bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malignancy without immortality? Cellular immortalization as a possible late event in melanoma progression
Authors: Soo Julia K. , MacKenzie Ross Alastair D. , Kallenberg David M. , Milagre Carla , Heung Chong W. , Chow Jade , Hill Lucy , Hoare Stacey , Collinson Rebecca S. , Hossain Mehnaz , Keith W. Nicol , Marais Richard , Bennett Dorothy C. 
Published: March 2011

SummaryCell senescence is a permanent growth arrest following extended proliferation. Cultured cancer cells including metastatic melanoma cells often appear immortal (proliferate indefinitely), while uncultured benign nevi (moles) show senescence markers. Here, with new explantation methods, we investigated which classes of primary pigmented lesions are typically immortal. Nevi yielded a few proliferating cells, consistent with most nevus cells being senescent. No nevus culture (0/28) appeared immortal. Some thin and thick melanoma cultures proved immortal under these conditions, but surprisingly few (4/37). All arrested cultures displayed three senescence markers in some cells: β‐galactosidase, nuclear p16, and heterochromatic foci/aggregates. However, melanoma cultures also showed features of telomeric crisis (arrest because of ultrashort telomeres). Moreover, crisis markers including anaphase bridges were frequent in uncultured vertical growth‐phase (VGP) melanomas. Conversely, all immortal melanoma cultures expressed telomerase reverse transcriptase and telomerase, showing aneuploidy. The findings suggest that primary melanomas are typically precrisis, with immortalization/telomere maintenance as a late event.
Modeling the Dementia Epidemic
Authors: Treves T. A. , Korczyn A. D. 
Published: March 2011

SUMMARYThe incidence of dementia increases steeply with age in older people, although from the tenth decade the slope may be smoother, perhaps reflecting different pathological processes in the oldest old. The prevalence depends upon interaction of age with other factors (e.g., comorbidities, genetic or environmental factors) that in turn are subject to change. If onset of dementia could be postponed by modulating its risk factors, this could significantly affect its incidence. Analysis of risk and protection factors should take into account the critical period during which these factors play a role. For example, the impact of education and diabetes mellitus occurs in early‐ and midlife, respectively, while maintaining optimal physical and mental activity and controlling vascular factors later in life may slow the rate of cognitive decline. Modifying factors need to be evaluated for different clinical groups, taking into account genetic background, age, and duration at exposure. The aim of the present article is to try to take stock of epidemiological data concerning factors affecting the prevalence of dementia and predict future developments, as well as to look for possible interventions that could affect outcome.
Does medically induced weight loss improve obstructive sleep apnoea in the obese: review of randomized trials
Authors: Hemmingsson E. 
Published: March 2011

SummaryObstructive sleep apnoea is characterized by repeated periods of breathing cessation during sleep. Obstructive sleep apnoea is both common and underdiagnosed in the obese. A recent study found that as many as 86% of older obese type 2 diabetics had obstructive sleep apnoea. Obesity is independently associated with developing obstructive sleep apnoea, and the reverse may also occur. The prevalence of obstructive sleep apnoea is therefore expected to rise in the wake of the obesity epidemic. The number of partial (hypopnoea) or complete (apnoea) airway obstructions per hour (apnoea‐hypopnoea index) is used to classify obstructive sleep apnoea as mild (5–14 events per hour), moderate (15–30) or severe (>30). Severe obstructive sleep apnoea is associated with a two to sixfold increase in all‐cause mortality; the impact of mild and moderate obstructive sleep apnoea is less clear. Until recently, the evidence supporting a beneficial effect of weight loss on obstructive sleep apnoea has been limited by a lack of randomized trials. In 2009, at least three randomized controlled trials evaluated whether medically induced weight loss improves obstructive sleep apnoea. The treatment effect ranged from 42% to 62% improvement, although the highest estimate was seen in a very short duration study (9 weeks). Patients who either lost 10–15 kg or more, or had severe obstructive sleep apnoea at baseline, benefited most from treatment.
Osteoarthritis – a role for weight management in rheumatology practice: an update
Authors: Bliddal H. , Christensen P. , Riecke B. F. , Aaboe J. , Frederiksen R. , Bartels E. , Christensen R. 
Published: March 2011

SummaryOsteoarthritis (OA) and obesity are related diseases, which occur in a large proportion of the population. Epidemiological evidence show that weight is of great importance for the development of OA in the knee, and to some extent also in hip and finger joints. Once acquired, the OA contributes to further weight problems by decreasing the daily activity level. Weight loss will be beneficial for the knee and experimental data point at a highly significant effect on knee function and recent results even point at a positive effect on the cartilage of the knee joint. Recommending patients with a combination of knee OA and obesity to lose at least 5% body weight, and aim for 10% is predicted to correspond to 26% improvement in physical function. A programme for this weight loss has been tested with good results applying an initial formula diet with maintenance therapy in groups during follow‐up.
Comparison of a low‐energy diet and a very low‐energy diet in sedentary obese individuals: a pragmatic randomized controlled trial
Authors: Christensen P. , Bliddal H. , Riecke B. F. , Leeds A. R. , Astrup A. , Christensen R. 
Published: March 2011

SummaryThere is no consensus on whether ‘very low‐energy diets’ (VLED; <800 kcal d−1) cause greater weight loss in obese individuals than ‘low‐energy diets’ (LED; 800–1200 kcal d−1). The objective was to determine whether a very low‐energy formula diet would cause greater weight loss than a formula 810 kcal d−1 LED in older sedentary individuals. This is a pragmatic randomized controlled trial. Inclusion criteria: obesity (body mass index [BMI] > 30); age >50 years, with knee osteoarthritis. Participants were randomized to VLED (420–554 kcal d−1) or LED (810 kcal d−1) for 8 weeks, followed by a fixed‐energy (1200 kcal d−1) diet with food and two diet products daily for 8 weeks. In all, 192 participants were randomized. Mean age was 63 years (standard deviation: 6), mean weight 103.2 kg (15.0) and BMI of 37.3 kg m−2 (4.8) at baseline. Mean weight losses in VLED and LED groups were 11.4 kg (standard error: 0.5) and 10.7 kg (0.5) at week 8 and 13.3 kg (0.7) and 12.2 kg (0.6) at week 16. Mean differences between groups were 0.76 kg (95% confidence interval: −0.59 to 2.10; P = 0.27) and 1.08 kg (−0.66 to 2.81; P = 0.22) at 8 and 16 weeks, respectively. Loss of lean body mass was 2.1 kg (0.2) and 1.2 kg (0.4) (17% and 11% of the weight lost, respectively) at week 16 in the VLED and LED group with a mean difference of 0.85 kg (0.01 to 1.69; P = 0.047). Significant adverse effects comparing VLED and LED, were bad breath: 34 (35%) vs. 21 (22%), intolerance to cold: 39 (41%) vs. 17 (18%) and flatulence: 43 (45%) vs. 28 (29%) for VLED and LED at 8 weeks (P < 0.05 in all cases). The VLED and LED regimens were equally successful in inducing weight loss. The significantly lower loss of lean tissue in the LED group together with more frequently reported side effects in the VLED group, favours the choice of low‐energy diet (LED) for the treatment of obesity.
Splenectomy reduces fibrosis and preneoplastic lesions with increased triglycerides and essential fatty acids in rat liver cirrhosis induced by a choline‐deficient L‐amino acid‐defined diet
Authors: Oishi Toshiyuki , Terai Shuji , Iwamoto Takuya , Takami Taro , Yamamoto Naoki , Sakaida Isao 
Published: March 2011

Aim:  This study investigated whether splenectomy is of significance in non‐alcoholic steatohepatitis (NASH).Methods:  Five‐week‐old Wistar rats were fed a choline‐deficient diet for 8 weeks to create a NASH model. A sham‐operation or splenectomy was then performed, and rats were killed 4 weeks later.Results:  Liver fibrosis and liver preneoplastic lesions were significantly reduced in the splenectomy group compared to the sham‐operation group, and α‐smooth muscle actin (SMA) expression was significantly inhibited (liver fibrosis area: sham 8.63 ± 4.09%, splenectomy 5.45 ± 3.69%, P < 0.01; preneoplastic lesion size: sham 6.56 ± 3.68 ×106 µm2/cm2, splenectomy 4.63 ± 3.27 ×106 µm2/cm2, P < 0.05; the number of preneoplastic lesions: sham 8.33 ± 3.96/cm2, splenectomy 5.17 ± 1.80/cm2, P < 0.01; α‐smooth muscle actin‐positive area: sham 4.41 ± 2.48%, splenectomy 2.75 ± 1.66%, P < 0.01) On the other hand, liver triglycerides and essential fatty acids were significantly increased in the splenectomy group (liver triglycerides: sham 182 ± 35.0 mg/g, splenectomy 230 ± 35.0 mg/g, P < 0.05; liver linoleic acid: sham 17.2 ± 4.9 mg/g, splenectomy 23.3 ± 6.9 mg/g, P < 0.05; liver α‐linolenic acid: sham 118 ± 36.6 µg/g, splenectomy 162 ± 51.4 µg/g, P < 0.05). In addition, expressions of hepatic fatty acid metabolism‐related genes (e.g. acyl‐CoA oxidase, liver carnitine palmitoyl‐CoA transferase I, cytochrome P450 4A, long‐chain acyl‐CoA dehydrogenase and medium‐chain acyl‐CoA dehydrogenase) were significantly inhibited in the splenectomy group.Conclusion:  These findings suggest that spleen plays an important regulatory role in the fibrosis, preneoplastic lesion and lipid metabolism of liver in a rat choline‐deficient L‐amino acid model.
HCV core protein promotes heparin binding EGF‐like growth factor expression and activates Akt
Authors: Nakamura Hitomi , Aoki Hiroshi , Hino Okio , Moriyama Mitsuhiko 
Published: March 2011

Aims:  Persistent hepatitis C virus (HCV) infection is a major cause of chronic liver dysfunction and is closely associated with the development of human hepatocellular carcinoma (HCC). Among HCV components, core protein is implicated in cell growth regulation, and we previously demonstrated that HCV core protein interacted with 14‐3‐3 protein and activated the kinase Raf‐1 and mitogen‐activated protein kinase (MAPK)/extracellular regulated kinase (ERK) pathway. In the present study, we investigated the expression levels and function of downstream molecules in the MAPK/ERK signaling pathway in cells expressing HCV core protein.Method:  Heparin‐binding EGF‐like growth factor (HB‐EGF) mRNA, in HepG2 cells stably expressing HCV core protein, was detected by RT‐PCR. The soluble HB‐EGF in culture media was measured by heparin agarose chromatography/Western blot analysis. Immunodetection of Akt and IKK and IB, in HeLa cells and HepG2 cells expressing HCV core protein, were performed with neutralizing antibody for HB‐EGF, phospatidylinositol‐3‐kinase [PI(3)K] inhibitor and dominant‐negative mutant of Ras (DN‐Ras).Results:  HB‐EGF expression was significantly elevated in cells expressing HCV core protein. HCV core protein activated Akt through the Ras/PI(3)K pathway by autocrine secretion of HB‐EGF. Also, HCV core protein activated IKK through Ras/PI(3)K/Akt pathway by autocrine secretion of HB‐EGF. As the Ras/PI(3)K/Akt pathway is critical in anti‐apoptotic HB‐EGF signaling, we examined the possible role of this pathway in cells expressing HCV core protein. In addition, we investigated the relationship between IB kinases (IKK) and Akt in cells expressing HCV core protein, since IKKs are known to be activated by HCV core protein and by Akt in the presence of potent mitogen. We showed that HCV core protein promoted autocrine secretion of HB‐EGF and activated Akt through the Ras/PI(3)K pathway. This model indicates a new approach to mechanism of proliferation and anti‐apoptosis in HCC.Conclusion:  HCV core protein is a potent activator of mitogenic and anti‐apoptotic signaling involved in hepatocarcinogenesis.
Effect of Experimental Endotoxemia on Thrombelastography Parameters, Secondary and Tertiary Hemostasis in Dogs
Authors: Eralp O. , Yilmaz Z. , Failing K. , Moritz A. , Bauer N. 
Published: March 2011

Background: Thrombelastography (TEG) and indicators of secondary and tertiary hemostasis might be altered in dogs with endotoxemia.Hypothesis: Endotoxemia influences measures of coagulation in dogs.Animals: Ten healthy cross‐bred dogs.Material and Methods: Prospective laboratory study between controls (n = 5) receiving 0.9% saline IV and the study group (n = 5) treated with low‐dose lipopolysaccharide (0.02 mg/kg IV). Physical examination and sampling for measurement of leukocytes, platelets, and coagulation variables were performed at time points 0, 1, 4, and 24 hours. Coagulation variables included kaolin‐activated TEG, 1‐stage prothrombin time (OSPT), activated partial thromboplastin time (aPTT), fibrinogen, factor VIII, antithrombin, protein C, protein S, activated protein C (APC)‐ratio calculated from aPTT with and without presence of APC), and D‐Dimers.Results: Endotoxemia‐induced clinical signs included lethargy (n = 5/5), diarrhea (n = 4/5), emesis (n = 4/5), and abdominal pain (2/5). After 1 hour there was severe leukopenia (2.5 ± 0.7 × 109/L; mean ± SD, P < .0001) and a 2.2‐fold increase in D‐Dimers (0.81 ± 0.64 mg/L, P < .0001). After 4 hours there was hyperthermia (40.3 ± 0.4°C, P < .0001) and increases in OSPT (10.5 ± 2.7 seconds, P < .0001), aPTT (16.7±5.2 seconds, P= 0.002). A significant decrease in fibrinogen (1.5±1.0 g/L, P= 0.001), protein C (31 ± 33%, P <.0001), protein S (63 ± 47%, P < .0001), TEG α (58 ± 19, P= .007), and TEG maximal amplitude (50 ± 19 mm, P= .003) was seen compared with the controls. APC‐ratio rose significantly (2.5 ± 0.2, P < .0001) without exceeding the reference interval (n = 4/5).Conclusion and Clinical Importance: D‐Dimers are the earliest indicator for endotoxemia‐associated coagulation abnormalities followed by decreased protein C concentration. APC‐ratio and TEG were not good screening variables.
A Pilot Study to Assess Tolerability of Early Enteral Nutrition via Esophagostomy Tube Feeding in Dogs with Severe Acute Pancreatitis
Authors: Mansfield C.S. , James F.E. , Steiner J.M. , Suchodolski J.S. , Robertson I.D. , Hosgood G. 
Published: March 2011

Background: The putative role of the gut in amplification of systemic inflammation in acute pancreatitis is gaining credence, and intraluminal nutrition has been shown to decrease inflammation in experimental models of pancreatitis. Prepyloric feeding often is used in people with acute pancreatitis, but has not been evaluated in dogs.Hypothesis: Early intervention with enteral nutrition (EN) delivered proximal to the pylorus will be well tolerated in dogs with acute pancreatitis and provide justification for further larger trials.Animals: Ten dogs with severe acute pancreatitis in an open‐label, prospective pilot study.Methods: Dogs were treated with plasma transfusion and standard care, and then consecutively assigned to receive either EN via esophagostomy tube feeding or parenteral nutrition (PN). Outcome was used to determine optimal study size for future studies, and complications were compared between the 2 groups.Results: A significantly greater number of vomiting or regurgitating episodes occurred in dogs receiving PN. The dogs receiving EN did not demonstrate any noticeable postprandial pain. There were more catheter‐related complications in the PN group. There was no difference in outcome between the 2 treatments, and 43 dogs for each treatment would be required in future studies to determine a difference in outcome.Conclusions and Clinical Relevance: Early EN delivered proximal to the pylorus is well tolerated in dogs with severe pancreatitis and resulted in fewer complications than PN. Prospective trials in a larger cohort are justified to fully establish the potential benefit of early EN, preferably compared with minimal enteral nutrition.
Variability in Results of the Microscopic Agglutination Test in Dogs with Clinical Leptospirosis and Dogs Vaccinated against Leptospirosis
Authors: Miller M.D. , Annis K.M. , Lappin M.R. , Lunn K.F. 
Published: March 2011

Background:The microscopic agglutination test (MAT) is commonly used for the diagnosis of canine leptospirosis. In dogs it is sometimes suggested that the serogroup with the highest MAT titer is the infecting serogroup; however, this is not true in humans with confirmed leptospirosis. We sought to investigate the value of MAT results in predicting the infecting serogroup by comparing results across several laboratories and within individual dogs over time.Objectives:To examine the variability in MAT results across different laboratories in dogs recently vaccinated against leptospirosis, and in dogs with clinical leptospirosis, and to investigate variability over time in MAT results in individual dogs with leptospirosis.Animals:Eighteen dogs from a research colony, 9 of which had been vaccinated against leptospirosis, and 17 dogs clinically diagnosed with leptospirosis.Methods:Serum samples were submitted to up to 5 veterinary diagnostic laboratories for MAT titers from each dog on at least 1 occasion. MAT results also were followed over time in 6 dogs diagnosed with leptospirosis.Results:MAT results were discordant across different laboratories in dogs recently vaccinated against leptospirosis and in dogs with clinical leptospirosis. MAT results varied over time in individual dogs with the disease.Conclusions and Clinical Importance:The MAT is a valuable test for the diagnosis of leptospirosis in dogs, but it is unlikely that test results can be used to predict the infecting serogroup. Laboratories offering the MAT should consider participation in a proficiency scheme.
Role of Oxidative Tissue Injury in the Pathophysiology of Experimentally Induced Equine Laminitis: A Comparison of 2 Models
Authors: Burns T.A. , Westerman T. , Nuovo G.J. , Watts M.R. , Pettigrew A. , Yin C. , Belknap J.K. 
Published: March 2011

Background:Oxidative stress reportedly plays a role in sepsis‐induced organ dysfunction and failure in many species. In septic horses, laminae are targeted; evidence of laminar oxidative stress has been reported experimentally in the black walnut extract (BWE) model. Carbohydrate (CHO)‐induced laminitis may be more similar to clinical sepsis‐related laminitis than the BWE model in that animals with CHO‐induced disease commonly develop laminar failure. The role of oxidative stress in the CHO model remains unknown.Hypothesis/Objectives:Markers of oxidative stress will be increased in laminae from horses with BWE‐ and CHO‐induced laminitis.Animals:Banked laminar tissue from various time points from animals subjected to BWE (n = 15) and CHO (n = 20) protocols.Methods:Laminar 4‐hydroxynonenal (4‐HNE) and protein carbonyl content were evaluated by slot blot analysis. Laminar 3‐nitrotyrosine (3‐NT) immunohistochemistry was performed.Results:The number of laminar 3‐NT (+) cells was increased at developmental and Obel grade 1 (OG1) time points in the BWE model (versus control [CON];P= .013) and lower in OG1 tissues than CON in the CHO model (P= .04). No change in 4‐HNE content was observed in the CHO model, and no increase in laminar protein carbonyl content was present in either model (P> .05).Conclusions and Clinical Importance:These results do not support a prominent role for oxidative stress at examined time points in CHO‐overload laminitis and support transient oxidative stress in the BWE model. Tissue oxidation does not appear to be a central early pathophysiologic event in CHO‐associated laminitis.
Retrospective Evaluation of Parenteral Nutrition in Alpacas: 22 Cases (2002–2008)
Authors: Clore E.R.S. , Freeman L.M. , Bedenice D. , Tony Buffington C.A. , Anderson D.E. 
Published: March 2011

Background:Parenteral nutrition is an important method of nutritional support in hospitalized animals, but minimal information has been published on its use in camelids.Hypothesis/Objectives:The purpose of this study was to characterize the use of total parenteral nutrition (TPN) in alpacas, evaluate the formulations used, and determine potential complications.Animals:Twenty‐two alpacas hospitalized at the Tufts Cummings School for Veterinary Medicine (site 1: n = 8) and the Ohio State University Veterinary Teaching Hospital (site 2: n = 14).Methods:A retrospective analysis of all alpacas that received TPN between 2002 and 2008 was performed to assess clinical indications, clinical and clinicopathologic data, and outcome.Results:The most common underlying diseases in animals receiving TPN were gastrointestinal dysfunction (n = 16), hepatic disease (n = 2), and neoplasia (n = 2). Several metabolic abnormalities were identified in animals (n = 20/22) before TPN was initiated, including lipemia (n = 12/22), hyperglycemia (11/22), and hypokalemia (n = 11/22). Median age was significantly lower for site 1 cases (0.1 years; range, 0.01–11.0) compared with those from site 2 (4.9 years; range, 0.1–13.7;P= .03). Animals at site 2 also had a longer duration of hospitalization (P= .01) and TPN administration (P= .004), as well as higher survival rate (P< .02). Twenty‐one of 22 alpacas developed at least 1 complication during TPN administration. Metabolic complications were most prevalent (n = 21/22) and included hyperglycemia (n = 8/21), lipemia (n = 7/21), hypokalemia (n = 3/21), and refeeding syndrome (n = 3/21).Conclusions and Clinical Importance:TPN is a feasible method of nutritional support for alpacas when enteral feeding is not possible. Prospective studies are warranted to determine optimal TPN formulations for alpacas.
Concentration of Lipocalin Region of Collagen XXVII Alpha 1 in the Serum of Dogs with Hemangiosarcoma
Authors: Kirby G.M. , Mackay A. , Grant A. , Woods P. , McEwen B. , Khanna C. , Macri J. , Hayes M.A. , Stalker M. 
Published: March 2011

Background: Hemangiosarcoma (HSA) is a common malignancy of dogs with characteristic early, aggressive metastasis. Diagnosis of HSA is challenging because of lack of sensitive and specific diagnostic tests.Hypothesis: Specific proteins that are increased in serum of dogs with HSA might represent useful biomarkers of the disease.Animals: Thirty‐four dogs with HSA and 42 healthy dogs from the Ontario Veterinary College Teaching Hospital.Methods: This case‐control study compared serum proteins in dogs with HSA and healthy dogs. Proteins were separated by 2‐dimensional difference gel electrophoresis and identified by liquid chromatography and tandem mass spectrometry.Results: Western blot analysis showed that serum collagen XXVII peptide concentration in serum of dogs with large metastatic HSA burdens (1,488, 231–3,754 DU; median, minimum‐maximum); was, on average, 9.5‐fold higher than in healthy dogs (156; 46–2,101 DU). While concentrations for dogs with osteosarcomas (678; 124–3,251 DU), lymphomas (423; 92–2,777 DU), carcinomas (1,022; 177–3,448 DU), and inflammatory disease were also increased, values were consistently lower than those for HSA. Receiver operating characteristic curves revealed an estimated area under the curve of 83% for HSA cases whereas areas for other neoplastic and nonneoplastic diseases were nondiscriminatory. Serum collagen XXVII peptide concentration before splenectomy (1,350; 1,156–1,929 DU) was reduced after tumor removal (529; 452–562 DU) and chemotherapy but increased in 2 dogs with tumor recurrence (511–945 DU; 493–650 DU).Conclusions and Clinical Importance: Collagen XXVII peptide might be useful for diagnosis and monitoring of advanced HSA.