bluuebunny/crossref_metadata_2025_split huggingface dataset:
Newly diagnosed exudative age-related macular degeneration treated with pegaptanib sodium monotherapy in US community-based practices: medical chart review study
Authors: Weber Pamela A , Wirostko Barbara M , Xu Xiao , Goss Thomas F , Zlateva Gergana 
Published: February 2010

Abstract

Background
Studies have shown that early detection and treatment of neovascular age-related macular degeneration (NV-AMD) can delay vision loss and blindness. The objective of this study was to evaluate the efficacy/safety of intravitreal pegaptanib sodium monotherapy in treatment-naïve subjects with newly diagnosed NV-AMD and to gain insight into characteristics of lesions treated in community-based practices.

Methods
From seven private US practices, charts were retrospectively reviewed on 73 subjects with previously untreated subfoveal choroidal NV-AMD treated with their first dose of pegaptanib monotherapy on/after 4/1/2005 through 6/5/2006, receiving ≥4 treatments at 6-week intervals over 21 weeks. Primary endpoint: mean visual acuity (VA) change from baseline to month 6.

Results
75% of lesions were occult, and 82% were subfoveal. From baseline to month 6, mean VA change was -0.68 lines; 58% and 16% gained ≥0 and ≥3 lines of VA, and 70% were responders (<3 lines lost). In 35 subjects with early disease, 80% were responders with a mean gain of 0.46 lines.

Conclusion
Pegaptanib is effective in real-world patients with treatment-naïve NV-AMD in uncontrolled community-based retina practices.
Warburg effect in chemosensitivity: Targeting lactate dehydrogenase-A re-sensitizes Taxol-resistant cancer cells to Taxol
Authors: Zhou Ming , Zhao Yuhua , Ding Yan , Liu Hao , Liu Zixing , Fodstad Oystein , Riker Adam I , Kamarajugadda Sushama , Lu Jianrong , Owen Laurie B , Ledoux Susan P , Tan Ming 
Published: February 2010

AbstractBackgroundTaxol is one of the most effective chemotherapeutic agents for the treatment of patients with breast cancer. Despite impressive clinical responses initially, the majority of patients eventually develop resistance to Taxol. Lactate dehydrogenase-A (LDH-A) is one of the predominant isoforms of LDH expressed in breast tissue, which controls the conversion of pyruvate to lactate and plays an important role in glucose metabolism. In this study we investigated the role of LDH-A in mediating Taxol resistance in human breast cancer cells.ResultsTaxol-resistant subclones, derived from the cancer cell line MDA-MB-435, sustained continuous growth in high concentrations of Taxol while the Taxol-sensitive cells could not. The increased expression and activity of LDH-A were detected in Taxol-resistant cells when compared with their parental cells. The downregulation of LDH-A by siRNA significantly increased the sensitivity of Taxol-resistant cells to Taxol. A higher sensitivity to the specific LDH inhibitor, oxamate, was found in the Taxol-resistant cells. Furthermore, treating cells with the combination of Taxol and oxamate showed a synergistical inhibitory effect on Taxol-resistant breast cancer cells by promoting apoptosis in these cells.ConclusionLDH-A plays an important role in Taxol resistance and inhibition of LDH-A re-sensitizes Taxol-resistant cells to Taxol. This supports that Warburg effect is a property of Taxol resistant cancer cells and may play an important role in the development of Taxol resistance. To our knowledge, this is the first report showing that the increased expression of LDH-A plays an important role in Taxol resistance of human breast cancer cells. This study provides valuable information for the future development and use of targeted therapies, such as oxamate, for the treatment of patients with Taxol-resistant breast cancer.
Decreased NPC1L1 expression in the liver from Chinese female gallstone patients
Authors: Cui Wei , Jiang Zhao-Yan , Cai Qu , Zhang Ru-Yuan , Wu Wei-Ze , Wang Jian-Cheng , Fei Jian , Zhang Sheng-Dao , Han Tian-Quan 
Published: February 2010

Abstract

Background
Cholesterol gallstone disease is a very common disease in both industrialized and developing countries. Many studies have found that cholesterol gallstones are more common in women than men. The molecular mechanisms underlying the relationship between female gallstone disease and hepatic sterol transporters are still undergoing definition and have not been evaluated in humans.

Aims
The aim of this study is to probe for underlying hepatic molecular defects associated with development of gallstones in female.

Methods/Results
Fifty-seven nonobese, normolipidemic Chinese female gallstone patients (GS) were investigated with 12 age- and body mass index-matched female gallstone-free controls (GSF). The bile from the female GS had higher cholesterol saturation than that from the female GSF. The hepatic NPC1L1 mRNA levels were lower in female GS, correlated with SREBP2 mRNA. NPC1L1 downregulation was confirmed at protein levels. Consistently, immunohistochemistry showed decreased NPC1L1 expression in female GS.

Conclusions
The decreased hepatic NPC1L1 levels in female GS might indicate a downregulated reabsorption of biliary cholesterol in the liver, which, in turn, leads to the cholesterol supersaturation of bile. Our data are consistent with the possibility that hepatic NPC1L1 may be mediated by SREBP2.
Effect of chronic treatment with Rosiglitazone on Leydig cell steroidogenesis in rats: In vivo and ex vivo studies
Authors: Couto Janaína A , Saraiva Karina LA , Barros Cleiton D , Udrisar Daniel P , Peixoto Christina A , Vieira Juliany SB César , Lima Maria C , Galdino Suely L , Pitta Ivan R , Wanderley Maria I 
Published: February 2010

Abstract

Background
The present study was designed to examine the effect of chronic treatment with rosiglitazone - thiazolidinedione used in the treatment of type 2 diabetes mellitus for its insulin sensitizing effects - on the Leydig cell steroidogenic capacity and expression of the steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage enzyme (P450scc) in normal adult rats.

Methods
Twelve adult male Wistar rats were treated with rosiglitazone (5 mg/kg) administered by gavage for 15 days. Twelve control animals were treated with the vehicle. The ability of rosiglitazone to directly affect the production of testosterone by Leydig cells ex vivo was evaluated using isolated Leydig cells from rosiglitazone-treated rats. Testosterone production was induced either by activators of the cAMP/PKA pathway (hCG and dbcAMP) or substrates of steroidogenesis [22(R)-hydroxy-cholesterol (22(R)-OH-C), which is a substrate for the P450scc enzyme, and pregnenolone, which is the product of the P450scc-catalyzed step]. Testosterone in plasma and in incubation medium was measured by radioimmunoassay. The StAR and P450scc expression was detected by immunocytochemistry.

Results
The levels of total circulating testosterone were not altered by rosiglitazone treatment. A decrease in basal or induced testosterone production occurred in the Leydig cells of rosiglitazone-treated rats. The ultrastructural and immunocytochemical analysis of Leydig cells from rosiglitazone-treated rats revealed cells with characteristics of increased activity as well as increased StAR and P450scc expression, which are key proteins in androgen biosynthesis. However, a number of rosiglitazone-treated cells exhibited significant mitochondrial damage.

Conclusion
The results revealed that the Leydig cells from rosiglitazone-treated rats showed significant reduction in testosterone production under basal, hCG/dbcAMP- or 22 (R)-OH-C/pregnenolone-induced conditions, although increased labeling of StAR and P450scc was detected in these cells by immunocytochemistry. The ultrastructural study suggested that the lower levels of testosterone produced by these cells could be due to mitochondrial damage induced by rosiglitazone.
Complete genome sequence of human astrovirus genotype 6
Authors: Guo Li , Gonzalez Richard , Wang Wei , Li Yongjun , Paranhos-Baccalà Gláucia , Vernet Guy , Wang Jianwei 
Published: February 2010

AbstractBackgroundHuman astroviruses (HAstVs) are one of the important causes of acute gastroenteritis in children. Currently, eight HAstV genotypes have been identified and all but two (HAstV-6 and HAstV-7) have been fully sequenced. We here sequenced and analyzed the complete genome of a HAstV-6 strain (192-BJ07), which was identified in Beijing, China.ResultsThe genome of 192-BJ07 consists of 6745 nucleotides. The 192-BJ07 strain displays a 77.2-78.0% nucleotide sequence identity with other HAstV genotypes and exhibits amino acid sequence identities of 86.5-87.4%, 94.2-95.1%, and 65.5-74.8% in the ORF1a, ORF1b, and ORF2 regions, respectively. Homological analysis of ORF2 shows that 192-BJ07 is 96.3% identical to the documented HAstV-6 strain. Further, phylogenetic analysis indicates that different genomic regions are likely undergoing different evolutionary and selective pressures. No recombination event was observed in HAstV-6 in this study.ConclusionThe completely sequenced and characterized genome of HAstV-6 (192-BJ07) provides further insight into the genetics of astroviruses and aids in the surveillance and control of HAstV gastroenteritis.
The prevalence of atypical scrapie in sheep from positive flocks is not higher than in the general sheep population in 11 European countries
Authors: Fediaevsky Alexandre , Maurella Cristiana , Nöremark Maria , Ingravalle Francesco , Thorgeirsdottir Stefania , Orge Leonor , Poizat Renaud , Hautaniemi Maria , Liam Barry , Calavas Didier , Ru Giuseppe , Hopp Petter 
Published: February 2010

Abstract

Background
During the last decade, active surveillance for transmissible spongiform encephalopathies in small ruminants has been intensive in Europe. In many countries this has led to the detection of cases of atypical scrapie which, unlike classical scrapie, might not be contagious. EU legislation requires, that following detection of a scrapie case, control measures including further testing take place in affected flocks, including the culling of genotype susceptible to classical scrapie. This might result in the detection of additional cases. The aim of this study was to investigate the occurrence of additional cases in flocks affected by atypical scrapie using surveillance data collected in Europe in order to ascertain whether atypical scrapie, is contagious.

Results
Questionnaires were used to collect, at national level, the results of active surveillance and testing associated with flock outbreaks in 12 European countries. The mean prevalence of atypical scrapie was 5.5 (5.0-6.0) cases per ten thousand in abattoir surveillance and 8.1 (7.3-9.0) cases per ten thousand in fallen stock. By using meta-analysis, on 11 out of the 12 countries, we found that the probability of detecting additional cases of atypical scrapie in positive flocks was similar to the probability observed in animals slaughtered for human consumption (odds ratio, OR = 1.07, CI95%: 0.70-1.63) or among fallen stock (OR = 0.78, CI95%: 0.51-1.2). In contrast, when comparing the two scrapie types, the probability of detecting additional cases in classical scrapie positive flocks was significantly higher than the probability of detecting additional cases in atypical scrapie positive flocks (OR = 32.4, CI95%: 20.7-50.7).

Conclusions
These results suggest that atypical scrapie is not contagious or has a very low transmissibility under natural conditions compared with classical scrapie. Furthermore this study stressed the importance of standardised data collection to make good use of the analyses undertaken by European countries in their efforts to control atypical and classical scrapie.
Dynamic transport and localization of alpha-synuclein in primary hippocampal neurons
Authors: Yang Mong-Lin , Hasadsri Linda , Woods Wendy S , George Julia M 
Published: February 2010

Abstract

Background
Alpha-synuclein is a presynaptic protein with a proposed role in neurotransmission and dopamine homeostasis. Abnormal accumulation of α-synuclein aggregates in dopaminergic neurons of the substantia nigra is diagnostic of sporadic Parkinson's disease, and mutations in the protein are linked to early onset forms of the disease. The folded conformation of the protein varies depending upon its environment and other factors that are poorly understood. When bound to phospholipid membranes, α-synuclein adopts a helical conformation that mediates specific interactions with other proteins.

Results
To investigate the role of the helical domain in transport and localization of α-synuclein, eGFP-tagged constructs were transfected into rat primary hippocampal neurons at 7 DIV. A series of constructs were analyzed in which each individual exon was deleted, for comparison to previous studies of lipid affinity and α-helix content. A53T and A30P substitutions, representing Parkinson's disease-associated variants, were analyzed as well. Single exon deletions within the lipid-binding N-terminal domain of α-synuclein (exons 2, 3, and 4) partially disrupted its presynaptic localization at 17-21 DIV, resulting in increased diffuse labeling of axons. Similar results were obtained for A30P, which exhibits decreased lipid binding, but not A53T. To examine whether differences in presynaptic enrichment were related to deficiencies in transport velocity, transport was visualized via live cell microscopy. Tagged α-synuclein migrated at a rate of 1.85 ± 0.09 μm/s, consistent with previous reports, and single exon deletion mutants migrated at similar rates, as did A30P. Deletion of the entire N-terminal lipid-binding domain (Δ234GFP) did not significantly alter rates of particle movement, but decreased the number of moving particles. Only the A53TGFP mutant exhibited a significant decrease in transport velocity as compared to ASGFP.

Conclusions
These results support the hypothesis that presynaptic localization involves a mechanism that requires helical conformation and lipid binding. Conversely, the rate of axonal transport is not determined by lipid affinity and is not sufficient to account for differences in presynaptic localization of α-synuclein-eGFP variants.
Mongolian and Japanese Joint Conference on "Echinococcosis: diagnosis, treatment and prevention in Mongolia" June 4, 2009
Authors: Gurbadam A , Nyamkhuu D , Nyamkhuu G , Tsendjav A , Sergelen O , Narantuya B , Batsukh Z , Battsetseg G , Oyun-Erdene B , Uranchimeg B , Otgonbaatar D , Temuulen D , Bayarmaa E , Abmed D , Tsogtsaikhan S , Usukhbayar A , Smirmaul K , Gereltuya J , Ito A 
Published: February 2010

Abstract
The first Mongolian-Japanese Joint Conference on "Echinococcosis: diagnosis, treatment and prevention in Mongolia" was held in Ulaanbaatar on June 4th, 2009. It was the first chance for Mongolian experts (clinicians, pathologists, parasitologists, biologists, epidemiologists, veterinarians and others working on echinococcosis) joined together. Increase in the number of cystic echinococcosis (CE) cases year by year was stressed. CE in children may be more than adult cases. Alveolar echinococcosis was suspected chronic malignant hepatic tumors or abscesses. Main discussion was as to how to introduce modern diagnostic tools for pre-surgical diagnosis, how to establish the national system for the data base of echinococcosis with the establishment of a network system by experts from different areas. The importance of molecular identification of the parasites in domestic and wild animals was also stressed.
Four different malignancies in one patient: a case report
Authors: Demirci Umut , Coşkun Ugur , Göçün Pinar Uyar , Gurlek Bahar , Saka Burcu , Öztürk Banu , Benekli Mustafa , Büyükberber Süleyman 
Published: February 2010

Abstract
Cancer survivors have a higher risk of new primary cancer, in the same or in another organ, than the general population. We report a 78-year-old women who has metachronous quadruple adenocarcinoma, includes bilateral breast cancer, ovarian cancer and retroperitoneal neuroendocrine carcinoma. The development of second cancer in cancer survivors can be expected but third or higher order malignancies are rare.
Local leptin production in osteoarthritis subchondral osteoblasts may be responsible for their abnormal phenotypic expression
Authors: Mutabaruka Marie-Solange , Aoulad Aissa Mohamed , Delalandre Aline , Lavigne Martin , Lajeunesse Daniel 
Published: February 2010

Abstract
Introduction
Leptin is a peptide hormone with a role in bone metabolism and rheumatic diseases. The subchondral bone tissue plays a prominent role in the pathophysiology of osteoarthritis (OA), related to abnormal osteoblast (Ob) differentiation. Although leptin promotes the differentiation of Ob under normal conditions, a role for leptin in OA Ob has not been demonstrated. Here we determined if endogenous leptin produced by OA Ob could be responsible for the expression of the abnormal phenotypic biomarkers observed in OA Ob.

Methods
We prepared primary normal and OA Ob from subchondral bone of tibial plateaus removed for knee surgery of OA patients or at autopsy. We determined the production of leptin and of the long, biologically active, leptin receptors (OB-Rb) using reverse transcriptase-polymerase chain reaction, ELISA and Western blot analysis. We determined the effect of leptin on cell proliferation by BrdU incorporation and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, and we determined by Western blot analysis phospho 42/44 MAPK (p42/44 Erk1/2) and phospho p38 levels. We then determined the effect of the addition of exogenous leptin, leptin receptor antagonists, inhibitors of leptin signaling or siRNA techniques on the phenotypic features of OA Ob. Phenotypic features of Ob were determined by measuring alkaline phosphatase activity (ALP), osteocalcin release (OC), collagen type 1 production (CICP) and of Transforming Growth Factor-β1 (TGF-β1).

Results
Leptin expression was increased approximately five-fold and protein levels approximately two-fold in OA Ob compared to normal. Leptin stimulated its own expression and the expression of OB-Rb in OA Ob. Leptin dose-dependently stimulated cell proliferation of OA Ob and also increased phosphorylated p42/44 Erk1/2 and p38 levels. Inactivating antibodies against leptin reduced ALP, OC, CICP and TGF-β1 levels in OA Ob. Tyrphostin (AG490) and piceatannol (Pce), inhibitors of leptin signaling, reproduced this effect. Inhibition of endogenous leptin levels using siRNA for leptin or inhibiting leptin signaling using siRNA for OB-Rb expression both reduced ALP and OC about 60%. Exogenous leptin addition stimulated ALP, yet this failed to further increase OC or CICP.

Conclusions
These results suggest that abnormal production of leptin by OA Ob could be responsible, in part, for the elevated levels of ALP, OC, collagen type 1 and TGF-β1 observed in these cells compared to normal. Leptin also stimulated cell proliferation, and Erk 1/2 and p38 signaling. Taken together, these data suggest leptin could contribute to abnormal osteoblast function in OA.
Brain metabolism is significantly impaired at blood glucose below 6 mM and brain glucose below 1 mM in patients with severe traumatic brain injury
Authors: Meierhans Roman , Béchir Markus , Ludwig Silke , Sommerfeld Jutta , Brandi Giovanna , Haberthür Christoph , Stocker Reto , Stover John F 
Published: February 2010

Abstract
Introduction
The optimal blood glucose target following severe traumatic brain injury (TBI) must be defined. Cerebral microdialysis was used to investigate the influence of arterial blood and brain glucose on cerebral glucose, lactate, pyruvate, glutamate, and calculated indices of downstream metabolism.

Methods
In twenty TBI patients, microdialysis catheters inserted in the edematous frontal lobe were dialyzed at 1 μl/min, collecting samples at 60 minute intervals. Occult metabolic alterations were determined by calculating the lactate- pyruvate (L/P), lactate- glucose (L/Glc), and lactate- glutamate (L/Glu) ratios.

Results
Brain glucose was influenced by arterial blood glucose. Elevated L/P and L/Glc were significantly reduced at brain glucose above 1 mM, reaching lowest values at blood and brain glucose levels between 6-9 mM (P < 0.001). Lowest cerebral glutamate was measured at brain glucose 3-5 mM with a significant increase at brain glucose below 3 mM and above 6 mM. While L/Glu was significantly increased at low brain glucose levels, it was significantly decreased at brain glucose above 5 mM (P < 0.001). Insulin administration increased brain glutamate at low brain glucose, but prevented increase in L/Glu.

Conclusions
Arterial blood glucose levels appear to be optimal at 6-9 mM. While low brain glucose levels below 1 mM are detrimental, elevated brain glucose are to be targeted despite increased brain glutamate at brain glucose >5 mM. Pathogenity of elevated glutamate appears to be relativized by L/Glu and suggests to exclude insulin- induced brain injury.
Posttraumatic stress, anxiety and depression symptoms in patients during the first year post intensive care unit discharge
Authors: Myhren Hilde , Ekeberg Øivind , Tøien Kirsti , Karlsson Susanne , Stokland Olav 
Published: February 2010

Abstract
Introduction
To study the level and predictors of posttraumatic stress, anxiety and depression symptoms in medical, surgical and trauma patients during the first year post intensive care unit (ICU) discharge.

Methods
Of 255 patients included, 194 participated at 12 months. Patients completed the Impact of Event Scale (IES), Hospital Anxiety and Depression Scale (HADS), Life Orientation Test (LOT) at 4 to 6 weeks, 3 and 12 months and ICU memory tool at the first assessment (baseline). Case level for posttraumatic stress symptoms with high probability of a posttraumatic stress disorder (PTSD) was ≥ 35. Case level of HADS-Anxiety or Depression was ≥ 11. Memory of pain during ICU stay was measured at baseline on a five-point Likert-scale (0-low to 4-high). Patient demographics and clinical variables were controlled for in logistic regression analyses.

Results
Mean IES score one year after ICU treatment was 22.5 (95%CI 20.0 to 25.1) and 27% (48/180) were above case level, IES ≥ 35. No significant differences in the IES mean scores across the three time points were found (P = 0.388). In a subgroup, 27/170 (16%), patients IES score increased from 11 to 32, P < 0.001. No differences in posttraumatic stress, anxiety or depression between medical, surgical and trauma patients were found. High educational level (OR 0.4, 95%CI 0.2 to 1.0), personality trait (optimism) OR 0.9, 95%CI 0.8 to 1.0), factual recall (OR 6.6, 95%CI 1.4 to 31.0) and memory of pain (OR 1.5, 95%CI 1.1 to 2.0) were independent predictors of posttraumatic stress symptoms at one year. Optimism was a strong predictor for less anxiety (OR 0.8, 0.8 to 0.9) and depression symptoms (OR 0.8, 0.8 to 0.9) after one year.

Conclusions
The mean level of posttraumatic stress symptoms in patients one year following ICU treatment was high and one of four were above case level Predictors of posttraumatic stress symptoms were mainly demographics and experiences during hospital stay whereas clinical injury related variables were insignificant. Pessimism was a predictor of posttraumatic stress, anxiety and depression symptoms. A subgroup of patients developed clinically significant distress symptoms during the follow-up period.