bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered fibrin clot structure/function in patients with idiopathic venous thromboembolism and in their relatives
Authors: Undas Anetta , Zawilska Krystyna , Ciesla-Dul Mariola , Lehmann-Kopydłowska Agata , Skubiszak Agnieszka , Ciepłuch Katarzyna , Tracz Wiesława 
Published: August 2009

AbstractWe tested the hypothesis that fibrin structure/function is unfavorably altered in patients after idiopathic venous thromboembolism (VTE) and their relatives. Ex vivo plasma fibrin clot permeability, turbidimetry, and efficiency of fibrinolysis were investigated in 100 patients with first-ever VTE, including 34 with pulmonary embolism (PE), 100 first-degree relatives, and 100 asymptomatic controls with no history of thrombotic events. Known thrombophilia, cancer, trauma, and surgery were exclusion criteria. VTE patients and their relatives were characterized by lower clot permeability (P < .001), lower compaction (P < .001), higher maximum clot absorbancy (P < .001), and prolonged clot lysis time (P < .001) than controls, with more pronounced abnormalities, except maximum clot absorbance, in the patients versus relatives (all P < .01). Fibrin clots obtained for PE patients were more permeable, less compact, and were lysed more efficiently compared with deep-vein thrombosis patients (all P < .05) with no differences in their relatives. Being VTE relative, fibrinogen, and C-reactive protein were independent predictors of clot permeability and fibrinolysis time in combined analysis of controls and relatives. We conclude that altered fibrin clot features are associated with idiopathic VTE with a different profile of fibrin variables in PE. Similar features can be detected in VTE relatives. Fibrin properties might represent novel risk factors for thrombosis.
Involvement of potential pathways in malignant transformation from Oral Leukoplakia to Oral Squamous Cell Carcinoma revealed by proteomic analysis
Authors: Wang Zhi , Feng Xiaodong , Liu Xinyu , Jiang Lu , Zeng Xin , Ji Ning , Li Jing , Li Longjiang , Chen Qianming 
Published: August 2009

Abstract

Background
Oral squamous cell carcinoma (OSCC) is one of the most common forms of cancer associated with the presence of precancerous oral leukoplakia. Given the poor prognosis associated with oral leukoplakia, and the difficulties in distinguishing it from cancer lesions, there is an urgent need to elucidate the molecular determinants and critical signal pathways underlying the malignant transformation of precancerous to cancerous tissue, and thus to identify novel diagnostic and therapeutic target.

Results
We have utilized two dimensional electrophoresis (2-DE) followed by ESI-Q-TOF-LC-MS/MS to identify proteins differentially expressed in six pairs of oral leukoplakia tissues with dysplasia and oral squamous cancer tissues, each pair was collected from a single patient. Approximately 85 differentially and constantly expressed proteins (> two-fold change, P < 0.05) were identified, including 52 up-regulated and 33 down-regulated. Gene ontological methods were employed to identify the biological processes that were over-represented in this carcinogenic stage. Biological networks were also constructed to reveal the potential links between those protein candidates. Among them, three homologs of proteosome activator PA28 a, b and g were shown to have up-regulated mRNA levels in OSCC cells relative to oral keratinocytes.

Conclusion
Varying levels of differentially expressed proteins were possibly involved in the malignant transformation of oral leukoplakia. Their expression levels, bioprocess, and interaction networks were analyzed using a bioinformatics approach. This study shows that the three homologs of PA28 may play an important role in malignant transformation and is an example of a systematic biology study, in which functional proteomics were constructed to help to elucidate mechanistic aspects and potential involvement of proteins. Our results provide new insights into the pathogenesis of oral cancer. These differentially expressed proteins may have utility as useful candidate markers of OSCC.
Effect of CAR activation on selected metabolic pathways in normal and hyperlipidemic mouse livers
Authors: Režen Tadeja , Tamasi Viola , Lövgren-Sandblom Anita , Björkhem Ingemar , Meyer Urs A , Rozman Damjana 
Published: August 2009

Abstract

Background
Detoxification in the liver involves activation of nuclear receptors, such as the constitutive androstane receptor (CAR), which regulate downstream genes of xenobiotic metabolism. Frequently, the metabolism of endobiotics is also modulated, resulting in potentially harmful effects. We therefore used 1,4-Bis [2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) to study the effect of CAR activation on mouse hepatic transcriptome and lipid metabolome under conditions of diet-induced hyperlipidemia.

Results
Using gene expression profiling with a dedicated microarray, we show that xenobiotic metabolism, PPARα and adipocytokine signaling, and steroid synthesis are the pathways most affected by TCPOBOP in normal and hyperlipidemic mice. TCPOBOP-induced CAR activation prevented the increased hepatic and serum cholesterol caused by feeding mice a diet containing 1% cholesterol. We show that this is due to increased bile acid metabolism and up-regulated removal of LDL, even though TCPOBOP increased cholesterol synthesis under conditions of hyperlipidemia. Up-regulation of cholesterol synthesis was not accompanied by an increase in mature SREBP2 protein. As determined by studies in CAR -/- mice, up-regulation of cholesterol synthesis is however CAR-dependent; and no obvious CAR binding sites were detected in promoters of cholesterogenic genes. TCPOBOP also affected serum glucose and triglyceride levels and other metabolic processes in the liver, irrespective of the diet.

Conclusion
Our data show that CAR activation modulates hepatic metabolism by lowering cholesterol and glucose levels, through effects on PPARα and adiponectin signaling pathways, and by compromising liver adaptations to hyperlipidemia.
Association of hypoxia inducible factor-1 alpha gene polymorphism with both type 1 and type 2 diabetes in a Caucasian (Hungarian) sample
Authors: Nagy Geza , Kovacs-Nagy Reka , Kereszturi Eva , Somogyi Aniko , Szekely Anna , Nemeth Nora , Hosszufalusi Nora , Panczel Pal , Ronai Zsolt , Sasvari-Szekely Maria 
Published: August 2009

Abstract

Background
Hypoxia inducible factor-1 alpha (HIF-1α) is a transcription factor that plays an important role in neo-vascularisation, embryonic pancreas beta-cell mass development, and beta cell protection. Recently a non synonymous single nucleotide polymorphism (g.C45035T SNP, rs11549465) of HIF-1α gene, resulting in the p.P582S amino acid change has been shown to be associated with type 2 diabetes (T2DM) in a Japanese population. Our aim was to replicate these findings on a Caucasian (Hungarian) population, as well as to study whether this genetic effect is restricted to T2DM or can be expanded to diabetes in general.

Methods
A large Caucasian sample (N = 890) was recruited including 370 T2DM, 166 T1DM and 354 healthy subjects. Genotyping was validated by two independent methods: a restriction fragment analysis (RFLP) and a real time PCR using TaqMan probes. An overestimation of heterozygotes by RFLP was observed as a consequence of a nearby SNP (rs34005929). Therefore genotyping results of the justified TaqMan system were accepted. The measured genotype distribution corresponded to Hardy-Weinberg equilibrium (P = 0.740)

Results
As the TT genotype was extremely rare in the population (0.6% in clinical sample and 2.5% in controls), the genotypes were grouped as T absent (CC) and T present (CT and TT). Genotype-wise analysis showed a significant increase of T present group in controls (24.0%) as compared to patients (16.8%, P = 0.008). This genetic effect was demonstrated in the separated samples of type 1 (15.1%, P = 0.020), and also in type 2 (17.6%, P = 0.032) diabetes. Allele-wise analysis gave identical results showing a higher frequency of the T allele in the control sample (13.3%) than in the clinical sample (8.7%, P = 0.002) with similar results in type 1 (7.8%, P = 0.010) and type 2 (9.1%, P = 0.011) diabetes. The odds ratio for diabetes (either type 1 or 2) was 1.56 in the presence of the C allele.

Conclusion
We confirmed the protective effect of a rare genetic variant of HIF-1α gene against type 2 diabetes in a Caucasian sample. Moreover we demonstrated a genetic contribution of the same polymorphism in type 1 diabetes as well, supporting a possible overlap in pathomechanism for T2DM and a T1DM.
Self-reported pediatricians' management of the well-appearing young child with fever without a source: first survey in an European country in the anti-pneumococcal vaccine era
Authors: Chiappini Elena , Galli Luisa , Bonsignori Francesca , Venturini Elisabetta , Principi Nicola , de Martino Maurizio 
Published: August 2009

Abstract

Background
Recent studies suggest a substantially reduced risk of invasive bacterial infection in children vaccinated with heptavalent pneumococcal conjugate vaccine (PCV). To investigate whether the introduction of PCV might affect clinical decision making, we conducted a cross-sectional survey aimed at Italian Pediatric physicians.

Results
The study included 348 (46.5%) primary care pediatricians; 251 (36.4%) hospital pediatricians, and 139 (20.1%) pediatric residents. In an hypothetical scenario, a well-appearing 12-month-old child with fever without source would be sent home with no therapy by 60.7% (419/690) of physicians if the child was not vaccinated with PCV. The proportion increased to 74.2% (512/690) if the child had received PCV (P < 0.0001). Also, physicians would obtain blood tests less frequently in the vaccinated than in unvaccinated children (139/690 [20.1%] vs. 205/690 [29.7%]; P < 0.0001), and started empiric antibiotic therapy less frequently (3.0% vs. 7.5%; P < 0.0001). In the hypothetical event that white blood cell count was 17,500/μL, a significantly lower proportion of physicians would ask for erythrocyte sedimentation rate (P < 0.017), C reactive protein (P < 0.0001), blood culture (P = 0.022), and urine analysis or dipstick (P = 0.028), if the child had received PCV. Only one third of participants routinely recommended PCV.

Conclusion
Our data suggest that implementation of educational programs regarding the proper management of the febrile child is needed.
T-cell-based diagnosis of tuberculosis infection in children in Lithuania: a country of high incidence despite a high coverage with bacille Calmette-Guerin vaccination
Authors: Hansted Edita , Andriuskeviciene Angele , Sakalauskas Raimundas , Kevalas Rimantas , Sitkauskiene Brigita 
Published: August 2009

Abstract

Background
Lithuania is a country with a high incidence of tuberculosis (TB), despite a high coverage with bacille Calmette-Guerin (BCG) vaccination. Until now the only method used to detect latent TB infection was the tuberculin skin test (TST). However, TST may have a cross reactivity to the BCG vaccine and to environmental mycobacteria. The aim of this study was to conduct assessments of the diagnostic accuracy of the T-cell based test (T SPOT TB) for TB in children who had previously been BCG vaccinated and compare these with the results of the TST.

Methods
Between January 2005 and February 2007, children with bacteriologically confirmed TB, children having contacts with a case of infectious pulmonary TB and children without any known risk for TB were tested with both the TST and T SPOT TB.

Results
The TST and T SPOT TB tests were positive for all patients in the „culture-confirmed TB“ group. Whereas, in the „high risk for TB“ group, the TST was positive for 60%, but the T SPOT TB test, only for 17.8%. Meanwhile the results for the „low risk for TB“ group were 65.4% and 9.6%, respectively. A correlation between the TST and T SPOT TB was obtained in the "culture-confirmed TB" group where the TST ≥15 mm (r = 0.35, p < 0.001).

Conclusion
The T-cell based method is more objective than the TST for identifying latent TB infection in children who had been previously BCG vaccinated. This method could be useful in countries like Lithuania where there is a high incidence of TB despite a high coverage with BCG vaccination. It may also help to avoid unnecessary chemoprophylaxis when TST reactions are false-positive.
pRb2/p130 protein expression and RBL2 mutation analysis in Burkitt lymphoma from Uganda
Authors: Kalungi Sam , Steine Solrun J , Wabinga Henry , Bostad Leif , Molven Anders 
Published: August 2009

Abstract

Background
The members of the retinoblastoma protein family, pRb, p107 and pRb2 (p130), are central players in controlling the cell cycle. Whereas disturbed function of pRb is commonly seen in human cancers, it is still an open question whether pRb2 is involved in tumorigenic processes. However, altered subcellular localization of pRb2 and mutations in the pRb2-encoding gene RBL2 have been described for some tumours, including Burkitt lymphomas (BL).

Methods
We retrieved 51 biopsy specimens of endemic BL cases from Uganda. The expression of pRb2 was determined by immunohistochemistry. Exons 19-22 of the RBL2 gene, the region known to contain a nuclear localization signal, were screened for mutations by PCR amplification and direct DNA sequencing.

Results
Nearly all of our cases (84.0%) were positive for pRb2 protein expression although this protein is a marker for growth arrest and Burkitt lymphoma is characterized by a high proliferation rate. Of the positive cases, 73.8% were scored as expressing the protein at a high level. Subcellular pRb2 localization was predominantly nuclear and no cases with expression restricted to the cytoplasm were observed. We did not detect any RBL2 mutations in the part of the gene that encodes the C-terminal end of the protein.

Conclusion
The majority of endemic BL cases from Uganda express pRb2, but somatic RBL2 mutations affecting the protein's nuclear localization signal appear to be rare.
Gender-based reciprocal expression of transforming growth factor-β1 and the inducible nitric oxide synthase in a rat model of cyclophosphamide-induced cystitis
Authors: Tyagi Pradeep , Tyagi Vikas , Yoshimura Naoki , Witteemer Erich , Barclay Derek , Loughran Patricia A , Zamora Ruben , Vodovotz Yoram 
Published: August 2009

AbstractBackgroundThe pluripotent cytokine transforming growth factor-β1 (TGF-β1) is the central regulator of inducible Nitric Oxide Synthase (iNOS) that is responsible for nitric oxide (NO) production in inflammatory settings. Previous studies have implicated a role for NO, presumably derived from iNOS, in cyclophosphamide (CYP)-induced cystitis in the bladder. TGF-β1 is produced in latent form and requires dissociation from the latency-associated peptide (LAP) to act as primary anti-inflammatory and pro-healing modulator following tissue injury in the upper urinary tract. Since the role of TGF-β1 in lower urinary tract inflammation is currently unknown, and since gender-based differences exist in the setting of interstitial cystitis (IC), the present study examined the relationship between TGF-β1 and iNOS/NO in the pathogenesis of CYP-induced cystitis in both male and female rats.MethodsSprague-Dawley rats, 4 months of age, of either gender were given 150 mg/kg CYP intraperitoneally. Urinary and bladder tissue TGF-β1 and NO reaction products (NO2-/NO3-) were quantified as a function of time following CYP. Expression of active and latent TGF-β1 as well as iNOS in harvested bladder tissue was assessed by immunohistochemistry.ResultsFemale rats had significantly higher levels of NO2-/NO3-in urine even at baseline as compared to male rats (p < 0.001), whereas there was no gender based significant difference in urine levels of active or latent TGF-β1 prior to CYP injection. Inflammatory and cytotoxic changes were induced by CYP in the bladder of both sexes that were accompanied by differences in the urine levels of NO2-/NO3-and TGF-β1. Male rats responded to CYP with significantly lower levels of NO2-/NO3-and significantly higher levels of TGF-β1 in urine (p < 0.05) as compared to females at all time points after CYP. The urine levels of NO2-/NO3-after CYP were inversely correlated to latent and active TGF-β1 (Pearson coefficient of -0.72 and -0.69 in females and -0.89 and -0.76 in males, respectively; p < 0.01). Bladder tissue of male rats exhibited significantly higher levels of both latent and active TGF-β1 (p < 0.01) compared to female rats after CYP. TGF-β1 and iNOS protein was mostly localized in the urothelium.ConclusionThe results of this study suggest that there exists an inverse relationship between the expression of TGF-β1 and iNOS/NO2-/NO3-in CYP-inflamed bladder. The gender of the animal appears to magnify the differences in urine levels of TGF-β1 and NO2-/NO3-in this inflammatory setting. These results support the hypothesis that TGF-β1 can suppress iNOS expression associated with bladder inflammation and reduce systemic levels of NO2-/NO3-, and further suggest that this feature of TGF-β1 can be harnessed for therapy and diagnosis of interstitial cystitis.
Environmental supportiveness for physical activity in English schoolchildren: a study using Global Positioning Systems
Authors: Jones Andrew P , Coombes Emma G , Griffin Simon J , van Sluijs Esther MF 
Published: August 2009

Abstract

Background
There is increasing evidence that the environment plays a role in influencing physical activity in children and adults. As children have less autonomy in their behavioural choices, neighbourhood environment supportiveness may be an important determinant of their ability to be active. Yet we know rather little about the types of environment that children use for bouts of physical activity. This study uses accelerometery and global positioning system technologies to identify the charactieristics of environments being used for bouts of continuous moderate to vigorous physical activity (MVPA) in a sample of English schoolchildren.

Methods
The study used a convenience sample of 100 children from SPEEDY (Sport, Physical activity and Eating behaviour: Environmental Determinants in Young people), a cohort of 2064 9–10 year-olds from Norfolk, England, recruited in 2007. Children wore an ActiGraph GT1M accelerometer and a Garmin Forerunner 205 GPS unit over four consecutive days. Accelerometery data points were matched to GPS locations and bouts (5 minutes or more) of MVPA were identified. Bout locations were overlaid with a detailed landcover dataset developed in a GIS to identify the types of environment supporting MVPA. Findings are presented using descriptive statistics.

Results
Boys were also more active than girls, spending an average of 20 (SD 23) versus 11 (SD 15) minutes per day in MVPA bouts. Children who spent more time outside the home were more active (p = 0.002), especially girls and children living in rural locations (both p < 0.05). Children tended to be active close to home, with 63% of all bout time occurring inside neighbourhoods, although boys (p = 0.05) and rural children (p = 0.01) were more likely to roam outside their neighbourhood. Amongst urban children, gardens (28% of bout time) and the street environment (20%) were the most commonly used environments for MVPA bouts. Amongst rural children farmland (22%) and grassland (18%) were most frequently used.

Conclusion
The study has developed a new methodology for the identification of environments in which bouts of continuous physical activity are undertaken. The results highlight the importance of the provision of urban gardens and greenspaces, and the maintenance of safe street environments as places for children to be active.
Control of chicken CR1 retrotransposons is independent of Dicer-mediated RNA interference pathway
Authors: Lee Sung-Hun , Eldi Preethi , Cho Soo-Young , Rangasamy Danny 
Published: August 2009

Abstract

Background

Dicer is an RNase III-ribonuclease that initiates the formation of small interfering RNAs as a defence against genomic parasites such as retrotransposons. Despite intensive characterization in mammalian species, the biological functions of Dicer in controlling retrotransposable elements of the non-mammalian vertebrate are poorly understood. In this report, we examine the role of chicken Dicer in controlling the activity of chicken CR1 retrotransposable elements in a chicken-human hybrid DT40 cell line employing a conditional loss-of-Dicer function.

Results

Retrotransposition is detrimental to host genome stability and thus eukaryotic cells have developed mechanisms to limit the expansion of retrotransposons by Dicer-mediated RNAi silencing pathways. However, the mechanisms that control the activity and copy numbers of transposable elements in chicken remain unclear. Here, we describe how the loss of Dicer in chicken cells does not reactivate endogenous chicken CR1 retrotransposons with impaired RNAi machinery, suggesting that the control of chicken CR1 is independent of Dicer-induced RNAi silencing. In contrast, upon introduction of a functionally active human L1 retrotransposable element that contains an active 5' UTR promoter, the Dicer-deficient chicken cells show a strong increase in the accumulation of human L1 transcripts and retrotransposition activity, highlighting a major difference between chicken CR1 and other mammalian L1 retrotransposons.

Conclusion

Our data provide evidence that chicken CR1 retrotransposons, unlike their mammalian L1 counterparts, do not undergo retrotransposition because most CR1 retrotransposons are truncated or mutated at their 5'UTR promoters and thus are not subjected to Dicer-mediated RNAi-silencing control.
Safety and effectiveness of bariatric surgery: Roux-en-y gastric bypass is superior to gastric banding in the management of morbidly obese patients: a reply to the response by Bhoyrul et al
Authors: Guller Ulrich , Klein Lazar V , Hagen John A 
Published: August 2009

Abstract

Background
We have read the letter by Bhoyrul et al. in response to our recently published article "Safety and effectiveness of bariatric surgery: Roux-en-Y gastric bypass is superior to gastric banding in the management of morbidly obese patients". We strongly disagree with the content of the letter.

Results and discussion
Bhoyrul et al. base their letter mostly on low level evidence such as single-institutional case series (level IV evidence) and expert opinion (level V evidence). Surprisingly, they do not comment on the randomized controlled trial, which clearly favours gastric bypass over gastric banding.

Conclusion
The letter by Bhoyrul et al. is based on low level evidence and is itself biased, unsubstantiated, and not supported by the current literature.