bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mycobacterium avium subsp. paratuberculosis as a trigger of type-1 diabetes: destination Sardinia, or beyond?
Authors: Rani Pittu Sandhya , Sechi Leonardo A , Ahmed Niyaz 
Published: July 2012

Abstract
Type 1 diabetes mellitus (T1DM) is a multifactorial autoimmune disease in which the insulin producing β cell population is destroyed by the infiltrated T lymphocytes. Even though the exact cause of T1DM is yet to be ascertained, varying degree of genetic susceptibility and environmental factors have been linked to the disease progress and outcome. Mycobacterium avium subsp. paratuberculosis (MAP) is an obligate zoonotic pathogen that causes chronic infection of intestines in ruminants, the Johne's disease. MAP that can even survive pasteurization and chlorination has also been implicated to cause similar type of enteritis in humans called Crohn's disease. With the increasing recognition of the link between MAP and Crohn's disease, it has been postulated that MAP is an occult antigen which besides Crohn's could as well be thought to trigger T1DM. Epitope homologies between mycobacterial proteins (Hsp 65) and pancreatic glutamic acid decarboxylase (GAD 65) and infant nutrition studies implicate MAP as one of the triggers for T1DM. PCR and ELISA analyses in diabetic patients from Sardinia suggest that MAP acts as a possible trigger for T1DM. Systematic mechanistic insights are needed to prove this link. Unfortunately, no easy animal model(s) or in-vitro systems are available to decipher the complex immunological network that is triggered in MAP infection leading to T1DM.
Nuclear Pedigree Criteria for the Identification of Individuals Suspected to be at Risk of an Inherited Predisposition to Renal Cancer
Authors: Tołoczko-Grabarek Aleksandra , Sikorski Andrzej , Brzosko Marek , Lubiński Jan 
Published: July 2012

AbstractRenal clear cell carcinomas represent about 3% of all visceral cancers and account for approximately 85% of renal cancers in adults. Environmental and genetic factors are involved in the development of renal cancer. Although to date there are 19 hereditary syndromes described in which renal cell cancer may occur, only four syndromes with an unequivocal genetic predisposition to renal cell carcinoma have been identified: VHL syndrome (mutations in the VHL gene), hereditary clear cell carcinoma (translocations t(3:8), t(2:3)), hereditary papillary carcinoma (mutations in the MET protooncogene) and tuberous sclerosis (mutations in the TSC1 and TSC2 genes). Little is known genetically about the other forms of familial renal cell cancer. Since there is a growing awareness about the necessity of early intervention, clinical criteria have been developed that aid in the identification of hereditary forms of renal cancer. The aim of the current study was to identify minimal inclusion criteria so that nuclear pedigree families can be ascertained for risk assessment and/or kidney tumour screening. The results reveal that inclusion features described herein, such as (a) renal clear cell cancer diagnosed before 55 years of age, and (b) renal clear cell cancer and gastric cancer or lung cancer among first degree relatives, are useful in identifying suspected hereditary clear cell renal cancer patients.
Functional Impact of Sequence Alterations Found in BRCA1 Promoter/5'UTR Region in Breast/Ovarian Cancer Families from Upper Silesia, Poland
Authors: Pamuła Jolanta , Krześniak Małgorzata , Zientek Helena , Pękala Wioletta , Rusin Marek , Grzybowska Ewa 
Published: July 2012

Abstract
The 5' region of BRCA1 contains multiple regulatory sequences flanking the two alternative promoters α and β and two alternative, non-coding exons, 1a and 1b. Aberrations within the 5' region BRCA1 (encompassing two alternative promoters α and β and exons 1a and 1b) may be associated with an increased risk of breast and ovarian cancer. In this study we screened 150 patients for polymorphism and mutations in this region of BRCA1. All probands came from familial breast and/or ovarian cancer that had been found to be mutation-negative in a previous search for founder mutations in BRCA1 (185delAG, C61G, 4153delA, 5382insC) or BRCA2 (6174delT, 9631delC). In our study we found several sequence alterations within the non-coding region of BRCA1 by using direct DNA sequencing and allele-specific PCR amplification. Three families with a polymorphic deletion in BRCA1 exon 1b (2223delAAAAA, Acc. U37574) were found. Moreover, two linked nucleotide substitutions (2642A>T, 2743T>C, Acc. U37574) in BRCA1 intron 1 were detected in 16 patients. In order to assess the functional significance of these two sequence variants, we constructed a reporter vector encoding firefly luciferase under the transcriptional and translational control of wild type and altered BRCA1 promoter region. The reporter assay was performed using a lung cancer cell line (NCI-H1299) and a breast cancer cell line (MCF7). We have demonstrated that the analysed sequence variants have no functional significance in our experimental system. However, we have found that the BRCA1 promoter has lower relative activity in the breast cancer cell line compared with the lung cancer cell line. Based on the results of our functional experiments we conclude that the polymorphic deletion 2223delAAAAA and two linked substitutions 2642A>T and 2743T>C do not significantly alter BRCA1 expression and are probably not disease-causing mutations.
Comparing intra-abdominal pressures in different body positions via a urinary catheter and nasogastric tube: a pilot study
Authors: Rooban Nirooshan , Regli Adrian , Davis Wendy A , De Keulenaer Bart L 
Published: July 2012

Abstract

Objectives
Intra-abdominal pressure (IAP) is most commonly measured via the bladder with the patient in the supine position. In the ICU, patients are nursed with the head of the bed elevated at 30° (HOB30) to reduce the risk of ventilator-associated pneumonia. This study investigated whether gastric pressure at HOB30 can be used as a surrogate measure of IAP via the bladder in the supine position.

Methods
A prospective observational study was conducted in a single-centre intensive care unit. A total of 20 patients were included. IAP was recorded simultaneously via the bladder catheter (bladder pressure, IBP) and via nasogastric tube (gastric pressures, IGP) in the supine and HOB30 position. Each patient had three sets of IAP measurements performed at least 4 h apart.

Results
In the supine position, mean IBP was 12.3 ± 4.5 mmHg compared to IGP of 11.8 ± 4.7 mmHg. The bias between the two groups was 0.5 and precision of 3.7 (LA, -6.8 to 7.5 mmHg). At 30 degrees, mean IBP was 15.8 ± 4.9 mmHg compared to IGP of 13.1 ± 6.1 mmHg. The bias between both groups was 2.7 with a precision of 5.5 (LA, -8.0 to 13.5). Comparing IBP in the supine position with IGP at 30° showed a bias of -0.8 and precision of 5.6 (LA, -10.1 to 11.6 mmHg).

Conclusion
IAP measured via a nasogastric tube was less influenced by changing the body position from supine to HOB30 than was bladder pressure.
Aiming for a negative fluid balance in patients with acute lung injury and increased intra-abdominal pressure: a pilot study looking at the effects of PAL-treatment
Authors: Cordemans Colin , De laet Inneke , Van Regenmortel Niels , Schoonheydt Karen , Dits Hilde , Martin Greg , Huber Wolfgang , Malbrain Manu LNG 
Published: July 2012

Abstract

Introduction
Achievement of a negative fluid balance in patients with capillary leak is associated with improved outcome. We investigated the effects of a multi-modal restrictive fluid strategy aiming for negative fluid balance in patients with acute lung injury (ALI).

Methods
In this retrospective matched case-control study, we included 114 mechanically ventilated (MV) patients with ALI. We compared outcomes between a group of 57 patients receiving PAL-treatment (PAL group) and a matched control group, abstracted from a historical cohort. PAL-treatment combines high levels of positive end-expiratory pressure, small volume resuscitation with hyperoncotic albumin, and fluid removal with furosemide (Lasix®) or ultrafiltration. Effects on extravascular lung water index (EVLWI), intra-abdominal pressure (IAP), organ function, and vasopressor therapy were recorded during 1 week. The primary outcome parameter was 28-day mortality.

Results
At baseline, no significant intergroup differences were found, except for lower PaO2/FIO2 and increased IAP in the PAL group (174.5 ± 84.5 vs 256.5 ± 152.7, p = 0.001; 10.0 ± 4.2 vs 8.0 ± 3.7 mmHg, p = 0.013, respectively). After 1 week, PAL-treated patients had a greater reduction of EVLWI, IAP, and cumulative fluid balance (-4.2 ± 5.6 vs -1.1 ± 3.7 mL/kg, p = 0.006; -0.4 ± 3.6 vs 1.8 ± 3.8 mmHg, p = 0.007; -1,451 ± 7,761 vs 8,027 ± 5,254 mL, p < 0.001). Repercussions on cardiovascular and renal function were limited. PAL-treated patients required fewer days of intensive care unit admission and days on MV (23.6 ± 15 vs 37.1 ± 19.9 days, p = 0.006; 14.6 ± 10.7 vs 25.5 ± 20.2 days, respectively) and had a lower 28-day mortality (28.1% vs 49.1%, p = 0.034).

Conclusion
PAL-treatment in patients with ALI is associated with a negative fluid balance, a reduction of EVLWI and IAP, and improved clinical outcomes without compromising organ function.
Contribution of KIR3DL1/3DS1 to ankylosing spondylitis in human leukocyte antigen-B27 Caucasian populations
Authors: Lopez-Larrea Carlos , Blanco-Gelaz Miguel Angel , Torre-Alonso Juan Carlos , Armas Jacome Bruges , Suarez-Alvarez Beatriz , Pruneda Laura , Couto Ana Rita , Gonzalez Segundo , Lopez-Vázquez Antonio , Martinez-Borra Jesus 
Published: July 2012

AbstractKiller cell immunoglobulin-like receptors (KIRs) and humaAn leukocyte antigen (HLA) loci are both highly polymorphic, and some HLA class I molecules bind and trigger cell-surface receptors specified by KIR genes. We examined whether the combination of KIR3DS1/3DL1 genes in concert with HLA-B27 genotypes is associated with susceptibility to ankylosing spondylitis (AS). Two HLA-B27-positive Caucasian populations were selected, one from Spain (71 patients and 105 controls) and another from the Azores (Portugal) (55 patients and 75 controls). All were typed for HLA-B and KIR (3DS1 and 3DL1) genes. Our results show that in addition to B27, the allele 3DS1 is associated with AS compared with B27 controls (p < 0.0001 and p < 0.003 in the Spanish population and Azoreans, respectively). We also observed that the association of KIR3DS1 to AS was found in combination with HLA-B alleles carrying Bw4-I80 in trans position in the Spanish population (30.9% in AS versus 15.2% in B27 controls, p = 0.02, odds ratio (OR) = 2.49) and in Azoreans (27.2% in AS versus 8.7% in B27 controls, p = 0.01, OR = 4.4 in Azoreans). On the other hand, 3DL1 was decreased in patients compared with B27 controls (p < 0.0001 in the Spanish population and p < 0.003 in Azoreans). The presence of this allele in combination with Bw4-I80 had a protective effect against the development of AS in the Spanish population (19.7% in AS, 35.2% in B27 controls; p = 0.03, OR = 0.45). The presence of KIR3DS1 or KIR3DL1 in combination with HLA-B*27s/HLA-B Bw4-I80 genotypes may modulate the development of AS. The susceptibility to AS could be determined by the overall balance of activating and inhibitory composite KIR-HLA genotypes.
Mild autonomic dysfunction in primary Sjögren's syndrome: a controlled study
Authors: Cai Fin ZJ , Lester Sue , Lu Tim , Keen Helen , Boundy Karyn , Proudman Susanna M , Tonkin Anne , Rischmueller Maureen 
Published: July 2012

Abstract
Introduction
The aim of this study was to compare cardiovascular autonomic nervous system function in patients with primary Sjögren's syndrome (pSS) with that in control individuals, and to correlate the findings with autonomic symptoms and the presence of exocrine secretory dysfunction.

Methods
Twenty-seven female patients with pSS and 25 control individuals completed the COMPASS (Composite Autonomic Symptom Scale) self-reported autonomic symptom questionnaire. Beat-to-beat heart rate and blood pressure data in response to five standard cardiovascular reflex tests were digitally recorded using a noninvasive finger pressure cuff and heart rate variability was analyzed by Fourier spectral analysis. Analysis was performed by analysis of variance (ANOVA), multivariate ANOVA and repeated measures ANOVA, as indicated. Factor analysis was utilized to detect relationships between positive autonomic symptoms in pSS patients.

Results
Multiple, mild autonomic disturbances were observed in pSS patients relating to decreased heart rate variability, decreased blood pressure variability and increased heart rate, which were most evident in response to postural change. There was a strong trend toward an association between decreased heart rate variability and increased severity of the secretomotor, orthostatic, bladder, gastroparesis and constipation self-reported autonomic symptom cluster identified in pSS patients. This symptom cluster was also associated with fatigue and reduced unstimulated salivary flow, and therefore may be an important component of the clinical spectrum of this disease.

Conclusion
There was evidence of mild autonomic dysfunction in pSS as measured with both cardiovascular reflex testing and self-reported symptoms. Pathogenic autoantibodies targeting M3 muscarinic receptors remain a strong candidate for the underlying pathophysiology, but practical assays for the detection of this autoantibody remain elusive.
The 5.5-year results of MegaOATS – autologous transfer of the posterior femoral condyle: a case-series study
Authors: Braun Sepp , Minzlaff Philipp , Hollweck Regina , Wörtler Klaus , Imhoff Andreas B 
Published: July 2012

Abstract
Introduction
Large osteochondral defects of the weight-bearing zones of femoral condyles in young and active patients were treated by autologous transfer of the posterior femoral condyle (large osteochondral autogenous transplantation system (MegaOATS)). The technique presented is a sound and feasible salvage procedure to address large osteochondral defects in weight-bearing zones.

Methods
Thirty-six patients between July 1996 and December 2000 were included. Thirty-three patients (10 females, 23 males) were evaluated by the Lysholm score and X-ray scans. A random sample of 16 individuals underwent magnetic resonance imaging analysis. The average age at the date of surgery was 34.3 (15 to 59) years, and the mean follow up was 66.4 (46 to 98) months. The mean defect size was 6.2 (2 to 10.5) cm2, in 27 patients affecting the medial femoral condyle and in six patients affecting the lateral femoral condyle. Trauma or osteochondrosis dissecans were pathogenetic in 82%.

Results
The Lysholm score in all 33 individuals showed a highly significant increase from a preoperative median 49.0 points to a median 86.0 points (P ≤ 0.001). Twenty-seven patients returned to recreational sports. X-ray scans showed a rounding of the osteotomy edge in 24 patients, interpreted as a partial remodelling of the posterior femoral condyle. Preoperative osteoarthritis in 17 individuals was related to significant lower Lysholm scores (P = 0.014), but progression in 17 patients did not significantly influence the score results (P = 0.143). All 16 magnetic resonance imaging examinations showed vital and congruent grafts.

Conclusion
Patients significantly improve in the Lysholm score, in daily-life activity levels and in return to recreational sports. Thirty-one out of 33 patients were comfortable with the results and would undergo the procedure again. The MegaOATS technique is therefore recommended as a salvage procedure for young individuals with large osteochondral defects in the weight-bearing zone of the femoral condyle.
Enhanced interleukin-1β production of PBMCs from patients with gout after stimulation with Toll-like receptor-2 ligands and urate crystals
Authors: Mylona Eleni E , Mouktaroudi Maria , Crisan Tania O , Makri Stamatoula , Pistiki Aikaterini , Georgitsi Marianna , Savva Athina , Netea Mihai G , van der Meer Jos WM , Giamarellos-Bourboulis Evangelos J , Joosten Leo AB 
Published: July 2012

Abstract

Introduction

Monosodium urate monohydrate (MSU) crystals synergize with various toll-like receptor (TLR) ligands to induce cytokine production via activation of the NOD-like receptor (NLR) family, pyrin domain-containing 3 (NLPR3) inflammasome. This has been demonstrated in vitro using human cell lines or monocytes of healthy volunteers. In the present study, we have investigated the effect of MSU crystals and of their combination with TLR ligands in peripheral blood mononuclear cells (PBMC) of patients with gout.

Methods

PBMCs from 18 patients with primary gout and 12 healthy donors were exposed to MSU crystals in the presence or absence of saturated fatty acid C18:0 (free fatty acid, TLR2 ligand), palmitoyl-3-cystein (Pam3Cys, TLR1/2 ligand) and fibroblast stimulating factor-1 (FSL-1, TLR 2/6 ligand). Production of IL-1β, IL-6, IL-8, IL-17 and tumor necrosis factor alpha (TNFα) was determined by ELISA. mRNA transcripts of IL-1β were measured by real-time PCR.

Results

MSU crystals alone failed to induce IL-1β, IL-6 or TNFα in both patients and control groups, but a stronger synergy between MSU/Pam3Cys and MSU/C18:0 for the induction of IL-1β was found in patients with gout compared to healthy controls. IL-6, but not IL-8, followed the kinetics of IL-1β. No production of the neutrophil-recruiting IL-17 was detectable after stimulation of the patients' PBMCs with MSU in both the presence or absence of TLR ligands. No change of gene transcripts of IL-1β after stimulation with MSU and Pam3Cys or with MSU and C18:0 was found. A positive correlation was found between synergy in IL-1β production from PBMCs of patients between C18:0 and MSU crystals, as well as the annual number of attacks of acute gouty arthritis (rs: +0.649, P: 0.022).

Conclusions

The synergy between MSU crystals and TLR-2 ligands is more prominent in patients with gout than in controls. This is likely mediated by the enhanced maturation of pro-IL-1β into IL-1β.
Promoter hypermethylation in male breast cancer: analysis by multiplex ligation-dependent probe amplification
Authors: Kornegoor Robert , Moelans Cathy B , Verschuur-Maes Anoek HJ , Hogenes Marieke CH , de Bruin Peter C , Oudejans Joost J , van Diest Paul J 
Published: July 2012

Abstract
Introduction
Epigenetic events are, along with genetic alteration, important in the development and progression of cancer. Promoter hypermethylation causes gene silencing and is thought to be an early event in carcinogenesis. The role of promoter hypermethylation in male breast cancer has not yet been studied.

Methods
In a group of 108 male breast cancers, the methylation status of 25 genes was studied using methylation-specific multiplex ligation-dependent probe amplification. Methylation of more than 15% was regarded indicative for promoter hypermethylation. Methylation status was correlated with clinicopathological features, with patients' outcome and with 28 female breast cancer cases.

Results
Promoter hypermethylation of the genes MSH6, WT1, PAX5, CDH13, GATA5 and PAX6 was seen in more than 50% of the cases, but was uncommon or absent in normal male breast tissue. High overall methylation status was correlated with high grade (P = 0.003) and was an independent predictor of poor survival (P = 0.048; hazard ratio 2.5). ESR1 and GSTP1 hypermethylation were associated with high mitotic count (P = 0.037 and P = 0.002, respectively) and high grade (both P = 0.001). No correlation with survival was seen for individual genes. Compared with female breast cancers (logistic regression), promoter hypermethylation was less common in a variety of genes, particularly ESR1 (P = 0.005), BRCA1 (P = 0.010) and BRCA2 (P < 0.001). The most frequently hypermethylated genes (MSH6, CDH13, PAX5, PAX6 and WT1) were similar for male and female breast cancer.

Conclusion
Promoter hypermethylation is common in male breast cancer and high methylation status correlates with aggressive phenotype and poor survival. ESR1 and GSTP1 promoter hypermethylation seem to be involved in development and/or progression of high-grade male breast cancer. Although female and male breast cancer share a set of commonly methylated genes, many of the studied genes are less frequently methylated in male breast cancer, pointing towards possible differences between male and female breast carcinogenesis.
Symmetry-Itemized Enumeration of Cubane Derivatives as Three-Dimensional Entities by the Elementary-Superposition Method of the USCI Approach
Authors: Fujita Shinsaku 
Published: July 2012

Abstract
Cubane derivatives with a given chemical formula and a given symmetry are enumerated by applying the elementary-superposition method (S. Fujita, Theor. Chim. Acta1992, 82, 473–498) of the unit-subduced-cycle-index (USCI) approach to a cubane skeleton of the point group Oh. A cycle index (CI) for a regular or an irregular case of chiral and achiral ligands is calculated in accord with such a given chemical formula. The CI is superposed elementarily onto respective subduced cycle indices with chirality fittingness (SCI-CFs), which are calculated by starting from unit subduced cycle indices with chirality fittingness (USCI-CFs). Thereby, the numbers of fixed points (derivatives) are obtained with respect to the respective SCI-CFs to give a fixed-point vector (FPV). The resulting FPV is multiplied by an inverse matrix of the mark table of Oh to give an isomer-counting vector (ICV), which contains the numbers of 3D-structural isomers in an itemized fashion with respect to point-group symmetries. The concept of prochirality is examined by using cubane derivatives enumerated by the ICV.
Evaluation of the N Latex FLC free light chain assay on the Siemens BN analyser: precision, agreement, linearity and variation between reagent lots
Authors: Pretorius Carel J , Klingberg Sandra , Tate Jill , Wilgen Urs , Ungerer Jacobus P J 
Published: July 2012

Background The clinical utility of serum κ and λ free light chains (FLC) for the diagnosis and prognosis of plasma cell proliferative disorders is well established. We assessed the analytical performance of the N Latex FLC assays and compared it with the Freelite™ assays. Methods Analytical precision was assessed according to the CLSI EP5-A2 protocol. Method comparison was performed with 116 clinical samples and linearity was assessed on samples with monoclonal and polyclonal elevations of FLC. Analytical bias and variance was measured with two lots of N Latex FLC reagent. Results The N Latex FLC κ and λ assays had a total coefficient of variation of 5–7% across the analytical range. The slopes were 1.36 and 1.37 and the between-method variances were 40.0% and 45.4%, respectively, compared with the Freelite™. Good agreement in classification was observed for κ, λ and the κ/ λ ratio (Cohen's κ 0.84, 0.76 and 0.89). Statistical non-linearity occurred commonly, but clinically significant non-linearity was observed in only one instance. Between-reagent lot variation was 7.3% and 10% for κ and λ, respectively. Conclusions The N Latex FLC assay has good precision, did not exhibit gross antigen excess and can be used in clinical practice based on the analytical performance characteristics.