caper = 1.61, 1.56 and 1.56 for the 70, 100 and 160um filter, respectively. Applied colour-correction factors for a 5000K black-body SED are cc = 1.016, 1.033, and 1.074 for the 70, 100, and 160um filter, respectively. The final stellar flux is derived as fstar=faper*caper/cc. Maximum and minimum FWHM of the star PSF are determined by an elliptical fit of the intensity profile. Chop/nod observations: The chop/nod point-source mode is described in this paper. An outline of the data processing is presented in Nielbock et al. (2013ExA....36..631N). Processing proceeded from Herschel Science Archive SPG v11.1.0 level 1 products with HIPE version 13 build 2768. Gyro correction was applied for most of the cases to improve the pointing reconstruction performance. Fluxes faper were obtained by aperture photometry with aperture radii of 5.6, 6.8 and 10.7 arcsec for the 70, 100 and 160um filter, respectively. Noise per pixel sigpix was determined with the histogram method, described in this paper, for coverage values greater than or equal to 0.5*maximum coverage. The number of map pixels (1.1, 1.4, and 2.1 arcsec pixel size, respectively) inside the photometric aperture is Naper = 81.42, 74.12, and 81.56, respectively. The corresponding correction factors for correlated noise are fcorr = 6.33, 4.22, and 7.81, respectively. The noise for the photometric aperture is calculated as sigaper=sqrt(Naper)*fcorr*sigpix. Signal-to-noise ratios are determined as S/N=faper/sigaper. Aperture-correction factors to derive the total flux are caper = 1.61, 1.56 and 1.56 for the 70, 100 and 160um filter, respectively. Applied colour-correction factors for a 5000K black-body SED are cc = 1.016, 1.033, and 1.074 for the 70, 100, and 160um filter, respectively. Maximum and minimum FWHM of the star PSF are determined by an elliptical fit of the intensity profile. (7 data files).

Interaction between the physical form of the starter feed and straw provision on growth performance of Holstein calves.

PubMed

Terré, M; Castells, Ll; Khan, M A; Bach, A

2015-02-01

Two experiments were conducted to assess the effect of physical form of a starter feed with or without straw supplementation on growth performance of Holstein calves. In experiment 1, a total of 32 calves were randomly assigned at 7 d of age to texturized starter feed (containing rolled barley, corn, and oats) without straw, texturized starter feed with chopped straw, and pelleted starter feed with chopped straw. All calves were offered 4 L of pasteurized whole milk twice daily from 7 to 35 d of age, 2 L of milk twice daily from 36 to 42 d of age, and 2 L of milk from 43 to 49 d of age. Animals were weaned at 50 d of age, and the study finished when calves were 63 d old. In experiment 2, a total of 60 calves (8 d of age) were randomly assigned to texturized starter feed (containing whole corn) without straw, pelleted starter feed without straw, and pelleted starter feed with chopped straw. All calves were offered the same milk replacer (MR; 23% crude protein and 19.5 fat) at 11% dry matter concentration, 4 L/d of MR until 14 d of age, 6 L/d of MR from 14 to 37 d, 3 L/d of MR from 38 to 44 d, and 1.5 L/d of MR from 45 to 52 d of age. The experiment finished when calves were 58 d old (1 wk after weaning). Rumen liquid pH was measured after weaning. In both studies, calves were individually housed in pens on sawdust bedding and starter feed and chopped straw were offered free choice in separate buckets. In experiment 1, starter feed and straw intake and growth did not differ among treatments. However, calves receiving straw showed a greater rumen pH compared with those not receiving straw. In experiment 2, pelleted started feed supplemented with straw fostered an increase in solid feed intake (as percentage of body weight) compared with a pelleted or texturized starter feed without straw supplementation. However, calves that received the texturized starter feed containing whole corn had rumen pH similar to those fed a pelleted starter feed with straw. Feeding a texturized starter feed containing rolled barley, corn, and oats (with or without straw provision) was not able to maintain rumen pH or promote growth and intake compared with offering a pelleted starter feed with chopped straw. However, when whole corn was used in the texturized starter feed, rumen pH was equivalent to that obtained with a pelleted starter feed and straw supplementation. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Cooking without salt

MedlinePlus

... onion and garlic powder. Try different types of pepper, including black, white, green, and red. Experiment with ... and spice, try: Dry mustard Fresh chopped hot peppers A sprinkle of paprika, cayenne pepper, or dried ...

Silica nanoparticles mediated neuronal cell death in corpus striatum of rat brain: implication of mitochondrial, endoplasmic reticulum and oxidative stress

NASA Astrophysics Data System (ADS)

Parveen, Arshiya; Rizvi, Syed Husain Mustafa; Mahdi, Farzana; Tripathi, Sandeep; Ahmad, Iqbal; Shukla, Rajendra K.; Khanna, Vinay K.; Singh, Ranjana; Patel, Devendra K.; Mahdi, Abbas Ali

2014-11-01

Extensive uses of silica nanoparticles (SiNPs) in biomedical and industrial fields have increased the risk of exposure, resulting concerns about their safety. We focussed on some of the safety aspects by studying neurobehavioural impairment, oxidative stress (OS), neurochemical and ultrastructural changes in corpus striatum (CS) of male Wistar rats exposed to 80-nm SiNPs. Moreover, its role in inducing mitochondrial and endoplasmic reticulum (ER) stress-mediated neuronal apoptosis was also investigated. The results demonstrated impairment in neurobehavioural indices, and a significant increase in lipid peroxide levels (LPO), hydrogen peroxide (H2O2), superoxide (O2 -) and protein carbonyl content, whereas there was a significant decrease in the activities of the enzymes, manganese superoxide dismutase (Mn SOD), glutathione peroxidase (GPx), catalase (CAT) and reduced glutathione (GSH) content, suggesting impaired antioxidant defence system. Protein (cytochrome c, Bcl-2, Bax, p53, caspase-3, caspase 12 and CHOP/Gadd153) and mRNA (Bcl-2, Bax, p53 and CHOP/Gadd153, cytochrome c) expression studies of mitochondrial and ER stress-related apoptotic factors suggested that both the cell organelles were involved in OS-mediated apoptosis in treated rat brain CS. Moreover, electron microscopic studies clearly showed mitochondrial and ER dysfunction. In conclusion, the result of the study suggested that subchronic SiNPs' exposure has the potential to alter the behavioural activity and also to bring about changes in biochemical, neurochemical and ultrastructural profiles in CS region of rat brain. Furthermore, we also report SiNPs-induced apoptosis in CS, through mitochondrial and ER stress-mediated signalling.

Aging and sleep deprivation induce the unfolded protein response in the pancreas: implications for metabolism

PubMed Central

Naidoo, Nirinjini; Davis, James G; Zhu, Jingxu; Yabumoto, Maya; Singletary, Kristan; Brown, Marishka; Galante, Raymond; Agarwal, Beamon; Baur, Joseph A

2014-01-01

Sleep disruption has detrimental effects on glucose metabolism through pathways that remain poorly defined. Although numerous studies have examined the consequences of sleep deprivation (SD) in the brain, few have directly tested its effects on peripheral organs. We examined several tissues in mice for induction of the unfolded protein response (UPR) following acute SD. In young animals, we found a robust induction of BiP in the pancreas, indicating an active UPR. At baseline, pancreata from aged animals exhibited a marked increase in a pro-apoptotic transcription factor, CHOP, that was amplified by SD, whereas BiP induction was not observed, suggesting a maladaptive response to cellular stress with age. Acute SD increased plasma glucose levels in both young and old animals. However, this change was not overtly related to stress in the pancreatic beta cells, as plasma insulin levels were not lower following acute SD. Accordingly, animals subjected to acute SD remained tolerant to a glucose challenge. In a chronic SD experiment, young mice were found to be sensitized to insulin and have improved glycemic control, whereas aged animals became hyperglycemic and failed to maintain appropriate plasma insulin concentrations. Our results show that both age and SD cooperate to induce the UPR in pancreatic tissue. While changes in insulin secretion are unlikely to play a major role in the acute effects of SD, CHOP induction in pancreatic tissues suggests that chronic SD may contribute to the loss or dysfunction of endocrine cells and that these effects may be exacerbated by normal aging. PMID:24102714

Prognostic significance of clinical presentation, induction and rescue treatment in 42 cases of canine centroblastic diffuse large B-cell multicentric lymphoma in the United Kingdom.

PubMed

Davies, O; Szladovits, B; Polton, G; Garden, O A; Leo, C; Lara-Garcia, A

2018-06-01

Canine lymphoma is a heterogeneous group of diseases and many previous studies have evaluated the response of a mixed population of lymphoma cases to one specific treatment protocol. The aim of this retrospective study was to describe the outcome and prognostic factors in 42 cases of multicentric centroblastic diffuse large B-cell lymphoma treated with either a COP-type (35%) or CHOP-type (64%) induction chemotherapy. The objective response rate to induction therapy was 94%; entire dogs had a greater rate of complete vs partial remissions than neutered dogs (P = .017). Median progression-free survival for the first remission (PFS1) was 182 days; absence of anaemia at diagnosis (P = .002) and pretreatment neutrophil:lymphocyte ratio (NLR) below 9.44 (P = .015) were independently predictive of longer PFS1. Fifty-eight percent of dogs received rescue protocols with an objective response rate of 81%; 31% of dogs received further rescue protocols (up to a total of 5) and the median number of protocols administered were 2. Median overall survival (OS) was 322 days, the 1-year survival rate was 38% and the 2-year survival rate was 9%. Lymphocyte:monocyte ratio above 1.43 (P = .031), NLR below 11.44 (P = .009), the combination of induction and rescue therapy (P = .030) and the total number of doxorubicin doses used (P = .002) were independently predictive of longer OS. Use of a COP-type protocol induction compared with CHOP did not undermine OS providing doxorubicin was used as rescue therapy. © 2017 John Wiley & Sons Ltd.

MyPlate Food Guide

MedlinePlus

... that mixes different foods together, like a salad, pasta dish, stew, or stir-fry? That's when you ... example, a spaghetti dish could be whole-wheat pasta with a meatball, tossed with chopped tomato along ...

Structure-activity relationship of piperine and its synthetic amide analogs for therapeutic potential to prevent experimentally induced ER stress in vitro.

PubMed

Hammad, Ayat S; Ravindran, Sreenithya; Khalil, Ashraf; Munusamy, Shankar

2017-05-01

Endoplasmic reticulum (ER) is the key organelle involved in protein folding and maturation. Emerging studies implicate the role of ER stress in the development of chronic kidney disease. Thus, there is an urgent need for compounds that could ameliorate ER stress and prevent CKD. Piperine and its analogs have been reported to exhibit multiple pharmacological activities; however, their efficacy against ER stress in kidney cells has not been studied yet. Hence, the goal of this study was to synthesize amide-substituted piperine analogs and screen them for pharmacological activity to relieve ER stress using an in vitro model of tunicamycin-induced ER stress using normal rat kidney (NRK-52E) cells. Five amide-substituted piperine analogs were synthesized and their chemical structures were elucidated by pertinent spectroscopic techniques. An in vitro model of ER stress was developed using tunicamycin, and the compounds of interest were screened for their effect on cell viability, and the expression of ER chaperone GRP78, the pro-apoptotic ER stress marker CHOP, and apoptotic caspases 3 and 12 (via western blotting). Our findings indicate that exposure to tunicamycin (0.5 μg/mL) for 2 h induces the expression of GRP78 and CHOP, and apoptotic markers (caspase-3 and caspase-12) and causes a significant reduction in renal cell viability. Pre-treatment of cells with piperine and its cyclohexylamino analog decreased the tunicamycin-induced upregulation of GRP78 and CHOP and cell death. Taken together, our findings demonstrate that piperine and its analogs differentially regulate ER stress, and thus represent potential therapeutic agents to treat ER stress-related renal disorders. Graphical Abstract Piperine (PIP) reduces the expression of ER stress markers (GRP78 and CHOP) induced by pathologic stimuli and consequently decreases the activation of apoptotic caspase-12 and caspase-3; all of which contributes to its chemical chaperone and cytoprotective properties to protect renal cells against ER stress and ER stress-induced cell death, and would ultimately prevent the development of chronic kidney disease.

Technical note: use of belt grill cookery and slice shear force for assessment of pork longissimus tenderness.

PubMed

Shackelford, S D; Wheeler, T L; Koohmaraie, M

2004-01-01

The present experiments were conducted to determine whether improved beef longissimus shear force methodology could be used to assess pork longissimus tenderness. Specifically, three experiments were conducted to: 1) determine the effect of belt grill (BG) cookery on repeatability of pork longissimus Warner-Bratzler shear force (WBSF), 2) compare the correlation of WBSF and slice shear force (SSF) with trained sensory panel tenderness ratings, and 3) estimate the repeatability of pork longissimus SSF for chops cooked with a BG. In Exp. 1 and 2, the longissimus was removed from the left side of each carcass (Exp. 1, n = 25; Exp. 2, n = 23) at 1 d postmortem and immediately frozen to maximize variation in tenderness. In Exp. 1, chops were cooked with either open-hearth electric broilers (OH) or BG, and WBSF was measured. Percentage of cooking loss was lower (P < 0.001) and less variable for chops cooked with a BG (23.2%; SD = 1.7%) vs. OH (27.6%; SD = 3.0%). Estimates of the repeatability of WBSF were similar for chops cooked with OH (0.61) and BG (0.59). Although significant (P < 0.05), differences in WBSF (4.1 vs. 3.9 kg) between cooking methods accounted for less than 5% of the total variation in WBSF. In Exp. 2, the correlation of SSF (r = -0.72; P < 0.001) with trained sensory panel tenderness ratings was slightly stronger than the correlation of WBSF (r = -0.66; P < 0.001) with trained sensory panel tenderness ratings, indicating that the two methods had a similar ability to predict tenderness ratings. In Exp. 3, duplicate samples from 372 carcasses at 2 and 10 d postmortem were obtained, cooked with BG, and SSF was determined. The repeatability of SSF was 0.90, which is comparable to repeatability estimates for beef and lamb. Use of BG cookery and SSF could facilitate the collection of accurate pork longissimus tenderness data. Time and labor savings associated with BG cookery and the SSF technique should help to decrease research costs.

Genetics Home Reference: CHOPS syndrome

MedlinePlus

... complex (SEC) and MLL in development and disease. Genes Dev. 2011 Apr 1;25(7):661-72. doi: 10.1101/gad.2015411. Review. Citation ... are genome editing and CRISPR-Cas9? What is precision medicine? What ...

Acute care. Who's for the chop.

PubMed

Gainsbury, Sally

Sixty-eight trusts have barely begun the process towards foundation status. Financial struggles are a major cause of failure to make progress. For some trusts, merger, takeover or franchise may be the final outcome.

Performance of 22.4-kW nonlaminated-frame dc series motor with chopper controller. [a dc to dc voltage converter

NASA Technical Reports Server (NTRS)

Schwab, J. R.

1979-01-01

Performance data obtained through experimental testing of a 22.4 kW traction motor using two types of excitation are presented. Ripple free dc from a motor-generator set for baseline data and pulse width modulated dc as supplied by a battery pack and chopper controller were used for excitation. For the same average values of input voltage and current, the motor power output was independent of the type of excitation. However, at the same speeds, the motor efficiency at low power output (corresponding to low duty cycle of the controller) was 5 to 10 percentage points lower on chopped dc than on ripple free dc. The chopped dc locked-rotor torque was approximately 1 to 3 percent greater than the ripple free dc torque for the same average current.

3D Representative Volume Element Reconstruction of Fiber Composites via Orientation Tensor and Substructure Features

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

Li, Yi; Chen, Wei; Xu, Hongyi

To provide a seamless integration of manufacturing processing simulation and fiber microstructure modeling, two new stochastic 3D microstructure reconstruction methods are proposed for two types of random fiber composites: random short fiber composites, and Sheet Molding Compounds (SMC) chopped fiber composites. A Random Sequential Adsorption (RSA) algorithm is first developed to embed statistical orientation information into 3D RVE reconstruction of random short fiber composites. For the SMC composites, an optimized Voronoi diagram based approach is developed for capturing the substructure features of SMC chopped fiber composites. The proposed methods are distinguished from other reconstruction works by providing a way ofmore » integrating statistical information (fiber orientation tensor) obtained from material processing simulation, as well as capturing the multiscale substructures of the SMC composites.« less

Mechanistic elucidation of the antitumor properties of withaferin A in breast cancer

PubMed Central

Nagalingam, Arumugam; Kuppusamy, Panjamurthy; Singh, Shivendra V.; Sharma, Dipali; Saxena, Neeraj K.

2014-01-01

Withaferin A (WFA) is a steroidal lactone with antitumor effects manifested at multiple levels which are mechanistically obscure. Using a phospho-kinase screening array, we discovered that WFA activated phosphorylation of the S6 kinase RSK in breast cancer cells. Pursuing this observation, we defined activation of ERK-RSK and Elk1-CHOP kinase pathways in upregulating transcription of the death receptor DR5. Through this route, WFA acted as an effective DR5 activator capable of potentiating the biological effects of celecoxib, etoposide and TRAIL. Accordingly, WFA treatment inhibited breast tumor formation in xenograft and MMTV-neu mouse models in a manner associated with activation of the ERK/RSK axis, DR5 upregulation and elevated nuclear accumulation of Elk1 and CHOP. Together, our results offer mechanistic insight into how WFA inhibits breast tumor growth. PMID:24732433

ASCO 2017 meeting summary: updates to practice-changing studies in untreated non-Hodgkin lymphoma

PubMed Central

Laneuville, P.; Larouche, J.F.; Tosikyan, A.; Christofides, A.

2017-01-01

The 2017 annual meeting of the American Society of Clinical Oncology took place in Chicago, Illinois, 2–6 June. At the meeting, results from key studies in the first-line treatment of indolent non-Hodgkin lymphoma (inhl) were presented. Of those studies, two were selected for oral presentations: 9-year follow-up data from the stil nhl1 trial, which compared the efficacy and safety of bendamustine plus rituximab (br) with those of rituximab plus cyclophosphamide–vincristine–prednisone–doxorubicin (r-chop); and 5-year follow-up data from the bright study, which compared br with r-chop and r-cvp (rituximab plus cyclophosphamide–vincristine–prednisone) combined. Our meeting report describes the foregoing studies and includes interviews with key investigators, plus commentaries from three Quebec hematologists on the potential effects for Canadian practice.

Coatings with a Mole-hill Structure of Nanoparticle-Raspberry Containers for Surfaces with Abrasion-Refreshable Reservoir Functionality.

PubMed

Ballweg, Thomas; Gellermann, Carsten; Mandel, Karl

2015-11-11

Active silica nanoparticle-based raspberry-like container depots for agents such as antimicrobial substances are presented. The nano raspberry-containers are integrated into coatings in a way that they form a mole-hill structure; i.e., they are partly standing out of the coating. As an application example, it is demonstrated that the containers can be filled with antimicrobially active agents such as nano ZnO or Ag or organic molecules such as thymol. It is demonstrated that the containers can be partly chopped-off via abrasion by rubbing over the surface. This mechanism proves to be an attractive approach to render surfaces refreshable. A first proof of principle for antimicrobial activity of the intact containers in the coatings and the abrasion treated, chopped-off (and thereby reactivated) containers is demonstrated.

Further studies on staphylococci in meats. III. Occurrence and characteristics of coagulase-positive strains from a variety of nonfrozen market cuts.

PubMed

JAY, J M

1962-05-01

From 34 retail grocery stores and meat markets, 209 samples of nonfrozen meats were obtained and analyzed for coagulase-positive Staphylococcus aureus, employing six selective media. Sixty-seven (38.7%) of 173 samples obtained from 27 stores yielded S. aureus. No coagulase-positive S. aureus was isolated from 36 samples obtained from 7 of the stores. The 67 meats yielded 272 isolates from 10 different kinds of meats. There were 162 physiological strains represented when classified by store and 36 strains classified without regard to store of origin. The larger stores yielded fewer meats with staphylococci than the smaller stores. The meats from which S. aureus was recovered in the order of frequency of percentage recovery are as follows: chicken, pork liver, fish, spiced ham, round beef steak, hamburger, beef liver, pork chops, veal steak, and lamb chops. The following seven meats did not yield staphylococci: bologna, shucked oysters, olive and pickle loaf, salami, wieners, and chopped ham. Eighty-eight per cent of the isolates produced pigment, 85% were gelatinase positive, only 1 strain failed to form a precipitate on egg yolk agar, 92% formed deoxyribonuclease, 87% produced bound coagulase, 91% produced the alpha-hemolysin, 70% the delta-, 22% the beta-, and 6% were nil in this regard. The isolates are compared with hospital and other food strains, and their possible source in the meats is discussed.

l-Glutamine Attenuates Apoptosis Induced by Endoplasmic Reticulum Stress by Activating the IRE1α-XBP1 Axis in IPEC-J2: A Novel Mechanism of l-Glutamine in Promoting Intestinal Health

PubMed Central

Chen, Jiashun; Liu, Shaojuan; Yao, Kang; Yin, Yulong

2017-01-01

Intestinal absorption and barrier malfunctions are associated with endoplasmic reticulum stress (ERS) in the intestine. We induced ERS by exposing the intestinal porcine epithelial cell line J2 (IPEC-J2) to tunicamycin (TUNI) to explore the potential of l-glutamine to reduce ERS-induced apoptosis. Our experiments demonstrated that exposing cells to TUNI results in spontaneous ERS and encourages the upregulation of glucose-regulated protein 78 (GRP78). Prolonged TUNI-induced ERS was found to increase apoptosis mediated by C/enhancer binding protein homologous protein (CHOP), accompanied by GRP78 downregulation. Treatment with l-glutamine was found to promote cell proliferation within the growth medium but to have little effect in basic Dulbecco’s modified Eagle medium. Finally, in the milieu of TUNI-induced ERS, l-glutamine was found to maintain a high level of GRP78, alleviate CHOP-mediated apoptosis and activate the inositol requiring enzyme 1α (IRE1α)-X-box binding protein 1 (XBP1) axis. A specific inhibitor of the IRE1α-XBP1 axis reversed the protective effect of l-glutamine by blocking the expression of IRE1α/XBP1s. We propose that the functional effect of l-glutamine on intestinal health may be partly due to its modulation of ERS and CHOP-mediated apoptosis. PMID:29206200

Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells

PubMed Central

Ren, Zhen; Chen, Si; Qing, Tao; Xuan, Jiekun; Couch, Letha; Yu, Dianke; Ning, Baitang; Shi, Leming; Guo, Lei

2017-01-01

Leflunomide, used for the treatment of rheumatoid arthritis, has been reported to cause severe liver problems and liver failure; however, the underlying mechanisms are not clear. In this study, we used multiple approaches including genomic analysis to investigate and characterize the possible molecular mechanisms of the cytotoxicity of leflunomide in hepatic cells. We found that leflunomide caused endoplasmic reticulum (ER) stress and activated an unfolded protein response, as evidenced by increased expression of related genes including CHOP and GADD34; and elevated protein levels of typical ER stress markers including CHOP, ATF-4, p-eIF2α, and spliced XBP1. The secretion of Gaussia luciferase was suppressed in cells treated with leflunomide in an ER stress reporter assay. Inhibition of ER stress with an ER stress inhibitor 4-phenylbutyrate, and knockdown of ATF-4 and CHOP genes partially protected cells upon leflunomide exposure. In addition, both genomic and biochemical analyses revealed that JNK and ERK1/2 of MAPK signaling pathways were activated, and both contributed to the leflunomide-induced cytotoxicity. Inhibiting JNK activation using a JNK inhibitor attenuated the ER stress and cytotoxicity of leflunomide, whereas inhibiting ERK1/2 using an ERK1/2 inhibitor or ERK1/2 siRNA increased the adverse effect caused by leflunomide, suggesting opposite roles for the two pathways. In summary, our data indicate that both ER stress and the activation of JNK and ERK1/2 contribute to leflunomide-induced cytotoxicity. PMID:28988120

CD20-positive primary gastric T-cell lymphoma poorly responding to initial treatment with rituximab plus CHOP, and a literature review.

PubMed

Kakinoki, Yasutaka; Hashiguchi, Junichi; Ishio, Takashi; Chiba, Koji; Niino, Daisuke; Ohshima, Koichi

2015-12-01

There have been rare reported cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) that co-expressed CD20. A 44-year-old Japanese male was initially misdiagnosed as CD20-positive diffuse large B-cell lymphoma with a background of reactive CD3-positive T-cells in the stomach. After four cycles of R-CHOP [rituximab plus cyclophosphamide (CY), doxorubicin, vincristine, and prednisolone (PSL)], total gastrectomy with regional lymph node dissection was performed due to the poor response to R-CHOP. A final diagnosis of CD20-positive primary gastric PTCL-NOS was made based on the immunohistochemical, flow cytometric, and molecular genetic findings. In the present case, CD20 immunostaining for T-cell lymphoma cells in tumor tissue varied; in a large part, these were strong to weak-positive, and in some parts, absent. We additionally reviewed the literature focusing on CD20-positive PTCL-NOS treated with rituximab. The administration of rituximab has been performed as an initial treatment in 11 cases, including the case reported here. The response was good in cases with high expression of CD20, while it was poor in cases with variable intensity in CD20 staining, which is consistent with our experience in the present case. The efficacy of rituximab may be associated with intensity of CD20 expression in T cells and its homogeneity in the tumor tissue.

The effect of alcohol and hydrogen peroxide on liver hepcidin gene expression in mice lacking antioxidant enzymes, glutathione peroxidase-1 or catalase.

PubMed

Harrison-Findik, Duygu Dee; Lu, Sizhao

2015-05-06

This study investigates the regulation of hepcidin, the key iron-regulatory molecule, by alcohol and hydrogen peroxide (H2O2) in glutathione peroxidase-1 (gpx-1(-/-)) and catalase (catalase(-/-)) knockout mice. For alcohol studies, 10% ethanol was administered in the drinking water for 7 days. Gpx-1(-/-) displayed significantly higher hepatic H2O2 levels than catalase(-/-) compared to wild-type mice, as measured by 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The basal level of liver hepcidin expression was attenuated in gpx-1(-/-) mice. Alcohol increased H2O2 production in catalase(-/-) and wild-type, but not gpx-1(-/-), mice. Hepcidin expression was inhibited in alcohol-fed catalase(-/-) and wild-type mice. In contrast, alcohol elevated hepcidin expression in gpx-1(-/-) mice. Gpx-1(-/-) mice also displayed higher level of basal liver CHOP protein expression than catalase(-/-) mice. Alcohol induced CHOP and to a lesser extent GRP78/BiP expression, but not XBP1 splicing or binding of CREBH to hepcidin gene promoter, in gpx-1(-/-) mice. The up-regulation of hepatic ATF4 mRNA levels, which was observed in gpx-1(-/-) mice, was attenuated by alcohol. In conclusion, our findings strongly suggest that H2O2 inhibits hepcidin expression in vivo. Synergistic induction of CHOP by alcohol and H2O2, in the absence of gpx-1, stimulates liver hepcidin gene expression by ER stress independent of CREBH.

Comparison of the Microbial Quality of Lamb and Goat Meat Acquired from Internet and Local Retail Markets.

PubMed

Kim, Chyer; Stein, Roslyn A; Pao, Steven

2015-11-01

This study was conducted to evaluate the microbial quality of lamb and goat meat sold through local (Virginia) and Internet (U. S.) retail markets. A total of 134 frozen meat products consisting of locally purchased lamb ground (LLG) and lamb chops and Internet-procured lamb ground, goat ground, lamb chops (ILC), goat chops (IGC), lamb stew, and goat stew were tested. Significantly higher levels of aerobic mesophiles, psychrotrophs, and coliforms were found in the meat locally acquired than in the meat procured from the Internet. Similar average prevalence (27%) of Escherichia coli was observed regardless of market source. Ground meat had significantly high levels and prevalence of mesophiles, psychrotrophs, coliforms, and Listeria spp. One sample of LLG contained Campylobacter, and one sample of IGC contained Salmonella. Listeria spp. were present in 23 to 40% and 17 to 80% of samples from local and Internet markets, respectively. Pulsed-field gel electrophoresis (PFGE) of isolated E. coli strains revealed brand specificity and genomic diversity. No isolate from different brands and market sources had matching PFGE profiles. The average price of Internet meat ($23.4/kg) was about 1.2 times higher than the price of local meat, except for ILC, whose price was 2.7 times higher. This study revealed differences in microbial quality of lamb and goat meat based on market source; thus, meat products should be handled carefully regardless of market source because of the presence of high microbial levels and the high prevalence of pathogens.

The Repeated Replacement Method: A Pure Lagrangian Meshfree Method for Computational Fluid Dynamics

PubMed Central

Walker, Wade A.

2012-01-01

In this paper we describe the repeated replacement method (RRM), a new meshfree method for computational fluid dynamics (CFD). RRM simulates fluid flow by modeling compressible fluids’ tendency to evolve towards a state of constant density, velocity, and pressure. To evolve a fluid flow simulation forward in time, RRM repeatedly “chops out” fluid from active areas and replaces it with new “flattened” fluid cells with the same mass, momentum, and energy. We call the new cells “flattened” because we give them constant density, velocity, and pressure, even though the chopped-out fluid may have had gradients in these primitive variables. RRM adaptively chooses the sizes and locations of the areas it chops out and replaces. It creates more and smaller new cells in areas of high gradient, and fewer and larger new cells in areas of lower gradient. This naturally leads to an adaptive level of accuracy, where more computational effort is spent on active areas of the fluid, and less effort is spent on inactive areas. We show that for common test problems, RRM produces results similar to other high-resolution CFD methods, while using a very different mathematical framework. RRM does not use Riemann solvers, flux or slope limiters, a mesh, or a stencil, and it operates in a purely Lagrangian mode. RRM also does not evaluate numerical derivatives, does not integrate equations of motion, and does not solve systems of equations. PMID:22866175

Molecular mode of action of NKP-1339 - a clinically investigated ruthenium-based drug - involves ER- and ROS-related effects in colon carcinoma cell lines.

PubMed

Flocke, Lea S; Trondl, Robert; Jakupec, Michael A; Keppler, Bernhard K

2016-06-01

Sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (NKP-1339) is a clinically investigated ruthenium-based metal complex, which shows promising results in solid tumors, such as non-small cell lung cancer, colorectal carcinoma, and most distinctively in gastrointestinal neuroendocrine tumors. In previous studies, fast binding to albumin as well as transferrin could be shown. The enhanced permeability and retention (EPR) effect, which is diversely being exploited for tumor targeting, could therefore be applicable for NKP-1339. Here we studied the serum dependence of its biological activity in various methods, influencing its cellular accumulation, cytotoxicity as well as the generation of reactive oxygen species (ROS). ROS lead to Nrf2 activation, which is known to activate antioxidant response gene transcription. GRP78 down-regulation on the protein level suggests ER associated protein degradation (ERAD) as a mode of action, as RNA levels are only mildly affected. Another important part for the mode of action is endoplasmic reticulum (ER) stress, as different factors are highly upregulated on the protein level. For example PERK, a transmembrane receptor which is released by GRP78 when the ER is disturbed, is upregulated and phosphorylated. EIF2α is phosphorylated, which leads to an inhibition of CAP-dependent translation and other stress responses. The transcription factor CHOP (DDIT3), which promotes ER stress dependent apoptosis, is time and concentration dependently upregulated. Finally cytotoxicity tests could prove that inhibition of ER stress and ER stress-mediated apoptosis leads to decreased cytotoxic effects of NKP-1339, which highlights the involvement of this mechanism in the mode of action.

Method and apparatus for measuring film spectral properties

DOEpatents

Forrest, Stephen R.; Burrows, Paul E.; Garbuzov, Dmitri Z.; Bulovic, Vladimir

1999-12-21

Film spectral properties are measured by projecting chopped monochromatic light onto a luminescent film sample deposited on a substrate, and coupling through use of immersion oil the reflection of light therefrom to a light detector.

Zesty Tomato Soup

MedlinePlus

... added diced tomatoes 1 cup jarred roasted red peppers, drained (or substitute fresh roasted red peppers) 1 cup fat-free evaporated milk 1 tsp garlic powder 1/4 tsp ground black pepper 2 Tbsp fresh basil, rinsed and chopped (or ...

9 CFR 319.143 - Breakfast sausage.

Code of Federal Regulations, 2011 CFR

2011-01-01

.... The finished product shall not contain more than 50 percent fat. To facilitate chopping or mixing, water or ice may be used in an amount not to exceed 3 percent of the total ingredients used. Binders or...

9 CFR 319.143 - Breakfast sausage.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... The finished product shall not contain more than 50 percent fat. To facilitate chopping or mixing, water or ice may be used in an amount not to exceed 3 percent of the total ingredients used. Binders or...

Sight-threatening optic neuropathy is associated with paranasal lymphoma

PubMed Central

Hayashi, Takahiko; Watanabe, Ken; Tsuura, Yukio; Tsuji, Gengo; Koyama, Shingo; Yoshigi, Jun; Hirata, Naoko; Yamane, Shin; Iizima, Yasuhito; Toyota, Shigeo; Takeuchi, Satoshi

2010-01-01

Malignant lymphoma around the orbit is very rare. We present a rare case of optic neuropathy caused by lymphoma. A 61-year-old Japanese woman was referred to our hospital for evaluation of idiopathic optic neuropathy affecting her right eye. The patient was treated with steroid pulse therapy (methyl-predonisolone 1 g daily for 3 days) with a presumed diagnosis of idiopathic optic neuritis. After she had been switched to oral steroid therapy, endoscopic sinus surgery had been performed, which revealed diffuse large B cell lymphoma of the ethmoidal sinus. Although R-CHOP therapy was immediately started, prolonged optic nerve compression resulted in irreversible blindness. Accordingly, patients with suspected idiopathic optic neuritis should be carefully assessed when they show a poor response, and imaging of the orbits and brain should always be done for initial diagnosis because they may have compression by a tumor. PMID:20390034

Setting kinetics and mechanical properties of flax fibre reinforced glass ionomer restorative materials

PubMed Central

Abou Neel, Ensanya Ali; Young, Anne M.

2017-01-01

Regardless of the excellent properties of glass ionomer cements, their poor mechanical properties limit their applications to non-load bearing areas. This study aimed to investigate the effect of incorporated short, chopped and randomly distributed flax fibers (0, 0.5, 1, 2.5, 5 and 25 wt%) on setting reaction kinetics, and mechanical and morphological properties of glass ionomer cements. Addition of flax fibers did not significantly affect the setting reaction extent. According to their content, flax fibers increased the compressive (from 148 to 250 MPa) and flexure strength (from 20 to 42 MPa). They also changed the brittle behavior of glass ionomer cements to a plastic one. They significantly reduced the compressive (from 3 to 1.3 GPa) and flexure modulus (from 19 to 14 GPa). Accordingly, flax fiber-modified glass ionomer cements could be potentially used in high-stress bearing areas. PMID:28808218

Outcome and toxicity associated with a dose-intensified, maintenance-free CHOP-based chemotherapy protocol in canine lymphoma: 130 cases.

PubMed

Sorenmo, Karin; Overley, B; Krick, E; Ferrara, T; LaBlanc, A; Shofer, F

2010-09-01

A dose-intensified/dose-dense chemotherapy protocol for canine lymphoma was designed and implemented at the Veterinary Hospital of the University of Pennsylvania. In this study, we describe the clinical characteristics, prognostic factors, efficacy and toxicity in 130 dogs treated with this protocol. The majority of the dogs had advanced stage disease (63.1% stage V) and sub-stage b (58.5%). The median time to progression (TTP) and lymphoma-specific survival were 219 and 323 days, respectively. These results are similar to previous less dose-intense protocols. Sub-stage was a significant negative prognostic factor for survival. The incidence of toxicity was high; 53.9 and 45% of the dogs needed dose reductions and treatment delays, respectively. Dogs that required dose reductions and treatment delays had significantly longer TTP and lymphoma-specific survival times. These results suggest that dose density is important, but likely relative, and needs to be adjusted according to the individual patient's toxicity for optimal outcome.

9 CFR 319.142 - Fresh beef sausage.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 318 of this subchapter. The finished product shall not contain more than 30 percent fat. To facilitate chopping or mixing, water or ice may be used in an amount not to exceed 3 percent of the total ingredients...

9 CFR 319.160 - Smoked pork sausage.

Code of Federal Regulations, 2011 CFR

2011-01-01

... part 318 of this subchapter. The finished product shall not contain more than 50 percent fat. To facilitate chopping or mixing, water, or ice may be used in an amount not to exceed 3 percent of the total...

9 CFR 319.160 - Smoked pork sausage.

Code of Federal Regulations, 2010 CFR

2010-01-01

... part 318 of this subchapter. The finished product shall not contain more than 50 percent fat. To facilitate chopping or mixing, water, or ice may be used in an amount not to exceed 3 percent of the total...

9 CFR 319.142 - Fresh beef sausage.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 318 of this subchapter. The finished product shall not contain more than 30 percent fat. To facilitate chopping or mixing, water or ice may be used in an amount not to exceed 3 percent of the total ingredients...

9 CFR 319.141 - Fresh pork sausage.

Code of Federal Regulations, 2011 CFR

2011-01-01

... subchapter. The finished product shall not contain more than 50 percent fat. To facilitate chopping or mixing, water or ice may be used in an amount not to exceed 3 percent of the total ingredients used. [35 FR...

9 CFR 319.141 - Fresh pork sausage.

Code of Federal Regulations, 2010 CFR

2010-01-01

... subchapter. The finished product shall not contain more than 50 percent fat. To facilitate chopping or mixing, water or ice may be used in an amount not to exceed 3 percent of the total ingredients used. [35 FR...

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

Peplov, Vladimir V; Saethre, Robert B

The Spallation Neutron Source (SNS) Linac Low Energy Beam Transport (LEBT) chopper system provides fast chopping of the H- ion beam in the LEBT structure. Four identical pulsed power supplies (pulsers) create a series of 2.5 kV pulses to the four deflection electrodes floating on the focusing voltage of -50 kV. Each pulser is connected to the electrode through the network which consists of high voltage (HV) cables, a blocking capacitor, HV feed-through connectors, current-limiting resistors and transient voltage suppressors. Effective beam chopping requires minimal rise/fall time of the rectangular HV pulses on the load. In the present configuration thesemore » values are approximately 100 ns. Methods of reducing rise/fall time on the LEBT electrodes are discussed. Results of simulation and comparative measurements of the original and upgraded system on the test stand are presented. Furthermore, the effect of these changes on reliability degradation caused by arcing in the LEBT structure is discussed.« less

[Original method of extracapsule fragmentation of the lens nucleus during phacoemulsification].

PubMed

Avetisov, S E; Iusef, Iusef Naim; Mamikonian, V R; Vvedenskiĭ, A S; Iusef, Said Naim; Mutonen, N V

2002-01-01

Clinical estimation of different modifications of phacoemulsification revealed the formation of the second tunnel in the nucleus for its division into quadrants in "four-quadrant phaco" increases the required duration of ultrasonography (US) and irrigation, which causes greater endothelial losses associated with the use of nuclear breakdown by means of a chopper tunnel. When the authors used their own methods of "extracapsular half-nuclei" fragmentation, endothelial losses are rather greater than those with the similar method "stop & "chop", which is associated with closer disposition of the US tip to the posterior corneal surface. At the same time nuclear breakdown by means a chapper in the capsular sac by the "stop & chop" method causes dilation of Zinn's ligaments, fraught by their rupture, particularly if latent derangement or defects of the zonular apparatus, and increases the risk of damage to the posterior capsule by the chopper.

Consumer choice of pork chops in Taiwan.

PubMed

Chen, M T; Guo, H L; Tseng, T F; Roan, S W; Ngapo, T M

2010-07-01

Digital photographs of pork chops varying systematically in appearance were presented to 716 Taiwanese consumers in a study that aimed to identify the most important characteristics of fresh pork which determine consumer choice in Taiwan. Relationships between consumer segmentation in choice and socio-demographic and cultural differences were also investigated. Colour and fat cover were the most frequently chosen of the four characteristics studied. Dark red colour was preferred by 64% of consumers and lean fat cover by 44%. Marbling and drip were less important in the decision making process being used by less than a half of consumers. The four preference-based clusters of consumers showed no correlation with socio-demographic-based consumer clusters, but did show significant links with possession of a refrigerator, age at which schooling was completed, liking pork for its price and gender of consumer. Crown Copyright 2010. Published by Elsevier Ltd. All rights reserved.

Flavor compounds and quality parameters of chevon as influenced by sericea lespedeza hay.

PubMed

Lee, Jung Hoon; Vanguru, Manohar; Moore, Danier A; Kannan, Govind; Terrill, Thomas H; Kouakou, Brou

2012-04-18

This research assessed the utilization of sericea lespedeza (SL, Lespedeza cuneata ) hay, a highly condensed tannin (CT) forage (87-181 g CT/kg), as a dietary regimen of meat goats, and thereby the effects on physicochemical properties of goat meat (chevon) and flavor compounds in cooked chevon chops were evaluated. Although it is commonly believed that higher amounts of CT can have deleterious effects on animal performance due to low digestibility and low voluntary intakes in ruminants, feeding meat goats with SL hay increased the body weight compared to goats fed bermudagrass hay without altering the chemical composition and meat quality of chevon. Feeding SL hay to meat goats also did not significantly influence the flavor volatiles in cooked chevon chops. The findings indicate that SL hay can be used as a low-input forage to replace expensive forages.

Straight and chopped dc performance data for a Prestolite MTC-4001 motor and a general electric EV-1 controller

NASA Technical Reports Server (NTRS)

Edie, P. C.

1981-01-01

Performance data on the Prestolite MTC-4001 series wound dc motor and General Electric EV-1 Chopper Controller is supplied for the electric vehicle manufacturer. Data are provided for both straight and chopped dc input to the motor, at 2 motor temperature levels. Testing was done at 6 voltage increments to the motor, and 2 voltage increments to the controller. Data results are presented in both tabular and graphical forms. Tabular information includes motor voltage and current input data, motor speed and torque output data, power data and temperature data. Graphical information includes torque-speed, motor power output-speed, torque-current, and efficiency-speed plots under the various operating conditions. The data resulting from this testing show the speed-torque plots to have the most variance with operating temperature. The maximum motor efficiency is between 76% and 82%, regardless of temperature or mode of operation.

Design, Simulation and Characteristics Research of the Interface Circuit based on nano-polysilicon thin films pressure sensor

NASA Astrophysics Data System (ADS)

Zhao, Xiaosong; Zhao, Xiaofeng; Yin, Liang

2018-03-01

This paper presents a interface circuit for nano-polysilicon thin films pressure sensor. The interface circuit includes consist of instrument amplifier and Analog-to-Digital converter (ADC). The instrumentation amplifier with a high common mode rejection ratio (CMRR) is implemented by three stages current feedback structure. At the same time, in order to satisfy the high precision requirements of pressure sensor measure system, the 1/f noise corner of 26.5 mHz can be achieved through chopping technology at a noise density of 38.2 nV/sqrt(Hz).Ripple introduced by chopping technology adopt continuous ripple reduce circuit (RRL), which achieves the output ripple level is lower than noise. The ADC achieves 16 bits significant digit by adopting sigma-delta modulator with fourth-order single-bit structure and digital decimation filter, and finally achieves high precision integrated pressure sensor interface circuit.

[Preparation of carbon fiber reinforced fluid type resin denture (author's transl)].

PubMed

Kasuga, H; Sato, H; Nakabayashi, N

1980-01-01

Transverse strength of cured fluid resins is weaker than that of the heat cured. We have studied to improve the mechanical strength of self-cured acrylic resin by application of carbon fibers as reinforcement and simple methods which must be acceptable for technicians are proposed. A cloth type carbon fiber was the best reinforcement among studied carbon fibers such as chopped or mat. The chopped fibers were difficult to mix homogeneously with fluid resins and effectiveness of the reinforcement was low. Breaking often occurred at the interface between the reinforcement and resin in the cases of mat which gave defects to the test specimens. To prepare reinforced denture, the cloth was trimmed on the master cast after removal of wax and the prepreg was formed with the alginate impression on the cast by Palapress and the cloth. Other steps were same as the usual fluid resin.

Three Point Bending of Top-Hat Stiffened Chopped Short Fibre Ramie/HDPE Thermoplastic Composite Beam

NASA Astrophysics Data System (ADS)

Hadi, Bambang K.; Nuril, Yogie S.

2018-04-01

The use of natural fibre and thermoplastic matrices in composite materials increased significantly during the last decade especially in the automotive industries. Ramie is one of these potential natural fibres. In this paper, a three point bending of top-hat beam made of ramie/HDPE (High-Density-Polyethylene) composites was performed. Top-hat stiffened structures were common structures found in the aerospace industries. Nevertheless, these structures are beginning to be applied in automotive structures in the forms of chassis and bumpers. The ramie/HDPE composite was manufactured using hot-press technique. The temperature was set to be 135°C and the pressure was 6 bars. Chopped short ramie fibre was used, due to good drape ability characteristics. The experiments showed that the beams produced a large non-linearity. Linear Finite Element Analysis was carried out to be compared with the experimental data. The differences are reasonable.

Characterization of the mechanical properties of the SOFIA secondary mirror mechanism in a multi-stage approach

NASA Astrophysics Data System (ADS)

Greiner, Benjamin; Lammen, Yannick; Reinacher, Andreas; Krabbe, Alfred; Wagner, Jörg

2016-07-01

The Stratospheric Observatory for Infrared Astronomy (SOFIA) uses its compact and highly integrated Secondary Mirror Mechanism (SMM) to switch between target positions on the sky in a square wave pattern. This chopping motion excites eigenmodes of the mechanism structure, which limit controller and observatory performance. We present the setup and results of experimental modal tests performed on different building stages of a test-bench model as well as on the original flight hardware. Test results were correlated to simulations employing a finite element model in order to identify excited mode shapes and contributing flexible components of the Secondary Mirror Mechanism. It was possible to isolate the motion of the compensation ring and its elastic mounts as the vibration mode inducing the main disturbance at about 300 Hz, which is currently the main mode shape limiting the performance of the chopping controller.

Modulation of the Unfolded Protein Response by Tauroursodeoxycholic Acid Counteracts Apoptotic Cell Death and Fibrosis in a Mouse Model for Secondary Biliary Liver Fibrosis

PubMed Central

Paridaens, Annelies; Raevens, Sarah; Devisscher, Lindsey; Bogaerts, Eliene; Verhelst, Xavier; Hoorens, Anne; van Vlierberghe, Hans; Van Grunsven, Leo A.; Geerts, Anja; Colle, Isabelle

2017-01-01

The role of endoplasmic reticulum stress and the unfolded protein response (UPR) in cholestatic liver disease and fibrosis is not fully unraveled. Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, has been shown to reduce endoplasmic reticulum (ER) stress and counteract apoptosis in different pathologies. We aimed to investigate the therapeutic potential of TUDCA in experimental secondary biliary liver fibrosis in mice, induced by common bile duct ligation. The kinetics of the hepatic UPR and apoptosis during the development of biliary fibrosis was studied by measuring markers at six different timepoints post-surgery by qPCR and Western blot. Next, we investigated the therapeutic potential of TUDCA, 10 mg/kg/day in drinking water, on liver damage (AST/ALT levels) and fibrosis (Sirius red-staining), in both a preventive and therapeutic setting. Common bile duct ligation resulted in the increased protein expression of CCAAT/enhancer-binding protein homologous protein (CHOP) at all timepoints, along with upregulation of pro-apoptotic caspase 3 and 12, tumor necrosis factor receptor superfamily, member 1A (TNFRsf1a) and Fas-Associated protein with Death Domain (FADD) expression. Treatment with TUDCA led to a significant reduction of liver fibrosis, accompanied by a slight reduction of liver damage, decreased hepatic protein expression of CHOP and reduced gene and protein expression of pro-apoptotic markers. These data indicate that TUDCA exerts a beneficial effect on liver fibrosis in a model of cholestatic liver disease, and suggest that this effect might, at least in part, be attributed to decreased hepatic UPR signaling and apoptotic cell death. PMID:28117681

Effect of chronic treatment with the GABA transaminase inhibitors gamma-vinyl GABA and ethanolamine O-sulphate on the in vitro GABA release from rat hippocampus.

PubMed

Qume, M; Fowler, L J

1997-10-01

1. The effects of 2, 8 and 21 day oral treatment with the specific gamma-aminobutyric acid transaminase (GABA-T) inhibitors gamma-vinyl GABA (GVG) and ethanolamine O-sulphate (EOS) on brain GABA levels, GABA-T activity, and basal and stimulated GABA release from rat cross-chopped brain hippocampal slices was investigated. 2. Treatment with GABA-T inhibitors lead to a reduction in brain GABA-T activity by 65-80% compared with control values, with a concomitant increase in brain GABA content of 40-100%. 3. Basal hippocampal GABA release was increased to 250-450% of control levels following inhibition of GABA-T activity. No Ca2+ dependence was observed in either control or treated tissues. 4. GVG and EOS administration led to a significant elevation in the potassium stimulated release of GABA from cross-chopped hippocampal slices compared with that of controls. Although stimulated GABA release from control tissues was decreased in the presence of a low Ca2+ medium, GVG and EOS treatment abolished this Ca2+ dependency. 5. GABA compartmentalization, Na+ and Cl- coupled GABA uptake carriers and glial release may provide explanations for the loss of the Ca2+ dependency of stimulated GABA release observed following GVG and EOS treatment. 6. Administration of GABA-T inhibitors led to increases in both basal and stimulated hippocampal GABA release. However, it is not clear which is the most important factor in the anticonvulsant activity of these drugs, the increased GABA content 'leaking' out of neurones and glia leading to widespread inhibition, or the increase in stimulated GABA release which may occur following depolarization caused by an epileptic discharge.

Effect of chronic treatment with the GABA transaminase inhibitors γ-vinyl GABA and ethanolamine O-sulphate on the in vitro GABA release from rat hippocampus

PubMed Central

Qume, M; Fowler, L J

1997-01-01

The effects of 2, 8 and 21 day oral treatment with the specific γ-aminobutyric acid transaminase (GABA-T) inhibitors γ-vinyl GABA (GVG) and ethanolamine O-sulphate (EOS) on brain GABA levels, GABA-T activity, and basal and stimulated GABA release from rat cross-chopped brain hippocampal slices was investigated. Treatment with GABA-T inhibitors lead to a reduction in brain GABA-T activity by 65–80% compared with control values, with a concomitant increase in brain GABA content of 40–100%. Basal hippocampal GABA release was increased to 250–450% of control levels following inhibition of GABA-T activity. No Ca2+ dependence was observed in either control or treated tissues. GVG and EOS administration led to a significant elevation in the potassium stimulated release of GABA from cross-chopped hippocampal slices compared with that of controls. Although stimulated GABA release from control tissues was decreased in the presence of a low Ca2+ medium, GVG and EOS treatment abolished this Ca2+ dependency. GABA compartmentalization, Na+ and Cl− coupled GABA uptake carriers and glial release may provide explanations for the loss of the Ca2+ dependency of stimulated GABA release observed following GVG and EOS treatment. Administration of GABA-T inhibitors led to increases in both basal and stimulated hippocampal GABA release. However, it is not clear which is the most important factor in the anticonvulsant activity of these drugs, the increased GABA content ‘leaking' out of neurones and glia leading to widespread inhibition, or the increase in stimulated GABA release which may occur following depolarization caused by an epileptic discharge. PMID:9351512

Activation of endoplasmic reticulum stress response by enhanced polyamine catabolism is important in the mediation of cisplatin-induced acute kidney injury

PubMed Central

Barone, Sharon; Destefano-Shields, Christina; Brooks, Marybeth; Murray-Stewart, Tracy; Dunworth, Matthew; Li, Weimin; Doherty, Joanne R.; Hall, Mark A.; Smith, Roger D.; Cleveland, John L.; Casero, Robert A.; Soleimani, Manoocher

2017-01-01

Cisplatin-induced nephrotoxicity limits its use in many cancer patients. The expression of enzymes involved in polyamine catabolism, spermidine/spermine N1-acetyltransferase (SSAT) and spermine oxidase (SMOX) increase in the kidneys of mice treated with cisplatin. We hypothesized that enhanced polyamine catabolism contributes to tissue damage in cisplatin acute kidney injury (AKI). Using gene knockout and chemical inhibitors, the role of polyamine catabolism in cisplatin AKI was examined. Deficiency of SSAT, SMOX or neutralization of the toxic products of polyamine degradation, H2O2 and aminopropanal, significantly diminished the severity of cisplatin AKI. In vitro studies demonstrated that the induction of SSAT and elevated polyamine catabolism in cells increases the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) and enhances the expression of binding immunoglobulin protein BiP/GRP78) and CCAAT-enhancer-binding protein homologous protein (CHOP/GADD153). The increased expression of these endoplasmic reticulum stress response (ERSR) markers was accompanied by the activation of caspase-3. These results suggest that enhanced polyamine degradation in cisplatin AKI may lead to tubular damage through the induction of ERSR and the consequent onset of apoptosis. In support of the above, we show that the ablation of the SSAT or SMOX gene, as well as the neutralization of polyamine catabolism products modulate the onset of ERSR (e.g. lower BiP and CHOP) and apoptosis (e.g. reduced activated caspase-3). These studies indicate that enhanced polyamine catabolism and its toxic products are important mediators of ERSR and critical to the pathogenesis of cisplatin AKI. PMID:28886181

Activation of endoplasmic reticulum stress response by enhanced polyamine catabolism is important in the mediation of cisplatin-induced acute kidney injury.

PubMed

Zahedi, Kamyar; Barone, Sharon; Destefano-Shields, Christina; Brooks, Marybeth; Murray-Stewart, Tracy; Dunworth, Matthew; Li, Weimin; Doherty, Joanne R; Hall, Mark A; Smith, Roger D; Cleveland, John L; Casero, Robert A; Soleimani, Manoocher

2017-01-01

Cisplatin-induced nephrotoxicity limits its use in many cancer patients. The expression of enzymes involved in polyamine catabolism, spermidine/spermine N1-acetyltransferase (SSAT) and spermine oxidase (SMOX) increase in the kidneys of mice treated with cisplatin. We hypothesized that enhanced polyamine catabolism contributes to tissue damage in cisplatin acute kidney injury (AKI). Using gene knockout and chemical inhibitors, the role of polyamine catabolism in cisplatin AKI was examined. Deficiency of SSAT, SMOX or neutralization of the toxic products of polyamine degradation, H2O2 and aminopropanal, significantly diminished the severity of cisplatin AKI. In vitro studies demonstrated that the induction of SSAT and elevated polyamine catabolism in cells increases the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) and enhances the expression of binding immunoglobulin protein BiP/GRP78) and CCAAT-enhancer-binding protein homologous protein (CHOP/GADD153). The increased expression of these endoplasmic reticulum stress response (ERSR) markers was accompanied by the activation of caspase-3. These results suggest that enhanced polyamine degradation in cisplatin AKI may lead to tubular damage through the induction of ERSR and the consequent onset of apoptosis. In support of the above, we show that the ablation of the SSAT or SMOX gene, as well as the neutralization of polyamine catabolism products modulate the onset of ERSR (e.g. lower BiP and CHOP) and apoptosis (e.g. reduced activated caspase-3). These studies indicate that enhanced polyamine catabolism and its toxic products are important mediators of ERSR and critical to the pathogenesis of cisplatin AKI.

Histological analysis on adhesive molecules of renal intravascular large B cell lymphoma treated with CHOP chemotherapy and rituximab.

PubMed

Kusaba, T; Hatta, T; Tanda, S; Kameyama, H; Tamagaki, K; Okigaki, M; Inaba, T; Shimazaki, C; Sasaki, S

2006-03-01

A 48-year-old man was admitted to our hospital for investigation of mild renal dysfunction. A blood examination revealed mild elevation of creatinine level (1.77 mg/dl). Urinary examination revealed mild protein excretion (0.54 g/day) and microhematuria; renal biopsy revealed the focal proliferation of large mononuclear cells with mitosis in glomerular capillaries. According to immunohistochemical analysis, the intravascular lymphomatous cells stained positively with anti-leukocyte common antigen (LCA: CD45) and CD20, indicating a B lymphocyte lineage. In electron microscopy, the glomerular capillary was filled with lymphoma cells and epithelial foot process fusion was noted. Immunohistochemical analysis on adhesive molecules revealed a lack of CD11a expression on lymphoma cells, but positive CD54 expression on endothelial cells. Systemic 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed no abnormal uptake of isotopes. On the basis of these findings, we diagnosed intravascular diffuse large B cell lymphoma localized in the kidney. Despite treatment with rituximab and CHOP (prednisolone, doxorubicin, vincristine, cyclophosphamide) for 3 cycles at 1-month intervals, the renal dysfunction did not change. In histopathological analysis of the second biopsy, lymphoma cells disappeared, but focal segmental glomerulosclerosis and moderate interstitial fibrosis were noted. Electron microscopic findings revealed severe subendothelial edema with mesangial interposition, indicating severe endothelial damage. Epithelial foot process fusion was improved. These pathological analyses let us conclude that a lack of CD11a could be a candidate factor for prevention of the extravasation of lymphoma cells from blood vessels in our patient. We also presumed that the intraglomerular endothelial damage occurred due to chemotherapy-associated cell injury.

Mifepristone increases mRNA translation rate, triggers the unfolded protein response, increases autophagic flux, and kills ovarian cancer cells in combination with proteasome or lysosome inhibitors.

PubMed

Zhang, Lei; Hapon, Maria B; Goyeneche, Alicia A; Srinivasan, Rekha; Gamarra-Luques, Carlos D; Callegari, Eduardo A; Drappeau, Donis D; Terpstra, Erin J; Pan, Bo; Knapp, Jennifer R; Chien, Jeremy; Wang, Xuejun; Eyster, Kathleen M; Telleria, Carlos M

2016-08-01

The synthetic steroid mifepristone blocks the growth of ovarian cancer cells, yet the mechanism driving such effect is not entirely understood. Unbiased genomic and proteomic screenings using ovarian cancer cell lines of different genetic backgrounds and sensitivities to platinum led to the identification of two key genes upregulated by mifepristone and involved in the unfolded protein response (UPR): the master chaperone of the endoplasmic reticulum (ER), glucose regulated protein (GRP) of 78 kDa, and the CCAAT/enhancer binding protein homologous transcription factor (CHOP). GRP78 and CHOP were upregulated by mifepristone in ovarian cancer cells regardless of p53 status and platinum sensitivity. Further studies revealed that the three UPR-associated pathways, PERK, IRE1α, and ATF6, were activated by mifepristone. Also, the synthetic steroid acutely increased mRNA translation rate, which, if prevented, abrogated the splicing of XBP1 mRNA, a non-translatable readout of IRE1α activation. Moreover, mifepristone increased LC3-II levels due to increased autophagic flux. When the autophagic-lysosomal pathway was inhibited with chloroquine, mifepristone was lethal to the cells. Lastly, doses of proteasome inhibitors that are inadequate to block the activity of the proteasomes, caused cell death when combined with mifepristone; this phenotype was accompanied by accumulation of poly-ubiquitinated proteins denoting proteasome inhibition. The stimulation by mifepristone of ER stress and autophagic flux offers a therapeutic opportunity for utilizing this compound to sensitize ovarian cancer cells to proteasome or lysosome inhibitors. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Chronic sleep fragmentation during the sleep period induces hypothalamic endoplasmic reticulum stress and PTP1b-mediated leptin resistance in male mice.

PubMed

Hakim, Fahed; Wang, Yang; Carreras, Alba; Hirotsu, Camila; Zhang, Jing; Peris, Eduard; Gozal, David

2015-01-01

Sleep fragmentation (SF) is highly prevalent and may constitute an important contributing factor to excessive weight gain and the metabolic syndrome. Increased endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) leading to the attenuation of leptin receptor signaling in the hypothalamus leads to obesity and metabolic dysfunction. Mice were exposed to SF and sleep control (SC) for varying periods of time during which ingestive behaviors were monitored. UPR pathways and leptin receptor signaling were assessed in hypothalami. To further examine the mechanistic role of ER stress, changes in leptin receptor (ObR) signaling were also examined in wild-type mice treated with the ER chaperone tauroursodeoxycholic acid (TUDCA), as well as in CHOP-/+ transgenic mice. Fragmented sleep in male mice induced increased food intake starting day 3 and thereafter, which was preceded by increases in ER stress and activation of all three UPR pathways in the hypothalamus. Although ObR expression was unchanged, signal transducer and activator of transcription 3 (STAT3) phosphorylation was decreased, suggesting reduced ObR signaling. Unchanged suppressor of cytokine signaling-3 (SOCS3) expression and increases in protein-tyrosine phosphatase 1B (PTP1B) expression and activity emerged with SF, along with reduced p-STAT3 responses to exogenous leptin. SF-induced effects were reversed following TUDCA treatment and were absent in CHOP -/+ mice. SF induces hyperphagic behaviors and reduced leptin signaling in hypothalamus that are mediated by activation of ER stress, and ultimately lead to increased PTP1B activity. ER stress pathways are therefore potentially implicated in SF-induced weight gain and metabolic dysfunction, and may represent a viable therapeutic target. © 2014 Associated Professional Sleep Societies, LLC.

Central nervous system prophylaxis with intrathecal liposomal cytarabine in a subset of high-risk patients with diffuse large B-cell lymphoma receiving first line systemic therapy in a prospective trial.

PubMed

González-Barca, E; Canales, M; Salar, A; Ferreiro-Martínez, J J; Ferrer-Bordes, S; García-Marco, J A; Sánchez-Blanco, J J; García-Frade, J; Peñalver, J; Bello-López, J L; Sancho, J M; Caballero, D

2016-05-01

The dissemination in the central nervous system (CNS) is an uncommon but fatal complication occurring in patients with diffuse large B-cell lymphoma (DLBCL). Standard prophylaxis has been demonstrated to reduce CNS relapse and improve survival rates. Intrathecal (IT) liposomal cytarabine allows maintaining elevated drug levels in the cerebrospinal fluid for an extended period of time. Data on the efficacy and safety of liposomal cytarabine as CNS prophylaxis in patients with DLBCL are still insufficient. The objective of the present study was to evaluate the effectiveness and safety of the prophylaxis with IT liposomal cytarabine in prevention of CNS relapse in high-risk patients with DLBCL who were included in a trial of first line systemic therapy with 6 cycles of dose-dense R-CHOP every 14 days. Twenty-four (18.6 %) out of 129 patients were identified to have risk factors for CNS involvement, defined as follows: >30 % bone marrow infiltration, testes infiltration, retroperitoneal mass ≥10 cm, Waldeyer ring, or bulky cervical nodes involvement. Liposomal cytarabine (50 mg) was administered by lumbar puncture the first day of the 1st, 2nd, and 6th cycle of R-CHOP14 scheme. Among 70 IT infusions, grade 3-4 adverse events reported were headache (one patient) and nausea/vomiting (one patient). With a median follow-up of 40.1 months, no CNS involvement by DLBCL was observed in any patient. In conclusion, IT liposomal cytarabine is safe, feasible, and effective for CNS prophylaxis, causing few associated risks and little discomfort to patients with DLBCL.

Curcumin induces ER stress-mediated apoptosis through selective generation of reactive oxygen species in cervical cancer cells.

PubMed

Kim, Boyun; Kim, Hee Seung; Jung, Eun-Ji; Lee, Jung Yun; K Tsang, Benjamin; Lim, Jeong Mook; Song, Yong Sang

2016-05-01

Prolonged accumulation of misfolded or unfolded proteins caused by cellular stress, including oxidative stress, induces endoplasmic reticulum stress, which then activates an unfolded protein response (UPR). ER stress is usually maintained at higher levels in cancer cells as compared to normal cells due to altered metabolism in cancer. Here, we investigated whether curcumin is ER stress-mediated apoptosis in cervical cancer cells, and ROS increased by curcumin are involved in the process as an upstream contributor. Curcumin inhibited proliferation of cervical cancer cells (C33A, CaSki, HeLa, and ME180) and induced apoptotic cell death. Curcumin activated ER-resident UPR sensors, such as PERK, IRE-1α, and ATF6, and their downstream-signaling proteins in cervical cancer cells, but not in normal epithelial cells and peripheral blood mononuclear cells (PBMCs). CHOP, a key factor involved in ER stress-mediated apoptosis, was also activated by curcumin. CHOP decreased the ratio of anti-apoptotic protein Bcl-2 to pro-apoptotic protein Bax expression, and subsequently increased the apoptotic population of cervical cancer cells. Furthermore, curcumin elevated levels of intracellular reactive oxygen species (ROS) in cervical cancer cells, but not in normal epithelial cells. Scavenging ROS resulted in inhibition of ER stress and partially restored cell viability in curcumin-treated cancer cells. Collectively, these observations show that curcumin promotes ER stress-mediated apoptosis in cervical cancer cells through increase of cell type-specific ROS generation. Therefore, modulation of these differential responses to curcumin between normal and cervical cancer cells could be an effective therapeutic strategy without adverse effects on normal cells. © 2015 Wiley Periodicals, Inc.

Prognostic significance of MYC, BCL2, and BCL6 rearrangements in patients with diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab.

PubMed

Akyurek, Nalan; Uner, Aysegul; Benekli, Mustafa; Barista, Ibrahim

2012-09-01

Diffuse large B-cell lymphomas (DLBCLs) are a biologically heterogeneous group in which various gene alterations have been reported. The aim of this study was to investigate the frequency and prognostic impact of BCL2, BCL6, and MYC rearrangements in cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-CHOP)-treated DLBCL cases. Tissue microarrays were constructed from 239 cases of DLBCL, and the expressions of CD10, BCL6, MUM1/IRF4, and BCL2 were evaluated by immunohistochemistry. MYC, BCL2, and BCL6 rearrangements were investigated by interphase fluorescence in situ hybridization on tissue microarrays. Survival analysis was constructed from 145 R-CHOP-treated patients. MYC, BCL2, and BCL6 rearrangements were detected in 14 (6%), 36 (15%), and 69 (29%) of 239 DLBCL patients. Double or triple rearrangements were detected in 7 (3%) of 239 DLBCL cases. Of these, 4 had BCL2 and MYC, 2 had BCL6 and MYC, and 1 had BCL2, BCL6, and MYC rearrangements. The prognosis of these cases was extremely poor, with a median survival of 9 months. MYC rearrangement was associated with significantly worse overall survival (P = .01), especially for the cases with GC phenotype (P = .009). BCL6 rearrangement also predicted significantly shorter overall survival (P = .04), especially for the non-GC phenotype (P = .03). BCL2 rearrangement had no prognostic impact on outcome. International Prognostic Index (P = .004) and MYC rearrangement (P = .009) were independent poor prognostic factors. Analysis of MYC gene rearrangement along with BCL2 and BCL6 is critical in identifying high-risk patients with poor prognosis. Copyright © 2011 American Cancer Society.

ERAP2 functional knockout in humans does not alter surface heavy chains or HLA-B27, inflammatory cytokines or endoplasmic reticulum stress markers.

PubMed

Robinson, Philip C; Lau, Eugene; Keith, Patricia; Lau, Max C; Thomas, Gethin P; Bradbury, Linda A; Brown, Matthew A; Kenna, Tony J

2015-11-01

Single nucleotide polymorphisms in ERAP2 are strongly associated with ankylosing spondylitis (AS). One AS-associated single nucleotide polymorphism, rs2248374, causes a truncated ERAP2 protein that is degraded by nonsense-mediated decay. Approximately 25% of the populations of European ancestry are therefore natural ERAP2 knockouts. We investigated the effect of this associated variant on HLA class I allele presentation, surface heavy chains, endoplasmic reticulum (ER) stress markers and cytokine gene transcription in AS. Patients with AS and healthy controls with either AA or GG homozygous status for rs2248374 were studied. Antibodies to CD14, CD19-ECD, HLA-A-B-C, Valpha7.2, CD161, anti-HC10 and anti-HLA-B27 were used to analyse peripheral blood mononuclear cells. Expression levels of ER stress markers (GRP78 and CHOP) and proinflammatory genes (tumour necrosis factor (TNF), IL6, IL17 and IL22) were assessed by qPCR. There was no significant difference in HLA-class I allele presentation or major histocompatibility class I heavy chains or ER stress markers GRP78 and CHOP or proinflammatory gene expression between genotypes for rs2248374 either between cases, between cases and controls, and between controls. Large differences were not seen in HLA-B27 expression or cytokine levels between subjects with and without ERAP2 in AS cases and controls. This suggests that ERAP2 is more likely to influence AS risk through other mechanisms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Food patterns of Australian children ages 9 to 13 y in relation to ω-3 long chain polyunsaturated intake.

PubMed

Rahmawaty, Setyaningrum; Lyons-Wall, Philippa; Batterham, Marijka; Charlton, Karen; Meyer, Barbara J

2014-02-01

The aim of this study was to examine food patterns of Australian children ages 9 to 13 y in relation to ω-3 long-chain polyunsaturated fatty acid (ω-3 LCPUFA) intake. Secondary analysis was conducted on nationally representative food data of 1110 Australian children ages 9 to 13 y (525 boys and 585 girls) that was obtained using two 24-h recalls. Principle component factor analysis was used to identify food patterns. Discriminant function analysis was used to identify the relationship between the food patterns and total ω-3 LCPUFA intake. Four major food patterns emerged for each sex. For boys these were labeled: "snack foods," "soft drinks," "vegetables," and "pork and meat chops, steak, and mince." For girls they were labeled: "vegetables," "take-away," "tea, coffee, iced coffee drinks" and "canned meals and soup." Fish consumption bought from take-away outlets was more frequently consumed in the "soft drink" (r = 0.577) and take-away (r = 0.485) food pattern in boys and girls, respectively. In contrast, fish prepared at home was more often consumed in "vegetables" in both boys (r = 0.018) and girls (r = 0.106), as well as in the "pork and meat chops, steak and mince" food pattern in boys (r = 0.060). There was a trend that in boys, the "vegetables" group discriminated children who consumed ω-3 LCPUFA levels similar to adequate intakes (AI) (P = 0.067), whereas in girls, the take-away food pattern discriminated for being a fish consumer (P = 0.060). Dietary patterns associated with a high consumption of vegetables and "take-aways" food that include meat and fish are likely to positively influence dietary ω-3 LCPUFA intake in Australian children. Copyright © 2014 Elsevier Inc. All rights reserved.

Toll-like Receptor 4-mediated Endoplasmic Reticulum Stress in Intestinal Crypts Induces Necrotizing Enterocolitis*

PubMed Central

Afrazi, Amin; Branca, Maria F.; Sodhi, Chhinder P.; Good, Misty; Yamaguchi, Yukihiro; Egan, Charlotte E.; Lu, Peng; Jia, Hongpeng; Shaffiey, Shahab; Lin, Joyce; Ma, Congrong; Vincent, Garrett; Prindle, Thomas; Weyandt, Samantha; Neal, Matthew D.; Ozolek, John A.; Wiersch, John; Tschurtschenthaler, Markus; Shiota, Chiyo; Gittes, George K.; Billiar, Timothy R.; Mollen, Kevin; Kaser, Arthur; Blumberg, Richard; Hackam, David J.

2014-01-01

The cellular cues that regulate the apoptosis of intestinal stem cells (ISCs) remain incompletely understood, yet may play a role in diseases characterized by ISC loss including necrotizing enterocolitis (NEC). Toll-like receptor-4 (TLR4) was recently found to be expressed on ISCs, where its activation leads to ISC apoptosis through mechanisms that remain incompletely explained. We now hypothesize that TLR4 induces endoplasmic reticulum (ER) stress within ISCs, leading to their apoptosis in NEC pathogenesis, and that high ER stress within the premature intestine predisposes to NEC development. Using transgenic mice and cultured enteroids, we now demonstrate that TLR4 induces ER stress within Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5)-positive ISCs, resulting in crypt apoptosis. TLR4 signaling within crypts was required, because crypt ER stress and apoptosis occurred in TLR4ΔIEC-OVER mice expressing TLR4 only within intestinal crypts and epithelium, but not TLR4ΔIEC mice lacking intestinal TLR4. TLR4-mediated ER stress and apoptosis of ISCs required PERK (protein kinase-related PKR-like ER kinase), CHOP (C/EBP homologous protein), and MyD88 (myeloid differentiation primary response gene 88), but not ATF6 (activating transcription factor 6) or XBP1 (X-box-binding protein 1). Human and mouse NEC showed high crypt ER stress and apoptosis, whereas genetic inhibition of PERK or CHOP attenuated ER stress, crypt apoptosis, and NEC severity. Strikingly, using intragastric delivery into fetal mouse intestine, prevention of ER stress reduced TLR4-mediated ISC apoptosis and mucosal disruption. These findings identify a novel link between TLR4-induced ER stress and ISC apoptosis in NEC pathogenesis and suggest that increased ER stress within the premature bowel predisposes to NEC development. PMID:24519940

Toll-like receptor 4-mediated endoplasmic reticulum stress in intestinal crypts induces necrotizing enterocolitis.

PubMed

Afrazi, Amin; Branca, Maria F; Sodhi, Chhinder P; Good, Misty; Yamaguchi, Yukihiro; Egan, Charlotte E; Lu, Peng; Jia, Hongpeng; Shaffiey, Shahab; Lin, Joyce; Ma, Congrong; Vincent, Garrett; Prindle, Thomas; Weyandt, Samantha; Neal, Matthew D; Ozolek, John A; Wiersch, John; Tschurtschenthaler, Markus; Shiota, Chiyo; Gittes, George K; Billiar, Timothy R; Mollen, Kevin; Kaser, Arthur; Blumberg, Richard; Hackam, David J

2014-04-04

The cellular cues that regulate the apoptosis of intestinal stem cells (ISCs) remain incompletely understood, yet may play a role in diseases characterized by ISC loss including necrotizing enterocolitis (NEC). Toll-like receptor-4 (TLR4) was recently found to be expressed on ISCs, where its activation leads to ISC apoptosis through mechanisms that remain incompletely explained. We now hypothesize that TLR4 induces endoplasmic reticulum (ER) stress within ISCs, leading to their apoptosis in NEC pathogenesis, and that high ER stress within the premature intestine predisposes to NEC development. Using transgenic mice and cultured enteroids, we now demonstrate that TLR4 induces ER stress within Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5)-positive ISCs, resulting in crypt apoptosis. TLR4 signaling within crypts was required, because crypt ER stress and apoptosis occurred in TLR4(ΔIEC-OVER) mice expressing TLR4 only within intestinal crypts and epithelium, but not TLR4(ΔIEC) mice lacking intestinal TLR4. TLR4-mediated ER stress and apoptosis of ISCs required PERK (protein kinase-related PKR-like ER kinase), CHOP (C/EBP homologous protein), and MyD88 (myeloid differentiation primary response gene 88), but not ATF6 (activating transcription factor 6) or XBP1 (X-box-binding protein 1). Human and mouse NEC showed high crypt ER stress and apoptosis, whereas genetic inhibition of PERK or CHOP attenuated ER stress, crypt apoptosis, and NEC severity. Strikingly, using intragastric delivery into fetal mouse intestine, prevention of ER stress reduced TLR4-mediated ISC apoptosis and mucosal disruption. These findings identify a novel link between TLR4-induced ER stress and ISC apoptosis in NEC pathogenesis and suggest that increased ER stress within the premature bowel predisposes to NEC development.

Magnolol protects neurons against ischemia injury via the downregulation of p38/MAPK, CHOP and nitrotyrosine

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

Chen, Jiann-Hwa; School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan; Department of Emergency Medicine, Cathay General Hospital, Taipei, Taiwan

Magnolol is isolated from the herb Magnolia officinalis, which has been demonstrated to exert pharmacological effects. Our aim was to investigate whether magnolol is able to act as an anti-inflammatory agent that brings about neuroprotection using a global ischemic stroke model and to determine the mechanisms involved. Rats were treated with and without magnolol after ischemia reperfusion brain injury by occlusion of the two common carotid arteries. The inflammatory cytokine production in serum and the volume of infarction in the brain were measured. The proteins present in the brains obtained from the stroke animal model (SAM) and control animal groupsmore » with and without magnolol treatment were compared. Magnolol reduces the total infarcted volume by 15% and 30% at dosages of 10 and 30 mg/kg, respectively, compared to the untreated SAM group. The levels of acute inflammatory cytokines, including interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 were attenuated by magnolol. Magnolol was also able to suppress the production of nitrotyrosine, 4-hydroxy-2-nonenal (4-HNE), inducible NO synthase (iNOS), various phosphorylated p38 mitogen-activated protein kinases and various C/EBP homologues. Furthermore, this modulation of ischemia injury factors in the SAM model group treated with magnolol seems to result from a suppression of reactive oxygen species production and the upregulation of p-Akt and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). These findings confirm the anti-oxidative properties of magnolol, including the inhibition of ischemic injury to neurons; this protective effect seems to involve changes in the in vivo activity of Akt, GSK3β and NF-κB. - Graphical abstract: Schematic presentation of the signaling pathways involved in magnolol inhibited transient global ischemia brain apoptosis and inflammation in rats. The effect of magnolol on the scavenger of ROS, which inhibits p38 MAPK and CHOP protein inactivation. These results suggest that another role for the iNOS/Akt pathway may be involved in neuronal survival or plasticity by magnolol after ischemic injury. - Highlights: • Magnolol attenuates brain damage in ischemic rats. • Effects of magnolol on stroke animals in ROS and acute inflammation cytokines. • Oxidants and Akt/NF-κB signaling are involved in the neuroprotection of magnolol.« less

A cGMP-applicable expansion method for aggregates of human neural stem and progenitor cells derived from pluripotent stem cells or fetal brain tissue.

PubMed

Shelley, Brandon C; Gowing, Geneviève; Svendsen, Clive N

2014-06-15

A cell expansion technique to amass large numbers of cells from a single specimen for research experiments and clinical trials would greatly benefit the stem cell community. Many current expansion methods are laborious and costly, and those involving complete dissociation may cause several stem and progenitor cell types to undergo differentiation or early senescence. To overcome these problems, we have developed an automated mechanical passaging method referred to as "chopping" that is simple and inexpensive. This technique avoids chemical or enzymatic dissociation into single cells and instead allows for the large-scale expansion of suspended, spheroid cultures that maintain constant cell/cell contact. The chopping method has primarily been used for fetal brain-derived neural progenitor cells or neurospheres, and has recently been published for use with neural stem cells derived from embryonic and induced pluripotent stem cells. The procedure involves seeding neurospheres onto a tissue culture Petri dish and subsequently passing a sharp, sterile blade through the cells effectively automating the tedious process of manually mechanically dissociating each sphere. Suspending cells in culture provides a favorable surface area-to-volume ratio; as over 500,000 cells can be grown within a single neurosphere of less than 0.5 mm in diameter. In one T175 flask, over 50 million cells can grow in suspension cultures compared to only 15 million in adherent cultures. Importantly, the chopping procedure has been used under current good manufacturing practice (cGMP), permitting mass quantity production of clinical-grade cell products.

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

Huang, Tianyu; Xu, Hongyi; Chen, Wei

Fiber-reinforced polymer composites are strong candidates for structural materials to replace steel and light alloys in lightweight vehicle design because of their low density and relatively high strength. In the integrated computational materials engineering (ICME) development of carbon fiber composites, microstructure reconstruction algorithms are needed to generate material microstructure representative volume element (RVE) based on the material processing information. The microstructure RVE reconstruction enables the material property prediction by finite element analysis (FEA)This paper presents an algorithm to reconstruct the microstructure of a chopped carbon fiber/epoxy laminate material system produced by compression molding, normally known as sheet molding compounds (SMC).more » The algorithm takes the result from material’s manufacturing process as inputs, such as the orientation tensor of fibers, the chopped fiber sheet geometry, and the fiber volume fraction. The chopped fiber sheets are treated as deformable rectangle chips and a random packing algorithm is developed to pack these chips into a square plate. The RVE is built in a layer-by-layer fashion until the desired number of lamina is reached, then a fine tuning process is applied to finalize the reconstruction. Compared to the previous methods, this new approach has the ability to model bended fibers by allowing limited amount of overlaps of rectangle chips. Furthermore, the method does not need SMC microstructure images, for which the image-based characterization techniques have not been mature enough, as inputs. Case studies are performed and the results show that the statistics of the reconstructed microstructures generated by the algorithm matches well with the target input parameters from processing.« less

Alternating R-CHOP and R-cytarabine is a safe and effective regimen for transplant-ineligible patients with a newly diagnosed mantle cell lymphoma.

PubMed

Klener, Pavel; Fronkova, Eva; Belada, David; Forsterova, Kristina; Pytlik, Robert; Kalinova, Marketa; Simkovic, Martin; Salek, David; Mocikova, Heidi; Prochazka, Vit; Blahovcova, Petra; Janikova, Andrea; Markova, Jana; Obr, Ales; Berkova, Adela; Kubinyi, Jozef; Vaskova, Martina; Mejstrikova, Ester; Campr, Vit; Jaksa, Radek; Kodet, Roman; Michalova, Kyra; Trka, Jan; Trneny, Marek

2018-02-01

Implementation of cytarabine into induction therapy became standard of care for younger patients with mantle cell lymphoma (MCL). On the basis of its beneficial impact, many centers incorporated cytarabine at lower doses also into first-line treatments of elderly patients. We conducted a multicenter observational study that prospectively analyzed safety and efficacy of alternating 3 + 3 cycles of R-CHOP and R-cytarabine for newly diagnosed transplant-ineligible MCL patients. A total of 73 patients were enrolled with median age 70 years. Most patients had intermediate (39.7%) and high-risk (50.7%) disease according to MCL international prognostic index. Rituximab maintenance was initiated in 58 patients. Overall response rate reached 89% by positron emission tomography-computed tomography, including 75.3% complete remissions. Two patients (2.7%) did not complete the induction therapy because of toxicity. Three patients (4.1%) were considered nonresponders, which led to therapy change before completion of induction. Estimated progression-free survival and overall survival were 51.3% and 68.6% at 4 years, respectively. Mantle cell lymphoma international prognostic index, bulky disease (≥ 5 cm), and achievement of positron emission tomography-negativity independently correlated with progression-free survival. Grade 3 to 4 hematologic and nonhematologic toxicity was documented in 48% and 20.5% patients, respectively. Alternation of R-CHOP and R-cytarabine represents feasible and very effective regimen for elderly/comorbid MCL patients. This study was registered at GovTrial (clinicaltrials.gov) NCT03054883. Copyright © 2017 John Wiley & Sons, Ltd.

[Two HHV8-related illnesses in a HIV-negative patient: Kaposi's sarcoma and multicentric Castleman's disease. Response to treatment with Rituximab and CHOP].

PubMed

Pastor, M A; Vasco, B; Mosquera, J M; Debén, G; Bautista, P; Requena, L

2006-01-01

Human herpes virus 8 (HHV8) was discovered in 1994 in the biopsy of a Kaposi's sarcoma in a patient with AIDS. Since then it has been identified in all variants of Kaposi's sarcoma and in another two rare disorders: multicentric Castleman's disease and primary body-cavity based lymphomas. The case discusses a 68 year old, HIV-negative male patient, presenting Kaposi's sarcoma for one year and being monitored by dermatology, who presented for weakness, anorexia and fever. On examination, he was found to have adenitis of the lymph nodes in his neck, underarm and groin. A biopsy on one of the swellings led to findings characteristic of multicentric plasma cell variant Castleman's disease. Blood tests for HHV8 and HIV were carried out, resulting positive and negative respectively (IgG anti-HHV8 positive, title 1/640, indirect immunofluorescence). PCR amplification showed HHV8 in peripheral blood. Patient received 8 cycles of CHOP and rituximab, leading to complete disappearance of the adenitis and general symptoms, with no worsening of his Kaposi's sarcoma. Patient remained in complete remission for 10 months after treatment. This paper discusses the case of a HIV-, HHV8+ patient, diagnosed with classic Kaposi's sarcoma, who developed multicentric plasma cell variant Castleman's disease. The coincidence of two or more HHV8-related illnesses in a HIV-negative patient has rarely been described in medical literature. Treatment with rituximab combined with CHOP chemotherapy was effective in this case, and no worsening of the patient's KS was observed.

Multiplex polymerase chain reaction-based prognostic models in diffuse large B-cell lymphoma patients treated with R-CHOP.

PubMed

Green, Tina M; Jensen, Andreas K; Holst, René; Falgreen, Steffen; Bøgsted, Martin; de Stricker, Karin; Plesner, Torben; Mourits-Andersen, Torben; Frederiksen, Mikael; Johnsen, Hans E; Pedersen, Lars M; Møller, Michael B

2016-09-01

We present a multiplex analysis for genes known to have prognostic value in an attempt to design a clinically useful classification model in patients with diffuse large B-cell lymphoma (DLBCL). Real-time polymerase chain reaction was used to measure transcript levels of 28 relevant genes in 194 de novo DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Including International Prognostic Index (IPI) as a variable in a penalized Cox regression, we investigated the association with disease progression for single genes or gene combinations in four models. The best model was validated in data from an online available R-CHOP treated cohort. With progression-free survival (PFS) as primary endpoint, the best performing IPI independent model incorporated the LMO2 and HLADQA1 as well as gene interactions for GCSAMxMIB1, GCSAMxCTGF and FOXP1xPDE4B. This model assigned 33% of patients (n = 60) to poor outcome with an estimated 3-year PFS of 40% vs. 87% for low risk (n = 61) and intermediate (n = 60) risk groups (P < 0·001). However, a simpler, IPI independent model incorporated LMO2 and BCL2 and assigned 33% of the patients with a 3-year PFS of 35% vs. 82% for low risk group (P < 0·001). We have documented the impact of a few single genes added to IPI for assignment in new drug trials. © 2016 John Wiley & Sons Ltd.

Top Ten Reasons for DEOX as a Front End to Pyroprocessing

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

B.R. Westphal; K.J. Bateman; S.D. Herrmann

A front end step is being considered to augment chopping during the treatment of spent oxide fuel by pyroprocessing. The front end step, termed DEOX for its emphasis on decladding via oxidation, employs high temperatures to promote the oxidation of UO2 to U3O8 via an oxygen carrier gas. During oxidation, the spent fuel experiences a 30% increase in lattice structure volume resulting in the separation of fuel from cladding with a reduced particle size. A potential added benefit of DEOX is the removal of fission products, either via direct release from the broken fuel structure or via oxidation and volatilizationmore » by the high temperature process. Fuel element chopping is the baseline operation to prepare spent oxide fuel for an electrolytic reduction step. Typical chopping lengths range from 1 to 5 mm for both individual elements and entire assemblies. During electrolytic reduction, uranium oxide is reduced to metallic uranium via a lithium molten salt. An electrorefining step is then performed to separate a majority of the fission products from the recoverable uranium. Although DEOX is based on a low temperature oxidation cycle near 500oC, additional conditions have been tested to distinguish their effects on the process.[1] Both oxygen and air have been utilized during the oxidation portion followed by vacuum conditions to temperatures as high as 1200oC. In addition, the effects of cladding on fission product removal have also been investigated with released fuel to temperatures greater than 500oC.« less

Survival and growth of Salmonella in salsa and related ingredients.

PubMed

Ma, Li; Zhang, Guodong; Gerner-Smidt, Peter; Tauxe, Robert V; Doyle, Michael P

2010-03-01

A large outbreak of Salmonella Saintpaul associated with raw jalapeño peppers, serrano peppers, and possibly tomatoes was reported in the United States in 2008. During the outbreak, two clusters of illness investigated among restaurant patrons were significantly associated with eating salsa. Experiments were performed to determine the survival and growth characteristics of Salmonella in salsa and related major ingredients, i.e., tomatoes, jalapeño peppers, and cilantro. Intact and chopped vegetables and different formulations of salsas were inoculated with a five-strain mixture of Salmonella and then stored at 4, 12, and 21 degrees C for up to 7 days. Salmonella populations were monitored during storage. Salmonella did not grow, but survived on intact tomatoes and jalapeño peppers, whereas significant growth at 12 and 21 degrees C was observed on intact cilantro. In general, growth of Salmonella occurred in all chopped vegetables when stored at 12 and 21 degrees C, with chopped jalapeño peppers being the most supportive of Salmonella growth. Regardless of differences in salsa formulation, no growth of Salmonella (initial inoculation ca. 3 log CFU/g) was observed in salsa held at 4 degrees C; however, rapid or gradual decreases in Salmonella populations were only observed in formulations that contained both fresh garlic and lime juice. Salmonella grew at 12 and 21 degrees C in salsas, except for those formulations that contained both fresh garlic and lime juice, in which salmonellae were rapidly or gradually inactivated, depending on salsa formulation. These results highlight the importance of preharvest pathogen contamination control of fresh produce and proper formulation and storage of salsa.

[Effect of litter type on prevalence and severity of pododermatitis in male broilers].

PubMed

Berk, Jutta

2009-01-01

During the course of two trial periods on broilers (Ross 308), the effects of 5 different types of litter (chopped straw, wood shavings, spelt glumes, Pelletinos, HygieneWood-Shavings) on the development of pododermatitis and animal performance (body weight, feed conversion, mortality) were investigated. Pelletinos are for sale under the name Pelletino Strohstreugranulat G. HygieneWood-Shavings are a special product that currently is not available on the market. Male broilers were kept under practical conditions (feeding, light program) for 35 days. Foot pad lesions could already be observed at the first assessment on their 7th day after hatching. Broilers kept on chopped straw showed in both trials the highest score (trial 1: 1.50; trial 2: 1.58). Animals reared on Pelletinos (trial 1: 0.59; trial 2: 0.17) followed by HygieneWood-Shavings (trial 1: 0.63; trial 2: 0.47), wood shavings (trial 1: 1.30; trial 2: 0.71) and spelt glumes (trial 1: 1.13, trial 2:0.93) showed significant lower lesions. During the second trial, the average body weights were significantly higher while feed conversion was lower.The mortality on the other hand showed no significant differences between the trials. Groups kept on Pelletinos showed the best foot pads and the highest body weights in both trials at the end of experiments. The investigation showed that the prevalence and the severity of pododermatitis as well as the performance could be influenced by various types of litter. Chopped straw which is standard for the broiler industry in Germany, seems to be the least suitable variant in our study.

THERAPY-RELATED T/MYELOID MIXED PHENOTYPE ACUTE LEUKEMIA IN A PATIENT TREATED WITH CHEMOTHERAPY FOR CUTANEOUS DIFFUSE LARGE B CELL LYMPHOMA.

PubMed

Roberts, Evans; Oncale, Melody; Safah, Hana; Schmieg, John

2016-01-01

Mixed-phenotype acute leukemia is a rare form of leukemia that is associated with a poor prognosis. Most cases of mixed-phenotype acute leukemia are de novo. However, therapy-related mixed-phenotype acute leukemia can occur, and are often associated with exposure to topoisomerase-II inhibitors and alkylating agents. There are no known treatment guidelines for therapy-related mixed-phenotype acute leukemia. We present a patient with T/myeloid mixed-phenotype acute leukemia secondary to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone R-CHOP chemotherapy for primary cutaneous diffuse large B-cell lymphoma. The patient's leukemic cells express CD34, an immaturity marker, CD3, a T-cell marker, and myeloperoxidase, a myeloid marker, and her history of chemotherapy for previous lymphoma supports the diagnosis of therapy-related T/myeloid mixed phenotype acute leukemia. Clinicians should be aware that this entity could be associated with R-CHOP chemotherapy. Given the complexity in diagnosis, and lack of treatment guidelines, a further understanding of the pathological and genetic principles of therapy-related mixed-phenotype acute leukemia will assist in future efforts to treat and categorize these patients. Mixed phenotype acute leukemia is a rare entity that accounts for two to five percent of all acute leukemias. Therapy- related mixed phenotype acute leukemia is an exceedingly rare hematological neoplasm that accounts for less than one percent of acute leukemias. We describe a case of therapy-related T/myeloid mixed phenotype acute leukemia following rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone R-CHOP chemotherapy for primary cutaneous diffuse large B-cell lymphoma DLBCL. The patient is a 63-year-old female who presented with several cutaneous nodules diagnosed as primary cutaneous DLBCL. The patient received R-CHOP chemotherapy and achieved remission. She remained in remission for four years until she presented with dyspnea, night sweats, weakness, and diffuse lymphadenopathy. Her presentation was initially concerning for recurrent lymphoma; however, a bone marrow biopsy and aspirate and a lymph node biopsy revealed a distinct blast population consistent with T/myeloid mixed phenotype acute leukemia T/M-MPAL. Given the patient's history of previous chemotherapy exposure, our patient represents a case of therapy-related T/myeloid mixed phenotype acute leukemia t-MPAL.

Analysis of the prognostic value of BMI and the difference in its impact according to age and sex in DLBCL patients.

PubMed

Kanemasa, Yusuke; Shimoyama, Tatsu; Sasaki, Yuki; Tamura, Miho; Sawada, Takeshi; Omuro, Yasushi; Hishima, Tsunekazu; Maeda, Yoshiharu

2018-02-01

Studies that have evaluated the prognostic value of body mass index (BMI) in patients with diffuse large B-cell lymphoma have recently been reported. However, the impact of BMI on survival outcomes remains controversial. We retrospectively analyzed the data of 406 diffuse large B-cell lymphoma patients treated with R-CHOP or R-CHOP-like regimens. The number (%) of patients that were categorized into 1 of 4 groups according to BMI were underweight (<18.5 kg/m 2 ), 58 (14.3%); normal weight (≥18.5 to <25 kg/m 2 ), 262 (64.5%); overweight (≥25 to <30 kg/m 2 ), 75 (18.5%); and obese (≥30.0 kg/m 2 ), 11 (2.7%). While the prognosis of overweight patients was good, being similar to that of normal weight, underweight, and obese patients had a worse prognosis (5-y overall survival [OS] was 57.9%, 74.3%, 73.4%, and 40.9% for underweight, normal weight, overweight, and obese patients, respectively; P = .004). In multivariate analysis, underweight and obesity were independent prognostic factors for OS compared with normal weight (hazard ratios 2.90 and 5.17, respectively). In elderly female patients (≥70 y), patients with a low BMI (<25 kg/m 2 ) had significantly inferior OS than those with a high BMI (≥25 kg/m 2 ) (5-y OS, 61.5% vs 85.7%; P = .039). In contrast, in young female patients (<70 years), patients with a low BMI had significantly better OS than those with a high BMI (5-y OS, 88.6% vs 46.4%; P < .001). In male patients, there were no differences in the effect of BMI on OS between young and elderly patients. In this study, we demonstrated that being underweight and obese were independent prognostic factors compared with being normal weight. In female patients, BMI had a different impact on the prognosis of young and elderly patients, whereas in male patients, there was no difference in the effect of BMI on prognosis according to age. Copyright © 2017 John Wiley & Sons, Ltd.

Amelioration of bleomycin-induced pulmonary fibrosis by chlorogenic acid through endoplasmic reticulum stress inhibition.

PubMed

Wang, Yi-Chun; Dong, Jing; Nie, Jing; Zhu, Ji-Xiang; Wang, Hui; Chen, Qiong; Chen, Jun-Yi; Xia, Jia-Mei; Shuai, Wei

2017-09-01

To investigate the inhibitory effects of chlorogenic acid on pulmonary fibrosis and the internal mechanisms in vivo and in vitro. 30 male BALB/C mice were randomized into 5 groups: control group, pulmonary fibrosis model group, low, middle and high dose of chlorogenic acid groups. Mice in pulmonary fibrosis model group were administered 5.0 mg/kg bleomycin with intracheal instillation and mice in 3 chlorogenic acid groups were treated with chlorogenic acid every day for 28 days after bleomycin administration. Lung tissue histology was observed using HE staining. Primary pulmonary fibroblasts were isolated and cultured. The expressions of fibrosis related factors (α-SMA and collagen I), as well as ER stress markers (CHOP and GRP78) were determined by both real-time PCR assay and Western blotting, while the expressions of other ER stress signaling pathway factors PERK, IRE-1, ATF-6 and protein levels of caspase-12, caspase-9, caspase-3, PARP were determined by Western blotting. RLE-6TN cell line induced by TGF-β1 was also used to verify the amelioration effects in vitro study. In both in vivo and in vitro studies, TUNEL staining was used to evaluate cell apoptosis. Expressions of collagen I, α-SMA, GRP78, and CHOP were significantly inhibited by chlorogenic acid in dose-dependent manner. Similarly, decreasing levels of cleaved caspase-12, caspase-9, caspase-3 and increasing level of uncleaved PARP were observed in chlorogenic acid groups compared with those in the fibrosis group both in vivo and in vitro. Chlorogenic acid could also significantly down-regulate the level of phosphorylation of PERK and cleaved ATF-6 in vivo study. Moreover, MTT assay demonstrated chlorogenic acid could enhance proliferation of RLE-6TN cells induced by TGFβ1 in vitro. And the apoptosis assays indicated that chlorogenic acid could significantly inhibit cell apoptosis both in vivo and in vitro studies. Chlorogenic acid could inhibit the pulmonary fibrosis through endoplasmic reticulum stress inhibition in vivo and in vitro.

[Effect of endoplasmic reticulum stress on the expression and osteogenic differentiation of periodontal ligament stem cells].

PubMed

Xue, Peng; Li, Bei; Tan, Jun; An, Ying; Jin, Yan; Wang, Qintao

2015-09-01

To determine the activity of endoplasmic reticulum stress (ERS) and its effect on osteogenic differentiation of periodontal ligament stem cells (PDLSC) in inflammatory microenvironment. PDLSC were obtained from the primary culture of the human tooth and cloned with limited diluted method. Real-time reverse transcription (RT)-PCR was used to examine the different expression of thapsigargin (TG) treated PDLSC and lipopolysaccharide (LPS) treated PDLSC. Real-time RT-PCR, alizarin red staining and cetyl pyridine chloride quantitative analyze were used to examine the osteogenic differentiation of PDLSC, TG + PDLSC, LPS + PDLSC and LPS + PDLSC + 4-PBA. Protein kinase receptor like endoplasmic reticulum kinase (PERK), glucose regulated protein 78 (GRP78), transcription activation factor 4(ATF4), CCAAT/enhancer-binding protein-homologous protein (CHOP) mRNA expression in group PDLSC + TG in 6 h were respectively 1.49 ± 0.24, 2.77 ± 0.60, 1.75 ± 0.16, 2.16 ± 0.32, which were all greater than that in group PDLSC (P < 0.05). PERK, CHOP mRNA expression reached the peak at 6 h (1.76 ± 0.08, 2.31 ± 0.17) and were greater than group PDLSC (P < 0.05). ERS could suppress osteogenic differentiation of TG + PDLSC and LPS + PDLSC. The runt-related transcription factor-2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN) mRNA expression of group TG + PDLSC was respectively 0.73 ± 0.06, 0.01 ± 0.00, 0.20 ± 0.06 (P < 0.05). The RUNX2, ALP, OCN mRNA expression of group LPS + PDLSC was respectively 0.80 ± 0.06, 0.48 ± 0.05, 0.29 ± 0.04 (P < 0.05). The RUNX2, ALP, OCN mRNA expression of group PDLSC + TG + 4-PBA was respectively 1.10 ± 0.09, 0.74 ± 0.05, 0.67 ± 0.13, which were greater higher than that of group LPS + PDLSC (P < 0.05). ERS was activated in PDLSC and suppressed osteogenic differentiation of PDLSC, which can simulate inflammatory microenvironment in vitro. This effect can be recovered by using ERS inhibitor 4-PBA.

Involvement of the Nrf2-proteasome pathway in the endoplasmic reticulum stress response in pancreatic β-cells

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

Lee, Sanghwan; Hur, Eu-gene; Ryoo, In-geun

2012-11-01

The ubiquitin-proteasome system plays a central role in protein quality control through endoplasmic reticulum (ER)-associated degradation (ERAD) of unfolded and misfolded proteins. NF-E2‐related factor 2 (Nrf2) is a transcription factor that controls the expression of an array of phase II detoxification and antioxidant genes. Nrf2 signaling has additionally been shown to upregulate the expression of the proteasome catalytic subunits in several cell types. Here, we investigated the role of Nrf2 in tunicamycin-induced ER stress using a murine insulinoma β-cell line, βTC-6. shRNA-mediated silencing of Nrf2 expression in βTC-6 cells significantly increased tunicamycin-induced cytotoxicity, elevated the expression of the pro-apoptotic ERmore » stress marker Chop10, and inhibited tunicamycin-inducible expression of the proteasomal catalytic subunits Psmb5 and Psmb6. The effects of 3H-1,2-dithiole-3-thione (D3T), a small molecule Nrf2 activator, on ER stress were also examined in βTC-6 cells. D3T pretreatment reduced tunicamycin cytotoxicity and attenuated the tunicamycin-inducible Chop10 and protein kinase RNA-activated‐like ER kinase (Perk). The protective effect of D3T was shown to be associated with increased ERAD. D3T increased the expression of Psmb5 and Psmb6 and elevated chymotrypsin-like peptidase activity; proteasome inhibitor treatment blocked D3T effects on tunicamycin cytotoxicity and ER stress marker changes. Similarly, silencing of Nrf2 abolished the protective effect of D3T against ER stress. These results indicate that the Nrf2 pathway contributes to the ER stress response in pancreatic β-cells by enhancing proteasome-mediated ERAD. -- Highlights: ► Nrf2 silencing in pancreatic β-cells enhanced tunicamycin-mediated ER stress. ► Expression of the proteasome was inducible by Nrf2 signaling. ► Nrf2 activator D3T protected β-cells from tunicamycin-mediated ER stress. ► Protective effect of D3T was associated with Nrf2-dependent proteasome induction.« less